| Browse by: | GSEs  |
RefSeq trancript IDs | |||
| Human | Mouse | Rat |
| S.No | GSE ID | Profile | Summary |
| 1 | GSE21982 |
Profile | affy_fsh_human - affy_fsh_human - - G protein-coupled receptors (GPCR) are centrally involved in most physiological processes and are a major drug targets. They transduce extracellular signals inside the cells through at least two different mechanisms: i) the classical coupling to heterotrimeric G proteins and ii) a newly discovered beta-arrestin-dependent pathway. The fundamental issue of the respective impacts that these two transduction mechanisms exert on gene regulation has not been clearly addressed to date. To tackle this question we have developed two mutants of the follicle stimulating hormone (FSH) receptors which do not couple to G proteins upon FSH activation but continue to recruit beta-arrestins and signal through them.-In the present study, we compare the wild-type FSH receptor to either the R466A or the T469F mutants. These two mutations are localized in the second intra cellular loop of the FSH receptor and prevent G protein coupling to the active FSH receptor. Each receptor was permanently expressed in HEK-293 cells at comparable levels. Cells were treated or not for 6 hours with 3 nM FSH. Keywords: treated vs untreated comparison,wt vs mutant comparison |
| 2 | GSE10479 |
Profile | In vertebrates non-lens bg-crystallins are widely expressed in various tissues, but their functions are unknown. The molecular mechanisms of trefoil factors, initiators of mucosal healing and being greatly involved in tumorigenesis, have remained elusive.A naturally existing 72-kDa complex of non-lens bg-crystallin (a-subunit) and trefoil factor (b-subunit), named bg-CAT, was identified from frog Bombina maxima skin secretions. Its a-subunit and b-subunit (containing three trefoil factor domains), with a non-covalently linked form of ab2, show significant sequence homology to ep37 proteins, a group of non-lens bg-crystallins identified in newt Cynops pyrrhogaster and mammalian trefoil factors, respectively. The bg-CAT showed multiple cellular effects on human umbilical vein endothelial cells. Low dosages of bg-CAT (25-50 pM) were able to stimulate cell migration and wound healing. At high concentrations, it induced cell detachment (EC50 10 nM) and apoptosis. The bg-CAT was rapidly endocytosed via intracellular vacuole formation. Under confocal microscope, some of the vacuoles were translocated to nucleus and partially fused with nuclear membrane. However, what exactly target of bg-CAT act on HUVECs nuclear is still unknown. Primary cultured HUVECs treated with bg-CAT (25 nM, 2 h) were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the genome wide level of significant differential gene expression induced by bg-CAT on HUVECs in order to get clues about bg-CAT action mechanisms. These findings illustrate novel cellular functions of non-lens bg-cyrstallins and action mechanism via association with trefoil factors, serving as clues for investigating the possible occurrence of similar molecules and action mechanisms in mammals. |
| 3 | GSE36572 |
Profile | Microarray analysis revealed differential gene expression patterns of rhabdomyosarcoma (A-204) leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cells treated with TRAIL and/or taurolidine. To explore new therapeutic options in the treatment of sarcomas, we tested the antibiotic taurolidine (TRD) on A-204, SK-LMS-1 and VA-ES-BJ carcinoma cell lines alone and in combination with rhTRAIL (TNF related apoptosis-inducing ligand). Gene expression was analysed by RNA microarray. |
| 4 | GSE9574 |
Profile | Normal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER1 breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast disease (n = 15)). Cyber-T identi?ed differentially expressed genes. Quantitative RT-PCR (qRT-PCR) immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two-thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G-protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under-expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer-related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissue’s response to an existing tumor. Keywords: disease state analysis |
| 5 | GSE18931 |
Profile | Pathways that govern normal stem cell (SC) function are often subverted in cancer. Here we report the isolation to near purity of human normal mammary SC (hNMSCs), from cultured mammospheres, based on their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. We demonstrated that PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we could prospectively isolate SCs from the normal gland and from breast tumors. Poorly-differentiated aggressive (G3) cancers displayed higher content of prospectively isolated cancer SCs, than well-differentiated less aggressive (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in cancer SCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their SC content. |
| 6 | GSE30375 |
Profile | Experiments using xenografts show that some solid tumours and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSC). Despite promise the relevance of the CSC model to human disease remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model based on sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSC) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSC and HSC, revealing the molecular machinery underlying stemness properties. Both stem cell programs were highly significant independent predictors of patient survival and also found in existing prognostic signatures. Thus, determinants of stemness influence clinical outcome of AML establishing that LSC are clinically relevant and not mere artifacts of xenotransplantation. |
| 7 | GSE42867 |
Profile | In this study we have investigated the gene expression profiles of three different types of subclone all generated by single cell cloning of the same parental EBV positive Burkitt lymphoma cell line Awia-BL. These included EBV negative clones which have lost the virus episome EBV positive clones with a conventional Latency I form of infection and EBV positive clones with an atypical Wp-restricted form of infection. |
| 8 | GSE35452 |
Profile | Samples were prospectively collected during colonoscopic examination from 46 rectal cancer patients before starting preoperative chemoradiotherapy. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for prediction of the response to radiotherapy in rectal cancer. |
| 9 | GSE35478 |
Profile | Background: Isolation and characterization of tumourigenic colon cancer initiating cells may help to develop novel diagnostic and therapeutic procedures. Methods: We characterized a panel of fourteen human colon carcinoma cell lines and their corresponding xenografts for the surface expression of different potential stem cell markers: CD133 CD24, CD44, CDCP1 and CXCR4. In five cell lines and nine xenografts mRNA expression of the investigated markers was determined. Tumour growth behaviour of CD133+, CD133- and unsorted SW620 cells was evaluated in vivo. Results: All surface markers showed distinct expression patterns in the examined tumours. Analyses of the corresponding xenografts revealed a significant reduction of cell numbers expressing the investigated markers. CD44 and CXCR4 mRNA expression correlated within the cell line panel and CD44 and CDCP1 within the xenograft panel, respectively. Small subpopulations of double and triple positive cells could be described. SW620 showed significantly higher take rates and shorter doubling times in vivo when sorted for CD133 positivity. Conclusion: Our data support the hypothesis of a small subset of cells with stem cell-like properties characterized by a distinct surface marker profile. In vivo growth kinetics give strong relevance for an important role of CD133 within the mentioned surface marker profile. Key words: colon cancer, tumour stem cell, CD133 |
| 10 | GSE12399 |
Profile | Adipose tissue-derived mesenchymal stromal cells (ATSC) hold great promises in regenerative medicine due to their easy retrieval, their high proliferative capacity, and overall, their multi-lineages differentiation potential. In the last decade, several studies have reported the plasticity of ATSC toward a hepatic fate. Nonetheless, the molecular mechanisms allowing the conversion from a mesenchymal to an epithelial phenotype remain poorly understood. In this study, we investigated the full genome expression profiles of ATSC cultured for 4 weeks under pro-hepatogenic condition in comparison to control ATSC. Sets of differentially expressed genes were then functionally categorized to understand which pathways trigger the hepatic conversion. We showed that ATSC-derived hepatocyte-like cells overexpress sets of genes associated with hepatic functions, including protein metabolism, innate immune response regulation, and biodegradation of toxic compounds. Furthermore, microarray analysis highlighted the downregulation of several transcripts involved in stemness maintenance along with genes associated with the epithelial-mesenchymal-transition. Taken together, these data suggest that in vitro hepatogenic differentiation converts ATSC into immature hepatic cells, functionally related to liver progenitor cells. |
| 11 | GSE14429 |
Profile | The objective of this study is to identify the genes that are up-regulated amid proteasome dysfunction to facilitate the discovery of proteolytic pathways that are activated as a compensatory response to proteasome inhibition. Proteasome is a large multi-component proteolytic complex in the cell. It is responsible for the constitutive turn-over of many cellular proteins as well as the degradation of oxidized and/or unfolded proteins. With such a fundamental role in the cell disruption of proteasome understandably can lead to disastrous outcome. Oxidative stress has been postulated as the driving mechanism for aging. Oxidatively modified proteins, which usually have lost their activity, require immediate removal by proteasome to maintain normal cellular function. Dysfunction of proteasome has also been linked to neuro-degenerative diseases such as Alzheimer’s and Parkinson’s diseases, those that are most commonly seen in aged population. There is more than one proteolytic pathway in the cell, and it has been reported that obstruction of any one of these pathways may enhance the activity of the others. Proteasomal function has been found to have decreased during aging, prompting researchers to hypothesize that failure to remove oxidized proteins may play an important role in aging. It would be interesting to determine the other proteolytic pathways that are activated after proteasome inhibition by a relatively specific inhibitor epoxomicin to help understand their roles in aging processes. Keywords: time course, proteasome, inhibitor, oxidative stress, epoxomicin |
| 12 | GSE45276 |
Profile | Mutations in both RAS and the PTEN/PIK3CA/AKT signaling module are found in the same human tumors. PIK3CA and AKT are downstream effectors of RAS and the selective advantage conferred by mutation of two genes in the same pathway is unclear. Based on a comparative molecular analysis, we show that activated PIK3CA/AKT is a weaker inducer of senescence than is activated RAS. More-over, concurrent activation of RAS and PIK3CA/AKT impairs RAS-induced senescence. We used microarrays to detail the global programme of gene expression after transduction of AKT and RAS |
| 13 | GSE30524 |
Profile | Our previous studies have shown that inhibition of the IGF-1R pathway by the IGF-1RTK inhibitor picropodophyllin (PPP) can be achieved and also constitutes a favorable therapeutic window in multiple myeloma (MM). As no complete remission using in vivo models of MM could be obtained a combinatorial drug screen (HTS) was performed to select the most performant combination with PPP. The HDAC inhibitor LBH589 was shown to act in synergy with PPP on survival of MM cells. The contribution from both drugs and the combination were further monitored for apoptosis, cell cycle distribution, and the impact on downstream gene and protein expression in human and mouse MM models in vitro. In the RPMI 8226 human MM cell line, simultaneous treatment with both compounds for 48h caused a 5-fold increase of apoptotic and late apoptotic/necrotic cells as compared to controls, while treatment with either compound alone only induced a 3-fold increase. After 24h cleavage of apoptotic proteins caspase -9, -8 and -3 could be found in RPMI 8226 cells treated with both drugs individually, but in the combination we observed an additive effect on the cleavage of the active forms of caspase 8 as compared to single drug treatments. The combination of LBH589 and PPP could be monitored as an accumulation of cells in the G2/M phase, and subsequent down-regulation of cell cycle regulated proteins. The effect of both compounds on the expression of cyclin B1, -E and -D2 was additive, as demonstrated by western blot. These data were also confirmed in the mouse 5T33MM cells in vitro. Gene expression analysis and validations of the RPMI 8226 cells reveal that the drug combination has better effects than the single drug alone. Combined treatment in vivo resulted in a significant prolonged survival of 5T33MM inoculated mice when compared to the control group and to treatment with the drugs alone. In conclusion, the results indicate an improved MM treatment opportunity in using a combination of PPP and LBH589. We used whole genome Microarray to decipher the changes occuring after treatment of the single and combination of the drugs. And see if the combination has better effects. |
| 14 | GSE44335 |
Profile | We used microarrays to investigate the transcription profile of FOXC2 expression in a human mammary epithelial cell line. |
| 15 | GSE41663 |
Profile | cDNA and cRNA hybridization technologies have different probe-specific sensitivities. We used samples from an etanercept trial (GSE11903) to explore in a real-life setting the uniqueness of each platform. |
| 16 | GSE17409 |
Profile | Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a healthy donors signature comparing female healthy specimens before pregnancy with respect to female healthy specimens at ninth month pregnancy. |
| 17 | GSE15455 |
Profile | Genome-wide mRNA expression profiles of 25 unique gastric cancer cell lines (GCCLs). Gastric cancer (GC) is the second leading cause of global cancer mortality with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GCCLs, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Keywords: gastric cancer, cell culture |
| 18 | GSE26309 |
Profile | Stable knockdown of NET1 a RhoGEF, was achieved in AGS Gastric Cancer cells. This gene is known to be overexpressed in the disease. Knockdown was achieved using lentiviral shRNA particles. Gene expression was compared between knockdown and scrambled shRNA treated control cells. Cells were treated with and without LPA, a known activator of RhoA. |
| 19 | GSE19862 |
Profile | The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received bevacizumab therapy as first line or second line treatment. Responders and nonresponders were determined based on RECIST and confirmed by CT or MRI. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. |
| 20 | GSE26351 |
Profile | Analysis of mobilized peripheral blood CD34+ cells from a healthy volunteer under erythroid differentiation conditions with and without stimulation to the BMP or Wnt signaling pathways. For erythroid differentiation expanded CD34+ cells were placed in Stemspan SFEM medium supplemented with 2% pen/strep, 20ng/ml SCF, 1U/ml Epo, 5ng/ml IL3, 2uM dexamethasone, and 1uM beta-estradiol. Arrays were performed 2 hours after addition of cytokines. For signaling pathway stimulation, cells were exposed to 0.5uM BIO (a GSK3 inhibitor) for Wnt pathway activation, 25ng/ml rhBMP4 for BMP pathway activation, or vehicle control for 2 hours. Three biological replicates were performed per treatment group. We used microarrays to detail the global program of gene expression changes after Wnt or BMP pathway stimulation in human CD34+ hematopoietic progenitors under erythroid differentiation conditions. |
| 21 | GSE37168 |
Profile | As part of a large genetic evolution study we also acquired 3'UTR expression arrays at two time points for the same 18 patients with CLL. We have analysed the data to evaluate whether genetic evolution (somatic mutations and Somatic copy number alterations) also manifested at the transcriptome level either globally, or at the level of pre-defined curated geneset that correspond to specfic evolving genetic lesions. |
| 22 | GSE27974 |
Profile | human foreskin fibroblasts were infected with HCMV We monitor cellular gene expression network altered by HCMV entry using Affymetrix Human Genome U133 Plus 2.0 Array |
| 23 | GSE13276 |
Profile | Background: Glioblastoma multiforme (GBM) is the most aggressive and most lethal primary malignant brain tumor correlated with survival rates of less than one year from the time of diagnosis. Current surgical procedure attempts to remove the bulk of the tumor mass, whereas GBM frequently recurs within 1-3cm from the primary tumor resection site. Molecular mechanisms involved in the recurrence of the tumor are still poorly understood. The aim of the study was to define the molecular signature of GBM surrounding white matter (WM) in order to better understand the molecular mechanisms involved with tumor relapse. Material & Methods: Human GBM tumor bulk and surrounding tissue (1-3cm from the border of the tumor) were obtained from five patients who underwent total tumour resection, while normal white matter was harvested from patients who underwent surgical procedure for nonmalignant pathologies. Samples were processed for hybridization on the Affymetrix Human U133A arrays and data were examined with the GeneSpring analysis software. Results: Gene expression analysis of the samples was done in 2 independent steps. First, molecular profiling comparison of GBM surrounding WM and normal WM resulted in 59 genes differentially expressed between both tissues. Among these, numerous genes expressed by mature neural cells were down-regulated in GBM surrounding WM, while gene products supporting invasion were overexpressed. Moreover, KLRC1, a specific natural killer receptor naturally involved in the activation of antitumoral cells was drastically repressed in GBM surrounding WM, suggesting that the antitumoral immune surveillance is compromised in this tissue. Second, we focused our study on genes specifically regulated in GBM periphery respectively to GBM core. The highest up-regulated gene in GBM surrounding tissue encodes for DTX4, a regulator of NOTCH signalling pathway described for its key role in maintaining neural progenitors in an uncommitted state. Conclusion: This study revealed unique molecular characteristics of GBM surrounding tissue, showing the dysregulation of genes involved in immune surveillance along with genes associated to stemness maintenance. All together, these data may help to understand the molecular mechanisms associated with GBM recurrence |
| 24 | GSE10233 |
Profile | Cyclin T1-dependent genes in PMA-activated MM6 cells. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Keywords: shrna knockdown |
| 25 | GSE13525 |
Profile | We performed a time-course microarray experiment to define the transcriptional response to carboplatin in vitro and to correlate this with clinical outcome in epithelial ovarian cancer (EOC). RNA was isolated from carboplatin and control-treated 36M2 ovarian cancer cells at several time points, followed by oligonucleotide microarray hybridization. Carboplatin induced changes in gene expression were assessed at the single gene as well as at the pathway level. Clinical validation was performed in publicly available microarray datasets using disease free and overall survival endpoints. Time-course and pathway analyses identified 317 genes and 40 pathways (designated time-course and pathway signatures) deregulated following carboplatin exposure. Both types of signatures were validated in two separate platinum-treated ovarian and NSCLC cell lines using published microarray data. Expression of time-course and pathway signature genes distinguished between patients with unfavorable and favorable survival in two independent ovarian cancer datasets. Among the pathways most highly induced by carboplatin in vitro, the NRF2, NF-kB, and cytokine and inflammatory response pathways were also found to be upregulated prior to chemotherapy exposure in poor prognosis tumors. |
| 26 | GSE14359 |
Profile | In osteosarcoma patients the development of metastases, often to the lungs, is the most frequent cause of death. To improve this situation, a deeper understanding of the molecular mechanisms governing osteosarcoma development and dissemination and the identification of novel drug targets for an improved treatment are needed. Towards this aim, we characterized osteosarcoma tissue samples compared to primary osteoblast cells using Affymetrix HG U133A microarrays. |
| 27 | GSE12526 |
Profile | We used microarrays to examine gene expression levels in individuals from different populations (cephgp chb, jpt, yri). The chb and jpt populations are combined in the analysis. |
| 28 | GSE17714 |
Profile | Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 11 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. We used the l1-l2 regularization framework in order to select the significant probesets defining hypoxic versus normoxic cell lines. |
| 29 | GSE17347 |
Profile | 3D cultivation of cells lead to changes in morphology of the cells. This is likely to explain the higher radioresistance of cells growing in 3D compared to cells growing in 2D cell culture. Whole genome gene expression is performed to determine genes involved in changes of cell moroholgy and radioresistance. Keywords: comparison of 2D vs. 3D cell culture |
| 30 | GSE35414 |
Profile | Evaluation of specific coordinated pattern of transcriptional events consistent with anti-myeloma activity of FK866 (chemical Nampt inhibitor) |
| 31 | GSE8611 |
Profile | Multipotent progenitor cells (MPs) have been observed in human kidneys and particularly in Bowman's capsule and proximal tubules. The kidney owns the ability to repair local damage and renal MPs may play a role in the regenerative processes. Microarray technology was applied to identify differentially expressed genes among resident MPs isolated from glomeruli and tubules of normal renal tissue renal proximal tubular epithelial cells (RPTECs) and mesenchymal stem cells (MSCs). The results of our analysis represent a starting point for further functional studies. Keywords: cell type comparison |
| 32 | GSE46239 |
Profile | The purpose of this study was to use global gene expression analysis to determine major functional pathways and genes dysregulated in the skin of active rashes of dermatomyositis patients. These data will be used to help assign a diagnosis to skin biopsies from patients with rashes that are not clearly dermatomyositis. In addition we will correlate gene expression changes with specific histopathologic changes in skin biopsies that are taken adjacent to those analyzed for gene expression analysis. Finally, these data will be used to search for genes and pathways that are associated with clinical outcomes and autoantibody status in this cohort of patients. |
| 33 | GSE14244 |
Profile | Spontaneous cell fusion of MDA-MB-231 bone-metastatic subline Bm (i.e. SCP2) and lung metastatic subline Lm (i.e., LM2) gave rise to hybrid lines BLm-FACS or BLm-DRUG, as well as its single clones (#8, #12, #18). The hybrids acquired the metastasis tropisms from both parental cells. Expression profiles of the parental cells, the hybrids and several previously characterized MDA-MB-231 metastatic derivatives were compared. Hierarchical clustering showed the hybrids assimilated the organ-specific metastasis gene signatures from both parental cells. Keywords: Cell type comparison |
| 34 | GSE40613 |
Profile | Study designed to explore the effects of endothelial cell/MSC co-culture on individual gene expression profile of each cell type |
| 35 | GSE17832 |
Profile | Iron-deficiency affects 500 million people yet the molecular role of iron in gene expression remains poorly characterized. Moreover, the alterations in global gene expression after iron chelation remains unclear and are important to assess for understanding the molecular pathology of iron-deficiency and the biological effects of iron chelators. We assessed the effect on whole genome gene expression of two iron chelators (desferrioxamine and 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone) that have markedly different permeability properties. Sixteen genes were significantly regulated by both chelators, while a further 50 genes were regulated by either ligand. Most of the genes identified in this study have not been previously described to be iron-regulated and are important for understanding the molecular and cellular effects of iron-deficiency. |
| 36 | GSE41198 |
Profile | We used gene expression profiling of human DCIS and IBC to discover uniquely expressed genes that may also regulate progression. |
| 37 | GSE10089 |
Profile | In order to ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC) we analyzed the anti-tumour effects of Trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via MTT assay. TSA and vorinostat both displayed strong anti-tumor activities in a proportion of NSCLC cell lines, and suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified NCI program. In addition, pathway analysis was performed with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine (SVM) algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the SVM model was validated by an additional seven cell lines, resulting in a prediction value of 100% in respect to determining response to TSA. Our results suggested that [1] HDAC inhibitors may be promising anticancer drugs to NSCLC, and [2] the nine gene classifer is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients. training sample set: GSM94303 PC9 GSM94304 PC7 GSM94305 PC14 GSM94306 A549 GSM94308 LK2 GSM94313 RERF LC-KJ GSM94314 RERF LC-MS GSM94315 RERF-LC-AI GSM94316 PC-1 GSM94317 PC-3 GSM94319 PC-10 GSM94323 ABC-1 GSM94324 EBC-1 GSM94325 LC2/ad GSM94328 SQ-5 GSM94329 QG-56 test sample set: GSM94307 LU65 GSM94326 LC1/sq GSM94327 LC-1F GSM254967 LCOK GSM254968 LCD GSM254969 H1650 GSM254970 H1975 Keywords: HDAC inhibitor, NSCLC, cDNA array, drug sensitivity test, pathway analysis |
| 38 | GSE1923 |
Profile | Overall study: Identification of PDGF-dependent patterns of gene expression in U87 glioblastoma cells. RNA was obtained from triplicate dishes of 5 different groups of U87 cells each (total 15) analyzed with one U95 microarray chip. Three different comparisons were made: 1) Clone 3.1 (34580-34582) vs. clone 3.3 (34583-34585) vs. parent U87 (34592-34594). Purpose: demonstrate that the gene expression profiles between these 3 cell lines are not different, so they could be pooled as a single untreated group. 2) Pooled control group (34580-34585, 34592-34594) vs. clone 8.1 (34586-34588). Purpose: identify genes specifically controlled by autocrine PDGF activity. 3) Clone 8.1 (34586-34588) vs. clone 8.1 treated with PDGF (34589-34591) Purpose: Identify genes specifically induced by exogenous PDGF. Keywords = platelet-derived growth factor Keywords = glioblastoma Keywords = brain cancer Keywords = sterol regulatory element binding protein Keywords = SREBP Keywords: ordered |
| 39 | GSE6034 |
Profile | Adult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor bortezomib in ATL cells, we attempted to perform gene expression profiling. Keywords: dose response |
| 40 | GSE9770 |
Profile | Layer II stellate neurons (entorhinal cortex) and layer III cortical neurons (hippocampus CA1 middle temporal gyrus, posterior cingulate, superior frontal gyrus, primary visual cortex) were gene expression profiled. Brain regions are from non-demented individuals with intermediate Alzheimer's disease neuropathologies Keywords: neuronal gene expression profiling |
| 41 | GSE4069 |
Profile | The human nm23-H1 was discovered as a tumor metastasis suppressor based on its reduced expression in melanoma cell lines with low versus high metastatic potential. It encodes for one of two subunits of the nucleoside-diphosphate kinase. Besides its role in the maintenance of the cells NTP pool nm23 plays a key role in different cellular processes. The role of nm23-H1 in these processes still has to be elucidated. Our goal was to identify Nm23-H1 downstream targets by subjecting Nm23-H1 overexpressing CAL 27 cells oral squamous cell carcinoma (OSSC) to microarray analysis. The genes with changed expression patterns could be clustered into several groups: transforming growth factor (TGF) signaling pathway, cell adhesion, invasion and motility, proteasome machinery, cell-cycle, epithelial structural and related molecules and others. Based on the expression patterns observed we presume that nm23-H1 might have a role in OSSCs, which should be confirmed by future experiments. Keywords: disease state analysis |
| 42 | GSE41227 |
Profile | We used gene expression profiling of human DCIS and IBC to discover uniquely expressed genes that may also regulate progression. |
| 43 | GSE48258 |
Profile | Using a transcriptomics approach we explored the mechanism(s) of synergy observed between CDKI-73 and fludarabine in primary CLL cells. The cytotoxic effects of CDKI-73 were associated with transcriptional inhibition of cdk9 target genes including MCL1 and XIAP. In contrast fludarabine induced the transcription of these genes, an effect that was reversed by the combination of CDKI-73 and fludarabine. We used microarrays to explore the cytoxic synergy observed in primary CLL cells when we combined a novel CDK9 inhibitor with the purine nucleoside analogue fludarabine |
| 44 | GSE8167 |
Profile | GIST is considered to invariably arise through gain-of-function KIT or PDGFRA mutation of the interstitial cells of Cajal (ICC). However the genetic basis of the malignant progression of GIST is poorly understood. We analysed the expression levels of 54,613 probe sets in 32 surgical samples of untreated GIST of the stomach and small intestine with GeneChip Human Genome U133 Plus 2.0 arrays. Keywords: gene expression array-based, count |
| 45 | GSE18947 |
Profile | Metastasis of tumor consists of a complex serias of cascades . Molecular mechanisms needs to be elucidated. We used microarrays to explore the global change of gene expression betwwen two pairs of osteosarcoma sublines screened by different method. |
| 46 | GSE24026 |
Profile | CD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes – such as BATF – that inhibit T cell function. |
| 47 | GSE35200 |
Profile | Gene expression data from AML cell lines MOLM-14, U937, THP-1 and HL-60, that were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), or two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6). Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetic-based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3A (GSK-3A) in AML by performing two independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3A induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3A–specific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3B has been well studied in cancer development, these studies support a role for GSK-3A in AML. |
| 48 | GSE19285 |
Profile | The purpose of this study was to characterize the transcriptional effects induced by intramuscular IFN-beta-1a treatment (Avonex 30 µg once weekly) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 24 MS patients within the first four weeks of IFN-beta administration. Keywords: Multiple sclerosis, Interferon, Pharmacogenomics, Affymetrix |
| 49 | GSE17375 |
Profile | Primary colon CSC cultures were transduced with a Wnt responsive construct (TOP-GFP) and were single cell cloned. 10% highest and lowest TOP-GFP cell fractions were FACS sorted and arrayed. |
| 50 | GSE5390 |
Profile | Down syndrome (DS) is the result of trisomy chromosome 21 but the mechanisms by which the genotype leads to the characteristic disease phenotype are unclear. We performed a microarray study using human adult brain tissue (dorsolateral prefrontal cortex) from DS subjects and healthy controls to characterise for the first time the human adult Down syndrome brain Keywords: disease state analysis |
| 51 | GSE20847 |
Profile | Rapid advances in genotyping and sequencing technology have dramatically accelerated the discovery of genes underlying human disease. Elucidating the function of such genes and understanding their role in pathogenesis however, remains challenging. Here, we introduce a genomic strategy to functionally characterize such genes, and apply it to LRPPRC (leucine-rich PPR-motif containing), a poorly studied gene that is mutated in Leigh Syndrome, French Canadian type (LSFC). We utilize RNAi to engineer an allelic series of cellular models in which LRPPRC has been stably silenced to different levels of knockdown efficiency. Using expression profiling, we discovered a specific role for LRPPRC in the expression of all mitochondrial DNA (mtDNA)-encoded mRNAs, but not the rRNAs, without affecting nuclear genes encoding mitochondrial proteins. |
| 52 | GSE21912 |
Profile | The RPMI-8226 human multiple myeloma cell line was stably infected with either a validated shRNA against BMI1 or a control shRNA. RNA was prepared from these lines +/- doxycycline induction and at various time points post-induction. Samples were hybridized on the Affymetrix U133plus2 human genome expression microarray. |
| 53 | GSE46218 |
Profile | To identify molecular singnal alterations between androgen dependent prostate cancer and castration resistant prostate cancer we performed interspecies comparative microarray analyses using RNAs prepared from uncastrasion and castration tumor from LNCAP Orhotopic xenograft models of prostate cancer. microarray data from uncastrasion and castration tumor revealed that the gene expression profile is most significantly altered in between androgen dependent prostate cancer and castration resistant prostate cancer. Comparative analyses of LNCAP Orhotopic xenograft models of prostate cancer showed that genes involved in androgen dependent and androgen independent tumor were significantly altered. |
| 54 | GSE7621 |
Profile | We used microarrays to detail the global program of gene expression underlying Parkinson's disease Keywords: normal versus diseased |
| 55 | GSE30988 |
Profile | Activation of the immune system is a way for host tissue to defend itself against tumor growth. Hence treatment strategies that are based on immunomodulation are on the rise. Conventional cytostatic drugs such as the anthracycline doxorubicin can also activate immune cell functions of macrophages and natural killer cells. In addition, cytotoxicity of doxorubicin can be enhanced by combining this drug with the cytokine IFN-alpha. Although doxorubicin is one of the most applied cytostatics, the molecular mechanisms of its immunomodulation ability are not investigated thoroughly. In microarray analyses of HeLa cells, a set of 19 genes related to interferon signaling was significantly overrepresented among genes regulated by doxorubicin exposure including STAT-1, -2, IRF9, NMI, and caspase 1. Regulation of these genes by doxorubicin was verified with Real-Time PCR and immunoblotting. An enhanced secretion of IFN-alpha was observed when HeLa cells were exposed to doxorubicin as compared to untreated cells. IFN-alpha neutralizing antibodies and inhibitors of JAK-STAT signaling (ATA and AG490) significantly abolished doxorubicin-stimulated expression of interferon signaling-related genes. Furthermore, inhibition of JAK-STAT signaling significantly reduced doxorubicin induced caspase 3 activation and desensitized HeLa cells to doxorubicin cytotoxicity. In conclusion, we demonstrate that doxorubicin induces interferon-responsive genes via IFN-alpha-JAK-STAT1 signaling and that this pathway is relevant for doxorubicin’s cytotoxicity in HeLa cells. As immunomodulation is a promising strategy in anticancer treatment, this novel mode of action of doxorubicin may help to further improve the use of this drug among different types of anticancer treatment strategies. |
| 56 | GSE42802 |
Profile | We used microarrays to determine which genes are upregulated by IFNbeta stimulation in 293T cells. |
| 57 | GSE23627 |
Profile | This study investigates the molecular signatures that drive Renal Cell Carcinoma (RCC) metastatic conversion using the metastatic (LM2) and non-metastatic (SN12C) RCC cell lines. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. |
| 58 | GSE25724 |
Profile | We performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples. |
| 59 | GSE10746 |
Profile | Chemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis a dose-limiting side effect for effective cancer treatment. We used whole genome gene expression analysis to identify cellular damage to the mucosal tissue occuring two days post induction chemotherapy and identified gene expression patterns that may or may not be predictive of oral mucositis. Keywords: Treatment effect |
| 60 | GSE16354 |
Profile | Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The effects of KSHV infection of both LEC and BEC were assayed using Affymetrix hgu133plus2 chips at 72 hours post infection. |
| 61 | GSE40611 |
Profile | Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Here we use Affymetrix U133 plus 2.0 microarray gene expression data from human parotid tissue. Parotid gland tissues were harvested from 17 pSS and 14 14 non-pSS sicca patients and 18 controls. The data were used in the following article: Nazmul-Hossain ANM Pollard RPE, Kroese FGM, Vissink A, Kallenberg CGM, Spijkervet FKL, Bootsma H, Michie SA, Gorr SU, Peck AB, Cai C, Zhou H, Horvath S, Wong DTW (2012) Systems Analysis of Primary Sjögren’s Syndrome Pathogenesis in Salivary Glands: Comparative Pathways and Molecular Events in Humans and a Mouse Model. |
| 62 | GSE10040 |
Profile | We performed microarray to compare gene expression patterns of PBMC treated with rATG or hATG. Fold changes were compared using 2-way ANOVA tests for untreated rATG- and hATG-treated PBMC. In PBMC treated with 10 ug/mL rATG, compared with untreated PBMC, 478 genes showed up-regulation, and 341 genes showed down-regulation at 24 hours using 10% FDR and 2-fold change cutoff. Immediately striking was that 10 ug/mL hATG had affected many fewer genes than did rATG: only 3 genes were up-regulated and 6 genes were down-regulated at 24 hours in hATG-treated PBMC. When we compared rATG with hATG, rATG induced up-regulation of 268 genes and down-regulation of 95 genes. These genes belong to the categories of immune response (64 genes), cytokine-cytokine receptor interaction (36 genes), regulation of cell proliferation (24 genes), cell cycle (23 genes), cell growth (8 genes), apoptosis (7 genes), and others. Keywords: different treatment |
| 63 | GSE16097 |
Profile | Gene silencing via heterochromatin formation plays a major role in cell differentiation and maintenance of homeostasis. Here we report the identification and characterization of a novel heterochromatinization factor in vertebrates, Bromo Adjacent Homology Domain-containing protein 1 (BAHD1). BAHD1 interacts with HP1, MBD1, HDAC5 and with several transcription factors. Through electron and immunofluorescence microscopy studies, we show that BAHD1 overexpression directs HP1 to specific nuclear sites and promotes formation of large heterochromatic domains, which lack acetyl histone H3 and are enriched in H3 trimethylated at lysine 27. Furthermore, ectopically expressed BAHD1 colocalizes with the heterochromatic X inactive chromosome. As highlighted by whole genome microarray analysis of BAHD1 knock down cells, BAHD1 represses several proliferation and survival genes and in particular, the insulin-like growth factor II gene (IGF2). BAHD1 specifically binds the CpG-rich P3 promoter of IGF2. This region contains DNA binding sequences for the transcription factor SP1, with which BAHD1 co-immunoprecipitates. Collectively, these findings provide evidence that BAHD1 acts as a silencer by recruiting proteins that coordinate heterochromatin assembly at specific sites in the genome. We used microarrays to identify BAHD1 gene targets. We compared the transcriptome profile of BAHD1 depleted cells with siRNA to that of cells treated with control siRNA. |
| 64 | GSE13274 |
Profile | As an oncogene use of HER2 vaccines in humans requires the development of HER2 immunotherapies with maximal immunologic potential, but minimal oncologic potential. To address these issues, we developed a recombinant adenoviral vector expressing a mutated HER2 inactivated for kinase function (Ad-HER2-ki). Ad-HER2-ki was highly expressed, but non-phosphorylated and elicited minimal transcription dysregulation in primary cells. In contrast, Ad-HER2-wt elicited a strong oncogenic signature associated with tumorigenesis. |
| 65 | GSE5058 |
Profile | Upregulation of Expression of the Ubiquitin Carboxyl Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers The microarray data deposited here is from 39 HG-U133 Plus 2.0 GeneChips from 12 normal non-smokers, 12 phenotypic normal smokers, 9 Early COPD and 6 COPD individuals, all small airways, all small airway. A subset of these samples have been already submitted under GEO Accession Number GSE 4498. These are: 12 non-smokers samples (GSM101095-GSM101106) and 10 smoker samples (GSM101107-GSM101116). These 22 samples that are also in GSE4498 were described in Harvey, B-G; Heguy, A.; Leopold, P.L.; Carolan, B.; Ferris, B. and Crystal R.G. Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking. J. Mol. Med (in press). These data are part of a study aimed at understanding how cigarette smoking modifies neuroendocrine cells, in which microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals (normal nonsmokers, normal smokers, smokers with early COPD and smokers with established COPD). Of 11 genes considered to be neuroendocrine cell-specific, only ubiquitin C-terminal hydrolase L1(UCHL1), a member of the ubiquitin proteasome pathway, was consistently upregulated in smokers compared to nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemistry of bronchial biopsies of smokers compared to nonsmokers. Interestingly, however, while UCHL1 expression was present only in neuroendocrine cells of the airway epithelium in nonsmokers, UCHL1 expression was also expressed in ciliated epithelial cells in smokers, an intriguing observation in light of recent observations that ciliated cells can are capable of transdifferentiating to other airway epithelium. In the context that UCHL1 is involved in the degradation of unwanted, misfolded or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy. Keywords: non-smokers vs phenotypic normal smokers, smokers with early COPD, and smokers with COPD |
| 66 | GSE17551 |
Profile | Pirin (PIR) is a putative transcriptional regulator abundantly expressed in melanocytes and in a subset of primary and metastatic melanomas. Ablation of PIR in the melanoma cell lines results in induction of a senescence-like phenotype. Keywords: Transcriptional regulation knock-down using siRNA |
| 67 | GSE22842 |
Profile | Expression analysis of wild-type SAOS cells and SAOS cells transiently transfected with RB SMYD2, or RB and SMYD2. |
| 68 | GSE17540 |
Profile | Identification of genes involved in lumen formation: gene chip analysis was performed on mRNA isolated from both wild type and T457AS459A mutated CEACAM1-4S transfected MCF7 cells grown in Matrigel |
| 69 | GSE35711 |
Profile | The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found between unrelated healthy controls and non-diabetic cystic fibrosis patients possessing Pseudomonas aeruginosa pulmonary tract infection. |
| 70 | GSE44029 |
Profile | we performed genome-wide screening using SW480 cells with Gankyrin knockdown on an Affymetrix gene expression array to identify the transcriptional targets of Gankyrin |
| 71 | GSE12657 |
Profile | We used microarrays to determine the gene expression profile of different types of glioma Keywords: Disease state analysis |
| 72 | GSE13811 |
Profile | In the marrow and lymphatic tissues chronic lymphocytic leukemia (CLL) cells interact with accessory cells that constitute the leukemia microenvironment. In lymphatic tissues, CLL cells are interspersed with CD68+ nurselike cells (NLC) and T cells. However, the mechanism regulating co-localization of CLL cells and these accessory cells are largely unknown. To dissect the molecular cross-talk between CLL and NLC, we profiled the gene expression of CD19-purified CLL cells before and after co-culture with NLC. NLC co-culture induced high-level expression of B cell maturation antigen (BCMA) and two chemoattractants (CCL3, CCL4) by CLL cells. Supernatants from CLL-NLC co-cultures revealed high CCL3/CCL4 protein levels. B cell receptor triggering also induced a robust induction of CCL3 and CCL4 expression by CLL cells, which was almost completely abrogated by a specific Syc inhibitor, R406. High CCL3 and CCL4 plasma levels in CLL patients suggest that activation of this pathway plays a role in vivo. These studies reveal a novel mechanism of cross-talk between CLL cells and their microenvironment, namely the secretion of two T cell chemokines by CLL-NLC interaction and in response to BCR stimulation. Through these chemokines, CLL cells can recruit accessory cells, and thereby actively create a microenvironment that favors their growth and survival. |
| 73 | GSE18696 |
Profile | Specific vulnerability of neurons in the human entorhinal cortex has been associated with the onset of disease. Gene expression is analyzed to define the molecular characteristic of those neurons. |
| 74 | GSE9150 |
Profile | Response to allergen was studied in epithelial cells derived from allergic pantients and from healthy controls. Cells were cultured after isolation from a nasal biopsy. Cells were exposed to Housed dust mite or vessel (saline) Microarray data was analysed using bioinformatics and biostaistics. We conclude that a marked difference in basal expression and in response to hous dust mite exists Keywords: cellular response to allergen |
| 75 | GSE44238 |
Profile | To establish a robust cellular model system for screening genes associated with cell invasion we over-expressed the oncogenic translocated promoter region (Tpr)-MET proteins in SCC23 cells (SCC23/MET). Using a functional siRNA screen, we identified that the histone demethylase KDM4A played a critical role in the invasive growth and metastasis of SCC mediated by the Oncogenic MET. To investigate the molecular mechanism through which KDM4A inhibit the tumor cell invasion, we knock-down KDM4A in SCC23/MET cell and performed a gene microarray to examine which genes may be regulaged by kDM4A. |
| 76 | GSE14286 |
Profile | Mixed-lineage leukemias represent about 3-5% of acute leukemias occurring in patients of all ages and comprise several different subtypes (biphenotypic bilineal, and lineage switch). The optimal therapeutic approach to these cases, especially in pediatric patients, has not been defined. We used microarrays to detail the gene expression of pediatric patients with biophenotypic leukemia. Keywords: Patient sample accumulation |
| 77 | GSE23371 |
Profile | Little is known about the early transcriptional events in innate immune signaling in immature and tolerogenic monocyte-derived dendritic cells (DCs) the professional antigen-presenting cells of our immune system. TLR ligands usually induce a proinflammatory transcriptional response, whereas IL10 and/or dexamethasone induce a more tolerogenic phenotype. We used Affymetrix microarrays to obtain detailed information underlying pro- and anti-inflammatory transcriptional responsesand transcriptional networks in DCs |
| 78 | GSE8607 |
Profile | Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1 pT2, pT3) and in 3 normal testes. Keywords: ordered |
| 79 | GSE36287 |
Profile | The clinical features of psoriasis characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin. |
| 80 | GSE24506 |
Profile | Introduction: microRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression and may play a causal role in invasive breast cancer. Since many genetic aberrations of invasive disease are detectable in earlier stages we hypothesized that miRNA expression dysregulation and the predicted changes in gene expression would also be found in early breast neoplasias. Methods: Expression profiling of 365 miRNAs by RT-qPCR was combined with laser-capture microdissection to obtain an epithelial specific miRNA expression signature of normal breast epithelium (n=9) and of paired samples of histologically normal epithelium (HN) and ductal carcinoma in situ (DCIS) (n=16). To determine how miRNAs may control the expression of co-dysregulated mRNAs we also performed gene expression microarray analysis in the same paired HN and DCIS samples and integrated this with miRNA-target prediction. We further validated several target pairs by modulating the expression levels of miRNAs in MCF7 cells and measured the expression of target mRNAs and proteins. Results: Thirty-five miRNAs were aberrantly expressed between RM, HN and DCIS. Twenty-nine miRNAs and 420 mRNAs were aberrantly expressed between HN and DCIS. Combining these two datasets with miRNA-target prediction we identified two established target pairs (miR-195:CCND1 and miR-21:NFIB) and tested several novel miRNA:mRNA target pairs. Over-expression of the putative tumor-suppressor miR-125b, under-expressed in DCIS, repressed the expression of MEMO1, which is required for ErbB2-driven cell motility (also a target of miR-125b); and NRIP1/RIP140, which modulates the transcriptional activity of the estrogen receptor. Knockdown of the putative oncogenic miRNAs miR-182 and miR-183, both highly over-expressed in DCIS, increased the expression of CBX7 (which regulates E-cadherin expression), DOK4, NMT2, and EGR1. Augmentation of CBX7 by knockdown of miR-182 expression, in turn, positively regulated the expression of E-cadherin, a key protein involved in maintaining normal epithelial cell morphology which is commonly lost during neoplastic progression. Conclusions: These data provide the first miRNA expression profile of normal breast epithelium and of pre-invasive breast carcinoma. Further, we demonstrate that altered miRNA expression can modulate gene expression changes that characterize these early cancers. We conclude that miRNA dysregulation likely plays a substantial role in early breast cancer development. |
| 81 | GSE40971 |
Profile | We studied transcriptional changes by Affymetrix human microarrays in DLBCL cell lines as a result of treatment with GSK126 a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 In eukaryotes, epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations. Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma. |
| 82 | GSE11854 |
Profile | Scoliosis is a common disorder affecting one out of every twenty females. Some forms of scoliosis are congenital, resulting from disruptions in early spinal development. The spinal column is patterned during a cycling process called somitogenesis, and is the first musculoskeletal structure formed during development. Genes in the notch signaling pathway regulate somitogenesis, and display oscillatory expression in synchrony with somite formation. During somitogenesis, oscillatory expression of genes in the notch and wnt signaling pathways plays a key role in regulating segmentation. These oscillations in expression levels are elements of a species-specific developmental mechanism. The periodicity and components of the human clock have recently been described by our group (William et al., Dev Biol, 2007). In that publication, we showed that a human mesenchymal stem/stromal cell (MSC) model can be induced to display oscillatory gene expression, including known cycling genes such as HES1 that displayed a period of 5 hours. We also observed cycling of Hes1 expression in mouse C2C12 myoblasts with a period of 2 hours, consistent with previous in vitro and embryonic studies. Furthermore, we used microarray and quantitative PCR (Q-PCR) analysis to identify additional genes that display oscillatory expression both in vitro and in mouse embryos. We confirmed oscillatory expression of the notch pathway gene Maml3 and the wnt pathway gene Nkd2 by whole mount in situ hybridization analysis and Q-PCR. Studies in mouse cell lines, including fibroblasts and PC12 neuronal cells, by R. Kageyema (Kyoto University, Hirata et al., Science, 2002) have shown that a number of mouse cell types can be synchronized to display oscillatory expression. In this study, we extend our analysis of human cells to human primary fibroblasts. Developing an in vitro model of somitogenesis using human mesenchymal stem cells and fibroblasts a. Induce cycling gene expression in human mesenchymal stem cells (MSC) and fibroblasts and identify oscillatory genes (using Affymetrix U133 GeneChips®). Compare lists of oscillatory genes identified in these two human cell types. b. Characterize and validate mouse homologues of oscillatory genes for expression during somitogenesis. Using notch and wnt pathway mutants and cultured half embryos, determine if these oscillatory genes also display cycling expression during somitogenesis. We hypothesized that human fibroblasts could be synchronized to display oscillatory expression of notch and wnt pathway genes, including the marker gene HES1. Preliminary quantitative analysis by Taqman-based Real-Time PCR for these samples confirms that HES1 expression displays oscillatory expression. Homo sapiens fibroblasts were maintained in culture medium (DMEM high glucose with 10% fetal bovine serum, FBS), which was replaced twice weekly. The cells were then seeded at a density of 6,000-10,000 cells/cm2 and expanded in DMEM high glucose with 10% FBS. After 5-7 days of incubation at 37C in a humidified atmosphere containing 5% carbon dioxide, cells were detached with 0.05% trypsin for 2 minutes at confluency. Cells were synchronized using low serum treatment, which has been described previously for Hes1 (Hirata et al., 2002). Cell culture synchronization is required to assay oscillatory expression levels, otherwise the oscillations of individual cells would be out of phase and cancel one another. Synchronized cells will gradually desynchronize, leading to diminished oscillatory amplitude. Briefly, synchronization was carried out as follows: T-25 cm flasks were set up in parallel. These cells were grown to 90% confluence in DMEM supplemented with 10% FBS (UCB-MSC), then incubated in DMEM with only 0.2% FBS for 24 hours, and returned to DMEM supplemented with FBS. Samples were collected at 1 hr. intervals from 0 to 12 hours. In addition, an unsynchronized cell culture was sampled. Total RNA was isolated from cells in culture using the RNeasy Mini Kit (Qiagen) and quantitated using a Nanodrop 2000. Keywords: time-course |
| 83 | GSE34309 |
Profile | Although not an affected cell type skin fibroblasts from individuals with CC-ALD, an early onset X-linked neurological disorder, show defects in very long chain fatty acid (VLCFA) metabolism that provide the basis for clinical diagnostic tests. Skin fibroblasts from CC-ALD patients can be reprogrammed into iPS cells with all the hallmark properties of pluripotency. The iPS cell phenotypes may reflect the tissue-specificity of the lipid metabolic defects found in CC-ALD patients. We report the gene expression profiles of fibroblasts and fibroblast-reprogrammed iPSCs from childhood cerebral adrenoleukodystrophy patients and healthy controls |
| 84 | GSE48046 |
Profile | Early immature T-cell acute lymphoblastic leukemias (T-ALLs) account for about 5-10% of pediatric T-ALLs and are associated with poor prognosis. However the genetic defects that drive the biology of these tumors remain largely unknown. Analysis of microarray gene expression signatures in adult T-ALL demonstrated a high prevalence of early immature leukemias and revealed a close relationship between these tumors and myeloid leukemias. Consistently, adult immature T- ALLs showed characteristic mutations in myeloid specific oncogenes and tumor suppressors including IDH1, IDH2, DNMT3A, FLT3 and NRAS. Moreover, we identified ETV6 mutations as a novel genetic lesion uniquely present in immature adult T-ALL. All together, our results demonstrate that early immature adult T- ALL represents a heterogeneous category of leukemias characterized by the presence of overlapping myeloid and T-ALL characteristics and highlight the role of ETV6 mutations in these tumors. |
| 85 | GSE27316 |
Profile | Double-stranded RNA (dsRNA) can enter different pathways in mammalian cells including sequence-specific RNA interference, sequence-independent interferon response and editing by adenosine deaminases. To assess the potential of expressed dsRNA to induce interferon stimulated genes in somatic cells, we performed microarray analysis of HEK293 and HeLa cells transfected with a MosIR plasmid expressing an mRNA with a long inverted repeat structure in its 3’UTR (MosIR) or with a parental MosIR plasmid (without inverted repeat) as a control. Clustering analysis based on differentially expressed genes suggested that there was no common transcriptome signature in cells expressing dsRNA. Overall, the number of genes with altered expression upon transfection of the MosIR plasmid was rather small and only 19 probe sets, corresponding to 17 genes, were changed more than two-fold in both cell lines. |
| 86 | GSE12396 |
Profile | Although a considerable number of reports indicate an involvement of the Hox-A10 gene in the molecular control of hematopoiesis the conclusions of such studies are quite controversial since they support, in some cases, a role in the stimulation of stem cell self-renewal and myeloid progenitor expansion while, in others, implicate this transcription factor in the induction of monocyte - macrophage differentiation. To clarify this issue we analyzed the biological effects and the transcriptome changes determined in human primary CD34+ hematopoietic progenitors by retroviral transduction of a full length Hox-A10 cDNA. The results obtained clearly indicated that this homeogene is an inducer of monocyte differentiation, at least partly acting through the up-regulation of MafB gene, recently identified as master regulator of such maturation pathway. By using a combined approach based on computational analysis, EMSA experiments and luciferase assays, we were able to demonstrate the presence of a Hox-A10 binding site in the promoter region of the MafB gene, which suggested the likely molecular mechanism underlying the observed effect. Interestingly, stimulation of the same cells with the Vitamin D3 monocyte differentiation inducer resulted in a clear increase of Hox-A10 and MafB transcripts, indicating the existence of a precise transactivation cascade involving VDR, Hox-A10 and MafB transcription factors. Altogether these data allow to conclude that the Vitamin D3 / Hox-A10 pathway supports MafB function during the induction of monocyte differentiation. |
| 87 | GSE14000 |
Profile | Dendritic cells (DCs) are the sentinels of the mammalian immune system and they undergo a complex maturation process mediated by activation upon pathogen detection. Recent studies described the analysis of activated DCs by transcriptional profiling but translation regulation was never taken in account. Therefore, the nature of the mRNAs being translated at various stages of DC activation was determined with the help of translational profiling, which is the sucrose gradient fractionation of polysomal-bound mRNAs combined to microarrays analysis. Total and polysomal-bound mRNA populations were compared in immature (0h) and LPS-stimulated (4h and 16h) human monocyte-derived DCs with the help of Affymetrix microarrays. Biostatistical analysis indicated that 296 mRNA molecules are translationally regulated during DC-activation. The most abundant biological process among the regulated mRNAs was protein biosynthesis, indicating the existence of a negative feedback loop regulating translation. Interestingly, a cluster of 17 ribosomal proteins were part of the regulated mRNAs, indicating that translation may be fine-tuned by particular components of the translational machinery. Our observations highlight the importance of translation regulation during the immune response, and may favour the identification of novel gene clusters or protein networks relevant for immunity. Our study also provides information on the possible absence of correlation between gene expression and real protein production in DCs. |
| 88 | GSE16191 |
Profile | RNA was isolated from testicular biopsies of cryptorchid boys. Gene expression profiles for these samples were investigated using Affymetrix arrays |
| 89 | GSE22366 |
Profile | Gene expression profiling was performed on primary human erythroid progenitor cells expressing a control shRNA (luciferase) two different HDAC1 shRNAs, and two different HDAC2 shRNAs. The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a novel bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease. |
| 90 | GSE18811 |
Profile | The retinal pigment epithelium (RPE) is a polarized cell layer that is critical for photoreceptor function and survival. It’s unique relationship to the photoreceptors and its specific physiology makes the RPE a critical determinant of human vision. Therefore we performed global expression profiling of native and cultured human fetal and adult RPE and determined a unique set of highly-expressed genes (called the “signature” set) by comparing the observed RPE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues. |
| 91 | GSE24154 |
Profile | Nasopharyngeal carcinoma (NPC) is known for its high metastatic potential. From genomic expression profiles comparing clones derived from the NPC cell line CNE-2 serglycin (SRGN) was identified as one of the most up-regulated genes in the high-metastasis clone. Serglycin protein was secreted by the high-metastasis clone, but not by any of the low-metastasis clones. Suppression of serglycin by shRNA diminished serglycin secretion and subsequently inhibited the migration and invasion of high-metastasis clone, and also reduced its metastasis rate in vivo. Overexpression of serglycin in low-metastasis cells resulted in an increased metastasis rate in vivo. Moreover, secreted serglycin promoted cellular motility in the wild-type low-metastasis cells. Interestingly, suppression of serglycin reduced the protein level of vimentin but did not influence the level of E-cadherin in high-metastasis clone. Proliferation was not influenced by serglycin in both high-and low-metastasis clones. Clinically, serglycin expression was significantly elevated in liver metastases from NPC relative to its expression in primary tumors. The prognostic value of serglycin was evaluated by immunohistochemical staining of tissue microarrays of NPC tissues from 263 patients, followed by multivariate analyses. A high level of serglycin expression in primary NPC was found to be an independent unfavorable indicator for distant-metastasis-free survival and disease-free survival. In summary, serglycin regulates NPC metastasis via autocrine and paracrine means without influencing proliferation, and it serves as a prognostic indicator of metastasis-free survival and disease-free survival for NPC patients. Keywords: Gene Expression experiment |
| 92 | GSE40968 |
Profile | ACSL4 expression appears to be inversely associated with steroid hormone and growth factor receptor expression in breast cancer and positively correlated with an aggressive breast cancer phenotype. Neither MCF-7 nor SKBr3 cells normally express ACSL4 and when manipulated to do so, develop basal-like characteristics, including increased proliferation, migration and anchorage independent growth. We used an Affymetrix array platform to assess changes in individual gene expression as a function of conditional and stable expression of ACSL4 in MCF-7 and SKBr3 cells. |
| 93 | GSE9773 |
Profile | Invasion of cytotrophoblasts into uterine tissues is essential for placental development. To identify molecules regulating trophoblast invasion mRNA signatures of purified villous (CTB, poor invasiveness) and extravillous (EVT, high invasiveness) trophoblasts isolated from first trimester human placentae and villous explant cultures, respectively, were compared using GeneChip analyses yielding 991 invasion/migration related transcripts. Several genes involved in physiological and pathologic cell invasion, including ADAM-12,-19,-28 as well as Spondin-2, were upregulated in EVT. Pathway prediction analyses identified several functional modules associated with either the invasive or the non-invasive trophoblast phenotype. One of the genes which were downregulated in the invasive mRNA pool, heme oxygenase-1 (HO-1), was selected for functional analyses. Real-time PCR analyses, Western blottting, and immunofluorescene of first trimester placentae and differentiating villous explant cultures demonstrated downregulation of HO-1 in invasive EVT as compared to CTB. Modulation of HO-1 expression in loss-of as well as gain-of function cell models (BeWo and HTR8/SVneo, respectively) demonstrated an inverse relationship of HO-1 expression with trophoblast migration in transwell and wound healing assays. Importantly, HO-1 expression led to an increase in protein levels and activity of the nuclear hormone receptor PPARgamma. Pharmacological inhibition of PPARgamma abrogated the inhibitory effects of HO-1 on trophoblast migration. Collectively, our results demonstrate that gene expression profiling of EVT and CTB can be used to unravel novel regulators of cell invasion. Accordingly, we identify heme oxygenase-1 as a negative regulator of trophoblast motility acting via upregulation of PPARgamma. |
| 94 | GSE42058 |
Profile | CD11c+ Myeloid Dendritic Cells (mDCs) were isolated from the peripheral blood mononuclear cells (PBMCs) of HIV uninfected and HIV infected subjects. The expression of CD11c+ mDCs was accessed to determine how HIV infection may play a role on the expression profiles of these cells. mDCs are known to play a role in antigen presentation and thus are pivotal in immune sensing and priming of the adaptive immune response. We wanted to see if the change in immune system function during chronic HIV infection may be due to defects in this cell subtype. We used microarray analysis to detail the global program of gene expression underlying changes in mDC function during HIV infection. |
| 95 | GSE28305 |
Profile | Analysis of MDA-MB-453 breast cancer cells treated with the androgen 5a-dihydrotestosterone (DHT) for 6h 16h and 48h to define the genes that are differentially regulated in response to DHT. |
| 96 | GSE12200 |
Profile | Therapies targeting the androgen receptor are critical for treatment of hormone refractory prostate cancer. We have previously demonstrated that Ebp1 a protein isolated by its ability to bind ErbB3, is a downstream effector of heregulin activated pathways and an AR corepressor. As Ebp1 is decreased in preclinical models of hormone refractory prostate cancer, we studied the ability of Ebp1 to mitigate the hormone refractory phenotype. As we previously found that Ebp1 affected the expression of some androgen receptor target genes, we sought to determine a full spectrum of genes changed using an unbiased appraoch by microarry analysis. |
| 97 | GSE40464 |
Profile | Inflammatory breast cancer (IBC) is the most aggressive type of advanced breast cancer and is associated with a poor prognosis. We have developed a new model of IBC derivated from the pleural effusion of a 49-year-old woman with metastatic secondary IBC. FC-IBC02 tumor cells were isolated from the pleural effusion and cultured under non-adherent conditions resulting in the formation of spheroids or mammospheres. FC-IBC02 are triple negative (estrogen receptor negative, progesterone receptor negative and ErbB2 negative) and strongly positive for E-cadherin, beta-catenin and vimentin. FC-IBC02 cells developed breast tumors when they were injected into the mammary fat pad of SCID mice and characteristic tumor emboli were detected. Breast tumor xenografts were poorly differentiated triple negative carcinomas and all injected mice developed metastasis in the lungs and lymph nodes. These IBC tumor cells showed genomic alterations in all chromosomes, with the gains/amplifications more common than the deletions/losses. Duplicated regions were on 1q, 2p, 3q, 8q and 18p and chromosomes 7 and 9. The 8q chromosome arm where the MYC oncogene resides was amplified up to seven fold. Chromothripsis (local chromosome shattering) was observed on chromosome 11q and losses were found on 8p, 11q, 16q and 17p (location of TP53). FC-IBC-02 cells expressed the stem cell marker CD44, EpCAM and strongly expressed EGFR and ALK. In summary, this novel preclinical model demonstrated that IBC is a disease enriched for highly tumorigenic cells which harbor a stem cell phenotype. This IBC model is ideal for the study of the metastatic process and to evaluate targeting therapeutic modalities. |
| 98 | GSE35603 |
Profile | Mounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification. All function codes related to this project could be accessed at the supplementary website. |
| 99 | GSE8056 |
Profile | Thermal injury incites inflammatory responses that often transcend the local environment and lead to structural deficiencies in skin that give way to scar formation. We hypothesized that extensive perturbations within burned skin following thermal insult and during subsequent events of wound repair induce vast alterations in gene expression that likely serve as a wound and systemic healing deterrent. A high-throughput microarray experiment was designed to analyze genetic expression patterns and identify potential genes to target for therapeutic augmentation or silencing. The study compares gene expression from burn wound margins at various times following thermal injury to expression observed in normal skin. Utilizing this design we report that the totality of gene expression alterations is indeed enormous. Further, we observed that the differential expression of many inflammatory and immune response genes appear to be continually up-regulated in burn wound margins seven days or more after initial thermal insult. As it is well established that the inflammatory process must abate for wound healing to proceed, the finding of ongoing local inflammation is cause for further investigation. To our knowledge, this is the first report of the gene expression alterations induced by thermal injury of human skin. As such, it provides a wealth of data to mine with the ultimate goal of better understanding the local pathophysiologic changes at the site of thermal injury that not only affect wound healing capacity, but may also contribute to systemic derangements within the burn patient. Keywords: time course, disease state analysis |
| 100 | GSE45758 |
Profile | Analysis of mRNA profiles after MEK1/2 inhibition in human pancreatic cancer cell lines reveals pathways involved in drug sensitivity. We used microarrays to find gene expression patterns associated with drug response and also identified genes regulated by the MAP kinase pathway |
| 101 | GSE9118 |
Profile | Malignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine. Keywords: Expression changes following pharmacological reversal of epigenetic silencing |
| 102 | GSE5579 |
Profile | Lymphatic endothelial cells were grown under normoxia hypoxia (1% 0xygen) and conditioned medio from NSLCN growth under normoxia or hypoxia. Gene expression was measured and comparition between samples performed Keywords: Comparative genomic hybridization |
| 103 | GSE28019 |
Profile | 24 standard human Neuroblastoma Cell lines were profiled without applying any transfections in order to measure the expression profiles. Keywords: cell line neuroblastoma, mRNA profiling |
| 104 | GSE14062 |
Profile | Gene expression analysis identified a MLL translocation-specific signature of differentially expressed genes discriminating ALL and AML with and without MLL rearrangements. Gene expression signatures of acute lymphoblastic and myeloblastic leukemia samples with and without MLL rearrangements were analyzed using paired supervised analyses. |
| 105 | GSE16844 |
Profile | Neutrophil recruitment is pivotal to host defense against microbial infection but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was 'cell movement' including E-selectin, which was coordinately regulated with IL-1beta. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1beta, which together with IFN-gamma, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease. |
| 106 | GSE2361 |
Profile | We performed expression profiling of 36 types of normal human tissues and identified 2503 tissue-specific genes. We then systematically studied the expression of these genes in cancers by re-analyzing a large collection of published DNA microarray datasets. Our study shows that integration of each gene's breadth of expression (BOE) in normal tissues is important for biological interpretation of the expression profiles of cancers in terms of tumor differentiation, cell lineage and metastasis. Twenty five total RNA specimens were purchased from Clontech (Palo Alto, CA), Ambion (Austin, TX) and Strategene (La Jolla, CA). We tried to cover as many tissue types as possible by using pooled RNA samples. In order to define breadth-of-expression (BOE) accurately at a reasonable cost, we tried to cover as many tissue types as possible by using pooled RNA samples. Each specimen represents a human organ. We used RNA samples pooled from 2 to 84 donors to avoid differences at the individual level. Keywords = Normal human tissues Keywords = Tissue-specificity Detailed sample information and Affymetrix .CEL files are available at http://www.genome.rcast.u-tokyo.ac.jp/normal/ Publication:Ge X et al., Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-141. PMID: 15950434 Keywords: other |
| 107 | GSE25269 |
Profile | Morphogenesis of epithelial tissues relies on the precise developmental control of cell polarity and architecture. In the early Drosophila embryo the primary epithelium forms during cellularisation, following a tightly controlled genetic programme where specific sets of genes are up-regulated. Some of them, for instance, control membrane invagination between the nuclei anchored at the apical surface of the syncytium. |
| 108 | GSE18349 |
Profile | Human Neural progenitor cells have been found to have karyotypic abnormalities. In this study we explored the gene changes between hNPCs that are karyotypically normal and hNPCs with a trisomy of chromosome 7. We used Affymetrix GeneChips to study gene expression changes between karyotypically normal hNPCs and trisomy 7 hNPCs. |
| 109 | GSE9624 |
Profile | Characterization of genes associated with adipose tissue is key to understanding the pathogenesis of obesity and developing treatments for this disorder. Differential gene expression in the adipose tissue has been described in adulthood but none studies have been developed on childhood. The purpose of this study was to compare gene expression in omental adipose tissue from obese prepubertal and normal weight children. We selected 5 obese (BMI adjusted for age and sex z score >2) and 6 normal weight children. RNA was extracted from omental adipose tissue biopsies and cRNA was hybridizated on the human genome U133 Plus 2.0 Arrays (Affymetrix®). Microarray experiments were performed for each sample and selected group of gene expression values were confirmed with real-time RT-PCR in 10 obese and 10 normal weigth prepubertal children. 1276 genes were found to be differentially expressed at P<0.05. Of those differential genes, 201 were upregulated (Fc>2) and 42 were downregulated (Fc<-2). Genes involved in metabolic and signalling pathways were altered in childhood obesity. Keywords: disease state analysis |
| 110 | GSE13639 |
Profile | Anaysis of mRNA changes in HeLa cells following knockdown of Drosha or DGCR8. Drosha is a nuclear RNase III that carries out microRNA (miRNA) processing by cleaving primary microRNA transcript (pri-miRNA). DGCR8 is an essential co-factor of Drosha. Keywords: gene expression array-based (RNA / in situ oligonucleotide) |
| 111 | GSE16098 |
Profile | The Human T-cell Leukemia Virus (HTLV)-type-I non-structural protein p30 plays an important role in virus transmission and gene regulation. p30 has been documented to inhibit the export of certain viral mRNA transcripts from the nucleus to the cytoplasm. This nuclear retainment of RNA molecules essentially results in gene silencing where protein products are not produced. Considering this unique function of p30, we used microarray analysis to assess the ability of p30 to inhibit not only the regulation of transcription of cellular genes, but also the ability of p30 to regulate the export of cellular transcripts to the cytoplasm. |
| 112 | GSE16416 |
Profile | The intracellular pathogen Trypanosoma cruzi secretes an activity that blocks TGF-β-dependent induction of connective tissue growth factor (CTGF/CCN2). Here we address the mechanistic basis for T. cruzi-mediated interference of CTGF/CCN2 expression by examining host cell signaling pathways and the global inhibitory effect on TGF-β-dependent gene expression. We show that the expression of a discrete subset of TGF-β-inducible genes involved in cell proliferation, wound repair, and immune regulation are blocked by the soluble T. cruzi activity, demonstrating that this parasite-derived activity has broad, but specific effects on fibroblast gene regulation. |
| 113 | GSE7500 |
Profile | Cell-and context-specific activities of nuclear receptors may in part be due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We have shown previously that silencing of RIP140 enhances RA-induced differentiation and enhances the induction of model RA target genes in human embryonal carcinoma cells (EC). Through use of microarray technology we sought to elucidate in a de novo fashion the global role of RIP140 in RA-dependent signaling. RIP140-dependent gene expression was largely consistent with RIP140 functioning to limit RAR signaling. Few if any genes were regulated in a manner to support a role for RIP140 in “active repression”. Interestingly approximately half of the RA-dependent genes were unaffected by RIP140, suggesting that RIP140 may discriminate between different classes of RA target genes. RIP140 silencing also accelerated RA target gene activation and sensitized EC cells to low doses of RA. Together the data suggests that the RIP140-dependent RA target genes identified here may be particularly important in mediating RA-induced tumor cell differentiation. RIP140 may be an attractive target to sensitize tumor cells to retinoid-based differentiation therapy. Keywords: Drug treatment with siRNA |
| 114 | GSE39594 |
Profile | We used microarrays to detail the global gene transcription underlying T cells activation during the first 24 hours after stimulation. |
| 115 | GSE27562 |
Profile | We analyzed gene expression in human peripheral blood mononuclear cells (PBMCs) from breast cancer patients patients with benign breast abnormalities, healthy cancer-free individuals as well as patients with other types of cancer (gastrointestinal and brain cancers). |
| 116 | GSE5788 |
Profile | T-cell prolymphocytic leukemina (T-PLL) is an agressive lymphoma derived from mature T-cells which is in most cases characterized by the presence of an inv(14)(q11q32) and a characteristic pattern of secondary chromosomal abberations. We used microarrays to compare the transcriptomes of eight immunomagnetically purified CD3+ normal donor derived peripheral blood cells with five highly purified inv(14)-positive T-PLL blood samples. Keywords: desease state analysis |
| 117 | GSE19393 |
Profile | Full title: Expression data from human primary subcutaneous preadipocytes treated with glucocorticoids prior to the initiation of differentiation. Preadipocytes are continuously exposed to glucocorticoids in situ due to both steroid present in the circulatory system as well as adipose tissue specific 11βHSD1 activity. While the effects of glucocorticoids during differentiation are well studied the effect of exposure of preadipocytes to glucocorticoids prior to differentiation is unknown. We therefore treated confluent human primary preadipocytes drived from subcutaneous adipose tissue with the synthetic glucocorticoid dexamethasone for 48 hours prior to the initiation of differentiation and assessed what effect this had on their subsequent potential to differentiate. We found that pretreatment with glucocorticoids had a priming effect and resulted in increased differentiation of these preadipocytes. Furthermore, this treatment was additive to the effects of glucocorticoids during the initial phase of adipogenesis. Microarray analysis performed subsequent to the pretreatment with glucocorticoids (at the time point at which preadipocytes would have been induced to differentiate) identified glucocorticoid-responsive, candidate genes whose altered expression could mediate these effects. keywords: glucocorticoids, glucocorticoid receptor, preadipocytes, adipogenesis, human primary preadipocytes, subcutaneous, adipose tissue |
| 118 | GSE42064 |
Profile | Acute myeloid leukemia (AML) with CEBPA mutations is determined as provisional entity in the current WHO. A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported whereupon dm cases were shown to be associated with longer overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPAdm has not been assessed until now. Here, we investigated a cohort of 95 AML CEBPAdm cases for concomitant mutations. TET2 was found to be the most frequent mutation (32/94, 34.0%), followed by GATA2 (20/95, 21.0%), WT1 (13/95, 13.7%), DNMT3A (9/94, 9.6%), ASXL1 (9/95, 9.5%), NRAS (8/95, 8.4%), KRAS (3/94, 3.2%), IDH1/2 (6/95, 6.3%), FLT3-ITD (6/95, 6.3%), FLT3-TKD (2/95, 2.1%), NPM1 (2/95, 2.1%), and RUNX1 (1/94). No mutation was detected in MLL-PTD and TP53. With respect to prognostic impact, we observed that those cases harboring additional mutations in TET2 showed significant worse survival than wild-type cases (P=0.035), whereas GATA2 mutated cases showed improved survival (P=0.032). Further, using gene expression microarray analysis we identified no clear different clustering within the CEBPAdm cases with the distinct concomitant mutated genes. In conclusion, we demonstrated that 76.8% of CEBPAdm cases harbored additional alterations in other molecular markers and that CEBPA is a suitable MRD marker to control therapy. |
| 119 | GSE7904 |
Profile | bulk breast tumor RNA from patient Abstract: Sporadic basal-like cancers (BLC) are a distinct class of human breast cancers that are phenotypically similar to BRCA1-associated cancers. Like BRCA1-deficient tumors most BLC lack markers of a normal inactive X chromosome (Xi). Duplication of the active X chromosome and loss of Xi characterized almost half of BLC cases tested. Others contained biparental but nonheterochromatinized X chromosomes or gains of X chromosomal DNA. These abnormalities did not lead to a global increase in X chromosome transcription but were associated with overexpression of a small subset of X chromosomal genes. Other, equally aneuploid, but non-BLC rarely displayed these X chromosome abnormalities. These results suggest that X chromosome abnormalities contribute to the pathogenesis of BLC, both inherited and sporadic. total 62 sample incudes 43 tumor, 7 normal breast and 12 normal organelle Keywords: disease state analysis |
| 120 | GSE9599 |
Profile | Tumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis Keywords: Pharmacogenetics |
| 121 | GSE5850 |
Profile | Polycystic ovary syndrome (PCOS) the most common cause of anovulatory infertility, is characterized by increased ovarian androgen production, arrested follicle development, and is frequently associated with insulin resistance. These PCOS phenotypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss. To examine whether the perturbations in follicle growth and the intrafollicular environment affects development of the mature PCOS oocyte, genes that are differentially expressed in PCOS compared to normal oocytes were defined using microarray analysis. This analysis detected approximately 8000 transcripts. Hierarchical clustering and principal component analysis revealed differences in global gene expression profiles between normal and PCOS oocytes. 374 genes had a statistically-significant increase or decrease in mRNA abundance in PCOS oocytes. A subset of these genes was associated with chromosome alignment and segregation during mitosis and/or meiosis, suggesting that increased mRNAs for these proteins may negatively affect oocyte maturation and/or early embryonic development. Of the 374 differentially expressed genes, 68 contained putative androgen receptor, retinoic acid receptor, and/or peroxisome proliferating receptor gamma binding sites, including 9 of the genes involved in chromosome alignment and segregation. These analyses demonstrated that normal and PCOS oocytes that are morphologically indistinguishable and of high quality exhibit different gene expression profiles. Furthermore, altered mRNA levels in the PCOS oocyte may contribute to defects in meiosis and/or mitosis which might impair oocyte competence for early development and therefore contribute to poor pregnancy outcome in PCOS. Keywords: disease state analysis |
| 122 | GSE29115 |
Profile | The underlying mechanisms which are responsible and govern early haematopoietic differentiation during development are poorly understood. Gene expression comparison between pluripotent human embryonic stem cells and earliest haematopoietic progenitors may reveal novel transcripts and pathways and provide crucial insight into early haematopoietic lineage specification and development. Understanding of transcriptional cues that direct differentiation of human embryonic stem cells (hESC) to defined and functional cell types is essential for their future clinical applications. In this study we have undertaken a comparative transcriptional approach of haematopoietic progenitors derived from hESC at various stages of a feeder and serum free differentiation method and have shown that the largest transcriptional changes occur during the first four days of differentiation. Data mining based on molecular function pointed to RhoGTPase signalling as key regulator of this differentiation. Inhibition of this pathway using a chemical inhibitor (Y26732) resulted in a significant downregulation of haematopoietic progenitors throughout the differentiation window thus uncovering a previously unappreciated role for RhoGTPase signalling in differentiation of hESC to haematopoietic lineages. |
| 123 | GSE37120 |
Profile | Glioblastoma stem-like cells or their differentiated progeny were co-cultured for 48h with normal human astrocytes to detect if invasion associated genes were influenced |
| 124 | GSE12261 |
Profile | We used microarrays to detail transcriptional changes in cultured human smooth muscle cells in response to acute and chronic 2-methoxyestradiol treatment 2-ME an endogenous metabolite. of estradiol, not only exerts cytotoxic effects on cancer cells but it also protects against multiple proliferative disorders, including atherosclerosis and injury-induced intimal thickening Keywords: treatment vs. control |
| 125 | GSE9437 |
Profile | The TAP transporter is responsible for transferring cytosolic peptides into the ER where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC surface expression and alters the presented peptide pattern. Using the TAP deficient cell line LCL721.174 and its TAP expressing progenitor cell line LCL721.45 we have identified and quantified more than 160 HLA ligands, 50 out of which were presented TAP independently. Peptides which were predominantly presented on the TAP deficient LCL721.174 cell line had a decreased MHC binding affinity according to their SYFPEITHI and BIMAS score. About half of the identified TAP independently presented peptides were not derived from signal sequences and may partly be generated by the proteasome. Furthermore, we have excluded that different HLA presentation ratios were due to varying expression of the respective protein or due to changes in the antigen loading complex. Features of TAP-independently presented peptides as well as proteasomal contribution to their generation provides an insight into basic immunological mechanisms. Keywords: differential mass spectrometry, TAP independent, antigen presentation |
| 126 | GSE35712 |
Profile | The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found in pre H1N1 samples to the signature associated with active H1N1 flu. |
| 127 | GSE6907 |
Profile | From the results of gene expression analyses of HepG2 under the exposure of 23-Dimethoxy-1,4-naphthoquinone (DMNQ), N-nitrosodimethylamine (DMN), phenol and six heavy metals We showed that biological action of six heavy metals were clearly related to that of DMNQ and distinguishable from the other chemicals. These results suggest that oxidative stress is major apparent biological action of high dose heavy metals, supporting the previous reports. Keywords: other |
| 128 | GSE17354 |
Profile | Gene transfer into HSCs by gammaretroviral vectors (RV) is an effective treatment for inherited blood disorders although potentially limited by the risk of insertional mutagenesis. We evaluated the genomic impact of RV integration in T-lymphocytes from adenosine deaminase (ADA)-Severe combined immunodeficiency (SCID) patients 10 to 30 months after infusion of autologous, genetically-corrected CD34+ cells. Expression profiling on ex vivo T-cell bulk population revealed no difference with respect to healthy controls. To assess the effect of vector integration on gene expression at the single cell level, primary T-cell clones were isolated from two patients. T-cell clones harboured either one or two vector copies per cell and displayed partial to full correction of ADA expression, purine metabolism and TCR-driven functions. Analysis of retroviral integration sites (RIS) indicated a high diversity in T-cell origin, consistent with the polyclonal TCR-Vbeta repertoire. Quantitative transcript analysis of 120 genes within a 200kb-window around RIS showed modest (2.8- to 5.2-fold) disregulation of 5.8% genes in 18.6% of the T-cell clones compared to controls. Nonetheless, affected clones maintained a stable phenotype and normal functions in vitro. These results confirm that RV-mediated gene transfer for ADA-SCID is safe, and provide crucial information for the development of future gene therapy protocols. Global gene expression profiling was performed on CD4+ and CD8+ T-cell subsets purified ex vivo from three ADA-SCID patients at different times after gene therapy. The microarray analysis showed a substantial overlap with the expression patterns of T-cells from controls, indicating the absence of gross abnormalities in the development and function of T-cells derived from genetically corrected hematopoietic stem/progenitor cells. |
| 129 | GSE16798 |
Profile | Pirin (PIR) is a putative transcriptional regulator whose expression is silenced in cells bearing the AML1/ETO and PML/RAR leukemogenic fusion proteins and is significantly repressed in a large proportion of acute myeloid leukemias. PIR expression increases during in vitro myeloid differentiation of primary hematopoietic precursor cells and ablation of PIR in the U937 myelomonocytic cell line or in murine primary hematopoietic precursor cells results in impairment of terminal myeloid differentiation. Keywords: Transcriptional regulation, knock-down using shRNA |
| 130 | GSE29680 |
Profile | The hypothesis was that 6 months of dietary n-3 FA supplementation to humans affected expression of genes that might be of significance for inflammatory processes and for Alzheimer´s disease. |
| 131 | GSE4498 |
Profile | Modification of Gene Expression of the Small Airway Epithelium in Response to Cigarette Smoking The earliest morphologic evidence of changes in the airways associated with chronic cigarette smoking is in the small airways. To help understand how smoking modifies small airway structure and function we developed a strategy using fiberoptic bronchoscopy and brushing to sample the human small airway (10th-12th order) bronchial epithelium to assess gene expression (HG-133 Plus 2.0 array) in phenotypically normal smokers (n=10, 33 ± 7 pack-yr) compared to matched non-smokers (n=12). Even though the smokers were phenotypically normal, analysis of the small airway epithelium of the smokers compared to the non-smokers demonstrated up- and -down-regulation of genes in multiple categories relevant to the pathogenesis of chronic obstructive lung disease (COPD), including genes coding for cytokines/innate immunity, apoptosis, mucin, response to oxidants and xenobiotics, and general cellular processes. In the context that COPD starts in the small airways, these gene expression changes in the small airway epithelium in phenotypically normal smokers are candidates for the development of therapeutic strategies to prevent the onset of COPD. Keywords: smokers vs non-smokers |
| 132 | GSE17482 |
Profile | Identification of the molecular changes that promote viability and metastatic behavior of prostate cancer cells is critical for the development of improved therapeutic interventions for prostate cancer. Stat5a/b and Stat3 are both constitutively active in locally-confined and advanced prostate cancer and both transcription factors have been reported to be critical for the viability and growth of prostate cancer cells. We used microarrays to compare gene expression profiles regulated by Stat5a/b vs. Stat3 in human prostate cancer cells. |
| 133 | GSE22167 |
Profile | Human induced pluripotent stem (iPS) cells derived from somatic cells of patients hold great promise for modelling human diseases. Dermal fibroblasts are frequently used for reprogramming but require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Here, we report the derivation of iPS cells from multiple human blood sources including peripheral blood mononuclear cells (PBMCs) harvested by routine venipuncture. Peripheral blood-derived human iPS lines are comparable to human embryonic stem (ES) cells with respect to morphology, expression of surface antigens, activation of endogenous pluripotency genes, DNA methylation and differentiation potential. Analysis of Immunoglobulin and T-cell receptor gene rearrangement revealed that some of the PBMC iPS cells were derived from T-cells, documenting derivation of iPS cells from terminally differentiated cell types. Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture. Reprogramming from blood cells thus represents a fast, safe and efficient way of generating patient-specific iPS cells. |
| 134 | GSE1709 |
Profile | Peripheral blood leukocytes of three human donors (Donors 2 4, and 5) were isolated from blood bank buffy-coat preparations by Ficoll-Hypaque density gradient centrifugation, and T-cells were purified with high affinity negative selection human CD3+ T-cell enrichment columns. The cells were resuspended in RPMI-1640 with 10% FCS with approximately 3-8 millions cells/mL at room temperature overnight. T-cells were then either unactivated (1g 0 hr), activated (1g 4 hr) with a final concentration of 5 mg/mL Con A + 4 mg/mL anti-CD28 antibody and incubated for 4 hours at 37°C, or loaded onto a RPM rotating at 60°/s (vg). T-cells loaded on the RPM were cultured for 2 hours prior to collection or activation to allow equilibration of cells to the new environment. After incubation, 1 mL of 4 M guanidinium isothiocyanate in 750 mM sodium citrate buffer, pH 7, with N-lauroylsarcosine and beta-mercaptoethanol was added to lyse cells and stabilize RNA. Keywords: ordered |
| 135 | GSE10767 |
Profile | Background: While BMPR2 mutation strongly predisposes to pulmonary arterial hypertension (PAH) only 20% of mutation carriers develop clinical disease. This finding suggests that modifier genes contribute to FPAH clinical expression. Since modifiers are likely to be common alleles, this problem is not tractable by traditional genetic approaches. Further, examination of gene expression is complicated by confounding effects attributable to drugs and the disease process itself. Methods: To resolve these problems, B-cells were isolated, EBV-immortalized, and cultured from familial PAH patients with BMPR2 mutations, mutation positive but disease-free family members, and family members without mutation. This allows examination of differences in gene expression without drug or disease-related effects. These differences were assayed by Affymetrix array, with follow-up by quantitative RT-PCR and additional statistical analyses. Results: By gene array, we found consistent alterations in multiple pathways with known relationship to PAH, including actin organization, immune function, calcium balance, growth, and apoptosis. Selected genes were verified by quantitative RT-PCR using a larger sample set. Analysis of overrepresented gene ontology groups suggests that it is pathway-specific, not gene-specific changes that carry increased risk of disease. Conclusions: B-cell lines are a valuable and accessible tool for assaying alterations in gene expression free from drug and disease effects. Predisposition to disease within BMPR2 mutation carriers was linked to several pathways, including proliferation, GTP signaling, and stress response. Keywords: Search for modifier genes |
| 136 | GSE17129 |
Profile | Abstract. Deregulated c-MYC is found in a variety of cancers where it promotes proliferation as well as apoptosis. In many hematological malignancies enhanced NF-kB exerts prosurvival functions. Here we investigated the role of NF-kB in mouse and human c-MYC-transformed lymphomas. The NF-kB-pathway is extinguished in murine lymphoma cells and extrinsic stimuli typically inducing NF-kB activity fail to activate this pathway. Genetic activation of the NF-kB pathway induces apoptosis in these cells while inhibition of NF-kB by an IkBa superrepressor provides a selective advantage in vivo. Furthermore, in human Burkitt´s lymphoma cells we find that NF-kB activation induces apoptosis. NF-kB upregulates Fas and predisposes to Fas-induced cell death, which is caspase 8 mediated and can be prevented by CFLAR overexpression. We conclude that c-MYC overexpression sensitizes cells to NF-kB-induced apoptosis and persistent inacvtivity of NF-kB signaling is a prerequisite for MYC-mediated tumorigenesis. We could also show that low immunogenicity and Fas insensitivity of MYC driven lymphoma cells is reversed by activation of NF-kB. Our observations provide a molecular explanation for the described absence of the NF-kB signaling in Burkitt´s lymphoma and question the applicability of NF-kB inhibitors as candidates for treatment of this cancer. |
| 137 | GSE33643 |
Profile | The goal is the characterization of the off-target activity of BKM120 observed in A2058 human melanoma cell line at IC90 concentration (3.606 µM) but not at lower concentrations. Controls are BEZ235 GDC0941, showing no off-target activity. A secondary objective is the characterizations of drug effects on transcript expression with respect to a control treatment (DMSO) of those PI3K inhibitors. |
| 138 | GSE10809 |
Profile | This study aimed to understand the transcriptional networks regulating endoderm specification from HESC and therefore explored the phenotype of CA1 and CA2 HESC constitutively over-expressing SOX7 or SOX17. Cell lines were created using an inducible construct whereby clonal populations containing transgene integration are selected by Neomycin resistance without expressing of the gene of interest (NoCre controls). Transgene expression is induced via Cre-mediated recombination and selected for puromycin resistance (SOX O/E). The phenotype of the resulting cells suggests that SOX7 expressing HESC represent stable extraembryonic endoderm progenitors while SOX17 expressing HESC represent early definitive endoderm progenitors. Both in vitro and in vivo SOX7 expressing HESC are restricted to the extraembryonic endoderm lineage, while SOX17 expressing HESC demonstrate mesendodermal specificity. In vitro, SOX17 expressing HESC efficiently produce mature definitive endoderm derivatives. The molecular phenotype of the resulting SOX7 and SOX17 expressing HESC was characterized by microarray analysis Keywords: cell line comparison |
| 139 | GSE7835 |
Profile | Transcription mediated by hypoxia inducible factor (HIF-1) contributes to tumor angiogenesis and metastasis but is also involved in the activation of cell-death pathways and normal physiological processes. Given the complexity of HIF-1 signaling it could be advantageous to target a subset of HIF-1 effectors rather than the entire pathway. We compared the genome-wide effects of three molecules that each interfere with the HIF-1-DNA interaction: a polyamide targeted to the hypoxia response element (HRE) siRNA targeted to HIF-1α, and echinomycin, a DNA binding natural product with a similar but less specific sequence preference to the polyamide. The polyamide affects a subset of hypoxia-induced genes that are consistent with the binding site preferences of the polyamide. For comparison, siRNA targeted to HIF-1α and echinomycin each affect the expression of nearly every gene induced by hypoxia. Remarkably, the total number of genes affected by either polyamide or HIF-1α siRNA over a range of thresholds is comparable. The data shows how polyamides can be used to affect a subset of a pathway regulated by a transcription factor. In addition, this study offers a unique comparison of three complementary approaches towards exogenous control of endogenous gene expression. Keywords: Gene expression changes in cultured U251 cells after DFO-stimulation and various treatment conditions |
| 140 | GSE36245 |
Profile | Glioblastoma (GBM) is an incurable brain tumor carrying a dismal prognosis which displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical positions of histone H3.3 (K27, G34) in one-third of pediatric GBM. Here we show that each of these H3F3A mutations defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and are mutually exclusive with IDH1 mutation (characterizing a CpG-Island Methylator Phenotype (CIMP) subgroup). Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM (EGFR amplification, CDKN2A/B deletion) and/or known transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of OLIG1/2 and FOXG1, possibly reflecting different cellular origins. To further dissect the biological differences between epigenetic glioblastoma subgroups, we looked at the transcriptomic profiles of glioblastoma samples. |
| 141 | GSE20141 |
Profile | Genome-wide transcriptome analysis of expression changes in laser-dissected SNpc neurons from Parkinson's disease brain tissue versus control brain tissue. |
| 142 | GSE23427 |
Profile | Cholangiocarcinomac ells have bee treated with felodipine and gene expression analyzed. In order to identify genes with differential gene expression between the groups cb-f and cb-g we study 2 hybridizations on the HG-U133_Plus_2_IVT array using analysis of variance. The analysis identified 7068 genes with significant gene expression differences between the groups (p<0.01). |
| 143 | GSE7097 |
Profile | RNA expression analysis was performed to compare patterns to DNA copy number changes and sensitivity to BCL2 inhibitors. Keywords: cell line comparison |
| 144 | GSE12444 |
Profile | To identify the genes and pathways regulated by FOXF2 we investigated potential FOXF2 gene targets by microarray analyses of primary prostate stromal cells (PrSC) in which FOXF2 was knocked down by siRNA. 190 differentially expressed genes were selected, of which 104 genes were more highly expressed in PrSC cells treated with FOXF2 siRNA and 86 were more highly expressed in PRSC cells treated with negative control siRNA. |
| 145 | GSE36643 |
Profile | We FACS sorted Ras-transformed human mammary epithelial cells (HMLER cells) into GD2+ and GD2- as well as CD44high/CD24low and CD44low/Cd24highcells and comapred the four different population by array. |
| 146 | GSE38506 |
Profile | Although high mammographic density (MD) is considered one of the strongest risk factors for invasive breast cancer the genes involved in modulating this clinical feature are unknown. Histologically, areas of high MD are associated with low adipocyte content and high matrix content, both stromal phenotypes. We hypothesized that fibroblasts purified from low and high MD tissues would show gene expression differences responsible for these histologic differences. |
| 147 | GSE17480 |
Profile | Imatinib as the first-line agent of chronic myeloid leukemia (CML), is ineffective in eradicating CML stem/progenitor cells, thus unable to prevent late relapse. Here we present data indicating that fenretinide preferentially targets CD34+ CML cells and enhances the efficacy of imatinib in CML. As tested by colony forming cell assays, both number and size of total colonies derived from CD34+ CML cells were significantly reduced by fenretinide, and by combining fenretinide with imatinib. In particular, colonies derived from erythroid progenitors and those derived from more primitive pluripotent progenitor cells were highly sensitive to fenretinide/fenretinide plus immtinib. Further data showed that fenretinide was able to induce apoptosis in CD34+ CML cells which were refractory to imatinib. Through transcriptome analysis and followed by molecular validation, we further showed that apoptosis induced by fenretinide in CD34+ CML cells was mediated by complex mechanisms of stress responses, probably triggered by elevated levels of intracellular reactive oxygen species. Thus, fenretinide combines with imatinib may represent a new strategy for the treatment of CML, in which fenretinide targets primitive CD34+ CML cells whereas imatinib targets leukemic blasts. This strategy may eventually reduce the risk of relapse and probably resistant as well in CML patients. |
| 148 | GSE26541 |
Profile | The epithelial-mesenchymal transition (EMT) is an embryonic transdiffrentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression promoting metastatic dissemination. Herein, we demonstrate that EMT permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participate to the primary tumor growth long before the initiation of the invasion-metastasis cascade. |
| 149 | GSE19345 |
Profile | Our results suggest that HCMV infection disrupts the self-renewal capacity of NPCs and influences their differentiation. Whole genome expression analysis revealed many changes in cellular gene expression including downregulation of genes pertinent to the neuronal lineage. |
| 150 | GSE29437 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 151 | GSE14548 |
Profile | To better understand the role of tumor microenvironment in breast cancer progression we combined laser capture microdissection and microarray analysis to provide a comprehensive catalog of gene expression changes in both tumor and tumor-associated stroma. Keywords: cancer vs. normal |
| 152 | GSE16547 |
Profile | Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognizable by its distinctive red skin lesions. The lesions are KSHV infected spindle cells most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. Here we examine KSHVs modulation of Notch signaling using wild-type LEC cells co-cultured with DLL4 and JAG1 expressing LEC cells. |
| 153 | GSE26148 |
Profile | In these microarray experiments we characterize the gene expression of mammary epithelial cells (MCF10A cells) grown in either a traditional monolayer cell culture setting (2D) or on Matrigel, which induces single MCF10A cells to form organized acinar structures (3D). Morphogenesis of mammary epithelial cells into organized acinar structures in vitro is accompanied by widespread changes in gene expression patterns, including a substantial decrease in expression of Myc. The purpose of this study was to analyze the impact of morphogenesis and organization on gene expression with respect to changes in overall gene expression and Myc target gene expression. |
| 154 | GSE22761 |
Profile | Gene Expression of muscle tissue during microsurgical free tissue transfer was basicly studied in animal models. There was found activation of inflammatory and apoptotic cascades and of genes regulating intracellular metabolism. We used microarrays to detail the programme of gene expression in human muscle tissue which is activated during this process. |
| 155 | GSE16962 |
Profile | MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. Previously we demonstrated that miR-210 is a key player of endothelial cell (EC) response to hypoxia, modulating EC survival, migration and ability to form capillary like-structures. Moreover, the receptor tyrosine kinase ligand Ephrin-A3 was identified as one functionally relevant target. Since each miRNA regulates hundreds of mRNAs, different approaches were combined to identify new miR-210 targets: a Using target prediction software, 32 new miR-210 potential targets were identified. b The proteomic profiling of miR-210 over-expressing ECs identified 11 proteins that were specifically inhibited by miR-210, either directly or indirectly. c Affymetrix based gene expression profiles identified 51 genes that were both down-modulated by miR-210 over-expression and de-repressed when miR-210 was blocked. Surprisingly, only few genes identified either by proteomics or transcriptomics were recognized as miR-210 targets by target prediction algorithms. However, a low-stringency pairing research revealed enrichment for miR-210 putative binding sites, raising the possibility that these genes were targeted via non-canonical recognition sequences. To clarify this issue, miR-210-loaded RISC was purified by immuno-precipitation along with its mRNA targets. The presence of Ephrin-A3 mRNA in the complex validated this approach. We found that 32 potential targets were indeed enriched in miR-210-loaded RISC, and thus can be considered as genuine miR-210 targets. In keeping with this conclusion, we were able to further validate a sub-set of them by 3’UTR-reporter assays. Gene ontology analysis of the targets confirmed the known miR-210 activity in differentiation and cell cycle regulation, highlighting new functions such as involvement in RNA processing, DNA binding, development, membrane trafficking and amino acid catabolism. In conclusion, we validated a multidisciplinary approach for miRNAs target identification and indicated novel molecular mechanisms underpinning miR-210 role in EC response to hypoxia. |
| 156 | GSE31014 |
Profile | The underlying change of gene network expression of Guillain-Barre syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signalling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. |
| 157 | GSE17356 |
Profile | African-American (AA) men experience increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with potential to predispose AA men to prostate tumor progression and metastasis. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. |
| 158 | GSE11883 |
Profile | The association between chronic inflammation and the development and progression of malignancy is exemplified in the biliary tract where persistent inflammation strongly predisposes to cholangiocarcinoma. The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth in cholangiocarcinoma by altered gene expression via autocrine mechanisms. We therefore investigated the effect of chronic exposure to IL-6 on gene expression using malignant cholangiocytes stably transfected to overexpress IL-6. Comparison of gene expression identified several genes that were altered by enforced IL-6 expression. |
| 159 | GSE9438 |
Profile | Examine gene expression for meningioma cases by hormone receptor status and indicate a stronger association with progesterone than with estrogen receptors Keywords: comparative gene expression |
| 160 | GSE5090 |
Profile | This experiment was designed to study if there are differences in gene expression in the adipose tissue of women affected by polycystic ovary syndrome (PCOS) compared to non-hyperandrogenic women. PCOS is the most common endocrinopathy in women of reproductive age and is characterized by hyperandrogenism and chronic anovulation. This disease is frequently associated with obesity, insulin resistance, and defects in insulin secretion, predisposing these women to type 2 diabetes, atherosclerosis, and cardiovascular disease. We have applied high-density oligonucleotide arrays to omental adipose tissue samples obtained from eight morbidly obese PCOS patients and seven morbidly obese non-PCOS women at the time of bariatric surgery. Keywords: Disease state analysis |
| 161 | GSE40301 |
Profile | Tissue inhibitor of metalloproteinase 1 (TIMP-1) controls matrix metalloproteinase (MMP) activity through 1:1 stochiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol (GPI) anchor (TIMP-1-GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1-GPI treated renal cell carcinoma cells (RCC) show increased apoptosis and reduced proliferation. Transcriptomic profiling and regulatory pathway mapping were used to identify potential mechanisms driving these effects. Significant changes in inhibitor of DNA binding (IDs) TGF-β1/SMAD and BMP pathways resulted from TIMP-1-GPI treatment. These events were linked to reduced TGF-β1 signaling mediated by inhibition of proteolytic processing of latent TGF-β1 by TIMP-1-GPI. Activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1-GPI treated renal cell carcinoma cells (RCC) show increased apoptosis and reduced proliferation. Transcriptomic profiling and regulatory pathway mapping were used to identify potential mechanisms driving these effects. Significant changes in inhibitor of DNA binding (IDs), TGF-β1/SMAD and BMP pathways resulted from TIMP-1-GPI treatment. These events were linked to reduced TGF-β1 signaling mediated by inhibition of proteolytic processing of latent TGF-β1 by TIMP-1-GPI. |
| 162 | GSE46914 |
Profile | The rapid development in septic patients of features of marked immunosuppression associated with increased risk of nosocomial infections and mortality represents the rational for the initiation of immune targeted treatments in sepsis. However as there is no clinical sign of immune dysfunctions, the current challenge is to develop biomarkers that will help clinicians identify the patients that would benefit from immunotherapy and monitor its efficacy. Using an in vitro model of endotoxin tolerance (ET), a pivotal feature of sepsis-induced immunosuppression in monocytes, we identified using gene expression profiling by microarray a panel of transcripts associated with the development of ET which expression was restored after immunostimulation with interferon-gamma (IFN-γ). These results were confirmed by qRT-PCR. Importantly, this short-list of markers was further evaluated in patients. Of these transcripts, six (TNFAIP6, FCN1, CXCL10, GBP1, CXCL5 and PID1) were differentially expressed in septic shock patients’ blood compared to healthy blood upon ex vivo LPS stimulation and were restored by IFN-γ. In this study, by combining a microarray approach in an in vitro model and a validation in clinical samples, we identified a panel of six transcripts that could be used for the identification of septic patients eligible for IFNg therapy. The potential value of these markers should now be evaluated in a larger cohort of patients. Upon favorable results, they could serve as stratification tools prior to immunostimulatory treatment and to monitor drug efficacy. |
| 163 | GSE38666 |
Profile | RNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of 18 serous ovarian cancer patients (Cepi). For 7 of these patients a matched set of surrounding cancer stroma (CS) was also collected. For controls, surface ovarian epithelial cells (OSE) were isolated from the normal (non-cancerous) ovaries of 12 individuals including matched sets of samples of OSE and normal stroma (NS) from 8 of these patients. Unsupervised hierarchical clustering of the microarray data resulted in the expected separation between the OSE and Cepi samples. Consistent with models of stromal activation, we also observed significant separation between the NS and CS samples. Unexpectedly, the CS samples sub-divided into two distinct groups. Analysis of expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples are consistent with the hypothesis that the two CS sub-groups differ significantly in their relative propensities to support tumor growth.The results indicate the existence of distinct categories of ovarian cancer stroma and suggest that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development. |
| 164 | GSE18948 |
Profile | Alefacept treatment is highly effective in a select group patients with moderate-to-severe psoriasis and is an ideal candidate to develop systems to predict who will respond to therapy. A clinical trial of 22 patients with moderate to severe psoriasis treated with alefacept (7.5mg weekly i.v. x12 weeks) was conducted in 2002-2003, as a mechanism of action study. Patients were classified as responders or non-responders to alefacept based on histological criteria. Microarray data from PBMCs of 16 of these patients was analyzed to generate a treatment response classifier. We used a discriminant analysis method that performs sample classification from gene expression data, via nearest shrunken centroid method''. A disease response classifier using 23 genes was created to accurately predict response to alefacept (12.3% error rate in favour of responders). This preliminary study may provide a useful tool to predict response of psoriatic patients with alefacept. Keywords: class prediction |
| 165 | GSE11954 |
Profile | Cellular senescence is an irreversible proliferative arrest and can be triggered in many cell types in response to diverse forms of cellular damage or stress. We used microarrays to compare gene expression profile between growing and senescent human activated hepatic stellate cells. Keywords: cell type comparison |
| 166 | GSE16080 |
Profile | A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. |
| 167 | GSE29684 |
Profile | It is widely believed that the molecular and cellular features of a tumor reflect its cell-of-origin and can thus provide clues about treatment targets. The retinoblastoma cell-of-origin has been debated for over a century. Here we report that human and mouse retinoblastomas have molecular cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell type–specific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Importantly, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens. |
| 168 | GSE21654 |
Profile | We used microarrays to analyze the global expression patterns for 22 commercially available pancreatic cancer cell lines |
| 169 | GSE43653 |
Profile | some genes associated with cell growth cell differentiation, meiosis, migration, and apoptosis are regulated in ECC-1 after DEHP exposure. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. |
| 170 | GSE30423 |
Profile | FaDu treated with citric buffer vs. rCTGF |
| 171 | GSE22217 |
Profile | Tissue response following implantation determines the success of the healing process. This response is not only dependent on the chemical properties of the implant surface but also by the surface topography or its roughness. Although in vitro and in vivo studies show improved results with rough- and fluoride-modified implants the mechanisms behind these findings are still unknown. Here, we have used a two step procedure to identify novel genes related to the early cell response of primary human osteoblasts to roughness and fluoride-modified titanium implants. 217 genes were identified by microarray analysis as response genes to roughness and 198 genes as response genes to fluoride. 11 of these identified genes have been related to bone and mineralization and were further investigated by real-time RT-PCR. After one day of culture, TLR3, ANKH, DCN, OC and RUNX2 were classified as responsive genes to roughness; DLX2 and TUFT1 as responsive genes to fluoride treatment. COLL-I, PTHLH, HES1, FST, ENPP1 and THRA as responsive genes to both, roughness and fluoride treatment. In conclusion, our strategy was useful for identifying novel genes that might be involved in the early response of osteoblasts to roughness and fluoride treatment of titanium implants. Tissue response following implantation determines the success of the healing process. This response is not only dependent on the chemical properties of the implant surface but also by the surface topography or its roughness. Although in vitro and in vivo studies show improved results with rough- and fluoride-modified implants, the mechanisms behind these findings are still unknown. Here, we have used a two step procedure to identify novel genes related to the early cell response of primary human osteoblasts to roughness and fluoride-modified titanium implants. 217 genes were identified by microarray analysis as response genes to roughness and 198 genes as response genes to fluoride. 11 of these identified genes have been related to bone and mineralization and were further investigated by real-time RT-PCR. After one day of culture, TLR3, ANKH, DCN, OC and RUNX2 were classified as responsive genes to roughness; DLX2 and TUFT1 as responsive genes to fluoride treatment. COLL-I, PTHLH, HES1, FST, ENPP1 and THRA as responsive genes to both, roughness and fluoride treatment. In conclusion, our strategy was useful for identifying novel genes that might be involved in the early response of osteoblasts to roughness and fluoride treatment of titanium implants. |
| 172 | GSE14642 |
Profile | We compared PBMC genomic response to exercise in both early (EG) and late-pubertal girls (LG) Keywords: stress response |
| 173 | GSE42637 |
Profile | Recently global gene expression profiling of patients samples lead to a molecular definition of Burkitt Lymphoma (BL) with lymphocyte enhancer-binding factor 1 (LEF1) as a signature gene. Here we report the discovery of nucleic LEF1 in a very high proportion of BL cases (15/18) and LEF1 target genes. Germinal center B cells were devoid of detectable nuclear LEF1 expression as mantle cell lymphoma (0/5) marginal zone lymphoma (0/6), follicular lymphoma (0/12) or diffuse large B cell lymphoma (DLBCL) (1/31). Using whole genome gene expression profiling after transient knockdown of LEF1 in BL cell lines, new LEF1 target genes were identified. The joint expression of these genes in primary BL samples shows that LEF1 is not only expressed aberrantly in BL but also transcriptionally active. Our study identified aberrantly expressed LEF1 and its target genes suggesting an important functional role in BLs. |
| 174 | GSE23640 |
Profile | Most of the breast cancer samples used in clinical research contain multiple cell types other than epithelial cells alone. The non-epithelial cell types have have a substantial effect on the gene expression-profile which is used to define molecular subtypes of the tumours. The purpose of this data set is to retrieve gene-expression profile within tumour epithelial cells. We collected 9 breast cancer epithelial cell lines and 5 tumour sampes from which epithelial cells were sorted and enriched using BerEp4 antibody coated beads. We profiled the mRNA expression level of these samples and classified probe sets into epithelial genes which were those genes with present calls in at least 50% of the samples. Then we derived an 23-gene signature based on only the epithelial genes to stratify breast cancer. |
| 175 | GSE16051 |
Profile | Integrated microarray and multiplex cytokine analyses of Kaposi's Sarcoma Asssociated Herpesvirus viral FLICE Inhibitory Protein K13 affected genes and cytokines in human blood vascular endothelial cells. The KSHV-encoded K13 protein is one of the few proteins to be expressed in latently-infected spindle cells and the ectopic expression of K13 in human vascular endothelial cells is sufficient to transform them into spindle cells. |
| 176 | GSE15481 |
Profile | Overexpression of the AP-2γ transcription factor in breast tumours has been identified as an independent predictor of poor outcome and failure of hormone therapy even in ER positive, ErbB2 negative tumours; markers of a more favourable prognosis. To understand further the role of AP-2γ in breast carcinoma, we have used an RNA interference and gene expression profiling strategy using the MCF-7 cell line as a model for ER positive, ErbB2 negative tumours with AP-2γ overexpression. Gene expression changes between control and silenced cells implicate AP-2γ in the control of cell cycle progression and developmental signalling. Keywords: RNA interference |
| 177 | GSE24290 |
Profile | Diabetic neuropathy (DN) is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of DN there are no specific treatments for DN and currently it is not possible to predict DN onset or progression. To examine gene expression signatures related to DN, microarray experiments were performed on a subset of human sural nerves collected during a 52-week clinical trial of acetyl-L-carnitine. A series of bioinformatics analyses analyzed differential gene expression and identified gene networks and pathways potentially responsible for the progression of DN. We identified 532 differentially expressed genes (DEGs) between patient samples with progressing or non-progressing DN, which were functionally enriched in pathways involving defense and inflammatory responses and lipid metabolism. A literature-derived co-citation network of the DEGs revealed gene sub-networks centered on apolipoprotein E (APOE), jun oncogene (JUN), leptin (LEP), serpin peptidase inhibitor E Type 1 (SERPINE1) and peroxisome proliferator-activated receptor gamma (PPARG). DEGs were used to predict DN progression in a test set of patients. Ridge-regression classification models with 14 DEGs achieved an overall accuracy of 92%, correctly classifying the progression status of 11 out of 12 patients. To our knowledge, this is the first study to identify transcriptional changes associated with DN progression in human sural nerves biopsies and describe their potential utility for molecular prediction of DN. Our results identifying the unique gene signature of patients with progressive DN will facilitate the development of new mechanism-based diagnostics and therapies. |
| 178 | GSE10911 |
Profile | MCF-7aro cells were used to generate a cell culture model system that is resistant to 3 aromatase inhibitors (AIs) letrozole, anastrozole and exemestane. For comparison, the MCF-7aro cells were also used to generate the tamoxifen-resistant cells as well as long-term estrogen deprived, LTEDaro. Affymetrix microarray analysis was performed to determine changes in gene expression that are unique to AI-resistance. Keywords: cell lines, aromatase inhibitor resistance, tamoxifen resistance |
| 179 | GSE15799 |
Profile | The whole-genome oligonucleotide microarray analysis of NS398-treated HT29 colon adenocarcinoma cells samples can give an insight into global molecular background of selective COX2 inhibitor administration in order to find other target molecules and pathways influenced by NS398 selective COX2 inhibitor treatment in the epithelial cells. |
| 180 | GSE27820 |
Profile | Active HUMSC with distinct binding rate to MDA MB-231 breast cancer cells distinct ability in suppressing tumorigenesis,distinct cell in cell features and distinct features under TEM then inactive HUMSC We used microarrays to detail the difference gene expression between active HUMSC and inactive HUMSC |
| 181 | GSE33325 |
Profile | Organophosphorus compounds induce cardiotoxicity through currently unknown mechanisms which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human cardiomyocytes after exposure to VX, and identified pathways underlying these changes. |
| 182 | GSE40413 |
Profile | In this study we sought to determine how IL-17 and TNF influence normal human melanocytes, either alone, or with both cytokines together. We reveal a dichotomous effect of IL-17 and TNF, which not only elicit essential mitogenic cytokines but also suppress melanogenesis by down-regulating genes of melanogenesis pathway |
| 183 | GSE10821 |
Profile | In this study we have investigated the effect of LMP1 on gene expression in normal human GC B cells using a non-viral vector based system Keywords: transfection of viral oncogene in normal human B cells |
| 184 | GSE15220 |
Profile | Aberrant methylation has been postulated to play an important role in tumorigenesis. We report the use of methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to investigate methylation changes in testicular germ cell tumor (TGCT) cells. Coupled to expression profiling changes we found that only 22-26% of differentially methylated genes were also expressed differentially. This phenomenon was independent of the presence of CpG islands in the promoter. Differential methylation and expression of some of these genes were confirmed in testicular tumor tissue. A substantial number of differentially methylated regions in the human genome were not linked to annotated gene loci. Subsequent analysis indicated several microRNAs and small nucleolar RNAs were regulated by these differentially methylated regions. Our results demonstrate the power of the combination of MeDIP-chip analysis and expression profiling for discovery in cancer cells of epigenetically regulated genes and non-coding RNAs in cancer cells. |
| 185 | GSE27914 |
Profile | The proto-oncogenes ETV1 ETV4, and ETV5 encode members of the E26 transformation-specific (ETS) transcription factor family, which includes the most frequently rearranged and overexpressed genes in prostate cancer. Despite being critical regulators of development, little is known about their post-translational regulation. Here we identify the ubiquitin ligase COnstitutive Photomorphogenic-1 (COP1, also called RFWD2) as a tumor suppressor that negatively regulates ETV1, ETV4, and ETV5. ETV1, which is the member mutated more frequently in prostate cancer, was degraded after being ubiquitinated by COP1. Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs (degrons) and was 50-fold more stable than wild-type ETV1. Almost all patient translocations eliminate these ETV1 degrons, implying that translocations rendering ETV1 insensitive to COP1 confer a significant selective advantage to prostate epithelial cells. Indeed, COP1 deficiency in mouse prostate elevated ETV1 levels and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia. The combined loss of COP1 and PTEN enhanced the invasiveness of mouse prostate adenocarcinomas. Finally, relatively rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein expression, and abnormally elevated ETV1 protein while lacking a translocation event. These findings identify COP1 as a bona fide tumor suppressor whose down-regulation promotes prostatic epithelial cell proliferation and tumorigenesis. |
| 186 | GSE38720 |
Profile | Huh7/5-2 cells (Binder et al. Hepatology 2007) were mock infected (DMEM) (time points 4 and 48 h) or infected with the chimeric HCV virus Jc1 (Pietschmann et al., PNAS 2006) (all time points). Multiplicity of infection was 15 (TCID50). Cells were lysed after 4, 12, 24, 48 and 72 hours post infection and total cellular RNA was prepared. |
| 187 | GSE30127 |
Profile | Placental trophoblasts are key determinants of in utero development. Mouse trophoblast stem cells (mTSCs) which were first derived over a decade ago, are a powerful cell culture model for studying their self-renewal or differentiation. Our attempts to isolate an equivalent population from the trophectoderm of human blastocysts generated colonies that quickly differentiated in vitro. This finding suggested that the human placenta has another progenitor niche. Here we show that the chorion is one such site. Initially, we immunolocalized pluripotency factors and trophoblast fate determinants in the early-gestation placenta, amnion and chorion. Immunoreactive cells were numerous in the chorion. We isolated these cells and plated them in medium containing FGF and an inhibitor of activin/nodal signaling, which is required for human embryonic SC self-renewal. Colonies of polarized cells with a limited lifespan emerged. Trypsin dissociation yielded continuously self-replicating monolayers. Colonies and monolayers formed the two major human trophoblast lineages—multinucleate syncytiotrophoblasts and invasive cytotrophoblasts (CTBs). Transcriptional profiling experiments revealed the factors associated with the self-renewal or differentiation of human chorionic trophoblast progenitor cells (TBPCs). They included imprinted genes, NR2F1/2, HMGA2 and adhesion molecules that were required for TBPC differentiation. Together, the results of these experiments suggested that the chorion is one source of epithelial CTB progenitors. These findings explain why CTBs of fully formed chorionic villi have a modest mitotic index and identify the chorionic mesoderm as a niche for TBPCs that support placental growth. |
| 188 | GSE494 |
Profile | Non-union skeletal fractures are characterized by their inability to heal six months after injury. Left untreated the non-union fracture may cause advanced arthritis or loss of function in the affected limb. Arrays were used to identify the mechanisms that lead to lack of skeletal repair in non-unions. These profiles are the non-union callous samples pooled from five individuals Keywords: other |
| 189 | GSE10183 |
Profile | Cancer cells were MACS sorted from tumor tissue specimem 05-179. Self replicates of CD26+ cancer cells were generated and the expression profiles were determined using Affymetrix U133 Plus 2.0 arrays. These data represent cancer cell type specific transcriptome. Keywords: disease state analysis |
| 190 | GSE38885 |
Profile | In this study we focussed on malignant post-transplant lymphomas. Post-transplant lymphoma is strongly associated with Epstein-Barr Virus (EBV) infection in contrast to lymphoma arising in an immunocompetent population. Nevertheless about 1 in 3 PTLD cases are negative for EBV. We used a microarray to define the gene expression profile of different PTLDs to elucidate the pathogenesis of EBV(+) and EBV(-) PTLD and to define whether EBV(-) PTLD is biologically different from EBV(-) lymphoma arising in an immunocompetent host. |
| 191 | GSE976 |
Profile | We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. We tested several of these in duplicate replicates in blasts from a patient with APL. Also included in this data set are a collection of 6 primary patient AML cells, 3 normal neutrophils samples, and 3 normal monocyte samples. This data was used to evaluate whole genome effects of the compounds on APL cells in relation to AML versus normal neutrophils and monocytes. Keywords = Leukemia Keywords = APL Keywords = AML Keywords = chemical genomics Keywords: repeat sample |
| 192 | GSE43998 |
Profile | We defined the C/EBPa signature characterized by a set of genes which are upregulated upon C/EBPa activation. In order to identify the C/EBPa signature we performed microarray gene expression analysis of K562 cells stably expressing p42-C/EBPa-ER after activating the C/EBPa construct to translocate to the nucleus for 6 hours with beta-estradiol. |
| 193 | GSE20615 |
Profile | Analysis of gene expression changes due to nonviral gene delivery of DNA lipoplexes versus control in human HEK293T cells. |
| 194 | GSE40583 |
Profile | The FAT1 gene was knocked down using 2 independent siRNAs in immortalized human astrocytes and U87 and U251 glioma cell lines. A non-targeted scramble siRNA was used as a control. |
| 195 | GSE17032 |
Profile | Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis but the complex molecular rules that govern these interactions remain poorly understood, thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchyme, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. To gain insight into the molecular identity of these fibroblast activities, we isolated RNA from 36 human skin and lung fibroblast cell line monocultures from Coriell Repositories or ATCC and performed microarray-based gene expression profiling using Affymetrix gene chips. |
| 196 | GSE42222 |
Profile | Alkaline phosphatase (ALP) is known to be a marker for several somatic stem cells and cancer cells. We found that human squamous cell carcinoma HeLa cells are comprised by ALP-positive and negative cells. Single cell-derived colony assay revealed that the former cells are labile with respect to ALP activity but the latter are stable. We cloned ALP-negative cells from the HeLa cells, and named H-1 clone. DNA microarray analysis revealed that gene expression pattern of H-1 cells is almost the same with that of their parental HeLa cells, but several genes for glycoprotein hormone alpha chain, ras-related and estrogen-regulated growth inhibitor, ALP, and Frizzled-10 was respectively 18.2, 9.6, 9.2 and 10.5–fold are upregulated in the HeLa cells. Although there is no evidence that the ALP-positive cells are cancer stem cells (CSCs) at present, HeLa cells comprised by ALP-positive and -negative cells may be a good model for CSC study in future. |
| 197 | GSE28304 |
Profile | GATA2 is well recognized as a key transcription factor and regulator of cell type specificity and differentiation. Here we carried out comparative chromatin immunoprecipitation with comprehensive sequencing (ChIP-seq) to determine genome-wide occupancy of GATA2 in endothelial cells and erythroids, and compared the occupancy to the respective gene expression profile in each cell type. Although GATA2 was commonly expressed in both cell types, different GATA2 bindings and distinct cell specific gene expressions were observed. By using the ChIP-seq with epigenetic histone modifications and chromatin conformation capture assays; we elucidated the mechanistic regulation of endothelial-specific GATA2 mediated endomucin gene expression, that was regulated by the endothelial-specific chromatin loop with a GATA2 associated distal enhancer and core promoter. Knockdown of endomucin markedly attenuated endothelial cell growth, migration and tube formation. Moreover, abrogation of GATA2 in endothelium demonstrated not only a reduction of endothelial specific markers, but also induction of mesenchymal transition promoting gene expression. Our findings provide new insights into the correlation of endothelial expressed GATA2 binding, epigenetic modification, and the determination of endothelial cell specificity. |
| 198 | GSE19577 |
Profile | We retrospectively analyzed AML patients enrolled in the AIEOP since 2000 42 patients with 11q23 rearrangement were analyzed by gene expression profile Gene expression analyses were performed to compare AML MLL partner genes (AF9, AF10, AF6, ENL, ELL, Septin 6, and AF1q) Keywords: Expression data |
| 199 | GSE15499 |
Profile | Class IIa histone deacetylases (HDACs) are signal-responsive regulators of gene expression involved in vascular homeostasis. To investigate the differential role of class IIa HDACs for the regulation of angiogenesis we used siRNA to specifically suppress the individual HDAC isoenzymes. Among the HDAC isoforms tested, silencing of HDAC5 exhibited a unique pro-angiogenic effect evidenced by increased endothelial cell migration, sprouting and tube formation. Consistently, overexpression of HDAC5 decreased sprout formation, indicating that HDAC5 is a negative regulator of angiogenesis. The anti-angiogenic activity of HDAC5 was independent of MEF2 binding and its deacetylase activity, but required a nuclear localization indicating that HDAC5 might affect the transcriptional regulation of gene expression. To identify putative HDAC5 targets, we performed microarray expression analysis. Silencing of HDAC5 increased the expression of fibroblast growth factor 2 (FGF2) and angiogenic guidance factors including Slit2. Antagonization of FGF2 or Slit2 reduced sprout induction in response to HDAC5 siRNA. ChIP assays demonstrate that HDAC5 binds to the promoter of FGF2 and Slit2. In summary, HDAC5 represses angiogenic genes, like FGF2 and Slit2, which causally contribute to capillary-like sprouting of endothelial cells. The de-repression of angiogenic genes by HDAC5 inactivation may provide a useful therapeutic target for induction of angiogenesis. |
| 200 | GSE24132 |
Profile | Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T cell responses may contribute to RSV immunopathology which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections, however DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV-infection. Transcriptional profiling and biological network analysis identified transforming growth factor (TGF)-b and associated signaling molecules as differentially regulated in the two age groups. TGF-b1 was decreased in RSV-infected adult blood DCs, but increased in RSV-infected cord blood DCs. Co-culture of adult RSV-infected DCs with autologous T-cells induced secretion of interferon gamma (IFNg), IL-12p70, IL-2, and tumor necrosis factor alpha (TNFa). Conversely, co-culture of cord RSV-infected DCs and autologous T-cells induced secretion of IL-4, IL-6, IL-1b, and IL-17. Addition of purified TGF-b1 to adult DC-T cell co-cultures reduced secretion of IFNg, IL-12p70, IL-2, and TNFa, which addition of a TGF-b chemical inhibitor to cord DC-T cell co-cultures increased secretion of IL-12p70. These data suggest that TGF-b acts as a major regulator of RSV DC-T cell responses, which could contribute to immunopathology during infancy. |
| 201 | GSE10508 |
Profile | The Tesi system allows analysis of HTLV-1 Tax's impact on the transcriptome of a human CD4+ T-cell which is not derived from leukemia but directly from normal human lymphocytes. By comparing cells with and without Tax one can specifically filter for celluar genes that are either activated or repressed in the presence of Tax. Keywords: cell type comparison, Tax |
| 202 | GSE11971 |
Profile | Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Keywords: Disease progression; time course |
| 203 | GSE22875 |
Profile | The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients. Keywords: OTX2, medulloblastoma, mRNA profiling |
| 204 | GSE46493 |
Profile | The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels binding, expression and chromatin changes under diverse stresses. Human osteosarcoma U2OS cells treated with anti-cancer drugs Doxorubicin or Nutlin-3 led to strikingly different p53 gene binding patterns based on ChIP-seq experiments. While two contiguous RRRCWWGYYY decamers is the consensus binding motif, p53 can bind a single decamer and function in vivo. Although the number of sites bound by p53 was 6-times greater for Nutlin-3 than Doxorubicin, expression changes induced by Nutlin-3 were much less dramatic compared to Doxorubicin. Unexpectedly, the solvent DMSO alone induced p53 binding to many sites common to Doxorubicin; however, this binding had no effect on target gene expression. Together, these data imply a two-stage mechanism for p53 transactivation where p53 binding only constitutes the first stage. Furthermore, both p53 binding and transactivation were associated with increased active histone modification H3K4me3. We discovered 149 putative new p53 target genes including several that are relevant to tumor suppression, revealing potential new targets for cancer therapy and expanding our understanding of the p53 regulatory network. |
| 205 | GSE42174 |
Profile | The multifunctional protein lipopolysaccharide-induced TNFalpha factor (LITAF) induces the secretion of inflammatory cytokines in monocytes and regulates protein degradation in neural cells. In B-cell lymphomas LITAF is frequently inactivated by epigenetic mechanisms, but beyond these data little is known about its regulation and function. Immunohistochemical and gene expression profiling analyses of normal and malignant B-cells revealed that LITAF and BCL6 exhibited opposite expression patterns. Accordingly, chromatin immunoprecipitation and luciferase experiments showed that LITAF is transcriptionally repressed by BCL6 in germinal center (GC) lymphocytes and in B-cell lymphoma cells. Gain- and-loss-of-function assays demonstrated that LITAF does not exert any of its previous roles. Conversely, LITAF co-localized with autophagosomes in B-cells whereby activated autophagic responses, which were abrogated upon LITAF silencing. Therefore, BCL6-mediated transcriptional repression of LITAF may contribute to an appropriate GC reaction by suppressing autophagy in GC lymphocytes, whereas constitutive repression of autophagic responses may promote B-cell lymphoma development. |
| 206 | GSE19143 |
Profile | Although the prognosis for childhood Acute Lymphoblastic Leukemia (ALL) in general has improved tremendously over the last decades the survival chances for infants (<1 year of age) with ALL remains poor. A major obstacle hampering successful treatment results in infant ALL is cellular resistance to several drugs currently used in the treatment of ALL, especially to prednisolone (or prednisone). Therefore we set out to search for genes differentially expressed between from infant (children <1 year of age) and non-infant (children >1 year of age) ALL samples either resistant or sensitive to prednisolone. |
| 207 | GSE29008 |
Profile | Toxin A and B from Clostridium difficile are the primary virulence factors in Clostridium difficile disease. The changes in gene transcription of human colon epithelial cells were investigated in vitro in order to better understand the many effects of both toxins. |
| 208 | GSE7148 |
Profile | Gene expression profiling was carried out on peripheral blood leukocytes from 14 healthy older adults. The primary research question is whether gene expression differs in individuals experiencing chronically high levels of social isolation (by UCLA Loneliness Scale) vs chronically low levels of social isolation. Keywords: Risk prediction |
| 209 | GSE29700 |
Profile | Identification of genes up or down regulated in LPS stimulated samples in comparison to control samples. |
| 210 | GSE13569 |
Profile | The effects of ethanol may vary from induction of apoptosis to the inhibition of proliferation differentiation, migration or other function. The complex and diverse response of fetal cells to ethanol has prompted us to use a bioinformatics approach to study the effect of ethanol on fetal stem cells derived from the amniotic fluid-derived (AFSC). To characterize the global response of human AFSC to ethanol, gene expression profiles of AFSC treated with or without 100mM ethanol for 48 hours were analyzed. Keywords: stem cells, amniotic fluid-derived stem cells, ethanol, alcohol |
| 211 | GSE28646 |
Profile | Multiple DNA methylation changes have been associated with the acquisition of drug resistance; however it remains uncertain how many of these changes may represent critical DNA methylation drivers of chemoresistance. Using gene expression profiling method on HGU133plus2 array we identified a total of 1370 genes showing significant gene expression changes with 687 genes going up and 683 genes going down in the resistant (cp70) versus sensitive cell lines (A2780) by Rank Product (FDR<5%). Combining expression profiling with methylation profiling data we found out of 245 hypermethylated and down-regulated genes in the resistant cell line, 41 genes were up-regulated following Decitabine treatment alone, 45 genes up-regulated following combined treatment of Decitabine and PXD101, and only 10 genes up-regulated following PXD101 treatment alone. Altogether we found a small set of genes as being potential key drivers of chemoresistance and should be further evaluated as predictive biomarkers, both to existing chemotherapies, but also to epigenetic therapies used to modulate drug resistance. |
| 212 | GSE13806 |
Profile | RNA was isolated from ectopically sFRP1-expressing MDA-MB-231 cells and control MDA-MB-231 cells and as well from tumor lysates arising from these cells as nude mouse xenograft. Gene expression profiles for these samples were investigated using Affymetrix arrays. |
| 213 | GSE15918 |
Profile | ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events) the phase 3 morbidity and mortality trial of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified previously undescribed changes in plasma levels of potassium, sodium, bicarbonate, and aldosterone. A key question after this trial is whether the failure of torcetrapib was a result of CETP inhibition or of some other pharmacology of the molecule. The direct effects of torcetrapib and related molecules on adrenal steroid production were assessed in cell culture using the H295R as well as the newly developed HAC15 human adrenal carcinoma cell lines. Torcetrapib induced the synthesis of both aldosterone and cortisol in these two in vitro cell systems. Analysis of steroidogenic gene expression indicated that torcetrapib significantly induced the expression of CYP11B2 and CYP11B1, two enzymes in the last step of aldosterone and cortisol biosynthesis pathway, respectively. Transcription profiling indicated that torcetrapib and angiotensin II share overlapping pathways in regulating adrenal steroid biosynthesis. Hormone-induced steroid production is mainly mediated by two messengers, calcium and cAMP. An increase of intracellular calcium was observed after torcetrapib treatment, whereas cAMP was unchanged. Consistent with intracellular calcium being the key mediator of torcetrapib’s effect in adrenal cells, calcium channel blockers completely blocked torcetrapib-induced corticoid release and calcium increase. A series of compounds structurally related to torcetrapib as well as structurally distinct compounds were profiled. The results indicate that the pressor and adrenal effects observed with torcetrapib and related molecules are independent of CETP inhibition. |
| 214 | GSE28413 |
Profile | The second leading cause of cancer death for women in the U.S. is breast cancer. Moreover a significant number of patients with breast tumors acquire resistance to drugs during therapy. To develop targeted therapeutic strategies to combat drug resistance it is essential to understand the basic molecular mechanisms through which cancer cells control sensitivity to chemotherapeutics. To identify new candidate genes and facilitate the discovery of novel drug resistance pathways, we have generated a resistance profile or ‘resistome’ of etoposide resistant MCF7 breast cancer cells. Differential expression of over 5000 genes (fold change > 2, P value < 0.05) indicate that several drug resistance mechanisms may be operating in these cells, including up-regulation of ABC transporter genes, down-regulation of the drug target and down-regulation of apoptotic genes. Several transcription factors such as RUNX2, SOX9, ETS1 and SMAD3 were up-regulated in the drug resistant cells. Targeted RUNX2 knockdown in the resistant cells using siRNA increased sensitivity to etoposide and also upregulated expression of pro-apoptotic genes indicating that RUNX2 could be a molecular target against etoposide resistance. Differential miRNA (microRNA) expression was observed among the drug resistant and sensitive cells suggesting that miRNA may also play a role in regulation of drug resistance. Hsa-miR-218, which targets ABCC6, was down-regulated in the drug resistant cell line. Transfection of a miR-218 mimic could down-regulate the expression of the efflux pump ABCC6 by 65% in drug resistant cells suggesting that regulation of miRNA may play an important role in etoposide resistance. |
| 215 | GSE26176 |
Profile | Comparison of mRNA expression profiles in W12 Series 1 cervical ectokeratinocytes at passage number 22 versus 19 (during which time the cells gain an invasive phenotype) As these cells demonstrate gain of chromosome 5p during this time mRNA expression profiling data interrogated for over-expressed genes on 5p that may be important in cervical neoplastic progression. |
| 216 | GSE43777 |
Profile | Background: Dengue virus (DENV) infection often leads to acute illness lasting 2-7 days with severity ranging from dengue fever (DF) to hemorrhagic fever (DHF) and fatal dengue shock syndrome (DSS). The dynamic changes of host responses on the gene transcription level that accompany DENV infection and differences between DF and DHF cases have been poorly understood particularly for South American population. Methodology/Principal Findings: Supported by a longitudinal active surveillance program for dengue transmission in Maracay, Venezuela, we conducted a prospective study to investigate host responses in dengue patients. Blood specimens and clinical information were collected on a daily basis from febrile cases confirmed with DENV infection from their first day of enrollment to early defervescence together with one convalescent sample. A total of 49 and 13 study participants were defined as DF and DHF cases respectively based on their clinical and hematological information. Using convalescent specimens as baseline, day-to-day gene expression was evaluated ex vivo in peripheral blood mononuclear cells of the study participants. Two waves of gene expression were detected: the first wave peaked at day 1 from the onset of fever (day 0) then declined at days 3-4; the second wave emerged from day 4 and peaked around day 5-6. Genes associated with innate immune process, including type I interferon signaling, cytokine-mediated signaling, chemotaxis, and antiviral responses, dominated the first wave; whereas genes involved in cell cycle processes, including cell division, mitosis, DNA replication, chromosome, and spindle organization dominated the second wave. Measureable genomic markers predicted early acute, late acute and convalescent phases with 91% accuracy. Gene signatures expressed in early acute phase predicted disease severity (DF vs DHF) with 96% accuracy. Conclusions/Significance: Our study established a dynamic pattern of detailed host immune responses to DENV infection and revealed genomic signatures valuable for diagnostics purposes. |
| 217 | GSE19136 |
Profile | [original title] Gene expression response to the implantation of drug (paclitaxel)-eluting or bare metal stents in denuded human LIMA arteries. Different clinical outcomes have been observed for paclitaxel-eluting and bare metal cardiovascular stents. The aim of this project was to identify genes that might be associated with the observed clinical outcomes. |
| 218 | GSE12452 |
Profile | Nasopharyngeal carcinoma is an Epstein-Barr virus-associated epithelial cancer with high prevalence in Southeast Asia. mRNA expression levels were measured for essentially all human genes and all latent Epstein-Barr virus (EBV) genes in nasopharyngeal carcinoma tissue samples and normal nasopharyngeal tissues. Data were analyzed for differential gene expression between tumor and normal tissue and for correlations with levels of viral gene expression. Primary publications: Sengupta et al 2006, Cancer Research 66(16): 7999-8006. Dodd et al, 2006, Cancer Epidemiology, Biomarkers & Prevention 15(11): 2216-2225. In subsequent studies using the same set of tissue samples, microRNA levels were measured in tumors and normal tissues and analyzed for correlations with differential target gene expression (Sengupta et al, 2008, Proc. Nat. Acad. Sci. USA 105: 5874-5878.) Keywords: mRNA expression profiling |
| 219 | GSE45665 |
Profile | Decoy receptor 3 (DcR3) a member of the tumor necrosis factor receptor (TNFR) superfamily, competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT, and TL1A. DcR3 was recently reported not only to act as a decoy receptor for these TNFRs but also to play a role as a ligand for the pathogenesis of RA. We hypothesized that DcR3 regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by the ligation of DcR3. |
| 220 | GSE20569 |
Profile | Carbonic anhydrase IX (CA 9) is a transmembrane isoform of carbonic anhydrase (CA) that contributes to an acidification of tumor microenvironment. The expression of CA 9 in cervical tumors was shown to be strongly involved in high incidence of metastasis and poor prognosis. To search for the key regulators of metastasis related to ectopic expression of CA 9 we investigated differentially expressed gene profiles in CA 9- transfected cervix carcinoma cell line C33-A (CF) compared with mock-transfected (CP) cell line, using Affymetrix Human Genome U133 Plus 2.0 Array. |
| 221 | GSE4217 |
Profile | Mammalian cells were grown as multicellular aggregates (spheroids) in an effort to determine the signaling events required for two cellular transformations states; primary foreskin fibroblasts (HFF-2) and glioblastoma cancer (T98G) cells to survive at room temperature under oxygen and nutrient-deprived conditions for extended periods of time (2 weeks) and subsequently grown out from the arrested state as adherent monolayers. HFF-2 cells were cultured in DMEM supplemented with 15% fetal bovine serum and 5% carbon dioxide humidified air at 37 degrees C. T98G cells were cultured in EMEM with 10% FBS, 5% non-essential amino acids and 5% carbon dioxide humidified air at 37 degreesC. Monolayers were grown in T-185 flasks to 60% confluency then split into T-185 flasks coated with a 1% agarose mix in a 2:1 media/water ratio. Cells were suspended in 30 ml of supplemented media and grown for 4 days in order to form multicellular spheroids as described previously by our group (J. Cell. Physiol., 206 [2006] 526-536; see GSE1364 and GSE1455 for similar experiments with HEK293 cells). The suspension was removed from the flasks and centrifuged (1500 x g, 2 min) and the media removed. The pellet was returned to the flasks and then placed in vacuum bags (Dri-shield 2000 moisture barrier bag from Surmount Inc., USA; Cat. number 70068), which were sealed immediately under vacuum (Deni Magic Vac, Champion model; Keystone Manufacturing, USA). Vacuum-sealed flasks were stored for 2 weeks (in the dark) at room temperature. Recovery was initiated by removing the flask from the bag and resuspending the spheroids in supplemented media and placing the flasks in a 5% CO2/humidified air incubator maintained at 37 degreesC. Timepoints for transcriptional analysis were monolayer (control), 4 day growth spheroids, 2 week stored spheroids and 7 day growth back to monolayers. There were 67 HFF-2 and 50 T98G genes that exhibited at least a 10-fold change in expression during the course of arrest and recovery. Eleven of these genes were common to both cell lines. While the trends were the same between the two cell lines for genes that were in common, the timing of the responses were clearly different. The primary fibroblasts showed significant gene expression changes during spheroid formation and returned to their initial monolayer state after the two week arrest, whereas the glioblastoma cells exhibited major changes in gene expression during the recovery process. Furthermore, the T98G cells never returned to the monolayer expression levels during the time course of the recovery phase (7 days growth under monolayer conditions). Major differences in the transcriptional data were also found between the cell lines with regards to the putative cellular location of the encoded proteins. Of the genes with significant fold changes (+/- 10-fold) for which location information is available, the primary fibroblasts were significantly enriched in genes encoding extracellular (32%) and membrane-associated (26%) proteins. The glioblastoma cells, on the other hand, had only 17% extracellular and 13% membrane-associated. The expression level trends for all genes above the 10-fold cutoff were as observed for the "in common" genes; HFF-2 genes had returned to monolayer expression levels after 7 days of recovery whereas the T98G line was still exhibiting expression values much different from that of the monolayer control. Keywords = human foreskin fibroblasts, desiccation, rehydration, monolayer, spheroid, stabilization, ambient temperature Keywords: other |
| 222 | GSE46538 |
Profile | In our lab we detected focal genomic amplification of PDE1C in 90% of short term GBM cultures. Knocking down of PDE1C was associated with compromised capacity opf these cultures to proliferate migrate and invade. Therefore we carried out affymetric whole genome expression analysis to identify the down stream gene effectors of this function effects. |
| 223 | GSE20876 |
Profile | We investigated the ability of HDAC inhibitors (HDACi) to target CML stem cells. Treatment with HDACi combined with IM effectively induced apoptosis in quiescent CML progenitors resistant to elimination by IM alone and eliminated CML stem cells capable of engrafting immunodeficient mice. In vivo administration of HDACi with IM markedly diminished LSC in a transgenic mouse model of CML. The interaction of IM and HDACi inhibited genes regulating hematopoietic stem cell maintenance and survival. HDACi treatment represents a novel and effective strategy to target LSC in CML patients receiving tyrosine kinase inhibitors. |
| 224 | GSE22580 |
Profile | There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate from normal stem cells based on initiation of a de novo stem cell program by reprogramming of a more differentiated cell type by oncogenic insults or both remains unresolved. A major hurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. We present evidence that normal and human telomerase reverse transcriptase (hTERT)-immortalized human mammary epithelial cells (hMECs) isolated and maintained in DFCI-1 medium retain a fraction with progenitor cell properties. These cells co-express basal, luminal and stem/progenitor cell markers. Clonal derivatives of progenitors co-expressing these markers fall into two distinct types: K5+/K19- (Type I) and K5+/K19+ (Type II). We show that both types of progenitor cells have self-renewal and differentiation ability. Through microarray analysis, we want to identify genes and pathways linked to human mammary epithelial stem/progenitor cell self-renewal and differentiation. |
| 225 | GSE24150 |
Profile | Microarray based mRNA profiling was used to identify the mechanism of action for the small molecule b-AP15. |
| 226 | GSE39999 |
Profile | Nematode derived substances are known to down regulate host immune responses in order to survive in the human host. Brugia malayi is a parasitic nematode responsible for long lasting and disabling infection known as lymphatic filariasis in humans. The therapeutic benefit of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) has been demonstrated in both animal and human models. However the inability of individual purified nematode proteins to recreate this beneficial effect has limited the application of component immunotherapy to human disease. This experiment addresses the hypothesis that the genes regulated by IL8 and recombinant Brugia malayi AsnRS (rBmAsnRS) are different even though it is known that both molecules interact with IL-8 receptors. Furthermore we theorize that the signal transduction pathways activated by IL-8 and rBmAsnRS are different because it is known that the extracellular G protein loops utilized by IL-8 and rBmAsnRS to activate IL8 receptors, are different. These results obtained with a single recombinant nematode protein, rBmAsnRS, share immunological features with those observed in a whole nematode infection and include desirable features for treatment of idiopathic inflammatory diseases, such as IBD. |
| 227 | GSE6338 |
Profile | Peripheral T-cell lymphoma unspecified (PTCL/U) the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and dismal prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T-cells. Comparison with the profiles of purified T-cell subpopulations [CD4+, CD8+, resting (HLA-DR-), and activated (HLA-DR+)] reveals that PTCLs/U are most closely related to activated peripheral T-lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T-cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g. apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic or stromal location. Among others, PTCLs/U aberrantly express PDGFRA, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRA and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone-deacetylase) are found. These results, which might be extended to other rarer PTCL categories, are provided with implications for tumor pathogenesis and clinical management. Keywords: Molecular pathogenesis, molecular classification |
| 228 | GSE31471 |
Profile | We used the microarray data to analyze host cells response on A549 cells infected with A/Duck/Malaysia/01 (H9N2) |
| 229 | GSE16130 |
Profile | The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity. |
| 230 | GSE16677 |
Profile | The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples. |
| 231 | GSE23882 |
Profile | Tazarotene-induced gene 1 (TIG1) also named as retinoic acid receptor responder 1 (RARRES1), is a retinoid inducible type II tumor suppressor gene; the TIG1B isoform inhibits growth and invasion of cancer cells. Expression of TIG1B is frequently downregulated in various cancer tissues; however, the expression and activities of the TIG1A isoform has yet to be analyzed. This study investigated the effects of TIG1A and TIG1B isoforms on gene expression profiles of colon cancer cells. TIG1A, TIG1B and control stable clones derived from HCT116 colon cells were established using the GeneSwitch system. TIG1 isoform expression was induced upon 5 micro Molar of mifepristone (MFP) treatment for 24 hr. Biological triplicate samples were prepared and gene expression profiles were determined by microarray using human genome HGU133 plus 2 array (Affymatrix). Upon induction of TIG1A and TIG1B expression for 24 hr, a total of 129 and 55 genes were significantly altered, respectively. Of the genes analyzed, 23 and 6 genes were up- and downregulated, respectively in both TIG1A and TIG1B expressing cells. |
| 232 | GSE35159 |
Profile | EVI1 is one of the famous poor prognostic markers for a chemotherapy-resistant acute myeloid leukemia (AML). To identify molecular targets on the surface of leukemia cells with EVI1high expression we compared the gene expression profiles of several AML cell lines by DNA microarray |
| 233 | GSE8668 |
Profile | Relatively brief bouts of exercise alter gene expression in peripheral blood mononuclear cells (PBMCs) but whether or not exercise changes gene expression in circulating neutrophils (whose numbers, like PBMCs, increase) is not known. We hypothesized that exercise would activate neutrophil genes involved in apoptosis, inflammation, and cell growth and repair, since these functions in leukocytes are known to be influenced by exercise. Blood was sampled before and immediately after 30-min of constant, heavy (about 80% peak O2 uptake) cycle-ergometer exercise in 12 healthy men (19-29 yr old) of average fitness. Neutrophils were isolated using density gradients; RNA was hybridized to Affymetrix U133+2 Genechip arrays. Using FDR<0.05 with 95% confidence a total of 526 genes were differentially expressed between before and after exercise. 316 genes had higher expression after exercise. The Jak/STAT pathway, known to inhibit apoptosis, was significantly activated (EASE score, p<0.005), but 14 genes were altered in a way likely to accelerate apoptosis as well. Similarly, both proinflammatory (e.g., IL32, TNFSF8 and CCR5) and anti-inflammatory (e.g., ANXA1) were affected. Growth and repair genes like AREG and FGF2 receptor genes (involved in angiogenesis) were also activated. Finally, a number of neutrophil genes known to be involved in pathological conditions like asthma and arthritis were altered by exercise, suggesting novel links between physical activity and disease or its prevention. In summary, brief heavy exercise leads to a previously unknown substantial and significant alteration in neutrophil gene expression. Keywords: stress response |
| 234 | GSE22868 |
Profile | Exposure to polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of different diseases and disorders are not fully understood. The knowledge of global gene expression will help us to develop early disease or disorder biomarkers for PCB-induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of high PCB exposure to Slovak 45-month-old children leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. |
| 235 | GSE28882 |
Profile | DZIP (DAZ-Interacting Protein) containing a C2H2 zinc-finger domain is expressed predominantly in human embryonic stem cells and fetal and adult germ cells; DZIP colocalizes with DAZ and/or DAZL proteins in these tissues. DZIP may associate with DAZ and its other cofactors in an RNA-binding protein complex that functions in both embryonic stem cells and germ cells. To identify mRNAs associated with human DZIP1 protein in HeLa cells we used a modified Ribonucleoprotein-ImmunoPrecipitation Microarray (RIP-Chip).DZIP1 ribonucleoprotein (RNP) complexes were performed with 2 µg of anti-DZIP1 antibody (rabbit polyclonal, Santa Cruz Biotechnology, CA, USA) bound to protein A-agarose beads (Sigma, Deisenhofen, Germany). HeLa cells were lysed in polysome lysis buffer (Tris-HCl pH 7,4 15mM, MgCl2 15 mM, NaCl 0,3 M, 1% Triton X-100, 1 mM DTT, 100 U / ml RNase Out, PMSF 1mM and E64 10uM) for one hour at 4°C. Beads were washed, then buffer and cell lysate were added, and the reaction mixtures were tumbled for 2 hours at 4°C. After this incubation, the beads were thoroughly washed again with polysome lysis buffer and then either RNA extracted for microarray and RT-PCR experiments using the RNeasy mini kit (Qiagen). To control for non-specifically enriched RNAs, identical IPs were performed with beads precoated with rabbit IgG as a negative control. RNA was processed for hybridization with GeneChip 3? IVT Express (Affymetrix - Santa Clara, USA), according to the manufacturers instruction. Briefly, cDNA was synthesized from immunoprecipitated RNA using reverse transcriptase followed by second strand synthesis to generate double-stranded cDNA. An in vitro transcription reaction was used to generate biotinylated cRNA. After purification and fragmentation, cRNA was hybridized onto GeneChip Affymetrix Human Genome U133 Plus 2.0 arrays. Post hybridization washes were preformed on an Affymetrix GeneChip® Fluidics Station 450. Arrays were scanned on an Affymetrix GeneChip® Scanner 3000. Scanned arrays were normalized using GCRMA in Partek software (Partek Incorporated. St. Louis, MO). Differentially enriched RNAs were found after performing One-way ANOVA analysis comparing immunoprecipitated samples against control samples. Final lists of genes were obtained by filtering the data from the statistical results according to fold enrichment more than 2 and false discovery rate (FDR 5%). |
| 236 | GSE14882 |
Profile | Background: The heteroplasmic mitochondrial DNA (mtDNA) mutation A3243G causes the MELAS syndrome as one of the most frequent mitochondrial diseases. The process of reconfiguration of nuclear gene expression profile to accommodate cellular processes to the functional status of mitochondria might be a key to MELAS disease manifestation and could contribute to its diverse phenotypic presentation. Objective: To determine master regulatory protein networks and disease-modifying genes in MELAS syndrome. Methods: Analyses of whole blood transcriptomes from 10 MELAS patients using a novel strategy by combining classic Affymetrix oligonucleotide microarray profiling with regulatory and protein interaction network analyses. Results and Interpretation: Hierarchical cluster analysis elucidated that the relative abundance of mutant mtDNA molecules is decisive for the nuclear gene expression response. Further analyses confirmed not only transcription factors already known to be involved in mitochondrial diseases (such as TFAM) but also detected the hypoxia-inducible factor 1α (HIF-1α)/HIF-1β complex, nuclear factor Y (NF-Y) and CREB-related transcription factors as novel master regulators for reconfiguration of nuclear gene expression in response to the MELAS mutation. Correlation analyses of gene alterations and clinico-genetic data detected significant correlations between A3243G-induced nuclear gene expression changes and mutant mtDNA load as well as disease characteristics. These potential disease-modifying genes influencing the expression of the MELAS phenotype are mainly related to clusters primarily unrelated to cellular energy metabolism, but important for nucleic acid and protein metabolism, and signal transduction. Our data thus provide a framework to search for new pathogenetic concepts and potential therapeutic approaches to treat the MELAS syndrome. |
| 237 | GSE36389 |
Profile | The present study has focused on the identification of the differences between expression patterns of kinin-dependent genes in endometrial cancer |
| 238 | GSE28359 |
Profile | Although practiced clinically for more than 40 years the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy. LGC006, a less potent SR1 analog, was also examined. KEYWORDS: two compounds, multiple doses, one time point |
| 239 | GSE24783 |
Profile | Hyperthermia is widely used to treat patients with various cancers. The 42.5˚C is well known as inflection point of hyperthermia and generally up to 42˚C of hyperthermia is used in clinical case to combine with other therapy. Here the effects of heat stress at 42 or 44˚C for 90 min on the gene expression in HSC-3 human oral squamous carcinoma cells were investigated using an Affymetrix GeneChip system. The cells were treated with heat stress (42 or 44°C for 90 min) and followed by incubation for 0, 6, or 12 h at 37°C. The percentage of cell death was 5.0 ± 1.5 (mean ± SD) at 42°C for 12 h and 17.4 ± 0.6 at 44°C for 12 h. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with heat stress at 42 and 44°C. |
| 240 | GSE21222 |
Profile | Human and mouse embryonic stem cells (ESCs) are derived from blastocyst stage embryos but have very different biological properties and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by exogenous induction of Oct4, Klf4 and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase (ERK) pathway. Forskolin, a protein kinase A pathway agonist that induces Klf4 and Klf2 expression, can transiently substitute for the requirement for ectopib transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X chromosome activation state (XaXa), a gene expression profile, and signaling pathway dependence that are highly similar to that of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of “naïve” human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans, and may open up new opportunities for patient-specific, disease-relevant research. |
| 241 | GSE12108 |
Profile | Differential expression in human peripheral blood monocytes between F. novicida-infected and uninfected and between Francisella tularensis tularensis isolate Schu S4 and uninfected. The goal was to examine genomewide transcriptional reponses to these two strains, and identify differentially-regulated genes that may help explain the virulence of Schu S4. Keywords: Immune Response, Human Monocytes, Bacteria, Francisella |
| 242 | GSE10615 |
Profile | To compare the transcriptome profiles of the two principal histological variants of malignant germ cell tumor that occur in childhood Keywords: Disease state analysis |
| 243 | GSE28548 |
Profile | SIRT6 has been implicated in a range of biological processes including inflammation aging and the control of metabolism. Hence inhibitors or activators of SIRT6 have the potential to be therapeutics for a number of indications. Genome wide expression studies were used to investigate the effect of overexpression of SIRT6 and mutant SIRT6 on a wide range of NFκB dependent gene expression |
| 244 | GSE14988 |
Profile | Expression data from DHT stimulation vs. control in LNCaP cells |
| 245 | GSE22246 |
Profile | Comparison of human iPSC lines ESC and fibroblasts to determine their expression patterns. All early passage female lines profiled expressed XIST RNA which is an indicator of an inactive X chromosome. Genes on the X-chromosome were also analyzed for overall levels of gene expression compared to human fibroblasts. |
| 246 | GSE7880 |
Profile | To identify genes associated with lung cancer progression we examined gene expression profiles of tumor cells from 20 patients with primary, untreated non-small cell lung cancer (10 adenocarcinomas (AC) and 10 squamous cell carcinomas (SCC)) in comparison to lung tissue of 23 patients with stage IIIB or stage IV non-small cell lung cancer (15 AC and 8 SCC). Bronchoscopical biopsies from patient with recurrent lung tumor were taken after initial treatment. Cancer cells were isolated using laser capture microdissection in order to obtain pure samples of tumor cells. For expression analysis, microarrays covering 8793 defined genes (Human HG Focus Array, Affymetrix) were used. Array data were normalized and analysed for significant differences using variance stabilizing transformation (VSN) and significance analysis of microarrays (SAM), respectively. Genes were considered to be up- or down-regulated when the ratio between primary and recurrent tumor samples were at least 1.5-fold differentially expressed with an estimated false discovery rate: < 5%. Based on differentially expressed genes, primary cancer samples could be separated from recurrent tumor samples. We identified 115 and 124 significantly regulates genes in AC and SCC, respectively. For example, in recurrent AC we found increased expression of genes related to the wingless (FZD6, RYK, MYC) and calcium (CALM1, ATB2B1, S100A2) signalling pathways which might play a role in metastasis of tumor cells. Other differentially expressed genes were related to cell cycle (CCND1, CDK2), transcription factors (TTF1, TAF2, YY1), nuclear mRNA splicing and mRNA processing (SFRS1, HNRPL), protein-nucleus import (NUTF2, KPNB1, NUP50) and chromatin modification (HIST1H4C, SMARCC1). In SCC, we found an increased expression of CTNNB1, an important mediator in wingless signalling pathway. Among the down-regulated genes in SCC, the utmost fraction belonged to genes coding for ubiquitin mediated proteolysis (UCHL1, PSMA3, COPS6) and ribosomal proteins (RPS26, RPL7A, RPS15). Other down regulated genes were related to transcription factors (TCEA2, TAF10), nuclear mRNA splicing and mRNA processing (SNRPD2, HNRPM). In conclusion, a distinct pattern of gene expression is found during the progression from primary carcinoma to recurrent NSCLC. Our microarray-based expression profiling revealed interesting novel candidate genes and pathways that may contribute to lung cancer progression. Keywords: Lung cancer, NSCLC, gene expression, progression, Wnt signalling pathway |
| 247 | GSE26114 |
Profile | For the microarray experiments MV4-11 and MOLM-14 cells were treated with DMSO control, ABT-869 3 nM, SAHA 6 uM and combination therapy for 24 hours. Cells were then washed in PBS and high-quality total RNA was extracted RNeasy Midi Kit, according to the manufacturer’s instruction (Qiagen, Valencia, USA). RNA quantity, quality, and purity were assessed with the use of the RNA 6000 Nano assay on the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara CA, USA). Gene expression profiling was performed using Affymetric U133plus2.0 gene chip (Affymetrix, Santa Clara, CA, USA) according to the manufacturer’s protocol. |
| 248 | GSE31040 |
Profile | Human lymphoblastoid cell lines (EBV-immortalised B cells LcL) obtained from subjects of different age (young 28-40 years, centenarians >95 years) were analysed for gene expression at basal culture conditions and after 48 hours of serum starvation. Lymphoid B cells from centenarians were more resistant to apoptosis induction and displayed a more developed lysosomal compartment, the most critical component of phagic machinery. In addition, cells from centenarians were capable of engulfing and digesting other cells, i.e. their siblings (even entire cells). This behavior was improved by nutrient deprivation, but strikingly, it was unaffected by the autophagy-modulating drugs rapamycin, an autophagy inducer, and 3-methyladenine, an autophagy inhibitor. |
| 249 | GSE33109 |
Profile | Organophosphorus compounds may induce neurotoxicity through mechanisms other than the cholinergic pathway which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human neural cells after exposure to VX, and identified pathways underlying these changes. |
| 250 | GSE1417 |
Profile | Pharmacogenomic identification of targets for adjuvant therapy with the topoisomerase poison camptothecin. The response of tumor cells to the unusual form of DNA damage caused by topoisomerase poisons such as camptothecin (CPT) is poorly understood and knowledge regarding which drugs can be effectively combined with CPT is lacking. To better understand the response of tumor cells to CPT and to identify potential targets for adjuvant therapy, we examined global changes in mRNA abundance in HeLa cells after CPT treatment using Affymetrix U133A GeneChips, which include all annotated human genes (22,283 probe sets). Statistical analysis of the data using a Bayesian/Cyber t test and a modified Benjamini and Hochberg correction for multiple hypotheses testing identified 188 probe sets that are induced and 495 that are repressed 8 h after CPT treatment at a False Discovery Rate of <0.05 and a minimum 3-fold change. This pharmacogenomic approach led us to identify two pathways that are CPT induced: (a) the epidermal growth factor receptor; and (b) nuclear factor-kappaB-regulated antiapoptotic factors. Experiments using HeLa cells in our lab and prior animal model studies performed elsewhere confirm that inhibitors of these respective pathways super-additively enhance CPT's cytotoxicity, suggesting their potential as targets for adjuvant therapy with CPT. Cancer Res. 2004 Mar 15;64(6):2096-104 Keywords = HeLa Keywords = Camptothecin Keywords: ordered |
| 251 | GSE29313 |
Profile | Although EWS/FLI-1 fusion protein is responsible for most Ewing’s sarcoma family tumors (ESFT) the function of native EWS remains largely unknown. Here, we first showed that EWS repressed protein expression in a tethering assay. mRNAs bound to EWS were determined by RNA-immunoprecipitation Chip assay, and one of them, proline-rich Akt substrate of 40 kDa (PRAS40) mRNA, directly interacted with EWS. The inhibitor of AKT, API-2, repressed ESFT cell proliferation. We demonstrate that EWS negatively regulated PRAS40 protein expression through binding to PRAS40 3’UTR. Furthermore, PRAS40 knockdown inhibited the proliferation and metastatic potential of ESFT cells. |
| 252 | GSE6351 |
Profile | Characterization of the underlying genetic defects in patients with a rare and peculiar phenotype is challenging. Here we have utilized whole genome expression profiling and identified a homozygous germline mutation in the DDB2 gene in a patient with several facial tumors. The feasibility of using blood derived RNA, diminishing costs of the technology, and the limited number of samples needed provide this approach a powerful new tool that may substantially aid in such gene identification efforts. Keywords: disease vs control |
| 253 | GSE20505 |
Profile | Gene transfer vectors based on gamma-retroviruses target actively transcribing genes indicating that the cellular gene expression profile can be predictive of their integration pattern. Therefore different culture conditions leading to different transcriptional activity may translate into differences in the profile of targeted genes in cells transduced with these vectors. Recent data from two gene therapy trials for SCID-X1 conducted in France and the UK suggested that small differences between in vitro stimulation conditions could explain the disparity in the frequency of common integrations sites observed in the two studies. We set out to compare the transcriptional activity of human CD34+ bone marrow-derived cells cultured under the French (S1) or British (S2) culture conditions. |
| 254 | GSE15932 |
Profile | The prognosis of pancreatic cancer is still very poor how to detect pancreatic cancer from high-risk group in an early stage is essential for improving its long-time survival. Therefore, the purpose of this study was to explore specific biomarkers that can differentiate pancreatic cancer-associated diabetes from type-2 diabetes for the early detection of pancreatic cancer. In the current study, we used global gene transcription analysis with affymetrix gene chip to identify genes specifically expressed in pancreatic cancer-associated diabetes mellitus from peripheral blood samples in stead of from tissue samples. |
| 255 | GSE1004 |
Profile | Molecular profiles of dystophin-deficient patients and normal human skeletal muscles on Affymetrix HG-U95A arrays Keywords = DMD Keywords = Duchenne muscular dystrophy Keywords = dystrophin Keywords = Affymetrix U95A array Keywords = skeletal muscle Keywords = gene expression profiles Keywords: other |
| 256 | GSE9250 |
Profile | Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness with a variable clinical course. Loss of chromosomal material on chromosome 13 at cytoband 13q14 is the most frequent genetic abnormality in CLL but the molecular aberrations underlying del13q14 in CLL remain incompletely characterized. We analyzed 171 CLL cases for LOH and sub-chromosomal copy loss on chromosome 13 in DNA from FACS-sorted CD19+ cells and paired buccal cells using the Affymetrix XbaI 50K SNP-array platform. The resulting high-resolution genomic maps, together with array-based measurements of expression levels of RNA in CLL cases with and without del13q14 and Q-PCR-based expression analysis of selected genes support the following conclusions: i) del13q14 is heterogeneous and composed of multiple subtypes with deletion of Rb or the miR15a/16 loci serving as anatomic landmarks, respectively ii) del13q14 type Ia deletions are relatively uniform in length and extend from breakpoints close to the miR15a/16 cluster to a newly identified telomeric breakpoint cluster at ~50.2-50.5 Mb physical position iii) LATS2 RNA levels are ~2.6-2.8-fold lower in cases with del13q14 type I that do not delete Rb as opposed to all other CLL cases and iv) ~15% of CLL cases display marked reductions in miR15a/16 expression often but not invariably associated with bi-allelic miR15a/16 loss. This data should aid future investigations into biological differences imparted on CLL by different del13q14 subtypes including investigations into LATS2 as one of the genes found deregulated as part of del13q14. Keywords: Chronic lymphocytic leukemia, CLL, gene expression comparison, del13q14, del13q |
| 257 | GSE41662 |
Profile | To explore the psoriasis phenotype and pathways involved in psoriasis we characterized gene expression in lesional and non-lesional skin from psoriasis patients. |
| 258 | GSE29523 |
Profile | We used microarrays to examine the impact of AF1q/MLLT11 on the gene expression profile of CD34+CD45RA-Lin- and CD34+CD45RA+Lin- HPCs isolated from umbilical cord blood CD34+CD45RA-Lin- and CD34+CD45RA+Lin- HPCs correspond respectively to early multipotent and lympho-granulo-macrophagic precursors. A2M is a nuclear mutant-derivative of AF1q/MLLT11 |
| 259 | GSE12803 |
Profile | Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions. Keywords: cell differentiation |
| 260 | GSE18887 |
Profile | We here report transcriptome profiles of human embryos at six successive developmental stages (i.e. Carnegie Stages 9 to 14), representing the first comprehensive gene expression database of early human organogenesis. Through a series of data mining and comparisons with the transcriptome during mouse embryogenesis and the multi-layered genomic data in human embryonic stem cells, we revealed that development potential during early human organogenesis is orchestrated by two dominant categories of genes. Specifically, most gradually induced genes are largely differentiation-related and indicative of diverse organ formation, whereas those gradually repressed are involved in both stemness- and differentiation-relevant aspects of the developmental potential, which may be important for the initiation of organogenesis. Further through integrative mining we uncovered a molecular network (including a stemness-relevant module and a differentiation-relevant module) that may provide a framework for the regulation of early human organogenesis. Preliminary analysis of published data showed that the network could serve to evaluate various in vitro differentiation models. Our results make a significant step towards understanding of human embryogenesis at a molecular level and suggest that developmental potentials of early embryonic cells are under control of shared regulatory events. |
| 261 | GSE34055 |
Profile | Myc is an oncogenic transcription factor frequently dysregulated in human cancer. To identify pathways supporting the Myc oncogenic program we employed a genome-wide RNAi screen for Myc-synthetic-lethal (MySL) genes and uncovered a role for the SUMO-activating-enzyme (SAE1/2). Loss of SAE1/2 enzymatic activity drives synthetic lethality with Myc. Mechanistically, SAE2 inhibition switches a transcriptional subprogram of Myc from activated to repressed. A subset of these SUMOylation-dependent Myc-switchers (SMS genes) governs mitotic spindle function and is required to support the Myc oncogenic program. |
| 262 | GSE14017 |
Profile | Comparisons among breast cancer metastases at different organs revealed distinct microenvironments as characterized by cytokine content. Such microenvironment distinction might be important to dictate how the cancer cells adapt to survival before they successfully colonize. Keywords: Disease state analyses |
| 263 | GSE4488 |
Profile | While identification of genes mutated in high penetrance tumor predisposition syndromes has been a success story much less progress has been made in characterizing the genetic basis of low penetrance tumor susceptibility. Combining recently introduced chip-based technologies with traditional genealogy work we have identified inactivating germline mutations in patients with pituitary adenoma predisposition (PAP). The experiment consisted of a collection of blood samples from identified families where PAP was observed and analysis of gene expression data used together with SNP genoptyping and linkage analysis. The findings were further studied using direct screening and other supporting methods. Keywords: affected and obligatory carriers vs controls |
| 264 | GSE37768 |
Profile | Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory lung disease. The abnormal inflammatory response of the lung mainly to cigarette smoke, causes multiple cellular and structural changes affecting all of its compartments, which leads to disease progression. The molecular mechanisms underlying these pathological changes are still not fully understood The aim of this study was to identify genes and molecular pathways potentially involved in the pathogenesis of COPD |
| 265 | GSE28177 |
Profile | We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 T cells in peripheral blood was observed while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. |
| 266 | GSE19339 |
Profile | Inflammatory mechanisms and immune cells are involved in acute coronary syndromes (ACS) and may lead to acute plaque rupture. However the local expression of the different genes potentially involved is largely unknown. We therefore performed an Affymetrix analysis of genes expressed in white blood cells obtained from an occluding coronary thrombus or peripheral blood of patients with ST-elevation myocardial infarction. |
| 267 | GSE22979 |
Profile | Micro RNAs (miRNAs) miR-130a miR-203 and miR-205 are jointly downregulated in prostate cancer and act as repressors of AR-signaling. MiRNAs are small non-coding RNAs that regulate the expression of specific mRNA targets mainly by translational repression, mRNA deadenylation or cleavage. Reconstitution of these lost miRNAs in the LNCaP PCa cell line cause morphology changes, growth arrest, and apoptosis, increasing when the miRNAs were co-expressed. This series identifies direct targets of miR-130a, miR-203, and miR-205 by AGO2-RNA co-immunoprecipitation as described by (Beitzinger et al. 2007) upon miRNA reconstitution in LNCaP cells and analyzing AGO2-bound mRNAs using Affymetrix Genechips. Relative levels of AGO2 bound versus total RNA expression were compared between miRNA reconstituted and miR-scr transfected samples. |
| 268 | GSE28846 |
Profile | Expression profiles of aggressive versus non-aggressive ovarian breast, melanoma, and prostate cancer cell lines |
| 269 | GSE39730 |
Profile | Recently the p53-miR-34a network was identified to play an important role in tumorigenesis. As in acute myeloid leukemia with complex karyotype (CK-AML) TP53 alterations are the most common known molecular lesion, we further analyzed the p53-miR-34a axis in CK-AML with known TP53 status. Clinically, low miR-34a expression and TP53 alterations predicted for chemotherapy resistance and inferior outcome. Notably, in TP53unaltered CK-AML high miR-34a expression predicted for inferior overall survival (OS), whereas in TP53biallelic altered CK-AML high miR-34a expression pointed to better OS. To further investigate miR-34a-associated gene expression patterns, we analyzed distinct subgroups defined by TP53 alteration and miR-34a expression status. Exemplary samples from TP53unaltered (n=6) and TP53biallelic altered (n=6) CK-AML characterized by either high (CK+/miR-34ahigh expression, above median miR-34a expression of the entire cohort), or low (CK+/miR-34alow expression, below median miR-34a expression of the entire cohort) miR-34a expression (n=3 in each group), were analyzed. This molecular profiling linked impaired p53 to decreased miR-34a expression but also identified p53-independent miR-34a induction mechanisms, as shown in TP53biallelic altered cell lines treated with 15-deoxy-∆12,14-prostaglandin (PGJ2). An improved understanding of this mechanism might provide novel therapeutic options to restore miR-34a function and thereby induce cell cycle arrest and apoptosis in TP53altered CK-AML. |
| 270 | GSE18504 |
Profile | The effects of the CDK inhibitor Flavopiridol on the A2780 human adenocarcinoma ovary cell line were analysed by gene expression profiling. |
| 271 | GSE35208 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 272 | GSE19420 |
Profile | Skeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training Mitochondrial dysfunction has long been implicated to play a causative role in development of type 2 diabetes (T2DM). However a growing number of recent studies provide data that mitochondrial dysfunction is a consequence of T2DM development. The aim of our study is to clarify in further detail the causal role of mitochondrial dysfunction in T2DM by a comprehensive ex vivo analysis of mitochondrial function combined with global gene expression analysis in muscle of pre-diabetic newly diagnosed untreated T2DM subjects and long-standing insulin treated T2DM subjects compared with age- and BMI-matched controls. In addition, we assessed the impact of long-term interval exercise training on physical activity performance, mitochondrial function and glycemic control in long-standing insulin-treated T2DM subjects. Ex vivo mitochondrial density, quality and functioning was comparable between pre-diabetic subjects and matched controls, however, gene expression analysis showed a switch from carbohydrate toward lipids as energy source in pre-diabetes subjects. In contrast, long-term insulin treated T2DM subjects had slightly decreased mitochondrial density and ex vivo function. Expression of Krebs cycle and OXPHOS related genes were decreased, indicating a decreased capacity to use lipids as an energy source. The insulin-treated T2DM subjects had a lower physical activity level than pre-diabetic and normoglycemic subjects. A 52 weeks exercise training of these subjects increased submaximal oxidative efficiency, increased in vivo PCr recovery rate, as well as mildly increased in vitro mitochondrial function. Gene expression of β-oxidation, Krebs cycle and OXPHOS-related genes was increased. Our data demonstrate that mitochondrial dysfunction is rather a consequence than a causative factor in T2DM development as it was only detected in overt diabetes and not in early diabetes. Regular exercise training stabilized exogenous insulin requirement and improved mitochondrial functioning, fatty acid oxidation and general physical work load capacity in long-standing insulin-treated T2DM subjects. As such, the present study shows for the first time that long-term exercise interventions are beneficial in this group of complex diabetes patient and may prevent further metabolic deterioration. |
| 273 | GSE34514 |
Profile | Alterations in the presence of sperm RNAs have been identified using microarrays in teratozoospermic (abnormal morphology) or other types of infertile patients. However so far no studies had been reported on the sperm RNA content using microarrays in asthenozoospermic patients (low motility). We started the present project to with the goal to characterize the RNA expression in asthenozoospermic infertile patients as compared to normozoospermic fertile controls. |
| 274 | GSE46143 |
Profile | In this study we have investigated the effect of LMP2A on gene expression in normal human GC B cells using a non-viral vector based system Keywords: transfection of viral oncogene in normal human B cells |
| 275 | GSE20198 |
Profile | The aim of this study was to identify genes regulated by IL-12 IL-18 and IFN-alpha during early differentiation of human Th1 cells |
| 276 | GSE18113 |
Profile | The activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear. We used microarrays to detail the repsonse of endothelial cells to tumor cells in the presence or absence of blood components. |
| 277 | GSE36000 |
Profile | Gene expression analyis of primary MCL including IGHV mutated and unmutated cases Gene set analysis was perfomed in MCL samples comparing IGHV mutated cases vs. IGHV unmutated cases |
| 278 | GSE26704 |
Profile | DUSP1 is involved in different cellular pathways including cancer cell proliferation angiogenesis, invasion and resistance to chemotherapy. To gain insight into the cellular signaling pathways involving DUSP1 actions and the response to Cisplatin (CDDP) in non small cell lung cancer (NSCLC), we have used a double strategy that combines microarray and SiRNA technology. This strategy provided a differential expression profile of genes involved in CDDP response in NSCLC cell line regulated by DUSP1 using H460 and H460cri and a time course to CDDP. KEYWORDS: Expression profiling by array in cells with genetic modification in response to CCDP treatment |
| 279 | GSE12583 |
Profile | The generation of induced pluripotent stem (iPS) cells 1-4 has spawned unprecedented opportunities for investigating the molecular logic that underlies cellular pluripotency and reprogramming as well as for obtaining patient-specific cells for future clinical applications. However, both prospects are hampered by the low efficiency of the reprogramming process. Here, we show that juvenile human primary keratinocytes can be efficiently reprogrammed to pluripotency by retroviral transduction with Oct4, Sox2, Klf4 and c-Myc. Keratinocyte-derived iPS (KiPS) cells appear indistinguishable from human embryonic stem (hES) cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, as well as in vitro and in vivo differentiation potential. Notably, keratinocyte reprogramming to pluripotency is, at least, 100-fold more efficient and 2-fold faster than that of fibroblasts. This increase in reprogramming efficiency allowed us to expand the practicability of the technology and to generate KiPS cells from single plucked hairs from adult individuals. |
| 280 | GSE24082 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 281 | GSE33810 |
Profile | We used cDNA microarray to study the gene expression profile between the tumor and non-tumor tissue samples from patients with esophageal cancer |
| 282 | GSE19018 |
Profile | Senescent is an irreversible form of cell cycle arrest initiated by damaged cell constituents and subsequent pro-oncogenic signaling. Replicative senescence in vitro can be considered a model for human aging. When fibroblasts are cultured under atmospheric oxygen conditions of 20% typical of normal tissue culture procedure, fibroblasts generally reach their replicative capacity at 50-60 population doublings (PDs). When fibroblasts are cultured under normal physiological oxygen conditions of 3%, PDs increase about 30% relative to atmospheric levels. Hence while oxygen is a requirement for normal aerobic respiration, it can contribute to the total amount of oxidative stress to which cells are exposed to, leading to a long-term adverse effect in vitro. Inasmuch, cultures maintained under hyperoxic and hypoxic conditions provide a convenient model system for assessing the relationship between oxygen/oxidative stress and senescence. We used microarrays to profile the changes in global gene expression during aging and senescence of Imr90 cells under growth oxygen conditions of 3% and 20%. |
| 283 | GSE24202 |
Profile | Microarrays were used to determine relative global gene expression changes upon introduction of EMT-inducing or control vectors. |
| 284 | GSE42569 |
Profile | Th17 cells are believed to be a critical cell population for driving autoimmune diseases. However environmental factors that are directly related to the development of Th17 cells are largely unknown. High-salt (NaCl) concentrations enhance Th17 differentiation of human naive CD4+ T cells in vitro. The aim of the study was to analyse the changes in gene expression induced by high-salt conditions during Th17 differentiation. |
| 285 | GSE23586 |
Profile | Gene expressions relate to the pathogenesis of periodontitis and have a crucial role in local tissue destruction and susceptibility to the disease. The aims of the present study were to explore comprehensive gene expressions/transcriptomes in periodontitis-affected gingival tissues and to identify specific biological processes. The purpose of the present study was 1) to compare comprehensive gene expression/transcriptomes of periodontitis-affected gingival tissues with those of healthy tissues by using microarray and data mining technologies, and 2) to analyze significantly differentially expressed genes which belong to pathological pathways in periodontitis by qRT-PCR. |
| 286 | GSE27657 |
Profile | Different human adipose tissue depots may have functional differences. Subcutaneous human adipose tissue has been extensively studied but less is known about other depots. Perithyroid (PT) adipose tissue contains not only white adipocytes but also brown adipocytes. The aim of this study was to compare the expression of brown adipocyte containing perithyroid adipose tissue with s.c. adipose tissue.role in the development of obesity. Expression profiling of adipose tissue may give insights into mechanisms contributing to obesity and obesity-related disorders. |
| 287 | GSE30010 |
Profile | The objective of the study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. |
| 288 | GSE17440 |
Profile | Major depressive disorder (MDD) is a clinically defined entity with little understanding as to the underlying pathological substrate. Biologically MDD is characterized by disruption of neurotransmitters, especially serotonin and noradrenaline, which are the main targets of antidepressants. We previously demonstrated significant reduction of glial cell number in the cingulate and dorsolateral prefrontal cortical regions. Unfortunately, individuals living with HIV still have very high rates of MDD, despite the fact that mortality rates have fallen sharply with effective antiretroviral treatment. It is possible that in this treatment era, living with chronic HIV infection may result in long-term neuropathological changes that predispose to MDD. For example, it is known that HIV is associated with a range of inflammatory pathologies, neuronal loss, and dendrite-synaptic damage. In HIV, these neurodegenerative changes have been linked to neurocognitive impairments, however it is also possible that these changes potentiate MDD. In the current study, we sought to determine whether there are changes in gene expression in the MDD brain in the frontal cortex in HIV-context. We identify a large number of genes dysregulated at p<0.05 significance. |
| 289 | GSE25086 |
Profile | NDRG1 functions as a metastasis suppressor in pancreatic and other cancers. To determine the molecular function of NDRG1 in MIAPaCa-2 pancreatic cancer cells we performed a whole genome gene array analysis on these cells stably transfected with NDRG1 when compared to empty vector-transfected controls. The differentially expressed genes indetified in this microarray may represent potential molecular targets of NDRG1 in pancreatic cancer. |
| 290 | GSE19599 |
Profile | Gene expression profiling of normal hematopoietic cell subpopulations RNA extracted from flow sorted normal hematopietic cells were hybridized onto Affymetrix U133 Plus 2.0 arrays. |
| 291 | GSE4219 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 292 | GSE8977 |
Profile | tumor microenviroment facilitates metastatic spread by eliciting reversible changes in the phenotypes of cancer cells Keywords: expression analysis of breast tumor samples |
| 293 | GSE6920 |
Profile | Aberrant co-expression of LMO2 and TAL1 is regularly found in T cell acute lymphoblastic leukemia (T-ALL). Here we describe a xenotransplant model for primary T-ALL cells derived from a patient who developed LMO2/TAL1 associated T-ALL after gene therapy for X-SCID (gamma c deficiency) due to insertional activation and a SIL-TAL1 fusion as an additional independent event. We identified a protein complex containing LMO2 TAL1 and E47 in the patient’s T-ALL cells. This complex functions as a transcription regulation complex in undifferentiated hematopoietic cells. However, its role in T-ALL is not fully understood. By comparative gene expression profiling we identified retinaldehyde dehydrogenase (RALDH2) as one of the genes which was highly up regulated in the primary T-ALL cells; the gene product was N-terminally truncated (RALDH2-T), but enzymatically active. To investigate the interference of LMO2 in RALDH2-T expression as well as the role of RALDH2-T in T-ALL development, LMO1 (analogue of LMO2) was down regulated by RNA interference in the T-ALL cell line Jurkat which led to a decrease of RALDH2-T expression and cell viability, indicating that positive regulation of RALDH2-T through an LMO1 or 2 containing transcription regulation complex might be essential for maintaining the T-ALL phenotype. Keywords: Primary human T-ALL cells and CD8 cells of normal donors |
| 294 | GSE15367 |
Profile | Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of Saos2 cells lacking p53. |
| 295 | GSE6075 |
Profile | The goal of this study is to identify genes that are differentially expressed by E6 in oral epithelial cells that are stably expressing Bmi-1. Keywords: oncogenesis. |
| 296 | GSE5681 |
Profile | Aplidin (plitidepsin) is a novel marine-derived antitumor agent presently undergoing phase II clinical trials in hematological malignancies and solid tumors. Lack of bone marrow toxicity has encouraged further development of this drug for treatment of leukemia and lymphoma. Multiple signaling pathways have been shown to be involved in Aplidin-induced apoptosis and cell cycle arrest in G1 and G2 phase. However the exact mechanism(s) of Aplidin action remains to be elucidated. Here we demonstrate that mitochondria-associated or -localized processes are the potential cellular targets of Aplidin. Whole genome gene-expression profiling (GEP) revealed that fatty acid metabolism, sterol biosynthesis and energy metabolism, including the tricarboxylic acid cycle and ATP synthesis are affected by Aplidin treatment. Moreover, mutant MOLT-4, human leukemia cells lacking functional mitochondria, were found to be resistant to Aplidin. Cytosine arabinoside (araC), which also generates oxidative stress but does not affect the ATP pool, showed synergism with Aplidin in our leukemia and lymphoma models in vitro and in vivo. These studies provide new insights into the mechanism of action of Aplidin. The efficacy of the combination of Aplidin and araC is currently being evaluated in clinical phase I/II program for the treatment of patients with relapsed leukemia and high-grade lymphoma. Keywords: Aplidin, araC, drug combination, hematological malignancies |
| 297 | GSE8565 |
Profile | Reduction in the cellular levels of the cyclin kinase inhibitor p27kip1 are frequently found in many human cancers and correlate directly with patient prognosis. Specifically ubiquitin dependent proteasomal turnover has been shown to cause reduced p27 expression in many human cancers. We recently demonstated that expression of a stabilized version of p27kip1 (p27kip1T187A) in a genetically modified mouse significantly reduced the number of intestinal adenomatous polyps which progressed to invasive carcinomas. Based on this work we set out to identify compounds which lead to a re-expression of p27 in cancer tissues. In this work we identify Argyrin A a compound derived from myxobacterium archangium gephyra as a potent inducer of p27kip1 expression. Argyrin A induces apoptosis in human colon cancer xenografts and tumor vasculature in vivo leading to a profound reduction in tumor size at well tolerated levels. Argyrin A functions are strictly dependent on the expression of p27kip1 as neither tumor cells nor endothelial cells which do not express p27kip1 respond to this compound. Surprisingly the molecular mechanism by which Argyrin A exerts its p27 dependent biological function is through a potent inhibition of the 20S proteasome. Keywords: protasome inhibitor time course, MCF7 cells, genome wide gene expression response, siRNA |
| 298 | GSE35426 |
Profile | Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrative transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P <0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. |
| 299 | GSE15464 |
Profile | Angiogenesis the formation of new capillaries by sprouting from preexisting vessels, is mainly induced by VEGF-A. To identify genes which are induced by VEGF-A in endothelial cells, HUVEC were starved and induced by VEGF-A165 for 30, 60 and 150min. RNA of induced and uninduced cells was isolated and subjected to microarray analysis using Affymetrix microarray. |
| 300 | GSE17466 |
Profile | Gene expression was measured on the Affymetrix platform in iPrEC cell line transfected with wild-type USP2A mutant USP2A, or empty vector. |
| 301 | GSE29832 |
Profile | Samples collected from human subjects in clinical trials possess a level of complexity arising from multiple cell types, that can obfuscate the analysis of data derived from them. Blood, for example, contains many different cell types that are derived from a distinct lineage and carry out a different immunological purpose. Failure to identify, quantify, and incorporate sources of heterogeneity into an analysis can have widespread and detrimental effects on subsequent statistical studies. We used microarrays to detail a statistical approach to model expression from a mixed cell population as the weighted average of expression from different cell types. Consequently, we can accurately and efficiently estimate the abundance of various cell populations. Favoring computation over manual purification has its advantages, such as measuring responses of multiple cell types simultaneously, keeping samples intact, and identifying biologically relevant differentially expressed genes. |
| 302 | GSE7964 |
Profile | The role of acid and bile salts in the pathogenesis of esophageal carcinoma arising from Barrett's metaplasia has been well established. Cell proliferation of Barrett's epithelium in response to pulsatile acid exposure has since been confirmed in vivo using endoscopy specimens. Histone deactylases (HDACs) modulate nucleosomal packaging of DNA thereby influencing gene transcription and multiple cancer-associated processes. Thus, we conducted microarray analysis to assess the ability of HDAC-42 to modulate key acid-induced changes as well as to impact other genes altered as the normal esophageal epithelium progresses along the metaplasia-dysplasia-esophageal adenocarcinoma continuum. Keywords: acid-pulsed cells pretreated with HDAC inhibitor or vehicle |
| 303 | GSE23376 |
Profile | In this study we tested the hypothesis that pregnancy a physiologic condition of transient, organ system-based immune evasion, can integrate known and identify new mechanisms of immune modulation pertinent to metastatic melanoma. |
| 304 | GSE20602 |
Profile | Expression data from microdissected glomeruli to examine the role of hypoxia in glomerulosclerosis of human Nephrosclerosis (NSC). |
| 305 | GSE28996 |
Profile | Adenoid cystic carcinoma (ACC) is one of the most common malignancies that arise in the salivary glands with an incidence of 4.5 per 1,000,000. It can also arise in glandular tissue closely related to salivary glands in the lacrimal gland, nasal passages and tracheobronchial tree, as well as in glands of the breast and vulva. At all of these sites, it is characterized by a distinctive histology of basaloid epithelial cells arranged in cribriform or tubular patterns, usually demonstrating abundant hyaline extracellular matrix secretion and some degree of myoepithelial differentiation. ACC is generally a slow-growing tumor characterized by a protracted clinical course, usually well over 5 years in duration, marked by regional recurrence, distant metastasis and/or spread along peripheral nerves. A recurrent chromosomal translocation, t(6;9)(q23;p21), has been identified in ACC, and recently it has been discovered that in a majority of ACC the MYB gene on chromosome 6 is fused to the 3’ terminus of the NFIB gene on chromosome 9, creating a fusion gene product resulting in increased MYB-related transcriptional activation. Recently it has been determined that most cell lines with attribution of ACC derivation are either contaminants of other cell lines or do not have the characteristic MYB-NFIB translocation. Also, there are no animal models of this histologically and genetically defined tumor type. To address the paucity of experimental and pre-clinical models systems of ACC, we have for several years been establishing xenograft tumor lines from clinical samples of ACC. We describe our experience with these models and their characterization here. |
| 306 | GSE23583 |
Profile | Clinical application of induced pluripotent stem (iPS) cells is limited by low efficiency of iPS derivation and protocols that permanently modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPS cells towards clinically useful cell types are lacking. Here we describe a simple, non-mutagenic strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate anti-viral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem (RiPS) cells into terminally differentiated myogenic cells. Our method represents a safe, efficient strategy for somatic cell reprogramming and directing cell fates that has broad applicability for basic research, disease modeling and regenerative medicine. |
| 307 | GSE25472 |
Profile | Understanding the systemic regulation of normal prostate gene expression by cholesterol diet is critical for deciphering the mechanisms responsible for the transition from healthy to pathogenic prostate conditions. To understand mechanism under cholesterol effect on prostate we performed microarray analysis using LNCaP human prostate cells cultured in low cholesterol medium. |
| 308 | GSE28691 |
Profile | Despite advances in contemporary chemotherapeutic strategies long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer. |
| 309 | GSE26661 |
Profile | Kaposi’s sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response. In order to identify cellular genes regulated by vIRF-3, cells from the PEL cell line BC-3 (KSHV positive) were transfected with either siRNAs targeted at vIRF-3 (si463 or si716s) or a negative control siRNA without homology to a known gene (siN, siNs). |
| 310 | GSE29819 |
Profile | Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of 6 ARVC specimen derived from heart transplantation candidates and compared our findings to 6 non-failing donor hearts (NF) which could not be transplanted for technical reasons. In addition, we compared our findings to 7 hearts from patients with idiopathic dilated cardiomyopathy. From each heart left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the six sample groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, unsupervised cluster analyses revealed no distinct expression pattern in LV and RV samples from ARVC-hearts. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. |
| 311 | GSE21909 |
Profile | Fourteen human subjects (18-40 years of age) were studied. The control group (saline + LPS [n = 7]) received a 12 hour infusion of saline and the experimental group (cortisol + LPS [n = 7]) received a 12 hour infusion of cortisol (3 µg/kg/min). After 6 hours of saline or cortisol infusion intravenous lipopolysaccharide (2 ng/kg) was administered to all subjects. Blood samples were collected at -24 hours, 0 hours, 6 hours and 24 hours relative to LPS administration at 0 hours. Leukocytes and monocytes were isolated from these blood samples, total RNA extracted, and microarray analyses performed using Affymetrix Focus GeneChips®. |
| 312 | GSE43700 |
Profile | The immune mechanisms that control resistance vs. susceptibility to mycobacterial infection in humans were investigated by studying leprosy skin lesions the site where the battle between the host and the pathogen is joined. Using an integrative genomics approach, we found an inverse correlation between of IFN-beta and IFN-gamma gene expression programs at the site of disease. The Type II IFN, IFN-gamma and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in the lesions from patients with the self-healing tuberculoid form of the disease and mediated antimicrobial activity against the pathogen, Mycobacterium leprae in vitro. In contrast, the Type I IFN, IFN-beta and its downstream genes, including IL-27 and IL-10, were induced in monocytes by M. leprae in vitro, and were preferentially expressed in the lesions of disseminated and progressive lepromatous form. The IFN-gamma induced macrophage antimicrobial response was inhibited by IFN-beta/IL-10, by a mechanism involving blocking the generation of bioactive 1,25-dihyroxy vitamin D as well as inhibiting induction of antimicrobial peptides cathelicidin and DEFB4. The ability of IFN-B to inhibit the IFN-gamma induced vitamin D pathway including antimicrobial activity was reversed by neutralization of IL-10, suggesting a possible target for therapeutic intervention. Finally, a common IFN-beta and IL-10 gene signature was identified in both the skin lesions of leprosy patients and in the peripheral blood of active tuberculosis patients. Together these data suggest that the ability of IFN-beta to downregulate protective IFN-gamma responses provides one general mechanism by which some bacterial pathogens of humans evade protective host responses and contribute to pathogenesis. |
| 313 | GSE14970 |
Profile | To determine cardiac transcription profiles we collected myocardial samples immediately after institution of cardiopulmonary bypass from acyanotic or cyanotic Tetralogy of Fallot patients undergoing corrective surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology. |
| 314 | GSE2822 |
Profile | Cultured epidermal keratinocytes treated with OsM 1 4, 24 & 48hrs, and Skinethic epidermal substitutes treated 1, 4, 24, 48h & 7days, each with untreated control Keywords: Time course |
| 315 | GSE11058 |
Profile | Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. Its ability to discriminate related human cells is unknown. Here we test the ability of this technique to determine the fractions of transformed cells of immune origin in mixed samples. Keywords: cell type comparison |
| 316 | GSE10924 |
Profile | Patterns of expressed genes examined in cryopreserved peripheral blood mononuclear cells (PBMCs) of seropositive persons electing to stop antiretroviral therapy in the AIDS Clinical Trials Group Study A 5170 were scrutinized to identify markers capable of predicting the likelihood of CD4+ T cell depletion after cessation of ART. Two cohorts were matched for clinical characteristics in a study of the effects of therapy interruption (TI) in ART-treated patients with immunological preservation. Disease progression was determined by CD4+ T cell count decline 24 weeks after TI.Gene Set Enrichment Analysis (GSEA) identified a set of genes in the Ras signaling pathway, associated with the downregulation of apoptosis, as significantly upregulated in the good outcome group at cessation of ART. Keywords: Disease state analysis |
| 317 | GSE22593 |
Profile | Estradiol Timecourse of MDA-MB-231ER+ cells containing a WT-ER and DBDmut-ER |
| 318 | GSE26298 |
Profile | Under conditions of hormonal adjuvant treatment the estrogen receptor apoprotein supports breast cancer cell cycling through the retinoic acid receptor α1 apoprotein. Basal proliferation persisted in estrogen-sensitive breast cancer cells grown in hormone depleted conditioned media without or with 4-hydroxytamoxifen (OH-Tam). Downregulating ER using siRNA inhibited basal proliferation by promoting cell cycle arrest. The basal expression of RARα1 the only RARα isoform that was expressed in breast cancer cell lines and in most breast tumors, was supported by apo-ER but was unaffected by OH-Tam. The overlapping tamoxifen-insensitive gene regulation by apo-ER and apo-RARα1 comprised activation of mainly genes promoting cell cycle and mitosis and suppression of genes involved in growth inhibition. |
| 319 | GSE15658 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 320 | GSE43017 |
Profile | We recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11 we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients. The breakpoints accumulated frequently adjacent to the T cell receptor alpha/delta chain locus (TCRα/δ) with chromosomal deletions at 14q11 and a recurrent 0.9 Mb interstitial deletion was identified at a region including part of the TCRα/δ locus. Because leukemia-associated genes are frequently located near the breakpoint cluster regions, we then analyzed the gene expression profiles of ATL cells and identified N-myc downstream regulated gene 2 (NDRG2) as one of the genes that are down-regulated in ATLL cells among the 25 genes mapped to the region adjacent to the recurrently deleted regions at 14q11. |
| 321 | GSE16082 |
Profile | A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. |
| 322 | GSE8692 |
Profile | Background: microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of the miRNA to a target mRNA usually in its 3’ untranslated region (UTR). As a result, translation of the target mRNA is inhibited and sometimes the mRNA itself can be de-stabilized. The inhibitory effects of miRNAs have been linked to many diverse cellular processes including malignant proliferation and apoptosis, development and differentiation, metabolic processes and neural plasticity. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. Methodology/Principal Findings: Biopsies from 12 human primary brain tumors were used to extract RNA. These samples were used to determine genome-wide mRNA expression levels by microarray analysis and a miRNA profile by real-time reverse transcription PCR (RT-PCR). Correlation coefficients were determined for all possible mRNA-miRNA pairs and the distribution of these correlations compared to the random distribution. An excess of high positive and negative correlation pairs were observed at the tails of these distributions. Most of these highest correlation pairs do not contain sufficiently complementary sequences to predict a target relationship; nor do they lie in physical proximity to each other. However, by examining pairs in which the significance of the correlation coefficients is modestly relaxed, negative correlations do tend to predict targets and positive correlations do tend to predict physically proximate pairs. A subset of high correlation pairs were experimentally validated by over-expressing or suppressing a miRNA and measuring the correlated mRNAs. Conclusions/Significance: Sufficient information exists within a set of tumor samples to detect endogenous correlations between miRNA and mRNA levels. Based on the validations of the correlations the causal arrow for these correlations is likely to be directed from the miRNAs to the mRNAs. From these data sets, we inferred and validated a tumor suppression pathway linked to miR-181c. Keywords: cell type comparison |
| 323 | GSE43116 |
Profile | Background: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV |
| 324 | GSE27838 |
Profile | Natural Killer cells (NK) a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients |
| 325 | GSE26525 |
Profile | The statsitcal model latent pathway identification analysis (LPIA), was implemented for the analysis of A549 lung carcinoma cells treated with geldanamycin. Control and treated samples were assayed with Affymetrix HG_U133_plus_2 arrays and analyzed using LPIA. LPIA looks for statistically signficant evidence of dysregulation in a network of pathways constructed in a manner that explicitly links pathways through their common function in the cell. Geldanamycin (geld) is known to inhibit the molecular chaperone protein, Hsp90, and plays a role in preventing the malignant transformation and proliferation of healthy cells during oncogenesis. LPIA successfully identified pathways specific to geldanamycin effects at the gene transcription level. |
| 326 | GSE9517 |
Profile | First experiment: Cells were cultured in sulfur amino acid-free DMEM supplemented with 0.1 mM methionine + 0.1 mM cysteine (complete) or supplemented only with 0.1 mM methionine (cysteine-free). Cells were cultured in either medium for 42 h (Long + Cys; Long -Cys) or in cysteine-free medium for 36 h followed by 6 h in complete medium (Short +Cys) Second experiment: C3A/HepG2 cells were cultured in sulfur amino acid-free DMEM supplemented with 0.1 mM Met and 0.1 mM Cys (complete) or supplemented only with 0.1 mM Met (cysteine-devoid). Cells were cultured in complete medium for 42 h (Long +Cys) or in complete medium for 36 h followed by cysteine-devoid medium for 6 h (Short -Cys). Keywords: amino acid deprivation |
| 327 | GSE11761 |
Profile | We compared PBMC genomic response to exercise in both early (EB) and late-pubertal boys (LB) Keywords: stress response |
| 328 | GSE2450 |
Profile | Rationale: Immortalized cells may exhibit important differences relative to their primary cell counterparts. Microarrays were used compare primary human umbilical vein endothelial cells (HUVECs) and the immortalized HUVEC cell line EA.hy926 in their response to inhibition of the mevalonate pathway by a HMG-CoA reductase inhibitor (atorvastatin). The effects of atorvastatin were reversed by the addition of mevalonate, to subtract non-specific changes in gene expression. Methods: Confluent cell cultures of HUVECs and EA.hy926 cells (two independent experiments in each cell type) were incubated with 1) statin-free media; 2) 10 microM atorvastatin; 3) 500 microM mevalonate; or 4) a combination of 10 microM atorvastatin and 500 microM mevalonate. All cells were harvested at 24 h. Total RNA was isolated using Trizol reagent (Invitrogen). cDNA was prepared from 10 microgram total RNA using a double-stranded cDNA synthesis kit (Life Technologies) with a T7-dT24 primer for first-strand synthesis. cRNA was synthesized from cDNA and biotinylated using the BioArray High Yield RNA Transcript Labeling Kit (Enzo Diagnostics). Twenty microgram of cRNA was fragmented by heating at 94°C for 35 min in fragmentation buffer, containing 40 mM Tris-acetate, pH 8.1, 125 mM KOAc, 30 mM MgOAc. Fifteen micrgram of fragmented cRNA, together with control cRNAs and grid alignment oligonucleotides, were hybridized overnight to GeneChip Human Genome U133A 2.0 arrays (Affymetrix) at 45°C under constant rotation. Arrays were washed and incubated with an anti-streptavidin antibody. Fluorescent signals were measured using an Agilent Gene Array Laser Scanner and analyzed with MicroArray Suite 5.0 (Affymetrix). Microarrays were scaled using default settings. Keywords: other |
| 329 | GSE29435 |
Profile | Every year more than 42000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs) as well as progesterone receptor (PR) positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT). Paraffin sections from patients with (n=9) or without (n=10) progressive endometrial cancer (recurrent or metastatic disease) were assessed for the presence of CD4+ (helper), CD8+ (cytotoxic) and Foxp3+ (regulatory) T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunosurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4 and WIF1, quantitive RT-PCR was performed to verify down regulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK) endometrial cancer cell lines stably transfected with PRA (IKPRA), PRB (IKPRB) and PRA+PRB (IKPRAB) were cultured in the presence/absence of progesterone (MPA) and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT makers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA-regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signalling. Intact progesterone signaling in non-progressive endometrial cancer seems to be an important factor stimulating immunosurveillance and inhibiting transition from an epithelial to a more mesenchymal, more invasive phenotype. |
| 330 | GSE25085 |
Profile | Human fetal and adult hematopoietic stem cells (HSC) were obtained from fetal liver fetal bone marrow (BM), and adult BM. These were injected into human fetal thymic implants in SCID-hu Thy/Liv mice (4-6 separate mice per HSC donor) and allowed to mature into single positive CD4+ (SP4) thymocytes over the course of 7-8 weeks. SP4 thymocytes from injected stem cells were subsequently sort-purified from thymic implants and gene expression was performed. |
| 331 | GSE12654 |
Profile | We performed the oligonucleotide microarray analysis in bipolar disorder major depression, schizophrenia, and control subjects using postmortem prefrontal cortices provided by the Stanley Foundation Brain Collection. By comparing the gene expression profiles of similar but distinctive mental disorders, we explored the uniqueness of bipolar disorder and its similarity to other mental disorders at the molecular level. Notably, most of the altered gene expressions in each disease were not shared by one another, suggesting the molecular distinctiveness of these mental disorders. We found a tendency of downregulation of the genes encoding receptor, channels or transporters, and upregulation of the genes encoding stress response proteins or molecular chaperons in bipolar disorder. Altered expressions in bipolar disorder shared by other mental disorders mainly consisted of upregulation of the genes encoding proteins for transcription or translation. The genes identified in this study would be useful for the understanding of the pathophysiology of bipolar disorder, as well as the common pathophysiological background in major mental disorders at the molecular level. Keywords: disease state analysis |
| 332 | GSE13597 |
Profile | Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and South East Asia where more than 50000 new cases are diagnosed each year. We used microarrays to identify down or upregulated genes in NPC compared with non-malignant controls. Keywords: Diseased versus control |
| 333 | GSE25743 |
Profile | EpCAM is frequently overexpressed in human invasive breast cancer. We reported EpCAM overexpression to be an independent prognostic marker for poor overall survival in node-positive breast cancer. We used microarrays in order to investigate changes of the transcriptome on EpCAM gene overexpression in human breast cancer cells |
| 334 | GSE41855 |
Profile | Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and observed a progressive enrichment in quiescent cells in these with time of culture; these cells were sorted, as their cycling counterparts, and their transcriptomes were compared. We used microarrays to detail the differential global gene expression profile between quiescent and cycling cells isolated from MALC. |
| 335 | GSE7462 |
Profile | Background: Diesel exhaust (DE) is the primary source of urban fine particulate matter which has been associated with cardiovascular disease in epidemiological studies. These effects may be related to oxidative stress and systemic inflammation with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. Objectives: We conducted an exploratory study using microarray techniques to analyze whether global gene expression in peripheral blood mononuclear cells (PBMCs) can inform on potential mechanisms of effect of DE inhalation. Methods: In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in two-hour sessions. We isolated RNA (Trizol/Qiagen method) form PBMCs before, and two times after each exposure. RNA samples were arrayed using the Affymetrix® platform (GeneChip® Human Genome U133 Plus 2.0 Array). Results: Microarray analyses were conducted on five subjects with available RNA sample form exposures to FA and to the highest DE inhalation (200 µg/m³ of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets with significant evidence for differential expression (more than 1.5-fold up or down regulated with p < 0.05) were identified. These include genes involved in inflammatory response (e.g., IL8RA, TNFAIP6, FOS), oxidative stress (e.g., HMOX1, BAX, PRDX1,), and in biochemical pathways like mitogen-activated protein kinases (MAPK) and tight junction pathways. Conclusions: These data suggest that DE may exert time-dependent changes in gene expression in PBMCs in healthy individuals. Genes that may be affected by DE inhalation are involved in inflammatory and oxidative stress processes. Keywords: time course |
| 336 | GSE16836 |
Profile | Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCGRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2 while a minor CD16+ Mo subset expresses CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including HIV infection. To gain insight into the developmental relationship and functions of CD16+ and CD16- Mo, we examined transcriptional profiles of these Mo subsets in peripheral blood from healthy individuals. Of 16,328 expressed genes, 2,759 genes were differentially expressed and 228 and 250 were >2-fold upregulated and downregulated, respectively, in CD16+ compared to CD16- Mo. CD16+ Mo were distinguished by upregulation of dendritic cell (DC) (SIGLEC10, CD43, RARA) and macrophage (MF) (CSF1R/CD115, MafB, CD97, C3aR) markers together with transcripts relevant for DC-T cell interaction (CXCL16, ICAM-2, LFA-1), cell activation (LTB, TNFRSF8, LST1, IFITM1-3, HMOX1, SOD-1, WARS, MGLL), and negative regulation of the cell cycle (CDKN1C, MTSS1), whereas CD16- Mo were distinguished by upregulation of myeloid (CD14, MNDA, TREM1, CD1d, C1qR/CD93) and granulocyte markers (FPR1, GCSFR/CD114, S100A8-9/12). Differential gene expression in CD16+ and CD16- Mo was confirmed by quantitative real time RT-PCR (i.e., CD16, C3AR1, C1QR1, ICAM-2, CSF1R, CSF3R, CDKN1C, TNFRSF1, and LTB) and flow cytometry (i.e., CSF1R, CSF3R, C1QR1, C3AR1, CD1d, CD43, CXCL16, and CX3CR1). Furthermore, increased expression of RARA and KLF2 transcripts in CD16+ Mo coincided with absence of cutaneous lymphocyte associated antigen (CLA) expression, indicating potential imprinting for non-skin homing. These results suggest that CD16+ and CD16- Mo originate from a common myeloid precursor, with CD16+ Mo having a more MF- and DC-like transcription program suggesting a more advanced stage of differentiation. Distinct transcriptional programs, together with their recruitment into tissues via different mechanisms, also suggest that CD16+ and CD16- Mo give rise to functionally distinct DC and MF in vivo. |
| 337 | GSE2485 |
Profile | By comparing to common tumor cells genes were differencially expressed in pseudopalisading cells in human glioblastoma Keywords: parallel sample |
| 338 | GSE25471 |
Profile | Analysis of HEK293T cells overexpressing ZAPS (zinc finger antiviral protein short form; NP_078901), which is a member of the PARP (poly (ADP-ribose) polymerase)-superfamily. Results of gene profiles provide insight into the role of ZAPS in innate immunity. |
| 339 | GSE26459 |
Profile | Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreover, silencing HSBP8 induced autophagy and caused cell death. Tamoxifen itself induced autophagy in sensitive cells but not in resistant ones, and tamoxifen-resistant cells were sensitive to the induction of autophagy by other drugs. These results may point to an important role for autophagy in the sensitivity to tamoxifen. |
| 340 | GSE27280 |
Profile | Pompe disease is caused by autosomal recessive mutations in the GAA gene which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease. |
| 341 | GSE7879 |
Profile | Analysis of genes that were differentially expressed in MSC-derived hES cells (VUB01 and SA01) as compared to VUB01 and SA01 undifferentiated hES cells Keywords: differentiation state analysis |
| 342 | GSE23038 |
Profile | Duplication of chromosomal arm 20q occurs in prostate cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play key roles in inducing malignancy via20q amplification. |
| 343 | GSE22367 |
Profile | Gene expression profiling was performed on primary human erythroid progenitor cells left untreated or treated with 0.5uM SAHA. The worldwide burden of sickle cell disease is enormous with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a novel bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease. |
| 344 | GSE14054 |
Profile | Small regulatory RNAs including small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide Argonaute (Ago) proteins to specific target RNAs leading to mRNA destabilization or translational repression. We recently reported the identification of Importin 8 (Imp8) as a novel component of miRNA-guided regulatory pathways. Imp8 interacts with Ago proteins and localizes to cytoplasmic processing bodies (P-bodies) structures involved in RNA metabolism. For this micro-array dataset, we used immunoprecipitations of Ago2-associated mRNAs followed by micro-array analysis. The results demonstrate that Imp8 is required for recruiting Ago protein complexes to a large set of Ago2-associated target mRNAs allowing for efficient and specific gene silencing. Therefore, we provide evidence that Imp8 is required for cytoplasmic miRNA-guided gene silencing. |
| 345 | GSE35935 |
Profile | Evaluation of pretreatment gene expression profiling features in elderly CLL patients; correlation with clinical outcome |
| 346 | GSE21785 |
Profile | Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-specific transcript dataset (GTD) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with ‘a prior’i established known prominent glomerular expression served for validation and were all found in the novel expression library (e.g. CDKN1 DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression for several novel glomerulus-enriched genes identified in REGGEL was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. Glomerular disease associated differential mRNA regulation of ROBO2 was found in diabetic nephropathy. In summary, using a comparative strategy on microdissected nephrons novel transcripts with predominant expression in the human glomerulus could be identified. A systematic analysis of this glomerulus-specifc gene expression library allows the detection of target molecules and biological processes involved in glomerular biology and renal disease. |
| 347 | GSE12355 |
Profile | Notch1-IC Notch2-IC or EBNA2 have been induced in a conditionally immortalized human B cell line (EREB2-5) in order to identify similar and unique target genes in B cells. CAT was used as a control. Keywords: time course |
| 348 | GSE39904 |
Profile | To investigate the role of TAZ downstream of the abberrant Wnt signaling in CRC cells we compared the expression profiles of parental SW480 cells (empty vector) transfected with siControl, siTAZ, sibeta-catenin or reconstituted with wild type APC and transfected with siControl Keywords: expression profiling by array |
| 349 | GSE25136 |
Profile | The derivation of molecular signatures indicative of disease status and predictive of subsequent behavior could facilitate the optimal choice of treatment for prostate cancer patients. In this study we conducted a computational analysis of gene expression profile data obtained from 79 cases, 39 of which were classified as having disease recurrence, to investigate whether advanced computational algorithms can derive more accurate prognostic signatures for prostate cancer. At the 90% sensitivity level, a newly derived prognostic genetic signature achieved 85% specificity. This is the first reported genetic signature to outperform a clinically used postoperative nomogram. Furthermore, a hybrid prognostic signature derived by combination of the nomogram and gene expression data significantly outperformed both genetic and clinical signatures, and achieved a specificity of 95%. Our study demonstrates the feasibility of utilizing gene expression information for highly accurate prostate cancer prognosis beyond the current clinical systems, and shows that more advanced computational modeling of tissue-derived microarray data is warranted before clinical application of molecular signatures is considered. |
| 350 | GSE3926 |
Profile | Reliable clinical tests for predicting cancer chemotherapy response are not available and individual markers failed to correctly predict resistance against anticancer agents. We hypothesized that gene expression patterns attributable to chemotherapy-resistant cells can be used as a classification tool for chemoresistance and provide novel candidate genes involved in anthracycline resistance mechanisms. We contrasted the expression profiles of 4 different human tumor cell lines of gastric pancreatic, colon and breast origin and of their counterparts resistant to the topoisomerase inhibitors daunorubicin or doxorubicin. We also profiled the sensitive parental cells treated with doxorubicin for 24h. We interrogated Affymetrix HGU133A and U95A arrays independently. We applied two independent methods for data normalization and used Prediction Analysis of Microarrays (PAM) for feature selection. In addition, we established data sets related to drug resistance by using a “virtual array” composed of features represented on both types of oligonucleotide arrays. We identified 71 candidate genes associated with doxorubicine/daunorubicine resistance. To validate the microarray data, we also analyzed the expression of 12 selected genes by quantitative RT-PCR or immunocytochemistry, respectively. While the comparison of drug-sensitive versus drug-resistant cells yields candidates associated with drug resistance, the 24h treatment of sensitive parental cells produced a distinct transcriptional profile related to short-term drug effects. Keywords: cell type and treatment comparison |
| 351 | GSE17100 |
Profile | To identify gene expression that distinguishes hematopoietic cells that express PRAME from those that do not normal CD34+ cells with forced PRAME expression were compared to cells without PRAME expression in culture over time (days 4, 7, 14) using Affymetrix HU-133A microarrays |
| 352 | GSE7102 |
Profile | Multiple sclerosis (MS) is an inflammatory disease of the central nervous system and is generally considered to be autoimmune in nature. We previously demonstrated that the transcription factor Sp3 is significantly down-regulated in immune cells from MS patients. The potential role of Sp3 down-regulation in MS pathogenesis is not well understood. The function of endogenous Sp3 was assessed in vitro after siRNA-mediated knockdown of its transcript in Jurkat cells. Sp3 protein levels were reduced an average of 70%. ELISA studies demonstrated decreased endogenous production of IL-10 and TGFβ1 and increased endogenous production of TNFα (p<0.05 in all assays). Subsequent microarray analysis demonstrated significantly altered expression of 36 genes (p<0.001 for each gene) compared with control samples. Analysis showed differential expression (p<0.005) of 8 gene pathways. Many of the genes and pathways that were regulated by Sp3 are involved in immune function specifically with regard to apoptosis, cell-to-cell adhesion, integrin signaling, T-cell differentiation, and cytokine production. This study identifies mechanisms by which Sp3 may regulate immune function and suggests a basis for its potential contribution to MS disease pathogenesis. Keywords: siRNA knockdown; Jurkat T-cells; Multiple Sclerosis |
| 353 | GSE4107 |
Profile | Background: Causative genes for autosomal dominantly inherited familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) have been well characterized. There is however, another 10-15 % early onset colorectal cancer (CRC) whose genetic components are currently unknown. In this study, we used DNA chip technology to systematically search for genes differentially expressed in early onset CRC. Keywords: disease state analysis |
| 354 | GSE10520 |
Profile | Approximately 20% of Acute Myelogenous Leukemia (AML) cases carry the t(8;21) translocation which involves the AML1 and ETO genes, and express the resulting AML1/ETO fusion protein that functions as a transcriptional repressor by recruiting NCoR/SMRT/HDAC complexes to DNA. We used microarrays to identify genes differentially expressed in U937 cells expressing AML1/ETO compared to vector transfected U937 cells. Keywords: Transcriptional regulation |
| 355 | GSE7476 |
Profile | Using Affymetrix microarray technology we analyzed the gene expression profiles of the most important pathological categories of bladder cancer in order to detect potential marker genes. Applying an unsupervised cluster algorithm we observed clear differences between tumor and control samples as well as between superficial and muscle invasive tumors. According to cluster results, the T1 high grade tumor type presented a global genetic profile which could not be distinguished from invasive cases. We described a new measure to classify differentially expressed genes and we compared it against the B-rank statistic as a standard method. According to this new classification method, the biological functions overrepresented in top differentially expressed genes when comparing tumor versus control samples were associated with growth, differentiation, immune system response, communication, cellular matrix and enzyme regulation. Comparing superficial versus invasive samples, the most important overrepresented biological category was growth and, specifically, DNA synthesis and mitotic cytoskeleton. On the other hand, some under expressed genes have been clearly related to muscular tissue contamination in control samples. Finally, we demonstrated that a pool strategy could be a good option to detect the best differentially expressed genes between two compared conditions. Keywords: disease state analysis |
| 356 | GSE12471 |
Profile | Several studies described a role for the E2F/Rb pathway in ovarian serous carcinomas (SCAs). Since E2F/Rb pathway deregulation is a general hallmark of human cancer it remains unclear whether this deregulation is of particular importance in SCAs or whether it reflects a common oncologic feature. Here, we attempted to clarify this issue by the examination of microarray expression profiles of SCAs (10 SCA1s, 15 SCA3s) and particularly by the comparison with another, less malignant, ovarian cancer type, serous borderline tumours (13 SBTs). Results were further validated by quantitative RT-PCR, both on the microarray samples and an independent panel. In addition, TP53 mutation analysis was performed. This integrated analysis revealed a significant increase in the expression of the transcription factors E2F1 and E2F3 in SCAs, when compared to SBTs. This was associated with a vast overexpression of E2F target genes in SCAs compared to SBTs. Overall, at least 45% of those genes with a significantly higher expression in SCAs were E2F targets. When taking into account the different SCA tumour grades, particularly SCA3s exhibited a major deregulated E2F target expression pattern, compared to SBTs. To a lesser extent, this was also the case for SCA1s, although the E2F target expression pattern of several SCA1s appeared to be more similar to SBTs. Generally, overexpression of E2F targets in SCAs appeared to be well-structured since those targets considered as negative regulators of the cell cycle or promoters of apoptosis were usually not overexpressed in SCAs. Similar to E2F target deregulation, TP53 mutations were identified in SCA3s, to a lesser extent in SCA1s, and not in SBTs. These results suggest that a structured, generally upregulated, E2F transcription factor activity is associated with a global cell cycle disturbance in high grade SCAs, and exceeds typical E2F/Rb pathway disruption in tumours, at least compared with SBTs |
| 357 | GSE5823 |
Profile | Affymetrix Hu133 GeneCHIP Microarray data for Control and c-MYC knock-down (KD) human cancer cell lines. Data related to article 'Novel c-MYC target genes mediate differential effects on cell proliferation and migration' from D. CAPPELLEN et al., EMBO Reports Note: Samples GSM136093 and GSM136094 (Hela cell line, expt 1) were hybridized and normalized separately from the other 18 Samples. Keywords: siRNA analysis |
| 358 | GSE30775 |
Profile | Knock-down of LSD1 using siRNA approach induced regulation of several proliferation-associated genes in ER-negative breast cancer cells MDA-MB-231. |
| 359 | GSE10592 |
Profile | Microarrays were used to evaluate the effects of azithromycin and an inflammatory stimulus (SMM) on human airway epithelium. Effects of azithromycin treatment were evaluated at 6 24 and 48 hours. Effects of SMM were evaluated at 6 and 24 hours. In addition, pretreatment with azithromycin was used to evaluate the modulatory effects on SMM-induced inflammation. SMM=supernatant from microcorpulent material from human cystic fibrosis airways. Keywords: timecourse, treatment comparisons. |
| 360 | GSE24093 |
Profile | Endothelial cells were transduced with different genes modulating signaling pathways and compared to GFP transduced control group to identify changes in the expression of the angiocrine factors. |
| 361 | GSE20430 |
Profile | Results from 29 samples tested on the Affymetrix HG-focused target array identified transcriptional changes characteristic of ocular disease and ocular Chlamydia trachomatis infection phenotypes. Large numbers of differentially regulated genes were demonstrated. These were characteristic of the host defence response and typical of innate responses at epithelial surfaces and infiltrating leukocytes. These results provide an insight into the complexity of the acute response in trachoma. |
| 362 | GSE21592 |
Profile | Study objectives: The objectives of this study was perform the global gene expression profiling aimed at identifying differentially expressed genes in the circulating lympho-monocytes of NRLCP patients affected by Narcolepsy with Cataplexy (NRLCP). Based on the tight association to the HLA-DQB1*0602 haplotype in caucasians it could be hypotesized an immunological dysregulation underlying the pathogenesis of the disease. Design: 10 NRLCP patients with 10 healthy controls were compared. Total RNA isolated from blood specimens was analyzed using microarray technology followed by statistical data analysis to detect genome-wide differential gene expression between patients and controls. Functional analysis of the genelist was performed in order to interpret the biological significance of the data. Results: 173 genes showed significant (p<0.01) differential expression between the two tested conditions. The biological interpretation allowed to categorize differentially expressed genes into main functional groups including includes genes involved in brain development, which could be possibly regarded as peripheral markers of the disease, along with molecular markers of the NRLCP-related dysmetabolic syndrome and immuregulatory molecules. Moreover a striking correlation within selected HLA haplotypes and HLA gene expression was detected, indicating an allele-specific trend of gene expression for the DQB1, DQA1 and DRB4 genes across all the tested subject, regardless of the disease status. Conclusions: the molecular profile associated to NRLCP suggested that molecular markers of neural, metabolic and immunological dysregulation can be detected in blood of NRLCP patients. Moreover, the allele-specific HLA gene expression could suggest a possible direct role of MHCII as a co-factor in the disease etio-pathogenesis |
| 363 | GSE12345 |
Profile | The goal of our study was to molecularly dissect mesothelioma tumor pathways by mean of microarray technologies in order to identify new tumor biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. We performed Affymetrix U133A plus 2.0 microarray analysis comparing 9 human pleural mesotheliomas with 4 normal pleural specimen. Stringent statistical feature selection detected a set of differentially expressed genes that were further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes never associated before to mesothelioma and could be involved in tumor progression. Notable, the identification of MMP-14, a member of matrix metalloproteinase family. This molecule has been described as a new disease marker and could be used as biomarker also for mesothelioma early diagnosis and prognosis and that can be viewed as new and effective therapeutic target to test. Accepted for pubblication in PLoS ONE |
| 364 | GSE1485 |
Profile | We measured the baseline expression levels of genes in members of the CEPH pedigrees using Affymetrix Human Genome Focus Arrays. Arrays were analyzed using MAS 5.0 software (Affymetrix). Keywords = natural variation Keywords = human Keywords: other |
| 365 | GSE41326 |
Profile | It has been demonstrated that Ring finger protein 43 (RNF43) is overexpressed in colorectal cancer and mediates cancer cell proliferation. We found that RNF43 was frequently overexpressed in HCC and knockdown of RNF43 could induce apoptosis and inhibit proliferation, invasion, colony formation and xenograft growth of HCC cells. Suggesting that RNF43 is involved in tumorigenesis and progression of HCC. We used microarrays to profile gene expression patterns before and after RNF43 knockdown, and identified differentially expressed genes during this process. |
| 366 | GSE18640 |
Profile | Background Homeobox gene associated regulatory networks are among the key determinants of early hematopoietic development. Previously the ‘hematopoietic PBX interacting protein’ (HPIP) has been identified as a novel interacting partner of the TALE homeodomain protein PBX1, forming a microtubule signalling complex. Expression of HPIP has been associated with increased tumorigenicity of the MCF7 breast cancer cell line. We now demonstrate that HPIP is a novel regulatory protein in human hematopoiesis: constitutive expression of HPIP in human umbilical cord blood derived CD34+ cells increased the absolute number of clonogenic progenitors in liquid expansion culture as well as in methylcellulose assays with a significantly enhanced formation of erythroid colonies compared to the control (p≤0.01, n=6). Limiting dilution LTC-IC assays confirmed the hematopoietic activity of the protein on primitive human progenitor cells with an over 5fold increase in the absolute number of LTC-ICs compared to non-transduced cells (n=8; p<0.05). In vivo HPIP expression induced a significant shift towards myeloid engraftment (n=8;p<0.05) and doubled the proportion of hCD34+CD38+ human cells in transplanted mice (p≤0.05, n=8). Structure – function analyses identified the C - terminal nuclear receptor/PBX interacting domain (NRPID; LXXLL domain) as a critical domain for the hematopoietic activity of HPIP. Gene expression data by microarray and Q-RT-PCR analysis demonstrated that HPIP induced particularly differential expression of genes involved in the MAPK pathway and cytokine-cytokine interaction. Taken together, these data demonstrate that proteins involved in the organization of microtubular signalling complexes such as HPIP can act as regulators of early human hematopoiesis. |
| 367 | GSE37258 |
Profile | Klinefelter’s Syndrome (KS) is one of the common chromosome aneuploidy diseases in males with unexplained physiological mechanism. iPSCs are similar to ESCs in terms of indefinitive self-renewal and pluripotency, provided an alternative choice for modeling disease to facilitate the disease research in vitro. We used microarray to detect the global reprogramming of KS and normal fibroblast cells to iPSCs. Also we used microarray to explore the possible molecular varieties between KS patient and normal person in the early development. |
| 368 | GSE30563 |
Profile | Stem cells from various lineages have well known for its migration tendency toward glioma and become attractive vehicles to deliver therapeutic genes to brain tumors. However which factors and mechanisms work in these function is not yet known. To identify those factors and mechanisms, we analyzed the brain tumor-specific gene expression profile using microarray analysis |
| 369 | GSE29850 |
Profile | Human umbilical vein endothelial cells (HUVECs) were transduced with either MIY-N1IC (Notch1 intracellular domain) or MIY vector control. The cells were sorted for YFP and RNA was extracted using Trizol (Invitrogen) and analyzed by the Affymetrix Human Genome U133 Plus 2.0 Array. Results were analyzed using the GCRMA algorithm to identify genes with a minimum of 2-fold induction or reduction. This global gene expression study was used to identify Notch targets in the endothelium. |
| 370 | GSE7021 |
Profile | In the chorionic villi of placenta trophoblasts and endothelial cells are present, and moreover mesenchymal cells (stromal cells) can be obtained. We generated cells with the mesenchymal phenotype from the chorionic mesoderm, and showed that: a) physiologically functioning cardiomyocytes were transdifferentiated from human placenta-derived chorionic villi cells, but these cells did not induce to osteoblasts and adipocytes ; b) the cardiomyogenic induction rate obtained using our system was relatively high compared to that obtained using the previously described method ; c) co-cultivation with fetal murine cardiomyocytes alone without transdifferentiation factors such as 5-azaC or oxytocin is sufficient for cardiomyogenesis in our system; d) Chorionic villi cells have the electrophysiological properties of 'working' cardiomyocytes. The chorionic mesoderm contained a large number of cells with a cardiomyogenic potential. Keywords: Cardiomyogenic induction |
| 371 | GSE9984 |
Profile | We used a whole genome approach to identify major functional gene categories (including xenobiotic transporters and metabolizing enzymes) whose expression depends on gestational age. STUDY DESIGN: We compared gene expression profiles of 1st (45-59 days) and 2nd trimester (109-115 days) and C-section term placentae. RESULTS: In 1st trimester placentae, genes related to cell cycle, DNA, aminoacids and carbohydrate metabolism were significantly overrepresented, while genes related to signal transduction were downregulated. In the organism defense category, we identified genes involved in chemical response, metabolism, and transport. Analysis of signal transduction pathways suggested, and subsequently confirmed independently, that the Wnt pathway was regulated by gestational age. CONCLUSIONS: Our study will serve as a reference database to gain insight into the regulation of gene expression in the developing placentae and, thus, allow comparisons with placentae from complicated pregnancies such as those in women experiencing gestational diabetes, pre-eclampsia and teratogenic sequelae. Keywords: time series |
| 372 | GSE14955 |
Profile | To determine cardiac transcription profile in acyanotic Tetralogy of Fallot patients we collected myocardial samples immediately after institution of cardiopulmonary bypass from acyanotic Tetralogy of Fallot patients undergoing corrective surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology. |
| 373 | GSE16538 |
Profile | We hypothesized that tissue genome-wide gene expression analysis coupled with gene network analyses of differentially expressed genes, would provide novel insights into the pathogenesis of pulmonary sarcoidosis. Keywords: Disease state analysis |
| 374 | GSE15151 |
Profile | Many human oncogenes are challenging therapeutic targets. An alternative to direct targeting of oncogenes is to perform “synthetic lethality” screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of the broad spectrum of mutant KRAS-driven cancers, and demonstrate the potential of RNAi screens for discovering critical functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers associated with “undruggable” genetic alterations. |
| 375 | GSE26471 |
Profile | Gene expression in HeLa cells was profiled using Affymetrix gene expression Human HG-U133_Plus_2 array. Transcript signal was mapped against the chromosome coordinates (probe-by-probe basis) using the HG-U133A_2 Annotations CSV file for hg18 build of the human genome provided by Affymetrix. Karnani N Taylor C, Malhotra A, Dutta A (2007) Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas. Genome Res 17: 865-876. |
| 376 | GSE15192 |
Profile | CD44+/CD24- subpopulation of normal and cancerous breast epithelial cells are suggested to have stem cell properties. The goal of this study was to identify gene expression differences between CD44+/CD24- and CD44-/CD24+ subpopulation of cells from a same cell lines. We selected MCF-10A cells which are immortalized derived from a fibrocystic breast disease. These cells are immortalized but not transformed and express basal cell markers. Cells were from a single sort but plated into four 100 mm plates. RNA was prepared from each plate separately for the analysis. |
| 377 | GSE26920 |
Profile | The molecular role of iron in gene expression remains poorly characterized. Moreover the alterations in global gene expression after iron chelation remains unclear and are important to assess for understanding the molecular pathology of iron-depletion and the biological effects of iron chelators. We assessed the effect on whole genome gene expression of two iron chelators (desferrioxamine and Dp44mT). These studies are important for understanding the molecular and cellular effects of iron-depletion. |
| 378 | GSE35364 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 379 | GSE25157 |
Profile | Membrane-bound transcription factor CREB3L1 undergoes Regulated Intramembrane Proteolysis (RIP) in response to Hepatitis C infection. RIP activates CREB3L1 so that it can prevent the growth of HCV infected cells through the action of downstream genes. We over-expressed a truncated form of CREB3L1 that does not require RIP to enter the nucleus. Cells over-expressing this truncated form were isolated by Fluorescence Activated Cell Sorting (FACS). We used microarray to determine the downstream genes of CREB3L1 in comparison to a flow sorted empty vector control. |
| 380 | GSE44841 |
Profile | Brain tumor neurospheres (BTCSs) are cancer cells with neural stem cell-like properties found in the fatal brain tumor glioblastoma multiforme (GBM). These cells account for less than 1% of total tumor cells are poorly differentiated and are believed to be involved in tumor induction, progression, treatment resistance and relapse. Specific miRNAs play important roles in modulating the proliferation and differentiation of neural stem cells, therefore, we aimed to identify miRNAs controlling differentiation in GBM-BTSCs through high throughput screening miRNA array profiling. We compared the miRNA expression profiles at the neurosphere state and upon 4 and 14days of differentiation by using LIMMA, finding 21 differentially expressed miRNAs : hsa-miR-103, hsa-miR-106a, hsa-miR-106b, hsa-miR-15b, hsa-miR-17, hsa-miR-19a, hsa-miR-20a, hsa-miR-25, hsa-miR-301a and hsa-miR-93 were found up-regulated upon differentiation, while hsa-miR-100, hsa-miR-1259, hsa-miR-21, hsa-miR-22, hsa-miR-221, hsa-miR-222, hsa-miR-23b, hsa-miR-27a, hsa-miR-27b, hsa-miR-29a and hsa-miR-29b were down-regulated. Expression of 11 of the 21 miRNAs was examined by qPCR and 7 of them were validated: hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222 increased their expression upon differentiation, while hsa-miR-93 and hsa-miR-106a were inhibited. Functional studies demonstrated that miR-21 over-expression induced the expression of glial and/or neuronal cell markers in the neurospheres, possibly due to SPRY1 targeting by miR-21 in these cells, while miR-221 and miR-222 inhibition at the differentiated state reduced the expression of those differentiation markers. On the other hand, miR-29a and miR-29b targeted MCL1 in the GBM neurospheres and increased apoptotic cell death. |
| 381 | GSE6606 |
Profile | Prostate cancer is characterized by heterogeneity in the clinical course that often does not to correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogeneous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodeling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer. Keywords: disease state analysis |
| 382 | GSE44541 |
Profile | Analysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with purified antimycin A1a or unfractionated commercially available antimycin A (Sigma A8674). |
| 383 | GSE29524 |
Profile | We used microarrays to examine the impact of AF1q/MLLT11 on the gene expression profile of Notch-activated CD34+CD45RA-Lin- HPCs isolated from umbilical cord blood CD34+CD45RA-Lin- HPCs correspond to early multipotent progenitors. A2M is a nuclear mutant derivative of AF1q/MLLT11 |
| 384 | GSE48998 |
Profile | Transgelin was the top-ranked marker of metastatic potential identified in the comparison of node-positive colorectal cancer (CRC) versus node-negative CRC in our previous study. Transgelin is localized in the nucleus of cultured CRC cells and microRNA-mediated knockdown of TAGLN (the gene encoding transgelin) expression modulates the expression of genes involved in the epithelial-to-mesenchymal transition. We performed gene expression profiling on control and transgelin-overexpressing RKO cells using Affymetrix microarray technology. |
| 385 | GSE14452 |
Profile | From the result of the gene expression analyses of human hepatoma cell line HepG2, a number of genes associated with cell proliferation and DNA repair were distinctively up-regulated by Ag-nanoparticle exposure, suggesting that Ag-nanoparticles might stimulate cell proliferation and DNA damage, which are considered to be mechanisms playing an important role for carcinogenesis and tumor progression. The inductions of these genes involved in cell proliferation were also observed in PS-nanoparticles and Ag2CO3-exposed cells. In addition, the inductions of DNA repair-associated genes were also observed in Ag2CO3-exposure. These results suggest that both “nanoshape” and “silver” can cause the inductions of these gene expression patterns. Furthermore, cysteine, a strong ionic silver ligand partially abolished these gene expressions induced by silver nanoparticles. Ionic silver sourced from Ag-nanoparticles could not fully explain these gene expressions. |
| 386 | GSE10760 |
Profile | Muscle biopsies taken from vastus lateralis muscle of 30 normal subjects and 19 FSHD subjects (see PubMed ID 17151338) Affymetrix U133A and U133B arrays were scanned both before (S1) and after (S2) antibody enhancement. Effects of age and sex in normal subjects reported previously under GSE362 GSE674, and GSE9676. Keywords: facioscapulohumeral dystrophy, skeletal muscle |
| 387 | GSE1009 |
Profile | Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy Keywords = Diabetes Keywords = kidney Keywords = glomeruli Keywords: other |
| 388 | GSE28914 |
Profile | In order to clarify the human response of re-epithelialization we biopsied split-thickness skin graft donor site wounds immediately before and after harvesting, as well as during the healing process 3 and 7 days thereafter. Altogether 25 biopsies from 8 patients qualified for the study. All samples were analysed by genome-wide microarrays. Here we identified the genes associated with normal skin re-epithelialization on time-scale, and organized them by similarities according to their induction or suppression patterns during wound healing. |
| 389 | GSE11045 |
Profile | mRNA expression differences between the liver and kidney of an adult male (homo sapien) were investigated using three technical replicates. The purpose of the experiment was to compare array data generated using Affymetrix with measures of expression obtained using RNAseq (a sequencing approach for measuring expression that utilizes Solexa technology). Keywords: kidney liver |
| 390 | GSE46062 |
Profile | We used DNA microarray technology to assess changes in gene expression after treatment of 11 lymphoma cell lines with epigenetic drugs. We identified genes with upregulated expression in treated cell lines and with downregulated expression in B-cell lymphoma patient samples when compared to normal B cells. |
| 391 | GSE21251 |
Profile | Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. |
| 392 | GSE14987 |
Profile | Expression data from ERBB2 over-expression and EGF stimulation in MCF10A cells |
| 393 | GSE5816 |
Profile | Abstract Background: Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The “rules” governing which genes are methylated during the pathogenesis of individual cancers how specific methylation profiles are initially established, or what determines tumor-type specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype identify pathways important as therapeutic targets. Methods and Findings: In an effort to identify new cancer-specific methylation markers, we employed a high throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5’ CpG islands, are induced from undetectable levels by 5-aza-2’-deoxycytidine (5-aza) in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (N=20) and adjacent non-malignant tissue showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or lymphocytes. We studied the eight most frequently and specifically methylated genes from our lung cancer data set in breast cancer (N=37), colon cancer (N=24), and prostate cancer (N=24) along with counterpart non-malignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. Conclusions: By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent potential targets for early detection screening or therapeutic intervention. Keywords: Cell line comparison |
| 394 | GSE656 |
Profile | primary ALL cells (B-lineage) resistant to prednisolone by the MTT in vitro sensitivity assay Keywords = ALL Keywords: other |
| 395 | GSE8762 |
Profile | Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease modifying therapies. For Huntington's disease (HD) a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates. In an attempt to exploit the known neuroinflammatory and transcriptional perturbations of disease, we measured relevant mRNAs in peripheral blood cells. The performance of these potential markers was weak overall, with only one mRNA, immediate early response 3 (IER3), showing a modest but significant increase of 32% in HD samples compared to controls. No statistically significant differences were found for any other mRNAs tested, including a panel of 12 RNA biomarkers identified in a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV et al. (2005) Proc Natl Acad Sci U S A 102: 11023-11028]. The present results may nonetheless inform the future design and testing of HD biomarker strategies. Keywords: RNA biomarker screen |
| 396 | GSE43884 |
Profile | UCHL1 is related to apoptosis and proliferation in cancers and we sought to identify genes regulated by UCHL1 |
| 397 | GSE24250 |
Profile | To accelerate the development of disease-modifying therapeutics for Huntington’s disease (HD) a dynamic biomarker of disease activity and treatment response is critically needed. |
| 398 | GSE2280 |
Profile | Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible. Keywords = oral carcinoma lymphatic metastasis predict Keywords: repeat sample |
| 399 | GSE23973 |
Profile | lincRNA-ST8SIA3 was depleted using siRNAs and associated gene expression changes were profiled on Affymentrix arrays |
| 400 | GSE47352 |
Profile | This study investigates the genes that promote clear cell renal cell carcimoma (ccRCC) metastasis using 4 primary metastatic and 5 non-metastatic tumor samples. U133 plus 2.0 array was used to identify the diffrently expressed genes between the primary metastatic and non metastatic ccRCC samples |
| 401 | GSE1648 |
Profile | Human intervertebral disc tissue was obtained from patients (average age 51 yrs) undergoing surgery for lumbar interbody fusion (n=3) or lumbar disc herniation (n=1). Cells were isolated by sequential pronase-collagenase digestion [3]. Cells were passaged twice in monolayer and suspended at a density of 2 x 106 cells/ml in 1.2% alginate (low viscosity Sigma Chemical, St Louis, MO) dissolved in 150 mM NaCl. Alginate beads were formed by dropwise addition of the alginate from a 22 gauge needle into 102 mM CaCl2, followed by 10 minutes of curing, as described previously [13, 27]. Cell-gel beads were incubated in cell culture media consisting of Ham’s F-12 medium (Gibco BRL, Grand Island, NY), supplemented with 10% FBS (HyClone, Logan, UT), 25 μg/ml ascorbic acid (Sigma, St. Louis, MO), 100 U/ml penicillin, 100 μg/ml streptomycin, and 1 μg/ml Fungizone at 5% CO2 and 37° C. After 24 h, the cell culture medium was removed via pipette and exchanged for one of three osmotically active solutions, representing iso-osmotic, hyper-osmotic and hypo-osmotic media [12, 23, 34]. The iso-osmotic solution consisted of a defined cell culture medium (Ham’s F-12 with supplements as described above; 293 mOsm/kg H2O). The hypo-osmotic solution consisted of the same cell culture media diluted with de-ionized water to a final osmolarity of 250 mOsm/kg H2O. The hyper-osmotic solution consisted of the same cell culture media supplemented with sucrose to a final osmolarity of 450 mOsm/kg H20. The osmolarity of all solution formulations was determined using a freezing-point osmometer (Advanced Laboratory Wide Range 3W2, Advanced Instrument, Needham Heights, MA) as described previously [12]. Cell-alginate beads were cultured for a 4 hour period under one of these conditions, after which the cells were released from alginate in a dissolving buffer (55 mM Na-citrate and 150 mM NaCl), lysed and stored at –80°C. Intervertebral disc (IVD) cells experience a broad range of physical stimuli under physiologic conditions, including alterations in their osmotic environment. In this study, the gene expression profile of human IVD cells was quantified with gene array technology following exposure to varying osmolarity in order to capture the biological responses for a broad set of targets. A total of 42 genes were identified in IVD cells as significantly changed following culture under hyper-osmotic conditions, while a total of 18 genes were identified as significantly changed under hypo-osmotic conditions. Gene expression patterns were verified using RT-PCR. Genes identified in this study include those related to cytoskeleton remodeling and stabilization (ephrin-B2, sarcoglycan beta, IQGAP1), as well as membrane transport (ion transporter SLC21A12, osmolyte tranporter SLC5A3, monocarboxylic acid SLC16A6, and amino acid transporter SLC7A8). An unexpected finding was the differential regulation of the gene for the neurotrophin brain-derived neurotrophic factor by hyper-osmotic stimuli that may be indicative of a physiological response of IVD cells to physical stimuli important in regulating discogenic pain. Keywords = intervertebral disc Keywords = osmotic stimuli Keywords: other |
| 402 | GSE24739 |
Profile | In comparing gene expression of normal and CML CD34+ quiescent (G0) and proliferating (G1/S/G2/M) cells 292 genes were down-regulated and 192 genes were up-regulated in the CML G0 cells. The differentially expressed genes were grouped according to their reported functions and correlations were sought with biological differences previously observed between the same groups. The most apparent correlations include: i) Normal and CML G0 cells are more primitive than G1/S/G2/M cells; ii) CML G0 cells are in a more advanced stage of development and more poised to begin proliferating than normal G0 cells; iii) When CML G0 cells are stimulated to proliferate, they undergo further differentiation and maturation more rapidly than normal G0 cells, but both granulopoiesis and erythropoiesis are less efficient than normal; iv) Whereas normal G0 cells form only granulocyte/monocyte (GM) colonies when stimulated by cytokines, CML G0 cells consistently form a combination of GM and erythroid clusters and colonies; and v) Prominin-1 (CD133) is the gene most down-regulated in CML G0 cells and its down-regulation appears to be associated with the spontaneous formation of erythroid colonies by CML progenitors without EPO. The gene most over-expressed in CML G0 cells is LepR, but its role in contributing to the myeloid expansion and other abnormalities is unknown. It was hoped that LepR might serve as a therapeutic target, but leptin had no stimulatory or inhibitory effect on either normal or CML G0 cells, our attempts to make a specific LepR antibody were unsuccessful, and no other potentially targetable over-expressed surface antigens were identified. |
| 403 | GSE33112 |
Profile | Primary colon CSC cultures were transduced with a Wnt responsive construct (TOP-GFP). 10% highest and lowest TOP-GFP cell fractions were FACS sorted and arrayed. |
| 404 | GSE10463 |
Profile | VAF347 is a low molecular weight compound which inhibits allergic lung inflammation in vivo. This effect is likely due to a block of dendritic cell (DC) function to generate pro-inflammatory T-helper (Th) cells since VAF347 inhibits IL-6 CD86 and HLA-DR expression by human monocyte derived DC, three relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biological activity of VAF347 since, i) other AhR agonists display an identical activity profile in vitro, ii) gene silencing of wild type AhR expression or forced over-expression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line and iii) AhR deficient mice are resistant to the compound’s ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo. Keywords: effect of compound |
| 405 | GSE33831 |
Profile | It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether MSCs transfer mitochondria to the cells under several different conditions of mitochondrial dysfunction including human pathogenic mitochondrial DNA (mtDNA) mutations. Using biochemical selection methods, we found that exponentially growing cells in restrictive media (uridine- and bromodeoxyuridine [BrdU]+) after coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mtDNA identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B rho0 cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. A chemotaxis inhibitory agent blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential “cell therapy-based mitochondrial restoration or mitochondrial gene therapy” for human diseases caused by mitochondrial dysfunction. |
| 406 | GSE9971 |
Profile | Study to identify genes associated with NSCLC recurrence in patients not receiving adjuvant chemotherapy. Purpose: Recent clinical trials suggest improvement in survival with adjuvant chemotherapy in non-small cell lung cancer (NSCLC). This study's aim is to identify genes associated with NSCLC recurrence in patients not receiving adjuvant chemotherapy. Experimental design: Banked NSCLC tumors of patients who underwent resection of stage Ia-IIIb disease were identified. Patients were stratified into two groups: recurrent (R n=11) or non-recurrent (NR, n=16) 2 years after surgery. Microarray profiling and Cox multivariate analysis were performed. Conclusion: Increased CYP3A5 gene expression correlates with NSCLC recurrence and promotes proliferation through mechanisms that may involve, in part, CYP3A5 epoxygenase activity. Keywords: comparison of gene expression profiles for recurrent and non-recurrent cancer |
| 407 | GSE17785 |
Profile | The PTEN/PI3K pathway is commonly mutated in cancer and therefore represents a rational target for therapeutic intervention. In order to investigate the primary phenotype(s) mediated by mutant PIK3CA in a clean and highly patient-relevant context we utilized a non-tumorigenic MCF10A parental and isogenic knock-in cell line that harbors a common activating PIK3CA kinase domain mutation (H1047R). We found that introduction of an endogenously mutated PIK3CA primarily results in a marked epithelial-mesenchymal transition (EMT) and invasive phenotype compared to isogenic wild-type cells. Moreover, a potent and selective inhibitor of PIK3CA (GDC-0941) was highly effective and selective on reversing this phenotype compared to cell-proliferation, highlighting a potential new paradigm for studying PI3K-pathway targeted agents. Keywords: Expression Array |
| 408 | GSE19238 |
Profile | We report a highly-penetrant form of obesity initially observed in 31 heterozygous carriers of a 593kb or larger deletion at 16p11.2 from amongst subjects ascertained for cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16053 individuals from 8 European cohorts; such deletions was absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (p = 6.4x10-8, OR = 43). These findings highlight a promising strategy for identifying missing heritability in obesity and other complex traits, in which insights from rare extreme cases can be used to elucidate the basis for more common phenotypes. |
| 409 | GSE16554 |
Profile | MDA-MB-231 bone-metastatic subline 1833 and lung metastatic subline 4175 underwent spontaneous ploidy doubling in culture i.e. the genome approximately duplicated itself gradually. The modal- and hyper-ploid subpopulations during the ploidy transition were sorted into two separate sublines, 1833-Modal and 1833-Hyper for 1833, 4175-Modal and 4175-Hyper for 4175. Their expresssion patterns were compared to each other as well as to other MDA-MB-231 sublines isolated previously by Kang et al. 2003 and Minn et al. 2005. Keywords: Cell type comparison |
| 410 | GSE9171 |
Profile | We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM) identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation. Keywords: static expression |
| 411 | GSE29175 |
Profile | Ovarian clear cell carcinoma (OCCC) shows unique clinical features including an association with endometriosis and poor prognosis. We previously reported that the contents of endometriotic cysts especially high concentrations of free iron, are a possible cause of OCCC carcinogenesis through iron-induced persistent oxidative stress. In this study, we conducted gene expression microarray analysis using 38 ovarian cancer cell lines and identified genes commonly expressed in both OCCC cell lines and clinical samples, which comprise an OCCC gene signature. The OCCC signature reproducibly predicts OCCC specimens in other microarray data sets, suggesting that this gene profile reflects the inherent biological characteristics of OCCC. The OCCC signature contains known markers of OCCC, such as hepatocyte nuclear factor-1b (HNF-1b) and versican (VCAN), and other genes that reflect oxidative stress. Expression of OCCC signature genes was induced by treatment of immortalized ovarian surface epithelial cells with the contents of endometriotic cysts, indicating that the OCCC signature is largely dependent on the tumor microenvironment. Induction of OCCC signature genes is at least in part epigenetically regulated, as we found hypomethylation of HNF-1b and VCAN in OCCC cell lines. This genomewide study indicates that the tumor microenvironment induces specific gene expression profiles that contribute to the development of distinct cancer subtypes. |
| 412 | GSE40751 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 413 | GSE10147 |
Profile | We used microarrays to detail the global program of gene expression underlying the effect of p17 on human plasmacytoid dendritic cells and was compared to CpG profile. Keywords: gene expression study |
| 414 | GSE4030 |
Profile | Schwann cells expanded in number by exposure to growth factors in vitro, could be useful in nervous system repair. Our previous results suggest that long term exposure to heregulin and forskolin changes the functional properties of the human Schwann cells, including the ability to myelinate axons after transplantation. Here, we propose to determine the molecular changes in the Schwann cells that occur as a result of extended growth with mitogenic factors. We believe that the information obtained in these studies will provide clues about mechanisms underlying the already observed changes in function. This information will aid in the prediction of the safety and efficacy of neural repair approaches that use cultured, expanded Schwann cells. Finally this data may provide clues into the mechanisms underlying normal human Schwann cell function. To use gene array analysis to compare gene expression profiles in early and late passage human Schwann cells exposed to the growth factors heregulin and forskolin. Observed changes in the function of human Schwann cells, including their capacity for growth and differentiation, after prolonged exposure to heregulin and forskolin, are caused by changes in the gene expression profiles in these cells. Nerves from four different donors were obtained within 12-15 h postmortem, with full consent for research from the families of the donors (faxed). IRB approval not required because subjects were officially dead at nerve harvest (IRB confirmation faxed). The nerve tissue obtained consisted of the lower 15 cm of nerve extending from mid calf to ankle. Endoneurial fascicles were dissected from short (1-2 cm) nerve fragments and cultured with heregulin and forskolin for 1 week. The nerve fascicles were then treated overnight with collagenase and dispase and dissociated by gentle trituration. Cells were plated at low density on laminin coated dishes and maintained in culture with mitogens for 3 passages. Schwann cell purities during this period were > 95%. RNA was extracted from the cells at passage 1 ( i.e. after 2 population doublings) and passage 3 (i.e. after 8 population doublings) from the following donors: SN HSC 330, age 51; SN HSC 317, age 29; SN HSC 329, age 20 and SN HSC 351, age 42. Thus eight samples (2 groups, 4 independent samples per group) are to be analyzed. Because both groups in this comparison have been exposed to mitogens, differences in gene expression profiles will be interpreted as indicative of changes caused by prolonged versus short term exposure to mitogens. More RNA was prepared from each group of cells than was needed for gene array analysis to allow confirmation of differentially-expressed gene transcripts by real-time RT-PCR. Since the main purpose of this project is to detect any major changes in the molecular properties of the Schwann cells, we propose that these samples be analyzed using Affymetrix U133 + 2 arrays containing the complete human genome and request Option 1: Start to Finish Profiling of all samples. We have contacted Dr Stanley Nelson at UCLA and discussed the project with him. We request that the samples be analyzed in the UCLA facility. Keywords: time-course |
| 415 | GSE5225 |
Profile | To investigate genes that might influence resistance to infection through IGF1R we screened human breast cancer-derived OCUB-M cells transfected with expression vector encoding IGF1R using microarray analysis. Keywords: overexpression comparison |
| 416 | GSE8764 |
Profile | Previous studies suggest that there may be age and gender related differences in salivary gland function. However the limited and often conflicting information available from healthy populations makes it difficult to confirm these differences. The purpose of the present study was to evaluate and compare changes in gene expression associated with age and gender in the human parotid gland. Differential expression, defined as statistically significant differences with at least 1.5 fold changes, was detected using the Affymetrix® GeneChip® HGU133plus2.0 microarray in 787 gene probe sets; 320 showed higher expression in males, while 467 showed higher expression in females. Several genes associated with saliva secretion were differentially expressed in male and female parotid gland including vesicle-associated membrane protein 3 VAMP3, synaptosomal-associated protein SNAP23, RAS oncogene family member RAB1A, syntaxin binding protein STXBP1. When the gene expression results from the youngest (19-38 years old) and the oldest (65-69 years old) female subjects were further evaluated, it was found that the expression of 228 genes were altered during aging; 155 genes were down-regulated, whereas 73 genes were up-regulated in the female parotid gland. Of the genes that were altered during aging, 24 of the 28 genes (86%) classified as being associated with immune responses were down-regulated in the aged parotid gland. A panel of differentially expressed, age- and gender-related genes was selected for further study by quantitative, real-time RT-PCR. Comparable differences in gene expression were detected by both Affymetrix array and quantitative, real-time RT-PCR methods. Taken together, our data suggest that salivary gland function may be adversely affected in the aged population due, at least in part, to the down regulation of several categories of genes. Moreover, the gender specific gene expressions identified in the present study correlates with the previously observed sexual dimorphism in salivary gland function. Keywords: Human Parotid Gland |
| 417 | GSE26626 |
Profile | The presence of the PUF (Pumilio/FBF) domain defines a conserved family of RNA-binding proteins involved in repressing gene expression. It has been suggested that a conserved function of PUF proteins is to repress differentiation and sustain the mitotic proliferation of stem cells. In humans Pumilio2 (PUM2) is expressed in embryonic stem cells and adult germ cells. To identify mRNAs associated with human PUM2 protein in adipose tissue stem cells (ADSC), we used a modified Ribonucleoprotein-ImmunoPrecipitation Microarray (RIP-Chip). PUM2 ribonucleoprotein (RNP) complexes were performed with 2 µg of anti-Pum2 antibody (goat polyclonal, Santa Cruz Biotechnology, CA, USA) bound to protein G-agarose beads (Sigma, Deisenhofen, Germany). ADSCs were lysed in polysome lysis buffer (Tris-HCl pH 7.4 15mM, MgCl2 15 mM, NaCl 0,3 M, 1% Triton X-100, 1 mM DTT, 100 U/ml RNase Out, PMSF 1mM and E64 10uM) for one hour at 4°C. Beads were washed, then buffer and cell lysate were added, and the reaction mixtures were tumbled for 2 hours at 4°C. After this incubation, the beads were thoroughly washed again with polysome lysis buffer and then either RNA extracted for microarray and RT-PCR experiments using the RNeasy mini kit (Qiagen). To control for non-specifically enriched RNAs, identical IPs were performed with beads precoated with preimmune goat serum as a negative control. RNA was processed for hybridization with GeneChip 3’ IVT Express (Affymetrix - Santa Clara, USA), according to the manufacturers instruction. Briefly, cDNA was synthesized from immunoprecipitated RNA using reverse transcriptase followed by second strand synthesis to generate double-stranded cDNA. An in vitro transcription reaction was used to generate biotinylated cRNA. After purification and fragmentation, cRNA was hybridized onto GeneChip Affymetrix Human Genome U133 Plus 2.0 arrays. Post hybridization washes were preformed on an Affymetrix GeneChip Fluidics Station 450. Arrays were scanned on an Affymetrix GeneChip Scanner 3000. Scanned arrays were normalized using GCRMA in Partek software (Partek Incorporated. St. Louis, MO). Differentially enriched RNAs were found after performing One-way ANOVA analysis comparing immunoprecipitated samples against control samples. Final lists of genes were obtained by filtering the data from the statistical results according to fold enrichment more than 2 and a p value associated of less than 0.05 for features with signal well above the background. |
| 418 | GSE25087 |
Profile | We compared differences in fetal and adult T cells by performing whole genome profiling on sort-purified T cells (naïve CD4+ and Treg cells) from human fetal specimens (18-22 gestational weeks) and adult specimens (age 25-40 years old). Fetal and Adult Naïve CD4+ T cells phenotype: CD3+CD4+CD45RA+CCR7+CD27+ Fetal and Adult CD4+CD25+ Treg phenotype: CD3+CD4+CD25bright |
| 419 | GSE11118 |
Profile | Gene expression analysis identified 27 of these 744 p300 and pol II associated genes as significantly increased (p≤ 0.05) within the first hour following mitogen stimulation Keywords: time course |
| 420 | GSE6751 |
Profile | Periodontal infections have been associated with systemic inflammation and risk for atherosclerosis and vascular disease. We investigated the effects of comprehensive periodontal therapy on gene expression of peripheral blood monocytes. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity apoptosis, and cell signaling. We concluded that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect. Keywords: time course,disease state analysis |
| 421 | GSE47392 |
Profile | To understand the biological pathways involved in twin-twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA Analysis of paired data from TTTS cases and controls revealed differential expression of 801 genes which were significantly enriched for neurological disease and cardiovascular system pathways. We also identified cardiovascular genes and pathways associated with the presence of critically abnormal Doppler measurements in Stage III TTTS recipients. |
| 422 | GSE48611 |
Profile | Down syndrome (trisomy 21) is the most common genetic cause of intellectual disability but the precise molecular mechanisms underlying impaired cognition remain unclear. Elucidation of these mechanisms has been hindered by the lack of a model system that contains full trisomy of chromosome 21 (Ts21) in a human genome that enables normal gene regulation. To overcome this limitation,we created Ts21-induced pluripotent stem cells (iPSCs) from two sets of Ts21 human fibroblasts. One of the fibroblast lines had low level mosaicism for Ts21 and yielded Ts21 iPSCs and an isogenic control that is disomic for human chromosome 21 (HSA21). Differentiation of all Ts21 iPSCs yielded similar numbers of neurons expressingmarkers characteristic of dorsal forebrain neurons that were functionally similar to controls. Expression profiling of Ts21 iPSCs and their neuronal derivatives revealed changes in HSA21 genes consistent with the presence of 50% more genetic material as well as changes in non- HSA21 genes that suggested compensatory responses to oxidative stress. Ts21 neurons displayed reduced synaptic activity, affecting excitatory and inhibitory synapses equally. Thus, Ts21 iPSCs and neurons display unique developmental defects that are consistent with cognitive deficits in individuals with Down syndrome and may enable discovery of the underlying causes of and treatments for this disorder. |
| 423 | GSE23130 |
Profile | Although it is well-recognized that apoptosis senescence, and increased production of inflammatory cytokines and catabolic products are important factors in the degeneration of the human intervertebral disc, there is poor understanding of the underlying cause. The objective of the present study was to analyze gene expression patterns in the human annulus disc tissue. |
| 424 | GSE38232 |
Profile | Heat-Shock Factor 1 (HSF1) master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their non-transformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, even these genes are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications. |
| 425 | GSE26495 |
Profile | T cell dysfunction is an important feature of many chronic viral infections. In particular it was shown that PD-1 regulates T cell dysfunction during chronic LCMV infection in mice and PD-1 high cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, HCV and HBV. However, it is not known if PD-1 high cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function and gene expression profiles of PD-1 high versus PD-1 low CD8 T cells in the peripheral blood of healthy human adults as following: 1) The percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans and PD-1 was expressed by the memory CD8 T cells. 2) PD-1 high CD8 T cells in healthy humans did not significantly correlated with the PD-1 high exhausted gene signature of HIV specific human CD8 T cells or chronic LCMV specific CD8 T cells from mice. 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults. 4) PD-1 was expressed by the effector memory (TEM) compared to ‘terminally differentiated effector’ (TEMRA) CD8 T cells. 5) Finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. |
| 426 | GSE40184 |
Profile | This study characterizes the effects of chronic Hepatitis C virus (HCV) infection on gene expression by analyzing blood samples from 10 treatment-naive HCV patients and 6 healthy volunteers. Differential expression analysis of microarray data from peripheral blood mononuclear cells (PBMCs) identified a 136 gene signature including 66 genes elevated in infected individuals. Most of the up-regulated genes were associated with interferon (IFN) activity (including members of the OAS and MX families, ISG15 and IRF7), suggesting an ongoing immune response. This HCV signature was also found to be consistently enriched in many other viral infection and vaccination datasets. Validation of these genes was carried out using a second cohort composed of 5 HCV patients and 5 healthy volunteers, confirming the up-regulation of the IFN signature. In summary, this is the first study to directly compare blood transcriptional profiles from HCV patients with healthy controls. The results show that chronic HCV infection has a pronounced effect on gene expression in PBMCs of infected individuals, and significantly elevates the expression of a subset of interferon-stimulated genes. |
| 427 | GSE47685 |
Profile | Microarray profiles of native HeLa cells and RNF185/BSK65 gene silenced HeLa cells using siRNAs LMG2 and LMG4 were monitored using Affymetrix U133 Plus 2.0 microarrays. |
| 428 | GSE29561 |
Profile | We investigated whether we could identify gene expression profiles in initial core biopsies of breast cancer samples that would permit to a) predict a clinically meaningful response to Epi/Doc in terms of tumor size reduction b) predict a profound reduction in intratumoral Ki67 protein expression, and c) predict an in vitro response to Epi/Doc in the ATP-TCA. |
| 429 | GSE5372 |
Profile | Responses of the Human Airway Epithelium Transcriptome to In Vivo Injury To identify genes participating in repair of the human airway epithelium following injury we used bronchoscopy and brushing to denude the airway epithelium of healthy individuals, sequentially sampled the same region 7 and 14 days later, and assessed the recovered epithelium for relative levels of gene expression using Affymetrix high-density oligonucleotide microarrays with TaqMan PCR confirmation. Histologic assessment showed that the epithelium was denuded immediately following injury, at 7 days the epithelium was completely covered but partially de-differentiated, and by 14 days there was close to normal proportions of differentiated cells. Gene expression analysis was carried out with both the Affymetrix Microarray Suite 5.0 and Robust Multi-array Average algorithms, applying a multiple test correction to identify bona fide changes in gene expression. At day 7, there were substantial differences in the gene expression pattern compared to the resting epithelium, with a distinctive airway epithelial “repair transcriptome” of actively proliferating cells in the process of re-differentiation. The repair transcriptome at 7 days was dominated by genes encoding proteins involved in cell cycle regulation, transcription, signal transduction, metabolism and transport. Interestingly, the majority of cell cycle genes differentially expressed at day 7 belonged to the G2 and M late phases of the cell cycle, suggesting that the proliferating cells are relatively synchronized 1 wk following injury. At 14 days post-injury, the majority of the gene expression changes observed at day 7 were no longer observed, with the expression profile similar to that of resting airway epithelium. Using a class prediction algorithm, a group of 50 genes dominated by cell cycle genes, that represent a human airway epithelial “repair signature” was identified. These observations provide a baseline of the functional gene categories participating in the process of normal human airway epithelial repair that can be used in future studies of injury and repair in human airway epithelial diseases. Keywords: response to airway injury |
| 430 | GSE15495 |
Profile | Early onset sepsis due to Group B streptococcus (GBS) leads to neonatal morbidity increased mortality and long term neurological deficencies. Interaction between septicemic GBS and confluent monlayers of human coronary artery endothelial cells (HCAEC) was analyzed by a genome wide expression profiling. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real Time RT-PCR assay (Granulocyte chemotactic protein 2 (CXCL6)), ELISA (Urokinase, Cyclooxygenase 2 (COX2), Granulocyte chemotactic protein 1 (IL8)) and Western Blotting (Heme oxygenase1, BCL2 interacting protein (BIM)) at various time points between 4 and 24 hours. In total, 124 genes were differentially regulated (89 upregulated, 35 downregulated) based on a more than 3-fold difference to unstimulated HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection and inflammation. We confirmed upregulation of urokinase (UPA), COX2, HMOX1 and BCL2 interacting protein and downregulation of CXCL6 and IL8. These results indicate that GBS infection might lead to impaired function of the innate immune system and might contribute to hemorrhagic and inflammatory complications during GBS sepsis. Keywords: stimulated HCAEC (with S. agalactiae) vs unstimulated control cells |
| 431 | GSE15636 |
Profile | Analysis of differentiated Caco-2 intestinal epithelial cell line cocultured with probiotics L. acidophilus NCFM™ B. lactis 420, L. salivarius Ls-33 bacterial cells or treated with cell-free supernatant, and with E. coli O157:H7 cell-free supernatant. Lactobacillus and Bifidobacterium are important genera suggested to be beneficial for human health and E. coli O157:H7 is a pathogen causing hemorrhagic colitis and hemolytic uremic syndrome. Results provide insight into the mechanisms underlying the beneficial effects of probiotics on intestinal epithelial cells and a comparison to pathogenic E. coli. |
| 432 | GSE23405 |
Profile | Hyperthermia is widely used to treat patients with various cancers. 42.5˚C is well known as the inflection point of hyperthermia and generally up to 42˚C of hyperthermia is used in clinical cases combined with other therapies. Here the effects of heat stress at 42 or 44˚C for 15 min on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with heat stress (42 or 44°C for 15 min), followed by incubation for 0, 1, 3 or 6 h at 37°C. The percentage of DNA fragmentation was 8.4 ± 2.2 (mean ± SD) at 42°C for 6 h and 21.0 ± 2.0 at 44°C for 6 h. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with heat stress at 42 and 44°C. |
| 433 | GSE17302 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 434 | GSE23451 |
Profile | To identify candidate genes involved in enhanced tumorigenicity of CD133+ liver tumor-initiating cells Affymetrix Human Genome U133 Plus GeneChip 2.0 |
| 435 | GSE18235 |
Profile | Nine cigarette smoke condensates (CSCs) were produced under a standard ISO smoking machine regimen and one was produced by a more intense smoking machine regimen. These CSCs were used to treat primary normal human bronchial epithelial cells for 18 hours. |
| 436 | GSE14107 |
Profile | Identify Wnt3A responsive signature in lung adenocarcinoma cells |
| 437 | GSE46326 |
Profile | Embryos secrete preimplantation factor (PIF) a peptide present in maternal circulation during viable pregnancy. We compared downstream synthetic PIF effect on gene expression in non-pregnant Human Endometrial Stromal Cell (HESC) and First Trimester Decidual cell (FTDC) culture to mimic the maternal intrauterine environment during embryo implantation and trophoblast invasion. |
| 438 | GSE12643 |
Profile | Microarray-based studies of skeletal muscle from patients with type 2 diabetes and high-risk individuals have demonstrated that insulin resistance and reduced mitochondrial biogenesis co-exist early in the pathogenesis of type 2 diabetes independent of hyperglycaemia and obesity. It is unknown whether reduced mitochondrial biogenesis or other transcriptional alterations co-exist with impaired insulin-responsiveness in primary human muscle cells from patients with type 2 diabetes. Results: No single gene was differently expressed after correction for multiple testing and no biological pathway was differently expressed using both approaches for global pathway analysis. In particular, we found no evidence for differential expression of genes involved in mitochondrial oxidative metabolism. Consistently, there was no difference in mRNA levels of genes known to mediate the transcriptional control of mitochondrial biogenesis, PPARGC1A and NRF-1, or in mitochondrial mass between diabetic and control myotubes. Keywords: Cell culture, genetic, oxidative phosphorylation, microarray, skeletal muscle, type 2 diabetes |
| 439 | GSE28339 |
Profile | We have characterized gene expression changes in HeLa cells following long term depletion of Cyclin T2 or Cyclin T1 using shRNA |
| 440 | GSE2077 |
Profile | • The origin of biological samples (In vitro infection of HCT-8 cells with Cryptosporidium parvum) Monolayers of the HCT-8 cells (ATCC CCL-244 American Type Culture Collection) were cultured in RPMI 1640 medium containing 10% fetal bovine serum and additional nutritional supplements. Cells in log phase were plated at 2×106 cells per 150 mm tissue culture dish and infected with sterilised Cryptosporidium parvum oocysts (Iowa strain). Purified oocysts were suspended in phosphate buffered saline, sterilised in 33% bleach for 7 min on ice, washed in Hank's buffered saline solution, and added to HCT-8 cultures at a ratio of one oocyst per cell. Following a 2 h excystation period at 37 °C, cells were washed with warm Hank's buffered saline solution, and cells were incubated in fresh supplemented media. Mock-infected cultures were treated identically, with the exception that oocysts were not added to the cultures. Three independent mock- and C. parvum-infected cultures were prepared for analysis. • The origin of mRNA samples At 6, 12, 24, 48, and 72h post-inoculation, cell culture media were removed and cultures were immediately lysed by the addition of 3.5 ml of Trizol® reagent (GIBCO BRL Life Technologies) directly to the culture plate. Total RNA was prepared as described by the manufacturer, and poly(A) mRNA was isolated using oligo-dT cellulose columns (Amersham Pharmacia Biotech). The qualities of total RNA and poly(A) mRNA preparations were assessed by Northern blot. • Protocols for conducting microarray hybridization Poly(A) mRNA was converted into ‘target’ suitable for hybridisation to Affymetrix microarray chips according to protocols provided by Affymetrix Inc. (Santa Clara, CA). Briefly, 2.0 g of poly(A) mRNA was reverse-transcribed to prepare double-stranded cDNA using T7-(dT)24 primer (GENSET Corp., La Jolla, CA) and Superscript II reverse transcriptase (GIBCO). Approximately 1 g of cDNA was used for in vitro transcription in the presence of biotinylated UTP and CTP using the Enzo BioArray High Yield RNA Transcript Labelling Kit (Enzo Diagnostics, Inc). This labelled cRNA was fragmented in 40 mM Tris–acetate (pH 8.1), 100 mM potassium acetate, and 30 mM magnesium acetate at 94 °C for 35 min. The integrity of cRNA and the efficiency of fragmentation were monitored by Northern blot analysis (not shown). Fragmented biotinylated cRNA targets were hybridised to HG-U95Av2 chips (Affymetrix) that contain probe sets for 12,600 human gene/transcripts. Fifteen micrograms of fragmented cRNA and appropriate controls were hybridised to the chips at 45 °C for 16 h with constant rotation at 60 rev./min. The chips were subsequently washed and stained with streptavidin–phycoerythrin conjugate using the GeneChip Fluidics station protocol EukGE_WS2 (Affymetrix). Following washing and staining, microarray chips were scanned twice at 3 m resolution using a Hewlett-Packard confocal scanner and hybridisation intensities for each of the genes/transcripts were collected from scanned images. • Analysis of microarray data Gene expression data were initially analysed with the GeneChip® expression analysis software (Affymetrix Microarray Suite, version 5.0). The fluorescence intensity of the genes/transcripts was measured for each probe array and, to minimise discrepancies due to non-biological variations, normalised by global scaling to 1000. Further data analyses were performed using GeneSpring software (version 6.0; Silicon Genetics, Redwood City, CA). Per gene normalisation was applied in which the expression signal of each gene in C. parvum-infected cells (raw data) was normalised to the median of its measurements in the mock-infected samples (control); and the ratio of expression levels between mock and infected samples was calculated as the mean value of normalised signal vs. control signal among three replicates. To identify genes with significantly altered expression, a series of statistical analyses (filtering) were performed: cut-off values for ratio of expression levels 1.80 and 0.55 were used to filter genes with expression level fold changes greater than ±1.8 in all three independent samples. Genes with fold change variations >1.5 across the three samples were excluded. Furthermore, a ‘statistical group comparison’ using Student's t-test/ANOVA was conducted to compare mean expression levels between mock-infected and infected samples, and the genes with significant differential expression (P<0.05) were selected. Identified differentially expressed genes were then annotated using GeneSpring's ‘Build Simplified Ontology’ constructor which hierarchically groups genes into meaningful biological categories (gene lists) based on the Gene Ontology Consortium Classifications. Various lists of regulated genes were created by cross-referencing annotated gene lists and applying assorted statistical and visualisation methods. Keywords: time-course |
| 441 | GSE41239 |
Profile | We studied transcriptional changes by Affymetrix human microarrays in 2 DLBCL cell lines as a result of shRNA mediated knockdown of EZH2. In eukaryotes epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations. Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma. |
| 442 | GSE30499 |
Profile | Nonsense-mediated RNA decay (NMD) is regulated by a variety of cellular stresses. We expose U2OS cells to several stresses and assess RNA expression in the absence of transcription (i.e. stability). These studies identify transcripts that are stabilized by the physiological inhibition of NMD. |
| 443 | GSE28317 |
Profile | Compare the gene expression profile among human CD34+ cord blood cells infected with MIGR1 MIGR1-AML1-ETO or MIGR1-AML1-ETO∆NHR1 AML1-ETO promotes the self-renewal of human hematopoietic stem/progenitor cells (HSPCs). We found deletion of NHR1 domain abrogates AML1-ETO induced expasion of HSPCs. |
| 444 | GSE18309 |
Profile | With the aging population there is a growing focus on dementia, especially Alzheimer’s disease (AD). The molecular basis underlying the pathogenesis of AD is gradually being elucidated. Increasing evidence has shown that the immunological function of leukocytes plays a crucial role in the development of neurodegenerative disorders. However, there have been few studies among the Taiwanese population. The aim of this study was to investigate potential biomarkers for early diagnosis of Alzheimer’s disease from blood leukocytes. |
| 445 | GSE28379 |
Profile | We established two clones of induced pluripotent stem cells (iPSC) with the presenilin 2 mutation N141 (PS2-1 iPSC and PS2-2 iPSC) by retroviral transduction of primary human fibroblasts. To show the similarity among 201B7 iPSC, PD01-25 iPSC(Sporadic Parkinson's disease patient derived iPSC), PS2-1 iPSC, PS2-2 iPSC, this experiment was designed. |
| 446 | GSE14841 |
Profile | Micro-inflammation and gut dysfunction are features of diarrhea-irritable bowel syndrome (d-IBS) patients although the underlying interacting molecular mechanisms remain mostly unknown. Therefore, we aimed to identify critical networks and signaling pathways active in chronic diarrhea-associated inflammation. Keywords: Comparison of gene expression |
| 447 | GSE10979 |
Profile | The environmental carcinogen (±)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), causes bulky-adduct DNA damages, triggers certain signaling pathways, and elicits gene expression changes. Here, we focused on the temporal gene expression changes induced by a low concentration (0.05 µM) BPDE in human amnion epithelial FL cells. Differential gene expression profiles at 1, 10 and 22 h post BPDE treatment were obtained using Affymetrix HG-U133 Plus 2.0 oligonucleotide microarrays. A cohort of gene expression changes related to cell cycle progression, cell growth or apoptosis, stress response, and post-transcriptional regulation was validated with quantitative real-time RT-PCR. The alteration of several cell cycle-related genes was correlated and possibly contributed to the cell cycle arrest phenotype. Paradoxical transcriptional regulations regarding cell growth or apoptosis emerged in response to BPDE treatment, which indicated that cell fate was determined by integrated signals. The temporal transcriptional changes would be of help to clarify the molecular mechanism of cellular response to BPDE. Keywords: time course |
| 448 | GSE5547 |
Profile | Comparison of gene expression from subjects who resolved or formed pustules to H.ducreyi. In human inoculation experiments the cutaneous immune response to Haemophilus ducreyi consists of serum, PMN, macrophages, T cells and myeloid DC. In reinfection experiments, some subjects form pustules twice (PP group) or resolve infection twice (RR group). Although pustule formation is associated with serum resistance and phagocytic failure, there are no differences in the ability of isolated phagocytes or serum obtained from PP and RR subjects to ingest or kill H. ducreyi. To identify the basis for differential host susceptibility to H. ducreyi, we used microarrays to profile gene expression in infected and uninfected tissue and monocyte-derived DC obtained from PP and RR subjects. In infected tissue, both groups had a core response to H. ducreyi. Many additional transcripts that signify active immune function were upregulated exclusively in RR tissue, while PP tissue exclusively contained differentially regulated transcripts consistent with immune dysregulation. The core response of infected DC from both groups was typical of a DC1 response. RR DC exclusively expressed many additional transcripts indicative of DC1 function, while PP DC uniquely expressed differentially regulated transcripts characteristic of both DC1 and DCreg. The data suggest that DC from PP and RR subjects are prewired to respond differentially to H. ducreyi. Keywords: comparison of two phenotypes, resolver and pustule former |
| 449 | GSE10739 |
Profile | Parental MM6 cells as an additional control, were treated with LPS and PMA. Genes affected by the treatments were identified. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Keywords: knockdown |
| 450 | GSE13353 |
Profile | Background and Purpose Aneurysmal subarachnoid hemorrhage almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects working age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. Such knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. Methods We compared the whole genome expression profile of eleven ruptured sIA wall samples, resected at a median of 15 hours after rupture, to that of eight unruptured ones. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes. Results Overall, 686 genes were significantly upregulated and 740 downregulated in the ruptured sIA walls. Significantly upregulated biological processes included: response to turbulent blood flow; chemotaxis; leukocyte migration; oxidative stress; vascular remodelling; and extracellular matrix degradation. Toll like receptor (TLR) signalling and NF-κB, HIF1A and ETS transcription factor binding sites were significantly enriched among the upregulated genes. Conclusions We identified pathways and candidate genes associated to the rupture of human sIA wall. These results provide a molecular basis analysis (a) to identify rupture-prone sIAs and (b) to prevent their rupture. Novel measures to prevent the rupture of sIA wall may include inhibition of response to turbulent blood flow, leukocyte migration, TLR signalling, or blockade of NF-κB, HIF1A and ETS transcription factors. |
| 451 | GSE7236 |
Profile | B lymphoblastoid cell lines were obtained from Coriell Cell Repositories. Cell lines were grown according to Coriell guidelines and total RNA was extracted labeled, and hybridized to an Affymetrix Human Genome Focus Array as previously described. We found extensive variation in gene-expression levels and estimate that ~83% of genes are differentially expressed among individuals and that ~17% of genes are differentially expressed among populations. By decomposing total gene-expression variation into within- versus among-population components, we find that most expression variation is due to variation among individuals rather than among populations, which parallels observations of extant patterns of human genetic variation. Keywords: resting expression levels in B lymphoblastoid cell lines |
| 452 | GSE33425 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 453 | GSE15602 |
Profile | TNF antagonists are routinely used in severe rheumatoid arthritis (RA) patients who failed conventional DMARD therapy. According to large clinical trials the three available drugs (adalimumab, infliximab and etanercept) display similar effects in terms of efficacy, tolerability and side effects. These studies also indicate that about 25% of RA patients treated with TNF-antagonists do not display any significant clinical improvement. The aim of this study was to investigate global molecular patterns in synovial biopsies from RA patients obtained 12 weeks after initiation of adalimumab therapy. |
| 454 | GSE11792 |
Profile | The pathogenesis of acne has been linked to multiple factors such as increased sebum production inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of skin from 8 patients treated with isotretinoin was performed to gain insights into its mechanism of action. Skin biopsies were obtained from the patients at baseline and at 8 weeks isotretinoin treatment. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays in order to examine changes in gene expression as a result of treatment. After treatment, 784 genes were significantly changed: 197 up-regulated and 587 down-regulated. The majority of genes that were up-regulated at 8 weeks encode structural proteins of the extracellular matrix such as collagens, fibulin and fibronectin. The preponderance of genes that were down-regulated at 8 weeks are involved in the metabolism of steroids, cholesterol and fatty acids. Keywords: drug treatment effects |
| 455 | GSE12921 |
Profile | The similarity in gene-expression profiles suggest that PGL2 like SDHD, is involved in the functionality of the SDH complex, and that tumor formation in these three subgroups involves the same pathways as in SDH linked paragangliomas. We were not able to clarify the identity of PGL2 on 11q13. The lack of differential gene-expression of chromosome 11 genes might indicate that chromosome 11 loss, as demonstrated in SDHD-linked paragangliomas, is an important feature in the formation of a paraganglioma regardless of the genetic background. Keywords: disease state analysis |
| 456 | GSE2443 |
Profile | Affymetrix U133A comparison of two groups (10 samples each): untreated (androgen-dependent) primary prostate cancer (Gleasons 5-9) and androgen-independent primary prostate cancer. All samples were microdissected for tumor cells only. Keywords = advanced prostate cancer Keywords = androgen-independence Keywords = laser capture microdissection Keywords = RNA amplification Keywords: other |
| 457 | GSE7224 |
Profile | To study characteristics of the orapharyngeal epithelia which may influence susceptibility or resistance to HIV we performed microarray analysis of the tonsil and gingival epithelium.Tonsil epithelium has been implicated in HIV pathogenesis, but its role in oral transmission remains controversial. We performed microarray analysis of Laser Capture Microdissected tonsil and gingival epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared to the epithelium of another oro-pharyngeal site, gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV binding molecules, FcRγIII, complement receptor 2, and various complement components. This increased expression of molecules involved in viral recognition, binding and entry may favor virus-epithelium interaction in an environment with reduced innate anti-viral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate anti-viral factors may render the tonsil a potential site for oral transmission. Keywords: Cross sectional |
| 458 | GSE6728 |
Profile | Identification of potential tumor suppressor genes using the GINI strategy in Mantle Cell Lymphoma cell lines Keywords: response to drug treatment |
| 459 | GSE12211 |
Profile | Imatinib has become the current standard therapy for patients with chronic myelogenous leukaemia (CML). For a better understanding of the Imatinib-related molecular effects in vivo we assessed gene expression profiles of Philadelphia Chromosome positive (Ph+) CD34+ cells from peripheral blood of 6 patients with de novo CML in chronic phase. After 7 days of treatment with Imatinib the Ph+ CD34+ cells were reassessed to look for changes in the transcriptome. The expression level of 303 genes was significantly different comparing the transcriptome of the Ph+ CD34+ cells before and after 7 days of Imatinib therapy (183 down-regulated, 120 up-regulated, lower bound ≥1.2-fold). For a substantial number of genes governing cell cycle and DNA replication, the level of expression significantly decreased (CDC2, RRM2, PCNA, MCM4). On the other hand, therapy with Imatinib was associated with an increase of genes related to adhesive interactions, such as L-selectin or CD44. A group of 8 genes with differential expression levels were confirmed using a gene specific quantitative real-time PCR. Thus, during the first week of treatment, Imatinib is preferentially counteracting the bcr-abl induced effects related to a disturbed cell cycle and defective adhesion of leukemic Ph+ CD34+ cells. |
| 460 | GSE30807 |
Profile | To determine whether enhanced self-renewal and tumorigenicity in UT2 cells (derived from the second human–mouse xenotransplantation of U2OS cell-formed osteosarcoma tissues) correlate with increased expression of stem/progenitor cell-associated genes we measured global gene expression in MSC, U2OS and UT2 cells by microarray analysis. Compared to U2OS and MSC, molecules involved in regulation of self-renewal signaling pathways of cancer stem cells were also up-regulated in UT2 cells, including those in the Notch, Wnt, and TGF-beta pathways. These data suggest a genetic basis for the enhanced self-renewal and tumorigenicity of osteosarcoma-initiating cell in UT2 cells. |
| 461 | GSE14951 |
Profile | We have studied the genes activated in human liver transplantation to identify potential target genes for the prevention or treatment of related injuries. In a first protocol in order to evaluate the effect of Ischemia-Reperfusion Injury (IRI) on gene expression profile, we compared gene expression levels in transplanted-reperfused livers versus basal values in donor livers, identifying 795 genes significantly modified in human liver after transplantation. Some genes are likely to be completely activated by IRI, as they are not expressed at all in basal livers. In a second protocol, in order to identify gene dysregulations already present in donor livers, which might affect gene expression profile after transplantation, gene expression evaluated in the first study was compared to control livers (espression data retrieved from ArrayExpress database). About 900 genes in donor livers are dysregulated if compared to the control condition. At least 400 of them remain dysregulated or become more and more dysregulated after transplantation. |
| 462 | GSE27328 |
Profile | We are studying signaling pathways and growth properties of cultured human ovarian cancer cells that are expressing the G protein-coupled receptor luteinizing hormone receptor (LHR),particularly interested in the changes that occur when the receptor is activated by its cognate ligand, gonadotropin (LH). To investigate these questions, we have employed the SKOV3 ovarian cancer cell line that has been stably transfected with LHR, and can then test the response of these cells in culture following exposure to LH. |
| 463 | GSE46362 |
Profile | Combined overexpression of miR-125b with miR-99a and/or miR-100 induced VCR resistance in ETV6-RUNX1-positive leukemic cells Reh. We used microarrays to detail the global changes in gene expression of Reh cells upon enforced expression of miR-125 per se compared with combination of overexpression of miR-125b miR-100 and/or miR-99a |
| 464 | GSE32967 |
Profile | Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior resistance to androgen ablation, and frequent but short responses to chemotherapy. The model systems we report reflect the biology of the human disease and can be used to improve our understanding of SCPC and to develop new therapeutic strategies for it. Experimental Design: We developed a set of CRPC xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts and used a panel of 60 human tumors to validate our findings using immunohistochemistry. Results: We show that SCPC and LCNEC xenograft models retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other M-phase cell cycle genes in the absence of AR, retinoblastoma (RB1) and cyclin D1 (CCND1) expression and confirm these findings in a panel of CRPC patients’ samples. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts and that there is amplification of the UBE2C locus and microdeletions of RB1 in a subset of these, but no AR nor CCND1 deletions. Moreover, the AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts. Conclusion: Modeling human prostate cancer with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings. |
| 465 | GSE41075 |
Profile | Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium that frequently causes an asymptomatic genital tract infection gradually cleared by host immunity Transcriptome profiles were made of endometrial tissue from women with or without genital tract C. trachomatis infection, to characterize host responses to infection. Profiles showed that infection polarized host defense toward Type 2 immune responses. Responses included fibrin deposition, enhanced wound repair, and tissue remodeling. |
| 466 | GSE15091 |
Profile | We compared PC3 cells with or without harboring the wild-AR construct in the growth conditions of 1nM R1881 10nM R1881 and ethanol (the solvent for R1881). The MOCK control is PC3 cells transfected with the empty vectors. |
| 467 | GSE8865 |
Profile | From the result of comparative the gene expression analyses of human hepatoma cell line HepG2 following exposures of three heavy metals; arsenic, cadmium and nickel and three carcinogens; N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA) and tetrachloroethylene (TCE), 31-55% of the genes altered by As, Cd and Ni exposure were overlapped with those by three model carcinogen exposures in our experiments. In particular, three heavy metals shared certain characteristics with TPA and TCE in remarkable up-regulations of the genes associated with progression of cell cycle, which might play a central role in heavy metal carcinogenesis. In addition, this characteristic of gene expressions alteration was counteracted by intracellular accumulation of vitamine C in As-exposed cells but not in Cd- and Ni-exposed cells. These results suggest that the cell proliferative responses are caused by reactive oxygen species mainly in As exposure, while other mechanisms would be involved in these responses in Cd and Ni exposures. Keywords: other |
| 468 | GSE11281 |
Profile | The species Staphylococcus (S.) aureus harbors 19 superantigen gene loci six of which are located in the enterotoxin gene cluster (egc). While these egc superantigens are far more prevalent in clinical S. aureus isolates than non-egc superantigens, they are not a prominent cause of toxic shock. Moreover, neutralizing antibodies against egc superantigens are very rare, even among carriers of egc-positive S. aureus strains. In search of an explanation we have tested two non-exclusive hypotheses: 1) egc and non-egc superantigens have unique intrinsic properties and drive the immune system into different directions; 2) egc and non-egc-superantigens are released by S. aureus under different conditions, which shape the immune response. A comparison of three egc (SEI, SElM and SElO) and three non-egc superantigens (SEB, SElQ, TSST-1) revealed that both induced proliferation of human PBMC with comparable potency and elicited similar Th1/Th2-cytokine signatures. This was supported by gene expression analysis of PBMC stimulated with one representative superantigen from each group (SEI and SEB). They induced very similar transcriptional changes, especially of inflammation-associated gene networks, corresponding to a very strong Th1- and Th17-dominated immune response. In contrast, the regulation of superantigen release differed markedly between both superantigen groups. Egc-encoded proteins were secreted by S. aureus during exponential growth, while non-egc superantigens were released in the stationary phase. We conclude that the distinct biological behavior of egc and non-egc superantigens is not due to their intrinsic properties, which are very similar, but caused by their differential release by S. aureus. |
| 469 | GSE45535 |
Profile | Objective: Production of pathogenic autoantibodies by self-reactive plasma cells (PC) is a hallmark of autoimmune diseases. Investigating the prevalence of PC in autoimmune disease and their relationship with known pathogenic pathways may increase our understanding of the role of PC in disease progression and treatment response. Methods: We developed a sensitive gene expression based method to overcome the challenges of measuring PC using flow cytometry. Whole genome microarray analysis of sorted cellular fractions identified a panel of genes IGHA, IGJ, IGKC, IGKV, and TNFRSF17, expressed predominantly in PC. The sensitivity of the PC signature score created from the combined expression levels of these genes was assessed through ex vivo experiments with sorted cells. This PC gene expression signature was used for monitoring changes in PC levels following anti-CD19 therapy; evaluating the relationship between PC and other autoimmune disease-related genes; and estimating PC levels in affected blood and tissue from multiple autoimmune diseases. Results: The PC signature was highly sensitive and capable of detecting as few as 300 PCs. The PC signature was reduced over 90% in scleroderma patients following anti-CD19 treatment and this reduction was highly correlated (r = 0.77) with inhibition of collagen gene expression. Evaluation of multiple autoimmune diseases revealed 30-35% of lupus, rheumatoid arthritis, and scleroderma patients with increased PC levels. Conclusion: This newly developed PC signature provides a robust and accurate method to measure PC levels in the clinic. Our results highlight subsets of patients across multiple autoimmune diseases that may benefit from PC depleting therapy. |
| 470 | GSE19592 |
Profile | DUSP1 is involved in different cellular pathways including cancer cell proliferation angiogenesis, invasion and resistance to chemotherapy. To understand more about the cellular responses regulated by DUSP1 in NSCLC cells, we interfered DUSP1 expression in the NSCLC cell line H460 and studied the changes in gene expression differentially regulated by this phosphatase. Keywords: Expression profiling by array in cells with genetic modification |
| 471 | GSE29315 |
Profile | A cohort of distinct thyroid neoplasias was hybridized onto the Affymetrix U95 GeneChip |
| 472 | GSE23450 |
Profile | To identify candidate genes involved in enhanced tumorigenicity of CD133+ liver tumor-initiating cells Affymetrix Human Genome U133 Plus GeneChip 2.0 |
| 473 | GSE24743 |
Profile | Shikonin is a active component isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon and exhibits multiple pharmacological properties such as anti-oxidant, anti-inflammatory, and anti-tumor effects. Here, the effects of shikonin on the gene expression of human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with 100 nM shikonin, and followed by incubation for 3h at 37°C. Flow cytometry analysis with Annexin-V and propidium iodide demonstrated that no cell death was observed in the cells at 100 nM shikonin. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with the compound. |
| 474 | GSE15385 |
Profile | MicroRNAs are small non-coding RNA species some of which are playing important roles in cell differentiation. However, the level of participations of microRNAs in epithelial cell differentiation is largely unknown. Here, we found that expression levels of four microRNAs (miR-210, miR-338-3p, miR-33a and miR-451) were significantly increased in differentiated stage of T84 cells, compared with undifferentiated stage. Additionally, we demonstrate that miR-338-3p and miR-451 contribute to the formation of epithelial basolateral polarity by facilitating translocalization of beta1 integrin to the basolateral membrane. However, candidate target mRNAs of miR-338-3p and miR-451 and the mechanism behind observed phenomena is uncertain. Then, we performed comprehensive gene expression analysis to identify candidate target mRNAs and understand their mechanisms. |
| 475 | GSE9329 |
Profile | Rheumatoid arthritis (RA) a chronic and systemic disease of unknown etiology, is characterized by hyperplasia of synovial cells, which ultimately lead to the destruction of cartilage and bone. To elucidate the molecular mechanisms that lead to RA, we analyzed synovial cells established from patient with RA by oligonucleotide microarrays. Gene expression profiles reveal a novel pathophysiologic function of RA synovial cells as a generator of oxidative stress, and a self-defense mechanism against self-generated oxidative stress. Keywords: cell type comparison, disease state analysis |
| 476 | GSE10161 |
Profile | Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis. |
| 477 | GSE18906 |
Profile | B19V NS1 is known to be cytotoxic and involved in the pathogenesis of B19V infection. Our previous data demonstrated that NS1 impaired the cell-cycle progression of the CD36+ EPCs by inducing a stable G2 arrest. Microarray analysis was used to identify genes whose expressions were associated with the NS1-induced G2 arrest. A total of 1045 genes displayed a more than 1.5-fold differential expression in the NS1-transduced cells. Out of 1045 differentially expressed genes 177 were involved in cell-cycle regulation and 51 were involved in the regulation of cell differentiation. Keywords: RNA |
| 478 | GSE29402 |
Profile | The identification of a marker that is expressed in the conjunctival epithelium but not in the corneal epithelium has been a growing need. A more specific marker of limbal and conjunctival epithelia would be necessary to detect non-corneal epithelial cells on the corneal surface. To search for conjunctival specific marker(s) we first performed preferential gene profiling in the conjunctiva in direct comparison to that in the cornea using microarray technique. |
| 479 | GSE6257 |
Profile | The exit of antigen-presenting cells (APC) and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels is however unknown. Here we show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LEC) leading to expression of the key leukocyte adhesion receptors ICAM-1 VCAM-1 and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of DC via afferent lymphatics. Lastly, we show that TNF_-stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking mAbs. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for anti-inflammatory therapy. Keywords: TNFalpha, Lymphatic endothelium, induction, Inflammation |
| 480 | GSE28504 |
Profile | The trophoblast cell lineage is specified as early as the blastocyst stage leading to the individualization of trophectoderm from pluripotent cells of the inner cell mass. We used a double in vitro transcription mRNA amplification technique and compared trophectoderm with pluripotent stem cells. |
| 481 | GSE41196 |
Profile | We used gene expression profiling of human DCIS and IBC to discover uniquely expressed genes that may also regulate progression. |
| 482 | GSE23610 |
Profile | Traditional Chinese medicines (TCM) usually composed of a mixture of components, may simultaneously target multiple genes/pathways and thus achieve superior efficacy for complex diseases such as cancer. To identify novel mechanisms of action and potential health benefits for a TCM formula Si-Wu-Tang (SWT) widely used for women’s health, we obtained the DNA microarray expression profiles for SWT, its active component ferulic acid, and estradiol in human breast cancer cell line MCF-7 and analyzed the gene expression signatures associated with each treatment using the “Connectivity Map” (cMAP). This study indicates that DNA microarray profiling analysis and cMAP data mining provide a powerful approach to discover unknown mechanisms of actions and identify potential new health benefits for TCM. |
| 483 | GSE9101 |
Profile | We previously found that a native lipoprotein mix with a high VLDL+LDL/HDL ratio causes a global de novoDNA methylation in THP-1 macrophages. In the present experiment we assessed the consequences of global lipoprotein-induced de novo DNA methylation on global gene expression in the same cells. Moreover we sought to use gene expression array data to measure RNA expression levels for candidate factors mediating the epigenetic effects of lipoproteins. Keywords: comparison treated vs. control |
| 484 | GSE10831 |
Profile | Gene expression was compared between four B-cell derived HL cell lines (L428 L1236, L591, KMH2) and GC B cells from three different patients. Keywords: Cell type comparison |
| 485 | GSE23366 |
Profile | Expression patterns of Dendritic cells co cultured with cord blood MSC were compared with cord blood MSC (USSC). Putative immune suppressive candidates were tested to explain this inhibition. We find that cord blood MSC themselves are hardly immunogenic as tested with allogeneic T-cells. Dendritic cells cocultured with second party T-cells evoked abundant proliferation that was inhibited by third party cord blood USSC. Optimal inhibition was seen with one cord blood USSC for every dendritic cell. Blocking HLA-G only saw partial recovery of proliferation. Several cytokines prostaglandins, gangliosides, enzymes like arginase, NO synthase and indole amine 2,3-dioxygenase as well as the induction of Treg were not involved in the inhibition based on the microarrays and functional tests. Although the mechanism by which it does so remains partially undefined and subject to further study, cord blood multipotent stromal cells are strong inhibitors of the immune response and therefore allow their use in tissue regeneration settings in an allogeneic setting. Keywords: Adult stem cells, developmental biology, gene expression, genomics, human cord blood, mesenchymal stem cells, cel type comparison |
| 486 | GSE11330 |
Profile | SOX genes encode a family of high-mobility group transcription factors that play critical roles in organogenesis. Virtually all members of SOX family have been found to be deregulated in tumors of various origins. However little is known about the cellular and molecular behaviours involved in the oncogenic potential of SOX proteins. Cell culture experiments, tissue analysis, and molecular profiling revealed that SOX2 promotes cell proliferation and tumorigenesis through its transcription regulation of cell cycle related genes in breast cancer cells Keywords: Gene Transfection |
| 487 | GSE40893 |
Profile | Gene network of erythropoietic cells Special attention has recently been drawn to the molecular network of different genes that are responsible for the development of erythroid cells. The aim of our study was to establish in detail the phenotype of early erythroid cells and to compare the gene expression profile of separated early erythroid precursors with the CD34-positive compartment. Multicolor flow cytometric analyses of human bone marrow mononuclear cell fractions (n=20) defined three distinct early erythroid stages. Sorted populations were analyzed for their gene expression profile using Affymetrix array technology. In 4524 genes, a differential regulation was found in CD105-positive erythroid cells as compared to the CD34 common progenitor compartment (2,362 upregulated genes). A highly significant difference was observed in the expression level of genes with known functions, e.g. transcription factors, heme synthesis, iron and mitochondrial metabolism and transforming growth factor-ß signaling. A comparison with recently published data showed over 800* genes which as yet have not been reported to be upregulated in the early erythroid lineage as compared to the CD34 compartment . The gene expression level within distinct pathways can be illustrated directly by applying the Ingenuity software program. The results of the gene expression analyses can be seen at http://www.ncbi.nlm.nih.gov/geo/info/submission. |
| 488 | GSE12278 |
Profile | The MYC oncogene which is commonly mutated/amplified in tumors, represents an important regulator of cell growth owing to its ability to induce both proliferation and apoptosis. Recent evidence links MYC to altered miRNA expression, thereby suggesting that MYC-regulated miRNAs might contribute to tumorigenesis. To further analyze the impact of MYC-regulated miRNAs we investigated a murine lymphoma model harboring the MYC transgene in a Tet-off system in order to control its expression. Microarray-based miRNA expression profiling revealed both known and novel MYC targets. Among the miRNAs repressed by MYC we identified the potential tumor suppressor miR-26a, which possessed the ability to attenuate proliferation in MYC-dependent cells. Interestingly, miR-26a was also found to be deregulated in primary human Burkitt lymphoma samples, thereby likely being of clinical relevance. While today only few miRNA targets have been identified in human disease, we could show that ectopic expression of miR-26a influenced cell cycle progression by targeting the bona fide oncogene EZH2, a Polycomb protein and global regulator of gene expression yet unknown to be regulated by miRNAs. Thus, in addition to directly targeting protein-coding genes, MYC modulates genes important to oncogenesis via deregulation of miRNAs, thereby vitally contributing to MYC-induced lymphomagenesis. |
| 489 | GSE5993 |
Profile | We investigated the transcriptional effects of p63 binding by analyzing ME180 cells depleted for all p63 isoforms via expression of a small hairpin RNA (shRNA) targeting the p63 oligomerization domain. Keywords: differential expression profiling from transcription factor depletion |
| 490 | GSE19317 |
Profile | Peripheral blood samples were collected before (0 hour) and at 24 hours after exposure from healthy subjects who participated in previous controlled exposures to ultrafine carbon particles (UFP 50 microg/m3) or filtered air (FA)(n = 3 each). The exposure time was 2 hours. RNA from mononuclear cell fraction (>85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. We used microarray to explore significantly altered genes after ultrafine carbon particle exposure. |
| 491 | GSE11467 |
Profile | Study was carried out to examine how E2 and TNFa together influence gene expression in breast cancer cells compared to either factor alone. Keywords: drug response |
| 492 | GSE14334 |
Profile | We decompose the genome-wide expression patterns in 38 embryonic human lung (53-154 days post conception/dpc) into their independent dominant directions of transcriptomic sample variation in order togain global insight of the developing human lung transcriptome.The characteristic genes and their corresponding bio–ontologic attribute profile for the latter were identified. We noted the over–representation of lung specific attributes (e.g., surfactant proteins) traditionally associated with later developmental stages, and highly ranked attributes (e.g., chemokine–immunologic processes) not previously reported nor immediately apparent in an early lung development context. We defined the 3,223–gene union of the characteristic genes of the 3 most dominant sources of variation as the developing lung characteristic sub–transcriptome (DLCS). It may be regarded as the minimal gene set describing the essential biology of this process. The developing lung series in this transcriptomic variation perspectiveform a contiguous trajectory with critical time points that both correlate with the 2 traditional morphologic stages overlapping -154 dpc and suggest the existence of 2 novel phases within the pseudoglandular stage. To demonstrate that this characterization is robust, we showed that the model could be used to estimate the gestational age of independent human lung tissue samples with a median absolute error of 5 days, based on the DLCS of their lung profile alone. Repeating this procedure on the homologous transcriptome profiles of developing mouse lung 14–19 dpc, we were able to recover their correct developmental chronology. Whole human fetal lung gene expression profiling from estimated gestational ages 53 to 154 days post conception. Keywords: Whole lung gene expression profiling, lung development, human fetus. |
| 493 | GSE15047 |
Profile | Three nasopharyngeal carcinoma cell lines (CNE1 CNE2, and HONE1) expression patterns against an immortalized nasopharyngeal epithelial cell line NP69. |
| 494 | GSE8057 |
Profile | Time-course and concentration-effect experiments with multiple time points and drug concentrations provide far more valuable information than experiments with just two design-points (treated vs. control) as commonly performed in most microarray studies. Analysis of the data from such complex experiments, however, remains a challenge. Here we present a semi-automated method for fitting time profiles and concentration-effect patterns, simultaneously, to gene expression data. The submodels for time-course included exponential increase and decrease models with parameters such as initial expression level, maximum effect, and rate-constant (or half-time). The submodel for concentration-effect was a 4-parameter Hill model. The method was applied to an Affymetrix HG-U95Av2 dataset consisting of 51 arrays. The specific study focused on the effects of two platinum drugs, cisplatin and oxaliplatin, on A2780 human ovarian carcinoma cells. Replicates were available at most time points and concentrations. Eighteen genes were selected; time-course and concentration-effect were modeled simultaneously. Comparisons of model parameters helped distinguish genes with different expression patterns between the two drug treatments. This overall paradigm can help in understanding the molecular mechanisms of the agents, and the timing of their actions. Keywords: time course , dose response, cisplatin, oxaliplatin, Human ovarian carcinoma cells |
| 495 | GSE12446 |
Profile | Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007 |
| 496 | GSE14434 |
Profile | The goal of the microarray experiment was to do a head-to-head comparison of the U1 Adaptor technology with siRNA in terms of specificity at the genome-wide level. U1 Adaptors represent a novel gene silencing method that employs a mechanism of action distinct from antisense and RNA interference (RNAi). The U1 Adaptor is a bifunctional oligonucleotide having a “Target Domain” that is complementary to a site in the target gene's terminal exon and a “U1 Domain” that binds to the U1 small nuclear RNA (snRNA) component of the U1 small nuclear ribonucleoprotein (U1 snRNP) splicing factor. Tethering of U1 snRNP to the target pre-mRNA inhibits 3' end processing (i.e. polyA tail addition) leading to degradation of that RNA species within the nucleus thereby reducing mRNA levels. We demonstrate that U1 Adaptors can specifically inhibit both reporter and endogenous genes. Further, targeting the same gene either with multiple U1 Adaptors or with U1 Adaptors and small interfering RNAs (siRNAs), strongly enhances gene silencing, the latter as predicted from their distinct mechanisms of action. Such combinatorial targeting requires lower amounts of oligonucleotides to achieve potent silencing. |
| 497 | GSE17777 |
Profile | Human microvascular endothelial cells (HMVEC) treated with vascular endothelial growth factor (VEGF) Antrhax Edema Toxin (ET), or the Epac activator, 8-pCPT-2'-O-Me-cAMP (8CPT) Human microvascular endothelial cells (HMVEC) were treated with VEGF alone or VEGF in combination with either the the Epac-specific cAMP-mimetic, 8-pCPT-2'-O-Me-cAMP (8CPT), or anthrax edema toxin (ET), an adenylyl cyclase. ET or 8CPT can inhibit VEGF-mediated chemotaxis and angiogenesis. The goal of the study was to identify genes regulated by cAMP production (ET) or by activation of Epac/Rap (8CPT) that may mitigate the effects of VEGF treatment. |
| 498 | GSE25866 |
Profile | Activation of Signal Transducer and Activator of Transcription 3 (STAT3) is common in prostate cancers. STAT3 may induce cell proliferation and resistance to apoptosis as well as promote tumor angiogenesis, invasion, and migration by activating gene expression. Many STAT3-dependent transcriptional responses are mediated through protein-protein interactions that involve the amino-terminal domain (N-domain). In this study, we found that inhibition of the STAT3 N-domain using novel inhibitor ST3-Hel2A-2 induces apoptotic death in prostate cancer cells. The cell death was accomponied by robust activation of pro-apoptotic gene. Using chromatin immunoprecipitation and tiling human promoter arrays (ChIP-chip), we have defined genome-wide targets of STAT3 in DU145 prostate cancer cells. We found that upregulated pro-apoptotic genes were bound by STAT3 in prostate cancer cells, and that STAT3 binding was decreased following inhibition of the STAT3 N-domain. |
| 499 | GSE42344 |
Profile | JS-K a NO donor which capable to induce cancer apopotosis, it's killing mechanism was investigated in this study. We found out that JS-K induce apopotosis via deregulating the GSH/GSSG redox couple. |
| 500 | GSE27529 |
Profile | An Hodgkin Lymphoma cell line have been treated with an LNA inhibitor for miR-9 or with a scramble LNA to identify miR-9 regulated pathways that could be important for Hodgkin Lymphoma pathogenesis. |
| 501 | GSE24044 |
Profile | In this study we have investigated the effect of lysine-specific demethylase 6B (KDM6B) on gene expression in normal human germinal center (GC) B cells using a non-viral vector-based system. |
| 502 | GSE11783 |
Profile | Interstitial cystitis (IC) a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. The ultimate goal is the development of a diagnostic assay for IC on a molecular level. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. Candidate marker genes for ulcerative IC were identified. |
| 503 | GSE41485 |
Profile | Presently there is a deficiency of effective therapies designed to target clear cell renal cell carcinoma (ccRCC), with poor prognosis resulting in patients with advanced disease. Additionally, there is a lack of molecular factors which can be remedially targeted resulting in tumor specific inhibition, and therefore current therapeutic approaches often produce adverse side effects in patients. We identified that Stearoyl-CoA desaturase 1 (SCD1) was consistently overexpressed in patient ccRCC samples, and further investigation of SCD1 as a potential molecular target for ccRCC intervention utilizing a SCD1 inhibitor (A939572) resulted in tumor specific growth inhibition and induction of cell death. In order to understand the mechanism by which the SCD1 inhibitor mediated its anti-tumor effects, we performed gene array analysis and compared expression patterns between treated and untreated samples. |
| 504 | GSE27291 |
Profile | We used microarrays to detail the global programme of gene expression by circulating TCRVgamma9+ gamma delta T cells isolated from healthy individualstested either as resting cells or cells activated by phosphoantigen BrHPP and IL-2at an early(+6hrs) and a late (+7days) timepoint. We find that with more “NK cell” genes than alphabeta T cells and more “T cell” genes than NK cells, the circulating TCRVgamma9+ gamma delta T cells cells have a hybrid transcriptome. The gene signature of the activated cells recapitulates their physiological functions: Th1 cytokine, chemokine and cytotoxic activities at first and mitotic activity at later time points. The gene expression pattern of activated normal gamma delta T cells is nevertheless clearly distinctive from that of NK/T and peripheral T cell lymphomas of the gamma delta subtype. |
| 505 | GSE40512 |
Profile | D-cyclins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment we engineered mouse strains which allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D associated kinase activity in mice bearing ErbB2-driven mammary carcinomas halted cancer progression and triggered tumor-specific senescence, without compromising the animals' health. Ablation of cyclin D3 in mice bearing T-cell acute lymphoblastic leukemias (T-ALL) triggered tumorspecific apoptosis. Such selective killing of leukemic cells can be also achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Hence, contrary to what one might expect from ablation of a cell cycle protein, acute shutdown of a D-cyclin leads not only to cell cycle arrest, but it also triggers tumor cell senescence or apoptosis, and it affects different tumor types through distinct cellular mechanisms. Inhibiting cyclin D-activity represents a highly-selective anticancer strategy which specifically targets cancer cells without significantly affecting normal tissues. |
| 506 | GSE18552 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 507 | GSE44723 |
Profile | Genomic profiling of RNA from cultured human fibroblasts of donor samples in the 10-14th passage was carried out to determine expression changes in the fibroblasts of individual with different degrees of pulmonary fibrosis. Donors consisted of individuals with rapid progressing pulmonary fibrosis slow progressing pulmonary fibrosis, or no fibrosis. |
| 508 | GSE24042 |
Profile | The human liver plays a vital role in meeting the body's metabolic needs and maintaining homeostasis. To address the molecular mechanisms of liver function we integrated multiple gene expression datasets from microarray, MPSS, SAGE and EST platforms to generate a transcriptome atlas of the normal human liver. The integrated liver transcriptome data should provide a valuable resource for the in-depth understanding of human liver biology and liver disease. Microarray is one of these platforms. In this part, adult human liver tissues from 10 adult human were surgically resected due to hemangioma in the liver. The gene expression of normal human liver was detected by Microarray platform. |
| 509 | GSE25156 |
Profile | Drugs directly targeting Hepatitis C (HCV) are often rendered useless by the high mutation rate of the virus. Thus we deduce that targeting of host factor that affect HCV replication may provide enhanced therapy fort HCV infection. Hepatocyte cell line Huh7 is known to be non-permissive for Hepatits C (HCV) replication. Through a method developed by the Rice laboratory (Blight, K.J., et al., J Virol, 2002), selection of a small subset of permissive hepatocytes is possible. The Rice laboratory generated the first permissive cell line, Huh7.5, using this method. We generated another permissive cell line, HRP1, using the same method. With microarray, we compared the expression of host mRNAs in non-permissive Huh7 to both Huh7.5 and HRP1 searching for host factors lost in the cell lines permisive for HCV replication. |
| 510 | GSE13059 |
Profile | Time course comparison to tissue origin and with control cell line HT29 derived from colorectal adenocarcinoma. Status of expression pattern is different in adenocarcinoma of each patient. Human tumor cells extensively changes their gene- and protein expression patterns during their cultivation clonal selection and expansion, thereby loosing many of the characteristics of their primary origin. In this study we analyzed if these expression changes could be circumvented by using short-term primary cell culture models derived from colorectal cancer patients. We compared several primary cells from tumor tissues using a standardized protocol which yielded similar cell populations. For monitoring the gene expression changes induced by cell preparation and cultivation we collected the tissues immediately after resection and isolated cells before seeding, and after 24 and 72 hours of cultivation from each patient. Keywords: time course |
| 511 | GSE16193 |
Profile | Carbon monoxide (CO) is an endogenous messenger that suppresses inflammation modulates apoptosis and promotes vascular remodeling. Here, microarrays were employed to globally characterize the CO (250 ppm) suppression of early (1 h) LPS-induced inflammation in human monocytic THP-1 cells. CO suppressed 79 of 101 immediate-early genes induced by LPS; 19% (15/79) were transcription factors and most others were cytokines, chemokines and immune response genes. The prototypic effects of CO on transcription and protein production occurred early but decreased rapidly. CO activated p38 MAPK, ERK1/2 and Akt and caused an early and transitory delay in LPS-induced JNK activation. However, selective inhibitors of these kinases failed to block CO suppression of LPS-induced IL-1beta, an inflammation marker. Of CO-suppressed genes, 81% (64/79) were found to have promoters with putative NF-kappaB binding sites. CO was subsequently shown to block LPS-induced phosphorylation and degradation of IkappaBalpha in human monocytes, thereby inhibiting NF-kappaB signal transduction. CO broadly suppresses the initial inflammatory response of human monocytes to LPS by reshaping proximal events in TLR4 signal transduction such as stress kinase responses and early NF-kappaB activation. These rapid, but transient effects of CO may have therapeutic applications in acute pulmonary and vascular injury. |
| 512 | GSE7463 |
Profile | Gene expression profiles of malignant carcinomas surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pre-treated with chemotherapy prior to surgery (C-L) while the other clusters with non-malignant adenomas (A-L). Although the C-L cluster is preferentially associated with p53 loss-of-function (LOF) mutations the C-L cluster cancer patients display a more favorable clinical response to chemotherapy as evidenced by enhanced long-term survivorships. Keywords: Patient Tumor Samples |
| 513 | GSE24027 |
Profile | Primary cultures of patient tumor cells (PCPTC) were used in a cell-based cytotoxicity screen. Microarray-based mRNA profiling was used to identify the mechanism-of-action for the small molecule VLX 50. |
| 514 | GSE474 |
Profile | It has been found that fat oxidation is reduced in the skeletal muscle of obese humans. This study aims to identify the mRNA of proteins involved in fat oxidation that may be reduced in obese and morbidly obese individuals. Information gathered will help in understanding how obesity contributes to cardiovascular disease via insulin resistance. Keywords: other |
| 515 | GSE27128 |
Profile | Ventilator induced lung injury can lead to serious conditions like ARDS which are associated with a high mortality (around 30% Stapleton et al., Chest, 2005). We hypothesized that changes of expression levels of different genes would lead us to the identification of critical target genes, which might influence the inflammation and outcome associated with this condition. We used human whole genome U133 Plus 2.0 microarrays to detail the changes of gene expression and identified distinct classes of up-regulated genes during this process. |
| 516 | GSE16650 |
Profile | Acute respiratory distress syndrome (ARDS) is a catastrophic form of acute lung injury (ALI). The necessity for mechanical ventilation (MV) renders patients at risk for ventilator induced lung injury (VILI). Exposure to repetitive cyclic stretch (CS) and/or over-inflation exacerbates injury. Reducing tidal volume (VT) is the only therapeutic strategy shown to mitigate morbidity and mortality. Cyclic stretch has been shown to differentially regulate gene expression in part through the activation of mammalian mitogen-activated protein kinase (MAPK). Although these studies have shown both molecular and cellular alterations no unifying hypothesis to explain MV-induced lung injury has emerged. In the current study, we hypothesized that coordinated expression of cyclic stretch (CS)-responsive genes relies on the presence of common CS-sensitive regulatory elements. To identify CS-responsive genes, we undertook a comparative examination of the gene expression profile of human bronchial epithelial airway (Beas-2B) cells in response to various injurious stimuli involved in the pathogenesis of acute lung injury (ALI)/Ventilator induced lung injury (VILI): cyclic stretch, tumor necrosis factor alpha (TNF-a), and lipopolysaccharide (LPS). |
| 517 | GSE29406 |
Profile | Lactic acidosis and hypoxia are two prominent tumor microenvironmental stresses that are both known to exert important influences on gene expression and phenotypes of cancer cells. But very little is known about the cross-talk and interaction between these two stresses. We performed gene expression analysis of MCF7 cells exposed to lactic acidosis hypoxia and combined lactic acidosis and hypoxia. We found the hypoxia response elicited under hypoxia was mostly abolished upon simultaneous exposure to lactic acidosis. The repression effects are due to loss of HIF-1α protein synthesis under lactic acidosis. In addition, we showed lactic acidosis strongly synergizes with hypoxia to activate the unfold protein response (UPR) and inflammation response which are highly similar to amino acid deprivation responses (AAR). The statistical factor analysis of hypoxia and lactic acidosis responses indicated that ATF4 locus, an important activator in the UPR/AAR pathway, is amplified in subsets of breast tumors and cancer cell lines. Varying ATF4 levels dramatically affect the ability to survive the post-stress recovery from hypoxia and lactic acidosis and may suggest its selection of ATF4 amplification in human cancers. These data suggest that lactic acidosis interacts with hypoxia by both inhibiting the canonical hypoxia response and while activating the UPR and inflammation response. Gain of ATF4 locus may offer survival advantages to allow successful adaptation to frequent fluctuations of oxygen and acidity in tumor microenvironment. Collectively, our studies have provided linkage between the short-term transcriptional responses to the long term selection of the DNA copy number alterations (CNAs) under tumor microenvironmental stresses. |
| 518 | GSE12524 |
Profile | A long form (tRNase ZL) of tRNA 3' processing endoribonuclease (tRNase Z or 3' tRNase) can cleave any target RNA at any desired site under the direction of artificial small guide RNA (sgRNA). We discovered in human kidney 293 cell extracts various new small noncoding RNAs (ncRNAs) including 5'-half-tRNAs and 28S rRNA fragments, co-immunoprecipitated with tRNase ZL, and demonstrated that two of these ncRNAs work as sgRNAs for tRNase ZL in vivo as well as in vitro. In order to find genuine mRNA targets of tRNase ZL guided by ncRNAs, we performed DNA microarray analysis for mRNAs from the 293 cells transfected with the tRNase ZL expression plasmid, and found that PPM1F and DYNC1H1 mRNAs are its genuine targets. |
| 519 | GSE45016 |
Profile | To identify molecules to serve as diagnostic markers for high-grade prostate cancer (PC) and targets for novel therapeutic drugs we investigated the gene expression profiles of high-grade PCs using a cDNA microarray combined with laser microbeam microdissection. |
| 520 | GSE13987 |
Profile | PDE4 inhibitors which activate cAMP signaling by reducing cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic leukemia (CLL) cells but not normal human T cells. The explanation for such differential sensitivity remains unknown. Here, we report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T and B cells. Affymetrix gene chip analysis in the three cell populations following treatment with the PDE4 inhibitor rolipram identified a set of up-regulated transcripts with unusually high fold-changes in the CLL samples, several of which are likely part of compensatory negative feedback loops. The high fold-change were due to low basal transcript levels in CLL cells, suggesting that cAMP-mediated signaling may be unusually tightly regulated in this cell type. Keywords: drug response |
| 521 | GSE6465 |
Profile | Expression profiling of Xenografts of Hepatocellular Carcinoma Keywords: Human Cancer |
| 522 | GSE12102 |
Profile | The improvement of Ewing's sarcoma (EWS) therapy is currently linked to find strategies to select patients with poor and good prognosis at diagnosis and to generate modified treatment regimens. In this study we analyze the molecular factors governing EWS response to chemotherapy in order to identify genetic signatures that may be used for risk-adapted therapy. Keywords: Gene Expression Analysis. |
| 523 | GSE25458 |
Profile | Invasion into deep myometrium and/or lymphovascular space is a well-known risk factor for endometrial cancer metastasis resulting in poor prognosis. It is therefore clinically important to identify novel molecules that suppress tumor invasion. Reduced expression of the metastasis suppressor, KISS1 (kisspeptin), and its endogenous receptor, GPR54, has been reported in several cancers, but the significance of the KISS1/GPR54 axis in endometrial cancer metastasis has not been clarified. Metastin-10 is the minimal bioactive sequence of genetic products of KISS1. Clinicopathological analysis of 92 endometrial cancers revealed overall survival is improved in cancers with high expression of GPR54. Through RNAi and mousemodel analyses, metastin-10 was predicted to suppress invasion and metastasis of GPR54-expressing endometrial cancers. These data suggest that metastin-10 may induce genetic changes in the metastatic character of endometrial cancers. |
| 524 | GSE26487 |
Profile | Glucocorticoids (GCs) have a long history of use as therapeutic agents for numerous skin diseases. Surprisingly their specific molecular effects are largely unknown. To characterize GC action in epidermis, we compared the transcriptional profiles of primary human keratinocytes untreated and treated with dexamethasone (DEX) for 1, 4, 24, 48 and 72 hours using large-scale microarray analyses. The majority of genes were found regulated only after 24 hours and remained regulated throughout the treatment. In addition to expected anti-inflammatory genes, we found that GCs regulate cell fate, tissue remodeling, cell motility, differentiation and metabolism. GCs not only effectively block signaling by TNF-alpha and IL-1 but also by IFN-gamma, which was not previously known. Specifically, GCs suppress the expression of essentially all IFN-gamma-regulated genes, including IFN-gamma receptor and STAT-1. GCs also block STAT-1 activation and nuclear translocation. Unexpectedly, GCs have anti-apoptotic effects in keratinocytes by inducing the expression of anti-apoptotic and repressing pro-apoptotic genes. Consequently, GCs treatment blocked UV-induced apoptosis of keratinocytes. GCs have a profound effect on wound healing by inhibiting cell motility and the expression of pro-angiogenic factor VEGF. They play an important role in tissue remodeling and scar formation by suppressing the expression of TGF-beta-1 and -2, MMP1, 2, 9 and 10 and inducing TIMP-2. Finally, GCs promote terminal stages of epidermal differentiation while simultaneously inhibiting the early stages. These results provide new insights into the beneficial and adverse effects of GCs in epidermis, defining the participating genes and mechanisms that coordinate the cellular responses important for GC-based therapies. |
| 525 | GSE23604 |
Profile | Extracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T cell lymphoma graft versus host disease and allografted organ rejection. Its clinical and experimental efficacy in both cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the dendritic antigen presenting cell (DC) differentiation pathway, as determined by expression of relevant genes. The resulting DC are capable of processing and presentation of exogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of co-stimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome indicates that activation or suppression of more than 3500 genes produces a reproducible distinctive molecular signature. Pathway analysis suggests that DC maturation may be triggered by transient adherence of passaged monocytes to plasma proteins coating the ECP plastic ultraviolet exposure plate. Co-incubation with lymphocytes, simultaneously induced by ECP to undergo apoptosis, may accelerate conversion of monocytes to DC. The efficiency with which ECP induces new functional DC supports the possibility that these cells participate prominently in the clinical successes of the treatment. ECP may offer a practical source of DC for use in a spectrum of immunotherapeutic trials. We have used microarrays to analyze the expression of genes modulated by ECP treatment. |
| 526 | GSE8866 |
Profile | Genomic aberrations of Cyclin D1 (CCND1) and CDK4 in neuroblastoma indicate that dysregulation of the G1 entry checkpoint is an important cell cycle aberration in this pediatric tumor. Here we report that analysis of Affymetrix expression data of primary neuroblastic tumors shows an extensive over-expression of Cyclin D1 and CDK4 which correlates with histological subgroups and prognosis respectively. Immunohistochemical analysis demonstrated an over-expression of Cyclin D1 in neuroblasts and a low Cyclin D1 expression in all cell types in ganglioneuroma. This suggests an involvement of G1 regulating genes in neuronal differentiation processes which we further evaluated using RNA interference against Cyclin D1 and its kinase partner CDK4 in several neuroblastoma cell lines. This resulted in pRb pathway inhibition as shown by an almost complete disappearance of CDK4 specific pRb phosphorylation; reduction of E2F transcriptional activity and a decrease of Cyclin A protein levels. The Cyclin D1 and CDK4 knock-down resulted in a significant reduction in cell proliferation a G1 specific cell cycle arrest and moreover an extensive neuronal differentiation. Affymetrix microarray profiling of siRNA treated cells revealed a shift in expression profile towards a neuronal phenotype. Several new potential downstream players are identified. We conclude that neuroblastoma functionally depend on over-expression of G1 regulating genes to maintain their undifferentiated phenotype. Keywords: Neuroblastoma, CCND1, Cyclin D1, CDK4 |
| 527 | GSE20285 |
Profile | Expression of a constitutively active Notch-1 intracellular domain (NICD) in MCF-10A cells was found to induce two distinct types of 3D structures: large hyperproliferative structures and small, growth-arrested structures with reduced cell-to-matrix adhesion. These heterogeneous phenotypes reflect differences in Notch pathway activation levels. High Notch activity caused loss of cell adhesion and inhibition of proliferation, whereas low Notch activity maintained matrix adhesion and provoked a strong hyperproliferative response. In order to gain insight into the dosage-dependent transcriptional events triggered by Notch1 activation, gene expression profiles induced 48 hours after infection of MCF-10A cells with retroviral vectors expressing full-length Notch-1, L1601P+∆P, or NICD were compared. Full-length Notch-1 induced the weakest effect, L1601P+∆P induced an intermediate effect and NICD induced the strongest effect. Results provide insight into the dichotomous activites of Notch during development and tumorigenesis. |
| 528 | GSE14419 |
Profile | In order to define the inhibitory activity of PMN-Ectosomes we investigated the early gene expression profiles of resting and zymosan A-stimulated human monocyte-derived macrophages in the absence or presence of PMN-Ectosomes. |
| 529 | GSE28057 |
Profile | To identify CD24 signaling pathway Affymetrix Human Genome U133 Plus GeneChip 2.0 |
| 530 | GSE19510 |
Profile | Cellular responses to carcinogens are typically studied in transformed cell lines which do not reflect the physiological status of normal tissues. To address this question, we have characterized the transcriptional program and cellular responses of normal human lung WI-38 fibroblasts upon exposure to the ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE). Exposure to BPDE induces a strong inflammatory response in WI-38 primary fibroblasts. Whole-genome microarray analysis shows induction of several genes related to the production of inflammatory factors, including those that encode interleukins (ILs), growth factors, and enzymes related to prostaglandin synthesis and signaling. This is the first demonstration that a strong inflammatory response is triggered in primary fibroblasts in response to a reactive diol epoxide derived from a polycyclic aromatic hydrocarbon. |
| 531 | GSE23343 |
Profile | The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin by way of the production of secreted proteins, termed hepatokines. To identify hepatic secretory proteins involved in insulin resistance, we performed liver biopsies in humans with or without type 2 diabetes and conducted a comprehensive analysis of gene expression profiles. |
| 532 | GSE11959 |
Profile | The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II) which both signal through type I IGF receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-IIbinding and by inducing cell surface receptor down-regulation via internalization and degradation. In vitro, h10H5 exhibits anti-proliferative effects on cancer cell lines. In vivo, h10H5 demonstrates single-agent anti-tumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models, and even greater efficacy in combination with the chemotherapeutic agent Docetaxel or an anti-VEGF antibody. Anti-tumor activity of h10H5 is associated with decreased AKT activation and glucose uptake, and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors. Keywords: Gene expression changes as markers for drug activity |
| 533 | GSE11510 |
Profile | The placenta is considered one of the candidate cell sources in cellular therapeutics because of a large number of cells and heterogenous cell population with myogenic potentials. We first analyzed myogenic potential of cells obtained from six parts of the placenta i.e., umbilical cord, amniotic epithelium, amniotic mesoderm, chorionic plate, villous chorion (chorion frondosum), , and decidua basalis. Implantation of placenta-derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of human dystrophin. Co-existence of human and murine nuclei in one myotube and presence of human dystrophin in murine myotube suggests that human dystrophin expression is due to cell fusion between host murine myocytes and implanted human cells. In vitro analysis revealed that cells derived from amniotic mesoderm, chorionic plate, ,and villous chorion efficiently transdifferentiate into myotubes. These cells fused to C2C12 murine myoblasts by in vitro co-culturing, and murine myoblasts start to express human dystrophin after fusion. These results demonstrate that placenta-derived cells, especially extraembryonic mesodermal cells, have a myogenic potential and regenerative capacity of skeletal muscle. Determination of cell specification with the gene chip analysis revealed that each placental cell has a distinct expression pattern. Keywords: Determination of cell specification |
| 534 | GSE10879 |
Profile | Estrogen deprivation using aromatase inhibitors is currently the standard of care for patients with estrogen-receptor (ER)-positive breast cancer. Unfortunately prolonged estrogen deprivation leads to drug resistance (i.e. hormone-independent growth). We therefore used DNA microarray analysis to study the gene expression profiles of wild-type MCF-7 cells (which are sensitive to antihormone therapy) and long-term estrogen deprived MCF-7:5C and MCF-7:2A breast cancer cells (which are resistance to estrogen-deprivation; aromatase inhibitor resistant). Transcriptional profiling of wild-type MCF-7 cells and estrogen deprived MCF-7:5C and MCF-7:2A cells was performed using Affymetrix Human Genome U133 Plus 2.0 Array. Keywords: breast cancer cells, estrogen |
| 535 | GSE26813 |
Profile | 8-oxoguanine is excised from DNA by 8-oxoguanine DNA glycosylase-1 during DNA base excision repair. We used microarrays to gain insight into the potential biological function of the excised free 8-oxoguanine base. |
| 536 | GSE7967 |
Profile | We are investigating the transcriptional response of newborns in response to prenatal arsenic exposure We used microarrays to detail the global programme of gene expression response due to prenatal arsenic exposure Keywords: dose (arsenic) |
| 537 | GSE22250 |
Profile | Breast cancer is a molecularly biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known “expression subtypes” but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients. |
| 538 | GSE8615 |
Profile | To identify patterns of change in gene expression that correlated with drug treatment (saline control ADH-1 alone, melphalan alone and ADH-1 plus melphalan) in our animal model of regional therapy for extremity melanoma we evaluated gene expression using microarray genechips and a Pearson correlation analysis. Genes were ranked according to the degree to which expression correlated with systemic ADH-1 treatment alone or in combination with regional melphalan. Tissue samples were harvested at 4, 24 and 48 hours after treatment with melphalan. Specific cellular pathways associated with drug treatment were identified using gene set enrichment analysis (GSEA). Keywords: time course; chemotherapy; melanoma; melphalan; N-cadherin; ADH-1 |
| 539 | GSE20297 |
Profile | G-protein coupled receptors (GPCRs) have diverse roles in physiological processes including immunity. Gs-coupled GPCRs increase while Gi-coupled ones decrease intracellular cAMP. Previous studies suggest that, in epithelial cells, Gs-coupled GPCRs enhance whereas Gi-coupled GPCRs suppress pro-inflammatory immune responses. In order to examine the issue, we chose beta2 adrenergic receptor and GPR40 as representatives of Gs- and Gi- coupled GPCRs, respectively, and examined their effects on TNF-alpha and IFN-gamma-(TNF-alpha + IFN-gamma) induced gene expression by HaCaT. We used microarrays to detail the global changes of gene expression induced by a beta2 adrenergic receptor agonist terbutaline or GPR40 agonist GW9508 pre-treatment in TNF-alpha + IFN-gamma - stimulated HaCaT cells. |
| 540 | GSE19713 |
Profile | Transcriptional profile of PCSC spheres in SCM-1% KO (stem-like cells) vs adherent cultures in PCSC-Celprogen medium (differentiated-like cells) Two-condition experiment: Sphere vs. Parental/adherent cells. Biological replicates: 2 sphere replicates 2 adherent replicates. |
| 541 | GSE34599 |
Profile | An evaluation of biopsies from patients with in-transit extremity melanoma who have been treated with melphalan in the setting of isolated limb infusion or isolated limb perfusion. Gene expression profiles were obtained from 21 lesions across 19 patients and evaluated for expression that correlated with response to melphalan isolated limb infusion. |
| 542 | GSE42088 |
Profile | Leishmania major infected human dendritic cells (DCs) exhibit a marked induction of IL-12 ultimately promoting a robust Th1-mediated response associated with parasite killing and protective immunity. In this study we utilized Affymetrix Genechips to globally assess the host cell genes and pathways associated with L. major infection during early infection (2, 4, 8, and 24 hrs) in human myeloid-derived DCs. Bioinformatic analyses of the hybridized microarray chips identified 728 genes, represented by 848 unique probe sets, which, when compared to uninfected samples were observed to be significantly differentially expressed by one-way ANOVA. Altogether, the data provide a genome-wide perspective on the transcriptional influences Leishmania species exert within human DCs during early infection, and provides a platform for further investigations toward functionally characterizing candidate genes of importance to the IL-12 based immune response to infections. In the current study, we further investigate the L. major infected DC transcriptional during early time points after infection via microarray analysis. |
| 543 | GSE34846 |
Profile | Primary cilium serves as a cellular “antenna” to sense environmental signals. Ciliogenesis requires the removal of CP110 to convert the mother centriole into the basal body. Actin dynamics is also critical for cilia formation. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p a microRNA conserved in the vertebrates, controlled cilia assembly by down-regulating both CP110 and four proteins critical for actin dynamics, Arp2, Toca1, abLIM1, and abLIM3. Consistently, blocking miR-129-3p repressed cilia formation in cultured mammalian cells, whereas its overexpression potently induced ciliogenesis in proliferating cells and extraordinary cilia elongation. Moreover, inhibition of miR-129-3p in zebrafish embryos suppressed cilia assembly in the Kupffer’s vesicle and pronephric duct, leading to developmental abnormalities including curved body, pericardial oedema, and randomised left-right patterning. Our results thus unravel a novel mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly via microRNA-mediated posttranscriptional regulations. We want to find the targets of miR-129-3p by overexpressing miR-129-3p oligo or control oligo in hTERT-RPE1 cells. Through microarray analysis we could check the downregulated genes and these genes might be the targets of miR-129-3p. |
| 544 | GSE11941 |
Profile | Trovafloxacin is a broad spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. Specific members of this drug family display high activity against eukaryotic type II topoisomerase as well as cultured mammalian cells and in vivo tumor models. Trovafloxacin seems to have a higher affinity for eukaryotic polymerase II system than the other quinolone agents tested. This effect coupled with other factors, such as an inflammatory response, might result in a hepatotoxic reaction seen with drug. In this study we found genes regulated by trovafloxacin - induced and repressed - to be located much closer to each other than genes distributed randomly all over the genome (< 100 kbp). Keywords: Trovafloxacin-treated human hepatocytes versus non-treated human hepatocytes |
| 545 | GSE40709 |
Profile | The study was completed to compare expression profiles of primary human beta cells (in the form of adult human islets) to the expression profile of hESC-derived beta-like cells. A HES3 line modified by homologous recombination to express GFP under the insulin promoter allowed us to FACS sort the hESC-derived cells into purified insulin-positive (presumably beta-like cells), and insulin-negative populations. |
| 546 | GSE10437 |
Profile | The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4+ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. Corresponding ChIP-Seq data are available in NCBI's Short Read Archive at ftp://ftp.ncbi.nlm.nih.gov/sra/Studies/SRP000/SRP000105 We find that nucleosome phasing relative to the transcription start sites (TSSs) is directly correlated to RNA polymerase II binding. Furthermore, the first nucleosome downstream of TSSs exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome. This microarray dataset is the gene expression data from resting and activated CD4+ T cells. We used this data to look at nucleosome positioning, Pol II and a few chromatin modifications at genes that are silent and activated in both resting and activated T cells as well as genes that are induced or repressed with T cell activation. Keywords: nucleosome mapping, expression data complementary to Solexa ChIP-Seq data |
| 547 | GSE11115 |
Profile | In addition to their role in the development and function of the reproductive system estrogens have significant anti-inflammatory properties. Although both estrogen receptors (ERs) can mediate anti-inflammatory actions, ERbeta is a more desirable therapeutic target because ERalpha mediates the proliferative effects of estrogens on the mammary gland and uterus. In fact, selective ERbeta agonists have beneficial effects in preclinical models involving inflammation without causing growth-promoting effects on the uterus or mammary gland. However, their mechanism of action is unclear. The purpose of this study was to use microarray analysis to determine whether ERbeta-selective compounds produce their anti-inflammatory effects by repressing transcription of proinflammatory genes. We identified 49 genes that were activated by TNF-alpha in human osteosarcoma U2OS cells expressing ERbeta. Estradiol treatment significantly reduced the activation by TNF-alpha on 18 genes via ERbeta or ERalpha. Most repressed genes were inflammatory genes, such as TNF-alpha, IL-6, and CSF2. Three ERbeta-selective compounds, ERB-041, WAY-202196, and WAY-214156, repressed the expression of these and other inflammatory genes. ERB-041 was the most ERbeta-selective compound, whereas WAY-202196 and WAY-214156 were the most potent. The ERbeta-selective compounds repressed inflammatory genes by recruiting the coactivator, SRC-2. ERB-041 also repressed cytokine genes in PBMCs, demonstrating that ERbeta-selective estrogens have anti-inflammatory properties in immune cells. Our study suggests that the anti-inflammatory effects of ERB-041 and other ERbeta-selective estrogens in animal models are due to transcriptional repression of proinflammatory genes. These compounds might represent a new class of drugs to treat inflammatory disorders. Keywords: estrogen receptor, gene regulation, TNF |
| 548 | GSE10960 |
Profile | Small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide catalytic sequence-specific cleavage of fully or nearly fully complementary target mRNAs or control translation and/or stability of many mRNAs that share 6-8 nucleotides (nt) of complementarity to the siRNA and miRNA 5' end. siRNA- and miRNA-containing ribonucleoprotein silencing complexes are assembled from double-stranded 21- to 23-nt RNase III processing intermediates that carry 5' phosphates and 2-nt overhangs with free 3' hydroxyl groups. Despite the structural symmetry of a duplex siRNA the nucleotide sequence asymmetry can generate a bias for preferred loading of one of the two duplex-forming strands into the RNA-induced silencing complex (RISC). Here we show that the 5'-phosphorylation status of the siRNA strands also acts as an important determinant for strand selection. 5'-O-methylated siRNA duplexes refractory to 5' phosphorylation were examined for their biases in siRNA strand selection. Asymmetric, single methylation of siRNA duplexes reduced the occupancy of the silencing complex by the methylated strand with concomitant elimination of its off-targeting signature and enhanced off-targeting signature of the phosphorylated strand. Methylation of both siRNA strands reduced but did not completely abolish RNA silencing, without affecting strand selection relative to that of the unmodified siRNA. We conclude that asymmetric 5' modification of siRNA duplexes can be useful for controlling targeting specificity. Keywords: siRNA, transfection, chemical modification, off-targets |
| 549 | GSE7009 |
Profile | Nonsense-mediated mRNA decay (NMD) is a molecular pathway of mRNA surveillance that ensures rapid degradation of mRNAs containing premature translation termination codons (PTCs) in eukaryotes. Originally NMD was thought of as a quality control pathway that targets non-functional mRNAs arising from mutations and splicing errors. More recently, NMD has been shown to also regulate normal gene expression and NMD thus emerged as one of the key post-transcriptional mechanisms of gene regulation. We have now systematically analyzed the molecular mechanism of variable NMD efficiency and used different HeLa cell strains as a model system. The results of this analysis show that NMD efficiency can be remarkably variable and represents a stable characteristic of these strains. Low NMD efficiency is shown to be functionally related to the reduced abundance of the exon junction component RNPS1 in one of the HeLa strain analyzed. Furthermore, restoration of functional RNPS1 expression, but not of NMD-inactive mutant proteins, also restores efficient NMD in the RNPS1 deficient cell line. We conclude that cellular concentrations of RNPS1 modify NMD efficiency and propose that the cell type specific co-factor availability represents a novel principle that controls NMD. Keywords: NMD UPF1 knock down |
| 550 | GSE38516 |
Profile | Expression data from HT-29 human colon adenocarcinoma cells treated with IFN-γ for 24 hr |
| 551 | GSE25604 |
Profile | Ependymomas are glial tumors that share morphologic similarities with ependymal cells. Here we laser microdissected ependymoma cells of 15 infratentorial tumors and generated gene expression profiles. These profiles were compared to those of 7 laser microdissected ependymal tissues. |
| 552 | GSE9951 |
Profile | BACKGROUND: Cadmium is implicated in prostate carcinogenesis but its oncogenic action remains unclear. OBJECTIVES: In this study we aimed to decipher changes in cell growth and the transcriptome in an immortalized human normal prostate epithelial cell line (NPrEC) following exposure to low-dose Cd. METHODS: Synchronized NPrEC cells were exposed to different doses of Cd and assayed for cell viability and cell-cycle progression. We investigated changes in transcriptome by global profiling and used Ingenuity Pathways Analysis software to develop propositions about functional connections among differentially expressed genes. A neutralizing antibody was used to negate the effect of Cd-induced up-regulation of tumor necrosis factor (TNF) in NPrEC cells. RESULTS: Exposure of NPrEC to 2.5 μM Cd enhanced cell viability and accelerated cell-cycle progression. Global expression profiling identified 48 genes that exhibited ≥ 1.5-fold changes in expression after 4, 8, 16, and 32 hr of Cd treatment. Pathway analyses inferred a functional connection among 35 of these genes in one major network, with TNF as the most prominent node. Fourteen of the 35 genes are related to TNF, and 11 exhibited an average of > 2-fold changes in gene expression. Real-time reverse transcriptase-polymerase chain reaction confirmed the up-regulation of 7 of the 11 genes (ADAM8, EDN1, IL8, IL24, IL13RA2, COX2/PTGS2, and SERPINB2) and uncovered a 28-fold transient increase in TNF expression in Cd-treated NPrEC cells. A TNF-neutralizing antibody effectively blocked Cd-induced elevations in the expression of these genes. CONCLUSIONS: Noncytotoxic, low-dose Cd has growth-promoting effects on NPrEC cells and induces transient overexpression of TNF, leading to up-regulation of genes with oncogenic and immunomodulation functions. KEY WORDS: carcinogenesis, cytokine, global expression profiling, heavy metals, immune response, inflammation, Ingenuity Pathway Analysis, knowledge-based analysis, prostate cancer. |
| 553 | GSE15214 |
Profile | Oculo-facio-cardio-dental syndrome (OFCD) is a rare genetic disorder characterized by teeth with extremely long roots (radiculomegaly) and craniofacial, eye and cardiac abnormalities. The mutation of the transcriptional co-repressor BCOR has been identified as being responsible for oculo-facio-cardio-dental (OFCD) syndrome. Mesenchymal stem cells (MSCs) is isolated from the root apical papilla of an OFCD patient. Gene expression profiling is performed and compared between mutant MSCs and wild type MSCs. |
| 554 | GSE28807 |
Profile | Wilms tumor (WT) is one of the most common malignancies in childhood. With current therapy protocols up to 90 % of patients can be cured but there is still a need to improve therapy for patients with aggressive WT and to reduce treatment intensity where possible. Prior data suggested deregulation of the retinoic acid (RA) pathway in high-risk WT. This could be validated in a large independent tumor set. Reduced RA pathway activity and MYCN overexpression were found in high risk tumors as opposed to tumors with low/intermediate risk, suggesting a beneficial impact of RA on advanced WT. To investigate the possible mode of action of retinoids as a novel therapeutic agent we treated primary tumor cell cultures with all-trans-RA (ATRA), 9cis-RA, fenretinide and combinations of retinoids and a histone deacetylase (HDAC) inhibitor. Genes deregulated in high risk tumors showed opposite changes upon treatment suggesting a positive effect of retinoids. 6/7 primary cultures tested reduced proliferation, irrespective of prior RA signaling levels. The only variant culture was derived from mesoblastic nephroma, a distinct childhood kidney neoplasm. Retinoid / HDAC inhibitor combinations provided no synergistic effect. ATRA and 9cis-RA induced morphological changes suggestive of differentiation, while fenretinide induced apoptosis in several cultures tested. Microarray analysis of ATRA treated WT cells revealed differential expression of many genes involved in extracellular matrix formation and osteogenic, neuronal or muscle differentiation. Although some of the effects appear to be reversible, these findings provide further evidence of a potential utility of retinoids in Wilms tumor treatment. |
| 555 | GSE25427 |
Profile | Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. Diagnosis usually occurs after metastatic spread largely reflecting vague symptoms of early disease combined with lack of an effective screening strategy. Epigenetic mechanisms of gene regulation, including DNA methylation, are fundamental to normal cellular function and also play a major role in carcinogenesis. To elucidate the biological and clinical relevance of DNA methylation in ovarian cancer, we conducted expression microarray analysis of 39 cell lines and 17 primary culture specimens grown in the presence or absence of DNA methyltransferase (DNMT) inhibitors. Two parameters, induction of expression and standard deviation among untreated samples, identified 378 candidate methylated genes, many relevant to TGF-beta signaling. We analyzed 43 of these genes and they all exhibited methylation. Treatment with DNMT inhibitors increased TGF-beta pathway activity. Hierarchical clustering of ovarian cancers using the 378 genes reproducibly generated a distinct gene cluster strongly correlated with TGF-beta pathway activity that discriminates patients based on age. These data suggest that accumulation of age-related epigenetic modifications leads to suppression of TGF-beta signaling and contributes to ovarian carcinogenesis. |
| 556 | GSE7624 |
Profile | The expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences. Keywords: Monozygotic twin pair Expression Profiles |
| 557 | GSE16755 |
Profile | To study effects of IFNalpha treatment on monocyte-derived macrophages which may influence susceptibility or resistance to HIV. |
| 558 | GSE17889 |
Profile | From the parental breast cancer cell line MCF7 (weakly invasive) we progressively selected hyperinvasive subclones. We compared the gene expression between the parental MCF7-I0 and the hyper-invasive cells MCF7-I6. We used Affymetrix U133 Plus 2 microarrays to detail the global programme of gene expression underlying weakly and highly invasive breast cancer cells derived from the human breast cancer cell line MCF7. |
| 559 | GSE32876 |
Profile | Large-scale cancer genomics projects are profiling hundreds of tumors at multiple molecular layers including copy number, mRNA and miRNA expression, but the mechanistic relationships between these layers are often excluded from computational models. We developed a supervised learning framework for integrating molecular profiles with regulatory sequence information to reveal regulatory programs in cancer, including miRNA-mediated regulation. We applied our approach to 320 glioblastoma profiles and identified key miRNAs and transcription factors as common or subtype-specific drivers of expression changes. We confirmed that predicted gene expression signatures for proneural subtype regulators were consistent with in vivo expression changes in a PDGF-driven mouse model. We tested two predicted proneural drivers, miR-124 and miR-132, both underexpressed in proneural tumors, by overexpression in neurospheres and observed a partial reversal of corresponding tumor expression changes. Computationally dissecting the role of miRNAs in cancer may ultimately lead to small RNA therapeutics tailored to subtype or individual. |
| 560 | GSE42305 |
Profile | Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis. |
| 561 | GSE21382 |
Profile | ABSTRACT Background: The expression of BCL11B has been reported in normal and transformed cells derived from T-lymphocytes neurons, keratinocytes and recently in a subset of squamous cell carcinomas. Despite the rapidly accumulating knowledge concerning Bcl11b biology, the contribution of this protein to normal or transformed cell homeostasis remains open. Methodology/Principal Findings: Here, by employing an overexpression strategy and cells endogenously expressing BCL11B we revealed formerly unidentified features of Bcl11b which shed some light on the potential involvement of the protein in tumor maintenance. Two different T cell lines were forced to overexpress BCL11B which resulted in markedly increased resistance to radiomimetic drugs while no influence on death-receptor apoptotic pathway was observed. Apoptosis resistance triggered by BCL11B overexpression was accompanied by a cell cycle delay caused by accumulation of cells at G1. This cell cycle restriction was associated with upregulation of CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors. Moreover, p27 and p130 proteins accumulated and the SKP2 gene encoding a protein of the ubiquitin-binding complex responsible for their degradation was repressed. Furthermore, the expression of the MYCN oncogene was silenced which resulted in significant depletion of the protein in cells expressing high BCL11B levels. Both cell cycle restriction and resistance to DNA-damage-induced apoptosis coincided and required the histone deacetylase binding N-terminal domain of Bcl11b. The sensitivity to genotoxic stress could be restored by the histone deacetylase inhibitor trichostatine A. Conclusions: The data presented here suggest a potential role of BCL11B in tumor survival and encourage developing Bcl11b-inhibitory approaches as a potential tool to specifically target chemoresistant tumor cells. |
| 562 | GSE41498 |
Profile | Investigation of malignancy-associated expression of gene sets based on ovarian tumour histone modification status. |
| 563 | GSE25487 |
Profile | MDAMB231 cells express the SV40TAg signature. The normal mammary epithelial tissue does not express the signature. CK0082 Empty1 and Gata3 samples are not reported in this manuscript |
| 564 | GSE41627 |
Profile | The cellular response to DNA damage is mediated through multiple pathways that regulate and coordinate DNA repair cell cycle arrest and cell death. We show that the DNA damage response (DDR) induced by ionizing radiation (IR) is coordinated in breast cancer cells by selective mRNA translation mediated by high levels of translation initiation factor eIF4G1. Increased expression of eIF4G1, common in breast cancers, was found to selectively increase translation of mRNAs involved in cell survival and the DDR, preventing autophagy and apoptosis (Survivin, HIF1α, XIAP), promoting cell cycle arrest (GADD45a, p53, ATRIP, Chk1) and DNA repair (53BP1, BRCA1/2, PARP, Rfc2-5, ATM, MRE-11, others). Reduced expression of eIF4G1, but not its homolog eIF4G2, greatly sensitizes cells to DNA damage by IR, induces cell death by both apoptosis and autophagy, and significantly delays resolution of DNA damage foci with little reduction of overall protein synthesis. While some mRNAs selectively translated by higher levels of eIF4G1 were found to use internal ribosome entry site (IRES)-mediated alternate translation, most do not. The latter group shows significantly reduced dependence on eIF4E for translation, facilitated by an enhanced requirement for eIF4G1. Increased expression of eIF4G1 therefore promotes specialized translation of survival, growth arrest and DDR mRNAs that are important in cell survival and DNA repair following genotoxic DNA damage. The purpose of this study was to identify mRNAs that are selectively increased in translation by high levels of the initiation factor eIF4G1, which occurs in many advanced human cancers, in response to DNA damage caused by ionizing radiation, |
| 565 | GSE20689 |
Profile | Knockdown of Sox2 in SW620 colorectal cancer cells decrease their growth rates in vitro and in vivo in xenograft models. We used microarrays to detail the global programme of gene expression in Sox2 Knockdown sw620 cells compared with mock knockdown sw620 cells |
| 566 | GSE11622 |
Profile | Background. Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for hormone replacement therapy (HRT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology at the transcriptional level. This report describes an analysis of expression profiling data, comparing the responses of rat and human vaginae to estrogen treatment. Results. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene. A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation. Conclusions. At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples. Keywords: Disease State Analysis: Animal Model Validation |
| 567 | GSE12806 |
Profile | Infection with Chlamydia pneumoniae a human respiratory pathogen, has been associated with various chronic diseases such as asthma, coronary heart disease and importantly atherosclerosis. Possibly because the pathogen can exist in a persistent form. TNF-a has been reported to induce chlamydial persitence in epithelial cell lines, however the mechanism of TNF-a-induced persistence has not been reported. Moreover, C. pneumoniae persistently infect human dendritic cells (DCs) and activate DCs to produce cytokines including TNF-a. Induction of chlamydial persistence by other cytokines such as IFN-g is known to be due to indoleamine 2,3-dioxygenase (IDO) activity. The present study therefore, investigated whether C. pneumoniae infection can induce IDO activity in dendritic cells, and whether the restriction of chlamydial growth in the DCs by TNF-a is IDO-dependent. Our data indicate that infection of DCs with C. pneumoniae resulted in the induction of IDO expression. Reporting on our use of anti-TNF-a antibody adalimumab and varying concentrations of TNF-a, we further demonstrate that IDO induction following infection of DCs with C. pneumoniae is TNF-a-dependent. The anti-chlamydial activity induced by TNF-a and the expression of chlamydial 16S rRNA gene, euo, groEL1, ftsk and tal genes was correlated with the induction of IDO. Addition of excess amounts of tryptophan to the DC cultures resulted in abrogation of the TNF-a-mediated chlamydial growth restriction. These findings suggest that infection of DCs by C. pneumoniae induces production of functional IDO, which subsequently causes depletion of tryptophan. This may represent a potential mechanism for DCs to restrict bacterial growth in chlamydial infections. Keywords: Chlamydia pneumoniae, Dendritic cells, TNF-a, Indoleamine 2,3-dioxygenase |
| 568 | GSE40837 |
Profile | Growth factor signaling and angiogenesis may promote endocrine-resistance in breast cancer and blocking these pathways can overcome resistance in preclinical models. We conducted a phase-II study of adding the VEGFR/Ras/Raf/MAPK inhibitor sorafenib to endocrine therapy in metastatic ER-positive breast cancer either upon progression or after maximal response with measurable residual disease. Tumor biopsies and serum were collected on days 1 and 28. Primary endpoint was response by RECIST after 3 months and secondary endpoints included safety, time to progression (TTP), and biomarker assessment. Planned sample size was 43 patients but the study closed after 11 patients because of slow accrual. 8 patients had progressive disease (PD) on entry and 3 had stable disease (SD). One patient with SD discontinued sorafenib after 2-weeks because of grade 3 rash. Of the 10 remaining patients after adding sorafenib, 7 had SD (70%), 3 had PD (30%) and median TTP was 6.1-months. Of the 8 patients who entered the study with PD on endocrine therapy, 5 converted to SD (62%) with a median TTP of 6.4-months. Notably, patients on tamoxifen had a median TTP of 8.4-months. The most common adverse events were hypophosphatemia, hypokalemia, and rash, and the majority were grade 1&2 with no grade 4 toxicities. There was a significant reduction in serum VEGFR2 and PDGFR-α on day-28 (p-values 0.0035 and 0.017, respectively). Both serum VEGF and sVEGFR-1 were increased on day-28, but the differences were not statistically significant (p-values 0.3223 and 0.084, respectively). Microarray analysis identified 32 suppressed genes with an FDR of <0.20 and at least a 2-fold change with no induced genes and 29 KEGG pathways were enriched on day-28. Our study suggests that sorafenib can restore endocrine sensitivity, particularly tamoxifen, and this strategy of adding novel agents in patients progressing on endocrine therapy should be examined in future trials. |
| 569 | GSE28326 |
Profile | In multiple myeloma (MM) endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. EPCs from 20 newly diagnosed patients with advanced MM were examined for genomic instability by RNA microarrays to assess changes in gene expression. |
| 570 | GSE28117 |
Profile | Endothelial cell activation and dysfunction underlie many vascular disorders including atherosclerosis and inflammation. Here, we show that interleukin (IL)-4 markedly induced vascular cell adhesion molecule (VCAM)-1, both in cultured endothelial cells and in the intact endothelium in mice. Combined treatment with IL-4 and tumor necrosis factor (TNF)- alpha resulted in further, sustained induction of VCAM-1 expression. IL-4-mediated induction of VCAM-1 and secondary monocyte adhesion was predominantly regulated by the transcription factor, STAT6. Genome-wide survey of IL-4-mediated STAT6 binding from sequential chromatin-immunoprecipitation with deep-sequencing (ChIP-seq) in endothelial cells revealed regions of transient and sustained transcription factor binding. By combining DNA microarrays and ChIP-seq at the same time points, the majority of IL-4-responsive genes were shown to be STAT6-dependent and associated with direct STAT6 binding to their promoter. IL-4-mediated stable binding of STAT6 led to sustained target gene expression. Moreover, our strategy led to the identification of a novel functionally important STAT6 binding site within -16 kb upstream of the VCAM-1 gene. Taken together, these findings support a critical role for STAT6 in mediating IL-4 signal transduction in endothelial cells. Identification of a novel IL-4-mediated VCAM-1 enhancer may provide a foundation for targeted therapy in vascular disease (ChIP-seq data not submitted to GEO). |
| 571 | GSE16385 |
Profile | Human CD14 positive monocytes were purified from healthy volunteers’ blood and cultured in vitro for 4 12, 24, 72 hours. While culturing, macrophages were activated alternatively with interleukin-4 (IL-4 100 ng/ml) or classically with interferon-gamma (IFNg 100 ng/ml)+tumor necrosis factor (TNF 50 ng/ml) or left without activation. Simultaneously, macrophages were also treated with vehicle (DMSO:ethanol) or 1mM synthetic PPARg agonist, Rosiglitazone. We used Affymetrix microarrays (U133Plus 2.0) to analyze activation and PPARg-induced gene expression changes. |
| 572 | GSE30723 |
Profile | Abnormal function of genes is at the root of most cancers but heritable cancer syndromes account for a very small minority of all tumors in humans and domestic animals. The majority of cancers are “sporadic,” that is, they are not heritable in the strictest sense. Instead, sporadic cancers occur due to interactions of unknown intrinsic (heritable) and environmental factors that lead to malignant transformation and uncontrolled growth. Identification of heritable risk factors in sporadic human cancers is difficult because individual genetic backgrounds are very heterogeneous. To this end, individual genetic backgrounds of purebred dogs are more homogeneous, and dog breeds show different predilection to develop specific cancers. Here, we used genomic screens based on gene expression profiling to identify sets of genes that may contribute to the development of canine hemangiosarcoma, a relatively common endothelial sarcoma. Specific genes in a single breed (Golden Retrievers) are modulated by (or with) heritable risk traits, showing functional features that appear to modulate tumor behavior. Our results suggest these methods are suitable to identify genes that will enhance our understanding of how these cancers happen, as well as possible treatment targets that will improve outcomes of both human and canine cancer patients. 24 samples were analysed. 12 samples with ATII cells with without influenza virus infection at 4h and 24h; 12 samples with AMs with without influenza virus infection at 4h and 24h |
| 573 | GSE19279 |
Profile | Pancreatic cancer is a devastating disease with both local invasion and distant metastasis. Identifying the genes expressed in liver metastases and signatures of metastatic progression would therefore be of particular importance as they could aid in both recurrence prediction as well as representing novel therapeutic targets. Keywords: Gene expression profiling |
| 574 | GSE17061 |
Profile | Ficolled AML-M0 sample gene expression profiles on Affymetrix HGU133Plus2.0 GeneChips. Acute myeloid leukemia (AML) classified as FAB-M0 is defined as a subtype with minimally differentiated morphology. Here we investigated by gene expression (GEP) profiling whether AML-M0 cases should be considered as one or more unique molecular subgroups that discriminates them from other AML patients. By applying GEP and subsequent unsupervised analysis of 35 AML-M0 samples and 253 previously reported AML cases we demonstrate that AML-M0 cases express a unique signature. Hematological transcription regulators such as CEBPA, CEBPD, PU.1 and ETV6 and the differentiation associated gene MPO appeared strongly down-regulated, in line with the very primitive state of this type of leukemia. Moreover, AML M0 cases appeared to have a strong positive correlation with a previously defined immature AML subgroup with adverse prognosis. AML-M0 leukemias frequently carry loss-of-function RUNX-1 mutation and unsupervised analyses revealed a striking distinction between cases with and without mutations. RUNX1 mutant AML-M0 samples showed a distinct up-regulation of B-cell-related genes, e.g. members of the B-cell receptor complex, transcriptions regulators RUNX3, ETS2, IRF8 or PRDM1 and major histocompatibility complex class II genes. Importantly, expression of one single gene, i.e. BLNK, enabled prediction of RUNX1 mutations in AML-M0 with high accuracy. We propose that RUNX1 mutations in this subgroup of AML cause lineage infidelity, leading to aberrant co-expression of myeloid and B-lymphoid genes in the same cells. |
| 575 | GSE16461 |
Profile | To gain insight into the etiopathogenesis of Multiple sclerosis (MS) we investigated gene expression changes in CD4+ and CD8+ T lymphocytes from monozygotic twins (MZ) discordant for relapsing remitting MS. We studied 4 monozygotic twin pairs discordant for disease with the affected co-twin free of disease modifying therapies (F/M = 3/1, mean age 36.25±3.9). Following leukapheresis, CD4+ and CD8+ T cells were separated and studied by Affymetrix GeneChip® |
| 576 | GSE45113 |
Profile | During the human B cell (Bc) recall response rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27lo subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27hi plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27lo and proliferating CD27hi subpopulations. Our data supported an alternative hypothesis, that CD27lo cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27lo and CD27hi Bc differentiation. |
| 577 | GSE15553 |
Profile | Directing differentiation of human embryonic stem cells (hESC) into specific cell types using an easy and reproducible protocol is a perquisite for the clinical use of hESC in regenerative medicine protocols. Here we report the generation of mesodermal cells with differentiation potential to myocytes, osteoblasts, chondrocytes and adipocytes. We demonstrate that during hESC differentiation as embryoid bodies (EB), inhibition of TGF-b/Activin/Nodal signaling using SB-431542 (SB) markedly up-regulated paraxial mesodermal markers (TBX6, TBX5), early myogenic transcriptional factors (Myf5, Pax7) as well as myocyte committed markers (NCAM, CD34, Desmin, MHC (fast), alpha-smooth muscle actin, Nkx2.5, cTNT). Establishing EB outgrowth cultures (SB-OG) in the presence of SB (1 uM) led to further enrichment of cells expressing markers for myocyte progenitor cell: CD34+ (33%), NCAM+ (CD56) (73%), PAX7 (25%) and mature myocyte proteins (MYOD1, tropomyocin, fast MHC an d SERCA1). Further analysis using DNA microarray revealed differential up-regulation of 117 genes (>2-fold compared to control cells) annotated to myogenic development and function. During ex vivo culture, contracting myocytes were observed (80% of the population) and the cells formed myofibres when implanted intramuscularly in vivo. Furthermore, in the presence of fetal bovine serum (10% FBS), SB-OG cells developed morphologically and phenotypically into a homogeneous stromal (mesenchymal) stem cell (MSC)-like population expressing characteristic MSC CD markers: CD44 (100%), CD73 (98%), CD146 (96%) and CD166 (88%). They were karyotypically normal and were able to differentiate ex vivo and in vivo into osteoblasts, adipocytes and chondrocytes. |
| 578 | GSE10311 |
Profile | Osteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HOb) from bone explants render them a lucrative model for studying molecular physiology of bone turnover discovery of novel anabolic therapeutics and mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs and no studies have been conducted to date to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks using genomewide expression profiling in resting and Bone Morphogenic Protein (BMP)-2 and Dexamethasone induced cells. Our data showed a vast number of genes and networks expressed predominantly in HObs as compared to closely related cells such as fibroblasts or chondrocytes. For instance, genes in the insulin-like growth factor (IGF) signaling pathway were enriched in HObs (p=0.003) and included the binding proteins (IGFBP1, 2, 5) and IGF-2 and its receptor. Another HOb specific expression pattern included leptin and its receptor (p<10-8). Furthermore, after stimulating HObs with Dexamethasone or BMP-2, the expression of several interesting genes and pathways were observed where data supported the role of peripheral leptin signaling in bone cell function. In conclusion, we provide the landscape of tissue-specific and dynamic gene expression in HObs, a resource, which will allow utilization of osteoblasts as a model to study specific gene networks and gene families related to human bone physiology and diseases. Keywords: cell type comparison |
| 579 | GSE25336 |
Profile | The establishment of induced pluripotent stem (iPS) cells methodologies has widened the possibilities of stem cell related clinical therapies. However safety concerns over current reprogramming technologies as well as lack of efficient protocols for differentiation raise serious questions over their usage in clinical settings. Direct lineage conversion may represent a safer technology for cell-therapy. Here, we identify Sox2 as a factor able to transdetermine human mesenchymal stem cells (MSCs) to hematopoietic progenitor cells (HPCs), recapitulating the molecular events during in vivo hematopoiesis. This technology offers an efficiency of up to 70% HPC generation in less than 8 days under feeder-free conditions. With the goal of devising ways for transplantation into diseased patients we developed two different methodologies that avoid exogenous DNA integration or viral infections. The first, by transduction of recombinant Sox2 protein, and the second by functional replacement of Sox2 by inhibition of TGFß signaling. The DNA integration-, virus-, and feeder-free transdetermination system here described may complement and enhance current approaches for autologous as well as heterologous HPC transplantation in humans. |
| 580 | GSE36176 |
Profile | Genes responses in A549 and H460 cells after GSI (RO4929097-001-003 2 uM) treatment. Notch signaling is an area of great interest in oncology. RO4929097 is a potent and selective inhibitor of gamma-secretase, producing inhibitory activity of Notch signaling in tumor cells. The RO4929097 IC50 in cell-free and cellular assays is in the low nanomolar range with >100-fold selectivity with respect to 75 other proteins of various types (receptors, ion channels, and enzymes). RO4929097 inhibits Notch processing in tumor cells as measured by the reduction of intracellular Notch expression by Western blot. This leads to reduced expression of the Notch transcriptional target gene Hes1. RO4929097 does not block tumor cell proliferation or induce apoptosis but instead produces a less transformed, flattened, slower-growing phenotype. RO4929097 is active following oral dosing. Antitumor activity was shown in 7 of 8 xenografts tested on an intermittent or daily schedule in the absence of body weight loss or Notch-related toxicities. Importantly, efficacy is maintained after dosing is terminated. Angiogenesis reverse transcription-PCR array data show reduced expression of several key angiogenic genes. In addition, comparative microarray analysis suggests tumor cell differentiation as an additional mode of action. These preclinical results support evaluation of RO4929097 in clinical studies using an intermittent dosing schedule. A multicenter phase I dose escalation study in oncology is under way. |
| 581 | GSE13400 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 582 | GSE7664 |
Profile | analyzed changes in cytokine/chemokine production and gene expression levels in human peripheral blood mononuclear cells upon teratment with 15µM,2,4-benzenetriol Keywords: treatment with chemical compound |
| 583 | GSE38069 |
Profile | Human fetal liver fibroblast were reprogrammed to chiPS without exogenous DNA integration using a single episomal vector. The chiPS were then transplanted into SCID mice and HuSCID to form teratomas. We used microarrays to profile the gene expression differences between the teratomas formed by chiPS in SCID and HuSCID mice. |
| 584 | GSE21132 |
Profile | screenning the differentially expressed genes of Jurkat-FF3 Jurkat-miR146a, Jurkat-miR146a-sponge cell lines. |
| 585 | GSE19392 |
Profile | We defined the major transcriptional responses in primary human bronchial epithelial cells (HBECs) after either infection with influenza or treatment with relevant ligands. We used four different strategies each highlighting distinct aspects of the response. (1) cells were infected with the wild-type PR8 influenza virus that can mount a complete replicative cycle. (2) cells were transfected with viral RNA (‘vRNA’) isolated from influenza particles. This does not result in the production of viral proteins or particles and identifies the effect of RNA-sensing pathways (e.g., RIG-I.). (3) Cells were treated with interferon beta (IFNb), to distinguish the portion of the response which is mediated through Type I IFNs. (4) Cells were infected with a PR8 virus lacking the NS1 gene (‘DNS1’). The NS1 protein normally inhibits vRNA- or IFNb-induced pathways, and its deletion can reveal an expanded response to infection. |
| 586 | GSE34042 |
Profile | The insulin-like growth factor-I (IGF-IR) and androgen (AR) receptors are important players in prostate cancer biology. Functional interactions between the IGF-I and androgen signaling pathways seem to have crucial roles in the progression of prostate cancer from early (benign) to advanced (metastatic) stages. DNA methylation is a major epigenetic alteration affecting gene expression. Hypermethylation of tumor suppressor promoters is a frequent event in human cancer leading to inactivation and repression of specific genes. The aim of the present study was to identify the entire set of methylated genes (“methylome”) in a cellular model that replicates prostate cancer progression. |
| 587 | GSE9128 |
Profile | Inflammatory mediators play a role in the pathogenesis/progression of chronic heart failure (CHF). The aim of the present study was to identify diagnostic/prognostic markers and gene expression profiles of CHF vs control. Keywords: CHF patients profiling vs controls. |
| 588 | GSE31255 |
Profile | Using the surface marker EPHB2 we have FACS-purified and profiled stem cell-enriched cell fractions from normal human mucosa, crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal human colon epithelial stem cells |
| 589 | GSE30528 |
Profile | We identified 1700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples. |
| 590 | GSE14880 |
Profile | Expression profiling according to differentiation was analysed in 34 neuroblastomas |
| 591 | GSE14746 |
Profile | AHI-1 is an oncogene often targeted by provirus insertional mutagenesis in murine leukemias and lymphomas. Aberrant expression of human AHI-1 occurs in cutaneous T-cell lymphoma (CTCL) cells and in CD4+CD7- Sezary cells from patients with Sezary syndrome (SS). Stable knockdown of AHI-1 using retroviral-mediated RNA interference in CTCL cells inhibits their transforming activity in vitro and in vivo. To identify genes involved in AHI-1-mediated transformation microarray analysis was performed to identify differentially expressed genes in AHI-1 suppressed CTCL cells. Fifteen up-regulated and six down-regulated genes were identified and confirmed by Q-RT-PCR. Seven were further confirmed in a microarray analysis of CD4+CD7- Sezary cells from SS patients. HCK and BIN1 emerged as new candidate cooperative genes, with differential protein expression which correlates with observed transcript changes. Interestingly, changes in HCK phosphorylation and biological response to its inhibitor, dasatinib, were observed in AHI-1 suppressed or overexpressed cells. The tumor suppressor BIN1 physically interacts with MYC in CTCL cells, which also exhibit differential MYC protein expression. In addition, aberrant expression of alternative splicing forms of BIN1 was observed in primary and transformed CTCL cells. These findings indicate that HCK and BIN1 may play critical roles in AHI-1-mediated leukemic transformation of human CTCL cells. Keywords: Cell type comparison |
| 592 | GSE8954 |
Profile | Bone marrow (BM) has been considered so far the reference source for stromal cells (SC) originally called mesenchymal stem cells. Recently human adult adipose tissue (AT) has been reported as a valuable source for the isolation of cells exerting a mesenchymal-like phenotype. Though both BM- and AT- derived stromal cells (BMSC and ATSC) share similar immuno-phenotype and exhibit multi-lineage potential in vitro a consensual panel of specific markers is still debated and the precise molecular mechanisms governing their differentiated fate are not fully understood. The aim of this study was to compare the genome wide expression profiles of stromal cells isolated from AT and BM and to emphasize the core of MSC stemness properties. Moreover we focused on the molecular characteristics of ATSC, attempting to reveal their specific features.We identified an overlapping dataset of 190 genes commonly regulated by ATSC and BMSC. Among these, we were able to categorize 6 key biological families that could be regarded as a stemness signature that underlie the self-renewal potential and the ability to generate progenitor cells. In particular, a pivotal role of signalling pathways along with the expression of numerous transcription regulators emerged from this study. Genes specifically modulated in ATSC, suggested that these cells posses anti-oxidative and neuroprotective properties. Taken together, these results provide new hints towards the understanding of the molecular basis of MSC maintenance and suggest that ATSC have interesting properties which could be useful for several potential clinical applications. Keywords: genomic profiling |
| 593 | GSE40182 |
Profile | During human pregnancy a subset of placental cytotrophoblasts (CTBs) differentiates into cells that aggressively invade the uterus and its vasculature, anchoring the progeny and rerouting maternal blood to the placenta. In preeclampsia (PE), CTB invasion is limited, reducing placental perfusion and/or creating intermittent flow. This syndrome, affecting 4-8% of pregnancies, entails maternal vascular alterations (e.g., high blood pressure, proteinuria, and edema) ± fetal growth restriction. The only cure is removal of the faulty placenta, i.e., delivery. Previously we showed that defective CTB differentiation contributes to the placental component of PE, but the causes were unknown. Here, CTBs isolated from PE and control placentas were cultured for 48 h, enabling differentiation/invasion. In various severe forms of PE, transcriptomics revealed common aberrations in CTB gene expression immediately after isolation that resolved in culture. The upregulated genes included SEMA3B. Adding this protein to normal CTBs inhibited invasion and re-created aspects of the phenotype of these cells in PE. Additionally, SEMA3B downregulated VEGF signaling through the PI3K/AKT and GSK3 pathways, effects that were observed in PE CTBs. We propose that, in severe PE, the in vivo environment dysregulates CTB gene expression, the autocrine actions of the upregulated molecules, including SEMA3B, impair differentiation/invasion/signaling and patient-specific factors determine the signs. |
| 594 | GSE13110 |
Profile | The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define the role of c-Myb in human hematopoietic lineage commitment we studied the effects of its silencing during the commitment of human CD34+ Hematopoietic stem/progenitor cells. In CD34+ cells c-Myb silencing determined a cell cycle arrest in G0/G1 phase which strongly decreased the clonogenic efficiency, togheter with a reduction of erythroid colonies coupled with an increase of the macrophage and megakaryocyte ones. Moreover, morphological and flow cytometry data supported the preferential macrophage and megakaryocyte differentiation of c-Myb-silenced CD34+ cells. Taken together our data indicate that c-Myb is essential for the commitment along the erythroid and granulocyte lineages but not for the macrophage and megakaryocyte differentiation. Gene expression profiling of c-Myb-silenced CD34+ cells identified some potential c-Myb targets which can account for these effects, to study by Chromatin Immunoprecipitation and Luciferase Reporter Assay. |
| 595 | GSE18625 |
Profile | MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers but knowledge of its targets in colon cancer remains limited. To investigate the role of miR-145 in colon cancer, we have employed a microarray based approach to identify miR-145 targets. Based on seed site enrichment analyses and unbiased word analyses, we found a significant enrichment of miRNA binding sites in the 3’-untranslated regions (UTRs) of transcripts down-regulated upon miRNA overexpression, which represent potential miR-145 targets. Gene Ontology analysis showed an overrepresentation of genes involved in cell death, gene expression, cancer, cell cycle, DNA replication, recombination and repair. A number of the identified miRNA targets have previously been implicated in cancer, including YES, FSCN1, ADAM17, BIRC2, VANGL1 as well as the transcription factor STAT1. Both YES and STAT1 were verified as direct miR-145 targets based on 3’UTR luciferase assays and western blots for endogenous proteins. |
| 596 | GSE5827 |
Profile | The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T-cell development and in the pathogenesis over 50% of human T-cell lymphoblastic leukemia (T-ALL) cases. However little is known about the transcriptional programs activated by NOTCH1. Using an integrative systems biology approach we show that NOTCH1 controls a feed-forward loop transcriptional network that promotes cell growth. Inhibition of NOTCH1 signaling in T-ALL cells led to a reduction in cell size and elicited a gene expression signature dominated by downregulated biosynthetic pathway genes. By integrating gene expression array and ChIP-on-chip data, we show that NOTCH1 directly activates multiple biosynthetic routes and induces c-MYC gene expression. Reverse engineering of regulatory networks from expression profiles showed that NOTCH1 and c-MYC govern two directly interconnected transcriptional programs containing common target genes that together regulate the growth of primary T-ALL cells. These results identify c-MYC as an essential mediator of NOTCH1 signaling and integrate NOTCH1 activation with oncogenic signaling pathways upstream of c-MYC. Keywords: Drug treatment |
| 597 | GSE39218 |
Profile | Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene neuroblastoma derived [avian]) is amplified in 20% of neuroblastomas, and these tumors carry a poor prognosis. However, tumors without MYCN amplification also may have a poor outcome. Here, we identified downstream targets of MYCN by shRNA-mediated silencing MYCN in neuroblastoma cells. From these targets, 157 genes showed an expression profile correlating with MYCN mRNA levels in NB88, a series of 88 neuroblastoma tumors, and therefore represent in vivo relevant MYCN pathway genes. This 157-gene signature identified very poor prognosis tumors in NB88 and independent neuroblastoma cohorts and was more powerful than MYCN amplification or MYCN expression alone. Remarkably, this signature also identified poor outcome of a group of tumors without MYCN amplification. Most of these tumors have low MYCN mRNA levels but high nuclear MYCN protein levels, suggesting stabilization of MYCN at the protein level. One tumor has an MYC amplification and high MYC expression. Chip-on-chip analyses showed that most genes in this signature are directly regulated by MYCN. MYCN induces genes functioning in cell cycle and DNA repair while repressing neuronal differentiation genes. The functional MYCN-157 signature recognizes classical neuroblastoma with MYCN amplification, as well as a newly identified group marked by MYCN protein stabilization. |
| 598 | GSE9264 |
Profile | MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression by binding to 3’UTRs of target mRNAs. Kaposi’s sarcoma-associated herpesvirus (KSHV), a virus linked to malignancies including primary effusion lymphoma (PEL), encodes 12 miRNA genes, but only a few regulatory targets are known. We found that KSHV-miR-K12-11 shares 100% seed-sequence homology with hsa-miR-155, a miRNA frequently found up-regulated in lymphomas and critically important for B cell development. Based on this seed-sequence homology, we hypothesized that both miRNAs regulate a common set of target genes and as a result, could have similar biological activities. Examination of five PEL lines showed that PELs do not express miR-155, but do express high levels of miR-K12-11. Bioinformatics tools predicted the transcriptional repressor BACH-1 to be targeted by both miRNAs and ectopic expression of either miR-155 or miR-K12-11 inhibited a BACH-1 3'UTR containing reporter. . Furthermore, BACH-1 protein levels are low in cells expressing either miRNA. Gene expression profiling of miRNA-expressing stable cell lines revealed 66 genes that were commonly down-regulated. For select genes, miRNA targeting was confirmed by reporter assays. Thus, based on our in silico predictions, reporter assays, and expression profiling data, miR-K12-11 and miR-155 regulate a common set of cellular targets. Given the role of miR-155 during B cell maturation, we speculate that miR-K12-11 may contribute to the distinct developmental phenotype of PEL cells, which are blocked in a late stage of B cell development. Together, these findings indicate that KSHV miR-K12-11 is an ortholog of miR-155. Keywords: comparison, experiemental versus control |
| 599 | GSE21092 |
Profile | Gene expression microarray profile for human embryonic kidney cells (HEK293T CRL-11268) under untreated conditions. |
| 600 | GSE32482 |
Profile | Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells. Anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for maintaining the stem-like properties and tumorigenicity of glioblastoma stem cells. |
| 601 | GSE26921 |
Profile | The 3-Deazaneplanocin A (DZNep) one of S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors, has shown antitumor activities in a broad range of solid tumors and acute myeloid leukemia. Here, we examined its effects on multiple myeloma (MM) cells and found that, at 500 nM, it potently inhibited growth and induced apoptosis in 2 of 8 MM cell lines. RNA from un-treated and DZNep treated cells was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a significant change in gene expression were determined by significance analysis of microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in sensitive cells and was expressed at low level in resistant cells. The results were corroborated by quantitative RT-PCR. Western-blot analysis indicated ALOX5 was highly expressed only in sensitive cell line H929 and greatly decreased upon DZNep treatment. Ectopic expression of ALOX5 reduced sensitivity to DZNep in H929 cells. Furthermore, down-regulation of ALOX5 by RNA interference could also induce apoptosis in H929. Gene expression analysis on MM patient dataset indicated ALOX5 expression was significantly higher in MM patients compared to normal plasma cells. We also found that Bcl-2 was overexpressed in DZNep insensitive cells, and cotreatment with DZNep and ABT-737, a Bcl-2 family inhibitor, synergistically inhibited growth and induced apoptosis of DZNep insensitive MM cells. Taken together, this study shows one of mechanisms of the DZNep efficacy on MM correlates with its ability to down-regulate the ALOX5 levels. In addition, DZNep insensitivity might be associated with overexpression of Bcl-2, and the combination of ABT-737 and DZNep could synergistically induced apoptosis. These results suggest that DZNep may be exploited therapeutically for a subset of MM. |
| 602 | GSE7529 |
Profile | Tumor tissue heterogeneity is a well known feature of several solid tumors. Neuroblastic Tumors (NTs) is a group of paediatric cancers with a great tissue heterogeneity. Most of NTs are composed of undifferentiated poorly differentiated or differentiating neuroblastic (Nb) cells with very few or absent Schwannian stromal (SS) cells: these tumors are grouped as Neuroblastoma (Schwannian stroma-poor). The remaining NTs are composed of abundant SS cells and classified as Ganglioneuroblastoma (Schwannian stroma-rich) intermixed or nodular and Ganglioneuroma. The importance to understand Nb and SS gene signatures in NTs, is to clarify the complex network mechanism of tumor growth and progression. In order to identify the Nb and SS cells gene signatures, we analyzed the gene expression profiling of 19 cases of neuroblastic tumors: 10 stroma poor (NTs-SP) and 9 stroma rich (NTs-SR), by high density oligonucleotide microarrays. Moreover, the analysis was performed in parallel on both whole and laser microdissected tumor samples: from 4 of 19 cases, was isolated different areas all composed of pure cellular populations. We performed genome wide expression analysis by using Affymetrix technology and we used two different approaches for data analysis: SAM (Significance Analysis of Microarrays) and a method based on Game Theory (GT), to identify genes differently expressed in SS and Nb cells. Differently from the SAM method, the analysis based on GT (Moretti et al. (2006)) gives the advantage of selecting relevant genes not only according to the expression profile of each single gene, but considering also gene interaction. Keywords: Gene signature of Neuroblastic and Schwannian stromal cells. |
| 603 | GSE11559 |
Profile | The FHIT gene at 3p14.2, encompasses the common fragile site FRA3B and is frequently inactivated in primary tumors and cell lines of lung, head and neck, stomach, esophagus, cervix and breast cancer. In particular, loss of the FHIT protein is one of the most frequent alteration in lung tumors and pre-invasive lung lesions, suggesting a role for this gene in the early stages of lung carcinogenesis. Adenoviral-mediated restoration of FHIT expression in FHIT-negative cell lines results in cell cycle alteration, induction of apoptosis (through activation of the cytoplasmic apoptotic pathway) and regression of the tumorigenic phenotype. Taken together these observations support the hypothesis of a role for FHIT in human carcinogenesis, but little is known about its mechanism of action. Identification of transcriptional targets of FHIT is therefore critical to understand the pathways by which FHIT promotes growth arrest and apoptosis. |
| 604 | GSE34733 |
Profile | The clinical impact of aberrant CEBPA promoter methylation (PM) in AML is controversial discussed. The aim of this study was to clarify the significance of aberrant CEBPA PM with regard to clinical features in a cohort of 572 de novo AML with wildtype CEBPA and normal karyotype. The distal promoter was methylated in 54/572 cases (9.41%) whereas proximal PM was never detected. Methylation of the core promoter was detected in only 8 of 326 cases (2.45%) and thus seems to be a rare event in AML. There was no correlation between CEBPA distal PM age, sex, white blood cell (WBC) count or Hb levels at diagnosis. We also were not able to detect a significant correlation between the presence of CEBPA distal PM and molecular mutations such as FLT3-ITD, NPM1, AML1, MLL-PTD and IDH1. Solely the frequency of IDH2R140 mutations was significantly reduced in CEBPA distal PM positive compared to CEBPA distal PM negative cases (p=0.01). Furthermore, analysis of CEBPA mRNA expression level revealed no difference between CEBPA distal PM positive and CEBPA distal PM negative cases, suggesting that CEBPA distal PM has no influence on CEBPA expression. CEBPA distal PM did not show impact on overall survival (OS), event free survival (EFS) or incidence of relapse. Also when other mutations were taken into regard no prognostic impact of CEBPA distal PM could be shown. In contrast, a distinct expression profile of CEBPA distal PM positive cases compared to CEBPA mutated and CEBPA distal PM negative cases was observed. In addition, a significantly higher frequency of CEBPA distal PM was detected in RUNX1-RUNX1T1 positive AML compared to the CEBPA witdtype cases. We conclude that the presence of aberrant CEBPA PM has no clinical relevance and is therefore a negligible prognostic marker in de novo AML with normal karyotype. |
| 605 | GSE17186 |
Profile | Goals/objectives: to identify various gene expression in B cell subsets derived from human PBMC and cord blood |
| 606 | GSE39354 |
Profile | Chromosomal rearrangements involving ETS factors ERG and ETV1, occur frequently in prostate cancer. We here examine human prostate cancer cells control VCaP and LNCaP cells with ERG- or ETV1-silenced VCaP or LNCaP cells, respectively, in hormone deprived and stimulated conditions. |
| 607 | GSE3064 |
Profile | Investigation of expression profile in XDP brains. Keywords: an XDP patient and neurologically normal control |
| 608 | GSE1832 |
Profile | Four healthy human volunteers underwent an acute bout of resistance exercise with the right leg at 2 pm. Biopsies were removed from the Vastus Lateralis muscle 6 h (8 pm) and 18 h (8 am) after exericise Keywords = Human skeletal muscle Keywords = resistance exerise Keywords = diurnal Keywords = circadian Keywords: time-course |
| 609 | GSE1133 |
Profile | The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting. Keywords: different tissues |
| 610 | GSE8597 |
Profile | Estrogen receptors (ERs) which mediate the proliferative action of estrogens in breast cancer cells, are ligand-dependent transcription factors that regulate expression of their primary target genes through several mechanisms. In addition to direct binding to cognate DNA sequences, ERs can be recruited to DNA through other transcription factors (tethering), or affect gene transcription through modulation of signaling cascades by non-genomic mechanisms of action. To better characterize the mechanisms of gene regulation by estrogens, we have identified more than 700 putative primary and more than 1500 putative secondary target genes of estradiol in MCF7 cells through microarray analysis performed in the presence or absence of the translation inhibitor cycloheximide. Keywords: drug treatment |
| 611 | GSE30585 |
Profile | Homodimerization of Mpl can also be accomplished in the absence of Tpo by binding of a synthetic ligand (Chemical inducer of dimerization, CID) to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. In contrast to Tpo stimulation, F36VMpl dimerization in human CD34+ progenitor cells generates robust erythropoiesis. Microarray gene expression profiling of progenitors demonstrated that F36VMpl dimerization, but not Tpo, results in upregulation of critical erythroid genes. |
| 612 | GSE21364 |
Profile | Lipid rafts are cholesterol-rich cell signaling platforms and their physiological role can be explored by cholesterol depletion. To dress a global picture of transcriptional changes ongoing after lipid raft disruption we performed whole-genome expression profiling in epidermal keratinocytes, a cell type which synthesizes its cholesterol in situ. We used microarrays to identify transcriptional changes in gene expression of cholesterol-depleted keratinocytes. Cholesterol depletion by methyl-beta-cyclodextrin disrupts the organization of lipid rafts, which are cholesterol- and sphingolipid-rich membrane microdomains. |
| 613 | GSE20611 |
Profile | A weakly bone metastatic variant of the breast cancer cell line MDA-MB-231 SCP6, gave rise to highly bone metastatic sublines (PD1, PD2A-E) after long time dormancy in vivo. These cell lines were subjected to microarray analysis with data drawn from previous studies (Kang et al., 2003; Minn et al. 2005; Lu and Kang 2009; Lu and Kang 2010). Keywords: Cell type comparison |
| 614 | GSE6400 |
Profile | The goal of this project was to characterize changes in gene expression in response to the anti-cancer agent sapphyrin PCI-2050. Cultured A549 human lung cancer cells were treated with sapphyrin PCI-2050 or actinomycin D a known transcripitonal inhibitor. The gene expression profiles of drug-treated and control A549 cultures were determined using Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA). Further details are provided in our published manuscript: |
| 615 | GSE7153 |
Profile | Expression profiles of 17 melanoma cell lines were analysed to identify genes differentially expressed between cell lines harbouring wild-type or mutant p16INK4A. Relevant paper: Pavey et al. (2007). Note: all of these cell lines contained wild-type p14ARF so that the transcriptional effects of p16INk4A could be determined without interference from p14ARF. Keywords: Affymetrix Hu133_Plus microarrays |
| 616 | GSE49165 |
Profile | Ossifying fibroma (OF) is a common benign fibro-osseous neoplasm of orofacial bones showing progressive enlargement of the affected jaw with deficiency in bone formation. Our aim is to discover the molecular difference between mesenchymal stem cells from OF and normal jaw bone to provide basis for development of clinical therapy. Global gene expression comparison and gene ontology analysis found that several singaling pathways are involved in the process, including TGFb signaling and Notch signaling. Inhibition of TGFb signaling in mesenchymal stem cells of OF can increase the osteogenesis and decrease proliferation, shedding light on developing strategies for therapy. |
| 617 | GSE25493 |
Profile | The pituitary tumor-transforming gene (PTTG1) is a recently discovered oncogene implicated in the malignant progression of a number of neoplasms. It has been shown to drive both endocrine and non-endocrine malignancies but has not yet been studied in the context of renal cell carcinoma (RCC). Clear cell RCC (ccRCC) is cytogenetically characterized by deletion of chromosome 3p, harboring the von-Hippel Lindau tumor suppressor gene, and amplification of chromosome 5q. The significance of copy number gain of chromosome 5 is not clear, but is presumed to be the location of oncogenes that influence ccRCC development or progression. The PTTG1 oncogene maps to chromosome 5q, and here we show that PTTG1 is amplified in clear cell RCC, is overexpressed in tumor tissue relative to adjacent normal kidney, and expression is associated with high grade, high stage, and poor prognosis. Furthermore, we establish a functional role for PTTG1 in ccRCC tumorigenesis and progression. PTTG1 ablation reduces both the tumorigenic ability of ccRCC cells in vitro and in vivo and the invasive ability of these cells in vitro. An analysis of genes whose transcription is regulated by PTTG1 was supportive of an association with invasive and metastatic disease. PTTG1-dependent expression of the Rho-GEF ECT2, another proto-oncogene, is observed in a number of ccRCC cell lines, and ECT2 expression correlates with PTTG1 expression, high stage, high grade, and poor prognosis ccRCC. As GEF's have been promoted as potential drug targets for targeted cancer therapeutics, the relationship between the PTTG1 and ECT2 oncogenes may be able to be exploited for the treatment of this disease. |
| 618 | GSE10946 |
Profile | Objective: The etiology of PCOS is mostly unknown. Existing data support both genetic and environmental factors in its pathogenesis. Design: Prospective case - control study. Setting: University Hospital. Patients: 25 patients undergoing IVF-ICSI treatment. Intervention: Genome-wide oligonucleotide microarray technology was used to study differential gene-expression patterns of cultured human cumulus cells from IVF patients divided into 4 groups according to disease state (PCOS vs. Control) and BMI (Obese vs. Lean). Results: Two differential PCOS gene expression profiles were established: Lean-Type was formed by comparing PCOS lean (PL) vs. non-PCOS lean (NL) individuals; Obese-Type was formed by comparing PCOS obese (PO) vs. non-PCOS (NO) obese patients. Conclusions: Different molecular pathways are associated with PCOS in Lean and Obese individuals as demonstrated by gene expression profiling of cumulus cells. Our findings provide insights into the molecular pathogenesis of PCOS. We used microarrays to study the gene expression of human cultured cumulus cells. We compared the genes expression of lean PCOS, Obese PCOS, lean controls and obese controls. Different molecular pathways are associated with PCOS in Lean and Obese patients. Keywords: disease state analysis |
| 619 | GSE32108 |
Profile | Mediator complex has been known as pivotal regulator of RNA polymerase II. Mediator complex has two CDK subunits in vertebrates named CDK8 and CDK19. To elucidate functional difference between CDK8 and CDK19 in human cell, we employ siRNA mediate knockdown assay using HeLa S3 cell line. According to this assay these CDKs possess highly redundancy in HeLa S3 cell transcription regulation mechanism but in several genes, each CDK shows gene specific regulatory function. |
| 620 | GSE9212 |
Profile | We investigated the clinical implications of lung developmental transcription factors (TTF-1 NKX2-8, and PAX9) which we recently discovered as cooperating oncogenes activated by way of gene amplification at chromosome 14q13 in lung cancer. Using stable transfectants of human bronchial epithelial cells, RNA expression profiles (signatures) representing activation of the biological pathways defined by each of the three genes were determined and used to risk stratify a non-small cell lung cancer (NSCLC) clinical dataset consisting of ninety-one early stage tumors. Co-activation of the TTF-1 and NKX2-8 pathways identified a cluster of patients with poor survival, representing approximately 20% of patients with early stage NSCLC, whereas activation of individual pathways did not reveal significant prognostic power. Importantly, the poor prognosis associated with co-activation of TTF-1 and NKX2-8 was validated in two other independent clinical datasets. Further, lung cancer cell lines showing co-activation of the TTF-1 and NKX2-8 pathways were shown to exhibit resistance to cisplatin, the standard of care for the treatment of NSCLC. Since TTF-1 and NKX2-8 lack specific inhibitors at the current time, we explored an alternative therapeutic strategy. Using signatures of signaling pathway activation, we identified deregulation of specific oncogenic pathways (Ras and Myc) in the TTF-1/NKX2-8 co-activated cohort. In vitro experiments demonstrated the ability of a Ras pathway-specific therapy to inhibit tumor cell growth in TTF-1/NKX-2 activated cells, thus, suggesting that modulation of the Ras pathway is a rational strategy to targeted therapy in high risk NSCLC patients with co-activation of specific lung developmental pathways. Keywords: Transcription factor expression analysis |
| 621 | GSE14711 |
Profile | Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients by viral vector-mediated factor transduction represent a powerful tool for biomedical research and may provide a source for cell replacement therapies. However the proviruses encoding the reprogramming factors represent a major limitation of the current technology because even low vector expression may alter the differentiation potential of the iPSCs and induce malignant transformation. Here we show that fibroblasts from five patients with idiopathic Parkinson’s disease (PD) can be efficiently reprogrammed into hiPSCs and subsequently differentiated into dopaminergic neurons. Moreover, we derived PD specific hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Upon factor deletion these cells maintain a pluripotent state and intact karyotype. Importantly, these factor-free hiPSCs show a global gene expression profile, which is more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in conventional virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease. |
| 622 | GSE12679 |
Profile | We used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from patients with schizophrenia and bipolar disorder and healthy controls. RNA was isolated from these cell populations amplified, and analysed using Affymetrix HG133plus2.0 GeneChips. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology. Keywords: cell type comparison, laser capture microdissection |
| 623 | GSE44808 |
Profile | The airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated p63+ Krt5+ basal cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in co-ordinating the expression of numerous proteins required for epithelial morphogenesis differentiation, remodeling and repair. However, little is known about their function in the adult lung. We use Affymetrix microarray analysis to compare transcripts in lentivirus transfected primary human bronchial epithelial (HBE) cells expressing either EGFP or DN-GRHL2 for 48h when the transepithelial electrical resistance (TER) reached a threshold level. The goal is to identify direct target genes of GRHL2 and early events in the uncoupling of junctional interactions, including those regulating transepithelial resistance. |
| 624 | GSE21610 |
Profile | Mechanical unloading by ventricular assist devices (VAD) leads to significant gene-expression changes often summarized as reverse remodeling. However little is known on individual transcriptome changes during VAD-support and its relationship to non-failing hearts (NF). In addition no data are available for the transcriptome regulation during non-pulsatile VAD-support. Therefore we analysed the gene-expression patterns of 30 paired samples from VAD-supported (including 8 non-pulsatile VADs) and 8 non-failing control hearts (NF) using the first total human genome-array available. Transmural myocardial samples were collected for RNA-isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data was analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). 352 transcripts were differentially regulated between samples from VAD-implantation and NF, whereas 510 were significantly regulated between VAD-transplantation and NF (paired t-test p<0.001, fold change >=1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD-support. Unsupervised hierarchical clustering of paired VAD- and NF-samples revealed separation of HF- and NF- samples, however individual differentiation of VAD-implantation and VAD-transplantation was not accomplished. Clustering of pulsatile and non-pulsatile VAD did not lead to robust separation of gene expression patterns. During VAD-support myocardial gene expression changes do not indicate reversal of the HF-phenotype, but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and non-pulsatile VAD-supported hearts did not provide evidence for a pump-mode specific transcriptome pattern. |
| 625 | GSE8140 |
Profile | To investigate molecular mechanisms of resistance we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays. Keywords: multiple group comparison |
| 626 | GSE14964 |
Profile | Yin Yang 1 (YY1) is a critical transcription factor controlling cell proliferation development and DNA damage responses. Although two homologous Drosophila YY family members (pleiohomeotic (pho)) and pleiohomeotic-like (phol)) are redundant, the functional significance of a recently described mammalian YY1-like gene (YY2) is unknown. Using microarray and gene set enrichment analysis (GSEA), we found that lentiviral constructs containing short hairpin loop YY1- and YY2-specific inhibitory RNAs (shYY1 and shYY2) caused significant changes in both redundant and distinguishable expression patterns. Ribosomal protein genes were the most significant gene set up-regulated by both shYY1 and shYY2, although combined shYY1/shYY2 knockdowns were not additive. In contrast, shYY2 reversed anti-proliferative effects of shYY1 on E2F target genes, and shYY2 particularly altered UV damage response, platelet-specific genes and mitochondrial function genes. The most YY2-specific gene was the platelet glycoprotein CD36 whose ligand is thrombospondin - a key UV response gene. We found that decreases in YY1 or YY2 caused inverse changes in UV sensitivity, and that their combined loss reversed their respective individual effects. Taken together, our studies show that YY2 is not redundant to YY1, and YY2 is a significant regulator of genes previously thought to uniquely respond to YY1. Functions of thrombospondin and CD36 in inflammation, atherogenesis, innate immunity and malaria pathogenesis reveal new potential regulatory roles for YY1 and YY2. |
| 627 | GSE18271 |
Profile | A large proportion of patients suffering from the malignant pediatric tumor neuroblastoma die of progressive disease despite intensive therapy. Neuroblastomas belong to the group of neuroblastic tumors together with the more benign, differentiated ganglioneuroblastomas and ganglioneuromas. Little is known of the genes driving the differentiation processes in these tumor types. A search for the transcription factors differentially expressed between ganglioneuromas, ganglioneuroblastomas, and neuroblastomas in a series of 110 neuroblastic tumors (NB110) identified a large number of HOX- and TALE (Three Amino acid Loop Extension)-class homeobox transcription factor genes. The MEIS1-3, PBX1 and -3, and PKNOX1 TALE genes showed highest expression in neuroblastomas and lowest in ganglioneuromas and ganglioneuroblastomas. The PKNOX2 and TGIF1-2 genes showed the opposite expression pattern. This suggests an involvement of TALE genes in neuroblastoma differentiation. Expression of MEIS1, a known oncogene in haematopoietic tumors, was high in all neuroblastomas, and strongly correlated with undifferentiated histology. Consequently, we generated IMR-32 neuroblastoma cells capable of inducible shRNA-mediated MEIS1 knockdown. We observed differentiation, growth arrest and induction of apoptosis upon MEIS1 down-regulation. Affymetrix profiling of time-course experiments using these cells allowed the identification of MEIS1 target genes. Analysis of the target genes in the NB110 series showed that 323 of these were also significantly correlated to MEIS1 expression and to tumor differentiation in neuroblastic tumors. Genes involved in the cell cycle and in developmental pathways were over-represented in this gene set. We conclude that MEIS1 governs several of the signal transduction routes important for neuroblastoma survival and differentiation. |
| 628 | GSE13760 |
Profile | Gene expression profiling in arterial tissue from type 2 diabetic patients |
| 629 | GSE10282 |
Profile | An evaluation of multifocal lesions from patients with in-transit extremity melanoma to determine if all lesions from a patient harbor homogeneous patterns of gene expression Gene expression profiling studies can help guide treatment for cancer patients by providing tools in the form of gene-expression signatures to characterize a tumor in terms of underlying biology predicted response to therapy, metastatic progression and/or recurrence. The utility of gene signatures for defining therapeutic strategies in the treatment of extremity in-transit melanoma will be dependent on the genetic relationship between the multifocal lesions typically present in this disease and the extent to which a single lesion is representative of residual tumor burden. Using microarray-based gene expression profiling we examined 43 in-transit melanoma lesions across 17 patients with multifocal disease to determine whether one lesion could accurately characterize the underlying biology and genetic profile of a patient's tumor. Principal component analysis, unsupervised hierarchical clustering, one-way analysis of variance (ANOVA) and gene signatures predictive of chemosensitivity and oncogenic pathway activation showed gene expression patterns to be highly similar (p-values: <0.006; average r = 0.979) between lesions from a single patient but to be significantly different across patients (p<0.05). These findings demonstrate that individual melanoma tumor nodules in patients with multifocal disease are genetically similar and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the utilization of gene expression profiling in clinical trials of targeted therapy in melanoma allowing for more rational identification of candidates for specific therapies. Keywords: Disease state analysis |
| 630 | GSE11551 |
Profile | We used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone or in combination with NAC, to aide in identifing the mechnism of action of elesclomol. Keywords: treatment |
| 631 | GSE18826 |
Profile | Full title: Three-dimensional culture of AIDS-NHL cells influences gene expression related to B-cell development proliferation and survival The AIDS-NHL-derived cell line, UMCL01-101, representing diffuse large B-cell lymphoma of immunoblastic morphology (AIDS-IBL), was grown in conventional, static suspension culture or three-dimensionally (3D) in the Rotating Wall Vessel (RWV) bioreactor. The objective was to assess the impact on gene expression of growth as a three-dimensional tissue assembly. Global gene expression analysis was performed on UMCL01-101 cells grown under either condition using Affymetrix microarray. |
| 632 | GSE24733 |
Profile | To analyze the impact of Aire on gene expression profile in a model cell line we used 293T cells and transfected them either with an Aire expression plasmid pCMV-Aire (where mAire is driven by CMV promoter) or with a control plasmid pCMV2B. Total RNA was extracted 48 hours post transfection, processed and used for gene expression profiling by Affymetrix. The data demonstrate that Aire has a very broad impact, effecting (upregulating and downregulating) hundreds of differents genes, however these genes differ dramatically from its targets in medullary epithelial cells. Keywords: transfection |
| 633 | GSE10629 |
Profile | The small intestinal epithelium mediates vital functions of nutrient absorption and host defense. The spatial organization of the epithelial cells along the crypt-villus axis segregates them into regions of specialized function. However many of the mechanisms governing intestinal epithelial cell migration and the coordination of interactions with adjacent cells and the extracellular matrix are not fully understood. We have evaluated in vivo gene expression patterns of ileal epithelial cells in healthy human subjects, isolated by laser capture microdissection from either the villus epithelial or crypt cell regions of the small intestinal mucosa. Expression profiles in villus epithelium and Paneth cell lineages were determined by quantitative real-time PCR, DNA microarray, and immunohistochemistry based methods. Relative expression levels of selected epithelial biomarkers were compared between the ileum, jejunum, duodenum, colon, stomach, and esophagus. Previously established biomarkers as well as a novel and distinct set of genes believed to be linked to epithelial cell motility, adhesion, and differentiation were found to be enriched in each of the two corresponding cell populations. Additionally, high baseline expression levels of innate antimicrobials, alpha defensin 5 (HD5) and regenerating islet-derived 3 alpha (Reg3A), were detected exclusively within the small bowel, most notably in the ileum, in comparison to other sites along the gastrointestinal tract. Our findings provide new and important insights regarding the molecular machinery employed by small intestinal epithelial cells to mediate their function and spatial organization in vivo. Keywords: analysis of epithelial cells from crypt or upper villus regions |
| 634 | GSE36769 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 635 | GSE20923 |
Profile | Interferon-induced transmembrane protein 1 (IFITM1) is one of the three members of the interferon-induced transmembrane family and has recently been identified as a new molecular marker in human colorectal cancer. However its functional roles in colorectal cancer are still elusive. In this study, we investigate the gene expression profiling of HT-29 cells with IFITM1 knockdown. We revealed that several invasive- and carcinogenesis-related genes were differentially expressed. |
| 636 | GSE14926 |
Profile | Negative immunomagnetic selection has become the method of choice for isolating T cell subsets for functional studies due to concerns that directly binding antibody to the surface of a cell as occurs with positive selection, results in cross-linking of surface antigens, altered gene transcription and subsequent cellular activation. However there is little data to support this. We therefore examined the impact of the method of immunomagnetic cell selection on the gene expression profile of healthy human CD4 and CD8 T cells in a total of 21 cases. Keywords: Methodology |
| 637 | GSE34219 |
Profile | M21 or M21L cells were grown either in a 2-dimensional culture (on plastic) or in a 3-dimensional-collagen model. |
| 638 | GSE18005 |
Profile | Signal transduction processes mediated by phosphatidyl inositol phosphates affect a broad range of cellular processes such as cell cycle progression migration and cell survival. The protein kinase AKT is one of the major effectors in this signaling network. Chronic AKT activation contributes to oncogenic transformation and tumor development. Therefore, new small drugs were designed to block AKT activity for cancer treatment. Here we characterize the biological effects of the phosphatidyl inositol phosphate analogs SH-5 and SH-6 in colorectal cancer cell lines. We demonstrate that the two compounds did not reduce AKT phosphorylation significantly in the presence of growth factors, but induce a broad range of morphological and transcriptional alterations. Transcriptomic profiling in inhibitor-treated SW480 cells revealed a cluster of down- regulated genes associated with mitosis. Moreover, the treatment of SW480 cells with either SH-5 or SH-6 caused the formation of binucleated cells as a result of a specific abscission defect. |
| 639 | GSE11691 |
Profile | The pathophysiology of endometriotic lesion development remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesised that disruption of this interaction was likely to suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice as a first step towards testing this hypothesis. Human endometrium was xenografted into nude mice and the resulting lesions were analysed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified by the microarray analyses originated from human cells (endometrium) or mouse cells (stroma). Four key pathways (ubiquitin/proteosome, inflammation, tissue remodelling/repair and ras-mediated oncogenesis) were revealed, that demonstrated communication between host stromal cells and ectopic endometrium. Keywords: Disease state analysis |
| 640 | GSE27160 |
Profile | Gene expression profiles during the differentiation of HUVEC on matrigel were analyzed. |
| 641 | GSE18618 |
Profile | Transient expression of two factors or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference. Genetic reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells or iPSCs) by over-expression of specific genes has been accomplished using mouse and human cells. However, it is still unclear how similar human iPSCs are to human Embryonic Stem Cells (hESCs). Here, we describe the transcriptional profile of human iPSCs generated without viral vectors or genomic insertions, revealing that these cells are in general similar to hESCs but with significant differences. For the generation of human iPSCs without viral vectors or genomic insertions, pluripotent factors Oct4 and Nanog were cloned in episomal vectors and transfected into human fetal neural progenitor cells. The transient expression of these two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described here revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference. Moreover, the episomal reprogramming strategy represents a safe way to generate human iPSCs for clinical purposes and basic research. |
| 642 | GSE46509 |
Profile | Dysregulation of pyramidal cell network function by the soma- and axon-targeting inhibitory neurons that contain the calcium-binding protein parvalbumin (PV) represents a core pathophysiological feature of schizophrenia. In order to gain insight into the molecular basis of their functional impairment we used laser capture microdissection (LCM) to isolate PV-immunolabeled neurons from layer 3 of Brodmann’s area 42 of the superior temporal gyrus (STG) from postmortem schizophrenia and normal control brains. We then extracted ribonucleic acid (RNA) from these neurons and determined their messenger RNA (mRNA) expression profile using the Affymetrix platform of microarray technology. 739 mRNA transcripts were found to be differentially expressed in PV neurons in subjects with schizophrenia, including genes associated with WNT (wingless-type), NOTCH and PGE2 (prostaglandin E2) signaling, in addition to genes that regulate cell cycle and apoptosis. Of these 739 genes, only 89 (12%) were also differentially expressed in pyramidal neurons as found in the accompanying study, suggesting that the molecular pathophysiology of schizophrenia appears to be predominantly neuronal type-specific. Taken together, findings of this study provide a neurobiological framework within which hypotheses of the molecular mechanisms that underlie the dysfunction of PV neurons in schizophrenia can be generated and experimentally explored and, as such, may ultimately inform the conceptualization of targeted molecular intervention. |
| 643 | GSE33789 |
Profile | To broaden the appeal of the NIH Stem Cell Database we analyzed a subset of undifferentiated human embryonic stem cell lines (5 lines in duplicate) on the Affymetrix platform. One standard culture protocol was used in conjunction with rigorous quality control. Expanded description of methods used and are available at: http://stemcelldb.nih.gov. |
| 644 | GSE19330 |
Profile | This study provides a comparison of genes expressed in reconstructed cultured epidermis derived from four different donors. GeneChips were used to compare reconstructed human EpiDerm™ EPI-200 tissues prepared from four different neonatal foreskin donors (254 1188, 219 and 926). This work will assist in providing a deeper understanding of genes expressed in cultured skin equivalents. Keywords: Cell type/donor comparison |
| 645 | GSE16355 |
Profile | Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The KSHV virus expresses multiple microRNA in a single cluster. Here we test the effects of this KSHV microRNA cluster in LEC cells using Affymetrix hgu133plus2 chips. |
| 646 | GSE4182 |
Profile | In polygenic disorders we do not know exactly how many genes are involved in the pathomechanism, but the analysis of fetal gene expression can get us closer to the solution. In our study we were searching for the genetic background of the polygenic neural tube defect, which is the second most common birth defect in the world (1 in 1000 live births). Our data revealed novel candidate genes, like SLAP, LST1 and BENE, which can play an important role in the pathogenesis of neural tube defects. We created a data warehouse from the results, suitable for further analysis. This study also demonstrates that a routinely collected amount of amniotic fluid (as small as 6 mL) is enough to successfully hybridize isolated RNA to expression arrays, making the ability to use the technique from normally collected amniotic fluid samples. Keywords: Prenatal gene expression signature |
| 647 | GSE6236 |
Profile | RNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets Affymetrix HG-U133 arrays were hybridized with probe from total RNA isolated from blood sampled from 14 umbilical cords and 14 healthy adult humans. Keywords: Adult vs. fetal reticulocyte transcriptome comparison |
| 648 | GSE16464 |
Profile | Autologous chondrocyte transplantation (ACT) is a routine technique to regenerate focal cartilage lesions. However patients with osteoarthritis (OA) are lacking an appropriate long-lasting treatment alternative, partly since it is not known if chondrocytes from OA patients have the same chondrogenic differentiation potential as chondrocytes from donors not affected by OA. Articular chondrocytes from patients with OA undergoing total knee replacement (Mankin Score >3, Ahlbäck Score >2) and from patients undergoing ACT, here referred to as normal donors (ND), were isolated applying protocols used for ACT. Their chondrogenic differentiation potential was evaluated both in high-density pellet and scaffold (Hyaff-11) cultures by histological proteoglycan assessment (Bern Score) and immunohistochemistry for collagen types I and II. Chondrocytes cultured in monolayer and scaffolds were subjected to gene expression profiling using genome-wide oligonucleotide microarrays. Expression data were verified by using quantitative RT-PCR. Chondrocytes from ND and OA donors demonstrated accumulation of comparable amounts of cartilage matrix components, including sulphated proteoglycans and collagen types I and II. The mRNA expression of cartilage markers (COL2A1, COMP, aggrecan, CRTL1, SOX9) and genes involved in matrix synthesis (biglycan, COL9A2, COL11A1, TIMP4, CILP2) was highly induced in 3D cultures of chondrocytes from both donor groups. Genes associated with hypertrophic or OA cartilage (COL10A1, RUNX2, periostin, ALP, PTHR1, MMP13, COL1A1, COL3A1) were not significantly regulated between the two groups of donors. The expression of 661 genes, including COMP, FN1, and SOX9, were differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished between the OA and ND chondrocytes, and only 184 genes were differentially regulated. Only few genes were differentially expressed between OA and ND chondrocytes in Hyaff-11 culture. The risk of differentiation into hypertrophic cartilage does not seem to be increased for OA chondrocytes. Our findings suggest that the chondrogenic capacity is not significantly affected by OA and OA chondrocytes fulfill the requirements for matrix-associated ACT. Keywords: time course, cell type comparison, tissue engineered cartilage; osteoarthritis; Hyaff-11 scaffold; human chondrocytes; gene expression profiling; regenerative medicine; differentiation potential |
| 649 | GSE26332 |
Profile | MicroRNAs (miRNAs) have been globally profiled in cancers but there tends to be poor agreement between studies including in the same cancers. Additionally few putative miRNA targets have been validated. To overcome the lack of reproducibility, we profiled miRNAs by next generation sequencing and locked nucleic acid miRNA microarrays, and we verified concordant changes by quantitative RT-PCR. Notably, miR-125b and the miR-99 family members miR-99a, -99b, -100 were down-regulated in all assays in advanced prostate cancer cell lines relative to the parental cell lines from which they were derived. All four miRNAs were also down-regulated in human prostate tumor tissue compared to normal prostate. Transfection of miR-99a, -99b or -100 inhibited the growth of prostate cancer cells and decreased the expression of prostate-specific antigen (PSA), suggesting potential roles as tumor suppressors in this setting. To identify targets of these miRNAs, we combined computational prediction of potential targets with experimental validation by microarray and polyribosomal loading analysis. Three direct targets of the miR-99 family that were validated in this manner were the chromatin remodeling factors SMARCA5 and SMARCD1 and the growth regulatory kinase mTOR. We determined that PSA is post-transcriptionally regulated by the miR-99 family members at least partially by repression of SMARCA5. Together, our findings suggest key functions and targets of miR-99 family members in prostate cancer suppression and prognosis. |
| 650 | GSE35932 |
Profile | Total 23 samples were derived from [1] HUVEC treated in the absence (0h) or presence of hypoxia (1 2, 4, 8, 12, and 24 hrs) to determine hypoxia-regulated gene in endothelial cells, [2] control siRNA or HIF1α siRNA transfected HUVEC cells treated in the absence or presence of hypoxia, [3] control siRNA or KDM3A siRNA transfected HUVEC cells treated in the absence or presence of hypoxia, [4] ChIP-seq data for HIF1 binding sites and histone modifications under normoxia and hypoxia in endothelial cells. |
| 651 | GSE15960 |
Profile | The whole-genome oligonucleotide microarray analysis of laser microdissected human colonic epithelial cells can contribute to determination of disease-specific expression alterations in colonic epithelial cells and to localize the origin the expression changes measured in whole biopsy samples. Keywords: whole genomic expression |
| 652 | GSE22606 |
Profile | The androgen receptor (AR) is the principal target for treatment of non-organ confined prostate cancer (PCa). Systems and bioinformatics approaches suggest that considerable variation exists in the mechanisms by which AR regulates expression of effector genes and point towards a role for secondary transcription factors (TFs) therein. We identified a novel indirect mechanism of androgen action in which effects of androgens on PCa cells are mediated by Serum Response Factor (SRF). To identify and characterize genes and cellular processes that are androgen-regulated in an SRF-dependent manner in PCa Affymetrix HG-U133 Plus 2.0 GeneChip Array analysis was performed starting from RNA obtained from LNCaP cells in which androgen stimulation was combined with siRNA-mediated SRF silencing. To this end, LNCaP cells were seeded in 60 mm dishes at a density of 550,000 cells per dish in antibiotic-free medium. The next day, cells were transfected with siGenome SmartPool siRNA targeting SRF (Dharmacon, Lafayette, CO) or a custom-made control SmartPool targeting luciferase (LUC condition) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA) following the manufacturer’s instructions. Forty-two hours after transfection, cells were treated with 5nM R1881 or ethanol vehicle. 3 biological triplicates were included per treatment group. Forty-eight hours later, cells were harvested in Trizol reagent (Invitrogen). RNA was isolated, purified on RNeasy columns (Qiagen, Germantown, MD) and checked for integrity by Agilent testing (Affymetrix, Santa Clara, CA). cDNA was generated and hybridized to Human Genome U133 Plus 2.0 arrays (Affymetrix) according to the manufacturer’s instructions at the Mayo Clinic Advanced Genomics Technology Microarray Shared Resource core facility. |
| 653 | GSE6890 |
Profile | The three-dimensional (3D) folding of the chromosomal fibre in the human interphase nucleus is an important but poorly understood aspect of gene regulation. Especially basic principles of 3D chromatin and chromosome organisation are still elusive. In this paper, we quantitatively analyse the 3D structure of large parts of chromosomes 1 and 11 in the G1 nucleus of human cells and relate it to the human transcriptome map (HTM). Despite a considerable cell-to-cell variation, our results show that subchromosomal domains, which are highly expressed, are more decondensed, have a more irregular shape and are located in the nuclear interior compared to clusters of low expressed genes. These aspects of chromosome structure are shared by six different cell lines and therefore are independent of cell type specific differences in gene expression within the investigated domains. Systematic measurements show that there is little to no intermingling of chromatin from different parts of the same chromosome, indicating that the chromosomal fibre itself is a compact structure. Together, our results reveal several basic aspects of 3D chromosome architecture, which are related to genome function. Keywords: cell line comparison |
| 654 | GSE46106 |
Profile | Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (~23% and ~19%, respectively). Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing unique 25 patients. Most tumors yielding xenografts were “triple-negative” (ER-PR-HER2+) (n=19). However, we established lines from three ER-PR-HER2+ tumors, one ER+PR-HER2-, one ER+PR+HER2- and one “triple-positive” (ER+PR+HER2+) tumor. Serially passaged xenografts show biological consistency with the tumor of origin, are phenotypic stability across multiple transplant generations at the histological, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses. Xenografts representing 12 patients, including two ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis. |
| 655 | GSE7788 |
Profile | T-cell/histiocyte rich B cell lymphoma (THRBL) and nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) share some morphological characteristics including a prominent stromal reaction, but display a markedly different prognosis. To investigate the difference between the stromal reactions of these lymphomas at the molecular level, we performed microarray expression profiling on a series of THRBL and NLPHL cases. Keywords: lymphoma, NLPHL, THRBL, stromal reaction |
| 656 | GSE34602 |
Profile | We identified recurrent NOTCH1 mutations in 12% of MCLs. 2 out of 10 tested MCL cell lines (Rec-1 and SP-49) were sensitive to inhibition of the NOTCH pathway by gamma-secretase inhibition. The aim of this study was to identify transcriptional targets of NOTCH signaling in MCL. |
| 657 | GSE16694 |
Profile | Induced pluripotent stem (iPS) cells have generated interest for regenerative medicine as they allow for producing patient-specific progenitors in vitro with potential value for cell therapy. In many instances however, an off-the-shelf approach would be desirable, such as for cell therapy of acute conditions or when the patient's somatic cells are altered as a consequence of chronic disease or aging. Cord blood (CB) stem cells appear ideally suited for this purpose as they are newborn, immunologically immature cells with minimal genetic and epigenetic alterations, and several hundred thousand immunotyped CB units are readily available through a worldwide network of CB banks. Here, we show that CB stem cells can be reprogrammed to pluripotency by retroviral transduction with OCT4, SOX2, KLF4, and c-MYC, in a process that is extremely efficient and fast. The resulting CB-derived iPS (CBiPS) cells are phenotypically and molecularly indistinguishable from human embryonic stem (hES) cells. Furthermore, we show that generation of CBiPS can be efficiently achieved without the use of the c-MYC and KLF4 oncogenes and just by overexpression of OCT4 and SOX2. Our studies set the basis for the creation of a comprehensive bank of HLA-matched CBiPS cells for off-the-shelf applications. |
| 658 | GSE36487 |
Profile | Atherosclerosis (AT) is a chronic inflammatory disease characterized by the accumulation of inflammatory cells lipoproteins and fibrous tissue in the walls of arteries. AT is the primary cause of heart attacks and stroke and the leading cause of death in westernized countries. To date, the pathogenesis of AT is not well-defined. Studies have shown that the dedifferentiation of contractile and quiescent vascular smooth muscle cells (SMC) to the proliferative, migratory and synthetic phenotype in the intima is pivotal for the onset and progression of AT. To further delineate the mechanisms underlying the pathogenesis of AT, we have analyzed the early molecular pathways and networks of SMC phenotype transformation as induced by the presence of minimally-oxidized LDL (moxLDL). |
| 659 | GSE13376 |
Profile | The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrett’s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisons with data derived from gene expression studies of Barrett’s esophagus and associated adenocarcinoma. |
| 660 | GSE42926 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 661 | GSE14257 |
Profile | HT29 cells were transsfected with siRNA (siHX) which is targeting the human endogeous retrovirus HERV-HX. Cells were harvested 72 h after transfection and knock-down of HERV-HX was evaluated by quantitative RT-PCR. Keywords: Genetic modification |
| 662 | GSE13124 |
Profile | Transcriptional expression data for bioactive small molecules for mechanism identification. Keywords: Expression profiling by array |
| 663 | GSE39889 |
Profile | The response of human neutrophils to the emerging pathogen Mycobacterium abscessus has not been described. However M. abscessus infections are frequently associated with neutrophil-rich abscesses. To better understand the reponse of neutrophils to M. abscessus we performed gene expression analysis using Affymetrix HG-U133A Plus 2.0 microarrays. Human neutrophils from healthy donors were stimulated with isogenic rough and smooth morphotypes of M. abscessus. Staphylococcus aureus was used as a control. Gene expression was compared to neutrophils left unstimulated. Neutrophils from four individual donors were isolated on separate days and stimulated with freshly prepared bacteria. Neutrophils (stimulated and control) were left for 2 hours before total RNA was isolated, and biotinylated cRNA was prepared by standard methods. Analysis indicates that M. abscessus morphotypes induce a limited number of genes, when compared to S. aureus, which are enriched in genes for cytokines and chemokines, including neutrophil-specific chemokines. These data suggest that neutrophils have a limited response to M. abscessus, which may contribute to neutrophil-rich abscess formation.!Series_overall_design = Human neutrophils from healthy donors were exposed to rough Mab (ATCC 19977T), smooth Mab (ATCC 19977T) and S. aureus (CF clinical strain) for two hours; control cells were exposed to saline. |
| 664 | GSE31324 |
Profile | The dermal papilla (DP) of the hair follicle plays crucial roles in the hair follcie morphogenesis and cycling. Thus the elucication of human DP molecular signature is of great interest. DP cell culture by conventional method impairs intrinsic properties of DP cells. Isolatoion of human DP is hampered by the lack of specific cell surface markers. Thus, it still depends on manual microdissection, with which the removal of minor contamination is unfeasible. Cultured DP cells are mostly pure. Aggregation of cultured DP cells was shown to restore some intrinsic properties in cultured DP cells. Fibroblasts are distinct dermal cell population and provide baseline for DP arrays. |
| 665 | GSE16424 |
Profile | Advanced ovarian cancers are initially responsive to chemotherapy with platinum drugs but develop drug resistance in most cases. We showed recently that hepatocyte growth factor (HGF) enhances death of human ovarian cancer cell lines treated with cisplatin (CDDP) and that this effect is mediated by the p38 mitogen-activated protein kinase. In this work we integrated genome-wide expression profiling, in silico data survey, and functional assays to identify transcripts regulated in SK-OV-3 ovarian cancer cells made more responsive to CDDP by HGF. Using oligonucleotide microarrays, we found that HGF pretreatment changes the transcriptional response to CDDP. Quantitative reverse transcription-PCR not only validated all the 15 most differentially expressed genes but also confirmed that they were primarily modulated by the combined treatment with HGF and CDDP and reversed by suppressing p38 mitogen-activated protein kinase activity. Among the differentially expressed genes, we focused functional analysis on two regulatory subunits of the protein phosphatase 2A, which were down-modulated by HGF plus CDDP. Decrease of each subunit by RNA interference made ovarian cancer cells more responsive to CDDP, mimicking the effect of HGF. In conclusion, we show that HGF and CDDP modulate transcription in ovarian cancer cells and that this transcriptional response is involved in apoptosis regulation. We also provide the proof-of-concept that the identified genes might be targeted to either increase the efficacy of chemotherapeutics or revert chemotherapy resistance. |
| 666 | GSE22139 |
Profile | Medulloblastoma (MB) is the most common malignant brain tumor in children among whom overexpression or amplification of MYC oncogenes has been associated with poor clinical outcome. Although the MYC functions during normal development and oncogenesis in various systems have been extensively investigated, the transcriptional targets mediating MYC effects in MB are still elusive. Their identification and roles during MB onset and progression are important and will ultimately suggest novel potential therapeutic targets. cDNA microarray analysis was used to compare the effects of overexpressing and silencing MYC on the transcriptome of a MB-derived cell line. We identified 209 genes with potential relevance to MYC-dependent cellular responses in MB. Among the MYC-responsive genes, we found members of the bone morphogenetic protein (BMP) signaling pathway, which plays a crucial role during the development of the cerebellum. In particular, the cytokine gene BMP7 was identified as a direct target of MYC in MB cells. Similar to the effect induced by BMP7 silencing by siRNA, the use of a small-molecule inhibitor of the BMP/SMAD signaling pathway reduced cell viability in a panel of MB cells. Altogether, our findings indicate that high MYC levels drive BMP7 expression in MB to induce pro-survival and pro-proliferative cellular pathways. This observation suggests that targeting the BMP/SMAD pathway may be a new therapeutic concept for the treatment of childhood MB. |
| 667 | GSE22598 |
Profile | Purpose and Experimental Design: The purpose of this study is to find a methylation-related gene that could become a biomarker or therapeutic target in colorectal carcinoma (CRC). We screened candidate genes suspected to be silenced by DNA methylation using oligonucleotide microarray analysis. To investigate the clinical significance of one candidate gene (UNC5B) we analyzed the correlation between mRNA expression and clinicopathological features using clinical tissue samples. Finally, methylation specific PCR analysis was performed to reveal whether the promoter region was methylated in CRC cell lines. Results: We found 75 candidate genes that were potentially suppressed by DNA methylation in CRC. We focused on UNC5B, a possible tumor suppressor gene and regulator of apoptosis known to be inactivated in CRC. The mRNA expression analysis using tissue samples revealed that UNC5B mRNA was down-expressed in about 20% of CRC patients, and the patients with low-UNC5B-expression tumors showed a significantly higher recurrence rate after curative surgery. According to the univariate and multivariate analysis, low UNC5B expression was an independent risk factor for postoperative recurrence in stage I, II, and III CRC patients. Furthermore, patients with low expression of UNC5B in tumors had significantly poorer prognosis than those with high expression of UNC5B. Although UNC5B mRNA expression was restored by the demethylation treatment in CRC cell lines, the promoter region of UNC5B was not methylated. Conclusion: UNC5B is a potential biomarker for the selection of patients with high risk of postoperative recurrence and worse prognosis in CRC. |
| 668 | GSE24147 |
Profile | Inflammation is common to many disorders and responsible for tissue and organ damage. However the associated peripheral cytokine milieu is frequently dilute and difficult to measure, necessitating development of more sensitive and informative biomarkers for mechanistic studies, earlier diagnosis, and monitoring therapeutic interventions. Previously, we have shown that sera from type 1 diabetes (T1D) patients induces a unique disease-specific pro-inflammatory transcriptional profile in fresh peripheral blood mononuclear cells (PBMCs) compared to sera of healthy controls. To address the potential variance introduced by heterogeneity in responsiveness of PBMCs from different donors, we evaluated human leukemia cell lines as surrogates for fresh PBMCs. Expression signatures of 7 different cell lines were 1) tested in their power to differentiate sera of T1D patients from healthy controls; and 2) compared to the signature obtained with fresh PBMCs. |
| 669 | GSE37185 |
Profile | Introduction: Amplification at chromosome 8q24 is one of the most frequent genomic abnormalities in human cancers and is associated with reduced survival duration in breast and ovarian cancers. The minimal amplified region encodes c-MYC and the non-coding RNA PVT1 including miR-1204 encoded in exon 1b. Here we analyzed the genomic changes at chromosome 8q24.21 in breast cancer and the functional roles of miR-1204 in breast and ovarian cancer progression. Methods: The genomic changes at chromosome 8q24.21 were detected in 997 breast cancer tumors and 40 breast cancer cell lines. Expression of miR-1204 in breast and ovarian cancer cell lines was investigated by qRT-PCR method. The role of miR-1204 in the tumorigenesis of breast and ovarian cancer was explored using both knockdown and overexpression of miR-1204 in vitro. Candidate miR-1204 target genes from two independent expression microarray datasets and computational predict programs were identified and further validated by qRT-PCR and western blot methods. The role of inhibition of miR-1204 on tamoxifen sensitivity in breast cancer cells was also investigated. Results: MiR-1204 is frequently co-amplified with MYC and expression of miR-1204 is strongly correlated with the expression and amplification of the noncoding PVT1 transcript and less so with MYC in human breast and ovarian cancer cells. Inhibition of miR-1204 decreases cell proliferation and increased apoptosis in breast and ovarian cancer cell lines with 8q24 amplification, but not in lines without amplification and so may be involved in Myc-induced apoptosis. Additionally, overexpression of miR-1204 enhances both breast and ovarian cancer cell growth and Myc-initiated Rat1A cell transformation. Computational and experimental analyses 30 promising candidate miR-1204 target genes. mRNA levels for these genes were assessed after over expression and knockdown of miR-1204 as were protein levels for 10 genes for which antibodies were available. These studies implicated VDR and ESR1 as miR-1204 targets. Inhibition of miR-1204 increased response to tamoxifen in Estrogen Receptor negative breast cancer cell lines. Conclusions: We conclude that amplification of miR-1204 contributes to breast and ovarian pathophysiology at least in part, by increasing proliferation and down regulating apoptosis and by decreasing expression of VDR and ESR1. |
| 670 | GSE17251 |
Profile | Studies in mice have shown that PPARα is an important regulator of hepatic lipid metabolism and the acute phase response. However little information is available on the role of PPARα in human liver. Here we set out to compare the function of PPARα in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARα agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARα expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARα in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARα targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPARα in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPARα targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPARα activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARα as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARα regulates a mostly divergent set of genes in mouse and human hepatocytes. Keywords: Analysis of target gene regulation by using microarrays |
| 671 | GSE39949 |
Profile | Our previous studies have shown that bone morphogenetic protein 2 (BMP2) a morphogen belonging to the TGFβ superfamily, is markedly induced in human primary endometrial stromal cells (HESC) as they undergo differentiation in response to steroid hormones and cAMP. WNT4 is a downstream target of BMP2 regulation in these cells. To identify the common downstream targets of BMP2 and WNT4 in human endometrial stromal cells, we performed gene expression profling of human ensometrial stromal cell transduced with BMP2 or WNT4 adenovirus. Gene expression profiling revealed that FOXO1, a forkhead family transcription factor and a known regulator of HESC differentiation, is a common downstream mediator of both BMP2 and WNT4 signaling. These studies uncovered a linear pathway involving BMP2, WNT4, and FOXO1 that operates in human endometrium to critically control decidualization. |
| 672 | GSE26828 |
Profile | The immortalized human urothelial cell line UROtsa, was transformed in six parallel cultures with continual passaging in1 µM Cd+2 until the cells were able to attain the ability to form colonies in soft agar and subcutaneous tumors in nude mice. The gene expression profiles between cadmium-transformed and control samples were compared and the differentially expressed genes were identified. |
| 673 | GSE14018 |
Profile | Comparisons among breast cancer metastases at different organs revealed distinct microenvironments as characterized by cytokine content. Such microenvironment distinction might be important to dictate how the cancer cells adapt to survival before they successfully colonize. Keywords: Disease state analyses |
| 674 | GSE15811 |
Profile | The 8p11 myeloproliferative syndrome (EMS) also referred to as the stem cell leukemia/lymphoma syndrome, is a chronic myeloproliferative disorder that rapidly progresses into an acute leukemia. Molecularly, EMS is characterized by fusion of various partner genes to the FGFR1 gene, resulting in constitutive activation of the tyrosine kinase activity within FGFR1. The two most common fusion genes in human EMS are ZMYM2/FGFR1 (previously known as ZNF198/FGFR1) and BCR/FGFR1. To study the transcriptional programs becoming deregulated by the FGFR1 fusion genes, global gene expression analysis on human CD34+ cord blood cells expressing either of the fusion oncogenes ZMYM2/FGFR1 and BCR/FGFR1 was performed. As a reference gene we also included the more studied BCR/ABL1 fusion oncogene associated with chronic myeloid leukemia. We found that the 3 different fusion oncogenes had in common the upregulation of several genes involved in the JAK/STAT signalling pathway and also other sets of genes. However, the gene expression profiles were not identical, suggesting that both the tyrosine kinase containing gene and the partner gene would affect the transcription of downstream target genes. |
| 675 | GSE8665 |
Profile | We have examined the biological effect of EWS/ETS in human MPCs using UET-13 cells that are obtained by prolonging the lifespan of human bone marrow stromal cells using the retroviral transgenes hTERT and E7. By exploiting tetracycline-inducible systems for expressing EWS/ETS (EWS/FLI1 and EWS/ERG) we investigated candidates for genes whose expression is regulated by EWS/ETS in human MPCs. Keywords: Time course |
| 676 | GSE13496 |
Profile | To determine how aging impacts gene expression in hematopoietic stem cells (HSCs) human CD34+ cells from bone marrow (34BM) and mobilized stem cell products (34P38NPBSC) were examined using microarray-based expression profiling. Differential expression changes were confirmed by microarray comparisons of younger and older expanded T-cell populations. |
| 677 | GSE1455 |
Profile | This series represents the rehydration series of the human 293h media depleted storage on agarose / rehydration condition course analysis. Samples include Control Monolayer 0 hr desiccation, 0 hr rehydration, 6 hr rehydration, 24 hr rehydration, and 72 hr rehydration. Keywords = 293h cells Keywords = desiccation Keywords = rehydration Keywords = spheroid Keywords = stabilization Keywords = ambient temperature Keywords: other |
| 678 | GSE8096 |
Profile | Nonmalignant human mammary epithelial cells (HMEC) seeded in laminin-rich extracellular matrix (lrECM) form polarized acini and in doing so, transit from a disorganized proliferating state to an organized growth-arrested state. We hypothesized that the gene expression pattern of organized and growth-arrested HMECs would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in 184 (finite life span) and HMT3522 S1 (immortal nonmalignant) HMECs on successive days after seeding in a lrECM assay. Both HMECs underwent growth arrest in G0-G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines and examined the expression of these genes in a previously published panel of microarray data for 295 breast cancer samples. We show that genes that are significantly lower in the organized, growth-arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically. Keywords: time course |
| 679 | GSE9844 |
Profile | The head and neck / oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC) is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC. Keywords: Disease/Control analysis |
| 680 | GSE17114 |
Profile | Behçet’s disease (BD) is a multisystemic immuno-inflammatory disorder characterized by a generalized vasculitis particularly at the orogenital mucosa and eye. It is a complex disease with unclear pathogenesis. To better understand BD´s etiology, we performed genomic expression profiling of patients and controls. |
| 681 | GSE40220 |
Profile | This study utilise the examination of normal gastro-intestinal tissues to determine a tissue specific signal for use in deriving the intestinal signature of intestinal metaplasias of the oesophagus. Normal oesophageal colonic and duodenal tissue biopsies were taken after informed consent and RNA was extracted following histological examination of adjacent tissues for normal aperaing mucosa. |
| 682 | GSE20697 |
Profile | Human abdominal adipose tissue was obtained with informed consent from a 33-year old Caucasian female (BMI = 32.96 Kg/m2) undergoing lipoaspiration. Adipose stromal cells (hASCs) were isolated and differentiated into adipocytes in vitro. |
| 683 | GSE8546 |
Profile | In vivo changes of gene expression profiles (GEP) of tumor cells 48hr after single agent therapy may vary by treatment and provide added predictive power over baseline GEP information. In newly diagnosed patients with multiple myeloma (MM) GEP data were obtained on tumor cells prior to and 48hr after dexamethasone (n=45) or thalidomide treatment (n=42); in case of relapsed MM, GEP data were obtained prior to (n=36) and after (n=19) lenalidomide administration. Dexamethasone and thalidomide induced both common and unique GEP changes. Combined baseline and 48hr changes of GEP in a subset of genes that were discovered in newly diagnosed MM also predicted event-free and overall survival in relapsed patients receiving lenalidomide. Combined with baseline molecular features, changes in GEP following short-term single agent treatment may help guide treatment decisions for patients with MM. The genes whose altered expression is related to eventual survival may also point to mechanisms of action and resistance to different classes of drugs. Keywords: drug response |
| 684 | GSE2109 |
Profile | The mission of expO is to build on the technologies and outcomes of the Human Genome Project to accelerate improved clinical management of cancer patients. IGC's Expression Project for Oncology (expO) seeks to integrate longitudinal clinical annotation with gene expression data for a unique and powerful portrait of human malignancies providing critical perspective on diagnostic markers, prognostic indicators, and therapeutic targets. The goal of expO and its consortium supporters is to procure tissue samples under standard conditions and perform gene expression analyses on a clinically annotated set of deidentified tumor samples. The tumor data is updated with clinical outcomes and is released into the public domain without intellectual property restriction. Series-matrices are available at ftp://ftp.ncbi.nlm.nih.gov/pub/geo/DATA/SeriesMatrix/GSE2109/. For more information, see http://www.intgen.org/ Keywords: cancer portraits |
| 685 | GSE5968 |
Profile | PGC-1 transcription factor was customized to limit its interations to ERRalpha. This mutant (2x9) was used to dissect the transcription activation patterns that are attributable to the PGC1-ERR interaction and PGC-1 actions that are independent of ERR. Inactive mutant with the deleted LLXXL motifs (L2L3) and wt PGC-1 were used as negative and positive controls respectively. BGAL-expressing construct was used to control for non-specific effects of adenoviral infection. Keywords: ERRalpha PGC-1alpha, nuclear receptor, orphan nuclear receptor, coactivator, transcription factors |
| 686 | GSE12266 |
Profile | The aim of this study was to describe the gene expression patterns related to the differentiation and mineralization of bone-forming cells including activation and/or repression of osteogenic or non-osteogenic pathways, remodeling of cell architecture, cell adhesion, cell communication, and assembly of extracellular matrix. The study implied patient selection, tissue collection, isolation and culture of human marrow stromal cells (hMSC) and osteoblasts (hOB), and characterization of bone-forming cells. RNA samples were collected at defined time points, in order to understand the regulation of gene expression during the processes of cell differentiation/mineralization that occur during bone repair. Transcriptome analysis was performed by using the Affymetrix GeneChip microarray technology platform and GeneChip® Human Genome U133 Plus 2.0 Array. Our results help to design a gene expression profile of bone-forming cells during specific steps of osteogenic differentiation. These findings offer an useful tool to monitor the behaviour of osteogenic precursors cultured in presence of exogenous stimuli, i.e. growth factors, or onto 3D scaffolds for bone engineering. Moreover, they can contribute to identify and clarify the role of new genes for a better understanding of the molecular mechanisms regulating osteogenesis. Keywords: time course |
| 687 | GSE31773 |
Profile | Comparison of mRNA expression showed widespread changes in the circulating CD8+ but not CD4+ T-cells from patients with severe asthma. No changes were observed in the CD4+ and CD8+ T-cells in non-severe asthmatics versus healthy controls. Bioinformatics analysis showed that the changes in CD8+ T-cell mRNA expression were associated with multiple pathways involved in T-cell activation. As with mRNAs we also observed widespread changes in expression of non-coding RNA species including natural antisense, pseudogenes, intronic long ncRNAs and long intergenic long ncRNAs in CD8+ T-cells from severe asthmatics. Measurement of the miRNA expression profile showed selective down-regulation of miR-28-5p in CD8+ T-cells and reduction of miR-146a and miR-146b in both CD4+ and CD8+ T-cells. |
| 688 | GSE34440 |
Profile | There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate from normal stem cells based on initiation of a de novo stem cell program by reprogramming of a more differentiated cell type by oncogenic insults or both remains unresolved. A major hurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. Here we discribe Myoepithelial Progenitor Cells (MPCs) that show properties of EMT and claudin low subtype of breast cancers. Through microarray analysis, we have found that these K5-/K19- cells show similar gene expression pattens of the claudin-low subtype of breast cancer. |
| 689 | GSE22973 |
Profile | Gene expression profiling has demonstrated clinical utility as a predictive tool in clinical oncology. We have identified genes associated with invasion of pancreatic cancer and with potential for identifying early recurrence. We used Affymetrix Human U133 Plus 2.0 microarrays to identifiy specific predictive profiles in pancreatic cancer, and the evolution of gene expression. We identified distinct classes of up-regulated genes during this process. |
| 690 | GSE7127 |
Profile | 63 melanoma cell lines hybridized to Affymetrix Hu133_Plus 2 oligo arrays. The aim of this study was to identify potential downstream targets of key oncogenes and TSGs in melanoma (including p14ARF p16INK4A, BRAF etc). Publications relevant to this series include: Johansson et al. Pigment Cell Res 2007. Keywords: melanoma |
| 691 | GSE16450 |
Profile | Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections. We used microarrays to examine the transcriptional responses of the human BE(2)-C neuroblastoma cell line to retinoic acid-induced differentiation and type I IFN stimulation. |
| 692 | GSE37180 |
Profile | A phase I trial of a SRC kinase Inhibitor dasatinib, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Background: We conducted a phase I study of dasatinib, an oral SRC tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in advanced and recurrent epithelial ovarian cancer (EOC). Methods: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included toxicity, response rate (RR), pharmacokinetics and pharmacodynamics. Based on the 3+3 design, cohorts of 3-6 pts received paclitaxel 175 mg/m2 and carboplatin AUC 6 every three weeks with escalating doses of dasatinib (100, 120, 150 mg daily), followed by an 8 patient expansion cohort. Results: Twenty patients were enrolled between 06/07 and 12/09. The median age was 61 yrs (42-82) with a median of 2 prior regimens (0-6), and 71% had platinum-sensitive disease. There were 3-6 pts in each cohort, and 8 in the expansion cohort. Pharmacokinetics were observed over the first 2 cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia. Other toxicities in all cycles included neutropenia (95% grade 3-4), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 45% (complete responses, 3/18(17%); partial responses, 5/18(28%)) and 56% (10/18) had stable disease. The PFS6-month actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. Conclusions: Due to the high incidence of myelosuppression with subsequent cycles the recommended phase II dose is 150 mg daily of dasatinib in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity in advanced EOC. |
| 693 | GSE42925 |
Profile | HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFN’s. The three alleles and mutants with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFN’s. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. To investigate what domain of Tat are critical to the host-pathogen interactions that are Tat-dependent during HIV infection, we evaluated a variety of Tat-mutants and found that in antigen presenting cells, blood-derived myeloid iDC and macrophages, the second exon of Tat reduces innate immunological responses which are maximal when a Single exon Tat is expressed. |
| 694 | GSE3526 |
Profile | Normal human tissue samples from ten post-mortem donors were processed to generate total RNA which was subsequently analyzed for gene expression using Affymetrix U133 plus 2.0 arrays. Donor information: Donor 1 - 25 year old male; donor 2 - 38 year old male; donor 3 - 39 year old female; donor 4 - 30 year old male; donor 5 - 35 year old male; donor 6 - 52 year old male; donor 7 - 50 year old female; donor 8 - 48 year old female; donor 9 - 53 year old female; donor 10 - 23 year old female Keywords: normal human tissue comparison |
| 695 | GSE9000 |
Profile | Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition. Keywords: Androgen receptor, histone deacetylase, prostate cancer, dose response |
| 696 | GSE36238 |
Profile | Background Accurate assessment of treatment efficacy would facilitate clinical trials of new anti-tuberculosis drugs. TB patients exhibit altered peripheral immunity which reverts during successful treatment. We hypothesised that these changes could be observed in whole blood transcriptome profiles. Methods Ex vivo blood samples from 27 pulmonary TB patients were assayed at diagnosis and during conventional treatment. RNA was processed and hybridised to Affymetrix GeneChips to determine expression of over 47,000 transcripts. Findings There were significant changes in expression of over 4,000 genes during treatment. Rapid, large scale changes were detected, with down-regulated expression of ~1,000 genes within the first week, including inflammatory markers such as the complement components C1q and C2. This was followed by slower changes in expression of different networks of genes, including a later increase in expression of B cell markers, transcription factors and signalling molecules. Interpretation The expression of many genes is drastically altered during TB disease, with components of the humoral immune response being markedly affected. The treatment-induced restoration reflects the simultaneous suppression and activation of different immune responses in TB. The rapid initial down-regulation of expression of inflammatory mediators coincides with rapid killing of actively dividing bacilli, whereas slower delayed changes occur as drugs act on dormant bacilli and as lung pathology resolves. Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity. |
| 697 | GSE10444 |
Profile | In previous studies human dental pulp stem cells (hDPSCs) were mainly isolated from adults. In this manuscript, we tried characterization of hDPSCs isolated from an earlier developmental stage to evaluate potential usage of these cells for tissue regenerative therapy. hDPSCs isolated at the crown-completed stage showed a higher proliferation rate than those isolated at the later stage. When the cells from either group were cultured in medium promoting differentiation towards cells of the osteo/odontoblastic lineage, both became alkaline phosphatase positive, produced calcified matrix, and were also capable of forming dentin-like matrix on scaffolds in vivo. However, during long-term passage, these cells underwent a change in morphology and lost their differentiation ability. The results of a DNA array experiment showed that the expression of a number of genes, such as WNT16, was markedly changed with increasing number of passages, which might have caused the loss of their characteristics as hDPSCs. Keywords: gene expression study, long-term cultures |
| 698 | GSE17077 |
Profile | The presence of senescent cells in the aging/degenerating human disc is now well-recognized. Senescent cells are viable cannot divide, remain metabolically active and accumulate within the disc over time. Molecular analysis of senescent cells in tissue, however, offers a special challenge since there are no cell surface markers for senescence which would let one use fluorescence-activated cell sorting as a method for separating out senescent cells. Here we use a novel experimental design using laser capture microdissection to selectively separately harvest senescent and non-senescent annulus cells in paraffin-embedded tissue, and then compare their gene expression with microarray analysis. An initial in vitro study using cultured human annulus cells was first performed to test whether there was any difference in identification of senescent cells using the accepted histochemical methodology vs. the immunofluoresent identification of cells positive for senescence-associated-ß-galactosidase in control cells and cells induced into stress-induced premature senescence via hydrogen peroxide exposure. No statistically significant difference was found between the 2 methods. Laser capture microdissection was used to separately harvest senescent and non-senescent cells from 11 human annulus specimens, and microarray analysis was used to determine gene expression levels. Genes with established relationships to senescence were found to be significantly upregulated in senescent cells vs. non-senescent cells. Additional genes related to cytokines, cell proliferation, and other cell processes were also identified. |
| 699 | GSE12408 |
Profile | The Cohesin apparatus has a canonical role in sister chromatid cohesion. Heterozygous mutations in Nipped B-like (NIPBL) SMC1A, and SMC3 have been found in 60% of probands with Cornelia de Lange Syndrome (CdLS), a dominant multi-system genetic disorder with variable expression. We have performed a genome-wide transcription assessment as well as cohesin binding analysis using human lymphoblastoid cell lines (LCLs) from probands with CdLS and controls. Here, we report a unique profile of genes dysregulated in CdLS that correlates with different clinical presentations. Genome-wide analysis of cohesin binding demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of an insulator. However, the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS probands, indicating an alternative role of cohesin as a classic transcription factor. Cohesin also co-localizes with CTCF at the boundary elements affecting neighboring gene expression in CdLS probands. We propose that the CdLS phenotype is the result of dysregulated gene expression rather than defective sister chromatid cohesion. Phenotype specific expression profiles are also described. Keywords: Disease state analysis, Genetic modification |
| 700 | GSE40424 |
Profile | A549 and H1299 cell lines were transfected with hMOF specific siRNA or control siRNA and Affymetrix oligonucleotide microarray was conducted to systematically determine downstream targets regulated by hMOF. |
| 701 | GSE45295 |
Profile | The mammalian HIRA/UBN1/ASF1a complex is a histone chaperone complex that is conserved from yeast (Saccharomyces cerevisiae) to humans. This complex preferentially deposits the histone variant H3.3 into chromatin in a DNA replication-independent manner and is implicated in diverse chromatin regu- latory events from gene activation to heterochromatinization. In yeast the orthologous complex consists of three Hir proteins (Hir1p, Hir2p, and Hir3p), Hpc2p, and Asf1p. Yeast Hir3p has weak homology to CABIN1, a fourth member of the human complex, suggesting that Hir3p and CABIN1 may be orthologs. Here we show that HIRA and CABIN1 interact at ectopic and endogenous levels of expression in cells, and we isolate the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex, assembled from recombinant proteins. Mutational analyses support the view that HIRA acts as a scaffold to bring together UBN1, ASF1a, and CABIN1 into a quaternary complex. We show that, like HIRA, UBN1, and ASF1a, CABIN1 is involved in heterochromatinization of the genome of senescent human cells. Moreover, in proliferating cells, HIRA and CABIN1 regulate overlapping sets of genes, and these genes are enriched in the histone variant H3.3. In sum, these data demonstrate that CABIN1 is a functional member of the human HUCA complex and so is the likely ortholog of yeast Hir3p. We used microarrays to detail the global programme of gene expression after knockdown of HIRA and CABIN1 in 3 replicates |
| 702 | GSE8605 |
Profile | BACKGROUND: Cervical carcinoma develops as a result of multiple genetic alterations. Different studies investigated genomic alterations in cervical cancer mainly by means of metaphase comparative genomic hybridization (mCGH) and microsatellite marker analysis for the detection of loss of heterozygosity (LOH). Currently high throughput methods such as array comparative genomic hybridization (array CGH), single nucleotide polymorphism array (SNP array) and gene expression arrays are available to study genome-wide alterations. Integration of these 3 platforms allows detection of genomic alterations at high resolution and investigation of an association between copy number changes and expression. RESULTS: Genome-wide copy number and genotype analysis of 10 cervical cancer cell lines by array CGH and SNP array showed highly complex large-scale alterations. A comparison between array CGH and SNP array revealed that the overall concordance in detection of the same areas with copy number alterations (CNA) was above 90%. The use of SNP arrays demonstrated that about 75% of LOH events would not have been found by methods which screen for copy number changes, such as array CGH, since these were LOH events without CNA. Regions frequently targeted by CNA, as determined by array CGH, such as amplification of 5p and 20q, and loss of 8p were confirmed by fluorescent in situ hybridization (FISH). Genome-wide, we did not find a correlation between copy-number and gene expression. At chromosome arm 5p however, 22% of the genes were significantly upregulated in cell lines with amplifications as compared to cell lines without amplifications, as measured by gene expression arrays. For 3 genes, SKP2, ANKH and TRIO, expression differences were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSION: This study showed that copy number data retrieved from either array CGH or SNP array are comparable and that the integration of genome-wide LOH, copy number and gene expression is useful for the identification of gene specific targets that could be relevant for the development and progression in cervical cancer. Keywords: DNA copynumber RNA expression correlation |
| 703 | GSE11916 |
Profile | The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. Β-catenin a cytoplasmic component, plays a major role in the transduction of the canonical wnt/ β-catenin signaling. The aim of this study was to identify novel genes that are regulated by active β-catenin/TCF signaling in hepatocellular carcinoma. We selected and expanded isogenic clones from hepatocellular carcinoma-derived Huh7 cells with high and low β-catenin/TCF activities. We showed that, high TCF activity Huh7 cells lead to bigger and more aggressive tumors when xenografted into nude mice. We used SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis in parallel, to compare gene expression between low (basal) and high (transfected) β-catenin/TCF activity clones, those had been xenografted into nude mice. We compared and contrasted SAGE and genome-wide microarray data, in parallel. Finally; after combined analysis, we identified BRI3 and HSF2 as novel targets of Wnt/β-catenin signaling in hepatocellular carcinoma. |
| 704 | GSE29232 |
Profile | Transcriptional profiling of RWPE-1 cells stably expressing human androgen receptor (as described in Altintas et al. Mol Cell Endocrinol 2011) treated with a non-metabolisable androgen, R1881 |
| 705 | GSE20874 |
Profile | Mature NK and T-cell lymphomas are occasionally encountered in Asia but are very rare in Western populations. In part due to its rarity little is known about this group of neoplasms, and despite being rather different disease entities, they are all treated similarly but with diverse clinical outcomes. Novel biomarkers (at both the genetic and protein levels) are needed to resolve diagnostic difficulties, improve prognostication and develop targeted therapies. To rectify this deficiency, we interrogated the transcriptome of several NK and mature T-cell lymphomas by whole-genome expression profiling for new markers that may further stratify this diverse group of conditions. Our initial efforts have identified a promising candidate marker that appears to differentiate NKTL lymphoma from other forms of T-cell neoplasms, and this finding has been validated by immunohistochemistry on archival material in a large number of patient cases. |
| 706 | GSE10867 |
Profile | Background and aims: Dysregulation of intestinal epithelial cells performance associates with an array of pathologies whose onset mechanisms are incompletely understood. The aim of the present study was to provide a map of gene expresssion patterns along the human healthy adult gastro-intestinal tract and to implement a new procedure for microarray data noise filtering that would allow their use as a reference when screening for pathological deviations such as inflammatory bowel disease (IBD). Methods: Gene expression profiles in antrum, duodenum, jejunum, ileum and transverse colon biopsies were measured with the Affymetrix U133A array and principal component analysis was used to identify region-selective biomarkers. These data were intersected with highly variable genes from a public dataset of gene expression in the ileal and colonic healthy regions of UC and Crohn’s disease patients. Moreover, gene sets covering gut functions not entirely accounted for by the available public tools were constructed to monitor their expression along the GI tract. Results: 166 genes were found to be responsible for distinguishing the five regions considered. Fourteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion, and six other novel genes. Similar analysis of the IBD datasets revealed that samples stratify based on disease rather than on the intestinal region. This withstanding, eleven genes were identified as possible early predictors of Crohn’s and/or UC in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. Conclusions: This novel approach, validated by retrieving known gene profiles, allowed the identification of promising new leads both in health and IBD state. Keywords: gastro-intestinal tract comparison |
| 707 | GSE41827 |
Profile | Copper-based chemotherapeutic compounds Casiopeinas have been presented as able to promote selective programmed cell death in cancer cells, thus being proper candidates for targeted cancer therapy. DNA fragmentation and apoptosis -in a process mediated by reactive oxygen species- for a number of tumor cells, have been argued to be the main mechanisms. However, a detailed functional mechanism (a model) is still to be defined and interrogated for a wide variety of cellular conditions; before establishing settings and parameters needed for their wide clinical application. Microarrays were used to determine the expression profile from HeLa cells in order to propose a model for the role played by intrinsic apoptosis triggered by the oxidative stress caused by Cas-II-gly. |
| 708 | GSE21293 |
Profile | Human squamous cell cancers are the most common epithelially derived malignancies. One example is esophageal squamous cell carcinoma (ESCC) which is associated with a high mortality rate that is related to a propensity for invasion and metastasis. We report that periostin, a highly expressed cell adhesion molecule, is a key component of a novel tumor invasive signature obtained from an organotypic culture model of engineered ESCC. This tumor invasive signature classifies with human ESCC microarrays, underscoring its utility in human cancer. Genetic modulation of periostin promotes tumor cell migration and invasion as revealed in gain of and loss of function experiments. Inhibition of EGFR signaling and restoration of wild-type p53 function were each found to attenuate periostin, suggesting interdependence of two common genetic alterations with periostin function. Our studies reveal periostin as an important mediator of ESCC tumor invasion and they indicate that organotypic (3D) culture can offer an important tool to discover novel biologic effectors in cancer. |
| 709 | GSE16249 |
Profile | The transcription factors PAX3 and MITF are required for the development of the neural crest and melanocyte lineage and both proteins play important roles in melanoma cell growth and survival. PAX3 transcriptionally activates MITF expression during neural crest development, but the relationship between these transcription factors during melanocyte development and in melanoma cells is currently poorly understood. This study aimed to further our understanding of the interaction between transcriptional networks controlled by PAX3 and MITF by assessing the effect of siRNA-mediated knockdown of PAX3 and MITF in metastatic melanoma cell lines. The goals of this study were to determine (i) if PAX3 is required for maintaining expression of MITF in melanoma and melanocyte cell lines; (ii) whether PAX3 and MITF independently, or redundantly, influence growth and survival in melanoma cell lines; and (iii) to investigate the respective roles of PAX3 and MITF expression in melanoma cell differentiation. Microarrays were used to measure global changes in transcript expression in response to siRNA-mediated knockdown of PAX3 or MITF compared to non-targeting controls in two metastatic melanoma cells lines. |
| 710 | GSE13714 |
Profile | Leukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biological characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression of select Homeobox genes including HOXA9. Here we investigated the effects of HOXA9 suppression in MLL-rearranged and MLL-germline leukemias utilizing RNAi. Gene expression profiling after HOXA9 suppression demonstrated co-downregulation of a program highly expressed in human MLL-AML (this study) and murine MLL-leukemia (Krivtsov et al. 2006) stem cells including HOXA10, MEIS1, PBX3 and MEF2C. Our data indicates an important role for HOXA9 in human MLL-rearranged leukemias, and suggests targeting HOXA9 or downstream programs may be a novel therapeutic option. |
| 711 | GSE6629 |
Profile | Transcription factor complexes bind to regulatory sequences of genes providing a system of individual expression regulation. Targets of distinct transcription factors usually map throughout the genome, without clustering. Nevertheless, highly and weakly expressed genes do cluster in separate chromosomal domains with an average size of 80 to 90 genes. We therefore asked whether, besides transcription factors, an additional level of gene expression regulation exists that acts on chromosomal domains. Here we show that identical green fluorescent protein (GFP) reporter constructs integrated at 90 different chromosomal positions determined by sequencing, obtain expression levels that correspond to the activity of the domains of integration. These domains are about 80 genes long and can exert an effect of up to 8-fold on the expression of integrated genes. 3D-FISH shows that active domains of integration have a more open chromatin structure than integration domains with weak activity. These results reveal a novel domain-wide regulatory mechanism that, together with transcription factors, exerts a dual control over gene transcription. Keywords: HEK293 cells |
| 712 | GSE17371 |
Profile | Skeletal muscle (rectus femoris) gene expression was analyzed from diet-resistant and diet-sensitive obese women undergoing clinically supervised weight-loss at a weight management clinic The goal of the study was to characterize global gene expression profiles in skeletal muscle from obese women prior to their participation in a clinically supervised, low-calorie diet, weight management program. Following entry into the weight-loss program, subjects can be categorized as being 'diet-sensitive' or 'diet-resistant' depending on the rates of weight loss achieved. In the current study, we selected an equal number of diet-sensitive and diet-resistant subjects for comparative expression profiling |
| 713 | GSE26146 |
Profile | In order to find the difference between human lung tissue-derived fibroblasts and human vascular adventitial fibroblasts for enhancing tumor formation ablity of human lung adenocarcinoma cell line A549 we found that human vascular adventitial fibroblasts enhance A549 tumor formation in vivo compared to human lung tissue-derived fibroblasts. To find the responsible genes for this phenomena, we used microarray analysis to find the expression difference between lung tissue-derived fibroblasts and vascular adventitial fibroblas |
| 714 | GSE29061 |
Profile | The hepatitis E virus (HEV) a non enveloped RNA virus, causes viral hepatitis. The viral open reading frame 2 (ORF2) protein represents the capsid protein of HEV which is known to cause endoplasmic reticulum stress in ORF2 expressing cells. The initiation of endoplasmic reticulum stress induced apoptosis mainly involves the transcriptional activation of pro-apoptotic gene CHOP which will further trigger the major apoptotic pathways. However, the activation of CHOP by ORF2 protein in this study does not induce apoptotic markers such as Bax translocation to mitochondria. We have used the Affymetrix microarray platform to screen the pro-apoptotic effects induced by the expression of ORF2 protein in human hepatic cell lines (Huh7). The Huh7 cells were transduced either with recombinant adenovirus encoding the HEV ORF2 (Ad-ORF2) or an adenovirus encoding the green fluorescent protein (Ad-GFP). The array results consistently showed an ORF2 specific induction of mRNA corresponding to the chaperones Hsp72, Hsp70B’ and co-chaperone Hsp40. These studies provide further mechanisms of the ER stress mediated pro apoptotic effects caused by the ORF2 protein and its potential role for the activation of anti-apoptotic activity of the host cell. |
| 715 | GSE14801 |
Profile | ERG (Ets Related Gene) is an ETS transcription factor that was originally described for its role in a number of human cancers. Our preliminary data demonstrate that ERG exhibits a highly EC restricted pattern of expression in cultured primary cells and several adult tissues including the heart lung, and brain. In response to inflammatory stimuli, such as TNF-alpha, we observed a marked reduction of ERG expression in EC. To further define the role of ERG in the regulation of normal EC function we used RNA interference to knockdown ERG. Knockdown of ERG in human umbilical vein EC (HUVEC) using siRNA was associated with the reduction of a number known ERG targets. Keywords: SIRNA Functional Role |
| 716 | GSE42392 |
Profile | Biopsies (lymph nodes ascites or hydrothorax) from 60 patients with cancer of unknown primary origin were analyzed. Results provide insight into the molecular pathogenesis of CUP. |
| 717 | GSE40281 |
Profile | Highly pathogenic avian influenza viruses (HPAIV) induce severe inflammation in poultry and men. There is still an ongoing threat that these viruses may acquire the capability to freely spread as novel pandemic virus strains that may cause major morbidity and mortality. One characteristic of HPAIV infections is the induction of a cytokine burst that strongly contributes to viral pathogenicity. It has been suggested that this cytokine overexpression is an intrinsic feature of infected cells and involves hyperinduction of p38 mitogen activated protein kinase (MAPK). Here we investigate the role of MAPK p38 signaling in the antiviral response against HPAIV in mice as well as in endothelial cells, the latter a primary source for cytokines during systemic infections. Global gene expression profiling of HPAIV infected endothelial cells in the presence of the MAP kinase p38-specific inhibitor SB202190 revealed, that inhibition of MAPK p38 leads to reduced expression of interferon (IFN) and other cytokines after A/Thailand/1(KAN-1)/2004 (H5N1) and A/FPV/Bratislava/79 (H7N7) infection. Furthermore, the expression of interferon stimulated genes (ISGs) after treatment with IFN or conditioned media from HPAIV infected cells was decreased when the target cells were preincubated with SB202190. Finally, promoter analysis confirmed a direct impact of p38 MAPK on the IFN-enhanceosome and ISG-promoter activity. In vivo inhibition of MAP kinase p38 greatly diminishes virus induced cytokine expression concomitant with reduced viral titers, thereby protecting mice from lethal infection. These observations show, that MAPK p38 acts on two levels of the antiviral IFN response: Initially the kinase regulates IFN induction and at a later stage MAPK p38 controls IFN signaling and thereby expression of IFN-stimulated genes. Thus, inhibition of MAP kinase p38 may be an antiviral strategy that significantly protects mice from lethal influenza via suppression of overshooting cytokine expression. |
| 718 | GSE19860 |
Profile | The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined based on the best observed response at the end of the first-line treatment mFOLFOX6. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. |
| 719 | GSE25725 |
Profile | compare the gene expression profile between cep701 treated HEL cells with shPRMT5 knockingdown HEL cells. HEL cells contain homologous alells with mutation Jak2V617F. We found JAK2V617F can inactivate PRMT5 activity by directly phosphorylating PRMT5 through histone methylation. |
| 720 | GSE33825 |
Profile | Resident stem/progenitor cells in lungs are important for tissue homeostasis and repair. We isolated human lung progenitor cells and named alveolar epithelial progenitor cells (AEPCs)(Fujino N et al. 2011. Lab Invest. 91:363). AEPCs have phenotypes of both alveolar epithelial type II (ATII) cells and mesenchymal stem cells. AEPCs had the potential to generate ATII-like cells in vitro. ATII-like cells derived from AEPCs expressed protein and mRNA of pulmonary surfactant, and displayed lamellar bodies containing the surfactants. However, it has not been evaluated whether global gene expression of the ATII-like cells from AEPCs was similar to that of mature ATII cells isolated from human lung tissues. This study demonstrated gene expression profiles of ATII-like cells from AEPCs. In addition, transcriptomes in AEPCs and mature ATII cells were deposited in the GEO website (GSE21095 and GSE29133, respectively). |
| 721 | GSE35340 |
Profile | Langerhans cell histiocytosis (LCH) is a disease characterized by the accumulation of eponymous CD1a+ Langerin+ Langerhans-cell (LC)-like dendritic cells (DC) of largely unknown origin. Here we have performed comparative transcriptome analysis of highly purified CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations and disease courses and three major human dendritic cell lineages: epidermal Langerhans cells myeloid dendritic cells (mDC1) and plasmacytoid dendritic cells (pDC) in order to investigate the relationship between LCH cells and naturally occurring dendritic cells. Data obtained indicate that LCH cells form a distinct DC entity. Furthermore, we have identified transcripts that are uniquely expressed by LCH cells in comparison to LC, mDC1, and pDC, and induce LCH-specific features in human DC. |
| 722 | GSE17645 |
Profile | The purpose of this experiment was to identify oestrogen regulated genes in human primary cell cultures of neuronal cells modelling the developing human nervous system. We were especially interested in genes involved in proliferation differentiation and migration of neuronal cells and genes involved in or linked to neurodegenerative diseases. We have therefore assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of oestrogen treated human neuronal cell cultures. |
| 723 | GSE15162 |
Profile | Quercetin is a flavonol modifying numerous cell processes with potent antiproliferative effects on cancer cell-lines. The aim of this study was to explore by gene-array analysis the effect of quercetin on cancer-related gene expression in HepG2 cells followed by verification with RT-PCR and analysis of the expected phenotypic changes (migration, cell cycle, cell proliferation). Quercetin induces significant changes on cell-adhesion related genes, leading to reduced migratory capacity and disorganization of the actin cytoskeleton. Several genes related to DNA functions, cellular metabolism and signal-transducer activities were also modified, while an early effect on G–protein related cascades possibly via protease-activated receptor 2 and phospholipase C-γ1 was identified. Cyclin-D associated events in G1 and ubiquitin-dependent degradation of cyclin-D1 were also affected, resulting in cell-cycle arrest without activation of apoptosis pathways. In conclusion quercetin (3μM) exerts its cellular effects by modifying numerous genes related to mechanisms involved in cancer initiation and promotion. |
| 724 | GSE28274 |
Profile | Treatment of MCF7 breast cancer cells by cisplatin leads to a very specific metabolic response and an onset of cell death about 10-11 h after beginning of treatment. For more detailed understanding of the molecular processes underlying the specific metabolic response mRNA was isolated from MCF7 cells when the specific changes, (i) induction of glycolysis and (ii) onset of cell death, were detected during online measurement in the cell biosensor system. |
| 725 | GSE48237 |
Profile | Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) frequently complicates combined anti-retroviral therapy (ART) and anti-tubercular therapy in HIV-1 co-infected tuberculosis (TB) patients. The immunopathological mechanism underlying TB-IRIS is incompletely defined. Differential transcript abundance in PBMC from IRIS and control patients stimulated with heat killed H37Rv was determined by microarray |
| 726 | GSE6731 |
Profile | Ulcerative colitis (UC) and Crohn’s disease (CD) are inflammatory bowel diseases (IBD) with variable overlapping clinical features and complex pathophysiologies. To identify pathogenic processes underlying these disease subtypes, using single endoscopic pinch biopsies to estabolish 36 expression profiles, we elucidated gene expression patterns of active and inactive areas of UC and CD, and compared these to infectious colitis and healthy controls. Keywords: RNA |
| 727 | GSE3202 |
Profile | In this experiments different treatments were applied to lung cancer cell lines 1)H720 cell line suspension was treated by 1 micromole of 5-lipoxygenase activating protein inhibitor MK886 serum-free in TIS medium for 24 h. 2) A549 cell line was treated as H720 by MK886 3) A549 was treated by 100 nM of silencing cocktail (siRNA) prepared against the 4-th exon of the gene and generated by RNASEIII digestion of double stranded RNA. The cocktail was prepared by Ambion technology see the manufacturer's protocol. The observed silencing was >90% 4) Based on Oligoengine vectors, silencing constructs were created against HRPA2B1 transcript(HNRPA2B1 is a subunit of spliceosome). Stable transfectants were raised harboring the construct. Keywords: drug treatment |
| 728 | GSE44537 |
Profile | Cancer stem cells (CSCs) are plastic in nature a characteristic that hampers cancer therapeutics. Neuroblastoma (NB) is a pediatric tumor of neural crest origin, and half of the cases are highly aggressive. By treating NB cell lines (SKNAS, SKNBE(2)C, CHP134, SY5Y) with epigenetic modifiers for a short time followed by sphere-forming culture conditions, we have established stem cell-like NB cells that are phenotypically stable for over a year. These cells are characterized by their high expression of stemness factors, stem cell markers, and open chromatin structure. We referred to these cells as induced CSC (iCSC). SKNAS iCSC and SKNBE(2)C iCSC clones (as few as 100 cells) injected subcutaneously into SCID/Beige mice formed tumors, and in one case, SKNBE(2)C iCSC metastasized to the adrenal gland, suggesting their increased metastatic potential. SKNAS iCSC xenografts showed the histologic appearance of totally undifferentiated “large-cell” NBs (LCNs), the most aggressive and deadly form of NB in humans. Immunohistochemical analyses showed that SKNAS iCSC xenografts expressed high levels of the stem cell marker CXCR4, while the SKNAS monolayer cell xenografts did not. The patterns of CXCR4 and MYC expression in SKNAS iCSC xenografts resembled those in the LCNs. The xenografts established from the NB iCSCs shared two common features: the LCN phenotype and high-level MYC/MYCN expression. These observations suggest that NB cells with large and vesicular nuclei, representing their open chromatin structure, are indicative of stem cell-like tumor cells, and that epigenetic changes may have contributed to the development of these most malignant NB cells. |
| 729 | GSE17301 |
Profile | IFN alpha mediated gene expression pattern. The effect of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs. This analysis examined the effects of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs. Magnetically sorted untouched CD8+CD45R0- T cells from three different donors were unstimulated or stimulated with IFNa2b or with anti-CD3/CD28 Beads alone or along with IFNa2b or IFNa5 for 48 hours. Individual mRNA samples were analyzed using HG-U133A 2.0 array gene chips. Keywords: Gene expression analysis after different stimulation |
| 730 | GSE5716 |
Profile | Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSI) which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Analysis of gene expression in GSI-responsive and GSI-resistant cell lines treated with Compound E identifies differential resopnses to GSI. Keywords: Drug response |
| 731 | GSE11839 |
Profile | Purpose: Evaluate gene expression profiles after inducing differentiation in cultured interstitial cystitis (IC) and control urothelial cells. Materials and Methods: Bladder biopsies were taken from IC patients and controls (women having surgery for stress incontinence). Primary cultures were grown in Keratinocyte Growth Medium with supplements. To induce differentiation in some plates the medium was changed to DMEM-F12 with supplements. RNA was analyzed with Affymetrix chips. Three nonulcer IC patients were compared with three controls. Results: After inducing differentiation, 302 genes with a described function were altered at least 3-fold with p <0.01 in both IC and control cells. Functions of the162 upregulated genes included cell adhesion (e.g. claudins, occludin, cingulin); urothelial differentiation, retinoic acid pathway and keratinocyte differentiation (e.g. skin cornified envelope components). The 140 downregulated genes included genes associated with basal urothelium (e.g. p63, integrins ?4, ?5 and ?6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins and members of the Wnt and Notch pathways. Comparing IC vs. control cells after differentiation, only seven genes with a described function were altered at least 3-fold with p <0.01. PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased in IC; AKR1C2 and MKNK1 were increased in IC. Conclusions: Differentiation-associated changes occurred in both IC and control cells. Comparing IC vs. control revealed very few differences. This study may have included IC patients with minimal urothelial deficiency and/or selected the cells that were most robust in culture. Also, the abnormal urothelium in IC may be due to post-translational changes and/or the bladder environment. |
| 732 | GSE37427 |
Profile | We found microRNA miR-23b was down-regulated in local inflammatory tissues of autoimmune disease such as RA SLE and related mouse models such as CIA, lpr, EAE. Re-expression of miR-23b significantly inhibits autoimmune pathogenesis of CIA, Lpr and EAE. To identify potential targets of miR-23b, we use microarray gene-expression analysis to identify transcripts which could be repressed by miR-23b. RA: rheumatoid arthritis, CIA: Collagen-induced arthritis, SLE: systemic lupus erythematosus, EAE: experimental autoimmune encephalomyelitis |
| 733 | GSE19959 |
Profile | Premature progesterone (P) rise during GnRH antagonist cycles for IVF is a frequent phenomenon and has been associated with lower pregnancy and implantation rates. Different thresholds of progesterone have been used so far to define its premature rise during the follicular phase of an IVF stimulated cycle. In this study we evaluated endometrial gene expression on the day of oocyte retrieval according to the level of serum progesterone on the day of hCG administration in GnRH antagonist cycles.Endometrial biopsies from eleven patients were taken with a Pipelle de Cornier (Prodimed, Neuilly-en-Thelle, France) on the day of oocyte retrieval in a GnRH antagonist/rec-FSH stimulated IVF cycle with fresh embryo transfer. Biopsies were analysed for gene expression with Affymetrix Human Genome (HG) U133 Plus 2.0 Arrays and GCOS software (Affymetrix, Santa Clara, CA, USA). Patients were divided into three different groups according to their progesterone serum concentration on the day of hCG administration (A) P <= 0.9 ng/mL, (B) 1 < P < 1.5 ng/mL, and (C) P > 1.5 ng/mL. Serum P was measured with the automated Elecsys immunoanalyser (Roche Diagnostics, Mannheim, Germany). Selected differentially expressed genes were validated with quantitative real-time PCR (QPCR) with TaqMan Gene Expression Assays (Applied Biosystems, Foster City, CA, USA). Keywords: gene expression analysis, premature progesterone rise |
| 734 | GSE49506 |
Profile | Approximately KSHV vIRF4 deregulate 284 genes by two-folds |
| 735 | GSE3058 |
Profile | Investigation of Gene Expression Profiling in Unstaged Head Hair Follicles Plucked from Men and Women Keywords: Gene Expression Profiling of Normal Hair Follicles |
| 736 | GSE35566 |
Profile | Expression profiling was used to identify genes differentially expressed in MSS (microsatellite stable) and MSI (microsatellite unstable) colon cancer cell lines. Data submitted in support of manuscript entitled Villin expression is frequently lost in poorly differentiated colon cancer Diego Arango, Sheren Al-Obaidi, David S. Williams, Jose Dopeso, Rocco Mazzolini, Georgia Corner, Do-Sun Byun, Carmel Murone, Lars Tögel, Nikolajs Zeps, Lauri A. Aaltonen, Barry Iacopetta and John M. Mariadason, American Journal of Pathology, 2012. |
| 737 | GSE25145 |
Profile | MEK5 is activated by shear stress in large vessel endothelial cells (ECs) and contributes to the suppression of pro-inflammatory changes in the arterial wall. We used microarray analyses of total RNA from MEK5/CA-transduced HDMECs compared to LacZ control-transduced HDMECs to identify distinct classes of several regulated genes including KLF4, eNOS, and ICAM. We conclude that MEK5 activation by shear stress may modulate inflammatory responses in the microvasculature, and these actions are partly mediated by KLF4. |
| 738 | GSE11819 |
Profile | Inflammatory hepatocellular adenomas (IHCA) are benign liver tumours defined by the presence of inflammatory infiltrates and by the elevated expression of inflammatory proteins in tumour hepatocytes12. Here we show a striking activation of the IL6 signalling pathway in this tumour type, and sequencing candidate genes pinpointed this response to somatic gain-of-function mutations in the IL6ST gene that encodes the signalling co-receptor gp130. Indeed, ~70% of IHCA harbour small in-frame deletions that target the binding site of gp130 for IL6, and expression of the most frequent gp130 mutant, Delta-STVY190, in hepatocellular cells activates STAT3 in absence of ligand. Further, analysis of hepatocellular carcinomas revealed rare gp130 alterations always accompanied by ß-catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant conversion of hepatocytes. The recurrent gain-of-function gp130 mutations in these human hepatocellular adenomas explains their inflammatory phenotype, and suggest that similar alterations may occur in other inflammatory epithelial tumours with STAT3 activation. |
| 739 | GSE13083 |
Profile | To begin to identify genes involved in the transdifferentiation process we analyzed Barrett’s esophagus (with no dysplasia) normal esophagus and small intestine biopsy samples by Affymetrix microarray. Keywords: microarray expression analysis |
| 740 | GSE19445 |
Profile | Microarray experiments were carried out to ascertain whether TOP2β is required for DHT induced androgen receptor target gene expression. We investigated the effect of pharmacological inhibition or RNA interference-mediated depletion of TOP2β on gene expression in androgen-dependent LNCaP prostate cancer cells. |
| 741 | GSE7321 |
Profile | The periodontium are the tissues supporting and investing the tooth and consists of the periodontal ligament the gingiva, the root cementum, and the alveolar bone. The functions of the cell populations in health and disease regarding the host-mediated tissue destruction are not well understood. To get a first idea, of which genes might play a distinct role in chronic periodontal disease in vivo, we compared the genom-wide gene expressions of chronic inflamed and healthy periodontal ligament cells by microarray analysis and validated the data by real-time RT-PCR. The expression rates of 14.239 genes were investigated and 3.018 of them were found differentially expressed by at least two-fold, the expression rates of 1.451 genes were significantly up-regulated and the expression rates of 1.567 genes were significantly down-regulated in inflamed PDL cells. We focused on mainly structural components, for example, laminins and integrins, as well as degrading enzymes, for example, MMPs and cathepsins. The molecular composition of the laminin network varies in chronic inflamed compared to healthy PDL cells in vivo. Furthermore, integrin alpha6beta4, together with laminin-332, might be involved in chronic periodontal inflammation. Findings that diverse keratins were upregulated in chronic disease indicate that the epithelial cell rests of Malassez might also be involved in chronic periodontal inflammation. Also cathepsin B and cathepsin C might participate in the connective tissue destruction. The microarray analysis has identified a profile of genes potentially involved in chronic periodontal inflammation in vivo. Further studies are needed to entirely understand cellular activities during chronic periodontal inflammation in vivo. Keywords: expression analysis |
| 742 | GSE44905 |
Profile | Enzalutamide (formerly MDV3100 and available commercially as Xtandi) a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA. Here we used Affymetrix human genome microarray technology to investigate the global programme of gene expression of LNCaP cells in response to enzalutamide alone and in the context of DHT-stimulated androgen receptor gene expression. |
| 743 | GSE18265 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 744 | GSE2396 |
Profile | gd T cells recognize unprocessed or non-peptide antigens respond rapidly to infection, and localize to mucosal surfaces. We have hypothesized that the innate functions of gd T cells may be more similar to those of cells of the myeloid lineage than to other T cells. To begin to test this assumption, we have analyzed the direct response of cultured human and peripheral blood bovine gd T cells to pathogen associated molecular patterns (PAMPs) in the absence of APCs using microarray, real time RT-PCR, proteome array, and chemotaxis assays. Our results indicate that purified gd T cells respond directly to PAMPs by increasing expression of chemokine and activation related genes. The response was distinct from that to known gd T cell antigens and different from the response of myeloid cells to PAMPs. In addition, we have analyzed the expression of a variety of PAMP receptors in gd T cells. Freshly purified bovine gd T cells responded more robustly to PAMPs than did cultured human cells and expressed measurable mRNA encoding a variety of PAMP receptors. Our results suggest that rapid response to PAMPs through the expression of PAMP receptors may be another innate role of gd T cells. Keywords: parallel sample |
| 745 | GSE10718 |
Profile | Gene expression patterns were assessed in normal human bronchial epithelial (NHBE) cells exposed to cigarette smoke (CS) from a typical "full flavor" American brand of cigarettes in order to develop a better understanding of the genomic impact of tobacco exposure which can ultimately define biomarkers that discriminate tobacco-related effects and outcomes in a clinical setting. NHBE cells were treated with CS for 15 minutes and alterations to the transcriptome assessed at 1,2,4 and 24 hours post-CS-exposure using high-density oligonucleotide microarrays. Keywords: Time course |
| 746 | GSE9159 |
Profile | Distinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens. Keywords: myometrial gene expression, preterm versus term labor |
| 747 | GSE19625 |
Profile | Coenzyme Q10 (CoQ10) is an obligatory element in the respiratory chain and functions as a potent antioxidant of lipid membranes. More recently anti-inflammatory effects as well as an impact of CoQ10 on gene expression have been observed. To reveal putative effects of Q10 on LPS-induced gene expression, whole genome expression analysis was performed in the monocytic cell line THP-1. 1129 probe sets have been identified to be significantly up-regulated (p < 0.05) in LPS-treated cells when compared to controls. Text mining analysis of the top 50 LPS up-regulated genes revealed a functional connection in the NFκB pathway and confirmed our applied in vitro stimulation model. Moreover, 33 LPS-sensitive genes have been identified to be significantly down-regulated by Q10-treatment between a factor of 1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q10-sensitve genes a primary involvement in protein metabolism, cell proliferation and transcriptional processes. Three genes were either related to NFκB transcription factor activity, cytokinesis or modulation of oxidative stress. In conclusion, our data provide evidence that Q10 down-regulates LPS-inducible genes in the monocytic cell line THP-1. Thus, the previously described effects of Q10 on the reduction of pro-inflammatory mediators might be due to its impact on gene expression. |
| 748 | GSE18913 |
Profile | Analysis of umbilical vein endothelial cells (HUVEC) treated with Egr-3 siRNA under the VEGF treatment for 01, and 4 h. Egr-3, a member of early growth response family, is immediately and dramatically induced by VEGF in HUVEC, which regulates expression of many genes related to endothelial activation. |
| 749 | GSE17643 |
Profile | The purpose of the dataset is to analyze expression of genes induced by KRAS and regulated by TBK1 The proto-oncogene KRAS is mutated in a wide array of human cancers most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. An alternative strategy for targeting KRAS is to identify gene products that, when suppressed or inhibited, result in cell death only in the presence of an oncogenic allele. Here we have used systematic RNA interference (RNAi) to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IkB kinase, TBK1, was selectively essential in cells that harbor mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF- B anti-apoptotic signals involving cREL and BCL-XL that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations identify TBK1 as a potential therapeutic target in KRAS mutant tumors and establish a general approach for the rational identification of co-dependent pathways in cancer. |
| 750 | GSE27524 |
Profile | Translocations of ETS transcription factors are driver mutations in diverse cancers. We investigated the genomic network of the ETS fusion EWS/FLI1 in Ewing's sarcoma (ESFT) as a model of ETS-driven tumorigenesis. ChIP-Seq and transcriptional analysis identified E2F3 as a principle co-factor of EWSFLI1 defining functionally distinct gene sets. While EWS/FLI1 binding independent of E2F3 predominantly associated with repressed differentiation genes significant co-localization with E2F3 was discovered at proximal promoters of activated growth-related genes. Thus, EWS/FLI1 promotes oncogenesis by simultaneously perturbing differentiation state and augmenting the expression of genes co-regulated by E2F3. Integration of additional E2F3 and ERG localization data from prostate cancer containing TMPRSS2/ERG verified that the ETS-E2F module is also found in prostate cancer and may be of general relevance to ETS driven cancers. |
| 751 | GSE7579 |
Profile | Objective: Thyroid hormone receptors (TRs) are ligand-dependent transcription factors with a major impact on erythroid cell development. Here we investigated TR activity on red cell gene expression and identified TR target genes. The impact of the TR target gene GAR22 (growth arrest specific 2 [GAS2]-related gene on chromosome 22) on red cell differentiation was determined. Methods: SCF/Epo dependent red cell progenitors were differentiated in vitro in the presence or absence of thyroid hormone. Hormone-induced changes in gene expression were measured by a genome-wide approach with DNA microarrays. Ectopic expression of the TR target gene GAR22 was used to determine its impact on red cell differentiation. Results: Ligand-activated TR effectively accelerated red cell progenitor differentiation in-vitro concomitantly with inducing growth arrest. We demonstrate that activated TR induced specific gene expression patterns of up- or down-regulated genes including distinct clusters associated with accelerated differentiation in response to treatment. Mining for T3 induced genes identified BTEB1 (basic transcription element binding protein 1/Krüppel-like factor 9) and GAR22 as TR target genes. BTEB1/KLF9 is a known TR target gene while GAR22, initially identified as a putative tumor suppressor, represents a novel TR target gene. We demonstrate that ectopic GAR22 expression in red cell progenitors lengthens the cell cycle and causes growth inhibition, but leaves red cell gene expression unaffected. Conclusion: This study identifies GAR22 as a novel and direct TR target gene. Our results suggest that hormone-induced GAR22 might represent an important trigger of growth inhibition induced by thyroid hormone in red cell progenitors. |
| 752 | GSE21354 |
Profile | In this study we performed gene expression profiling of 14 cases of grade II gliomas. The results of these analysis were used in unsupervised analyses to compare correlations between the histological subtype of grade II gliomas and gene expression profiles |
| 753 | GSE1462 |
Profile | Extremely variable clinic and genetic features characterize Mitochondrial Encephalomyopathy Disorders (MED). Pathogenic mitochondrial DNA (mtDNA) defects can be divided into large-scale rearrangements and single point mutations. Clinical manifestations become evident when a threshold percentage of the total mtDNA is mutated. In some MED the "mutant load" in an affected tissue is directly related to the severity of the phenotype. However, the clinical phenotype is not simply a direct consequence of the relative abundance of mutated mtDNA. Other factors, such as nuclear background, can contribute to the disease process, resulting in a wide range of phenotypes caused by the same mutation. Using Affymetrix oligonucleotide cDNA microarrays (HG-U133A), we studied the gene expression profile of muscle tissue biopsies obtained from 12 MED patients (4 common 4977-bp deleted mtDNA and 8 A3243G: 4 PEO and 4 MELAS phenotypes) compared with age-matched healthy individuals. Keywords = mtDNA mutation Keywords = muscle biopsy Keywords = human Keywords = mitochondrial disease Keywords: other |
| 754 | GSE9419 |
Profile | Inadequate protein intake initiates an accommodative response with adverse changes in skeletal muscle function and structure. mRNA level changes due to short-term inadequate dietary protein might be an early indicator of accommodation. The aims of this study were to assess the effects of dietary protein and the diet-by-age interaction on the skeletal muscle transcript profile. Self-organizing maps were used to determine expression patterns across protein trials. 958 transcripts were differentially expressed (P<0.05) with diet and 853 had a diet-by-age interaction (P<0.05) using ANOVA. The results for diet alone revealed that P63 was associated with up-regulation of transcripts related to ubiquitin-dependent protein catabolism and muscle contraction and P63 and P94 resulted in up-regulation of transcripts related to apoptosis and down-regulation of transcripts related to cell differentiation; muscle and organ development; extracellular space; and responses to stimuli and stress. The diet-by-age expression patterns demonstrated that across the three protein trials transcripts related to protein metabolism were affected by age. Changes in skeletal muscle mRNA levels in the younger and older males to protein intake near or below the RDA are indicative of an early accommodative response. 5052 transcripts were determined as differentially expressed (P<0.05) between the younger and older males of which 2556 met the False Discovery Rate correction (P=0.0081). The age-related changes in the transcript profile were consistent with aging skeletal muscle phenotypes including; mitochondrial dysfunction (UP- and DOWN-regulation), RNA splicing (UP), oxidative stress (UP), apoptosis (UP), and energy metabolism (DOWN). Keywords: Age and dietary protein response |
| 755 | GSE10087 |
Profile | This study used microarray expression analysis to identify global changes in transcript alteration in response to MEK inhibition. Genes under ERK control were identified in a panel of V600E BRAF and RTK-activated tumor cells and xenografts using short-term inhibition of ERK activity using the MEK inhibitor PD0325901 (Pfizer). Keywords: paired treatment and control |
| 756 | GSE16648 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 757 | GSE20266 |
Profile | A sensitive assay to identify biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. In this study we have conducted a prospective sample collection and retrospective blinded validation (PRoBE design) to evaluate the performance and translational utilities of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. The Affymetrix HG U133 Plus 2.0 Array and 2D-DIGE were used to profile transcriptomes and proteomes in saliva supernatants respectively. Significant variations of salivary transcriptomic and proteomic profiles were observed between breast cancer patients and healthy controls. Eleven transcriptomic biomarker candidates and two proteomic biomarker candidates were selected for a preclinical validation using an independent sample set. Transcriptomic biomarkers were validated by RT-qPCR and proteomic biomarkers were validated by quantitative protein immunoblot. Eight mRNA biomarkers and one protein biomarker have been validated for breast cancer detection, yielding ROC-plot AUC values between 0.665 and 0.959. This report provides proof of concept of salivary biomarkers for the non-invasive detection of breast cancer. The salivary biomarkers’ discriminatory power paves the way for a PRoBE-design definitive validation study. Keywords: Salivary biomarker, Breast cancer, Early detection, Salivary transcriptome, Salivary proteome |
| 758 | GSE24265 |
Profile | Spontaneous intracerebral hemorrhage (ICH) represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH) and the corresponding contralateral white (CW) and grey (CG) matter. |
| 759 | GSE2292 |
Profile | U2OS-ERa U2OS-ERb, and U2OS-ERab cells treated with 4HT or E2 Keywords: other |
| 760 | GSE36149 |
Profile | Effects of the pan-anti-apoptotic BCL-2 family small molecule inhibitor obatoclax mesylate (GeminX Pharmaceuticals), on gene expression were evaluated by microarray analysis in order to gain insights into the killing mechanism by this compound in two human MLL-AF4 cell lines. The results of the gene expression profiling substantiated other lines of evidence derived from genetic and chemical cell death pathway inhibition, Western blot analysis, flow cytometric apoptosis assays, and electron microscopic analyses, showing triple apoptosis, autophagy, and necroptosis death pathway activation by this agent. The results also demonstrated modulation of a number of novel targets of obatoclax encoding various cell death factors at the gene expression level. |
| 761 | GSE30540 |
Profile | Samples were taken from colorectal cancers in surgically resected specimens in 35 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for CIN phynotype. |
| 762 | GSE18331 |
Profile | Treating unselected cancer patients with new drugs dilutes proof of efficacy when only a fraction of patients respond to therapy. We conducted a meta-analysis on eight primary breast cancer microarray datasets representing diverse breast cancer phenotypes. We present a high-throughput protocol which incorporates drug sensitivity signatures to guide preclinical testing for effective therapeutic agents. Specifically we focus on drug classes currently undergoing early phase clinical testing. Our genomic and experimental results suggest that the majority of basal-like breast cancers should respond to inhibitors of the phosphatidylinositol-3-kinase pathway, and that a relatively low toxicity histone deacetylase inhibitor, valproic acid, may target aggressive breast cancers. For a subset of drugs, prediction of sensitivity associates with tumor recurrence, suggesting clinical relevance. Preclinical studies using both cell lines and patient tumors grown in 3-dimensional in vitro and orthotopic in vivo preclinical models provide an efficient and highly relevant assessment of drug sensitivity in tumor phenotypes, and validate our genomic analyses. Together, our results show that high-throughput transcriptional profiling can significantly impact drug selection for breast cancer patients. Pre-identification of patient response may not only improve therapeutic response rates, it can also assist in quickly identifying the optimal inclusion criteria for clinical trials. Our model facilitates personalized drug therapy for cancer patients and may be generalized for study of drug efficacy in other diseases. |
| 763 | GSE17353 |
Profile | To delineate the role of hypoxia in esophageal epithelial biology we carried out gene array experiments using a non-transformed immortalized diploid human esophageal cell line, EPC2-hTERT (Mol Cancer Res. 2003;1:729-38). Unlike cancer cell lines, EPC2-hTERT has no genetic alterations at early passages that may affect the cellular response to hypoxia. |
| 764 | GSE18501 |
Profile | The effects of the CDK inhibitor PHA-848125 (referred to as CDK-125) on the MCF7 human adenocarcinoma mammary cell line were analysed by gene expression profiling. |
| 765 | GSE12034 |
Profile | The identification of genes and deduced pathways from the mature human oocyte can help us better understand oogenesis folliculogenesis, fertilization, and embryonic development. Human metaphase II oocytes were used within minutes after removal from the ovary, and its transcriptome was compared with a reference sample consisting of a mixture of total RNA from 10 different normal human tissues not including the ovary. RNA amplification was performed by using a unique protocol. Affymetrix Human Genome U133 Plus 2.0 GeneChip arrays were used for hybridizations. Compared with reference samples, there were 5,331 transcripts significantly up-regulated and 7,074 transcripts significantly down-regulated in the oocyte. Of the oocyte up-regulated probe sets, 1,430 have unknown function. A core group of 66 transcripts was identified by intersecting significantly up-regulated genes of the human oocyte with those from the mouse oocyte and from human and mouse embryonic stem cells. GeneChip array results were validated using RT-PCR in a selected set of oocyte-specific genes. Within the up-regulated probe sets, the top overrepresented categories were related to RNA and protein metabolism, followed by DNA metabolism and chromatin modification. This report provides a comprehensive expression baseline of genes expressed in in vivo matured human oocytes. Further understanding of the biological role of these genes may expand our knowledge on meiotic cell cycle, fertilization, chromatin remodeling, lineage commitment, pluripotency, tissue regeneration, and morphogenesis. |
| 766 | GSE16768 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 767 | GSE12685 |
Profile | In Alzheimer’s disease (AD) early deficits in learning and memory are a consequence of synaptic modification which are likely induced by toxic beta-amyloid oligomers (oAβ). To identify molecular targets downstream of oAβ binding we prepared synaptoneurosomes from frontal cortex of control and IAD patients, and isolated mRNAs for comparison of gene expression. This approach elevated synaptic mRNAs above the threshold necessary for expression changes to be discriminated and also reduced other cellular mRNAs. In patients with minimal cognitive impairment (MCI) termed incipient AD (IAD) global measures of cognition declined with increasing levels of dimeric Aβ (dAβ). These patients also showed increased expression of neuroplasticity related genes, many encoding 3' UTR consensus sequences that regulate local translation in the synapse. One such gene, GluR2, displayed elevated mRNA and protein expression in IAD. Other neurotransmitter-related genes were also upregulated. Overexpressed genes may induce compensatory as well as negative effects on cognition and provide targets for intervention to moderate the response to dAβ. |
| 768 | GSE12161 |
Profile | The proinflammatory cytokine TNFalpha is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Considering this, gene transcription profiling was examined in control and TNFalpha treated HepG2 cells. Results indicated that TNFalpha could significantly alter the expression of a significant number of genes; most of them were functionally distributed among molecular functions like catalytic activity, binding, molecular transducer activity, transporter activity, translation and transcription regulator activities or enzyme regulator activity. Also, within genes up-regulated by TNFalpha, several GO terms related to lipid and fat metabolism were significantly overrepresented indicating global dysregulation of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in immunoglobulin receptor activity and IgE binding thereby indicating a compromise in immune defense mechanism(s) apart from those involved the DNA binding and protein binding categories. The interacting network of “lipid metabolism, small molecule biochemistry” was derived to be significantly affected that correlated well with the top canonical pathway of “biosynthesis of steroids” and molecular and cellular function of “lipid metabolism”. All these indicate TNFalpha to be significantly altering the transcriptome profiling within HepG2 cells with genes involved in lipid and steroid metabolism being the most favoured. This study suitably addresses the genes that determine TNFalpha mediated alterations within the hepatocyte mainly the phenotypes of hepatic steatosis and fatty liver that are associated with several hepatic pathological states. |
| 769 | GSE18409 |
Profile | Neurotrophin receptors play a pivotal role in the biology and prognosis of neuroblastoma (NB). While expression of TrkA/NTRK1 confers a good prognosis to NB patients expression of TrkB/NTRK2 is associated with unfavorable outcome. We have transfected the neurotrophin-receptor null cell line SY5Y with either full-length TrkA or TrkB and performed transcriptional profiling to analyse the effects of Trk-expression without activation and in a time course after activation. |
| 770 | GSE27909 |
Profile | Immature cell populations including stem cells and progenitor cells, can be found in “side-population (SP)” cells. Although SP cells isolated from some adult tissues have been reported elsewhere, isolation and characterization of human trophoblast SP cells remained to be reported. We used microarrays to detail the global program of gene expression underlying cell differentiation and identified up-regulated genes of SP cells. |
| 771 | GSE12141 |
Profile | Study of a metastatic progression of an ependimoma. Chromosomal imbalances metaolic and gene expression profiles. Keywords: comparative genomics |
| 772 | GSE17625 |
Profile | Previously we constructed a coculture model to analyze the effect of macrophages on intestinal epithelial cells, and found that TNF-a secreted from human macrophage-like THP-1 cells induced cell damage to intestinal epithelial Caco-2 cells (Exp.Cell.Res. 2006, 312(19):3909-19). In this study, we present activation of NF-kB in Caco-2 cells within 15 min after coculturing. To reveal how TNF-a secreted from THP-1 cells affects Caco-2 cells in an early stage of coculture, we exhaustively analyzed the changes of gene expression in Caco-2 cells cocultured with THP-1 cells over the time periods of 0, 1, 3, 6, 24, and 48 h by using a DNA microarray. Differentially expressed genes extracted with maSigPro demonstrated that IEX-1 was the lowest p-value gene, that is, the most significantly changed gene among the up-regulated genes. The genes expressed in a similar pattern to IEX-1 involved immunity, apoptosis, and protein kinase cascade. These findings suggest that the stimuli of TNF-a from THP-1 cells activates NF-kB, leading induction of various gene expression. This pattern of gene expression indicates that not only early defense response but also cell death occurs at the same time, causing inflammatory condition. |
| 773 | GSE11238 |
Profile | Smallpox is a highly communicable often fatal diseae. There is currently no licensed treatment for smallpox and vaccinia virus (VV) is currently used for immunization. While immunization with VV can provide good protection against exposure to the smallpox virus, the current vaccine is far from optimal. Complications occur in 1/1,000-1/10,000 vaccinees, with at least one death per million vaccinees. We have constructed recombinant VV strains which are less pathogenic, yet provide a protective immune response. These viruses contain various mutations in the E3L which is known to block the host antiviral response. Identifying the host genes involved in producing a strong protective immunological response to these attenuated viruses would not only increase our understanding of the proteins and pathways involved in effective smallpox vaccination, but aid in the development of alternative vaccine strains which enhance these specific immune responses. We will determine gene expression patterns in HeLa cells at various times following infection with wtVV and several VV constructs containing mutations in the E3L gene. The VV E3L gene product blocks the host antiviral response by sequestering viral danger signals, including double-stranded RNA and Z-DNA. VV constructs containing mutations in E3L which allow host cell recognition of either of these danger signals leads to a decrease in viral pathogensis. In this project we will dissect the cellular inflammatory response to infection with wtVV in comparison to VV containing mutations in the E3L gene. By understanding why certain strains of VV are non-pathogenic, yet highly immunogenic, it is possible to gain a better understanding on the mechanisms of poxvirus pathogenesis and the host response. We will examine three times points following infection with VV: 2 HPI, 6 HPI and 9 HPI. These times points represent keys points in the virus replication cycle. Several VV constructs will be used which contain mutations in the E3L gene. These constructs alter the ability of E3L to sequester double-stranded RNA and/or Z-DNA and therefore have a direct effect on viral pathogenesis. Fourteen constructs will be used including: mock, wtVV, VVdelE3L, VVE3Ldel83N, VVE3Ldel37N, VVE3Ldel26C, VVE3Ldel7C, VVE3L Y48A, VVE3L P63A, VVE3L K167T, VV-ATV, VV-ADAR/E3L, VVdelK3L, VVdelK3L-E3Ldel37N. Cells will be infected at an MOI of 5 to allow infection of all cells. At each time point, cells will be harvested by scraping. RNA will be isolated using a Trizol RNA extraction protocol (Invitrogen) followed by RNA purification using the RNeasy cleanup kit available from Qiagen. Keywords: time-course |
| 774 | GSE18739 |
Profile | We established a novel model to assess the function of proteins under in vivo conditions. The model relies on the expansion of HEK293 cells in immunodeficient NOD.Scid mice. To validate the novel model we performed microarray gene expression profiling of NOD.Scid-expanded HEK293 cells relative to conventionally cultivated cells. Microarray analysis revealed that cell expansion in NOD.Scid mice restored an imbalanced chaperone system without inducing a major upregulation of the entire protein folding machinery. |
| 775 | GSE12264 |
Profile | The aim of this study was to describe the gene expression patterns related to the differentiation and mineralization of bone-forming cells including activation and/or repression of osteogenic or non-osteogenic pathways, remodeling of cell architecture, cell adhesion, cell communication, and assembly of extracellular matrix. The study implied patient selection, tissue collection, isolation and culture of human marrow stromal cells (hMSC) and osteoblasts (hOB), and characterization of bone-forming cells. RNA samples were collected at defined time points, in order to understand the regulation of gene expression during the processes of cell differentiation/mineralization that occur during bone repair. Transcriptome analysis was performed by using the Affymetrix GeneChip microarray technology platform and GeneChip® Human Genome U133 Plus 2.0 Array. Our results help to design a gene expression profile of bone-forming cells during specific steps of osteogenic differentiation. These findings offer an useful tool to monitor the behaviour of osteogenic precursors cultured in presence of exogenous stimuli, i.e. growth factors, or onto 3D scaffolds for bone engineering. Moreover, they can contribute to identify and clarify the role of new genes for a better understanding of the molecular mechanisms regulating osteogenesis. Keywords: time course |
| 776 | GSE16934 |
Profile | We developed an experimentally derived molecular signature from mouse tumor models that is closely associated with survival of colorectal cancer (CRC) patients. |
| 777 | GSE29450 |
Profile | To identify the gene signature accounting for the distinct clinical outcomes in ovarian clear cell cancer patients Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. Arrays analyzed using BRB ArrayTools and PathwayStudio software was used to identify the signaling pathways. |
| 778 | GSE17014 |
Profile | Pericytes derived from skin dermis can substantially enhance the short-term tissue-regenerative capacity of human epidermal cells already committed to differentiation; they also display both phenotypic and functional properties of mesenchymal stem cells. In this microarray analysis we compared the gene expression profile of dermal pericytes to that of the remaining dermal cells of neonatal human foreskin. |
| 779 | GSE34781 |
Profile | 20 patients with unstable angina were divided into patient group by using coronary angiography. The sex- and age-matched healthy individuals were enrolled as control group. Venous bloods were collected for extracting RNA. |
| 780 | GSE23362 |
Profile | We used Affymetrix HG U133 Plus 2.0 GeneChips to compare the transcriptome of MDA-MB-231 cells transfected with SDC1-siRNA against negative control siRNA-transfected cells. |
| 781 | GSE28750 |
Profile | Introduction: Sepsis is a complex immunological response to infection characterized by early hyperinflammation followed by severe and protracted immunosuppression suggesting that a multi-marker approach has the greatest clinical utility for early detection, within a clinical environment focused on SIRS differentiation. Pre-clinical research using an equine sepsis model identified a panel of gene expression biomarkers that define the early aberrant immune activation. Thus, the primary objective was to apply these gene expression biomarkers to distinguish patients with sepsis from those who had undergone major open surgery and had clinical outcomes consistent with systemic inflammation due to physical trauma and wound healing. Methods: This was a multi-centre, prospective clinical trial conducted across 4 tertiary critical care settings in Australia. Sepsis patients were recruited if they met the 1992 Consensus Statement criteria and had clinical evidence of systemic infection based on microbiology diagnoses (n=27). Participants in the post-surgical (PS) group were recruited pre-operatively and blood samples collected within 24 hours following surgery (n=38). Healthy controls (HC) included hospital staff with no known concurrent illnesses (n=20). Each participant had minimally 5ml of PAXgene blood collected for leucocyte RNA isolation and gene expression analyses. Affymetrix array and multiplex tandem (MT)-PCR studies were conducted to evaluate transcriptional profiles in circulating white blood cells applying a set of 42 molecular markers that had been identified a priori. A LogitBoost algorithm was used to create a machine learning diagnostic rule to predict sepsis outcomes. Results: Based on preliminary microarray analyses comparing HC and sepsis groups. A panel of 42-gene expression markers were identified that represented key innate and adaptive immune function, cell cycling, WBC differentiation, extracellular remodelling and immune modulation pathways. Comparisons against GEO data confirmed the definitive separation of the sepsis cohort. Quantitative PCR results suggest the capacity for this test to differentiate severe systemic inflammation from HC is 92%. AUC ROC curve findings demonstrated sepsis prediction within a mixed inflammatory population, was between 86 - 92%. Conclusions: This novel molecular biomarker test has a clinically relevant sensitivity and specificity profile, and has the capacity for early detection of sepsis via the monitoring of critical care patients. GEO Note: Data made available represents the preliminary microarray investigation performed on Human U133 Plus 2.0 GeneChips (Affymetrix), assaying 41 patient samples (Sepsis n=10, Post-Surgical n=11, Control n=20). |
| 782 | GSE28724 |
Profile | The hallmark of human cancer is heterogeneity mirroring the complexity of genetic and epigenetic alterations acquired during oncogenesis. We extracted RNA of 34 cultured human ovarian carcinoma cell lines and performed expression microarrays so that cultured cell lines can represent in vivo human tumors. |
| 783 | GSE5110 |
Profile | Our results suggest that 48h of immobilization increases expression of mRNA for components of the UPP and MT function while decreasing mRNA and protein for components involved in ECM integrity. We hypothesized that 48h of immobilization would increase gene expression and respective protein products for components of the ubiquitin proteasome pathway (UPP). Keywords: stimulus or stress design |
| 784 | GSE13671 |
Profile | Female BRCA1 mutation carriers have a nearly 80% probability of developing breast cancer during their life-time. We hypothesized that the breast epithelium at risk in BRCA1 mutation carriers harbors mammary epithelial cells (MECs) with altered proliferation and differentiation properties. Microarray studies revealed that PMEC colonies from BRCA1 mutation carriers anticipate expression profiles found in BRCA1-related tumors and that the EGFR pathway is upregulated in BRCA1 mutation carriers compared ton non BRCA1 mutation carriers. Keywords: Class comparison and pathway analysis |
| 785 | GSE10957 |
Profile | Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in normal eukaryotic cellular function. Here we characterized the metabolic and transcriptional properties of A549 lung cancer cells and their isogenic mitochondrial DNA (mtDNA)-depleted rho zero counterparts grown in cell culture and as tumor xenografts in immune-deficient mice. A manuscript summarizing our conclusions is under review. Keywords: genetic modification and culture conditions |
| 786 | GSE12734 |
Profile | Comparison of Chronic Lymphocytic Leukemia patients expressing high or low levels of ZAP70 mRNA: prognostic factors and interaction with the microenvironment. Zeta-associated protein 70 (ZAP70) is a widely recognized prognostic factor in chronic lymphocytic leukemia (CLL) but mechanisms by which its higher expression leads to a poor outcome remain to be fully explained. In an attempt to unveil unfavorable cellular properties linked to high ZAP70 expression, we used gene expression profiling to identify genes associated with disparities in B-cells from CLL patients expressing high versus low ZAP70 mRNA, measured by quantitative real-time PCR. Keywords: comparison of poor and good prognosis CLL patient transcriptome regarding ZAP70 expression |
| 787 | GSE10880 |
Profile | Expression profiling of MRC5 IFN gamma treated MRC5 and PGF cells. Keywords: cell type comparison, IFN gamma treatment. |
| 788 | GSE18269 |
Profile | The aim of this experiment is to determine the similarities and differences between gene expression profiles in HepaRG cells versus primary human hepatocytes human liver, and the commonly used HepG2 cell. |
| 789 | GSE15646 |
Profile | Kasumi-1 AML cells that were transfected in triplicate with AML1-ETO or luciferase siRNA constructs by either Amaxa nucleofection or Biorad siLentFect and incubated for 96 hours. Microarrays used to discover an AML1-ETO signature for a GE-HTS screen to identify AML1-ETO modulators. |
| 790 | GSE48944 |
Profile | Epidemiological studies indicate that adverse intrauterine and postnatal environment has a long-lasting role in chronic kidney disease (CKD) development. Epigenetic information can represent a plausible carrier for mediating this programming effect. Here we demonstrate that genome-wide cytosine methylation patterns of healthy and CKD tubule samples obtained from patients show significant differences. Cytosine methylation changes showed high concordance (98%) with a large (n=87) replication dataset. We rarely observed differentially methylated regions (DMR) on promoters. Histone modification-based kidney specific genome-wide gene regulatory region annotation maps (promoters enhancers, transcribed and repressed regions) were generated. DMRs mostly overlapped with putative enhancer regions and were enriched in consensus binding sequences for important renal transcription factors, indicating their importance in gene expression regulation. A core set of genes, including transforming growth factors and collagens, showed cytosine methylation changes correlating with downstream transcript levels. Our report raises the possibility that epigenetic dysregulation plays a role in CKD development via influencing core profibrotic pathways. We used microarrays to detail the differences of gene expression of human tubule epithelial cells between chronic kidney disease and normal. |
| 791 | GSE25191 |
Profile | Side populations have recently been identified in ovarian cancers and may play an important role in post treatment relapse and resistance to chemotherapeutic drugs. In this study we aimed to identify the differential expression between IGROV1 SP and NSP on Affymetrix HG-U133plus2 microarrays. We found ovarian tumour SP cells frequently over-express the multi-drug resistance associated P-glycoprotein (ABCB1) by Rank Product (FDR<0.05), and by geneset enrichment analysis, embryonic stem cell-associated ‘NOS’ signature (Notch/Oct4/Sox2 regulated genes) and Polycomb Repressive Complex 2 (PRC2) genes were over-expressed, while PRC2-repressed target genes were significantly under-expressed in the SP from ovarian cell lines compared to non-SP (FDR<10-4). |
| 792 | GSE37409 |
Profile | Transient transfection of a Ewing's Sarcoma cell line expressing type I EWS-FLI1 fusion and doxycycline-inducible short hairpin RNA against EWS-FLI1 (A673sh) |
| 793 | GSE14537 |
Profile | Relative contribution of sequence and structural features to the mRNA-binding of Argonaute/miRNA complexes and the degradation of miRNA targets How miRNAs recognize their target sites is a puzzle that many experimental and computational studies aimed to solve. Several features such as perfect pairing of the miRNA seed additional pairing in the 3’ region of the miRNA, relative position in the 3’ UTR and the A/U content of the environment of the putative site have been found to be relevant. Here we have used a large number of previously published data sets to assess the power that various sequence and structure features have in distinguishing between putative sites that do and those that do not appear to be functional. We found that although different data sets can give widely different answers when it comes to ranking the relative importance of these features, the sites inferred from most transcriptomics experiments as well as from comparative genomics appear similar at this level. This suggests that miRNA target sites have been selected in evolution on their ability to trigger mRNA degradation. To understand at what step in the miRNA induced response individual features play a role, we further transfected human HEK293 cells with miRNAs and analyzed the association of Argonaute/miRNA complexes with target mRNAs and the degradation of these messages. We found that structural features are only important for Argonaute binding, while sequence features such as the A/U content of the 3’ UTR are important for mRNA degradation. Keywords: IP-array analysis |
| 794 | GSE23687 |
Profile | Gene expression on peripheral blood mononuclear cells (PBMC) from SPARKS CHARMS juvenile idiopathic arthritis (JIA) cohort pre and post methotrexate therapy. This is the first study to our knowledge to evaluate gene expression profiles in children with JIA before and after MTX, and to analyze genetic variation in differentially expressed genes. We have identified a gene, which may contribute to genetic variability in MTX response in JIA. |
| 795 | GSE23764 |
Profile | Actomyosin contractility regulates cell morphology and movement. The objective of this study was to identify whether actomyosin contractility regulates gene expression in tumour cells and whether such genes are involved in cell morphology and movement. Gene expression analysis was carried out on highly contractile melanoma cell line A375M2 plated on a deformable collagen matrix under conditions where actomyosin contractility could be altered following treatment with blebbistatin a direct inhibitor of myosin II, or Rho-kinase inhibitors Y27632 or H1152 that interfere with signalling to myosin II. |
| 796 | GSE32670 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 797 | GSE12390 |
Profile | Direct reprogramming of human fibroblasts to a pluripotent state has been achieved through ectopic expression of the transcription factors OCT4 SOX2, and either cMYC and KLF4 or NANOG and LIN28. Little is known, however, about the mechanisms by which reprogramming occurs, which is in part limited by the low efficiency of conversion. To this end, we sought to create a doxycycline-inducible lentiviral system to convert primary human fibroblasts and keratinocytes into human induced pluripotent stem (hiPS) cells. hiPS cells generated with this system were molecularly and functionally similar to human embryonic stem (hES) cells, demonstrated by gene expression profiles, DNA methylation status, and differentiation potential. While expression of the viral transgenes was required for several weeks in fibroblasts, we found that 10 days was sufficient for the reprogramming of keratinocytes, suggesting that the kinetics of reprogramming are cell-type dependent. Using our inducible system, we developed a strategy to induce hiPS cell formation at high frequency by generating differentiated cells that contain the viral transgenes in a pattern that enables successful induction of pluripotency. Upon addition of doxycycline to differentiated hiPS-derived cells, we obtained “secondary” hiPS cells at a frequency at least 100-fold greater than the initial conversion. The ability to reprogram cells with high efficiency provides a unique platform to dissect the underlying molecular and biochemical processes that accompany nuclear reprogramming. |
| 798 | GSE19315 |
Profile | Shiga toxins (Stxs) are bacterial cytotoxins produced by the enteric pathogens Shigella dysenteriae serotype 1 and some serotypes of Escherichia coli that cause bacillary dysentery and hemorrhagic colitis respectively. To date, approaches to studying the capacity of Stxs to alter gene expression in intoxicated cells have been limited to individual genes. However, it is known that many of the signaling pathways activated by Stxs regulate the expression of multiple genes in mammalian cells. To expand the scope of analysis of gene expression and to better understand the underlying mechanisms for the various effects of Stxs on cell functions, we carried out comparative microarray analyses to characterize the global transcriptional response of human macrophage-like THP-1 cells to Shiga toxin type 1 (Stx1) and LPS. Data were analyzed using a rigorous combinatorial approach with three separate statistical algorithms. Thirty-six genes met the criteria of up-regulated expression in response to Stx1 treatment with 14 genes uniquely up-regulated by Stx1. Microarray data were validated by real time RT-PCR for genes encoding Egr-1 (transcriptional regulator), COX-2 (inflammation), and DUSP1, 5 and 10 (regulation of MAPK signaling). Stx1-mediated signaling through ERK1/2 and Egr-1 appears to be involved in the increased expression of the proinflammatory mediator TNF-α. Activation of COX-2 expression is associated with the increased production of proinflammatory and vasoactive eicosanoids. However, the capacity of Stx1 to increase the expression of genes encoding phosphatases suggests that mechanisms to dampen the macrophage proinflammatory response may be built into host response to the toxins. |
| 799 | GSE41889 |
Profile | Microvesicles (MV) are small membrane-bound particles comprised of exosomes and various sized extracellular vesicles. These are released by a number of cell types. Microvesicles have a variety of cellular functions from communication to mediating growth and differentiation. Microvesicles contain proteins and nucleic acids. Previously we showed that plasma microvesicles contain microRNAs (miRNAs). Based on our previous report, the majority of peripheral blood microvesicles are derived from platelets while mononuclear phagocytes, including macrophages, are the second most abundant population. Here, we characterized macrophage-derived microvesicles and whether they influenced the differentiation of naïve monocytes. We also identified the miRNA content of the macrophage-derived microvesicles. We found that RNA molecules contained in the macrophage-derived microvesicles were transported to target cells, including monocytes, endothelial cells, epithelial cells and fibroblasts. Furthermore, we found that miR-223 was transported to target cells and was functionally active. Based on our observations, we hypothesize that microvesicles bind to and activate target cells. Furthermore, we find that microvesicles induce the differentiation of macrophages. Thus, defining key components of this response may identify novel targets to regulate host defense and inflammation. We used GeneChip microarrays to examine changes in gene expression induced by MV in primary monocyte-derived macrophages (MDM) and in THP1 cells, and compare this to cells treated with GM-CSF and PMA, respectively. |
| 800 | GSE24378 |
Profile | Analysis of human dopamine (DA) from postmortem brains of 8 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. |
| 801 | GSE18668 |
Profile | Knockdown of the oncogene BRD4-NUT, in a rare cancer, termed NUTmidline carcinoma (NMC), results in morphologic features consistent with squamous differentiation. Treatment with the HDAC-inhibitor, TSA, appears to cause the same phenotype. Here, we use gene expression profiling to compare the changes in gene expression following BRD4-NUT knockdown and TSA treatment. |
| 802 | GSE10737 |
Profile | Cyclin T1-dependent genes in non-activated Jurkat cells. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Keywords: cyclin T1 knockdown |
| 803 | GSE29436 |
Profile | Every year more than 42000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs) as well as progesterone receptor (PR) positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT). Paraffin sections from patients with (n=9) or without (n=10) progressive endometrial cancer (recurrent or metastatic disease) were assessed for the presence of CD4+ (helper), CD8+ (cytotoxic) and Foxp3+ (regulatory) T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunosurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4 and WIF1, quantitive RT-PCR was performed to verify down regulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK) endometrial cancer cell lines stably transfected with PRA (IKPRA), PRB (IKPRB) and PRA+PRB (IKPRAB) were cultured in the presence/absence of progesterone (MPA) and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT makers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA-regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signalling. Intact progesterone signaling in non-progressive endometrial cancer seems to be an important factor stimulating immunosurveillance and inhibiting transition from an epithelial to a more mesenchymal, more invasive phenotype. |
| 804 | GSE43762 |
Profile | Glioma initiating cells (GICs) are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanism of GIC maintenance/differentiation we established GIC clones from GBM patient tumors having the potential to differentiate into malignant gliomas in mouse intracranial xenograft, and established an in vitro glioma induction system by using serum stimulation. Upon the serum stimulation, the GIC spheres showed increased cellular proliferation, motility, filopodia/lameripodia formation and adhesion to the culture dishes. Simultaneously, the NSC marker proteins such as CD133 and Sox2 were down-regulated, and the astrocyte/glioma marker GFAP and the malignancy marker CD44 dramatically up-regulated. To identify genes/proteins whose expression changes dynamically during the differentiation of GICs into glioma cells, these GICs were subjected to DNA microarray/iTRAQ based integrated proteomics. |
| 805 | GSE15205 |
Profile | Aberrant epithelial-mesenchymal transition (EMT) is involved in pathological processes including fibrotic disorders and cancer invasion and metastasis. Alterations of the cell-extracellular matrix (ECM) interaction also contribute to those pathological settings. However the functional interplay between EMT and cell-ECM interaction is poorly understood. Here, we show that tumor necrosis factor (TNF)-α, a potent mediator of inflammation, induces EMT-associated fibrosis in retinal pigment epithelial cells, and that this is regulated by hyaluronan (HA)-CD44-Moesin interaction. TNF-α elicits both HA synthesis and Moesin phosphorylation through protein kinase C activation, promoting binding of CD44 to the newly synthesized HA. The HA-CD44-Moesin interaction leads to cell-cell dissociation through actin remodeling and increased cellular motility associated with mesenchymal phenotype. Furthermore, we established an in vivo model of TNF-α-induced fibrosis in the mouse eye, and the ocular fibrosis was completely suppressed in CD44-null mice. Therefore, HA production and its interaction with CD44 plays essential role in TNF-α-induced-EMT, and the interference of the complex formation can be a new strategy for the fibrotic disorders. |
| 806 | GSE22337 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 807 | GSE15949 |
Profile | Ischemia exists in many diseased tissues including arthritic joints atherosclerotic plaques and malignant tumors. Macrophages accumulate in these sites and upregulate genes in response to the hypoxia present. We used microarrays to detail the hypoxia upregulated gene in human primary macrophages. |
| 808 | GSE23391 |
Profile | MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. We report the results of a systems analysis of miRNA regulation in ovarian cancer. We found that 33 miRNAs are up-regulated and 9 down-regulated in CEPI relative to OSE (p<0.01 ≥2 fold change). Of these, 12 were previously annotated miRNAs (Sanger miRBase) of which 9 are up-regulated and 3 are down-regulated in CEPI relative to OSE. Current models predict that changes in levels of miRNAs will be inversely correlated with changes in the levels of targeted mRNAs due to miRNA regulation. This predicted inverse correlation held for only ~9% of predicted target mRNAs. Computational analyses indicate the unexpected low inverse correlation may be at least partially explained by variation in the number of miRNA binding sites within the 3’ UTRs of targeted mRNAs and by miRNA-mediated changes in levels of transcription factors that can exert overriding trans-regulatory controls on target loci. |
| 809 | GSE39976 |
Profile | Approximately 5% of all breast cancers can be attributed to an inherited mutation in one of two cancer susceptibility genes BRCA1 and BRCA2. We searched for genes that have the potential to distinguish healthy BRCA1 and BRCA2 mutation carriers from non-carriers based on differences in expression profiling. Using expression microarrays we compared gene expression of irradiated lymphocytes from BRCA1 and BRCA2 mutation carriers versus control non-carriers. We identified 137 probe sets in BRCA1 carriers and 1345 in BRCA2 carriers with differential gene expression. Gene Ontology analysis revealed that most of these genes relate to regulation pathways of DNA repair processes, cell cycle regulation and apoptosis. Real-time PCR was performed on the 36 genes which were most prominently differentially expressed in the microarray assay; 21 genes were shown to be significantly differentially expressed in BRCA1 or BRCA2 mutation carriers as compared to controls (p<0.05). Based on a validation study with 40 mutation carriers and 17 non-carriers, a multiplex model that included six or more coincidental genes of 18 selected genes was constructed in order to predict the risk of carrying a mutation. The results using this model showed sensitivity 95% and specificity 88%. In summary, our study provides insight into the biological effect of heterozygous mutations in BRCA1 and BRCA2 genes in response to ionizing irradiation induced DNA damage. We also suggest a set of 18 genes that can be used as a prediction and screening tool for BRCA1 or BRCA2 mutational carriers by using easily obtained lymphocytes. Using expression microarrays we compared gene expression of irradiated lymphocytes from BRCA1 and BRCA2 mutation carriers versus control non-carriers |
| 810 | GSE33606 |
Profile | Organophosphorus compounds induce hepatotoxicity through currently unknown mechanisms which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. We used microarrays to study gene expression changes in human hepatocytes after exposure to VX, and identified pathways underlying these changes. |
| 811 | GSE11336 |
Profile | Glucocorticoids (GC) have a major impact on the biology of normal and malignant cells of the lymphoid lineage. This includes induction of apoptosis which is exploited in the therapy of acute lymphoblastic leukemia (ALL) and related lymphoid malignancies. MicroRNAs (miRNAs) and the related mirtrons are ~22 nucleotide RNA molecules implicated in the control of essential biological functions including proliferation differentiation and apoptosis. They derive from polymerase-II transcripts but whether GCs regulate miRNA-encoding transcription units is not known. We investigated miRNA/mirtron expression and GC regulation in 8 ALL in vitro models and 13 ALL children undergoing systemic GC monotherapy using a combination of expression profiling techniques, real time RT-PCR and northern blotting to detect mature miRNAs and/or their precursors. We identified a number of GC-regulated miRNAs/mirtrons, including the myeloid-specific miR-223 and the apoptosis and cell cycle arrest-inducing mir15~16 cluster. Thus, the observed complex changes in miRNA/mirtron expression during GC treatment might contribute to the anti-leukemic GC effects in a cell context dependent manner. Keywords: treatment response |
| 812 | GSE20089 |
Profile | Cell body and pseudopod RNA are differentially regulated during the migration of the metastatic cancer cells.We wanted to identify the RNA which are upregulated in the pseudopodial (PS) fraction as compared to cell body fraction (CB). We used microarray to see which are the RNAs upregulated in the PS fraction as compared to CB fraction |
| 813 | GSE35314 |
Profile | Although an important association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago an active role for the lymphatic system in metastatic dissemination has only recently been examined. We demonstrate that the Six1 homeoprotein promotes peri- and intra-tumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. We identify the pro-lymphangiogenic factor, VEGF-C, as required for this process, and demonstrate transcriptional induction as the mechanism of regulation of VEGF-C expression by Six1. Using a different, but complementary animal model, we show that while required, VEGF-C is not sufficient for the pro-metastatic effects of Six1. Verifying the clinical significance of this pro-metastatic Six1-VEGF-C axis, we demonstrate co-expression of Six1 and VEGF-C in human breast cancer. |
| 814 | GSE12800 |
Profile | To study the gene expression changes in mesenchymal stem cells from bone marrow stroma (MSCs) during in vitro expansion (from low density) passage 1 MSC were grown in culture for 15 days with medium change every 2-3 days. Samples for microarrays were taken at day 5 (early log-phase), 10 (late log-phase) and 15 (stationary phase). The data was queried for expression changes in Wnt signaling molecules and cell surface markers. Several components of the canonical Wnt signaling pathway were expressed, including Dkk-1; Wnt-5a; alpha-catenin; beta-catenin; frizzled 1, 4, 6, and 7; disheveled; glycogen synthetase kinase 3 beta; and glycogen synthetase kinase 3 alpha. In addition, the expression of over 10 cell surface transcripts decreased and an almost equal number increased during expansion. The two of the transcripts with the largest decreases coded for proteins previously shown to be linked to cell motility and tumor progression: PODXL, and alpha6-integrin (CD49f). As the cultures expanded, the largest increase was for mRNA for the cell adhesion protein VCAM-1. To study the gene expression changes in more detail, real-time RT-PCR, RT-PCR, ELISAs, FACS, and western blotting were performed for additional MSC donors. The results demonstrated dramatic changes in the transcriptome of MSCs during in vitro expansion. |
| 815 | GSE44652 |
Profile | Targeted molecular therapy has yielded remarkable outcomes in certain cancers but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the JAK tyrosine kinase family, TYK2, and its downstream effector STAT1 in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently demonstrated TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK kinase activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of IL-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the anti-apoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway. |
| 816 | GSE48157 |
Profile | Effect of chlorination on the toxicity of wastewater effluents treated by activated sludge (AS) and submerged membrane bioreactor (S-MBRB) systems to HepG2 human hepatoblastoma cells was investigated. In addition to cytotoxicity assay the DNA microarray-based transcriptome analysis was performed to evaluate the change in modes of toxic actions (MOAs) of effluents by chlorination. Effluent organic matters (EfOM) and disinfection by-products (DBPs) were characterized by using Fourier transform mass spectrometry (FT-MS). The cytotoxicity of AS effluent was elevated by chlorination, while the toxicity of S-MBRB effluent was reduced. The averaged O/C ratio of EfOM in S-MBRB effluent was lower than that in AS effluent. The results of the transcriptome and FT-MS analyses suggested that lower O/C molecules influenced on “response to hormone stimulus” and “acute inflammatory response” but those were decreased by chlorination, which consequently reduced cytotoxicity. On the other hand, larger number of DBPs and other molecules were increased in AS effluents by chlorination. Those molecules might influence on “cellular metabolic process”, which consequently elevated cytotoxicity. Therefore, the combination of the toxicity assays and chemical analysis demonstrated the changes in severity of cytotoxicity and MOAs by chlorination, and the difference of chemical characteristics which relate to those toxicity changes. |
| 817 | GSE2816 |
Profile | The transcriptional activities of c-Myb and its oncogenic variant v-Myb were compared by expressing them in primary human monocytes using recombinant adenovirus vectors. All the samples were compared to cells infected with a control adenovirus expressing only GFP. The results showed that v-Myb which differs from c-Myb only by N- and C-terminal deletions and eleven amino acid substitutions, has a qualitatively different transcriptional activity. Keywords: repeat |
| 818 | GSE2225 |
Profile | Anti-estrogens and aromatase inhibitors are important drugs in the treatment of estrogen-dependent breast cancer. In order to investigate the effects of these drugs on gene expression in breast cancer cells we treated estrogen receptor-positive MCF-7 cells, stably transfected with the aromatase gene (known as MCF-7aro cells), with testosterone, 17β-estradiol, two aromatase inhibitors (letrozole and anastrozole), and an anti-estrogen (tamoxifen). Microarray analyses using Affymetrix Human Genome U133A GeneChips were carried out using total RNA isolated from the control and treated cells. When comparing the effect of each inhibitor on gene expression we observe that letrozole and anastrozole are more similar in terms of the genes they affect, compared to treatment with tamoxifen. The results of this study provide us with a better understanding of the actions of both aromatase inhibitors and anti-estrogens at the molecular level. We believe that the results of this study serve as the first step in identifying unique expression patterns following drug treatment, and that this will ultimately be useful in customizing patient treatment strategies for estrogen-dependent breast cancer. The data presented here have been processed using the R-Project Bioconductor statistical tools package using the affy library. The following were applied: RMA background correction, pmonly probe-level correction, quantile normalization, avgdiff summary method. Raw data is provided in the form of .CEL files. Keywords = estrogen-dependent breast cancer Keywords = aromatase Keywords: other |
| 819 | GSE38121 |
Profile | Targeted therapies have provided advantages to cancer patients but these therapies are limited by differential responses and developed resistance. To discover mechanisms of resistance, we developed drug-resistant cell lines and have their gene expressions profiled and compared. |
| 820 | GSE10474 |
Profile | The Acute Respiratory Distress Syndrome (ARDS)/Acute Lung Injury (ALI) was described 30 years ago yet the interaction between specific sets of genes involved in this syndrome remains incompletely understood. Keywords: disease state analysis |
| 821 | GSE19500 |
Profile | Normal human bronchial epithelial cells were studied under four different conditions: control pressure 30 cmH2O, AG1478 (1 microM), and pressure plus AG1478 at 1, 3, and 8 hours, all in the absence of exogenous EGF. Keywords: Normal human bronchial epithelial cells. |
| 822 | GSE40839 |
Profile | Pulmonary fibrosis develops as a consequence of environmentally induced lung injury and/or an inherent disease susceptibility causing fibroblast activation proliferation and extracellular matrix deposition. The study was undertaken to characterise global gene expression in pulmonary fibroblasts to better understand the mechanisms underlying the fibrotic fibroblast phenotype. |
| 823 | GSE16910 |
Profile | Human embryonic stem (hES) cells have the capacities to propagate for extended periods and to differentiate into cell types from all three germ layers both in vitro and in vivo. These characteristics of self-renewal and pluripotency enable hES cells having the potential to provide an unlimited supply of different cell types for tissue replacement drug screening, and functional genomics studies. The hES-T3 cells with normal female karyotype cultured on either mouse embryonic fibroblasts (MEF) in hES medium (containing 4 ng/ml bFGF) (T3MF) or feeder-free Matrigel in MEF-conditioned medium (supplemented with additional 4 ng/ml bFGF) (T3CM) were found to express very similar profiles of mRNAs and microRNAs, indicating that the unlimited self-renewal and pluripotency of hES cells can be maintained by continuing culture on these two conditions. However, the expression profiles, especially microRNAs, of the hES-T3 cells cultured on Matrigel in hES medium supplemented with 4 ng/ml bFGF and 5 ng/ml activin A (T3BA) were found to be different from those of T3MF and T3CM cells. In T3BA cells, four hES cell-specific microRNAs miR-372, miR-302d, miR-367 and miR-200c, as well as three other microRNAs miR-199a, miR-19a and miR-217, were found to be up-regulated, whereas five miRNAs miR-19b, miR-221, miR-222, let-7b and let-7c were down-regulated by activin A. Thirteen abundantly differentially expressed mRNAs, including NR4A2, ERBB4, CXCR4, PCDH9, TMEFF2, CD24 and COX6A1 genes, targeted by seven over-expressed miRNAs were identified by inverse expression levels of these seven microRNAs to their target mRNAs in T3BA and T3CM cells. The NR4A2, ERBB4 and CXCR4 target genes were further found to be regulated by EGF and/or TNF. The 50 abundantly differentially expressed genes targeted by five under-expressed miRNAs were also identified. The abundantly expressed mRNAs in T3BA and T3CM cells were also analyzed for the network and signaling pathways, and roles of activin A in cell proliferation and differentiation were found. These findings will help elucidate the complex signaling network which maintains the self-renewal and pluripotency of hES cells. |
| 824 | GSE33168 |
Profile | Amniotic fluid (AF) is a complex biological material that provides a unique window into the developing human. Residual AF supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the AF core transcriptome by identifying the transcripts ubiquitously present in the AF supernatant of euploid midtrimester fetuses. We detected 476 well-annotated genes present in all twelve AF samples. Functional analysis identified 6 physiological systems represented in the AF core transcriptome including musculoskeletal and nervous system development and function and embryonic/ organismal development. mTOR signaling was identified as a key canonical pathway. Twenty-three highly organ-specific transcripts were identified; six of these are known to be highly expressed by fetal brain. This study demonstrates that AF cell-free fetal RNA can provide biological information about multiple fetal organ systems. |
| 825 | GSE12488 |
Profile | Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal TCRalphabeta+/CD4+/NKa+/CD8-/+dim T-large granular lymphocyte (LGL) lymphocytosis. Since healthy individuals show (oligo)clonal expansions of hCMV-specific TCRVbeta+/CD4+/cytotoxic/memory T-cells we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+ T-LGL. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile (GEP) analysis. |
| 826 | GSE26866 |
Profile | In this study we sought to establish the usefulness of LCM on cDNA microarray analysis. We reported that LCM samples improved the sensitivity of detection of differentially expressed genes over conventional bulk tissue analysis. We also provided the new information of chemokine and its receptor interaction within psoriatic lesional skin. |
| 827 | GSE28059 |
Profile | Dysregulation of ceramide synthesis has been associated with metabolic disorders such as atherosclerosis and diabetes mellitus. Using a human hepatoma cell line (Huh7) we investigated the changes in lipid homeostasis and gene expression when the synthesis of ceramide is perturbed by knocking down serine transferases subunits 1, 2 and 3 (SPTLC123) or dihydroceramide desaturase (DEGS1). While the inhibition of serine palmitoyl transferase (SPTLC) affects ceramide production differently at the subspecies level depending upon which SPTLC subunit is silenced; depleting DEGS1 is sufficient to produce a similar outcome as knocking down all SPTLC subunits. Both the distribution of multiple lipid classes, especially at the subspecies level, and the global transcriptional profile is altered differently when either SPTLC123 or DEGS1 were silenced. The overall transcriptional changes indicate a negative regulation in biosynthetic processes and a down-regulation of genes involved in general endomembrane trafficking for both DEGS1 and SPTLC123 siRNA treated cells, but also the up-regulation of genes involved with cell migration function in DEGS1 siRNA cells. Pathway analysis indicate changes in amino acid, sugar and nucleotide metabolisms as well as vesicle trafficking between organelles occurred more robustly in DEGS1 silenced cells. Although either SPTLC123 or DEGS1 siRNA treatment positively regulated numerous genes involved with endocytosis and endosomal recycling, depleting SPTLC123 caused transcriptional changes in genes primarily involved with lipid metabolism. The alterations reflect how SPTLC or DEGS1 silenced cells respond differently to disruption in lipid flux, but also maintain cellular lipid pools through increasing endocytotic processes and down-regulating metabolic biosynthesis without developing endoplasmic reticulum stress. Also, these results are the first to demonstrate that reducing ceramide synthesis by decreasing the function of either SPTLC or DEGS1 affects cellular function differently at the level of lipid synthesis and gene expression. |
| 828 | GSE17548 |
Profile | Hepatocellular carcinoma (HCC) is the fifth most-common cancer worldwide causing nearly 600000 deaths esch year. Approximately 80% of HCC develops on the background of cirrhosis.It is necessary to identify novel genes involved in HCC to implement new diagnostic and treatment options. However, the molecular pathogenesis of HCC largely remains unsolved. Only a few genetic alterations, namely those affecting p53, β-catenin and p16INK4a have been implicated at moderate frequencies of these cancers. Early detection of HCC with appropriate treatment can decrease tumor-related deaths We used microarrays to detail the global programme of gene expression profiles of cirrhosis and tumor liver samples. |
| 829 | GSE26865 |
Profile | The aim of this study was to benchmark digital gene expression (DGE) profiling by massively parallel sequencing against the most commonly used method for gene expression analysis. We compared the DGE levels to expression levels from Affymetrix arrays. Data from Affymetrix Human Genome U133 plus 2.0 GeneChips was available for 12 of the 21 RNA samples from ALL patient cells analyzed by DGE. |
| 830 | GSE46842 |
Profile | Our previous study implied a correlation of inhibitors of differentiation-1 (Id-1) to cervical cancer development. However how Id-1 contributes to cervical carcinogenesis is unknown. In the present study, we investigated the role of Id-1 in transforming cervical cells with an in vitro transformation model. The human papillomavirus (HPV) immortalized cervical epithelial cells (H8) were successfully transformed by exposure to the carcinogen N-nitrosopyrrolidine (NPYR). The results showed that both Id-1 RNA and protein expression were significantly increased in transformed H8 cells, suggesting a possible role of Id-1 in cervical cell transformation. Ectopic expression of Id-1 in H8 cells potentiated NPYR-induced cell transformation. In contrast, silencing of Id-1 suppressed NPYR-induced H8 cell transformation. A cDNA microarray assay was performed, which identified suggested potential cell signaling pathways for NPYR-induced H8 cell transformation. The results suggest that Id-1 plays an oncogenic role in the cervix, which sheds light on cervical cancer development and implies potential target for cervical cancer prevention and therapy. |
| 831 | GSE40422 |
Profile | We recently reported an oncogenomics-guided screening approach designed to identify genetic drivers of early stage melanoma metastasis and in this study we functionally validate the top-scoring candidate, homeobox transcription factor A1 (HOXA1), by demonstrating HOXA1‘s robust effects on melanoma cell invasion, metastasis and tumorigenicity. Transcriptome and pathway profiling analyses of cells expressing HOXA1 reveal up-regulation of factors involved in diverse cytokine pathways that include the TGFβ signaling axis, which we further demonstrate to be required for HOXA1-mediated cell invasion. Transcriptome profiling also informed HOXA1’s ability to potently down-regulate expression of microphthalmia-associated transcription factor (MITF) and other genes required for melanocyte differentiation, suggesting a mechanism by which HOXA1 expression de-differentiates cells into a pro-invasive precursor cell state concomitant with TGFβ activation. Our analysis of publicly available datasets indicate that the HOXA1-induced gene signature successfully categorizes melanoma specimens based on their metastatic potential and, importantly, is capable of stratifying melanoma patient risk for metastasis based on expression in primary tumors. |
| 832 | GSE42259 |
Profile | Expression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation. |
| 833 | GSE13712 |
Profile | Laminar shear stress due to constant blood flow is known to play a critical role in maintaining vascular health. In contrast endothelial cell senescence appears to be closely associated with the incidence of vascular disorder. In an attempt to identify functional biomarkers for age-related vascular health/disease, the present study investigated differential gene expression of young and senescent human umbilical vein endothelial cells (HUVECs) under static and laminar shear stress. We used a cDNA microarray method to compare gene expression profiles of young and senescent HUVECs under static and laminar shear stress conditions. Keywords: stress response, age state analysis |
| 834 | GSE40988 |
Profile | By using high-density DNA microarrays we analyzed the gene-expression profile of Hodgkin's lymphoma cell line L-428 after knock-down of the tumor antigen PRAME (preferentially expressed antigen in melanoma) Kewitz and Staege, submitted |
| 835 | GSE23614 |
Profile | UOK257 cell line was derived from a BHD patient. It harbors a germline mutation in FLCN (c.1285dupC) and LOH. UOK257-2 cells were generated from UOK257 cells by introducing wildtype FLCN using retrovirus. FLCN inactivation induces TFE3 transcriptional activity by increasing its nuclear localization. Thus expression microarray was used to identify the genes regulated by FLCN and TFE3. |
| 836 | GSE14805 |
Profile | Development of model systems that recapitulate the molecular heterogeneity observed amongst GBM tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from The Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7-gain/chromosome-10-loss, a poor prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBMs genomic amplification and overexpression of known GBM oncogenes such as EGFR, MDM2, CDK6 and MYCN, and novel genes including NUP107, SLC35E3, MMP1, MMP13 and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M-phase, DNA Replication, and Chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis-and-cell-cycle-module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M- progression and/or -checkpoint activation. In conclusion, our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment. Keywords: Disease state analysis |
| 837 | GSE18637 |
Profile | Human airway epithelial cells cultured in vitro at air-liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia and produces mucin, and are widely used as a model of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed global gene expression correlated well between ALI cells and brushed cells, but there were some differences. Gene expression patterns mirrored differences in proportions of cell types (ALI have higher percentages of basal cells, brushed cells have higher percentages of ciliated cells), with ALI cells expressing higher levels of basal cell-related genes and brushed cells expressing higher levels of cilia-related genes. Pathway analysis showed ALI cells had increased expression of cell cycle and proliferation genes, while brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells are a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences in the in vitro vs in vivo environments need to be considered. |
| 838 | GSE45516 |
Profile | Gene expression profile comparison from fibroblasts of Huntington individuals and normal ones We used microarrays to detail the global gene expression of fibroblasts from Huntington patients |
| 839 | GSE10943 |
Profile | To determine the IFN-alpha signature in non-side population of ovarian cancer Keywords: response to interferon-alpha |
| 840 | GSE49701 |
Profile | Technologies allowing for specific regulation of endogenous genes are valuable for the study of gene functions and have great potential in therapeutics. We created the CRISPR-on system a two-component transcriptional activator consisting of a nuclease-dead Cas9 (dCas9) protein fused with a transcriptional activation domain and single guide RNAs (sgRNAs) with complementary sequence to gene promoters. We demonstrate that CRISPR-on can efficiently activate exogenous reporter genes in both human and mouse cells in a tunable manner. In addition, we show that robust reporter gene activation in vivo can be achieved by injecting the system components into mouse zygotes. Furthermore we show that CRISPR-on can activate the endogenous IL1RN, SOX2, and OCT4 genes. The most efficient gene activation was achieved by clusters of 3 to 4 sgRNAs binding to the proximal promoters suggesting their synergistic action in gene induction. Significantly, when sgRNAs targeting multiple genes were simultaneously introduced into cells, robust multiplexed endogenous gene activation was achieved. Genome-wide expression profiling demonstrated high specificity of the system. |
| 841 | GSE16176 |
Profile | In order to characterize the differences between second trimester Down syndrome (DS) and euploid fetuses we compared gene expression in uncultured amniotic fluid supernatant samples. We identified individually differentially expressed genes via paired t-tests in the matched samples, and a set of differentially expressed genes on chromosome 21 using Gene Set Enrichment Analysis. Functional pathway analysis of the resulting genes highlighted the importance of oxidative stress, ion transport, and G-protein signaling in the DS fetuses. |
| 842 | GSE10299 |
Profile | Protein Kinase C alpha (PKC) is a critical mediator of cell signaling and cancer growth. We show that PKC inhibitors decrease proliferation in squamous cell carcinoma of the head and neck (SCCHN) cells and abrogate growth of SCCHN tumors in mouse xenografts. Analysis of gene expression arrays reveals that PKC regulates cell cycle genes required for DNA synthesis. In particular PKC increases cyclin E protein expression, cyclinE/cdk2 complex formation, and transcription of cyclin E and E2F target genes. Consistent with this mechanism, expression of cyclin E rescues the block in DNA synthesis caused by PKC inhibition. In SCCHN tissue, PKC and cyclin E expression increase progressively from normal and dysplastic to malignant human head and neck tissue. Furthermore, PKC expression correlates with poor prognosis in SCCHN. These results demonstrate that PKC regulates growth by stimulating DNA synthesis through cyclin E and E2F and identify PKC as a therapeutic target that is highly expressed in aggressive SCCHN. Keywords: time course; dose response |
| 843 | GSE9827 |
Profile | The JAK2V617F mutation has been reported in about 40-60% of Essential Thrombocythemia (ET) patients. However little is known about specific molecular abnormalities of the hematopoietic stem cell compartment of ET according to JAK2 mutation. Therefore, we compared the gene expression profiles of bone marrow (BM) CD34+ cells from 16 patients with and without the JAK2V617F mutation to identify differentially expressed genes. Keywords: cell type comparison |
| 844 | GSE46302 |
Profile | We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. R940406 (R406, the active metabolite of fostamatinib) was supplied by Rigel Pharmaceuticals, Inc., South San Francisco, CA, and AstraZeneca Pharmaceuticals, Wilmington, DE, USA. R406 was resuspended in dimethyl sulfoxide (DMSO) (Sigma-Aldrich) and stored at −80°C. . HL-60, U937 and KG-1 cell lines were purchased from the American Type Culture Collection. MOLM-14 cell lines were provided by Dr. Scott Amstrong (Dana-Farber Cancer Institute, Boston MA, USA.) All cell lines were maintained in RPMI 1640 (Cellgro) supplemented with 1% penicillin-streptomycin and 10% fetal bovine serum (FBS, Sigma-Aldrich) at 37 °C with 5% CO2. |
| 845 | GSE25148 |
Profile | This study set out to identify global changes in gene expression in human embryonic kidney (HEK) cells stably transfected with Toll-like receptor 2 (TLR2) over a 48 hour time-course following stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point. |
| 846 | GSE8346 |
Profile | The series represent gene expression profiles of T4-2 neoplastic breast epithelial cells that overexpressed N-CoR2 and were treated with the death ligand TRAIL in three-dimensional reconstituted basement membrane culture. Keywords: Genetic modification; response to death induction |
| 847 | GSE15653 |
Profile | Hepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2) we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays. |
| 848 | GSE20196 |
Profile | Poorly differentiated type synovial sarcoma (PDSS) is a variant of synovial sarcoma characterized by predominantly round or short-spindled cells. Although accumulating evidence from clinicopathological studies suggests a strong association between this variant of synovial sarcoma and poor prognosis little has been reported on the molecular basis of PDSS. To gain insight into the mechanism(s) that underlie the emergence of PDSS, we analyzed the gene expression profiles of 34 synovial sarcoma clinical samples, including 5 cases of PDSS, using an oligonucleotide microarray. In an unsupervised analysis, the 34 samples fell into 3 groups that correlated highly with histological subtype, namely, monophasic, biphasic, and poorly differentiated types. PDSS was characterized by down-regulation of genes associated with neuronal and skeletal development and cell adhesion, and up-regulation of genes on a specific chromosomal locus, 8q21.11. This locus-specific transcriptional activation in PDSS was confirmed by reverse transcriptase (RT)-PCR analysis of 9 additional synovial sarcoma samples. Our results indicate that PDSS tumors constitute a distinct genetic group based on expression profiles. |
| 849 | GSE6817 |
Profile | Melanoma tumor antigen p97 or melanotransferrin (MTf) is an iron (Fe)-binding protein with high homology to serum transferrin. MTf is expressed at very low levels in normal tissues and in high amounts in melanoma cells. The over-expression of MTf in tumor cells was hypothesized to assist rapidly proliferating neoplastic cells with their increased Fe requirements. However our recent characterization of the MTf knockout (MTf -/-) mouse demonstrated that MTf did not have an essential role in Fe metabolism. To understand the function of MTf, we utilized whole-genome microarray analysis to examine the gene expression profile of five models after modulating MTf expression. These models included two new stably transfected MTf hyper-expression models (SK-N-MC neuroepithelioma and LMTK- fibroblasts) and one cell type (SK-Mel-28 melanoma) where MTf was down-regulated by post-transcriptional gene silencing. These findings were compared to alterations in gene expression identified using the MTf -/- mouse. In addition, the changes identified from the gene array data were also assessed in a new model of MTf down-regulation in SK-Mel-2 melanoma cells. In the cell line models, MTf hyper-expression led to increased cellular proliferation, while MTf down-regulation resulted in decreased proliferation. Across all five models of MTf down- and up-regulation, we identified three genes modulated by MTf expression. These included ATP-binding cassette sub-family B member 5 (Abcb5), whose change in expression mirrored MTf down- or up-regulation. In addition, thiamine triphosphatase (Thtpa) and transcription factor 4 (Tcf4) were inversely expressed relative to MTf levels across all five models. The products of these three genes are involved in membrane transport, thiamine phosphorylation and cell proliferation/survival, respectively. This study identifies novel molecular targets directly or indirectly regulated by MTf and potential pathways involved in its function. These molecular targets could be involved, at least in part, to the role of MTf in modulating proliferation. Keywords: Melanotransferrin, siRNA, comparative genomic hybridization |
| 850 | GSE20125 |
Profile | Human Wharton’s jelly stem cells (hWJSCs) are derived ethically in large amounts from the umbilical cord matrix. Besides their differentiation capabilities WJSCs also display a notable lack of ability to form teratoma. hWJSCs have been shown to exert immunomodulatory effects and have recently been reported to kill or diminish cancer cell growth. These characteristics are important considerations for their use in cell therapy. In this transcriptome analysis, hWJSCs were profiled using Affymetrix DNA microarrays and compared to a panel of human stem cells and stromal cells. Although hWJSCs are multipotent, they expressed very low levels of the majority of stem cell markers, including POU5F1, NANOG, SOX2 and LIN28. BIRC5 has recently been shown to be required for teratoma formation in SCID mice. The lower levels of BIRC5 expression in hWJSCs compared to hESCs and the very low levels of stem cell markers might account for hWJSCs inability to form teratomas. IL12A which is known to be associated with the induction of apoptosis, was amongst the several cytokines identified to be significantly upregulated in hWJSCs. The ability of hWJSCs to compliment the host immune responses was further highlighted with the GO Biological Process analysis showing high association with immune system, chemotaxis and cell death. The ability to modulate immune responses confers hWJSCs an additional advantage in stem cell therapy and potentially allows hWJSCs as a form of treatment for cancer and immune disorders. In summary, the transcriptome profile of hWJSCs has provided indications on the genetic basis for their biological characteristics in immunomodulatory response, anti-cancer effects, and the lack of teratoma formation. |
| 851 | GSE39204 |
Profile | Ovarian cancer often progresses by disseminating to the peritoneal cavity but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. |
| 852 | GSE11309 |
Profile | Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. AIRE functions as a transcriptional regulator and it has a central role in the development of immunological tolerance. AIRE regulates the expression of ectopic antigens in epithelial cells of the thymic medulla and has been shown to participate in the development of peripheral tolerance. However the mechanism of action of AIRE has remained elusive. To further investigate the role of AIRE in host immune functions, using microarray technology, we studied the properties and transcript profiles in in vitro monocyte-differentiated dendritic cells (moDCs) obtained from APECED patients and healthy controls. Keywords: patient vs. healthy control comparative analysis |
| 853 | GSE12100 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 854 | GSE31229 |
Profile | 8 neuroblastoma (NB) cell lines (CLB-GA IMR-32, SH-SY5Y, N206, CHP-902R, LAN-2, SK-N-AS, SJNB-1) were profiled on the Affymetrix HGU-133plus2,0 platform before and after treatment with DAC (2'-deoxy-5-azacytidine) to investigate the influence on expression after inhibiting DNA-methylation |
| 855 | GSE20292 |
Profile | Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects |
| 856 | GSE44613 |
Profile | Human LIN28A and B are RNA-binding proteins (RBPs) conserved in animals with important roles during development and stem cell reprogramming. We used Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) in HEK293 cells and identified a largely overlapping set of ~3000 mRNAs at ~9,500 sites located in the 3’UTR and CDS. In vitro and in vivo, LIN28 preferentially bound single-stranded RNA containing a uridine-rich element and one or more flanking guanosines, and appeared to be able to disrupt base-pairing to access these elements when embedded in predicted secondary structure. In HEK293 cells, LIN28 protein binding mildly stabilized target mRNAs and increased protein abundance. The top targets were its own mRNAs and those of other RBPs and cell-cycle regulators. Alteration of LIN28 protein levels also negatively regulated the abundance of some, but not all let-7 miRNA family members, indicating sequence-specific binding of let-7 precursors to LIN28 proteins and competition with cytoplasmic miRNA biogenesis factors. To assess whether the transcripts identified by PAR-CLIP are regulated by LIN28B we analyzed the mRNA levels of LIN28B overexpressing and LIN28B-depleted cells using microarrays. Transcripts crosslinked to LIN28B were slightly downregulated upon LIN28B knockdown compared to LIN28B overexpression indicating that LIN28B stabilizes transcripts. The RBP LIN28B was depleted by siRNAs and the expression levels was compared to mock-transfected HEK293 cells |
| 857 | GSE27390 |
Profile | Gene expression profiling of BMMC from patients with rheumatoid arthritis (RA) vs. osteoarthritis (OA). |
| 858 | GSE9254 |
Profile | Normal human colorectal mucosa was sampled at points along the colon. Keywords: normal human tissue |
| 859 | GSE42853 |
Profile | Analysis of global gene expression profiles of flow cytometry-sorted different pathogen-specific CD4+ T cell populations from the same peripheral blood mononuclear cells (PBMC), to identify molecular parameters that regulate differential susceptibilities of these CD4+ T cells to HIV infection. The results reveal distinct gene expression profiles between CMV-specific and tetanus toxoid/Candida-specific CD4+ T cells that involved selective upregulation of comprehensive innate antiviral |
| 860 | GSE10178 |
Profile | We have performed whole genome expression arrays covering over 47000 transcripts comparing the transcriptional profile of NKp80+ to NKp80- CD8+ CCR7- alpha beta T cells. A highly similar global gene expression profile was observed between both memory phenotype T cell subsets. Interestingly the majority of differentially expressed genes are immune-associated. NKp80+ cells contained markedly increased levels of transcripts encoding for MHC class I and II molecules and for numerous members of the KIR family. Also other NK-related transcripts were more abundantly expressed in the NKp80+ subset. With regards to cytokines, chemokines and their receptors, transcripts important for homeostasis and proliferation are expressed differently. Also transcripts encoding for adhesion molecules are present at different levels in both T cell subsets. Further cytotoxic effector molecules are expressed differently. Keywords: cell type comparsion |
| 861 | GSE17393 |
Profile | Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a MS signature comparing female healthy specimens with respect to MS patients |
| 862 | GSE18232 |
Profile | The perturbation of the genetic program due to mutational activation of KRAS- or BRAF-mediated signal transduction is a prerequisite for the expression of neoplastic phenotypes; however the mechanisms of cancer cell-specific transcriptional deregulation are poorly understood. We have analyzed the human colorectal cancer cell lines HCT116, HT29 and SW480 using an integrated approach combining transcriptional profiling, small molecule inhibitors targeting signaling pathway effectors, and computational prediction of regulatory elements in promoters of co-expressed genes with chromatin-based and cellular assays. We identified groups of coexpressed genes involved in similar biological processes, demonstrating a link between biological function and transcriptional organization. Among them we found groups of proliferation associated genes which responded to MEK/MAPK inhibition in all three cell lines. We predicted by computational analysis of the promoter regions of these genes, that NFY binding sites might be important regulatory elements for the MEK/MAPK-dependent transcriptional control. We validated this prediction in reporter gene assays by using a fragment of the CCNB1 promoter as a model. We discovered YBX1 to be associated with the endogenous CCNB1 promoter and the promoters of 62 additional genes within the proliferation associated gene groups by a ChIP-on-chip assay. Silencing of YBX1 expression by siRNA prevents CCNB1 expression and partially inhibits proliferation of HCT116 cells. In view of multiple known YBX1 functions in stress response, chromatin remodeling, transcriptional and translational regulation, our results indicate that this factor may also contribute to RAS-induced pleiotropic effects in cancer. |
| 863 | GSE42073 |
Profile | As PSCs differentiate they display characteristics of EMT as well as PTK7 expression. We sought to discover novel markers and regulators of this process by comparing purified PTK7+ and PTK7- populations We used microarrays to detail the global program of gene expression underlying this EMT process and identified distinct classes of up-regulated genes during this process. |
| 864 | GSE30950 |
Profile | Purified NK cells were co-cultured with M. bovis BCG or M. tuberculosis H37Rv (1:1) in the presence of IL-2 (100U/ml) or IL-12 (10pg/ml) for 24h before trizol extraction. We used microarrays to detail the global gene expression underlying NK cell activation by mycobacteria. |
| 865 | GSE26451 |
Profile | Assessing relevant differences between human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells is important given that such differences may impact their potential therapeutic use. We used microarray to profile the changes in global gene expression arising from the reprogramming of somatic cells to induced pluripotent stem cells. |
| 866 | GSE15823 |
Profile | Asthma pathogenesis and susceptibility involves a complex interplay between genetic and environmental factors. We report the results of expression microarray studies using tissue obtained from bronchial biopsies of healthy controls and of subjects with allergic asthma both before and following inhaled corticotherapy. |
| 867 | GSE40496 |
Profile | A need exists for biomarkers in T1D that can 1) sensitively and specifically detect disease-related immune activity prior to and independent of, measurement of auto-antibodies towards islet cell antigens; 2) define immunopathological mechanisms; and 3) monitor changes in the inflammatory state associated with disease progression or response to therapeutic intervention. In an effort to fill this gap, we have applied a novel bioassay to both human and BB rat T1D whereby the complex milieu of inflammatory mediators present in plasma can be indirectly detected through their ability to drive transcription in peripheral blood mononuclear cells drawn from healthy, unrelated donors. The resultant gene expressions are comprehensively measured with a microarray. In our human studies, we find that plasma of recent-onset T1D patients induces expression of a pro-inflammatory signature consisting in part of many interleukin-1 (IL-1) regulated genes related to immunological activation and immunocyte chemotaxis compared to unrelated healthy controls. This signature has been found to resolve in long-standing T1D subjects (>10 years post-onset), thus associating it with active autoimmunity. Importantly, this signature has been detected in pre-onset samples of progressors to T1D years prior to onset and prior to development of auto-antibodies directed towards islet antigens. |
| 868 | GSE13330 |
Profile | Alterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute to neoplastic progression. The importance of the microenvironment in neoplastic progression is underscored by studies demonstrating that fibroblasts isolated from a tumor stimulate the growth of preneoplastic and neoplastic cells in xenograft models. Similarly senescent fibroblasts promote preneoplastic cell growth in vitro and in vivo. Because senescent cells accumulate with age, their presence is hypothesized to facilitate preneoplastic cell growth and tumor formation in older individuals. To identify senescent stromal factors directly responsible for stimulating preneoplastic cell growth, we carried out whole genome transcriptional profiling and compared senescent fibroblasts to their younger counterparts. We identified osteopontin (OPN) as one of the most highly elevated transcripts in senescent fibroblasts. Importantly, reduction of OPN protein levels by RNAi did not impact senescence induction in fibroblasts; however, it dramatically reduced the growth-promoting activities of senescent fibroblasts in vitro and in vivo, demonstrating that OPN is necessary for paracrine stimulation of preneoplastic cell growth. In addition, we found that recombinant OPN was sufficient to stimulate preneoplastic cell growth. Finally, we demonstrate that OPN is expressed in senescent stroma within preneoplastic lesions that arise following DMBA/TPA treatment of mice, suggesting that stromal-derived OPN-mediated signaling events impact neoplastic progression. |
| 869 | GSE31747 |
Profile | Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP1,2) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP1,2 (VLPVP40-GP) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLPVP40 (particles lacking GP1,2) caused an aberrant response. Notably, some cellular interferon-inducible genes were upregulated six hours after exposure to virions and LPS, but not after exposure to VLPVP40-GP. This suggests that GP1,2 binding to macrophages plays an important role in the immediate cellular response. |
| 870 | GSE8590 |
Profile | The transcriptome analysis was performed in triplicate using two human embryonic stem cells lines (hES_VUB01 and hES_SA01) by comparing the expression profiles of the undifferentiated hES cells and two types of progenitors derived from the hES cell lines: Neural progenitors (NPC) and Mesodermal progenitors (MSC). Keywords: Cell type comparison |
| 871 | GSE24206 |
Profile | Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets. |
| 872 | GSE4250 |
Profile | All experiment was done according to the Affymetrix manufacturer’s protocol. The resulting HGF gingiva expression profile(Hereditary gingival fibromatosis patient Gingiva replicate1 and replicate 2)was compared to normal gingiva control(Normal Gingiva replicate1 and replicate2). The data were collected and analyzed by GCOS 1.2 and GeneSpring 7.2 1-way T test. Keywords: tissue specific expression profile |
| 873 | GSE6962 |
Profile | We have demonstrated that water-soluble zinc ionophores can be administered to mice at relatively high doses and inhibit the growth of A549 lung cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice four hours after treatment confirmed that the activation of stress responsive genes occurs in vivo. These findings lead us to propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Keywords: Dose response |
| 874 | GSE20510 |
Profile | Invasive extravillous trophoblasts (EVTs) of the human placenta are critically involved in successful pregnancy outcome since they remodel the uterine spiral arteries to increase blood flow and oxygen delivery to the placenta and the developing fetus. To gain more insights into their biological role different primary cell culture models are commonly utilised. However access to early placental tissue may be limited and primary trophoblasts rapidly cease proliferation in vitro impairing genetic manipulation. Hence, trophoblastic cell lines have been widely used as surrogates to study EVT function. Although the cell lines share some molecular marker expression with their primary counterpart, it is unknown to what extent they recapture the invasive phenotype of EVT. Therefore, we here report the first thorough GeneChip analyses of SGHPL-5, HTR-8/SVneo, BeWo, JEG-3 and the novel ACH-3P trophoblast cells in comparison to previously analysed primary villous cytrophoblasts and extravillous trophoblasts. |
| 875 | GSE10591 |
Profile | TMPRSS6 is a type II transmembrane serine protease and is revealed by our work to be part of a low-iron sensing pathway. When animal gets iron deficient TMPRSS6 is required to shut off hepcidin gene, so as to allow iron to be uptaken from GI tract. The mutant mouse, which was generated by ENU mutagenesis, has developed microcytic anemia. The phenotype is caused by a splicing error in Tmprss6 gene. However, the mechanism of TMPRSS6 effect remains elusive. To gain further insight into the molecular components of the TMPRSS6 signaling pathway, we overexpressed either TMPRSS6 or its mutant version of protein in human liver carcinoma cell line HepG2 cells, and compared the transcription status betweem these two treatments. Keywords: genetic modification |
| 876 | GSE35864 |
Profile | Finding the differences in gene expression in three regions of the brain basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV infected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients. |
| 877 | GSE8045 |
Profile | Aldehyde dehydrogenase isozymes ALDH1A1 and ALDH3A1 are highly expressed in non small cell cell lung cancer. Neither the mechanism nor the biological significance for such over expression have been studied. We used microarrays to analyze changes in A549 lung cancer cell line in which ALDH activity was reduced using lentiviral mediated expression of siRNA against both isozymes (Lenti 1+3) Keywords: Gene Profiling after ALDH Knock Down |
| 878 | GSE41078 |
Profile | We sought to define the cutaneous response at 24 hours following erythemogenic doses of narrow-band UVB (NB-UVB 312 nm peak) exposure and determine the differences between irradiated and non-irradiated skin. |
| 879 | GSE6869 |
Profile | Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of different diseases is not fully understood. The knowledge of global gene expression will help us to develop early diagnostic biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB77 on human liver cells leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. Keywords: time course |
| 880 | GSE15903 |
Profile | High metastatic nasopharyngeal carcinoma cell line 5-8F expression patterns against low metastatic nasopharyngeal carcinoma cell line 6-10B. |
| 881 | GSE17054 |
Profile | We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells. |
| 882 | GSE18161 |
Profile | Post-hybridization washing is an essential part of microarray experiments. Both the quality of the experimental washing protocol and the adequate consideration of washing in intensity calibration ultimately affect the quality of the expression estimates extracted from the microarray intensities. We conducted experiments on GeneChip microarrays with altered protocols for washing, scanning and staining to study the probe-level intensity changes as a function of washing cycles. Particularly, three Affymetrix GeneChip HGU133plus2 arrays were hybridized and equilibrated for 16 hours in the hybridization oven. For one of the three arrays washing and staining was performed according to the manufacturer’s instructions. For another array the first scan was done immediately after low stringent wash and staining without intermitting stringent washing. Then, the array was stringently washed and scanned in alternating order three more times where each washing step consists of a definite number of washing cycles. The third array was low stringently washed followed by two stringent washing cycles and staining before the first scan. Subsequently it was analogously processed as array A. All three chips are repeatedly processed in a second series of alternating wash/scan-cycles which was performed using the same protocol for each chip as in the first series as described above. As in the first series the arrays were also stained a second time to compensate for any loss of bleached fluorescent dye. Analysis of the washing kinetics shows that the signal-to-noise ratio doubles roughly every ten stringent washing cycles. Washing can be characterized by time-dependent rate constants which reflect the heterogeneous character of target binding to microarray probes. We propose an empirical washing function which estimates the survival of probe bound targets. The washing function allows calibrating probe intensities for the effect of washing. On a relative scale, proper calibration for washing markedly increases expression measures especially in the limit of small and large values. |
| 883 | GSE39744 |
Profile | We used microarrays to detail the global programme of gene expression to identify TNF-induced genes that are negatively regulated by EHMT1 Transcriptional homeostasis relies on the balance between positive and negative regulation of gene transcription. Methylation of histone H3 lysine 9 (H3K9) is commonly correlated with gene repression. Here we report that a euchromatic H3K9 methyltransferase, EHTM1, functions as a negative regulator in both the NF-κB- and type I interferon-mediated gene induction pathways. EHMT1 catalyzes H3K9 methylation at promoters of NF-κB target genes. Moreover, EHMT1 interacts with p50 and, surprisingly, p50 appears to repress the expression of type I interferon genes and genes activated by type I interferons by recruiting EHMT1 to catalyze H3K9 methylation at their promoter regions. Silencing the expression of EHMT1 by RNA interference enhances expression of a subset NF-κB regulated genes, augments interferon production and augments antiviral immunity. |
| 884 | GSE35640 |
Profile | Purpose: To evaluate the presence of a gene expression signature present before treatment as predictive of response to treatment with MAGE‑A3 immunotherapeutic in metastatic melanoma patients and to validate its predictivity in adjuvant therapy of early-stage lung cancer. |
| 885 | GSE7850 |
Profile | Consistent with clinical observations that posterior uveitis frequently involves the retinal vasculature and recent recognition of vascular heterogeneity we hypothesized that retinal vascular endothelium was a cell population of unique molecular phenotype. Donor-matched cultures of primary retinal and choroidal endothelial cells from 6 human cadavers were incubated with either Toxoplasma gondii tachyzoites (10:1, parasite:cell) or Escherichia coli lipopolysaccharide (100 ng/mL); control cultures were simultaneously incubated with medium. Gene expression profiling of endothelial cells was performed using oligonucleotide arrays containing probes designed to detect 8747 human transcripts. After normalization, differential gene expression was assessed by the significance analysis of microarrays, with the false discovery rate set at 5 %. For selected genes, differences in level of expression between retinal and choroidal cells were evaluated by real-time RT-PCR. Graphical descriptive analysis demonstrated strong correlation between gene expression of unstimulated retinal and choroidal endothelial cells, but also highlighted distinctly different patterns of expression that were greater than differences noted between donors or between unstimulated and stimulated cells. Overall, 779 of 8,747 transcripts (8.9 %) were differentially represented. Notably, the 330 transcripts that were present at higher levels in retinal cells included a larger percentage of transcripts encoding molecules involved in the immune response. Differential gene expression was confirmed for 12 transcripts by RT-PCR. Retinal and choroidal vascular endothelial cells display distinctive gene expression profiles. Our findings suggest the possibility of treating posterior uveitis by targeting specific interactions between the retinal endothelial cell and an infiltrating leukocyte. Keywords: Cell type comparison, stress response |
| 886 | GSE3524 |
Profile | There are limited studies attempting to correlate the expression changes in oral squamous cell carcinoma with clinically relevant variables. We determined the gene expression profile of 16 tumor and 4 normal tissues from 16 patients by means of Affymetrix Hu133A GeneChips. The hybridized RNA was isolated from cells obtained with laser capture microdissection then was amplified and labeled using T7 polymerase-based in vitro transcription. The expression of 53 genes was found to differ significantly (33 upregulated, 20 downregulated) in normal versus tumor tissues under two independent statistical methods. The expression changes in four selected genes (LGALS1, MMP1, LAGY, and KRT4) were confirmed with reverse transcriptase polymerase chain reaction. Two-dimensional hierarchical clustering of the 53 genes resulted in the samples clustering according to the extent of tumor infiltration: normal epithelial tissue, tumors less than or equal to 4 cm in dimension, and tumors more than 4 cm in dimension (P=0.0014). The same pattern of clustering was also observed for the 20 downregulated genes. We did not observe any associations with lymph node metastasis (P=0.097). Keywords: TNM,Tumor-node-metastasis LCM,Laser capture microdissection OSCC,Oral squamous cell Carcinoma |
| 887 | GSE21164 |
Profile | Ischaemic preconditioning is a method of protecting tissue against ischaemia-reperfusion injury. It is an innate protective mechanism that increases a tissue's tolerance to prolonged ischaemia when it is first subjected to short burst of ischaemia and reperfusion. It is thought to provide this protection by increasing the tissue's tolerance to ischaemia therby reducing oxidative stress, inflammation and apoptosis in the preconditioned tissue. We used microarrays to investigate the genomic response induced by ischaemic preconditioning in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the ischaemic preconditioning mechanism. |
| 888 | GSE12666 |
Profile | We describe six novel lead compounds activating the p53 tumor suppressor pathway. Transcriptional profiling indicated that they invoked highly similar responses involving p53 and cell cycle pathways and DNA damage response signaling. Keywords: Stress response |
| 889 | GSE38718 |
Profile | The aim of this investigation was to develop a global view of muscle transcriptional differences between older men and women and with aging for each sex. |
| 890 | GSE17385 |
Profile | MM1.S cells stably transduced with control or b-catenin shRNA were established. Total RNA was isolated from 5x 10^6 cells of each in triplicate. |
| 891 | GSE29883 |
Profile | Core binding factor (CBF) leukemias characterized by translocations t(8;21) or inv(16)/t(16;16) targeting the core binding factor, constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, about 40% of patients relapse, and the current classification system does not fully reflect this clinical heterogeneity. Previously, gene expression profiling (GEP) revealed two distinct CBF leukemia subgroups displaying significant outcome differences and identified apoptotic signaling, MAPKinase signaling and chemotherapy-resistance mechanisms among the most significant differentially regulated pathways. We now tested different inhibitors of the respective pathways in a cell line model (six cell lines reflecting the CBF subgroup specific gene expression alterations), and found apoptotic signaling to be differentiating between the CBF subgroup models. In accordance, primary samples from newly diagnosed CBF AML patients (n=23) also showed differential sensitivity to in vitro treatment with a Smac mimetic such as BV6, an antagonist of inhibitor of apoptosis (IAP) proteins , and ABT-737, a BCL2 inhibitor. Furthermore, GEP revealed the BV6 resistant cases to resemble the previously identified unfavorable CBF subgroup. Thus, our current findings show deregulated IAP expression and apoptotic signaling to differentiate clinically relevant CBF subgroups, which were independent of known molecular markers, thereby providing a starting point for novel therapeutic approaches. |
| 892 | GSE18560 |
Profile | Microarray-based gene expression data were generated from RNA from Ls174T colorectal carcinoma cell lines in which Wnt-dependent transcriptional activity can be abrogated by inducible overexpression of a dominant-negative form of Tcf4 or siRNA against β-catenin. |
| 893 | GSE13909 |
Profile | Molecular mechanisms of cell cycle exit are poorly understood. A group of genes required for cell cycle exit and maintenance of cell quiescence in human fibroblasts following serum deprivation has been recently identified. Studies on lymphocytes following growth factor deprivation-induced cell cycle exit have predominantly focused on the initiation of apoptosis. A set of genes involved in lymphocyte quiescence have also been identified among genes highly expressed in resting lymphocytes and down-regulated after cell activation. In our study proliferating IL-2-dependent human T cells were forced to exit cell cycle by growth factor withdrawal, and their gene expression profiles were examined. The differential gene expression analysis was performed in primary and immortalized IL-2-dependent T lymphocytes. Cell samples were collected directly from the IL-2-containing cultures and 8-hrs following IL-2 withdrawal, before apoptosis could be evidenced by the Annexin-V staining. The three primary T lymphoblast cell populations were obtained from the peripheral blood mononuclear cells (PBMC) stimulated for 24h by wheat germ agglutinin and cultured in the presence of IL-2 up to 4-8 population doublings. As shown by the cell surface analysis, these populations were composed of T cells exclusively. Samples of these cell populations were subsequently analyzed as biological replicates. Two spontaneously immortalized IL-2-dependent T cell lines were derived from normal spleen and from PBMC derived from Nijmegen Breakage Syndrome patient. Gene expression was assessed by the Affymetrix microarray HG-U133 2.0 Plus that detects 38,500 genes. The expression of a selected number of genes was verified by the qRT-PCR method. We have identified a set of 53 genes that we called a “T lymphocyte cell cycle exit signature”, comprised of 13 up-regulated and 40 down-regulated genes. Genes linked to transcription, cell cycle, cell growth, proliferation and differentiation, cell adhesion and immune functions were found to be overrepresented among the differentially expressed, before and after IL-2 deprivation. Among those, PIM1, BCL2, IL-8, HBEGF, DUSP6, OSM, CISH, SOCS2, SOCS3, LIF and IL13 were down-regulated and RPS24, SQSTM1, TMEM1, LRRC8D, ECOP, YY1AP1, C1orf63, ASAH1, SLC25A46 and MIA3 were up-regulated. Identification of genes involved in cell cycle exit and quiescence, may provide new insights into the mechanisms of tissue repair and regeneration as well as of cancer development. |
| 894 | GSE6927 |
Profile | Transcriptional profiling was utilized to define the biological pathways of gingival epithelial cells modulated by co-culture with the oral commensal S. gordonii and the opportunistic commensal F. nucleatum. We used microarrays to detail the global programme of gene expression underlying infection and identified distinct classes of up- and down-regulated genes during this process. Keywords: infection state |
| 895 | GSE35896 |
Profile | We stratified colorectal tumor samples using a new unsupervised iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes. |
| 896 | GSE29077 |
Profile | Azacitidine (AZA) and decitabine (DAC) are cytidine azanucleoside analogs with clinical activity in myelodysplastic syndromes (MDS) and potential activity in solid tumors. To better understand the mechanism of action of these drugs we examined the effects of AZA and DAC in a panel of non-small cell lung cancer (NSCLC) cell lines. Of 5 NSCLC lines tested in a cell viability assay, all were sensitive to AZA (EC50 of 1.8–10.5 µM), while only H1299 cells were equally sensitive to DAC (EC50 of 5.1 µM). In the relatively DAC-insensitive cell line A549, both AZA and DAC caused DNA methyltransferase I depletion and DNA hypomethylation; however, only AZA significantly induced markers of DNA damage and apoptosis, suggesting that mechanisms in addition to, or other than, DNA hypomethylation are important for AZA-induced cell death. Cell cycle analysis indicated that AZA induced an accumulation of cells in sub-G1 phase, whereas DAC mainly caused an increase of cells in G2/M. Gene expression analysis of AZA- and DAC-treated cells revealed strikingly different profiles, with many genes distinctly regulated by each drug. In summary, while both AZA and DAC caused DNA hypomethylation, distinct effects were demonstrated on regulation of gene expression, cell cycle, DNA damage, and apoptosis. |
| 897 | GSE1844 |
Profile | A cDNA microarray analysis of asymptomatic patients presenting moderately elevated serum Creatine Kinase levels Keywords = Creatine Kinase Keywords = Skeletal muscle Keywords: ordered |
| 898 | GSE44809 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 899 | GSE7451 |
Profile | 10 saliva samples from patients with primary Sojgren's syndrome and 10 saliva samples from control subjects Keywords: Biomarker development |
| 900 | GSE27424 |
Profile | To determine the role of NOTCH3 in human esophageal epitheila homeostasis/squamous cell differentiation Zinc finger E-box binding (ZEB) proteins ZEB1 and ZEB2 are transcription factors essential in transforming growth factor (TGF)-β-mediated epithelial to mesenchymal transition (EMT) senescence and cancer stem cell maintenance through mutual negative regulation of the microRNA (miR)-200 family members. However, little is known as to how ZEB expressing tumor cells may emerge during invasive growth. We find that canonical Notch signaling prevents expansion of a unique subset of cells expressing ZEBs through NOTCH3 (N3). In primary esophageal squamous cell carcinoma (ESCC), ZEB1 is induced in tumor cells displaying EMT-like dedifferentiation at the invasive front of tumor nests with reciprocal downregulation of the miR-200. ZEB expression was associated with the lack of cellular capability of undergoing squamous differentiation through dysfunction of N3, implicated at the onset of normal esophageal squamous differentiation. Dominant-negative Mastermind-like1 (DNMAML1), a genetic pan-notch inhibitor, prevented CSL-dependent transcription, resulting in suppression of N3 expression and squamous differentiation while enriching EMT competent cells with robust upregulation of ZEBs and downregulation of the miR-200. Such a cell population demonstrated enhanced anchorage independent growth as well as tumor formation in nude mice. RNA interference (RNAi) experiments documented the requirement of ZEBs in TGF-β-mediated EMT. Invasive growth and impaired squamous differentiation was recapitulated upon Notch inhibition in organotypic 3D culture, a form of human tissue engineering. Finally, RNAi experiments revealed N3 as a key factor limiting the expansion of the ZEB expressing cells, providing novel mechanistic insights into the role of Notch signaling in ESCC cell fate regulation and disease progression. |
| 901 | GSE8908 |
Profile | The goal of this study was to compare the gene expression profiles of chronically inflamed human peri-implant and chronically inflamed human periodontal tissues in order to elucidate potential changes at the molecular level. Cells out of the pocket depth of the inflamed peri-implant and periodontal ligament as well as from the middle third of healthy periodontal ligament were applied. Genome-wide gene expression was compared with the help of microarray analysis and the data were validated by real-time RT-PCR. The expression rates of 14,239 genes were investigated and 2,079 of them were found differentially expressed by at least two-fold; the expression rates of 1,093 genes were significantly up-regulated and the expression rates of 986 genes were significantly down-regulated in inflamed peri-implant cells compared to inflamed periodontal cells. We focused on genes coding for extracellular matrix components and those that degrade them. Only genes of non-fibril-forming collagens (types IV, VI, VII, and XVII) were increased in inflamed peri-implant tissue, whereas only the genes of two fibril-forming collagens (types III and XVII) were decreased, suggesting that peri-implant tissue re-models faster than periodontal tissue. Furthermore, cathepsin D and cathepsin S might participate to a greater extent in connective tissue destruction of peri-implant tissue. The present investigation demonstrated that, despite their clinical similarities, periimplantitis and periodontitis are two different diseases at the genetic level. Keywords: inflammation, peri-implant, periodontal ligament cells |
| 902 | GSE2171 |
Profile | We used Affymetix HG Focus GeneChip to measure the expression levels of HIV seronegative and seropositive individuals in human PBMCs in vivo. GSM39104 -GSM39115 are HIV seronegative samples; GSM39116-GSM39137 are HIV seropositive but drug naive samples; GSM39138-GSM39147 are HIV seropositive samples used to test serostatus biomarker; GSM39148-GSM39170 are HIV seropositive individuals whose CD4 cells decrease over time; GSM39171-GSM39187 are HIV seropositive individuals whose CD4 cells increase over time; GSM39188-GSM39190 are HIV seropositive samples used to test CD4 cell increase/decrease over time. Keywords: other |
| 903 | GSE21306 |
Profile | RECK a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of some matrix metalloproteinases (MMP), thereby suppressing tumor cell metastasis; however, the detailed mechanism is still obscure. In this study, we compared the gene expression profiles between mock- and RECK-transfected HT1080 cells. |
| 904 | GSE24199 |
Profile | Tumours contain heterogeneous cell populations. A population enriched in tumour-initiating potential has been identified in soft-tissue sarcoma (STS) by the isolation of side population (SP) cells. In this study we compared the gene expression profiles of SP and non-SP cells in STS and identified Hedgehog (Hh) and Notch pathways as potential candidates for the targeting of SP cells. Upon verification of the activation of these pathways in SP cells, using primary tumor xenografts in NOD-SCID mice as our experimental model, we used the Hh blocker Triparanol and the Notch blocker DAPT to demonstrate that the suppression of these pathways effectively depleted the abundance of SP cells, reduced tumour growth, and inhibited the tumour-initiating potential of the treated sarcoma cells upon secondary transplantation. The data provide additional evidence that SP cells act as tumour initiating cells and points to Hh and Notch pathways as enticing targets for developing potential cancer therapies. We used microarrays to detail the difference in gene expressions between the side population cells in soft-tissue sarcoma in comparison to the bulk non-side-population cells. |
| 905 | GSE32100 |
Profile | Transcriptomic analyses of the oxygen response of two glioma cell lines at 20% versus 0.3% O2 and 3% vs 0.3% O2 in the presence or absence of serum |
| 906 | GSE36668 |
Profile | Objectives and goals: The causes and molecular pathology of ovarian cancer are essentially unknown. However it is generally understood that serous ovarian borderline tumors (SBOT) and well differentiated (WD) serous ovarian carcinomas (SC) have a similar tumorigenetic pathway, distinct from moderately (MD) and poorly differentiated (PD) SC. The aim of this study was to identify mRNAs differentially expressed between MD/PD SC, SBOT and superficial scrapings from normal ovaries (SNO),and to correlate these mRNAs with clinical parameters. Results: From the global gene expression analyses, thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected and validated by RT-qPCR, verifying 21 mRNAs to be significantly differentially expressed (p<0.01). Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p<0.01) and were correlated with clinical parameters. VEGFA was significantly upregulated (FC=6.1, p=6.0x10-6), and correlated with progression-free survival (p=0.037). ZNF385B was significantly downregulated (FC=-130.5, p=1.2x10-7), and correlated with overall survival (p=0.03). An increased TPX2 (p=0.03) and FOXM1 (p=0.044) expression correlated with optimal normalization of serum CA125 after treatment. Furthermore, we present a common molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and interacting with TP53. Conclusions: We have identified 21 mRNAs differentially expressed (p<0.01) between MD/PD SC, SBOT and SNO. Thirteen were differentially expressed in MD/PD SC, including VEGFA and ZNF385B, correlating with survival, and FOXM1 and TPX2, correlating with normalization of serum CA125. |
| 907 | GSE48842 |
Profile | PML functions as a platform for the interaction of transcription factors and coactivators. Role of PML in erythroid clone formation has been reported but the detail mechanism is unclear. We used microarrays to identify downstream-regulated genes of PML4. |
| 908 | GSE40567 |
Profile | The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains that contribute to the viral life cycle including the DNA binding and helicase domains. In addition, the LT the C-terminal region is required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells and identified interacting cellular proteins and performed expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. |
| 909 | GSE349 |
Profile | These patients proved resistant to docetaxel treatment exhibiting residual tumor of 25% or greater remaining volume. Keywords: repeat sample |
| 910 | GSE15323 |
Profile | Virus infection may shut off host protein synthesis in order to achieve the replicative advantage over host cells. It is well known that human pathogenic viruses particularly the picornaviruses, can block host protein synthesis by cleavage or inhibition of eukaryotic initiation factors (eIFs). In this study we found a novel mechanism that microRNA (miRNA) is involved in viral pathogenesis. Infection of enteroviruses can disturb the expression of host miRNAs, in which miR-141 is up-regulated and inhibits host protein synthesis by post-transcriptional repression of the target gene eIF4E, a key element for cap-dependent translation of host proteins. Knockdown of miR-141 by a specific siRNA, antagomiR-141, could restore host eIF4E expression, delay the occurrence of cytopathic effect (CPE), and impair virus propagation. We demonstrated that EV71 infection could increase early growth response 1 (EGR1) expression which induced miR-141 causing the eIF4E suppression; while silencing of EGR1 attenuated virus production. Our results suggest that enterovirus infection causes the EGR1-mediated upregulation of host miR-141, further lead to the translational switch from cap-dependent to cap-independent protein synthesis in the host cells, an environmental beneficial for viral propagation. This novel mechanism may highlight a new approach for future development of antiviral therapy. |
| 911 | GSE6784 |
Profile | MCF10A cells derived from spontaneously immortalized normal human mammary epithel were subjected to EGF/SERUM stimulation for 020,40,60,120,240 and 480 minutes. We used microarrays to understand the temporal regulation of the cellular EGFR cascade. Keywords: time course |
| 912 | GSE16659 |
Profile | DU145 prostate cancer cells were treated with 25 ng/ml hepatocyte growth factor (HGF) or vehicle for 2 8, or 24 hours. HGF stimulates the cMET protein, a tyrosine kinase transmembrane protein. The aim of this study is to determine the role of the HGF/cMET pathway in immature cells of established prostate cancer. HGF stimulation of DU145 prostate cancer cell line led to cell migration in culture, formation of sprouts in Matrigel and inhibition of growth. These biological effects went together with induction of a stem-like phenotype as defined by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 on gene-expression arrays and quantitative PCR. The shift towards a stem-like phenotype was reflected by protein modifications on FACS, Western blot, and enhanced rapid adhesion to collagen I. Small molecules SU11274 and PHA665752 were able to inhibit both morphologic and molecular HGF effects. |
| 913 | GSE29884 |
Profile | In this study we performed gene transcription analysis of parental MACF7 cell and MCF7 engineered to overexpress oncoprotein RAF1. We demonstrate that overexpression of RAF1 leads to development of ivasive phenotype. |
| 914 | GSE8531 |
Profile | In an acute skin wound newly released serum growth factors in the wound bed drive lateral migration of human keratinocytes (HKs) to re-epithelialize the wound. However, profiling the migration signal-specific genes has long been challenged by pleiotropic effects of a given growth factor, including proliferation, migration and factor-specific responses. To overcome these technical problems, we 1) took advantage of a unique response of HKs to transforming growth factor-beta (TGFbeta) to selectively suppress growth signal-responding genes and identify motility-specific genes and 2) employed dual stimulation of HKs with TGFalpha and insulin to identify the common genes and eliminate factor-specific genes. Under these conditions, DNA microarray analyses were utilized to study the profiles of both TGFalpha-regualted and insulin-regulated immediate early (IE, 30 min), early (E, 60 min) and delayed early (DE, 120 min) genes. Keywords: time course, growth factor response |
| 915 | GSE4561 |
Profile | NOX1 gene is member of the NADPH-dependent superoxide producing enzyme family. It generates reactive oxygen species (ROS) in regulated manner in response to growth factors cytokines and calcium signal. Low levels of ROS play role in many processes including cell proliferation, inflammatory response and mitogenesis. NOX1 over-expression in colon cancer cell lines as well as surgical samples suggests a role in colon cancer. We identified unique target sequences of siRNAs for post-transcriptional silencing of NOX1. Gene specific and scrambled (control) sequence carrying U6 promoter/shRNA cassettes were cloned into GFP expression vector. Stable clones were selected based on NOX1 expression after transient transfection of HT-29 cells. Clone 6A and 6C showed 70-80% decrease in NOX1 expression. The cells were expanded and analyzed further. We measured decreased ROS production, cell proliferation and G1/S block of the cell cycle. HT-29 parental cells, clone SA (scrambled) and clone 6A (gene specific) were utilized to establish xenografts in athymic mice to investigate the effect of NOX1 silencing on tumor growth and gene expression in vivo. Significant decrease was measured in the volume of forming tumors. The stable clones and corresponding xenografts were analyzed on microarray. The microarray data was validated with real-time PCR and western-blot analysis demonstrating the inhibition of genes important in cell cycle regulation and angiogenesis. The results of this study show silencing NOX1 levels of generated ROS decreased, the tumor formation attenuated in vivo suggesting NOX1 may be a therapeutic target for colon cancer. Keywords: gene silencing with shRNA |
| 916 | GSE3678 |
Profile | we analyzed the gene expression profiles of 7 PTC samples compared to 7 paired normal samples using Affymetrix tools and dChip software. The objective was to find potential molecular markers for this disease Keywords: gene expression analysis |
| 917 | GSE8527 |
Profile | Infection of the human host by Streptococcus pneumoniae begins with colonization of the nasopharynx which is mediated by adherence of bacteria to respiratory epithelium. Several studies have indicated an important role for the pneumococcal capsule in this process. Here, we used microarrays to characterize the in vitro transcriptional response of human nasopharyngeal epithelial Detroit 562 cells to adherence of serotype 2-encapsulated strain D39, serotype 19F-encapsulated strain G54, serotype 4-encapsulated strain TIGR4, and their nonencapsulated derivatives (Δcps). In total, 322 genes were found to be upregulated in response to adherent pneumococci. Twenty-two genes were commonly induced, including those encoding several cytokines (e.g., IL-1β, IL-6), chemokines (e.g., IL-8, CXCL1/2), and transcriptional regulators (e.g., FOS), consistent with an innate immune response mediated by Toll-like receptor signaling. Interestingly, 85% of genes was induced specifically by one or more encapsulated strains, suggestive of a capsule-dependent response. Importantly, purified capsular polysaccharides alone had no effect. Over a third of these loci encoded products predicted to be involved in transcriptional regulation and signal transduction, in particular MAPK signaling pathways. Real-time PCR of a subset of ten genes confirmed microarray data and showed a time-dependent upregulation of especially innate immunity genes. Downregulation of epithelial genes was most pronounced upon adherent D39Δcps, as 68% of the 161 genes identified was only repressed using this nonencapsulated strain. In conclusion, we identified a subset of host genes specifically induced by encapsulated strains during in vitro adherence, and have demonstrated the complexity of interactions occurring during the initial stages of pneumococcal infection. Keywords: Paired measurements |
| 918 | GSE27931 |
Profile | Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor. The brain-infiltrative character of glioblastoma makes complete surgical removal of the tumor impossible and neither radiation nor current chemotherapy provide cure. Recent evidence shows that glioblastoma multiforme consists of heterogeneous cell populations which differ in tumor-forming potential. Enriched tumor-initiating capacity has been linked to poorly differentiated glioblastoma cells sharing features with neural stem cells. Thus these cells are important targets for new therapeutic strategies. We aim to identify novel targets controlling maintenance and differentiation in glioblastoma-initiating cells through high throughput screening. To this end, we utilized libraries of small chemical compounds and small interference RNAs in combination with automated imaging and data analysis. Patient-derived glioblastoma cells were expanded and characterized using neural stem cell conditions. In culture, the cells showed low differentiation but expression of neural stem cell markers such as Nestin and Sox2. Upon intracranial injection into SCID mice these cells gave rise to tumors displaying the hallmarks of the human disease. Differentiation of glioblastoma-initiating cells (for example elicited through bone morphogenetic protein, BMP) was associated with strong morphological changes. Hence, cellular morphology, as well as markers specific for differentiation or death were used as screen readout. Lentiviral RNA interference-based screening yielded several gene knockdowns leading to ‘forced’ differentiation of glioblastoma-initiating cells. For example, knockdown of TRRAP (transformation/transcription domain associated protein) led to strongly increased differentiation and loss of proliferative and self-renewing capacity in these cells. TRRAP is an adapter protein implicated in oncogenic transformation through c-MYC transcription activation, also participating in chromatin remodeling and DNA repair. Glioblastoma-initiating cells with reduced TRRAP displayed increased apoptosis upon treatment with the genotoxic agent temozolomide. In vivo, Trapp knockdown cells were not able to give rise to glioblastoma upon transplantation into the brain of SCID mice. Together, these findings support a crucial role for TRRAP in maintenance and tumorigenicity of glioblastoma-initiating cells and might offer future therapeutic options. |
| 919 | GSE15103 |
Profile | The overall goal and objective is to study the degree to which PAX3-FKHR accounts for differences between ARMS and ERMS by expressing a construct (termed P3FK/ER) consisting of PAX3-FKHR joined to the estrogen receptor ligand binding domain in an ERMS cell culture system. |
| 920 | GSE12288 |
Profile | Gene expression profile in circulating leukocytes identifies patients with coronary artery disease Peter Sinnaeve Mark Donahue, Peter Grass, Jacky Vonderscher, David Seo, Pascal Goldschmidt, Christopher Granger Department of Medicine, Duke University, Durham, NC, USA, Novartis Institute for Biomedical Research, Cambridge, Boston, MA, USA Introduction Systemic and local inflammation plays a prominent pathogenetic role in atherosclerotic coronary artery disease (CAD), but the relationship of phenotypic changes in circulating leukocytes and extent of CAD remains unclear. We have investigated whether gene expression patterns in circulating leukocytes are associated with presence and extent of CAD. Methods Patients undergoing coronary angiography were selected according to their Duke CAD index (CADi), a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from 110 patients with CAD (CADi>23) and from 112 partially matched controls without CAD (CADi=0). Gene expression was assessed using Affymetrix U133A chips. Genes correlating with CAD were identified using Spearman’s rank correlation, and predictive gene expression patterns were identified using a partial least squares (PLS) regression analysis. Results 160 individual genes were found to significantly correlate with CADi (rho>0.2, P<0.0027), although changes in individual gene expression were relatively small (1.2 to 1.5 fold). Using these 160 genes, the PLS multivariate regression resulted in a highly predictive model (r2=0.764, P<0.001). Cross-validation showed that most of the predictive model was carried by only 8 genes (r2=0.752) (table 1). Conclusion Simultaneous expression pattern of 8 genes appears to be highly predictive for CAD. Peripheral leukocyte gene expression pattern could be a novel non-invasive biomarker for CAD and lead to new pathophysiologic insights. |
| 921 | GSE12513 |
Profile | We and others have shown that AGR2 is frequently upregulated during the development of pancreatic cancer. We used microarray to look at the target genes regulated by AGR2 in pancreatic cancer cell lines FA6 and MiaPaCa2. Keywords: gene knock-down overexpression |
| 922 | GSE13205 |
Profile | Septic patients treated in the intensive care unit (ICU) often develop multiple organ failure including persistent skeletal muscle dysfunction which results in the patient’s protracted recovery process. We have demonstrated that muscle mitochondrial enzyme activities are impaired in septic ICU patients resulting in decreased cellular energy which will interfere with muscle function and metabolism. Here we use detailed phenotyping and genomics to elucidate mechanisms leading to these impairments. Methodology/Principle Findings Utilising biopsy material from seventeen patients and ten age-matched controls we demonstrate that neither mitochondrial in vivo protein synthesis nor expression of mitochondrial genes are compromised. Indeed there was partial activation of the mitochondrial biogenesis pathway involving NRF2?/GABP and its target genes TFAM, TFB1M and TFB2M yet clearly this failed to maintain mitochondrial function. We therefore utilised transcript profiling and pathway analysis of ICU patient skeletal muscle to generate insight into the molecular defects driving loss of muscle function and metabolic homeostasis. Gene ontology analysis of Affymetrix analysis demonstrated substantial loss of muscle specific genes, a global oxidative stress response related to most probably cytokine signalling, altered insulin related signalling and a substantial overlap between patients and muscle wasting/inflammatory animal models. MicroRNA 21 processing appeared defective suggesting that post-transcriptional protein synthesis regulation is altered by disruption of tissue microRNA expression. Finally, we were able to demonstrate that the phenotype of skeletal muscle in ICU patients is not merely one of inactivity, it appears to be an actively remodelling tissue, influenced by several mediators, all of which may be open to manipulation with the aim to improve clinical outcome. Conclusions/Significance This first combined protein and transcriptome based analysis of human skeletal muscle obtained from septic patients demonstrated that losses of mitochondria and muscle mass are accompanied by sustained protein synthesis (anabolic process) while dysregulation of transcription programmes appears to fail to compensate for increased damage and proteolysis. Our analysis identified both validated and novel clinically tractable targets to manipulate these failing processes and pursuit of these could lead to new potential treatments. Keywords: Disease state analysis |
| 923 | GSE22573 |
Profile | Refined cancer models are required to assess the burgeoning number of potential targets for cancer therapeutics within a rapid and clinically relevant context. Here we utilize tumor-associated genetic pathways to transform primary human epithelial cells from epidermis oropharynx, esophagus, and cervix into genetically defined tumors within an entirely human 3-dimensional (3-D) tissue environment incorporating cell-populated stroma and intact basement membrane (BM). These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through the BM, a complex process critically required for biologic malignancy in 90% of human cancers. Invasion was rapid, and potentiated by stromal cells. Oncogenic signals in 3-D tissue, but not 2-D culture, resembled gene expression profiles from spontaneous human cancers. Screening well-characterized signaling pathway inhibitors in 3-D organotypic neoplasia helped distil a clinically faithful cancer gene signature. Multi-tissue 3-D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterize cancer progression. |
| 924 | GSE20333 |
Profile | Affymetrix HG-Focus array was used to determine a global gene expression profile of clinically and neuropathologically confirmed cases of sporadic Parkinson's disease compared to controls. Major alterations were detected in signal transduction protein degradation, dopaminergic transmission/metabolism, energy pathways/glycolysis, cell adhesion/cytoskeleton, extracellular matrix components and cell cycle functional classes. |
| 925 | GSE44946 |
Profile | Three master regulatory transcription factors Pdx1 MafA and Ngn3 have the ability to transdifferentiate pancreatic acinar cells to insulin-producing beta cells in mice. BRD7552 was identified as a small-molecule inducer that can upregulate the expression of Pdx1 in PANC-1 cells by high-throughput qPCR screening. We used microarrays to illustrate the mechnism of BRD7552 for PDX1 and insulin induction. |
| 926 | GSE16748 |
Profile | ET-743 (trabectedin Yondelis®) and PM00104 (Zalypsis®) are marine derived compounds that have antitumor activity. ET-743 and PM00104 exposure over sustained periods of treatment will result in the development of drug resistance, but the mechanisms which lead to resistance are not yet understood. Human chondrosarcoma cell lines resistant to ET-743 (CS-1/ER) or PM00104 (CS-1/PR) were established in this study. The CS-1/ER and CS-1/PR exhibited cross resistance to cisplatin and methotrexate but not to doxorubicin. Human Affymetrix Gene Chip arrays were used to examine relative gene expression in these cell lines. |
| 927 | GSE14883 |
Profile | We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells). |
| 928 | GSE9601 |
Profile | Human cytomegalovirus induces a pro-inflammatory monocyte following infection and we have evidence that NF-κB and phosphatidylinositol 3-kinase [PI(3)K] are key mediators in this early activation. To begin to address how these signalling pathways are responsible for the rapid activation of infected monocytes we examined the role these pathways played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes, including inflammatory genes, were regulated in a NF-κB- and/or PI(3)K-dependent manner, identifying these pathways as key cellular control points in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection. Keywords: disease state analysis |
| 929 | GSE41635 |
Profile | To evaluate the function of ALK in breast cancer we enforcing expressed full length wild type ALK in the parental MCF-7 breast cancer cell line that we have established in previous studies have a very low invasive capacity, do not form tumor emboli nor do they invade into the dermal lymphatics when grown as xenografts. |
| 930 | GSE22255 |
Profile | Stroke is a “brain attack” cutting off vital blood and consequently the nutrients and oxygen vital to the brain cells that control everything we do. Stroke is a complex disease with unclear pathogenesis resulting from environmental and genetic factors. To better understand IS´s etiology, we performed genomic expression profiling of patients and controls. |
| 931 | GSE19699 |
Profile | Normal lung function relies on mature function of alveolar type II cels which have numerous functions including to regulate ion and fluid flux, produce immune molecules, and synthesize and secrete surfactant to stabilize air spaces. Differentiation of type II cells from precursor epithelial cells is accelerated by exposure of cultured cells to glucocorticoid and cAMP. In these studies we used DNA microarray analysis to identify genes of both fetal and adult type II cells that are regulated by glucocorticoid plus cAMP. |
| 932 | GSE15578 |
Profile | The human kinome is incolved in multiple function in the life cycle of cells and ther differntial expression in cacner suggests that protein kinases play an important role in tumor progression and proliferation. To delineate pathways that may be important for neoplastic change in women at high risk for ovarian cancer, we compared the expression signature of surface kinases in normal ovarian surface epithelium with ovarian epithelium from patients at high risk, and epithelial ovarian cancer using Affymetrix expresion array HG U133Plus2. |
| 933 | GSE10097 |
Profile | The purpose of this experiment was to identify oestrogen regulated genes in human primary cell cultures of neuronal and glial cells modelling the developing human nervous system. We were especially interested in genes involved in proliferation differentiation and migration of neuronal cells and genes involved in or linked to neurodegenerative diseases. We have therefore assessed gene expression changes, using Affymetrix GeneChips (HG-U133A), of oestrogen treated human neuronal/ glial cell cultures. We continued with 14 selected genes and confirmed the gene expression changes, by relative quantitative real time PCR, of 6 genes (p< 0.05) important in neuronal development, three of which also are suggested to have links to neurodegenerative diseases. Keywords: Treatment vs Control |
| 934 | GSE10232 |
Profile | Cyclin T1-dependent genes in activated Jurkat cells. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Keywords: shrna knockdown |
| 935 | GSE41197 |
Profile | We used gene expression profiling of human DCIS and IBC to discover uniquely expressed genes that may also regulate progression. |
| 936 | GSE29367 |
Profile | We investigated the molecular mechanisms for osteolytic bone metastasis by selecting human lung cancer cell line subpopulations with elevated metastatic activity and validating genes that are overexpressed in these cells. A bone-seeking squamous lung cancer cell line (HARA-B4) was established by sequentially injecting parental HARA cells into the left ventricle of male 5-week-old nude mice 4 times. |
| 937 | GSE12621 |
Profile | The retinas of simian primates include a specialized cone-rich, macula which regards the central visual field and mediates high acuity and colour vision. A prominent feature of the macula is the fovea centralis - a 1 mm-wide, avascular depression in the inner retinal surface that corresponds with a local absence of rods and a peak spatial density of cones in the outer photoreceptor layer. The arrangement of macular photoreceptors, and their specialized ‘midget’ circuits, are the neural substrate for high resolution vision in primates. Macular-specific photoreceptor loss and abnormal blood vessel growth within the macula are the major causes of untreatable vision loss worldwide. However, the genes that regulate specialization of the macula, and the causes of its vulnerability to degeneration, remain obscure. Microarrays were used to compare gene expression between macula and non-macular regions during a critical phase of human retinal vascular development. Keywords: Comparison of developing anatomical regions |
| 938 | GSE29084 |
Profile | HNF4a is an important liver transcription factor that regulates at least a thousand genes in the liver. Here we used expression profiling in HepG2 cells a hepatocellular carcinoma cell line, in which HNF4a was knocked down by RNAi to identify some of those target genes. This dataset accompanies the article in Hepatology 2010 Feb;51(2):642-53. Integrated approach for the identification of human hepatocyte nuclear factor 4alpha target genes using protein binding microarrays by Bolotin E, Liao H, Ta TC, Yang C, Hwang-Verslues W, Evans JR, Jiang T, Sladek FM. |
| 939 | GSE16058 |
Profile | Molecular distinctions between the stasis and telomere attrition senescence barriers in cultured human mammary epithelial cells Normal human epithelial cells in culture have generally shown a limited proliferative potential of ~10-40 population doublings before encountering a stress-associated senescence barrier (stasis) associated with elevated levels of cyclin-dependent kinase inhibitors p16 and/or p21. We now show that simple changes in media composition can expand the proliferative potential of human mammary epithelial cells (HMEC) initiated as primary cultures to 50-60 population doublings followed by p16(+), senescence-associated b-galactosidase(+) stasis. We compared the properties of growing and senescent pre-stasis HMEC with growing and senescent post-selection HMEC, i.e., cells grown in a serum-free medium that overcame stasis via silencing of p16 expression and that display senescence associated with telomere dysfunction. Cultured pre-stasis populations contained cells expressing markers associated with luminal and myoepithelial HMEC lineages in vivo, in contrast to the basal-like phenotype of the post-selection HMEC. Gene transcript and protein expression, DNA damage-associated markers, mean TRF length, and genomic stability, differed significantly between HMEC populations at the stasis vs. telomere attrition senescence barriers. Senescent isogenic fibroblasts showed greater similarity to HMEC at stasis than at telomere attrition, although their gene transcript profile was distinct from HMEC at both senescence barriers. These studies support our model of the senescence barriers encountered by cultured HMEC in which the first barrier, stasis, is Rb-mediated and independent of telomere length, while a second barrier (agonescence or crisis) results from telomere attrition leading to telomere dysfunction. Additionally, the ability to maintain long-term growth of genomically stable multi-lineage pre-stasis HMEC populations can greatly enhance experimentation with normal HMEC. |
| 940 | GSE18680 |
Profile | We have previously described how TNF-α IL-6, CXCR4 and the CXCR4 ligand CXCL12 are expressed by human ovarian cancer cells in vitro. By comparing four ovarian cancer cell lines with varying levels of constitutive TNF-α production we found that CXCR4, CXCL12, TNF-α and IL-6 were linked in an autocrine network in malignant cells that had an effect on tumour growth and angiogenesis in one xenograft model of ovarian cancer. Using Affymetrix microarrays we compared in vitro gene expression in parental IGROV-1 and TOV21 cells (high CXCR4 expression) with TOV112D and SKOV-3 cells (low CXCR4 expression). Gene Set Enrichment Analysis (GSEA) of those genes which were differentially expressed between cell lines with high versus low CXCR4 expression revealed evidence for a cell autonomous signaling network involving CXCR4, TNF-a, IL6 and Notch pathways in ovarian cancer cells. |
| 941 | GSE6679 |
Profile | It is currently unknown how extensively the double-stranded RNA binding protein Staufen (Stau)1 is utilized by mammalian cells to regulate gene expression. To date Stau1 binding to the 3’ untranslated region (3’UTR) of ARF1 mRNA has been shown to target ARF1 mRNA for Stau1-mediated mRNA decay (SMD). ARF1 SMD depends on translation and recruitment of the nonsense-mediated mRNA decay factor Upf1 to the ARF1 3’UTR by Stau1. Here, we use microarray analyses to examine changes in the abundance of cellular mRNAs that occur when Stau1 is depleted. Results indicate that 1.1% and 1.0% of the 11,569 HeLa-cell transcripts that were analyzed are, respectively, upregulated and downregulated at least two-fold in three independently performed experiments. Additionally, we localize the Stau1 binding site to the 3’UTR of four mRNAs that we define as natural SMD targets. Together, these and substantiating results suggest that Stau1 influences the expression of a wide variety of physiologic transcripts and metabolic pathways. Keywords: Staufen1-mediated mRNA decay; Stau1 downregulation by siRNA. |
| 942 | GSE20033 |
Profile | Owing to the risk of insertional mutagenesis viral transduction has been increasingly replaced by nonviral methods to generate induced pluripotent stem (iPS) cells. We report the use of ‘minicircle’ DNA, a vector type that is free of bacterial DNA and capable of high expression in cells. Here we use a single minicircle vector to generate transgene-free iPSCs from adult human adipose stem cells. (Note: Our Nature Methods publication included analysis of array data from GSM378832 (Foreskin), GSM378833-GSM378838 (JT-iPSC), and GSM378817-GSM378820 (H1, H7, H9, H13, H14) in conjunction with this series). |
| 943 | GSE16477 |
Profile | Migratory embryonal neuroblasts give rise to several tissues including the sympathetic nervous system (SNS). Neuroblastomas are paediatric tumours of the peripheral SNS with a highly variable prognosis. We observed that high NOTCH3 expression in neuroblastomas correlated with a poor prognosis. Expression of a NOTCH3 transgene in neuroblastoma cells induced many motility genes and conferred a highly motile phenotype. Expression of these motility genes strongly correlated with NOTCH3 expression in neuroblastomas and many other tumours, suggesting a general role for NOTCH3 in regulation of these genes. Silencing of NOTCH3 or genes of the Notch-processing γ-secretase complex induced apoptosis in all neuroblastoma cell lines tested. These data suggest that NOTCH3 is a key-regulator of motility, and indispensable for survival of neuroblastoma cells. |
| 944 | GSE43289 |
Profile | Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of gliomas) and the histopathology. |
| 945 | GSE45605 |
Profile | The transcriptome analysis by the human DNA microarray was applied to evaluate the impacts of whole wastewater effluents from the membrane bioreactors (MBRs) and the activated sludge process (AS) on the biological processes of human hepatoma HepG2 cells. The three conventional bioassays (i.e., cytotoxicity tests and bioluminescence inhibition test) and chemical analysis of the domestic effluent standards were conducted in parallel since they are well-established methods with previous applications to wastewater. A significant variation of effluent quality was sdemonstrated among the tested effluents despite that all effluents met the 40 national effluent standards. The three conventional bioassays supported the result of the transcriptome analysis, indicating the comparable or even higher sensitivity of the new assay. The most superior effluent quality was found in the MBR operated at a relatively long sludge retention time (i.e., 40 days) and small membrane pore size (i.e., 0.03 μm). In addition, functional analysis of the differentially expressed genes revealed that the effluents made various impacts on the cellular functions, suggesting the transcriptome analysis by DNA microarray as more comprehensive, rapid and sensitive tool to detect multiple impacts of the whole effluents. Moreover, the potential genetic markers were proposed to quantitatively evaluate the treatability of the wastewater effluents. |
| 946 | GSE23704 |
Profile | All-trans retinoic acid (ATRA) is a potent retinoid which has been used successfully in different clinical settings as a potential drug to treat COPD and emphysema. In alveolar macrophages, ATRA selectively down-regulates MMP-9 and up-regulates TIMP-1 expression. In the present study, we analyzed additional genes modulated by ATRA by performing mRNA expression array on alveolar macrophages after treatment with ATRA. |
| 947 | GSE22331 |
Profile | Analysis of ejaculated spermatozoav from normozoospermic men and asthenozoospermic men. Some of genes were up-regulated or down-regulated in asthenozoospermia and their abnormal expression were the causes of the impaired sperm motility. Results provide insight into the mechanisms by which asthenozoospermia is controlled. We used microarrays to detail the global programme of gene expression of ejaculated spermatozoa between normozoospermic and asthenozoospermic men and identified distinct classes of genes expressed differentially in two groups. |
| 948 | GSE18454 |
Profile | Analysis of 2 cultured normal lung cell lines Normal Human Bronchial Epithelial (NHBE) and Human Small Airway Epithelial (SAEC) cells (Lonza, Walkersville, MD), following treatment with 5-aza-dC to induce DNA demethylation. These results provide insight into the role of epigenetic alterations, specifically demethylation, in differential gene expression in various lung neoplasms. |
| 949 | GSE29721 |
Profile | Extensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer. |
| 950 | GSE13434 |
Profile | Comparison of gene expression changes between aiRNA and siRNA. |
| 951 | GSE15431 |
Profile | This study describes a temporal profile of gene expression from normal human fetal testes and ovaries. Gonads from 34 fetuses between 9 weeks and 20 weeks of gestation were obtained from the Department of Pathology and the Birth Defects Research Laboratory at the University of Washington. Relative transcript levels were determined using the Affymetrix Human Genome U133A Plus 2.0 arrays. Sex determination occurs in the human gonad at approximately 6 weeks gestation with development of the testis driven by expression of SRY. In this study SRY transcript was present and elevated at 9 weeks gestation in the testis but absent in the ovary. The transcript levels of other testis-specific factors SOX9, AMH, and the steroidogenic genes CYP17a1, CYP11a1, STAR and HSD17β3 were all significantly higher in the testis. In contrast, transcripts known to be involved in meiosis including STRA8, SPO11, SYCP3, TEX11, TEX14 and STAG3 showed highest expression in the fetal ovary beginning at week 12. These gene expression profiles will be a resource for understanding and defining normal gonad development and provide the opportunity to dissect abnormal development. |
| 952 | GSE2189 |
Profile | Human lung cancer (A549) cells were treated 50uM of the metal cation-containing chemotherapeutic drug motexafin gadolinium (MGd) for 4 12, and 24 hrs and expression compared to control cells (treated with 5% mannitol for the same length of time) Keywords: dose response |
| 953 | GSE22225 |
Profile | Mutations in the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis a pediatric neurodegenerative disorder characterized by visual loss, epilepsy and psychomotor deterioration. Although most CLN3 patients carry the same 1 kb deletion in the CLN3 gene, their disease phenotype can be variable. The aims of this study were (1) to identify genes that are dysregulated in CLN3 disease regardless of the clinical course that could be useful as biomarkers, and (2) to find modifier genes that affect the progression rate of the disease. Genome-wide expression profiling was performed in 8 CLN3 patients, homozygous for the 1 kb deletion, with different disease progression and compared to seven age and gender matched controls. |
| 954 | GSE11812 |
Profile | Gene expression profile of cancer cell lines of breast lung, pancreatic, gasctric, ovarian, hepatocellular, prostate carcinomas and melanomas. |
| 955 | GSE39890 |
Profile | Despite their distinct biology granulosa cell tumours (GCTs) are treated the same as other ovarian tumours. Intriguingly, a recurring somatic mutation in the transcription factor Forkhead Box L2 (FOXL2) 402C>G has been found in nearly all GCTs examined. This investigation aims to identify the pathogenicity of mutant FOXL2 by studying its altered transcriptional targets. The expression of mutant FOXL2 was reduced in the GCT cell line KGN, and wildtype and mutant FOXL2 were overexpressed in the GCT cell line COV434. Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2. Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2. |
| 956 | GSE42270 |
Profile | To understand the molecular process associated with tissue morphogenesis of pancreatic epithelial cells we profiled the transcriptomes of normal or malignant pancreatic organoids formed in three-dimenstional reconsitututed basement membrance (rBM). Cell monolayers cultured on rBM-coated culture plastics were used as controls. |
| 957 | GSE12265 |
Profile | The aim of this study was to describe the gene expression patterns related to the differentiation and mineralization of bone-forming cells including activation and/or repression of osteogenic or non-osteogenic pathways, remodeling of cell architecture, cell adhesion, cell communication, and assembly of extracellular matrix. The study implied patient selection, tissue collection, isolation and culture of human marrow stromal cells (hMSC) and osteoblasts (hOB), and characterization of bone-forming cells. RNA samples were collected at defined time points, in order to understand the regulation of gene expression during the processes of cell differentiation/mineralization that occur during bone repair. Transcriptome analysis was performed by using the Affymetrix GeneChip microarray technology platform and GeneChip® Human Genome U133 Plus 2.0 Array. Our results help to design a gene expression profile of bone-forming cells during specific steps of osteogenic differentiation. These findings offer an useful tool to monitor the behaviour of osteogenic precursors cultured in presence of exogenous stimuli, i.e. growth factors, or onto 3D scaffolds for bone engineering. Moreover, they can contribute to identify and clarify the role of new genes for a better understanding of the molecular mechanisms regulating osteogenesis. Keywords: time course |
| 958 | GSE30220 |
Profile | Global gene-expression profiles analysis of hESCs patient-specific iPSCs, gene-corrected iPSCs, and patient fibroblast cells. |
| 959 | GSE26272 |
Profile | ZNF145 is shown to be upregulated during three linage differentiation of MSCs especially in chondrogenesis. To understand the molecular basis of ZNF145 underlying MSCs targets of ZNF145 in MSCs are determined by microarray We used microarrays to detail the change in gene expression profile upon overexpression of ZNF145 compared with control in undifferentiated MSCs |
| 960 | GSE15773 |
Profile | Obesity is a risk factor for numerous metabolic disorders; however not all obese individuals are prone to insulin resistance. The central aim of this study was to identify molecular pathways directly related to insulin resistance independent of BMI in obesity. We sought to determine the gene expression signature of adipose tissue in a body mass index (BMI)-matched obese cohort of patients that are either insulin sensitive or insulin resistant. |
| 961 | GSE17861 |
Profile | Specific early diagnosis of renal allograft rejection is gaining importance in the current trend to minimize and individualize immunosuppression. Gene expression analyses could contribute significantly by defining “molecular Banff” signatures. Several previous studies have applied transcriptomics to distinguish different classes of kidney biopsies. However the heterogeneity of microarray platforms, clinical samples and data analysis methods complicates the identification of robust signatures for the different types and grades of rejection. To address these issues, a comparative meta-analysis was performed across five different microarray datasets of heterogeneous sample collections from two published clinical datasets and three own datasets including biopsies for clinical indications, protocol biopsies, as well as comparative samples from non-human primates (NHP). This work identified conserved gene expression signatures that can differentiate groups with different histopathological findings in both human and NHP, regardless of the technical platform used. The marker panels comprise genes that clearly support the biological changes known to be involved in allograft rejection. A characteristic dynamic expression change of genes associated with immune and kidney functions was observed across samples with different grades of CAN. In addition, differences between human and NHP rejection were essentially limited to genes reflecting interstitial fibrosis progression. This data set comprises all renal allograft biopsies for clinical indications from patients at Hôpital Tenon, Paris (February 2003 until September 2004) and few respective patients from Hôpital Bicêtre, Paris, Hôpital Pellegrin, Bordeaux, and Hôpital Dupuytren, Limoges, plus control normal kidney samples from Hôpital Tenon, Paris, France (first batch). We used microarrays to identify different gene expression signatures of renal allograft biopsies that can classify them according to different types of allograft rejection or CAN. Keywords: disease state analysis Keywords: Expression profiling by array |
| 962 | GSE7757 |
Profile | Microarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies. For the first time we present a study focused on analyzing the impact of different RNA preparation procedures on gene expression data for different subtypes of pediatric acute leukemias. Keywords: comparison of various total RNA preparation procedures |
| 963 | GSE48876 |
Profile | SupB15 cells are highly sensitive to Mitoxantrone treatment. To obtain drug resistant subpopulations SupB15 cells were incubated in normal medium or BMSC derived conditioned medium, treated with 10nM of Mitoxantrone for 6 days. SupB15 cells in normal medium could not survive. a small population of SupB15 cells in conditioned medium group survived the treatment and ecpanded, termed as SupB15-MR. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. |
| 964 | GSE6972 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 965 | GSE37982 |
Profile | We generated iPSCs from imatinib-sensitive chronic myelogenous leukemia (CML) patient samples. We used microarrays tc ompare the gene expression pattern among CML-iPSCs and normal cord blood (CB) iPSCs. |
| 966 | GSE29908 |
Profile | Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approaches that can improveβcell function in type 1 diabetic (T1D) patients. This study was designed to investigate the potential mechanisms involved.We applied AHST to nine T1D patients diagnosed within six months and analyzed the acute response in peripheral blood genomic expression profiling at the six-month follow-up. |
| 967 | GSE25311 |
Profile | Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs. Gene expression changes in human Huh7 cells with familial hypercholesterolemia HDL treatment. |
| 968 | GSE24736 |
Profile | Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene segregates with most autoimmune diseases; its risk allele encodes overactive PTPN22 phosphatases that alter B cell receptor (BCR) signaling potentially involved in the regulation of central B cell tolerance. To assess whether PTPN22 risk allele affects the removal of developing autoreactive B cells we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from asymptomatic healthy individuals carrying one or two PTPN22 risk allele(s). We found that new emigrant/transitional and mature naive B cells from PTPN22 risk allele carriers contained high frequencies of autoreactive clones compared to non-carrier control donors. Hence, a single PTPN22 risk allele has a dominant effect on altering autoreactive B cell counterselection, suggesting that early B cell tolerance checkpoint defects precede the onset of autoimmunity. In addition, gene array experiments comparing mature naïve B cells from healthy individuals carrying or not PTPN22 risk allele(s) revealed that the strength of association of PTPN22 for autoimmunity, second in importance only to the MHC, may not only be due to BCR signaling alteration but also to the regulation of other genes, which themselves have also been identified as involved in the development of autoimmune diseases. The PTPN22 risk allele is a single nucleotide change (cytidine to thymidine) at residue 1858, which results in a single amino acid substitution from arginine to tryptophan at position 620 of the PTPN22/Lyp protein. |
| 969 | GSE10070 |
Profile | To further understand the differences occurring in MCF10A cells as they polarize and differentiate in the Transwell® model we performed gene expression profiling with Affymetrix Human Genome U133 Plus 2.0 Arrays. Four experimental time points, were sampled: conventional cultures of MCF10A cells grown on plastic (Monolayer) and MCF10A cells plated on Transwells® sampled at three TEER values, 200-300 Ω cm2 (Base), 1400-1600 Ω cm2 (Midpoint), and 3000-3200 Ω cm2 (Plateau). Keywords: Mammary Epithelial Cell Differentiation |
| 970 | GSE28571 |
Profile | Hypothesis: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n=50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term survivors. In squamous cell carcinoma (n=28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, mRNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic and clinical data. We identified gene copy number gains and losses, with corresponding changes in mRNA levels, that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung. |
| 971 | GSE22035 |
Profile | PI3K/AKT pathway plays one of pivotal roles in breast cancer development and maintenance. PIK3CA coding PIK3 catalytic subunit, is the oncogene which shows the high frequency of gain-of-function mutations leading to the PI3K/AKT pathway activation in breast cancer. In particular in the ERα-positive breast tumors PIK3CA mutations have been observed in 30% to 40%. However, genes expressed in connection to the pathway activation in breast tumorigenesis remain largely unknown. To identify downstream relevant target genes (and signaling pathways) turned on by the aberrant PI3K/AKT signal in breast tumors, we analyzed gene expression by pangenomic oligonucleotide microarray in a series of 43 ERα-positive tumors with and without PIK3CA mutations. |
| 972 | GSE7888 |
Profile | Human mesenchymal stem cells (hMSCs) which are multipotent cells to differentiate into several cell types, are expected to be a useful tool for cellular therapy. In some clinical settings, hMSCs have immuno-suppressive effects for GVHD (Graft-versus-host disease) and are expanded in vitro before application. To find biomarkers that indicate the culture stage of hMSCs, we performed microarray analysis for hMSCs derived from bone marrow, using Affymetrix GeneChip Human Genome U133 Plus 2.0 (54,613 probe sets). Keywords: mesenchymal stem cells, culture stage |
| 973 | GSE40749 |
Profile | Neural stem cells can migrate towards tumors of both neural and non-neural origins which is crucial for the success in treating disseminated tumors. Although the understanding of the molecular mechanisms underlying NSC tumor tropism is limited, it has been noted that several cytokines, growth factors and receptors direct the migration in vitro. A proper understanding of the basic molecular mechanisms of NSC migration towards tumors, especially identification of key cellular regulators of the migration, will have important implications in improving the effectiveness of engineering and employing NSCs as tumor therapy agents. We compared gene expression profiles between migratory and non-migratory hiPSC-NSCs towards cancer cells using cDNA microarray profiling. |
| 974 | GSE23293 |
Profile | Epidemiological data show that the immune system may control or promote emergence and growth of a neoplastic lymphomatous clone. Conversely systemic lymphomas, especially myeloma and CLL, are associated with clinical immunodeficiency. This prospective controlled study demonstrates substantially reduced circulating T helper cells, predominantly naive CD4+ cells, in patients with non-leukemic follicular and extranodal marginal zone lymphomas, but not in monoclonal gammopathy and early CLL. These numerical changes were correlated with a preactivated phenotype, hyperreactivity in vitro, presenescence, and a Th2 shift of peripheral T helper cells. No prominent alterations were found in the regulatory T cell compartment. Gene expression profiling of in vitro-stimulated CD4+ cells revealed an independent second alteration of T helper cell physiology which was most pronounced in early CLL but also detectable in FL/eMZL. This pattern consisted of downregulation of proximal and intermediate T-cell receptor signaling cascades and globally reduced cytokine secretion. Both types of T cell dysfunction may contribute to significant immunodeficiency in non-leukemic indolent B-cell lymphomas as demonstrated by refractoriness to hepatitis B vaccination. The precise definition of systemic T cell dysfunction serves as the basis to study its prognostic impact, its relationship to the established influence of the lymphoma microenvironment, and its therapeutic manipulation |
| 975 | GSE5287 |
Profile | BACKGROUND Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is around 50% and tumor derived molecular prognostic markers are needed for estimation of response and survival. METHODS Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes having an expression with high correlation to survival time after chemotherapy was identified. Two of these genes were selected for validation by immunohistochemistry (IHC) in tumor tissue from 149 cisplatin treated patients having complete follow-up data. RESULTS Fifty-five differentially expressed genes correlated significantly to survival time. Two of these (Emmprin and Survivin) were validated using IHC and multivariate analysis (n=145) identified Emmprin expression (hazard ratio 2.38; p<0.0001) and Survivin expression (hazard ratio 2.34; p<0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio 2.72; p<0.0001). In the good prognosis group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (p<0.0001). Within this group of patients, the subgroups of patients with no positive, one positive or two positive IHC stainings (Emmprin and Survivin) had estimated 5-year survival rates (+- SE) of 35.6+-?%, 6.3+-?%, and 0+?%, respectively. Response to chemotherapy could also be predicted with an OddsRatio of 4.60 (2.13-9.93) and 2.59 (1.25-5.38) for Emmprin and Survivin respectively. CONCLUSION Emmprin and Survivin proteins were identified as strong independent prognostic predictors for response and survival after cisplatin-containing chemotherapy in patients with bladder cancer. Keywords: Analysis of gene expression differences between responders and non-responders to chemotherapy |
| 976 | GSE33455 |
Profile | Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However most patients eventually develop resistance to this treatment. The aim of the study was to identify key molecular genes and networks associated with docetaxel resistance in 2 models of docetaxel-resistant castration-resistant prostate cancer cell lines. |
| 977 | GSE42952 |
Profile | Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed genes or pathways that specifically drive tumour progression or metastasis are not well understood. Therefore, we performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e., good outcome (OS and DFS > 50 months) versus bad outcome (OS < 19 months and DFS < 7 months). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue. The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components, such as ITGB1 and EPHA2, were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/β-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with β-catenin being also highly upregulated in metastatic tissue. Thus, we conclude that components of the integrin and ephrin pathways and EMT-related genes might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis. |
| 978 | GSE28160 |
Profile | Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. |
| 979 | GSE11100 |
Profile | Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. Keywords: Disease State Analysis |
| 980 | GSE18000 |
Profile | We recently identified the nonreceptor tyrosine kinase syk as a tumor suppressor in pancreatic ductal adenocarcinoma cells. Reintroduction of syk into Panc1 cells promoted a more differentiated phenotype and retarded invasion and tumorigenic growth. Gene array analysis identified over 2000 transcripts differentially expressed at FDR<0.01. Among these were members of the MMP2 axis, which were subsequently shown to regulate Panc1 invasion. Keywords: Genetic manipulation (stable transgene expression) |
| 981 | GSE19406 |
Profile | Expression of HIF-1a or Twist1 or Bmi1 in human hypopharyngeal cancer cell line FADU results in the drift of transcriptome profile from an epithelial cell-like signature to a mesenchymal stem cell-like signature. |
| 982 | GSE31421 |
Profile | The precise molecular mechanism of action and targets through which thalidomide and related immunomodulatory drugs (IMiDs) exert their anti-tumor effects remains unclear. We investigated the role of cereblon (CRBN) a primary teratogenic target of thalidomide, in the anti-myeloma activity of IMiDs. CRBN depletion is initially cytotoxic to human myeloma cells but surviving cells with stable CRBN depletion become highly resistant to both lenalidomide and pomalidomide, but not to the unrelated drugs bortezomib, dexamethasone and melphalan. Acquired deletion of CRBN was found to be the primary genetic event differentiating isogenic MM1.S cell lines cultured to be sensitive or resistant to lenalidomide and pomalidomide. Gene expression changes induced by lenalidomide were dramatically suppressed in the presence of CRBN depletion further demonstrating that CRBN is required for lenalidomide activity. Downstream targets of CRBN include interferon regulatory factor 4 (IRF4) previously reported to also be a target of lenalidomide. Patients exposed to and putatively resistant to lenalidomide had lower CRBN levels in paired samples before and after therapy. In summary, CRBN is an essential requirement for IMiD activity, and a possible biomarker for the clinical assessment of anti-myeloma efficacy. |
| 983 | GSE33769 |
Profile | Coenzyme Q10 deficiency syndrome includes a clinically heterogeneous group of mitochondrial diseases characterized by low content of CoQ10 in tissues. The only currently available treatment is supplementation with CoQ10 which improves the clinical phenotype in some patients but does not reverse established damage. We analyzed the transcriptome profiles of fibroblasts from different patients irrespective of the genetic origin of the disease. These cells showed a survival genetic profile apt at maintaining growth and undifferentiated phenotype, promoting anti-apoptotic pathways, and favoring bioenergetics supported by glycolysis and low lipid metabolism. WE conclude that the mitochondrial dysfunction caused byCoQ10 deficiency induces a stable survival adaptation of somatic cells from patients. |
| 984 | GSE43552 |
Profile | KDM5A/LSD1 is an important epigenetic regulator in medulloblastoma the most frequent brain tumor of childhood. Here, the response of ONS76 medulloblastoma cells upon siRNA-mediated knockdown of KDM5A is analysed. |
| 985 | GSE43502 |
Profile | Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of chemoresistant TNBC patients with different prognosis. In this study, 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital) are chosen for study |
| 986 | GSE12845 |
Profile | B cells from human tonsil and blood were sorted using flow cytometry. The human samples were processed immediately ex-vivo using markers for known B cell subsets. |
| 987 | GSE18277 |
Profile | Previous reports demonstrate that the α2-integrin (α2) mediates pancreatic ductal adenocarcinoma (PDAC) cell interaction with collagens. We found that untransformed pancreatic ductal epithelial cells and well-differentiated PDAC cells use α2 exclusively to adhere and migrate on collagenI. In contrast poorly-differentiated PT45P1 and MIAPaCa2 cells demonstrate reduced reliance on, or complete loss of α2, respectively. Further, well-differentiated PDAC lines exhibit reduced in vitro invasion compared to poorly-differentiated lines, and α2-blockade suppressed invasion of well-differentiated lines exclusively. Based on these data and the demonstrated role of α2 in maintaining tissue architecture in other organs, we hypothesized that α2 may actually suppress the malignant phenotype in PDAC. Accordingly, stable ectopic expression of α2 in MIAPaCa2 cells (MP2-α2) retarded in vitro invasion. MP2-α2 cells maintained on collagenI were more invasion-retarded than MP2-α2 cells maintained in standard tissue culture, and demonstrated higher α2β1 expression that was reflected in faster and more complete adhesion/migration on collagenI. Affymetrix gene expression profiling of α2-expressing and mock-transfected cells revealed that kallikrein-related peptidases (KLK)-5, 6 and 7 were specifically upregulated by α2. Accordingly, well-differentiated PDAC lines express KLK-5, 6 and 7 and KLK blockade increased invasion as well as collagenI-migration in KLK-positive lines. Importantly, an α2 cytoplasmic deletion mutant promoted KLK expression and retarded invasion, while an α9α2 chimera retarded invasion less efficiently, and did not impact KLK expression. These data demonstrate for the first time that the α2-ectodomain and KLK’s coordinately regulate a less invasive phenotype in PDAC cells. |
| 988 | GSE17407 |
Profile | Multiple Myeloma (MM) remains incurable despite novel therapies suggesting the need for further identification of factors mediating tumorigenesis and drug resistance. We performed microarray analysis to identify the molecular mechanisms whereby pDCs confer growth and drug resistance in MM cells. |
| 989 | GSE4737 |
Profile | Summary: HEK293 cells were transfected with control plasmid (pcDNA1/Neo; Invitrogen) or with the plasmid encoding HCaRG by a standard calcium phosphate co-precipitation method. The clones expressing the highest levels of HCaRG HCaRG clone 8 and 9 were used in this experiment, while clone transfected with vector alone, Neo clone, served as control. Stable transfectants were synchronized and grown in the presence of 10% FBS for 48 h. Total RNAs were purified with the mini RNeasy kit (Qiagen). Keywords: parallel sample |
| 990 | GSE42291 |
Profile | HIV-1 infections of women are mainly acquired through female reproductive tract where cervical and vaginal epithelial cells are the first line of defense. Although HIV-1 does not directly infect epithelial cells HIV-1 obligatorily interacts with and crosses over epithelial layer to infect susceptible target cells, mainly CD4+ T cells, in the lamina propria to initiate an infection. However, the mechanism and ramification of the interaction of HIV-1 and epithelial cells in vaginal transmission of HIV-1 remain to be elucidated. We hypothesized that cervical epithelial cells are not a passive barrier, but actively respond to HIV-1 to change mucosal milieu and facilitate HIV-1 transmission. We tested this hypothesis by studying the responses of cervical epithelial cells to HIV-1 through profiling genome-wide transcription. We found 1) cervical epithelial cells actively respond to HIV-1. Five hundred forty-three transcripts/genes in cervical epithelial cells were significantly altered in expression at four hours post exposure to HIV-1, of which many relate to important signaling pathways, such as innate immune responses, pattern recognition receptors, apoptosis, biosynthesis, and energy production, 2) HIV-1 increases the expression of CXC Chemokines (IL-8, CXCL1 and CXCL3) in cervical epithelial cells. IL-8 and CXCL1 are potent chemotactic for multinuclear neutrophils (MNP), monocytes and a minority of lymphocytes, and CXCL3 is predominant chemotactic for monocytes, 3) HIV-1 increases the expression of key inflammatory enzymes-COX-1 and COX-2. COX-1 is responsible for the production of prostaglandins that are important for homeostatic functions, and COX-2 is a key enzyme to convert arachidonic acid to prostaglandins, key inflammatory mediators, and 4) the increased expression of IL-8 and COX-2 revealed using microarray analysis was mapped into the endocervical epithelial cells of macaques inoculated with inactivated SIV in vivo. Our date lead to a role model of epithelial cells in HIV-1 vaginal transmission, that is the axis of HIV-1, epithelial cells, proinflammatory molecules (IL-8, CXCL1, CXCL3, COX-1 and COX-2), cell recruitment (MNP, monocytes and T cells), and inflammation. This model implies that moderating epithelial proinflammatory response to HIV-1 may be utilized in prevention of HIV vaginal transmission. |
| 991 | GSE13787 |
Profile | Introduction Basal-like (BLCs) and epidermal growth factor receptor 2 overexpressing (HER2+) carcinomas are the subgroups of breast cancers which have the more aggressive clinical behavior. In contrast to HER2+ carcinomas no targeted therapy is currently available for the treatment of patients with BLCs. In order to discover potential therapeutic targets, we searched for deregulated signaling pathways in human BLCs. Methods In this study, we focused on the oncogenic phosphatidylinositol 3-kinase (PI3K) pathway in twelve BLCs, and compared it to a control series of eleven hormonal receptor negative- and grade III- matched HER2+ carcinomas. The two tumor populations were first characterized by immunohistochemistry and gene expression. The PI3K pathway was then investigated by gene copy-number analysis, gene expression profiling and at a proteomic level using reverse phase protein array technology and tissue microarray. The effects of PI3K inhibition pathway on proliferation and apoptosis was further analyzed in three human basal-like cell lines. Results The PI3K pathway was found to be activated in BLCs and up-regulated compared to HER2+ tumors as shown by a significantly increased activation of the downstream targets Akt and mTOR. BLCs expressed significantly lower levels of the tumor suppressor PTEN and PTEN levels correlated negatively in a significant manner with Akt activity within that population. PTEN protein expression correlated significantly with PTEN DNA copy number and more importantly, reduced PTEN DNA copy numbers were observed specifically in BLCs. Similarly to human samples, basal-like cell lines exhibited an activation of PI3K / Akt pathway and low/lack PTEN expression. Both PI3K and mTOR inhibitors led to basal-like cell growth arrest. However, apoptosis was observed specifically after PI3K inhibition. |
| 992 | GSE12843 |
Profile | Human mesenchymal stem cells (MSCs) have been isolated from adult adipose tissues and were shown to have ability to differentiate into multiple mesodermal lineages as well as non-mesodermal lineages. MSC had also been isolated from lipoma, and the lipoma-derived MSCs (LM6) showed very similar stem cell characteristics to adipose-derived MSCs (AM3). However, LM6 cells exhibited a higher cumulative population doubling levels as compared with AM3 cells. The expression profiles of both mRNAs and microRNAs (miRNAs) from AM3 and LM6 cells were compared to find considerable similarities except that miRNAs miR-99a and miR-152 were abundantly expressed in AM3, but absent in LM6 cells. The abundantly differentially expressed genes HAS2, VNN1, SLC16A6 and COL11A1 in LM6 cells were shown to be targets of miRNAs miR-99a and/or miR-152. Several additional genes were also found to be targets of miRNAs miR-99a and miR-152, as well as let-7g, let-7i, miR-199a, mir-134 and miR-374. The highly up-regulated expression of miRNA target genes such as SLC16A6, COL11A1 and TRHDE, as well as several other genes such as sushi domain containing 2, keratin associated proteins and tumor necrosis factor family, may explain the higher proliferation potential in LM6 cells compared with AM3 cells. Keywords: genetic modification |
| 993 | GSE9723 |
Profile | Transcriptional profiling was utilized to define the biological pathways of gingival epithelial cells modulated by co-culture with the oral pathogenic Porphyromonas gingivalis and Aggregatibacter (formerly actinobacillus) actinomycetemcomitans. We used microarrays to detail the global programme of gene expression underlying infection and identified distinct classes of up- and down-regulated genes during this process. Keywords: infection state |
| 994 | GSE16085 |
Profile | A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. |
| 995 | GSE35679 |
Profile | Global gene expression of 13 frozen samples 6 from typical and 7 from atypical surgically resected primary lung carcinoids All the patients not chemo-radio naïve and with a second tumor were excluded from the study. A written informed consent for research use of biological samples was obtained from all the patients. |
| 996 | GSE36765 |
Profile | CD4+ helper T (Th) cells are critical regulators of immune responses but their role in breast cancer is currently unknown. This work aims to characterize Th cells infiltrating invasive primary human breast tumors analyze the influence by the tumor microenvironment and identify Th cell specific prognostic gene signatures. CD4+ T cells isolated from the tumor (TIL), axillary lymph node (LN) and blood (PB) of 10 patients were analyzed on Affymetrix U133 Plus 2.0 arrays. A confirmation set of 60 patients were studied by flow cytometry, qRT-PCR or immunohistochemistry and analyzed according to the extent of the tumor immune infiltrate. Gene expression profiles of freshly isolated TIL were also compared with TIL that had been rested overnight or with CD4+ T cells [non-stimulated (NS) or stimulated (S)] from healthy donor PB treated with tumor supernatant (SN). Analysis of CD4+ TIL by comparing their expression profiles to those of their conterparts from patient axillary lymph nodes and peripheral blood and healthy donor blood |
| 997 | GSE27718 |
Profile | To metastasize a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets simultaneously. We performed a microRNA analysis of human melanoma, an aggressively invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential of primary tumors, shorter time to recurrence and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data point to a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immune suppression. MicroRNAs are emerging as key contributors to tumor metastasis because of their ability to regulate multiple targets, and thereby alter several functions, simultaneously. We found a miRNA cluster that promotes metastasis by concurrently enhancing invasive capabilities of melanoma cells and suppressing immune surveillance mechanisms, allowing the tumor cells to migrate and invade foreign tissue. Both these effects of miR-30b/30d are mediated by direct suppression of GalNAc transferases. Aberrant glycosylation has previously been connected to tumor progression, but the underlying molecular mechanisms and their impact on specific cellular pathways are poorly understood. Our work places the control of glycosylation as a novel molecular link between tumor cell migration and immune evasion, two processes that act synergistically during metastasis. |
| 998 | GSE36830 |
Profile | Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways which persists for at least 12 weeks. CRS is one of the most common chronic diseases in adults in the United States affecting over 30 million Americans. CRS is frequently divided into 2 types: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Histologic studies have demonstrated significant tissue eosinophilia in CRSwNP. T cells in the mucosa are elevated in both forms of CRS and are skewed towards Th2 cytokine expression in CRSwNP. However pathogenic role of CRS has not been fully explored. To screen for pathogenic factors in CRS, we performed a microarray study. We collected uncinate tissues (UT) from 6 subjects with CRSsNP, 6 subjects with CRSwNP and 6 control subjects and nasal polyp (NP) tissues from 6 subjects with CRSwNP and then evaluated gene expression profiles using Affymetrix Human Genome U133 plus 2.0 array. |
| 999 | GSE20011 |
Profile | Genomewide gene expression analysis of lymphoid cell lines of Hodgkin non-Hodgkin and acute leukemia origin |
| 1000 | GSE9940 |
Profile | Human embryonic stem cells not only provide a continuous cell source for potential cell therapy but also offer a system to unveil events of embryonic development in humans. This proposal will examine how the earliest neural cells neuroepithelia, are specified from the naïve ES cells, and test the hypothesis that neural specification in humans employs a similar mechanism as in other vertebrates. We will first re-create in culture the developmental events of the first 2-3 weeks of human embryonic development during which ES cells will be differentiated through the stages of embryoid bodies, primitive ectoderm cells, neural tube-like rosette cells. The stage-specific events will be defined by DNA microarray analysis along with the characteristic morphologic changes. This study will lead to an optimized procedure for generating enriched neural precursor cells, which will lay the groundwork for potential use of human ES cells in the treatment of neurological injuries and diseases. Aim 1: Establish a stepwise neural differentiation system from human ES cells. Aim 2. Determine the mechanism of Neural Specification in humans. Aim 3: Define the identity and function of ES cell-derived neural precursor cells. ES cells offer an alternative approach to study early developmental events in humans. This however requires re-creating the neural differentiation process in culture. Cell fate specification is determined by interactions between environmental factors and intrinsic signals. Our preliminary data suggest that the temporal pattern of neural differentiation and, to some degree, the spatial organization of neural precursors from human ES cells recapitulate in vivo neural development. We hypothesize that the intrinsic neural specification program may be preserved in culture, which offers a controlled system to examine the effect of extrinsic signals on neural specification. Distinctive morphological changes along the neural differentiation pathway are presumably accompanied by molecular changes. DNA microarray analysis will be used to determine the gene expression pattern by cells at each of the given stages. By analogy with early embryonic development and using morphological and antigenic markers, we can now subdivide the human ES cell neural differentiation process into four identifiable stages: ES, EB, PEL cells, and neural rosette cells. This definition is based on the assumption that early human development is the same as in other species, and employs the limited known markers from mouse ES cells. We will systematically investigate the molecular profile of cells at each of the neural differentiation stages using DNA microarray analysis. Total RNAs will be extracted from cells at the following developmental stages: ES cells, EBs grown in suspension (d6), PEL (d10) stage and neural rosettes (d17). Since the neural rosette culture contains non-neural lineage cells, we will separate the neural rosette cells from the surrounding non-neural cells through differential enzymatic response and differential adhesion. Three independent biological replicates consisting of three pooled experiments will be run for each of the four developmental time points, for a total of twelve chips. Keywords: time-course |
| 1001 | GSE660 |
Profile | primary ALL cells (B-lineage) resistant to daunorubicin by the MTT in vitro sensitivity assay Keywords = ALL Keywords: other |
| 1002 | GSE1563 |
Profile | We used DNA microarrays (HG-U95Av2 GeneChips) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients. Sample classes include kidney biopsies and PBLs from patients with 1) healthy normal donor kidneys 2) well-functioning transplants with no clinical evidence of rejection, 3) kidneys undergoing acute rejection, and 4) transplants with renal dysfunction without rejection. Nomenclature for samples is as follows: 1) all sample names include either BX or PBL to indicate that they were derived from biopsies or PBLs respectively, 2) C indicates samples from healthy normal donors, 3) TX indicates samples from patients with well-functioning transplants with no clinical evidence of rejection, 3) AR indicates samples from transplant patients with kidneys undergoing acute rejection, 4) NR indicates samples from transplant patients with renal dysfunction without rejection. Abbreviations used to describe patient samples include the following: BX - Biopsy; PBL- Peripheral Blood Lymphocytes; CsA -Cyclosporine; MMF - Mycophenolate Mofetil; P - Prednisone; FK - Tacrolimus; SRL - Sirolimus; CAD -Cadaveric; LD - Live Donor; Scr - Serum Creatinine; ATN - Acute Tubular Necrosis CNI - Calcineurin Inhibitor; FSGS - Focal Segmental Glomerulosclerosis several array data sets did not pass quality control and were not analyzed. These include AR1PBL, NR4BX, and NR6PBL Keywords = DNA microarrays, gene expression, kidney, rejection, transplant Keywords: other |
| 1003 | GSE11881 |
Profile | mmunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients commonly referred to as ‘operationally’ tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter ‘fingerprint’ of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for ?d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+CD25+ T-cells and Vd1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning. |
| 1004 | GSE29539 |
Profile | Expression of let-7i results in transcriptome alteractions in head and neck cancer cell line OECM1. |
| 1005 | GSE9579 |
Profile | Gene expression was evaluated in 9 appendix samples removed from patients who went to the operating room with the diagnosis of acute appendicitis and 4 samples removed for non-inflammatory reasons. A circumferential piece of tissue was obtained at the distal aspect of each specimen. The tissue was flash frozen at -80 degrees for later processing. Frozen specimens were homogenized into TriReagent and RNA was isolated according to the manufacturer's instruction. RNA was processed and hybridized to Affymetrix microarray. Keywords: Disease state analysis |
| 1006 | GSE5682 |
Profile | Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Here we show that NOTCH1 regulates PTEN expression and the activity of the PI3K-AKT signaling pathway in normal and leukemic T cells. Notch signaling and the PI3K-AKT pathway synergize in vivo in a Drosophila model of Notch-induced tumorigenesis, and mutational loss of PTEN is associated with increased glycolysis and resistance to NOTCH1 inhibition in human T-ALL. These findings identify the transcriptional regulation of PTEN and the control of cellular metabolism as key elements of the oncogenic program activated by NOTCH1 and provide the basis for the design of new therapeutic strategies for T-ALL. Keywords: Drug sensitivity comparison |
| 1007 | GSE3292 |
Profile | Introduction: Human Papilloma Virus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC) between 15% and 35% of HNSCC harboring HPV, almost exclusively of subtype 16. Demographic and exposure differences between HPV-positive (+) and negative (-) HNSCCs suggest that HPV(+) tumors may constitute a subclass with different biology, while clinical differences have also been observed. In this study, gene expression profiles of HPV(+) and (-) tumors were compared to further explore the biological effect of HPV in HNSCC. Methods: Thirty-six HNSCC tumors were analyzed for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV using consensus primers for HPV L1, E6 and E7 by PCR and RT-PCR. Results: Eight (22%) of 36 tumors were positive for HPV, all of the HPV 16 subtype, and the HPV positive samples also expressed viral HPV E6 mRNA determined by RT-PCR. Patients with HPV(+) HNSCCs were on average younger than those with HPV(-) tumors (mean age 50.2 vs. 58.7). Statistical analysis using Significance Analysis of Microarrays (SAM) based on HPV status as a supervising parameter resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a sub-set of these genes were verified by RT-PCR. Genes highly expressed in HPV(+) samples included cell cycle regulators (p16INK4A, p18 and CDK2) and transcription factors (TAF7L, RFC4, RPA2 and TFDP2). The microarray data were also investigated using DIGMap to map genes by chromosomal location. A large number of genes on chromosome 3q24-qter was found to be overrepresented in HPV(+) tumors. Conclusion: The gene expression profile associated with HPV reflects alterations in cell cycle and proliferation signals. Further investigation of differentially expressed genes may reveal the unique pathways in HPV(+) tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment. Keywords: HPV, HNSCC, head and neck cancer, human, human papilloma virus |
| 1008 | GSE26462 |
Profile | We recently showed that inactivation of the WASF3/WAVE3 gene in breast cancer cells results in loss of cell motility and invasion in vitro and metastasis in vivo. To obtain a better understanding of molecular mechanisms of action of WASF3 we have established the stable WASF3 knockdown MDA-MB-231 cells using shRNA strategy. We used microarrays to detail the global programme of gene expression after silencing WASF3 and identified distinct classes of up or down-regulated genes associated with breast cancer cell migration and motility |
| 1009 | GSE16356 |
Profile | Kaposi sarcoma is the most common cancer in AIDS patients and is typified by red skin lesions. The disease is caused by the KSHV virus (HHV8) and is recognisable by its distinctive red skin lesions. The lesions are KSHV-infected spindle cells most commonly the lymphatic endothelial and blood vessel endothelial cells (LEC and BEC), plus surrounding stroma. The KSHV virus expresses multiple MAF-downregulating microRNA. Here we test the effects of MAF silencing by siRNA in LEC cells using Affymetrix hgu133plus2 chips. |
| 1010 | GSE28645 |
Profile | The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity leading to the development of a steroid independent tumour. The p160 steroid coactivator protein SRC-1 through interactions with developmental proteins and other non-steroidal transcription factors drives this tumour adaptability. Here, using discovery studies we identify ADAM22, a non-protease member of the ADAMs family, as a direct target of SRC-1, independent of estrogen receptor(ER). Molecular, cellular, in vivo and clinical studies confirmed SRC-1 as a regulator of ADAM22 and established a role for ADAM22 in endocrine resistant tumour progression. ADAM22 has the potential to act as a therapeutic drug target and a companion predictive biomarker in the treatment of endocrine resistant breast cancer. |
| 1011 | GSE7152 |
Profile | 35 Melanoma cell lines hybridized to Affymetrix Hu133_Plus 2 microarrays were analysed for genes differentially expressed between cell lines carrying wild-type p14ARF and those with mutant 14ARF. All of these cell lines contained wild-type p53 (so that the effects of p14ARF mutations could be analysed without contamination from p53). Keywords: Affymetrix Hu133_Plus microarrays |
| 1012 | GSE13587 |
Profile | Human papilloma (HPV) virus-like particle (VLP) vaccines were recently licensed. Though neutralizing antibody titers are thought to be the main effectors of protection against infection early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMC from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization. Vaccination with HPV-16 L1 VLP was associated with modulation of genes involved in the inflammatory/defense response, cytokine, interferon and cell cycle pathways in VLP-stimulated PBMC. In addition, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing antibody titers were found for cyclin d2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with the microarray data was seen for over two-thirds of these probesets. Up-regulation of immune/defense response genes by VLP, in particular interferon-induced genes was observed in PBMC collected prior to vaccination, with many of these genes being further induced following vaccination. In conclusion, we used gene expression profiling to identify important innate and adaptive response related- genes induced by vaccination with HPV VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials. Keywords: Time course - pre and post HPV immunizaton |
| 1013 | GSE33845 |
Profile | Highly metastatic cancer cells have been observed to move directionally in response to direct current (dc) electric fields (EFs) of physiological strength. The phenomenon which is called electrotaxis or galvanotaxis, suggests the involvement of physiological EF in cancer metastasis. To explore this conjecture, we compared the influence of dcEF on gene expressions of a highly invasive (CL1-5) and a low invasive (CL1-0) lung cancer cell lines. |
| 1014 | GSE19397 |
Profile | Treatment-related DNA hypermethylation may play a role in creating drug resistant phenotypes by inactivating genes that are required for cytotoxicity but there have been no genome-wide studies to systematically investigate methylation of individual genes following exposure to chemotherapy. We used microarrays and a pharmacologic unmasking protocol in isogenic cisplatin-sensitive and -resistant cell lines to identify genes that were down-regulated in cisplatin-resistant cells and could be re-activated by the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-dC). We identified several hundred genes that were down-regulated in each resistant cell line. Of these, 30 genes were common to > 2 cell lines, and/or reported to be down-regulated in previous studies. siRNA knockdown of two candidate genes increased cell viability with cisplatin treatment in sensitive parental cell lines |
| 1015 | GSE13267 |
Profile | This study was designed to assess ependymoma global gene expression analyses. |
| 1016 | GSE43701 |
Profile | Hyperthermia (HT) is widely used to treat patients with various cancers. In general HT elicits a wide spectrum of stress responses such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown. The effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in human cervical squamous cell carcinoma HeLa cells were investigated using an Affymetrix GeneChip system. |
| 1017 | GSE45225 |
Profile | Many studies have characterized the results of shear stress changes on cultured endothelial cells in different bioreactor systems. However it is still unclear how an invasive intervention like stent procedure may influence the transcriptional response of endothelium. To study the simultaneous effects of shear stress changes and stent application on endothelial gene expression we have used an experimental apparatus of laminar flow bioreactor (LFB) system with human cultured endothelial cells exposed or not exposed to stent procedure with different flow conditions. Microarray analysis was evaluated in each experimental protocol. |
| 1018 | GSE42327 |
Profile | We found that CFIm68 a mRNA cleavage and polyadenylation factor implicated for alternative polyadenylation site choice, was co-purified with Thoc5, a component of human THO/TREX. Microarray analysis using human HeLa cells reveals knockdown of Thoc5 affects the expression of a subset of non-heat shock genes. Notably, depletion of Thoc5 attenuated the expression of the mRNAs polyadenylated at distal, but not proximal, polyadenylation sites, which phenocopied the depletion of CFIm68. |
| 1019 | GSE14842 |
Profile | Increased numbers of mast cells and their products have been linked to symptom onset and severity in patients with chronic diarrhea and abdominal pain. Although mast-cell inhibition ameliorates clinical manifestations and reduces mucosal inflammation underlying molecular mechanisms remain unknown. Keywords: Comparison of gene expression |
| 1020 | GSE23402 |
Profile | Knowledge of both the global chromatin structure and the gene expression programs of human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells should provide a robust means to assess whether the genomes of these cells have similar pluripotent states. Recent studies have suggested that ES and iPS cells represent different pluripotent states with substantially different gene expression profiles. We describe here a comparison of global chromatin structure and gene expression data for a panel of human ES and iPS cells. Genome-wide maps of nucleosomes with histone H3K4me3 and H3K27me3 modifications indicate that there is little difference between ES and iPS cells with respect to these marks. Gene expression profiles confirm that the transcriptional programs of ES and iPS cells show very few consistent differences. Although some variation in chromatin structure and gene expression was observed in these cell lines these variations did not serve to distinguish ES from iPS cells. |
| 1021 | GSE33169 |
Profile | Negative-pressure wound therapy (NPWT) is widely used to improve skin wound healing and to accelerate wound bed preparation. Although NPWT has been extensively studied as a treatment for deep wounds its effect on epithelialization of superficial dermal wounds remains unclear. To clarify the effect of NPWT on reepithelialization, we applied NPWT on split- thickness skin graft donor sites from the first postoperative day (POD) to the seventh POD. Six patients took part in the study and two samples were obtained from each. The first biopsy sample was taken at elective surgery before split-thickness skin grafting and the second one during reepithelialization on the seventh POD. In all 12 samples (eight from four NPWT patients, and four from two control patients) were collected for this study. From each sample, we carried out a comprehensive genome-wide microarray analysis. Data from patients receiving NPWT were compared groupwise with data from those not receiving NPWT. |
| 1022 | GSE4600 |
Profile | Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2 encoding methyl-CpG binding protein 2. MeCP2 is a transcriptional repressor elevated in mature neurons and is predicted to be required for neuronal maturation by regulating multiple target genes. Identifying primary gene targets in either Mecp2-deficient mice or human RTT brain has proven to be difficult, perhaps because of the transient requirement for MeCP2 during neuronal maturation. In order to experimentally control the timing of MeCP2 expression and deficiency during neuronal maturation, human SH-SY5Y cells undergoing mature neuronal differentiation were transfected with methylated MeCP2 oligonucleotide decoy to disrupt the binding of MeCP2 to endogenous targets. Genome-wide expression microarray analysis identified all four known members of the inhibitors of differentiation or inhibitors of DNA binding (ID1, ID2, ID3 and ID4) subfamily of helix-loop-helix (HLH) genes as novel neuronal targets of MeCP2. Chromatin immunoprecipitation analysis confirmed binding of MeCP2 near or within the promoters of ID1, ID2 and ID3, and quantitative RT-PCR confirmed increased expression of all four Id genes in Mecp2-deficient mouse brain. All four ID proteins were significantly increased in Mecp2-deficient mouse and human RTT brain using immunofluorescence and laser scanning cytometric analyses. Because of their involvement in cell differentiation and neural development, ID genes are ideal primary targets for MeCP2 regulation of neuronal maturation that may explain the molecular pathogenesis of RTT. Keywords: Neuronal Differentiation, Targets of MeCP2, Rett syndrome. |
| 1023 | GSE24584 |
Profile | In our continuing study of the desmosdumotin C (1) series twelve new analogues, 21–32, mainly with A-ring modifications, were prepared and evaluated for in vitro anticancer activity against several human tumor cell lines. Among them, the 4′-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant cytotoxicity against multiple human tumor cell lines with ED50 values of 1.1–2.8 microM. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an iso-butyl ether showed selective cytotoxicity against lung cancer A549 cells (ED50 1.7 microM). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase. We used microarrays to elucidate the underlying antitumor mechanism induced by Desmosdumotin C Analog |
| 1024 | GSE42677 |
Profile | Purpose: Primary cutaneous squamous cell carcinoma (SCC) can be an invasive cancer in skin and has the potential to metastasize. We aimed to define the cancer related molecular changes that distinguish non-invasive from invasive SCC. Experimental design: We used laser capture microdissection technique in combination with cDNA microarray analysis in order to determine molecular changes that associate with SCC progression. Results: We defined invasion-associated genes as those udifferentially regulated only in SCC invasive nests but not in actinic keratosis-like dysplasia or SCC in situ regions, compared to normal epidermis. We designated these genes as “invasion signature gene set of cutaneous SCC”. Overall we found 383 up- and 354 down-regulated probe-sets that constitute the invasion signature gene set. As part of this profile, SCC invasion is associated with aberrant gene expression changes of numerous MMPs including MMP7 (FCH=5.43, FDR<0.01) and MMP13 (FCH=12.53, FDR<0.01). IL-24 is also up-regulated in the leading invasive edge of SCC (FCH=6.74, FDR<0.01). IL-24 enhanced mRNA expression of both MMP7 and MMP13 in a human SCC cell line. Laminin332, which is one of the target molecules of MMP7, had altered expression at the leading edge of SCC invasion nests at both the genomic and protein level. Conclusions: We defined the distribution of MMPs within human cutaneous SCC tissue showing distinct expression with progression from normal skin to actinic keratosis to SCC in situ to invasive carcinoma. We further suggest a potential role for IL-24 in progression to invasion via MMP7 and MMP13. |
| 1025 | GSE35925 |
Profile | Background: Breast cancer patients present lower 125(OH)2D3 or 25(OH)D3 serum levels than unaffected women. Although 1,25(OH)2D3 pharmacological concentrations of 1,25(OH)2D3 may exert antiproliferative effects in breast cancer cell lines, much uncertainty remains about the effects of calcitriol supplementation in tumor specimens in vivo. We have evaluated tumor dimension (ultrassonography), proliferative index (Ki67 expression), 25(OH)D3 serum concentration and gene expression profile, before and after a short term calcitriol supplementation (dose to prevent osteoporosis) to post-menopausal patients. Results: Thirty three patients with operable disease had tumor samples evaluated. Most of them (87.5%) presented 25(OH)D3 insufficiency (<30 ng/mL). Median period of calcitriol supplementation was 30 days. Although tumor dimension did not vary, Ki67 immunoexpression decreased after supplementation. Transcriptional analysis of 15 matched pre/post-supplementation samples using U133 Plus 2.0 GeneChip (Affymetrix) revealed 18 genes over-expressed in post-supplementation tumors. As a technical validation procedure, expression of four genes was also determined by RT-qPCR and a direct correlation was observed between both methods (microarray vs PCR). To further explore the effects of near physiological concentrations of calcitriol on breast cancer samples, an ex vivo model of fresh tumor slices was utilized. Tumor samples from another 12 post-menopausal patients were sliced and treated in vitro with slightly high concentrations of calcitriol (0.5nM), that can be attained in vivo, for 24 hours In this model, expression of PBEF1, EGR1, ATF3, FOS and RGS1 was not induced after a short exposure to calcitriol. Conclusions: In our work, most post-menopausal breast cancer patients presented at least 25(OH)D3 insufficiency. In these patients, a short period of calcitriol supplementation may prevent tumor growth and reduce Ki67 expression, probably associated with discrete transcriptional changes. This observation deserves further investigation to better clarify calcitriol effects in tumor behavior under physiological conditions. |
| 1026 | GSE16386 |
Profile | Human CD14 positive monocytes were purified from healthy volunteers’ blood and cultured in vitro for 6 hours. While culturing macrophages were activated alternatively with interleukin-4 (IL-4 100 ng/ml). Simultaneously, macrophages were also treated with vehicle (DMSO:ethanol) or 1uM synthetic PPARg agonist, Rosiglitazone. We used Affymetrix microarrays (U133Plus 2.0) to analyze activation and PPARg-induced gene expression changes. |
| 1027 | GSE42407 |
Profile | A lung cancer cell model of invasive transformation was developed to select progressively invasive cell populations from a parental cell line of human lung adenocarcinoma CL1. Five progressive sub-clones namely, CL1-1, CL1-2, CL1-3 CL1-4, and CL1-5 were selected using transwell and displayed increasing invasion potential (Chu et al, 1997). Here, we used microarrays to analyze and compare gene expression profiles between CL1-0 and CL1-5 for the identification of invasion/metastasis associated gene signatures. |
| 1028 | GSE39156 |
Profile | Radiation is an established cause of thyroid cancer and growing evidence supports a role for H2O2 in spontaneous thyroid carcinogenesis. Little is known about the molecular programs activated by these agents in thyroid cells. We profiled the DNA damage response and cell death induced by γ-radiation (0.1–5Gy) and H2O2 (0.0025–0.3mM) in primary human thyroid cells and T-cells. While the two cell types had more comparable radiation responses 3- to 10-fold more H2O2 was needed to induce detectable DNA damage in thyrocytes. At H2O2 and radiation doses incurring double-strand breaks (DSB), cell death occurred after 24hrs in T-cells, but not in thyrocytes. We next prepared thyroid and T-cells primary cultures from 8 donors operated for non-cancerous pathologies and profiled their genome-wide transcriptional response 4hr after: 1) exposure to 1 Gy radiation, 2) treatment with H2O2, or 3) no treatment. Two H2O2 doses were investigated, calibrated in each cell type as to elicit levels of single- and double-strand breaks equivalent to 1 Gy γ-radiation. The transcriptional responses of thyrocyte and T-cells to radiation were similar, involving DNA repair and cell death genes. In addition to this transcriptional program, H2O2 also upregulated antioxidant genes in thyrocytes, including glutathione peroxidases (GPx) at the DSB-inducing dose. By contrast, a transcriptional storm involving thousands of genes was raised in T-cells. Finally, we showed that GPx inhibition reduced the DNA damaging effect of H2O2 in thyrocytes. We conjecture that defects of anti- H2O2 protection could promote spontaneous thyroid cancers. |
| 1029 | GSE17639 |
Profile | RNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets Affymetrix HG-U133Plus 2.0 arrays were hybridized with probe from total RNA isolated from blood sampled from 6 umbilical cords and 6 healthy adult humans. |
| 1030 | GSE24493 |
Profile | The Philadelphia chromosome (Ph) encodes the oncogenic BCR-ABL1 tyrosine kinase which is present in almost every patient with chronic myeloid leukemia. In this study, the tyrosine kinase inhibitor Imatinib was used for pharmacological inhibition of BCR-ABL1. Gene expression profiles of CML cell lines were analyzed in response to Imatinib treatment. |
| 1031 | GSE28167 |
Profile | The goal of this experiment was to compare the gene expression of glioma cells migrating on substrates of different topographies and to determine a migration-associated gene profile. Human malignant glioma U251MG cells were cultured on highly-aligned versus randomly-oriented electrospun nanofibers of poly-caprolactone. Cells migrated actively on aligned nanofibers but motility was very restricted on randomly-oriented fibers. Results of gene expression profiling indicated upregulation of a JAK/STAT signature in actively migrating glioma cells. |
| 1032 | GSE7010 |
Profile | The purpose of this study was to characterize global gene expression in human airway epithelial cells and identify cellular pathways associated with coarse fine and ultrafine particulate matter (PM) exposures. Ambient PM was collected in 3 different size fractions from Chapel Hill air, particles were extracted from foam or filter matrices and lyophilized. Human primary airway epithelial cells were exposed to particles at 250μg/ml or vehicle control for 6h in culture. Following exposure, RNA was isolated and hybridized to human HG U133A affymetrix chips. Keywords: particle treatment |
| 1033 | GSE35283 |
Profile | Highly pathogenic influenza virus inhibit Inflammatory Responses in Monocytes via Activation of the Rar-Related Orphan Receptor Alpha (RORalpha). Low (PR8) and high pathogenic influenza viruses (FPV and H5N1) were used. |
| 1034 | GSE36824 |
Profile | Copy number and expression profiling of multiple myeloma patients at multiple stages of their individual clinical course Identification of evolutionary patterns in multiple myeloma |
| 1035 | GSE23952 |
Profile | TGF-beta treatment of Panc-1 pancreatic adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells lose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets using standard techniques. |
| 1036 | GSE47172 |
Profile | There is differential expression of genes between cases and controls using microarray analysis and genes that are crucial for host defence responses are significantly up-regulated in cases during pneumococcal infection. |
| 1037 | GSE33298 |
Profile | Genetic mutations on leucine-rich repeat kinase 2 (LRRK2) have been associated with an increased risk of Parkinson's disease. The Gly2019Ser (G2019S) mutation on LRRK2 gene is a relatively common cause of familial Parkinson's disease in Caucasian population. In this study we generated human induced pluripotent stem cell (iPSC) lines from LRRK2 (G2019S) bearing patient fibroblasts by cell reprogramming. We performed global gene expression profiling of LRRK2 (G2019S) heterozygous and homozygous patient iPSC lines, and the corresponding fibroblast lines they originated from. An age-matched wildtype human fibroblast line and H1 human embryonic stem cell (ESC) line were used as controls. |
| 1038 | GSE12585 |
Profile | Little is known about alteration of the global gene expression by cigarette smoke (CS) and few biomarkers for smoking-related harm are available. We used Affymetrix HG-U133A GeneChips to measure the transcriptomes in lymphocytes of 23 current healthy smokers. When heavy smokers were compared with light smokers 311 genes demonstrated a significant difference in mRNA expression of their blood lymphocytes. Keywords: dose response |
| 1039 | GSE5145 |
Profile | Studied gene regulation in bronchial smooth muscle cells following vitamin D stimulation. Keywords: comparison |
| 1040 | GSE41856 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1041 | GSE15749 |
Profile | In current study DES could effectively suppress the expression of miR-9-3 through the ERa-dependent epigenetic machinery in MDECs and MCF-7 cells. We want to figure out the biological significance and the potential targets of miR-9-3 and the related signaling cascades. |
| 1042 | GSE12109 |
Profile | In this study we shought to identify the cytokines produced by skin-resident T cells in normal skin, localize the receptors for these cytokines, and examine how these cytokines alter gene expression profiles of the cells bearing cognate receptors. Keywords: repeated measures experiment |
| 1043 | GSE17368 |
Profile | Chondrocytes from extra fingers exhibited a high proliferative capacity: the cells reached to population doublings (PD) 30-35 within 4 weeks before replicative senescence. The propagated cells formed hyaline cartilage at 2 weeks after subcutaneous implantation of NOD/Scid/IL-2 receptor gamma knock out (NOG) mice and the generated cartilage showed enchondral ossification at 8 to 12 weeks. The cartilage formation with osteogenesis depends on the number of cell division in vitro. Keywords: NCCH BioResource |
| 1044 | GSE43257 |
Profile | We show that Retinal pigment epithelium (RPE) secreted-factor pigment epithelium derived factor (PEDF) secreted/derived from primary or iPSC-derived retinal pigment epithelium (RPE)RPE, dramatically inhibitsed the cell growth of iPSCs. PEDF was detected abundantly in culture supernatant media of primary and iPSC-derived RPE. We examined the gene expression in primary RPE and iPS-derived RPE. |
| 1045 | GSE14924 |
Profile | Work previously published by our group has demonstrated that T cells from patients with chronic lymphocytic leukaemia (CLL) show differentially regulated genes compared with healthy T cells. This study was initiated to examine if these gene expression changes were unique to CLL T cells or common to an alternative leukaemia acute myeloid leukaemia (AML). Keywords: Comparison of immune cells in health and disease |
| 1046 | GSE13309 |
Profile | Polycomb-mediated repression of Dkk-1 activates Wnt signaling and enhances tumorigenic potential of lung cancer cells following tobacco smoke exposure Keywords: tobacco Smoke lung cancer, epigenetics |
| 1047 | GSE23434 |
Profile | Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases is not fully understood. The knowledge of global gene expression will help us to devlop early diagnostic biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB153 on human Kidney cells leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. Keywords: time course |
| 1048 | GSE9492 |
Profile | Specific early diagnosis of renal allograft rejection is gaining importance in the current trend to minimize and individualize immunosuppression. Gene expression analyses could contribute significantly by defining “molecular Banff” signatures. Several previous studies have applied transcriptomics to distinguish different classes of kidney biopsies. However the heterogeneity of microarray platforms, clinical samples and data analysis methods complicates the identification of robust signatures for the different types and grades of rejection. To address these issues, a comparative meta-analysis was performed across five different microarray datasets of heterogeneous sample collections from two published clinical datasets and three own datasets including biopsies for clinical indications, protocol biopsies, as well as comparative samples from non-human primates (NHP). This work identified conserved gene expression signatures that can differentiate groups with different histopathological findings in both human and NHP, regardless of the technical platform used. The marker panels comprise genes that clearly support the biological changes known to be involved in allograft rejection. A characteristic dynamic expression change of genes associated with immune and kidney functions was observed across samples with different grades of CAN. In addition, differences between human and NHP rejection were essentially limited to genes reflecting interstitial fibrosis progression. This data set here comprises a small validation batch of renal allograft biopsies for clinical indications plus control normal kidney samples from patients at Hôpital Tenon, Paris (second batch) that complements the first batch of 60 samples. We used microarrays to identify different gene expression signatures of renal allograft biopsies that can classify them according to different types of allograft rejection or CAN. Keywords: disease state analysis |
| 1049 | GSE18608 |
Profile | Bone marrow-derived progenitor cells are under investigation for cardiovascular repair but may be altered by disease. We identified 82 differentially expressed genes in CD133+ cells from patients with coronary artery disease (CAD) versus controls, of which 59 were found to be up-regulated and 23 down-regulated. These genes were found to be involved in carbohydrate metabolism, cellular development and signaling, molecular transport and cell differentiation. Following completion of an exercise program, gene expression patterns resembled those of controls in 7 of 10 patients. |
| 1050 | GSE2513 |
Profile | Gene Expression profiling of pterygium. Analysis of conjunctiva and pterygium samples. Keywords = pterygium Keywords: repeat sample |
| 1051 | GSE11506 |
Profile | Estrogen receptor-{alpha} (ER{alpha}) and its ligand estradiol play critical roles in breast cancer growth and are important therapeutic targets for this disease. Using chromatin immunoprecipitation (ChIP)-on-chip ligand-bound ER{alpha} was recently found to function as a master transcriptional regulator via binding to many cis-acting sites genome-wide. Here, we used an alternative technology (ChIP cloning) and identified 94 ER{alpha} target loci in breast cancer cells. The ER{alpha}-binding sites contained both classic estrogen response elements and nonclassic binding sequences, showed specific transcriptional activity in reporter gene assay, and interacted with the key transcriptional regulators, including RNA polymerase II and nuclear receptor coactivator-3. The great majority of the binding sites were located in either introns or far distant to coding regions of genes. Forty-three percent of the genes that lie within 50 kb to an ER{alpha}-binding site were regulated by estradiol. Most of these genes are novel estradiol targets encoding receptors, signaling messengers, and ion binders/transporters. mRNA profiling in estradiol-treated breast cancer cell lines and tissues revealed that these genes are highly ER{alpha} responsive both in vitro and in vivo. Among estradiol-induced genes, Wnt11 was found to increase cell survival by significantly reducing apoptosis in breast cancer cells. Taken together, we showed novel genomic binding sites of ER{alpha} that regulate a novel set of genes in response to estradiol in breast cancer. Our findings suggest that at least a subset of these genes, including Wnt11, may play important in vivo and in vitro biological roles in breast cancer. Keywords: time course |
| 1052 | GSE41599 |
Profile | Transcriptome profile of highly purified multipotential (P) erythroid (E), and myeloid (M) bone marrow progenitors from three RPS19 mutated Diamond-Blackfan anemia and six control human subjects. |
| 1053 | GSE13762 |
Profile | We have carried out global gene expression analysis to clarify the interrelationship between 125-dihydroxyvitamin D3 and differentiation-driven gene expression patterns in developing human monocyte-derived dendritic cells. Monocytes were treated with 10 nM 1,25-dihydroxyvitamin D3 or vehicle 14 hours after plating for 12 hours or 5 days. Monocytes, differentiating dendritic cells (+/-1,25-dihydroxyvitamin D3 for 12 hours) and immature dendritic cells (+/-1,25-dihydroxyvitamin D3 for 5 days) were harvested. This design allows one to identify genes regulated by differentiation and/or 1,25-dihydroxyvitamin D3 in human monocyte-derived dendritic cells. |
| 1054 | GSE14098 |
Profile | Gene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy. |
| 1055 | GSE26104 |
Profile | We aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis. |
| 1056 | GSE18632 |
Profile | TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementias and amyotrophic lateral sclerosis. Besides aggregation of TDP-43 loss of nuclear localization is observed in disease. To identify relevant targets of TDP-43, we performed an expression profiling study. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered upon TDP-43 silencing on mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl-tubulin. Expression of wild-type but neither RNA-binding- nor nuclear-localization-deficient TDP-43 restored HDAC6 expression. Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster also showed HDAC6 mRNA decrease. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, downregulation of HDAC6 reduced aggregate formation and increased cytotoxicity of expanded poly-glutamine ataxin-3 in TDP-43 silenced cells. This was completely restored by co-transfection with HDAC6. In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis. |
| 1057 | GSE17189 |
Profile | Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype. |
| 1058 | GSE15543 |
Profile | Pancreatic islet transplantation as a cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of beta cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols and their potential for differentiation into functional beta cells, remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and attempted re-differentiation. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at re-differentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increases our understanding of the active pathways in expanded and re-differentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore beta cell mass in T1D patients. |
| 1059 | GSE45197 |
Profile | The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1) which is mutated in multiple human cancers. Here we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen dose-dependently blocked the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9M3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant - but not IDH1-wildtype – glioma cells without appreciable changes in genome wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects. |
| 1060 | GSE27220 |
Profile | Vitamin D may have anti-tumorigenic actions by influencing the gene expression profile of target tissues which possess vitamin D receptors. We used a more physiological in vitro model, represented by short-term culture of breast cancer tissue slices, to study the transcriptional effects of a near physiological concentration of calcitriol. Methods. Breast cancer fragments were sliced and maintained in culture for 24 hours in the presence or absence (control) of calcitriol 0.5nM or 100nM (called physiological or supra-physiological concentrations). Five and 16 samples were included in a test or validation group and gene expression was analyzed by microarray (using SAM paired analysis) or qPCR, respectively. Results. Nine genes were regulated by calcitriol 0.5nM including CYP24A1, DPP4, EFTUD1 (FDR£0.01), which were up-modulated. However, using a less stringent FDR value (0.25) 61 genes were differentially expressed. Among the down-regulated transcripts were members of the MHC class II complex (HLA-DPA1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB3) and IgG binding (FCGR2A, FCGR2B, FCGR2C). There was an enrichment of genes presenting transcription factor binding sites for vitamin D, among the up-regulated genes and for interferon regulatory factor IRF1, among the down-regulated genes. Analyzing calcitriol supra-physiological effects, a more impressive transcriptional modulation was identified and 136 and 60 genes (FDR 0.1) were more and less expressed in treated samples. Up-regulated genes were involved in vitamin metabolic process, regulation of leukocyte-mediated immunity and positive regulation of alpha-beta T cell activation. Many of the induced genes were already reported as vitamin D responsive genes, including CD14, which was also up-regulated in another set of 16 samples. Genes modulated by both calcitriol concentrations were CYP24A1, DPP4, CA2 (these three in both sets of samples), EFTUD1, TKTL1, KCNK3. Conclusion. Small increments in calcitriol concentration, within the physiological range, for a relatively short period of time may exert transcriptional effects in breast cancer samples. Further studies employing physiological concentrations of vitamin D for longer periods of time may help to elucidate the hormone effects in breast cancer treatment and prevention. |
| 1061 | GSE29246 |
Profile | Monastrol treatment of Leishmania donovani infected macrophages |
| 1062 | GSE2489 |
Profile | Cultured keratinocytes treated with TNFa in the presence or absence of NFkB inhibitor; time course 1 4, 24 & 48 hrs. Keywords = Epidermis Keywords = skin Keywords = keratinocytes Keywords = inflammation Keywords = NFkB Keywords = TNFa Keywords: time-course |
| 1063 | GSE3077 |
Profile | The growth in popularity of RNA expression microarrays has been accompanied by concerns about the reliability of the data especially when comparing between different platforms. Here we present an evaluation of the reproducibility of microarray results using two platforms Affymetrix GeneChips and Illumina BeadArrays. The study design is based on a dilution series of two human tissues (blood and placenta), tested in duplicate on each platform. By a variety of measures the two platforms yielded data of similar quality and properties. The results of a comparison between the platforms indicate very high agreement, particularly for genes which are predicted to be differentially expressed between the two tissues. Agreement was strongly correlated with the level of expression of a gene. Concordance was also improved when probes on the two platforms could be identified as being likely to target the same set of transcripts of a given gene. These results shed light on the causes or failures of agreement across microarray platforms. The set of probes we found to be most highly reproducible can be used by others to help increase confidence in analyses of other data sets using these platforms. Keywords: Dilution series, platform comparison, Affymetrix, Illumina |
| 1064 | GSE29959 |
Profile | Analysis of five Notch signaling-dependent human T-ALL cell lines (ALLSIL DND41, HPBALL, KOPTK1, TALL-1) treated with gamma-secretase inhibitor (GSI) to block Notch signaling. Samples include parental cells, cells rescued by retroviral transduction with ICN (a GSI-independent form of activated Notch1), and cells retrovirally transduced with c-Myc (an important downstream target of Notch1). Results allow segregation of bona fide Notch targets from other genes affected by gamma-secretase inhibition as well as from targets downstream of c-Myc. |
| 1065 | GSE34972 |
Profile | One of the long-standing goals in the field has been to establish a culture system that would allow maintenance of HSC properties ex vivo. In the absence of such system the ability to model human hematopoiesis in vitro has been limited, and there has been little progress in the expansion of human HSCs for clinical application. To that end, we defined a mesenchyml stem cell co-culture system for expansion of clonally multipotent human HSPCs that are protected from apoptosis and immediate differentiation, and retain the HSPC phenotype. By performing a genome-wide gene expression analysis of purified HSPCs isolated at different stages of co-culture, we asked at the molecular level, to what degree hematopetic stem cell properties can be preserved during culture. This temporal gene expression data from in vivo derived- and ex vivo expanded human HSPCs will serve as a resource to identify novel regulatory pathways that control HSC properties, and to develop clinically applicable protocols for HSC expansion. |
| 1066 | GSE14001 |
Profile | Objective: Ovarian tumors of low-malignant potential (LMP) and low-grade serous ovarian carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from that of high-grade serous ovarian carcinoma. Past studies have utilized gene expression profiles to support this theory. The objective of the current study was to identify new genes whose expression profiles in LMP ovarian tumors and low-grade ovarian carcinomas differ from that in high-grade ovarian carcinomas. Methods: We used RNA from 3 normal human ovarian surface epithelia (HOSE) and from 10 low-grade and 10 high-grade serous ovarian carcinoma samples to perform gene expression profiling. Using real-time reverse-transcription polymerase chain reaction (RT-PCR) we evaluated changes in PAX2 mRNA expression in cDNA created from RNA extracted from an independent set of ovarian tissue samples (7 LMP tumors and 17 low-grade and 23 high-grade serous carcinomas). We also examined PAX2 expression using Western blot analysis of protein extracted from a set of ovarian LMP and low- and high-grade carcinoma tissue samples. Additionally, we used immunohistochemistry (IHC) to validate PAX2 overexpression in a third independent set of paraffin ovarian tissue sections from 17 LMP tumors and 16 low- and 257 high-grade carcinomas. Results: Gene profiling revealed higher expression of PAX2 in low-grade than in high-grade ovarian carcinomas. Real-time RT-PCR demonstrated a statistically significant difference in median PAX2 mRNA expression, expressed as fold change, among ovarian LMP tumor (1837.38), low-grade (183.12), and high-grade (3.72) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian LMP and low-grade carcinoma samples but no PAX2 protein expression in high-grade carcinomas. On IHC, more LMP tumor and low-grade carcinoma samples expressed moderate to high levels of PAX2 than did high-grade ovarian carcinoma samples. The numbers of samples with strong nuclear staining was significantly higher for ovarian LMP tumors (10 of 17, p<0.001) and low-grade serous carcinomas (10 of 16, p<0.001) than for high-grade carcinomas (27 of 257). Discussion: Our identification and validation of higher PAX2 expression in ovarian LMP tumors and low-grade serous carcinomas than in high-grade carcinomas supports the two-tiered hypothesis that the first two are on a continuum and are distinct from high-grade ovarian carcinomas. PAX2 may represent a potential biomarker and future therapeutic target for individualizing chemotherapy for ovarian LMP tumors and low-grade carcinomas in the future. |
| 1067 | GSE27318 |
Profile | Analysis of differential expression genes in NESG1-overexpressed and negative nasopharyngeal carcinoma. NESG1 is a candidate tumor suppressor in NPC. Results provide insight into the molecular pathogenesis of NESG1 in NPC. |
| 1068 | GSE32052 |
Profile | Psoriasin (S100A7) has been shown to be highly expressed in invasive estrogen receptor negative breast cancers. Expression of S100A7 in human breast tumors represents a poor prognostic marker and correlates with lymphocyte infiltration in high-grade morphology. Recent studies have shown that S100A7 downregulation in ERα- cells lines inhibits tumor growth in in vivo mouse model systems. However not much is known about its mechanisms in regulating breast cancers. We used microarrays to determine the global differential gene expression in S100A7 overexpressing breast cells and vector control cells and found out that most of the genes involved in inflammatory pathways were differentially regulated. |
| 1069 | GSE29712 |
Profile | Copy number and Gene expression profiling of HT-29 wild-type and bortezomib resistant cell lines Identification of mechanisms of bortezomib resistance |
| 1070 | GSE2842 |
Profile | Glucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of Peripheral blood lymphoblasts purified at three time points (0h, 6-8h, 24h after treatment initiation) from 13 children under therapy for ALL . Treated samples were compared to untreated (0h). For comparison, expression profiles were generated from an adult ALL patient, peripheral blood lymphocytes from GC-exposed healthy donors, GC-sensitive and -resistant ALL cell lines and mouse thymocytes treated with GC in vivo and in vitro. This second series comprises the additional samples mentioned above. Findings. An essentially complete list of GC-regulated candidate genes in clinical settings experimental and was generated, enabling immediate analysis of any gene with respect to its potential significance for GC-induced apoptosis in these systems. Gene regulations previously thought responsible for cell death in experimental systems were reconfirmed in few children only. In contrast, a small number of genes, most not implicated in GC-induced apoptosis previously, were co-ordinately regulated in the majority of children. Keywords: treatment response |
| 1071 | GSE31434 |
Profile | We identified SLC44A5 as a gene associated with birth weight in cattle based on genome wide association studies. To identify the mechanisms involved in growth and choline transporter we performed genome-wide mRNA expression analysis in HeLa cells transfected with SLC44A5. |
| 1072 | GSE42253 |
Profile | Hsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells. |
| 1073 | GSE5040 |
Profile | Lymphoblast cells from a patient with Freidriech's Ataxia were incubated with pyrrole-imidazole polyamides targeted to the GAA triplet repeat in the intron 1. The polyamides were shown in cell culture to increase levels of endogenous frataxin mRNA. A normal sibling derived lymphoblast cell line was used as a control. Keywords: human lymphoblast cells |
| 1074 | GSE13504 |
Profile | The p53 family consists of three members p53, p73, and p63. These proteins share a high degree of amino-acid sequence similarity and major functional domains. The p53 gene, the first member of the family to be identified, is the most frequent target gene for genetic alterations in human cancers. In contrast, p73 and p63 are mainly involved in normal development and differentiation. These differences among the p53 family are likely to depend on activation or repression of different sets of target genes. In this study, to identify targets specifically regulated by p73, we performed microarray analysis and compared expression patterns in a human steosarcoma cell line Saos-2 infected separately with p53 and TAp73beta expressing adenovirus. |
| 1075 | GSE12274 |
Profile | In this series we have analyzed the effect of donor age on the gene expression profile of mesenchymal stromal cells (alternatively named mesenchymal stem cells; MSC) from human bone marrow. Cells were taken from bone marrow aspirates from iliac crest (BM) of healthy donors or from the caput femoris (HIP) of elderly patients that received femoral head prosthesis. |
| 1076 | GSE29628 |
Profile | The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF-1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon-inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen. |
| 1077 | GSE1428 |
Profile | This series includes the global gene expression profile of the vastus lateralis muscle for 10 young (19-25 years old) and 12 older (70-80 years old) male subjects. Keywords: other |
| 1078 | GSE27973 |
Profile | This study was performed to test the hypothesis that cigarette smoke extract would alter the responses of primary cultures of human bronchial epithelial cells to infection with purified human rhinovirus 16. The data show marked alterations in rhinovirus-induced expression profiles of a number of genes in the presence of cigarette smoke extract (CSE). |
| 1079 | GSE12791 |
Profile | Acquired drug resistance represents a major challenge in chemo-therapy treatment for various types of cancers. We have found that the retinoid X receptor–selective agonist bexarotene (LGD1069 Targretin) was efficacious in treating chemo-resistant cancer cells. The goal of this microarray study was to understand the mechanism of bexarotene’s role in overcoming acquired drug resistance using human breast cancer cells MDA-MB-231 as a model system and paclitaxel as model compound. After MDA-MB-231 cells were repeatedly treated with paclitaxel for 8 cycles with each cycle including a 3-day treatment with 30 nM paclitaxel and followed by a 7-day exposure to control medium, MDA cells resistant to paclitaxel were developed and their growth was no longer inhibited by paclitaxel treatment. Those MDA cells with acquired drug resistance, when treated with paclitaxel and bexarotene in combination, could regain their sensitivity and their growth were again inhibited. Therefore, RNA samples from parental MDA-MB-231 cells, paclitaxel-resistant MDA cells treated with vehicle, paclitaxel alone or in combination with bexarotene, were used for perform global gene expression profiling with Affymetrix HG-U133A gene chips. Keywords: Drug Treatment |
| 1080 | GSE12504 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1081 | GSE35006 |
Profile | The ts-p53 E285K protein is a rare p53 mutant with temperature-sensitive (ts) loss of function characteristics. In cancer cells which express ts-p53 E285K intriniscally, endogenous wild type p53 activity is reconstituted by appropriate cultivation temperature (permissive condition). At non-appropriate cultivation temperature (restrictive condition) this p53 mutant is inactive. The present study took advantage of this mechanism and employed IPH-926 lobular breast cancer cells and BT-474 ductal breast cancer cells, which both harbor endogenous ts-p53 E285K, for the transcriptional profiling of p53-responsive genes. This new approach eliminated the need for genetic modification or cytotoxic stimulation to achive a p53 response in the cells being investigated . |
| 1082 | GSE39001 |
Profile | The effect of preventive vaccination against Human Papillomavirus (HPV) in reducing the burden of cervical cancer (CC) will not be seen before 30 years. It is still necessary to improve the procedures of screening and treatment against CC. Current methods for screening have low sensitivity (Pap test) or specificity (HPV tests) to detect high-grade cervical intraepithelial neoplasias (CIN) and CC (CIN2+). The objective of this study was the identification and characterization of cellular targets present in most CC and absent in normal cervical tissue that can be considered as potential markers for screening or therapeutic targets. Methods and Findings. A pyramidal strategy was used. Initially the expression of 8638 genes was compared between 43 HPV16-positive CC and 12 healthy cervical epitheliums using the HG-Focus microarray. The expression intensity of 8,370 genes was validated in 24 samples with a second microarray (HG-ST1.0). A total of 997 genes were deregulated in CC and the 21 best ranked were validated and confirmed by qRT-PCR in 67 CC and 25 controls. According to the ROC analysis and the fold change (FC), the best (AUC ≥ 0.97 and FC ≥ 10) six genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored by qRT-PCR in 29 CIN1 and 21 CIN2/3 lesions to investigate whether they could differentiate CIN2+ from CIN1 and healthy cervical epitheliums (CIN1-). Three of these genes were associated exclusively with invasive tumors (CCNB2, PRC1, SYCP2) and three (CDC20, NUSAP1, CDKN3) also with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1, along with CDKN2A, to detect CIN2+ was around 90%. The protein codified by these genes was confirmed by immunohistochemistry in CC. The effect of these markers on the survival was investigated in 40 CC patients followed by 42 months. Only high-expression level of CDKN3 was associated with a poor survival (20%; p = 2 x 10-4, Long-rank test) and it was independent from FIGO staging. Conclusions. CDKN3 and NUSAP1, together with CDKN2A, may be potential targets for development of screening methods. However, further studies are needed from a screening population to define the optimal trade-off between sensitivity and specificity for detection of CIN2+. CDKN3 may be also considered as a survival marker. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be a potential therapeutic target in CC. However, it´s still necessary to demonstrate whether it´s indispensable for tumor growth. |
| 1083 | GSE28442 |
Profile | BACKGROUND: Regional lymph node (LN) status is a well-known prognostic factor for vulvar carcinoma (VC) patients. Although the reliable LN assessment in VC is crucial it presents significant diagnostic problems. PURPOSE: We aimed to identify specific mRNA markers of VC dissemination in the LN and to address the feasibility of predicting the risk of nodal recurrence by the patterns of gene expression. EXPERIMENTAL DESIGN: Sentinel and inguinal LN samples from 20 patients who had undergone surgery for stage T1-3, N0-2, M0 primary vulvar squamous cell carcinoma were analyzed. Gene expression profiles were assessed in four metastatic [LN(+)] and four histologically negative [LN(-)] lymph node samples obtained from four VC patients, by the Affymetrix U133 Plus 2.0 gene expression microarrays. Of the set of genes of the highest expression in the metastatic LNs compared to LN(-), seven candidate marker genes were selected PERP, S100A8, FABP5, SFN, CA12, JUP and CSTA, and the expression levels of these genes were further analyzed by the real-time reverse transcription polymerase chain reaction (qRT-PCR) in 71 LN samples. RESULTS: Five of the genes, PERP, S100A8, FABP5, SFN and CA12, were significantly increased in LN(+) compared to LN(-) samples. In the initial validation of the seven putative markers of metastatic LN, the Cox proportional hazard model pointed to SFN and CA12 expression to significantly relate to the time to groin recurrence in VC patients. CONCLUSIONS: PERP, S100A8, FABP5, SFN and CA12 have a potential of marker genes for the molecular testing of LN involvement in VC patients. |
| 1084 | GSE40960 |
Profile | BMP9 signaling has been implicated in hereditary hemorrhagic telangiectasia and vascular remodeling acting via the HHT target genes, endoglin and ALK1. This study sought to identify endothelial BMP9-regulated proteins that could affect the HHT phenotype. Gene ontology analysis of cDNA microarray data obtained following BMP9 treatment of primary human endothelial cells indicated regulation of chemokine, adhesion, and inflammation pathways. |
| 1085 | GSE34880 |
Profile | Reversing gene expression signatures in relapsed patient may restore chemosensitivity. We demonstrate that the histone deacetylase inhibitor vorinostat not only reprograms the aberrant gene expression profile of relapsed blasts but is synergistic when applied prior to chemotherapy in primary patient samples and leukemia cell lines |
| 1086 | GSE1577 |
Profile | T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are often thought to represent a spectrum of a single disease. The malignant cells in T-ALL and T-LL are morphologically indistinguishable and they share the expression of common cell surface antigens and cytogenetic characteristics. However, despite these similarities, differences in the predominant sites of disease in T-ALL and T-LL are observed. To determine if underlying biological distinctions may potentially contribute to some of these differences, we analyzed the global gene expression profiles of malignant T-cell precursors in ten T-ALL and nine T-LL using DNA arrays. Ten additional B-precursor ALL bone marrow samples, were used in a separate analysis. Keywords: ordered |
| 1087 | GSE21935 |
Profile | Transcriptional analysis of the superior temporal cortex (BA22) in schizophrenia: Pathway insight into disease pathology and drug development Schizophrenia is a highly debilitating psychiatric disorder which is known to have heritable genetic and environmental components. To gain some insight into the mechanisms underpinning both positive and negative symptoms of the disease we determined the genome wide expression of mRNA transcripts in post-mortem tissue from the superior temporal cortex (Brodmann Area 22, BA22) in schizophrenic and control patients. The BA22 region is known to mediate the positive pathophysiology of schizophrenia; we compared this to the anterior prefrontal cortex (BA10) from the same subjects, which is known to mediate negative symptoms. Following adjustments for confounding clinical, sample and experimental sources of variation, we carried out gene set enrichment analysis in each region using pathway data. We identified an over-representation of genes involved in cytoskeletal remodelling, neurodevelopment, cell adhesion, cellular signalling, neurotransmission and autophagy. Collectively our analysis indicates a disruption of processes underpinning synaptic plasticity in both regions. Region-specific changes support the dysregulation of distinct pathways in the BA10 and BA22 regions. This may highlight new therapeutic opportunities to treat both negative and positive symptoms of the disease. |
| 1088 | GSE8840 |
Profile | Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma and resembles developing skeletal muscle. Specific genomic alterations including translocations deletions and amplification events have been associated with the alveolar and embryonal subtypes of RMS. Characterizing these changes has led to increased understanding of the underlying molecular biology. However, further aberrations and their significance remain to be defined. Genomic copy number variations have been shown to affect the level of transcription in several tumor types. In this study, we have combined array comparative genomic hybridization analysis of 13 RMS cell lines, supported by confirmatory PCR analyses, with their corresponding expression profiles. This identified sets of genes that are altered in their level of expression by genomic imbalances. We also show that the effect on gene expression was proportional to the level of genomic gain or loss. Keywords: Rhabdomyosarcoma cell lines |
| 1089 | GSE28133 |
Profile | We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment. Data analysis reveals major involvement of the immune response in the disease and interindividual variation was monitored to unravel a second crucial aspect of the pathological process the death of photoreceptor cells. |
| 1090 | GSE37645 |
Profile | Pancreatic ductal adenocarcinoma (PDAC) is a nearly uniformly lethal malignancy with most patients facing an adverse clinical outcome. Given the pivotal role of aberrant Notch signaling in the initiation and progression of PDAC, we investigated the effect of MRK-003, a potent and selective γ-secretase inhibitor, in preclinical PDAC models. We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts, to determine whether pharmacological targeting of the Notch pathway could inhibit pancreatic tumor growth and potentiate gemcitabine sensitivity. In vitro, MRK-003 treatment downregulated the canonical Notch target gene Hes-1, significantly inhibited anchorage independent growth, and reduced the subset of CD44+CD24+ and aldehyde dehydrogenase (ALDH)+ cells that have been attributed with tumor initiating capacity. Ex vivo pretreatment of PDAC cells with MRK-003 in culture significantly inhibited the subsequent engraftment in immunocompromised mice. In vivo, MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) patient-derived PDAC xenografts. Moreover, a combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine alone in 4 of 9 (44%) PDAC xenografts. Baseline gene expression analysis of the treated xenografts indicated that upregulation of nuclear factor kappa B (NFκB) pathway components was associated with the sensitivity to single MRK-003, while upregulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. The preclinical findings presented here provide further rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC. |
| 1091 | GSE7637 |
Profile | Human mesenchymal stem cells are expected to be a useful tool for cellular therapy. We used microarrays to detail the gene expression profiles and selected candidate biomarkers that indicate the culture stage of the cells. Keywords: mesenchymal stem cells passage numbers |
| 1092 | GSE11024 |
Profile | Analysis of adult and childhood tumors reveals activation of an E2F3 signature unique to Wilms tumors. Keywords: Disease state analysis |
| 1093 | GSE43124 |
Profile | Bortezomib-based secondary induction therapy and mobilization could represent alternative strategies to reduce tumor burden. We used microarrays to investigate genome-wide expression changes between bortezomib and non-bortzomib mobilizaton strategies and identified distinct genes and pathways that were significantly differentially regulated. |
| 1094 | GSE470 |
Profile | The exacerbation of disease in asthmatics has been linked to both exposure to environmental agents as well as to the presence of virus in airways particularly rhinovirus. The hypothesis tested in these experiments is that differences in gene expression profiles in epithelial cells derived from asthmatic and normal airways can be linked to enhanced responsiveness of the epithelium in its pro-inflammatory, immulogic or other activities that may lead to the exacerbation of disease. Keywords: other |
| 1095 | GSE24422 |
Profile | There are an estimated 21million diabetics in the United States and 150 million diabetics worldwide. The World Health Organization anticipates that these numbers will double in the next 20 years. Metabolic syndrome is a well recognized set of symptoms that increases a patient’s risk of developing diabetes. Insulin resistance is a factor in both metabolic syndrome and Type 2 diabetes. It is characterized by decreased insulin stimulated glucose uptake in peripheral tissues decreased adiponectin levels, increased adipocyte FFA and cytokine production, and increased insulin and hepatic glucose output. Prevention or reversal of insulin resistance should serve as an important strategy in addressing the growing health concerns posed by the Diabetes epidemic. While increased adiposity is associated with insulin resistance, the role of the cell types present within adipose (adipocytes, pre-adipocytes, endothelial cells, macrophages, fibroblasts, leukocytes and smooth muscle cells) in insulin resistance is unclear. In an effort to begin dissection of this question, we examined the transcriptional response of the buoyant and non-buoyant fractions isolated from insulin sensitive or TNF induced insulin resistant hMSC derived adipocytes before and after treatment with insulin. |
| 1096 | GSE19627 |
Profile | Monocytes are key players in inflammatory processes which are triggered by lipopolysaccharide (LPS) the major outer membrane component of gram-negative bacteria. The present study in human monocytic THP-1 cells was designed in order to identify LPS-inducible genes which are down-regulated by the reduced form of CoQ10 (ubiquinol, Q10H2). For this purpose, THP-1 cells were incubated with 10 µM Q10H2 for 24 h. Subsequently, cells were stimulated for 4 h with 1µg/ml LPS and the resulting gene expression levels were determined using microarrays. 14 LPS-inducible genes were identified to be significantly (p < 0.05) down-regulated by Q10H2 pre-treatment between a factor of 1.32 and 1.65. The strongest effect of Q10H2 incubation was found for the nuclear receptor coactivator 2 gene (NCOA2). Gene Ontology (GO) terms revealed for the Q10H2-sensitive genes an involvement in e.g. signal transduction processes (CENTD1, NCOA2, PSD3, PPP2R5C), transcriptional regulation (NCOA2, POU2F1, ETV3) and cell proliferation pathways (CCDC100, EPS15). In conclusion, we provide evidence in THP-1 cells that the reduced form of CoQ10 (Q10H2) modulates LPS-induced gene expression. |
| 1097 | GSE17827 |
Profile | The pediatric tumor neuroblastoma is the second cause of cancer-related death in children. Although several recurrent gene aberrations have been found the main signaling networks in the neuroblastoma cell, that can give important clues for more specific, more efficient treatment, is still unknown. Here we demonstrate an analysis of the MEIS1 pathway in neuroblastic tumors. It suggests important regulatory connections to tumor differentiation, cell cycle, and cell death. |
| 1098 | GSE1719 |
Profile | Age-related macular degeneration has a strong epidemiological association with cardiovascular disease. One pathogenic hypothesis that applies to both diseases is the concept of an abnormal cellular response to injury resulting in a disease phenotype. It has been hypothesized that this phenotype is also present in dermal fibroblasts. This study tests this hypothesis by examination of the expression profiles of fibroblasts obtained from diseased patients and subjected to sublethal cell injury. Keywords: other |
| 1099 | GSE25330 |
Profile | M cells are the main site of bacterial translocation in the intestine. We used the in vitro M cell model to study the effect of the commensal bacteria; Lactobacillus salivarius Eschericha coli and Bacteroides fragilis, on M cell gene expression. Bacterial translocation across the gut mucosa has traditionally been based on the detection of commensals in the mesenteric lymph node. Differential rates of commensal translocation have been reported in vivo, however fewer studies have examined translocation of commensals at the level of the gut epithelial M cell. In this study we employed an in vitro M cell model to quantify translocation of various bacteria. C2BBe1 cells were differentiated into M cells and the gene expression profile and transport kinetics of different bacterial strains, namely Lactobacillus salivarius, Escherichia coli, and Bacteroides fragilis, was assessed. For comparison with M cell uptake, the THP-1 monocytic cell line was used to analyze bacterial internalization and resulting cytokine production. The commensal bacterial strains were translocated across M cells with different efficiencies; E. coli and B. fragilis translocated with equal efficiency while L. salivarius translocated with less efficiency. In contrast, L. salivarius was internalized by THP-1 cells to a higher degree than B. fragilis or E. coli and was associated with a different cytokine profile. Microarray analysis showed both common and differential gene expression amongst the bacteria and control polystyrene beads. In the presence of bacteria, but not beads, upregulated genes were mainly involved in transcription regulation and dephosphorylation, e.g. EGR1, JUN; whereas proinflammatory and stress response genes were primarily upregulated by E. coli and B. fragilis, but not L. salivarius nor beads, e.g. IL8, TNFAIP3. These results demonstrate that M cells have the ability to discriminate between different commensal bacteria and modify subsequent immune responses. |
| 1100 | GSE37418 |
Profile | Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different disease subgroups e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g., SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development. |
| 1101 | GSE33167 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1102 | GSE17044 |
Profile | Androgens are required for the development of normal prostate and they are also linked to the development of prostate cancer. We used microarrays to understand the role of androgen in an androgen dependent, androgen receptor (AR) positive human metastatic cell line, LNCaP. |
| 1103 | GSE38021 |
Profile | Previously we have shown that an AP-1 family member Fra-2, which is hardly expressed in normal mature T cells, is consistently over-expressed in adult T-cell leukemia/lymphoma (ATLL), and together with JunD, upregulates CCR4 and many other genes including proto-oncogenes c-Myb, MDM2, Bcl-6, and SOX4. SOX4 is frequently overexpressed in many solid tumors and considered to be a potential oncogene. To identify downstream target genes of SOX4 and analyze SOX4 oncogenic pathway in ATLL , we compared gene expression profiles of ST1 cells transfected with SOX4 siRNA or control siRNA using the Affymetrix high density oligonucleotide microarray. |
| 1104 | GSE27631 |
Profile | Smad1/5 are transcription factors that engage in BMP-induced transcription. We determined and analyzed Smad1/5 binding sites by ChIP-sequencing. We used expression microarrays to compare the Smad1/5 binding sites identified by ChIP-seq to BMP-induced gene expressions. |
| 1105 | GSE9576 |
Profile | We identify genes presenting a specific expression profile in midgut carcinoid cells primary carcinoids tumors and liver metastasis were gene profiled. Gene expression profiling of classical midgut carcinoid primary tumors and liver metastasis reveal potential novel therapeutic targets and molecular signatures. Keywords: disease state comparison |
| 1106 | GSE47855 |
Profile | A small subset of T cells also expresses kiler-cell immunoglobulin-like receptors (KIRs). We find that KIR+ T cells primarily reside in the CD56+ T population. However little is known on how these cells are different from the conventional CD56- T, NK, and iNKT cells. We used microarray profiling to compare and determine the distinctive differences of CD56+ T cell and its KIR subsets when compared to the conventional CD56- T, NK and iNKT cells. |
| 1107 | GSE29634 |
Profile | Neuroblastoma tumors frequently show loss of heterozygosity of chromosome 11q with a shortest region of overlap in the 11q23 region. These deletions are thought to cause inactivation of tumor suppressor genes leading to haploinsufficiency. Alternatively micro-deletions could lead to gene fusion products that are tumor-driving. To identify such events we analyzed a series of neuroblastomas by comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays and integrated these data with Affymetrix mRNA profiling data with the bioinformatic tool R2 (http://r2.amc.nl). We identified three neuroblastoma samples with small interstitial deletions at 11q23, upstream of the forkhead-box transcription factor FOXR1. Genes at the proximal side of the deletion were fused to FOXR1, resulting in fusion transcripts of MLL-FOXR1 and PAFAH1B2-FOXR1. FOXR1 expression has only been detected in early embryogenesis. Affymetrix microarray analysis showed high FOXR1 mRNA expression exclusively in the neuroblastomas with micro-deletions and rare cases of other tumor types, including osteosarcoma cell line HOS. RNAi silencing of FOXR1 strongly inhibited proliferation of HOS cells and triggered apoptosis. Expression profiling of these cells and reporter assays suggested that FOXR1 is a negative regulator of forkhead-box factor mediated transcription. The neural crest stem cell line JoMa1 proliferates in culture conditional to activity of a MYC-ER transgene. Over-expression of the wild-type FOXR1 could functionally replace MYC and drive proliferation of JoMa1. We conclude that FOXR1 is recurrently activated in neuroblastoma by intrachromosomal deletion/fusion events, resulting in over-expression of fusion transcripts. Forkhead-box transcription factors have not been previously implicated in neuroblastoma pathogenesis. Furthermore, this is the first identification of intrachromosomal fusion genes in neuroblastoma. |
| 1108 | GSE13568 |
Profile | Gene expression profiling has been widely used to screen for metastasis-associated genes by comparing the difference in paired primary and metastatic colorectal carcinomas orthotopic implantation mouse model or cells with different metastatic potential in the field of CRC research In our study, we observed that the genes differentially expressed in M5 relative to its parent SW480 cell line |
| 1109 | GSE17172 |
Profile | Human Burkitt's lymphoma ST486 cells were transduced with non-target control shRNA lentiviral vectors FOXM1 shRNA, and MYB shRNA lentiviral vectors. Total RNA was isolated 24h later. cRNA was produced with the standard one-step IVT protocol (Affymetix) and hybridized in U95Av2 gene chips (Affymetrix). |
| 1110 | GSE37290 |
Profile | Ovarian clear cell carcinoma (OCCC) is a morphologically and biologically distinct subtype of ovarian carcinomas. We previously reported a gene expression profile characteristic of OCCC (OCCC signature) which contains hepatocyte nuclear facter-1b ( HNF-1b). To elucidate the biological role of HNF-1b in OCCC, we performed the suppression of the HNF-1b expression in human ovarian cancer cell line RMG2 using short hairpin RNA. We are now evaluating the functional effect using these cells. |
| 1111 | GSE32569 |
Profile | Gene expression from pre- and post- Cediranib treated patients with metastatic Alveolar Soft Part Sarcoma (ASPS) |
| 1112 | GSE15615 |
Profile | TNFalpha and IL1beta play a pathogenic role in rheumatoid arthritis. Both cytokines are known to activate cytokine and metalloproteinase secretion by synovial fibroblasts. In the present study we wanted to investigate whether TNFalpha and IL1beta displayed differential effects on cultured Fibroblast-like Synovial Cells derived from RA patients. Global gene expression analyses indicated that both cytokines induced similar genes in these cells. |
| 1113 | GSE24473 |
Profile | RASSF1C unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells RASSF1C over-expression enhances T47D cell invasion/migration in vitro |
| 1114 | GSE16797 |
Profile | Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone. Intravenous immunoglobulin (IVIG) treatment-resistant patients are high risk of developing coronary artery lesions (CALs) with Kawasaki disease (KD). The IVIG-responsive (Group A; n = 6) and -resistant patients (Group B) were predicted before starting the initial treatment using the Egami scoring system and randomly allocated a single-IVIG treatment group (Group B1; n = 6) or a IVIG-plus-methylprednisolone (IVMP) combined therapy group (Group B2; n = 5). We investigated transcript abundance in the leukocytes of those patients using microarray analysis. Results: five patients in Group A and 1 patient in Group B1 responded to initial IVIG treatment. All Group B2 patients responded to IVIP-plus-IVMP combined therapy. Prior to performing these treatments, those transcripts related to IVIG-resistance and to the development of CALs, such as IL1R, IL18R, oncostatin M, suppressor of cytokine signaling-3, S100A12 protein, carcinoembryonic antigen-related cell adhesion molecule-1, matrix metallopeptidase-9 and polycythemia rubra vera-1 were more abundant in Group B patients in comparison to Group A patients. Moreover, those transcripts in Group B2 patients were more profoundly and broadly suppressed than Group B1 patients after treatment. Conclusion: this study elucidated the molecular mechanism of the effectiveness of IVIG-plus-IVMP combined therapy. |
| 1115 | GSE3585 |
Profile | Dilated cardiomyopathy (DCM) is a common cause of heart failure and a leading cause of cardiac transplantation in western countries. The robust predictive expression profile of cardiomyopathic and NF hearts as well as the functional classification can help to identify promising candidates for DCM and may improve the early diagnosis of cardiomyopathy. Keywords: disease state analysis |
| 1116 | GSE11408 |
Profile | Human cytomegalovirus induces a pro-inflammatory monocyte following infection. To begin to address how HCMV induces these rapid changes in infected monocytes we examined the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of pro-inflammatory genes were upregulated within 4 hours post infection. Keywords: Disease State |
| 1117 | GSE30536 |
Profile | Temporal changes of the expression levels of the complete human transcriptome during the first 24 hours following infection of IFN-pre-treated macrophages. This approach has allowed us to identify genes involved in the IFN signaling that have an impact on HIV-1 infection of macrophages KEYWORDS: time course |
| 1118 | GSE6932 |
Profile | An essential function of the human epidermis is the maintenance of a protective barrier against the environment. As a consequence keratinocytes, which make up this layer of the skin, undergo an elaborate process of self-renewal, terminal differentiation and cell death. Misregulation of these processes can lead to several human diseases including psoriasis and basal cell and squamous cell carcinomas. To identify novel regulators of keratinocyte differentiation, a cell-based screen of small molecule libraries was carried out for molecules that induce terminal differentiation of normal human epidermal keratinocytes (NHEKs). One class of molecules was identified, the 2-(3,4,5-trimethoxy-phenylamino)-pyrrolo[2,3-d]pyrimidines, which were shown to induce differentiation of epidermal progenitor cells to terminally differentiated keratinocytes. These molecules serve as useful mechanistic probes of the cellular differentiation programs that regulate the formation and homeostasis of the epidermis, and may lead to novel therapeutic approaches for the treatment of skin hyperproliferative disorders. Keywords: time course of compound treatment |
| 1119 | GSE17782 |
Profile | Autologous stem cell therapy has potential for biologic treatment of disc degeneration. Due to ease of harvest and abundance adipose-derived mesenchymal stem cells (AD-MSC) are readily available. Our objectives were: 1) To develop/validate methods to harvest AD-MSC and direct them to a disc-like phenotype by three-dimensional (3D) culture and TGF-ß3 exposure; 2) To perform gene expression profiling for human AD-MSC and annulus cells in 3D culture; 3) To test whether disc cell-AD-MSC co-culture could augment proteoglycan production. Stem cell plasticity offers potential for future biologic therapies for disc degeneration. Data indicated that human AD-MSC can successfully be manipulated in 3D culture to express gene products important in the disc ECM (types I and II collagen, chondroitin sulfate, keratin sulfate, decorin), and that co-culture of annulus cells with AD-MSC enhances proteoglycan production. Studies defined gene expression patterns of AD-MSC and human annulus cells in 3D culture, important as we explore the potential of MSC in biologic therapies for disc degeneration. |
| 1120 | GSE25300 |
Profile | Increased CREB levels and upregulation of its target genes expression resulted in increased myelopoiesis and colony formation. |
| 1121 | GSE11904 |
Profile | Human renal cell carcinomas (RCC) have differential expression of HIF-1alpha and HIF-2alpha depending on VHL genotype and other events. Here, we have divided a series of RCC samples for HIF-alpha expression and VHL genotype, in order to define differentially expressed genes Keywords: Patient Sample Study |
| 1122 | GSE15083 |
Profile | Children with oligoarticular JIA (arthritis in 4 or fewer joints) can either continue to have this mild form of arthritis (persistent oligoarticular JIA) or extend to a more sever form involving more than 4 joints (extended oligoarticular JIA) Synovial fluid mononuclear cell RNA was prepared from 21 recently diagnosed pre-treatment patients and grouped according to whether the patient had extended or persisted at one year after diagnosis |
| 1123 | GSE16066 |
Profile | A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. |
| 1124 | GSE7014 |
Profile | DM1 and DM2 biopsies from patients were compared to Normal adult individuals Keywords: 3 groups of samples |
| 1125 | GSE30439 |
Profile | In the clinical setting mutations in the CFTR gene enhance the inflammatory response to P. aeruginosa (PA01) infection, but measurements of the inflammatory response to pathogen stimulation by isolated airway epithelia can yield variable results. In this series, we exposed CFBE41o- cells over-expressing ∆F508/∆F508 CFTR and CFBE41o- cells rescued with wt-CFTR to P. aeruginosa biofilms. P. aeruginosa elicited a more robust increase in cytokine and chemokine expression (e.g., IL-8, CXCL2, CXCL3, CXCR4 and TNF-α) in CFBE-wt-CFTR cells compared to CFBE-∆F508-CFTR cells. These results demonstrate that CFBE41o- cells complemented with wt-CFTR mount a more robust inflammatory response to P. aeruginosa than CFBE41o- ∆F508/∆F508-CFTR cells. |
| 1126 | GSE5868 |
Profile | SV7tert AML cells were obtained from ATCC and cultured in Dulbecco's modified essential medium (DMEM) glutamine (4mmol) and 10% foetal bovine serum (FBS). Two million SV7tertAML cells were subcutaneously injected into nude mice either with or without subcutaneous oestrogen pellets (n=4 per group); oestrogen was added using 0.36mg 60 day release oestrogen pellets implanted sub-cutaneously. Mice were housed in pathoflex isolators at 26°C, on 12 hour light / dark cycles. Irradiated RB2 diet and autoclaved water provided ad libertum. All oestrogen treated mice inoculated with SV7tertAML cells developed subcutaneous tumours which required termination of the animals at six weeks due to tumour load. These primary tumours were removed and fragments placed subcutaneously in further nude mice which went on to develop tumours both in the presence and absence of oestrogen. Mice were weighed weekly and their clinical condition closely monitored by a trained observer. Mice were terminated individually when the tumour cross-sectional area reached 250mm2 or sooner, which has previously been seen to be below the limit of 10% of initial body weight set by the UKCCCR guidelines. Tumours were removed and a portion flash frozen in liquid nitrogen. RNA was extracted from five tumours from oestrogen treated and control animals. Equal quantities of RNA was pooled and quality checked by Agilent Bioanylyser. Experimenter name = Simon Johnson Experimenter institute = Queens Medical Centre Keywords: estrogen treatment, angiomyolipoma xenograft tumors |
| 1127 | GSE11375 |
Profile | Physiological anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. Contributor: The Inflammation and the Host Response to Injury Large Scale Collaborative Research Program Keywords: expression profiles |
| 1128 | GSE13548 |
Profile | The unfolded protein response (UPR) is a cellular defense mechanism against glucose deprivation a cell condition that occurs in solid tumors. A key feature of the UPR is the activation of the transcription program that allows the cell to cope with endoplasmic reticulum (ER) stress. We used micoarrays to show that the UPR transcription program is disrupted by the antitumor macrocyclic compound versipelostatin (VST) and antidiabetic biguanides metformin, buformin and phenformin, depending on cellular glucose availability. Keywords: stress response, drug response |
| 1129 | GSE38663 |
Profile | Background/Aims: Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C. Methods: 70 treatment-naïve patients were randomized to 4 weeks of ribavirin (1000-1200 mg/d) or none followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were randomized to undergo a liver biopsy either 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by the nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10. Results: After four weeks of ribavirin monotherapy, HCV levels decreased by 0.5±0.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting the induction of ISGs by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC. Conclusion: Ribavirin is a weak antiviral but its clinical effect in combination with PEG-IFN seems to be mediated by a separate, indirect mechanism, which may act to reset the interferon responsiveness in HCV-infected liver. Ribavirin pretreatment does not alter the clinical outcome of subsequent combination therapy. |
| 1130 | GSE12079 |
Profile | The clonal CD3- CD4+ Th2 cell population characterizing some hypereosinophilic syndrome patients stably endures for years provoking a chronic inflammatory skin disease with a subgroup of patients ultimately progressing to T-cell lymphoma. The aim of this study is the identification of the molecular changes (1) associated with the persistence of the pre-malignant clone (2) associated with the activation of co-stimulatory receptors and (3) associated with the emergence of malignant T-cell subclones. |
| 1131 | GSE20286 |
Profile | p63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates. The p63 transactivating (TA) isoforms contain an amino-terminal exon that encodes a p53-like transactivation domain whereas ΔN-isoforms lack this domain but contain the common DNA binding domain (DBD), suggesting that TAp63 and ΔNp63 isoforms may have opposing functions. By characterising transcriptional changes and cellular effects following modulation of p63 expression, we have defined a vital role for p63 in cellular adhesion. Knockdown of p63 expression caused downregulation of cell adhesion-associated genes, cell detachment and anoikis in mammary epithelial cells and keratinocytes. Conversely, overexpression of the TAp63γ or ΔNp63α isoforms of p63 upregulated cell adhesion molecules, increased cellular adhesion and conferred resistance to anoikis. |
| 1132 | GSE26969 |
Profile | The biological mechanisms by which cerebral aneurysms emerge enlarge and rupture are not totally understood. In the present study, we analyzed the genome-wide gene expression profile in human intracranial aneurysms using cDNA microarrays. |
| 1133 | GSE14278 |
Profile | Understanding why some indidivual resist HIV-1 infection despite continued exposure is an important goal for vaccine development. We compared CD4+ T cell gene expression at baseline in HIV-1 resistant commercial sex-workers from Nairobi Kenya to HIV-1 high-risk negative (non-resistant) commercial sex-workers using gene expression arrays Keywords: Case-control, disease state analysis |
| 1134 | GSE19678 |
Profile | Loss or reduction in function of tumor suppressor genes contributes to tumorigenesis. We identified a novel homozygous deletion of DACH1 in gliomas. We generated U87TR-Da glioma cell line where DACH1 expression could be activated by exposure of cells to doxycycline, and examined changing global gene expression by DACH1 expression. |
| 1135 | GSE41802 |
Profile | Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH and 2-HG alter signaling pathways to promote cancer, though, remains unclear. Additionally, there exist relatively few cell lines with IDH mutations. To examine the effect of endogenous IDH mutations and 2-HG, we created a panel of isogenic epithelial cell lines with either wild-type IDH1/2 or clinically relevant IDH1/2 mutations. Differences were noted in the ability of IDH mutations to cause robust 2-HG accumulation. IDH1/2 mutants that produce high levels of 2-HG cause an epithelial-mesenchymal transition (EMT)-like phenotype, characterized by changes in EMT-related gene expression and cellular morphology. 2-HG is sufficient to recapitulate aspects of this phenotype in the absence of an IDH mutation. In the cells types examined, mutant IDH-induced EMT is dependent on upregulation of the transcription factor ZEB1 and downregulation of the mir-200 family of microRNAs. Furthermore, sustained knockdown of IDH1 in IDH1 R132H mutant cells is sufficient to reverse many characteristics of EMT, demonstrating that continued expression of mutant IDH is required to maintain this phenotype. These results suggest mutant IDH proteins can reversibly deregulate discrete signaling pathways that contribute to tumorigenesis |
| 1136 | GSE26637 |
Profile | 5 arrays from obese insulin-resistant and lean insulin-sensitive females adipose tissue at fasting and after 3h hyperinsulinemia |
| 1137 | GSE13433 |
Profile | Alveolar soft-part sarcoma (ASPS) is an extremely rare highly vascular soft tissue sarcoma affecting predominantly adolescents and young adults. In an attempt to gain insight into the pathobiology of this enigmatic tumor, we performed the first genome-wide gene expression profiling study. |
| 1138 | GSE19610 |
Profile | Epigenetic mechanisms contribute to deregulated gene expression of hematopoietic progenitors in Myelodysplastic Syndromes (MDS). Hypomethylating agents are able to improve peripheral cytopenias in MDS patients. To identify critical gene expression changes induced by hypomethylating agents we analyzed gene expression profiling (GEP) of myelodysplastic and normal CD34+ hematopoietic stem cells treated in vitro with or without decitabine. Four MDS and two untreated early stage Hodgkin’s lymphomas were analyzed for GEP. Mock treated CD34+ stem cells segregate according to diagnosis and karyotype. After decitabine treatment, gene expression changes were more consistent on MDS CD34+ cells with abnormal kayotype. Comparing decitabine-induced genes with those found down-regulated in mock-treated MDS cells, we identified a list of candidate tumor suppressor genes in MDS. By real-time RT-PCR we confirmed expression changes for three selected genes CD9, CXCR4 and GATA2 in 12 MDS patients and 4 controls. CD9 was widely repressed in most MDS CD34+ cell samples, although similar levels of methylation were found in both normal and MDS total bone marrows. CXCR4 promoter methylation was absent in total bone marrows from 36 MDS patients. In conclusion, changes in gene expression changes induced by hypomethylating treatment are more pronounced in CD34+ cells from abnormal karyotype. |
| 1139 | GSE39091 |
Profile | Microarrays were used to determine the change in gene expression of genes involved in the p53 pathway after siRNA knock down of p53 CDT1 or BRCA1 A375 cells were grown, transfected with siRNA, incubated for 48hrs, then incubated for another 26hrs in the presence of either 0.065% DMSO as control, 650nM MLN4924, 5uM Nutlin or 100nM Daunorubicin. RNA extraction and hybridization on Affymetrix HG-U133Plus 2.0 arrays were performed. |
| 1140 | GSE40580 |
Profile | The aim of this study was to analyze the influence of PADMA28 ethanolic extracts on HepG2 gene expression. PADMA28 (Swissmedic Nr. 58436) is an Indo-Tibetan polyherbal preparation used for the treatment of symptoms associated with circulatory disorders. |
| 1141 | GSE14383 |
Profile | BEAS-2B cells have been treated with low doses (20µg/ml) of CSC for 4 months. As negative control BEAS-2B cells were treated with DMSO (the CSC solvent). Non-treated cells were cultivated in parallel. Keywords: time course stress response |
| 1142 | GSE46922 |
Profile | Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are destroyed prematurely. In the majority of children the disease resolves but in some it becomes chronic. To investigate whether the two forms of the disease are similar or separate entities we performed DNA microarray analysis of T-cells from newly diagnosed children and children with chronic ITP. We found complete separation of the expression files between the two forms of the disease. Furthermore the gene expression of several cytokines differed between the two forms of the disease. This was also reflected in plasma with increased levels of IL-16 and TWEAK and lower levels of IL-4 in newly diagnosed compared with chronic ITP. Thus, our data indicate that the two forms of the disease may be separate entities. |
| 1143 | GSE14596 |
Profile | This study examines the sites of HIV integration in quiescent CD4 T cells and compares them to activated T cells. The expression patterns of the sites hosting integration events were determined using microarray analysis data from quiescent and activated CD4 T cells. |
| 1144 | GSE18670 |
Profile | Most cancer deaths are caused by metastases which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC). A negative depletion fluorescence activated cell sorting (FACS) procedure was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumor (T), and non-tumoral pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. The ‘Ingenuity Pathway Analysis’ software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS). Using stringent statistical analysis, we finally retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway TGF-β1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were over-expressed in CTC. High co-expression of TGF-1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 4 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 – 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 – 1.861)). Pancreatic CTC isolated from blood samples using a FACS-based negative depletion method,express a cell motility gene signature. The expression of this newly defined cell motility gene signature in the primary tumor is able to predict survival of patients who undergo surgical resection for pancreatic cancer. |
| 1145 | GSE5679 |
Profile | Our data indicated that activation of the PPARg nuclear receptor induces a retinoid response in human dendritic cells. In order to assess the contribution of retinoid signaling to the PPARg response we decided to use a combination of pharmacological activators and inhibitors of these pathways. Cells were treated with the synthetic PPARg ligand rosiglitazone (RSG) or with RSG along with the RARa antagonist (AGN193109) to block RARa mediated gene expression, or the RARa specific agonists (AM580) alone. This design allows one to determine if retinoid signaling is a downstream event of PPARg activation and what portion of PPARg regulated genes are regulated via induced retinoid signaling. Keywords: ligand response |
| 1146 | GSE11373 |
Profile | Fascin an actin-binding protein, is upregulated in a variety of cancers, including esophageal squamous cell carcinoma (ESCC) and is proposed to function in cellular growth, mobility and invasiveness. Nonetheless, the molecular mechanisms through which fascin expression contributes to the proliferation and invasiveness of ESCC are unknown. To address this issue and to identify genes and biological pathways associated with fascin expression, a genome-wide gene expression analysis was performed on a fascin RNAi-depleted cell line and a corresponding ESCC cell line previously determined to express high levels of fascin. Keywords: cell type comparison |
| 1147 | GSE38972 |
Profile | Heat shock protein 90 (Hsp90) is an essential evolutionarily conserved molecular chaperone in eukaryotes. Cancer cells rely on Hsp90 to chaperone activated oncoproteins and its involvement in numerous signaling pathways makes it an attractive target for drug development. Surprisingly, however, the impact of Hsp90 inhibitors on cancer cells is most commonly cytostatic, and efforts to enhance the anti-tumor activity of Hsp90 inhibitors in the clinic remain a significant challenge. In this study, we show that dual inhibition of Wee1 tyrosine kinase and Hsp90 causes prostate cancer cells to undergo apoptosis. Gene-expression profiling revealed that induction of the intrinsic apoptotic pathway by this drug combination coincided with transcriptional down-regulation of Survivin and Wee1, an outcome not seen in cells treated separately with either agent. At the translational level, expression of these two proteins as well as activated Akt was completely abrogated. Similar results were obtained in prostate cancer xenografts. These data establish a novel therapeutic strategy to enhance the efficacy of Hsp90 inhibitors in prostate cancer, and they provide a mechanistic rationale for stimulating the pro-apoptotic activity of Hsp90 inhibitors. In order to explore the mechanism underlying the enhanced cell death caused by Wee1 inhibitorII and 17-AAG combination, we performed microarray analysis using PC3 cells treated with Wee1 inhibitorII alone, 17-AAG alone, or the two drugs in combination. |
| 1148 | GSE6043 |
Profile | Deregulation of translational control is an obligatory step in oncogenesis; however this step has not been addressed by prior genomic and transcriptional profiling studies of cancer biology. Here we simulate the translational deregulation found in cancer by ectopically over expressing translation initiation factor eIF4E in primary human mammary epithelial cells; and examine its impact on cell biology and the pattern of ribosomal recruitment to mRNA genome wide. Over expression of eIF4E allows cells to bypass M0 premature growth arrest, but does not confer other malignant properties. However, in concert with hTERT, eIF4E imparts cells with growth and survival autonomy - and profoundly alters the pattern of polyribosome-associated mRNA encoding cell cycle and apoptosis regulators. The translational response to increased eIF4E is not only a unidirectional activation of oncogenic drivers, but also consists of complex intrinsic translational mechanisms that mitigate the acquisition of neoplastic properties. Keywords: Cell line comparison using both total and polyribosomal RNA |
| 1149 | GSE31545 |
Profile | Brain tumors are among the most malignant cancers and can arise from neural stem cells or oligodendrocyte progenitor cells (OPCs). Glioma-propagating cells (GPCs) that have stem-like properties have been derived from tumor variants such as glioblastoma multiforme (GBM) and oligodendroglial tumors the latter being more chemosensitive with better prognosis. It has been suggested that such differences in chemosensitivity arise from the different profiles of OPCs versus neural stem cells. We thus explored if GPCs derived from these glioma variants can serve as reliable in vitro culture systems for studies. We utilized gene expression analyses, since GBM and oligodendrogliomas can be molecularly classified. Accordingly, we derived a gene signature distinguishing oligodendroglial GPCs from GBM GPCs collated from different studies, which was enriched for the Wnt, Notch and TGF-beta pathways. Using a novel method in glioma biology, the Connectivity Map, we mapped the strength of gene signature association with patient gene expression profiles in 2 independent glioma databases [GSE16011, http://caintegrator-info.nci.nih.gov/rembrandt]. Our gene signature consistently stratified survival in glioma patients. This data would suggest that in vitro low passage GPCs are similarly driven by transcriptomic changes that characterize the favorable outcome of oligodendrogliomas over GBM. Additionally, the gene signature was associated with the 1p/19q co-deletion status, the current clinical indicator of chemosensitivity. Our gene signature detects molecular heterogeneity in oligodendroglioma patients that cannot be accounted for by histology or the 1p/19q status alone, and highlights the limitation of morphology-based histological analyses in tumor classification, consequently impacting on treatment decisions. |
| 1150 | GSE30768 |
Profile | To understand the development of new psoriasis lesions we studied a group of moderate-to-severe psoriasis patients who experienced a relapse after ceasing efalizumab (anti-CD11a, Raptiva, Genentech). There were increased CD3+ T cells, neutrophils, CD11c+ and CD83+ myeloid DCs, but no increase in CD1c+ resident myeloid DCs. In relapsed lesions, there were many CD11c+CD1c-, inflammatory myeloid DCs identified by TNFSF10/TRAIL, TNF, and iNOS. CD11c+ cells in relapsed lesions co-expressed CD14 and CD16 in situ. Efalizumab induced an improvement in many psoriasis genes, and during relapse, the majority of these genes reversed back to a lesional state. Gene Set Enrichment Analysis (GSEA) of the transcriptome of relapsed tissue showed that many of the gene sets known to be present in psoriasis were also highly enriched in relapse. Hence, on ceasing efalizumab, T cells and myeloid cells rapidly enter the skin to cause classic psoriasis. |
| 1151 | GSE32920 |
Profile | Staphylococcus aureus produces the cyclic dipeptides tyrvalin and phevalin (aureusimine A and B respectively). A previous study reported that S. aureus mutants not capable of producing these compounds were less virulent in vivo through the deranged regulation of virulence factor genes. These findings, however, have been questioned as an unknown mutation in an operon that regulates virulence was discovered in the mutant strain. Here, we report that S. aureus biofilms produce greater amounts of phevalin than their planktonic counterparts. When administered to human keratinocytes, phevalin had no substantial effect on gene expression. Phevalin had no obvious impact on the extracellular metabolome of S. aureus. However, conditioned medium from S. aureus spiked with phevalin resulted in significant differences in keratinocyte gene expression compared to conditioned medium alone. A role for phevalin in manipulating host responses is apparent. Additionally, phevalin is a potential biomarker and/or therapeutic target for chronic, biofilm-based infections. |
| 1152 | GSE16615 |
Profile | Iisomer-specific effects of conjugated linoleic (CLA) supplementation on gene expression with particular consideration of the PPAR 2 Pro12Ala SNP in human adipose tissue. |
| 1153 | GSE23206 |
Profile | About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI. We used microarray to look at global gene expression changes in untreated cells vs gefitinib treated cells to identify key characters for the acquisition of resistance. |
| 1154 | GSE6872 |
Profile | Normal human spermatogenesis concludes with the formation of large numbers of morphologically well developed spermatozoa. While transcriptionally quiescent these cells carry an RNA payload that reflects the final spermiogenic phase of transcription. We report here the spermatozoal transcript profiles characteristic of normally fertile individuals and infertile males suffering from a consistent and severe teratozoospermia in which under 4% of spermatozoa are morphologically normal. RNA was extracted from the purified sperm cells of ejaculate and hybridized to Affymetrix U133 (v2) Microarrays. Keywords: disease state analysis |
| 1155 | GSE24249 |
Profile | The transcription factor GATA3 is essential for luminal cell differentiation during mammary gland development and critical for formation of the luminal subtypes of breast cancer. Ectopic expression of GATA3 promoted global alterations of the transcriptome of basal triple-negative breast cancer cells resulting in molecular and cellular changes associated with a more differentiated luminal tumor subtype and a concomitant reduction in primary tumor growth, lung metastasis, and macrophage recruitment at the metastatic site. Importantly, we demonstrate that the inhibition of metastases by GATA3 results from the suppression of lysyl oxidase (LOX) expression, a metastasis promoting matrix protein that affects cell proliferation, cross-linking of extracellular collagen types, and establishment of the metastatic niche. |
| 1156 | GSE27313 |
Profile | Wnt signaling is upregulated frequently in several cancers including sarcomas. Since, there is cell-context dependent variation in the target gene expression, to identify canonical Wnt targets in sarcomas, we used human mesenchymal stem cells. |
| 1157 | GSE1007 |
Profile | molecular profiles (HG-U95BC,D,E) of biopsy skeletal muscle samples obtained from 10 normal individuals and 10 DMD patients Keywords = gene expression profiles of normal human skeletal muscles Keywords = gene expression profiles of DMD patients' skelatal muscle samples Keywords = Affymetrix HG-U95B Keywords = Affymetrix HG-U95C Keywords = Affymetrix HG-U95D Keywords = Affymetrix HG-U95E Keywords: other |
| 1158 | GSE39339 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1159 | GSE6381 |
Profile | Right ventricular samples were serially acquired during surgical repair of ventricular septal defect. Expression profiling revealed three patterns of gene expression: (1) increased expression above control levels within one hour of cardioplegic arrest with further amplification during early reperfusion; (2) increased expression limited to the reperfusion phase; and (3) reduced expression during reperfusion. Keywords: VSD Patients |
| 1160 | GSE6054 |
Profile | Background: Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals. Methods: Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography ? mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p < 0.05; Benjamini Hochberg correction, False Discovery Rate = 0.05). The differential expression of FH associated genes was validated at the mRNA level by qRT-PCR and/or at the protein level by Western Blot or flow cytometry. Functional validation of monocyte scavenger receptor activities were done by binding assays and dose/time dependent uptake analysis using native and oxidized LDL. Results: Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Conclusion: Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease. Keywords: Micro-array analysis, cell type comparison, |
| 1161 | GSE14990 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1162 | GSE25550 |
Profile | Comparison of t(11;18)-positive MALT lymphoma to t(11;18)-negative MALT lymphoma with a special focus on the NF-KB pathway and it's targets |
| 1163 | GSE28618 |
Profile | HOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies. In this study we found high expression of the HOXD9 gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunocytochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role of HOXD9 in gliomas, we silenced its expression in the glioma cell line U87 using HOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested that HOXD9 contributes to both cell proliferation and/or cell survival. The HOXD9 gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells. HOXD9 siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation. Finally, we cultured human glioma cancer stem cells (GCSCs) from patient specimens found with high expression of HOXD9 in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs). Our results suggest that HOXD9 may be a novel marker of GCSCs and cell proliferation and/or survival factor in gliomas and glioma cancer stem-like cells, and a potential therapeutic target. |
| 1164 | GSE21496 |
Profile | Although short-term disuse does not result in measurable muscle atrophy studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men (n = 7, mean age ± S.D = 22.1 ± 3.7 yr) following 48h unloading (UL) via unilateral lower limb suspension and 24h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48h UL, and 24h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with qRT-PCR, and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway were related to protein ubiquitination. The oxidative stress response pathway was the second highest ranked canonical pathway. Of the downregulated genes, functions related to mitochondrial metabolism were the mostly highly enriched. In general, gene expression patterns following UL persisted following RL. qRT-PCR confirmed increases in mRNA for UPP-related E3 ligase Atrogin1 (but not accompanying increases in protein products) and stress response gene heme oxygenase-1 (HMOX, which showed a trend towards increases in protein products at 48h UL) as well as extracellular matrix (ECM) component COL4. The gene expression patterns were not readily reversed upon RL suggesting that molecular responses to short-term periods of skeletal muscle inactivity may persist after activity resumes. |
| 1165 | GSE23630 |
Profile | Background: In the last decade much attention has been drawn to probiotic bacteria in the context of inflammatory bowel disease (IBD), since the potential of certain strains to attenuate inflammation was demonstrated in several animal experiments and clinical studies. Data in humans elucidating the molecular mechanism of probiotic action are still scarce. To this end, we used an organ culture system of human colon mucosa and investigated the gene expression profiles after treatment with different probiotic bacteria in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)) stimulated samples using whole genome microarrays. Moreover, we analyzed changes occurring in the intestinal explants cultured for 8 hours when compared to fresh, directly frozen mucosa, in order to infer the suitability of the system to study an inflammatory stimulus and likely antiinflammatory responses. Results: Culturing intestinal colon fragments during 8 hours elicited differential gene expression in 283 genes, 229 upregulated and 54 downregulated. Upregulated genes were predominantly related to apoptosis, whereas downregulated genes encoded mitochondrial proteins. No specific enrichment of genes related to inflammation or immune response could be detected, confirming the suitability of the system to further study the inmunomodulatory/anti-inflammatory properties of Lactobacillus casei BL23 (BL23), L.plantarum 299v (LP299v) and L.plantarum 299v (A-) (LP299v (A-)), a mutant strain with reduced adhesive properties to enterocytes. Intestinal explants were stimulated with PMA/IO for 3 hours and subsequently incubated with probiotic bacteria for 4 h. ANOVA analysis (p ≤ 0,01) revealed 205 differentially expressed genes between Control, PMA/IO (Inflamed), and the 3 bacterial treatments. Most importantly, a number of PMA/IO induced genes related to immune response and immune system process such as IL-2, IFN-γ, IL17A and pro-inflammatory cytokines CXCL9 and CXCL11 were downregulated by BL23, LP299v and LP299v (A-). The behaviour of the three Lactobacillus strains was quite similar, although their presence induced differential expression of a small number of genes in a strain dependent manner. Conclusion: The human colon organ culture was found to be a suitable model for the study of inflammatory/anti-inflammatory stimuli, and therefore it constitutes a valuable tool to determine the inmunomodulatory effect of probiotic bacteria. The global transcriptional profile evoked by strains BL23, LP299v and LP299v (A-) in artificially inflamed tissue indicated a clear homeostasis restoring effect, including a decrease of the signals produced by activated T cells. |
| 1166 | GSE7161 |
Profile | The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out TOP1 is lethal in metazoans. To reveal the functions of human Top1 we have generated stable Top1siRNA cell lines from colon and breast carcinomas (HCT116-siTop1 and MCF-7-siTop1, respectively). In those cells, Top2 compensates for Top1 deficiency. A prominent feature of the siTop1 cells is genomic instability, with chromosomal aberrations and histone gamma-H2AX foci associated with replication. siTop1 cells also show rDNA and nucleolar alterations, and increased nuclear volume. Genome-wide transcription profiling revealed 55 genes with consistent changes in siTop1 cells. Among them, asparagine synthetase (ASNS) was reduced in siTop1 cells, as it also was in cells with transient Top1 downregulation. Conversely, Top1 complementation increased ASNS, indicating a causal link between Top1 and ASNS expression. Correspondingly, pharmacological profiling showed l-asparaginase hypersensitivity in the siTop1 cells. Resistance to camptothecin, aphidicolin, hydroxyurea and staurosporine, and hypersensitivity to etoposide and actinomycin D demonstrated that Top1, in addition to being the target of camptothecins, also regulates DNA replication, rDNA stability and apoptosis. Overall, our studies demonstrate the pleiotropic nature of human Top1 activities. In addition to its classical DNA nicking-closing functions, Top1 plays critical non-classical roles in genomic stability, gene-specific transcription, and response to various anticancer agents. Keywords: genetic modification design |
| 1167 | GSE12510 |
Profile | The two obstacles that impede a wider application of genetically modified cells expressing therapeutic transgenes for ex vivo gene therapy are the immune mediated rejection of the transplanted cells combined with their potential to cause iatrogenic oncogenesis. In this study we describe a new cellular vehicle for this form of therapy, termed the cord lining epithelial cell (CLEC). CLECs are derived from the human amnion and incorporate many of the immunoregulatory functions associated with the fetal/maternal interface. We show that CLECs can be safely transfected by phage φC31 integrase to accomplish site-specific integration of a therapeutic human transgene. We also show that transplanted CLECs are not oncogenic in vivo and can be maintained in immunocompetent mice where acute xeno-rejection rapidly destroys other human cell types. Finally, we demonstrate the utility of CLECs for ex vivo gene therapy by delivering human coagulation factor 8 to mice with Hemophilia A. |
| 1168 | GSE16614 |
Profile | Lim Mineralization Protein splice variant-3 (LMP3) is known to induce osteoblast differentiation as a result of active modulation of selected molecules involved in the osteogenic cascade. LMP3 seems to act as an upstream modulator of osteogenic differentiation, although the complete network of molecular events involved in this process are still largely unknown. In particular, LMP3 seems to act, at least in part, through the upregulation of bone morphogenetic proteins (BMPs) which are known to exert multiple functions, leading to the regulation of diverse cellular processes. Thus, LMP actions inside the cell are likely to involve the activation of main signaling pathways, suggesting a possible wider role of the molecule in cell homeostasis. The aim of this study is to analyze the gene expression profiles exhibited by human bone marrow mesenchymal stem cells (MSCs) expressing the LMP3 gene in order to investigate the early transcriptional events preceding the acquisition of a differentiated phenotype. For this purpose, MSCs were transduced using a replication-defective adenoviral vector carrying the human LMP3 gene. Gene expression profiling was then carried out by microarray analysis one day after cell transduction. The results obtained in this study suggest that in addition to activating the TGFB1-signaling pathway, LMP3 acts on the fine balance between proliferation and differentiation of mesenchymal cells. Gene modulation directly related to the reprogramming of the transcriptional machinery induced by the viral vector is also discussed. |
| 1169 | GSE25417 |
Profile | The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluritpotent cells into cells with hepatocyte characteristics. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation toward a hepatocyte–like fate appeared to recapitulate many of the stages normally associated with the formation of hepatocytes in vivo. In the current study we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate i) that human ES cells express a number of mRNAs that characterize each stage in the differentiation process, ii) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses, and iii) that the nuclear hormone receptor HNF4a is essential for specification of human hepatic progenitor cells by establishing expression of the network of transcription factors that control hepatocyte cell fate. |
| 1170 | GSE40635 |
Profile | Cyclin D3 is critical hematopoiesis and loss of cyclin D3 leads to resistance to transformation of bone marrow progenitors by Notch1-IC. We used a small molecule targeting cyclin D3:CDK4/6 activity to study whether its inhibition is an effective therapeutic strategy. We analyzed T-ALL lines in vitro with PD-0332991 or vehicle control to determine genes affected by the drug. |
| 1171 | GSE11367 |
Profile | Investigate the effect of recombinant human IL-17A on vascular smooth muscle cells cultured from human aortas. Keywords: Dose response |
| 1172 | GSE15322 |
Profile | We used microarrays to investigate gene expression changes in human colon normal fibroblasts exposed to a bitter orange extract enriched in flavanones (and previously subjected to in vitro gastro-duodenal digestion) to determine possible modulatory beneficial effects induced by these plant-derived compounds on the colon cells. Keywords: Comparative gene expression Control vs Treated cells (response to exposure with xenobiotics plant polyphenols) |
| 1173 | GSE2552 |
Profile | Baseline expression levels of genes in CEPH individuals from the International HapMap Project were measured using the Affymetrix Human Genome Focus Arrays. Arrays were analyzed using MAS 5.0 software (Affymetrix). Keywords = Gene Expression lymphoblastoid cells, human Keywords: other |
| 1174 | GSE20050 |
Profile | Most individuals infected with Mycobacterium tuberculosis can control the infection by forming and maintaining TB granulomas at the local infection foci. However when the chronic infection (also known as latency) becomes active, the caseous center of TB granuloma enlarges, and it liquefies and cavitates, ultimately releasing bacilli into airway. Deciphering how genes are regulated within TB granulomas will help to understand the granuloma biology. Therefore, we performed genome-wide microarray on caseous human pulmonary TB granulomas and compared with normal lung tissues. |
| 1175 | GSE20966 |
Profile | Changes in gene expression in pancreatic beta-cells from type 2 diabetes could provide insights into their abnormal insulin secretion and beta-cell turnover. The laser capture microdissection technique was used to acquire beta-cells from pancreatic tissue sections obtained from type 2 diabetic (T2D) and non-diabetic controls. We found that 4% of analyzed transcripts were differentially expressed between the two groups at the lower confidence bound cutoff of 1.2 and, among the differentially expressed transcripts, 62% were up-regulated and 38% down-regulated in samples of T2D subjects compared to non-diabetic controls. We observed: 1) changes in expression of genes linked to glucotoxicity, in particular, up-regulation of LDHA and PCK1, and down-regulation of GPD2, ME1 and ACLY; 2) evidence of oxidative stress, documented by up-regulation of metallothionein genes; 3) few changes in the major genes associated with cell cycle, apoptosis or endoplasmic reticulum stress; 4) differential expression of genes associated with pancreatic regeneration, most notably up-regulation of members of the regenerating islet gene (REG) family and metalloproteinase 7; and 5) differential expression of some genes found in genome wide association studies to be related to T2D (IGF2BP2, TSPAN8, and HNF1B were up-regulated, while JAZF1 and SLC30A8 were down-regulated). In conclusion, this study has identified many novel changes in pancreatic beta-cell gene expression that enhance the understanding of the pathogenesis of T2D. |
| 1176 | GSE12631 |
Profile | Side population (SP) cells isolated from limbal and conjunctival epithelia derive from cells that are slow cycling in vivo a known feature of tissue stem cells. The purpose of this study was to define the molecular signature of the conjunctival side population cells by global differential gene expression to identify markers and signaling pathways associated with this cell phenotype. Four overnight cultures of freshly isolated human conjunctival epithelial cells stained with Hoechst 3342 were cytometrically sorted into SP and non-SP cohorts. RNA was isolated and processed for microarray analysis using a commercial oligonucleotide array representing more than 55,000 transcripts derived from about 30,000 different genes. Selected microarray results were validated at the gene and protein levels by quantitative PCR, and immunological methods. Data mining methods were used to identify cellular processes relevant for stem cell function. Comparative analysis of transcripts expression based on expression levels and present/absent software calls across 4 replicate experiments identified 16993 expressed conjunctival epithelial transcripts including 10,266 unique known genes. Of those genes, 1254 and 363 were over expressed (> 2-fold ) or under expressed (< 0.5-fold), respectively, in the SP. The overexpressed set included genes coding for non-epithelial genes (e.g., CD62E/E-selectin and CD93), genes that have been associated with stem cell function in other cellular systems, including several homeodomain genes and genes whose over- or under-expression may underpin the stem cell slow cycling phenotype ( e.g., dual specificity phosphatases and cyclin kinases). |
| 1177 | GSE12205 |
Profile | Although the consequences of genotoxic injury include cell cycle arrest and apoptosis cell survival responses after genotoxic injury can produce intrinsic death-resistance and contribute to the development of a transformed phenotype. Protein tyrosine phosphatases (PTPs) are integral components of key survival pathways, and are responsible for their inactivation, while PTP inhibition is are often associated with enhanced cell proliferation. Our aim was to elucidate signaling events that modulate cell survival after genotoxin exposure. Diploid human lung fibroblasts (HLF) were treated with Cr(VI) (as Na2CrO4), a well known human respiratory carcinogen that induces a wide spectrum of DNA damage, in the presence and absence of a broad-range PTP inhibitor, sodium orthovanadate. Notably, PTP inhibition abrogated Cr(VI)-induced clonogenic lethality. The enhanced survival of Cr(VI)-exposed cells after PTP inhibition was predominantly due to a bypass of cell cycle arrest and was not due to decreased Cr uptake as evidenced by unchanged Cr-DNA adduct burden. Additionally, the bypass of Cr-induced growth arrest by PTP inhibition, was accompanied by a decrease in Cr(VI)-induced expression of cell cycle inhibiting genes, and an increase in the Cr(VI)-induced expression of cell cycle promoting genes. Importantly, PTP inhibition resulted in an increase in forward mutations at the HPRT locus, supporting the hypothesis that PTP inhibition in the presence of DNA damage may lead to genomic instability, via bypass of cell cycle checkpoints. |
| 1178 | GSE20086 |
Profile | Twenty-one genes (27 probe sets) were up-regulated in CAF as compared with NF. Known functions of these genes relate to paracrine or intracellular signaling, transcriptional regulation, extracellular matrix and cell adhesion/migration. Ten genes (14 probe sets) were down-regulated in CAF, including the pluripotency transcription factor KLF4. Quantitative RT–PCR analysis of 10 genes validated the array results. Immunohistochemical staining for three gene products confirmed stromal expression in terms of location and relative quantity. Surprisingly, the variability of gene expression was slightly higher in NF than in CAF, suggesting inter-individual heterogeneity of normal stroma. |
| 1179 | GSE45210 |
Profile | Mediator complex has been known as pivotal regulator of RNA polymerase II. Mediator complex has two CDK subunits in vertebrates named CDK8 and CDK19. To elucidate functional difference between CDK8 and CDK19 in human cell, we employ siRNA mediate knockdown assay using HeLa S3 cell line. According to this assay these CDKs possess highly redundancy in HeLa S3 cell transcription regulation mechanism but in several genes, each CDK shows gene specific regulatory function. |
| 1180 | GSE16070 |
Profile | A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. |
| 1181 | GSE23399 |
Profile | Systemic chemotherapy inflicts cytotoxic injuries on breast carcinoma-associated fibroblasts. We profiled the transcriptomes of human breast carcinoma-associated fibroblasts before and after clinically relevant cytotoxic stimuli induced by chemotheraputic agents. |
| 1182 | GSE18810 |
Profile | The establishment of bacterial infections at epithelial surfaces is determined by the balance of virulence attributes of the pathogen with the activity of innate host defenses. Polymorphonuclear leukocytes (PMN) are key responders in many bacterial infections but the mechanisms by which pathogens subvert these early responses to establish infection are largely undefined. Here, we model these early interactions between human PMN and the primary cause of urinary tract infections, namely uropathogenic Escherichia coli (UPEC). Our objective was to define virulence phenotypes of uropathogens (as compared with laboratory and commensal E. coli strains) that permit evasion of PMN activity. We found that UPEC strains resist phagocytic killing and dampen the production of antimicrobial reactive oxygen species by PMNs. Analysis of the global transcriptional responses of PMN to E. coli strains revealed that UPEC exposure downregulates the expression of PMN genes involved in proinflammatory signaling and PMN chemotaxis, adhesion, and migration. Consistent with these data, UPEC attenuated transepithelial neutrophil recruitment in an in vitro model of acute infection. We propose that these UPEC strategies are important in the establishment of epithelial infection, and that the findings are germane to a range of bacterial infections at epithelial surfaces. We used microarrays to detail the global program of gene expression in human neutrophils in response to a uropathogenic bacteria compared to a closely related non-pathogenic strain relative to control samples with no bacteria. Our goal was to elucidate a pathogen-specific response. We chose an early time point of 60 minutes to evaluate the accute response to infection. |
| 1183 | GSE33458 |
Profile | In the cancer stem cell model a cell hierarchy has been suggested as an explanation for intratumoral heterogeneity and tumor formation is thought to be driven by this tumor cell subpopulation. The identification of cancer stem cells in osteosarcoma (OS) and the biological processes dysregulated in this cell subpopulation, also known as tumor-initiating cells (TICs), may provide new therapeutic targets. The goal of this study, therefore, was to identify and characterize the gene expression profiles of TICs isolated from human OS cell lines. We analyzed the self-renewal capacity of OS cell lines and primary OS tumors based upon their ability to form sphere-like structures (sarcospheres) under serum-starving conditions. TICs were identify from OS cell lines using the long-term label retention dye PKH26. OS TICs and the bulk of tumor cells were isolated and used to assess their ability to initiate tumor in NOD/SCID mice. Gene expression profiles of OS TICs were obtained from fresh orthotopic tumor samples. We observed that increased sarcosphere efficiency correlated with an enhanced tumorigenic potential in OS. PKH26High cells were shown to constitute OS TICs based upon their capacity to form more sarcospheres, as well as to generate both primary bone tumors and lung metastases efficiently in NOD/SCID mice. Genomic profiling of OS TICs revealed that both bone development and cell migration processes were dysregulated in this tumor cell subpopulation. PKH26 labeling represents a valuable tool to identify OS TICs and gene expression analysis of this tumor cell compartment evidences potential therapeutic targets. |
| 1184 | GSE6914 |
Profile | Resistance of Calu3 NSCLC cells to the cytotoxic nucleoside analog gemcitabine (2'2'-difluorodeoxycytidine) can be prevented as well as reversed by the rexinoid X receptor selective agonist bexarotene. This study was designed to investigate the changes in gene expression associated with gemcitabine resistance and its reversal by bexarotene. In addition to the parental Calu3 cells and the 10 cycles of treatment of the gemcitabine resistant Calu3 cells with vehicle or bexarotene, analogous treatment paradigms with gemcitabine alone as well as the combination of both compounds have been included as controls. (However, it has to be noted that in the combination treatment, cells that were re-sensitized by bexarotene have largely been removed from the culture before harvest due to the cytotoxic activity of gemcitabine.) Keywords: cell type comparison, compound effects |
| 1185 | GSE11831 |
Profile | These samples were all taken from patients who underwent investigations including colonoscopy but where all tests were normal and the diagnosis of irritable bowel syndrome was reached. These observations have been used as references in studies of colonic gene expression in inflammatory bowel diseases |
| 1186 | GSE9633 |
Profile | Transcriptional profiling was conducted on RNA from 16 prostatic cancer cell lines to identify genes whose expression level correlate with sensitivity of an anti-tumor agent (dasatinib). Keywords: comparison of sensitive group versus resistant group of cell lines to agent |
| 1187 | GSE9455 |
Profile | All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2). Following data filtering only 3426 genes were retained for further downstream analysis (see 'Data_after_filtering.txt' at the foot of this record). For data filtering details, please see the 'Data processing' field in any of the associated Sample records. Keywords: Prospective Randomized trial |
| 1188 | GSE23360 |
Profile | Van Marck et al. (Cancer Research 2005) published that overexpression of P-cadherin in a melanoma cell line promoted homo- and heterotypic cell-cell adhesion, induced an epitheloïd morphology, and impaired cancer cell invasion. Therefore, we wanted to compare the RNA expression profile between the empty vector control cells and the P-cadherin overexpression variant. This experiment could provide us with effector molecules of P-cadherin that mediate its anti-invasive function. |
| 1189 | GSE2677 |
Profile | Glucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of Peripheral blood lymphoblasts purified at three time points (0h, 6-8h, 24h after treatment initiation) from 13 children under therapy for ALL . Treated samples were compared to untreated (0h). This series consists of this set of microarrays. For comparison, expression profiles were generated from an adult ALL patient, peripheral blood lymphocytes from GC-exposed healthy donors, GC-sensitive and -resistant ALL cell lines and mouse thymocytes treated with GC in vivo and in vitro. Findings. An essentially complete list of GC-regulated candidate genes in clinical settings experimental and was generated, enabling immediate analysis of any gene with respect to its potential significance for GC-induced apoptosis in these systems. Gene regulations previously thought responsible for cell death in experimental systems were reconfirmed in few children only. In contrast, a small number of genes, most not implicated in GC-induced apoptosis previously, were co-ordinately regulated in the majority of children. Keywords = ALL Keywords = apoptosis Keywords = glucocorticoid Keywords = leukemia Keywords = pediatric oncology Keywords: other |
| 1190 | GSE9713 |
Profile | Nu61 a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Keywords: Pair-wise comparison of radiosensitive vs radioresistant tumors; time course of irradation response |
| 1191 | GSE15271 |
Profile | Functional discrimination between normal centroblast and centrocyte obtained from human inflamed tonsils after cell sorting. We used microarrays to detail the segregation between these two B cell subsets |
| 1192 | GSE8023 |
Profile | AML1-ETO expression in normal human umbilical cord blood CD34+ cells leads to long-term proliferation of an early self-renewing primitive progenitor cell with multilineage potential and stem cell ability but these cells do not induce leukemia in immunodeficient mice. This comparative microarray study was initiated to determine the differences in the transcriptome of AML-ETO-expressing CD34+ cells after extended culture in vitro, using normal cord blood cells expanded for 6-8 weeks in vitro and subsequently purified for the CD34+ population as the control comparison. Keywords: Disease state analysis; comparison of changes in transcriptome due to long-term AML1-ETO expression in normal human hematopoietic CD34+ progenitor cells |
| 1193 | GSE12648 |
Profile | HIBM is a neuromuscular disorder characterized by adult-onset slowly progressive distal and proximal muscle weakness. Here, gene expression was measured in muscle specimens from 10 HIBM patients carrying the M712T Persian Jewish founder mutation in GNE and presenting with mild histological changes, and from 10 healthy matched control individuals. Keywords: Muscle specimen |
| 1194 | GSE25162 |
Profile | As miR-210 expression is correlated to poor prognosis both in estrogen-positive and in estrogen-negative breast cancer (BC) patients we aimed to investigate the biological processes regulated by miR-210 and which may elucidate its function in the aggressive phenotype of high grade breast cancer. We performed in silico functional analyses of the genes deregulated upon miR-210 overexpression in MCF7 BC cell line and upon miR-210 repression in MDA-MB-231 BC cell line using lentiviral transduction. Gene expression profiling analysis of these cells revealed the deregulation of genes involved in several biological pathways including cell adhesion, extracellular structure organization, epithelial cell proliferation, cell division, cell cycle and immune response. |
| 1195 | GSE10896 |
Profile | Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD) a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity. Keywords: time course |
| 1196 | GSE5808 |
Profile | Children with acute measles were admitted to the University Teaching Hospital in Lusaka Zambia. Peripheral blood was collected at hospital entry, discharge and 1-month follow-up. Control samples were also collected from uninfected children. All children were HIV negative. Keywords: Clinical timecourse |
| 1197 | GSE39733 |
Profile | The Sin3 histone deacetylase (HDAC) complex is a 1.2 MDa chromatin modifying complex that can repress transcription by binding to gene promoters and deacetylating histones. The Sin3/HDAC complex can affect cell cycle progression through multiple mechanisms and is among the targets of anticancer drugs called HDAC inhibitors. We describe the identification of a new subunit of the Sin3 complex named family with sequence similarity 60 member A (FAM60A). We show that FAM60A/Sin3 complexes normally suppress the epithelial-to-mesenchymal transition (EMT) and cell migration. This occurs through transcriptional repression of genes that encode components of the TGF-beta signaling pathway. This work reveals that FAM60A and the Sin3 complex are upstream repressors of TGF-beta signaling, EMT and cell migration and extends the known biological roles of the Sin3 complex. This experiment investigates the role of FAM60A in gene expression by comparing A549 lung cancer cells treated with or without siRNA against FAM60A. The Sin3 histone deacetylase (HDAC) complex is a 1.2 MDa chromatin modifying complex that can repress transcription by binding to gene promoters and deacetylating histones. SDS3 is a core component of the Sin3 complex. The Sin3/HDAC complex can affect cell cycle progression through multiple mechanisms and is among the targets of anticancer drugs, called HDAC inhibitors. We describe the identification of a new subunit of the Sin3 complex named family with sequence similarity 60 member A (FAM60A). We show that FAM60A/Sin3 complexes normally suppress the epithelial-to-mesenchymal transition (EMT) and cell migration. This occurs through transcriptional repression of genes that encode components of the TGF-beta signaling pathway. This work reveals that FAM60A and the Sin3 complex are upstream repressors of TGF-beta signaling, EMT and cell migration and extends the known biological roles of the Sin3 complex. As a base line to better understand the relationship between FAM60A and the Sin3 complex, this experiment investigates the gene expression changes which occur in A549 lung cancer cells when the Sin3 complex is perturbed by knockdown of a core component via siRNA against SDS3. |
| 1198 | GSE10971 |
Profile | The purpose of this study was to identify molecular alterations potentially involved in predisposition to adnexal serous carcinoma (SerCa) in the non-malignant fallopian tube epithelium (FTE) of BRCA1/2-mutation carriers given recent evidence implicating the distal FTE as a common source for SerCa. Keywords: disease state analysis |
| 1199 | GSE43923 |
Profile | Pigment Epithelium-Derived Factor (PEDF) has recently been identified as a factor that is significantly upregulated in late-stage osteoarthritic cartilage in which chondrocytes are confronted with terminal differentiation and cell death. Since PEDF is known to induce cell death of endothelial cells it may also be responsible for terminal differentiation and cell death in cartilage. |
| 1200 | GSE27505 |
Profile | Sox2 is expressed by neural stem and progenitor cells and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors. |
| 1201 | GSE18182 |
Profile | Non-metastatic 2 (NME2) is an established metastases suppressor in multiple human cancer types. However the molecular mechanisms of NME2 action remain insufficiently resolved. We recently validated the transcription regulatory activity of NME2 with respect to control of proto-oncogene c-MYC expression. We hypothesized that large scale transcriptional potential of NME2 may be at the core of metastases suppression by NME2. Using a combination of high throughput genomic assays such as chromatin immunoprecipitation coupled to promoter array hybridization (ChIP-chip) and gene expression profiling, we characterized the transcriptional roles of NME2. Specifically, we found a set of NME2 target genes which changed expression upon selective depletion of NME2 in a lung cancer cell line, A549. The analysis of gene expression suggested control of various biological pathways esp. cell adhesion and apoptosis by NME2 target genes which could be important in regulation of metastases. |
| 1202 | GSE16924 |
Profile | The transcription factor MIST1 is required for final maturation of secretory cells of diverse tissues including gastric digestive-enzyme secreting zymogenic (chief) cells (ZCs). Here, we show that MIST1 directly activates RAB26, RAB3D and several other genes. |
| 1203 | GSE4218 |
Profile | Mammalian cells were grown as multicellular aggregates (spheroids) in an effort to determine the signaling events required for two cellular transformations states; primary foreskin fibroblasts (HFF-2) and glioblastoma cancer (T98G) cells to survive at room temperature under oxygen and nutrient-deprived conditions for extended periods of time (2 weeks) and subsequently grown out from the arrested state as adherent monolayers. HFF-2 cells were cultured in DMEM supplemented with 15% fetal bovine serum and 5% carbon dioxide humidified air at 37 degrees C. T98G cells were cultured in EMEM with 10% FBS, 5% non-essential amino acids and 5% carbon dioxide humidified air at 37 degreesC. Monolayers were grown in T-185 flasks to 60% confluency then split into T-185 flasks coated with a 1% agarose mix in a 2:1 media/water ratio. Cells were suspended in 30 ml of supplemented media and grown for 4 days in order to form multicellular spheroids as described previously by our group (J. Cell. Physiol., 206 [2006] 526-536; see GSE1364 and GSE1455 for similar experiments with HEK293 cells). The suspension was removed from the flasks and centrifuged (1500 x g, 2 min) and the media removed. The pellet was returned to the flasks and then placed in vacuum bags (Dri-shield 2000 moisture barrier bag from Surmount Inc., USA; Cat. number 70068), which were sealed immediately under vacuum (Deni Magic Vac, Champion model; Keystone Manufacturing, USA). Vacuum-sealed flasks were stored for 2 weeks (in the dark) at room temperature. Recovery was initiated by removing the flask from the bag and resuspending the spheroids in supplemented media and placing the flasks in a 5% CO2/humidified air incubator maintained at 37 degreesC. Timepoints for transcriptional analysis were monolayer (control), 4 day growth spheroids, 2 week stored spheroids and 7 day growth back to monolayers. There were 67 HFF-2 and 50 T98G genes that exhibited at least a 10-fold change in expression during the course of arrest and recovery. Eleven of these genes were common to both cell lines. While the trends were the same between the two cell lines for genes that were in common, the timing of the responses were clearly different. The primary fibroblasts showed significant gene expression changes during spheroid formation and returned to their initial monolayer state after the two week arrest, whereas the glioblastoma cells exhibited major changes in gene expression during the recovery process. Furthermore, the T98G cells never returned to the monolayer expression levels during the time course of the recovery phase (7 days growth under monolayer conditions). Major differences in the transcriptional data were also found between the cell lines with regards to the putative cellular location of the encoded proteins. Of the genes with significant fold changes (+/- 10-fold) for which location information is available, the primary fibroblasts were significantly enriched in genes encoding extracellular (32%) and membrane-associated (26%) proteins. The glioblastoma cells, on the other hand, had only 17% extracellular and 13% membrane-associated. The expression level trends for all genes above the 10-fold cutoff were as observed for the "in common" genes; HFF-2 genes had returned to monolayer expression levels after 7 days of recovery whereas the T98G line was still exhibiting expression values much different from that of the monolayer control. Keywords = human foreskin fibroblasts, desiccation, rehydration, monolayer, spheroid, stabilization, ambient temperature Keywords: other |
| 1204 | GSE32984 |
Profile | The endothelial transcription factor Erg (Ets Related Gene) plays an important role in homeostasis and angiogenesis by regulating many endothelial functions including survival and junction stability. Here we show that Erg regulates endothelial cell migration. Transcriptome profiling of Erg-deficient endothelial cells (EC) identified 80 genes involved in cell migration as candidate Erg targets including regulators of the Rho GTPases. Inhibition of Erg expression in human umbilical vein endothelial cells (HUVEC) resulted in decreased migration in vitro, whilst Erg over-expression using adenovirus caused increased migration. Live-cell imaging of Erg-deficient HUVEC showed a reduction in lamellipodia, in line with decreased motility. Both actin and tubulin cytoskeletons were disrupted in Erg-deficient EC, with a dramatic increase in tubulin acetylation. Amongst the most significant microarray hit was the cytosolic histone deacetylase (HDAC)-6, a regulator of cell migration. Rescue experiments confirmed that HDAC6 mediates the Erg-dependent regulation of tubulin acetylation and actin localization. |
| 1205 | GSE980 |
Profile | Human CD14+ monocytes were isolated and grown in GM-CSF and IL-4 for six days. The cells were then infected with measles virus Chicago-1 strain, and RNA was isolated at 3, 6, 12, and 24 hours post-infection. Keywords: time-course |
| 1206 | GSE39395 |
Profile | The survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC) we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease. We purified by FACS [CD45(+),Epcam(-)], [CD45(-) Epcam(+)] and [CD45(-) Epcam(-)] cell populations from fresh CRC samples and assessed their gene expression profiles |
| 1207 | GSE42765 |
Profile | MLLT10 a 24 exons gene at 10p12, is known in leukemogenesis as partner of MLL or PICALM and recently NAP1L1. We identified HNRNPH1 and DDX3X, genes involved in RNA processing, as new MLLT10 partners in 2 cases of pediatric NOTCH1 positive T-ALL. HNRNPH1/5q35 encodes for a member of the ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) subfamily of RNA binding protein. DDX3X/Xp11.3, belongs to the big family of RNA helicases with a DEAD box domain. |
| 1208 | GSE13314 |
Profile | Molecular pathways activated in MALT lymphoma are not well defined. In this study we perform gene expression profiling on 35 pulmonary MALT lymphoma using fresh frozen biopsy samples Keywords: Cell type analysis and disease state analysis |
| 1209 | GSE13491 |
Profile | Human UCB-MSCs showed donor-specific variation of therapeutic efficacy in improving LV systolic function reducing infarct area, and preserving wall thickness after MI, even though there were no significant differences in MSC phenotypes. UCB-MSCs (M02) which showed better efficacy had better paracrine activity and unique gene expression profile than others. In DNA microarray, in contrast to M01, M02 showed unique gene expression profiles; up-regulated anti-apoptotic and down-regulated apoptotic gene expression. |
| 1210 | GSE24553 |
Profile | We developed a novel culture system to obtain multilineage undifferentiated stem/progenitor cells from normal human thyroid tissues. This seems to be achieved by direct reprogramming of thyroid follicular cells. The objective of the study was to reveal gene expression profile of the obtained cells compared to primary thyrocytes. After enzymatic digestion primary thyrocytes, expressing thyroglobulin and cytokeratin-18, were cultured in a serum-free medium called SAGM containing insulin and EGF. Although the vast majority of cells died, a small proportion (~0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined, suggesting that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. |
| 1211 | GSE40444 |
Profile | The OCT4 transcription factor is involved in many cellular processes including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11) could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. Importantly, the increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G. We also identified a novel OCT4 downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. This small molecule-based stabilization of synthetic mRNA expression may have multiple applications for future cell-based research and therapeutics. |
| 1212 | GSE49184 |
Profile | GAS2DN could suppress the growth of chronic myeloid leukemia cells including K562, MEG-01 and CD34+ cells from patients. In addition, GAS2DN inhibited the tumorigenic ability of MEG-01 cells in nude mice. To understand the molecular insight of this inhibitory effect of GAS2DN, global gene expression were performed. The control and GAS2DN-transduced MEG-01 cells were used for microarray analysis. |
| 1213 | GSE4773 |
Profile | Parkinson's disease is a prevalent neurodegenerative disorder for which there is no cure. The cause of PD symptoms is loss of dopamine neurons in the midbrain but it is not known why these neurons die. Pesticide exposure is epidemiologically associated with PD, and administration of the organic pesticide rotenone to rats recapitulates most of the behavioral, neurochemical, and neuropathological findings in PD, including specific death of dopamine neurons. We have developed an in vitro model of rotenone toxicity using a dopaminergic cell line (SK-N-MC neuroblastoma cells) that mimics many of the cellular changes seen with in vivo rotenone toxicity and with PD, such as alpha-synuclein aggregation and oxidative damage. We are currently using this simple model to explore mechanisms of dopaminergic neurodegeneration, with our ultimate goal being the discovery of novel mechanisms for dopaminergic neuroprotection in PD. We will examine gene expression profiles of cultured SK-N-MC cells at several time points during rotenone exposure to determine pathways involved in rotenone toxicity and dopaminergic degeneration. We will compare these profiles to baseline profiles of rodent dopaminergic neurons that we have already obtained, as well as to profiles of dopamine neurons from rotenone-treated rats that we will obtain in the near future. We will also compare these data to published results from SN neurons from human PD patients. This technique will not only help us to detect gene expression changes relevant to dopaminergic neurodegeneration in PD, but it will allow us to determine if the SK-N-MC system can be reliably used to screen for neuroprotective therapies for PD. We anticipate that SK-N-MC cells will show a relevant subset of the gene changes seen in dopamine neurons in vivo and that this will guide us in the sorts of mechanisms and drugs that can be screened in this system. Chronic exposure to low levels of rotenone causes changes in gene expression in SK-N-MC cells that sensitize the cells to toxic insults. We also hypothesize that there are several compensatory protective pathways that are stimulated by chronic rotenone, although these pathways are ultimately ineffective at preventing damage. We anticipate that gene expression profiling of rotenone-treated cells over time will suggest several novel strategies for neuroprotective intervention. SK-N-MC cells will be grown in three different media: media only, vehicle (EtOH), and rotenone (5 nM). All current experimental evidence in our lab indicates that vehicle-treated cells are indistinguishable from media-only cells. Rotenone-treated cellls have a stereotypical response in culture. At one week, the only noticed change is an increase in alph-synuclein aggregation. At two weeks, evidence of increased oxidative stress appears (increased protein carbonyls and lipid peroxidation). At four weeks, the cells are markedly sensitized to oxidative challenge with H2O2. Therefore, we will examine gene expression at baseline, and during 1, 2, and 4 weeks of rotenone treatment. Three experiments will be performed, each lasting 4 weeks. For each experiment, three separate dishes of vehicle-treated, and rotenone-treated cells will be harvested at 1, 2, and 4 weeks (18 independent samples). Untreated, media-only cells will be harvested after 1 week in vitro to serve as baseline cells. Total RNA will be isolated. An equal amount of RNA from one dish per experiment per group will be used to compose the final samples. Therefore, each independent sample will consist of RNA from 3 separate experiments. This will allow us to take advantage of a pooling strategy, yet not sacrifice technical and biological replication. 21 samples will be sent to the Consortium. Three will be from untreated cells. Nine will be vehicle-treated at 1, 2, and 4 weeks (3 each). Nine will be rotenone-treated at 1, 2 , and 4 weeks (3 each). Each sample will be labeled and hybridized to one Affymetrix Human Genome U133 Plus 2.0 Gene Chip. With assistance of the consortium, we will analyze the data using the Signifiance Analysis of Microarrays (SAM) program and self-organizing map algorithms. Keywords: time-course |
| 1214 | GSE28026 |
Profile | Molecular profiling of tumors has proven a valuable tool for identification of prognostic and diagnostic subgroups in medulloblastomas glioblastomas and other cancers. However, the molecular landscape of atypical teratoid / rhabdoid tumors (AT/RTs) remains largely unexplored. To address this issue, we used microarrays to measure the gene expression profiles of 18 AT/RTs, and performed unsupervised hierarchical clustering to determine molecularly similar subgroups. Four major subgroups (clusters) were identified. These did not conform to gender, tumor location, or presence of monosomy 22. Clusters showed distinct gene signatures and differences in enriched biological processes, including elevated expression of choroid plexus genes in Cluster 4. In addition, survival differed significantly by cluster, with shortest survival (mean 4.7 months) in both Clusters 3 and 4 compared to Clusters 1 and 2 (mean 28.1 months). Analysis showed that multiple bone morphogenetic protein (BMP) pathway genes were up-regulated in the short survival clusters, with BMP4 showing the most significant up-regulation (270-fold). Thus, high expression of BMP pathway genes was negatively associated with survival in this dataset. Our study indicates that molecular subgroups exist within AT/RTs, and that molecular profiling of these comparatively rare tumors may be of diagnostic, prognostic and therapeutic value. Key Words: atypical teratoid / rhabdoid tumor; bone morphogenetic protein pathway; BMP4; survival; microarray |
| 1215 | GSE22025 |
Profile | We examined the global gene expression pattern of T cells regulated by progesterone to gain further insights into the regulatory mechanisms of progesterone. We found 325-347 cord blood T cell genes up or down-regulated by P4 in the presence or absence of exogenous TGFb1. Peripheral blood T cells were relatively unresponsive with only 30-70 genes regulated by P4. IL-6 receptor (IL-6R) expression was greatly down-regulated by progesterone in cord blood but not PB, T cells. Overall, these differences in gene expression are consistent with the differential responses of cord blood and peripheral blood T cells to progesterone. To gain insights into the differences of progesterone and control dendritic cells, we performed a microarray study and found ~180 genes regulated by progesterone in dendritic cells. The gene expression information suggests that progesterone has the potential to alter dendritic cell responses to cytokines, chemokine production, and migration which in combination would control T cell differentiation. |
| 1216 | GSE6369 |
Profile | Expression profiling of prostate carcinoma tissue samples of benign and metastatic in disease progression. Keywords: disease-state analysis |
| 1217 | GSE21422 |
Profile | Human healthy tissue samples DCIS and invasive mammary tumors were analyzed in order to identify marker genes which show enhanced expresssion in DCIS and invasive ductal carcinomas. Using this approach, we were able to identify a set of genes which might allow a better detection of DCIS and invasive carcinomas in the future. |
| 1218 | GSE20070 |
Profile | We have previously reported that elevated fibroblast growth factor-2 (FGF-2) expression is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer and that these risks are reduced in tumors co-expressing an endogenous antisense (FGF-AS) RNA. In the present study we examined the role of the endogenous FGF-AS transcript in the regulation of FGF-2 expression in the human lung adenocarcinoma cell line, Seg-1. FGF-2 and FGF-AS were temporally and spatially co-localized in the cytoplasm of individual cells, and knock-down of either FGF-2 or FGF-AS by target specific siRNAs resulted in dose-dependent up-regulation of the complementary transcript and its encoded protein product. Using a luciferase reporter system we show that these effects are mediated by interaction of the endogenous antisense RNA with the 3’UTR of the FGF-2 mRNA. Deletion mapping identified a 392 nt sequence in the 5823 nucleotide FGF-2 untranslated tail which is targeted by FGF-AS. siRNA-mediated knockdown of either FGF-AS or FGF-2 significantly increased the stability of the complementary partner mRNA, demonstrating that these mRNAs are mutually regulatory. Knockdown of FGF-AS also resulted in reduced expression of argonaute-2 (AGO-2) and a number of other elements of the endogenous microRNA/RNAi pathways. Conversely, siRNA-mediated knockdown of AGO-2 significantly increased the stability of the FGF-2 mRNA transcript, and the steady-state levels of both FGF-2 mRNA and protein, suggesting a role for AGO-2 in the regulation of FGF-2 expression. |
| 1219 | GSE36667 |
Profile | We established induced pluripotent stem cells (iPSC) from centrenarians by retroviral transduction of primary human fibroblasts. To show the similarity between 201B7 iPSC and 100-1 #16 iPSC (induced pluripotent stem cells from centenarian) this experiment was designed. |
| 1220 | GSE28698 |
Profile | In order to investigate the mechanism whereby TEL-PDGF-beta (ETV6-PDGFRB) interferes with human hematopoietic progenitors proliferation and differentiation we analyzed the gene expression response downstream this oncogene. CD34+ cells infected with lentivirus coding for TEL-PDGFRb were cultured for 7 days in the absence of cytokines. Using Affymetrix microarrays, we compared gene expression in these cells and in cells treated for 4 h with low dose imatinib (Glivec), a potent PDGFR inhibitor, to switch off TEL-PDGFRb signaling. |
| 1221 | GSE18995 |
Profile | Lung donation after cardiac death (DCD) in contrast to donation after brain death (DBD), is a promising and increasingly common method to help relieve the shortage of donor organs. However, the pathogenetic consequences of retrieved lungs after DCD vs. DBD have not been clarified. We aimed to study the differential gene expression profiles in lungs of DCD and DBD patients. |
| 1222 | GSE39189 |
Profile | microRNA-155 acts as an oncogenic miRNA in B-cell lymphoproliferative disorders including Waldenstrom Macroglobulinemia (WM) and Chronic Lymphocytic Leukemia (CLL). we used an 8-mer LNA (locked nucleic acid) phosphorothioate oligonucleotide targeting the seed region of miR-155 to effectively antagonize in vitro tumor growth in WM. |
| 1223 | GSE32169 |
Profile | In theses experimetns we have analized the differential gene expression profile in human trabecular meshwork cells phagocytically challenged to E. coli and pigment under physiological and oxidative stress conditions using affymetrix microarrays |
| 1224 | GSE25436 |
Profile | Differential gene expression analysis of parental and sub-lines of melanoma cell line resistant to F5 CTL lymphocyte |
| 1225 | GSE12287 |
Profile | Heat shock protein 90 (Hsp90) is essential for the stability and the function of many client proteins such as ERB2, C-RAF, CDK4, HIF-1 aplha and AKT. Recent reports demonstrated that inhibition of Hsp90 modulates multiple functions required for survival of human cancer, such as myeloma (Mitsiades et al, Blood:107, 1092, 2006), The aim of this study is evaluate the effect of Hsp90 inhibition, and to identify molecular pathways responsible for anti-proliferative effect on ATL cells. For Hsp90 inhibition, Geldanamycin derivates, 17AAG (17-allylamino -17-demethoxygeldanamycin) and 17DMAG (17-(dimethylaminoethylamino) 17-demethoxygeldanamycin) were used in this study. Interleukin 2-independent ATL cell lines (MT-2 and MT-4) and an interleukin 2-dependent ATL cell line (TaY-E10) were incubated, with or without Hsp90 inhibitors. |
| 1226 | GSE19428 |
Profile | Melanomas are often infiltrated by activated inflammatory cells. Thus melanoma cells are very likely stimulated by inflammatory cytokines. In order to assess the impact of common inflammatory cytokines, we investigated the gene expression profile of melanoma cell lines before and after cytokine treatment in vitro. |
| 1227 | GSE18195 |
Profile | Microarrays were used to determine the efficacy of bevacizumab (a monoclonal antibody against the vascular endothelial growth factor and its receptors.) on endometrial cancer cells. Endometrial cancer is the most frequent gynecologic cancer in women. Long term outcomes for patients with advanced stage or recurrent disease are poor. Targeted molecular therapy against the vascular endothelial growth factor (VEGF) and its receptors constitute a new therapeutic option for these patients. The goal of our work was to assess the potential effectiveness of inhibition of VEGF/VEGFR signaling in a xenograft model of endometrial cancer using bevacizumab (Avastin a humanized antibody against VEGFA). We also aimed to identify molecular markers of sensitivity or resistance to this agent. We show that bevacizumab retards tumor growth in athymic mice by inhibiting molecular components of signaling pathways that sustain cell survival and proliferation. We also demonstrate that resistance to bevacizumab may involve up-regulation of antiapoptotic genes and certain proto-oncogenes. |
| 1228 | GSE17007 |
Profile | NC1153 was shown to inhibit JAK3 tyrosine kinase. Lymphocytes survival depends on the integrity of STAT5 the primary downstream target of JAK3. In this study microarrays were used to test the effect of a JAK3 inhibitor, NC1153, on the gene expression profile of a human leukemia cell line. |
| 1229 | GSE29137 |
Profile | Numb has 4 known variants and we are reporting two novel Numb variants Numb5 and Numb6 in this study. The metastaticability variations between the numb variants were evaulated through the transcriptome. |
| 1230 | GSE27206 |
Profile | Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease and is the second most common genetic disorder leading to death in childhood. Motoneurons derived from induced pluripotent stem cells (iPS cells) obtained by reprogramming SMA patient and his healthy father fibroblasts and genetically corrected SMA-iPSC obtained converting SMN2 into SMN1 with target gene correction (TGC), were used to study gene expression and splicing events linked to pathogenetic mechanisms. Microarray technology was used to assess global gene expression profiles of iPSC from SMA patient, unaffected father and iPS 19.9 (Prof. J. Thomson's lab) compared to transcriptomic data obtained by corresponding fibroblasts. |
| 1231 | GSE22132 |
Profile | Patients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in individuals with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (p<0.0001) were found to be up-regulated in platelets from SLE patients as compared to healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFNα which up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE. |
| 1232 | GSE21930 |
Profile | Although intestinal microbiota play a pivotal role in the development of host immune system this biological issue was not so far studied in great detail. In this study we examined immune response of Caco-2 enterocytes after incubation with common probiotic Bifidobacterium animalis subsp. lactis BB-12 for 4 hours. We used microarrays to inspect the global gene expression of Caco-2 cells upon co-culturing with B. animalis subsp. lactis BB-12 and several distinct immune-related genes up-regulated during this process. |
| 1233 | GSE39335 |
Profile | The beneficial effects of glucocorticoids (GCs) in acute lymphoblastic leukemia (ALL) are based on their ability to induce apoptosis. Omics technologies such as DNA microarray analysis are widely used to study the changes in gene expression and have been successfully implemented in biomarker identification. In addition time series studies of gene expression enable the identification of correlations between kinetic profiles of glucocorticoid receptor (GR) target genes and diverse modes of transcriptional regulation. This study presents a genome-wide microarray analysis of both our and published Affymetrix HG-U133 Plus 2.0 data in GCs-sensitive and -resistant ALL. GCs-sensitive CCRF-CEM-C7-14 cells were treated with dexamethasone at three time points (0 h, 2 h and 10 h). The treated samples were then compared to the control (0 h). The published data used were as follows: GSE2677: GSM51674: B-ALL-24-24h GSM51675: B-ALL-24-6h GSM51676: B-ALL-24-0h GSM51680: B-ALL-17-24h GSM51681: B-ALL-17-8h GSM51682: B-ALL-17-0h GSM51677: B-ALL-13-24h GSM51678: B-ALL-13-8h GSM51679: B-ALL-13-0h GSM51683: B-ALL-31-24h GSM51684: B-ALL-31-6h GSM51685: B-ALL-31-0h GSM51686: B-ALL-32-24h GSM51687: B-ALL-32-6h GSM51688: B-ALL-32-0h GSM51689: B-ALL-33-24h GSM51690: B-ALL-33-6h GSM51691: B-ALL-33-0h GSM51692: B-ALL-37-24h GSM51693: B-ALL-37-6h GSM51694: B-ALL-37-0h GSM51695: B-ALL-38-24h GSM51696: B-ALL-38-6h GSM51697: B-ALL-38-0h GSM51698: B-ALL-40-24h GSM51699: B-ALL-40-6h GSM51700: B-ALL-40-0h GSM51701: B-ALL-43-24h GSM51702: B-ALL-43-6h GSM51703: B-ALL-43-0h GSM51707: T-ALL-25-24h GSM51708: T-ALL-25-6h GSM51709: T-ALL-25-0h GSM51704: T-ALL-20-24h GSM51705: T-ALL-20-8h GSM51706: T-ALL-20-0h GSM51710: T-ALL-2-24h GSM51711: T-ALL-2-8h GSM51712: T-ALL-2-0h GSE2842 GSM60545: S-Line-PreB-6h-EtOH GSM60546: S-Line-PreB-6h-GC GSM60547: S-Line-PreB-24h-GC GSM60542: S-Line-C7H2-6h-EtOH GSM60543: S-Line-C7H2-6h-GC GSM60544: S-Line-C7H2-24h-GC GSM60560: R-Line-CEMC1-6h-EtOH GSM60561: R-Line-CEMC1-6h-GC GSM60562: R-Line-CEMC1-24h-GC GSM60564: R-Line-C7R1-6h-EtOH GSM60566: R-Line-C7R1-6h-GC GSM60576: R-Line-C7R1dim-low-6h-EtOH GSM60578: R-Line-C7R1dim-low-6h-GC GSM60579: R-Line-C7R1dim-low-24h-GC GSM60581: R-Line-PreB-6h-EtOH GSM60583: R-Line-PreB-6h-GC GSM60584: R-Line-PreB-24h-EtOH GSM60586: R-Line-PreB-24h-GC GSM60548: C-Line-CEMC1-ratGR-6h-EtOH GSM60549: C-Line-CEMC1-ratGR-6h-GC GSM60550: C-Line-CEMC1-ratGR-24h-GC GSM60551: C-Line-C7R1dim-high-6h-EtOH GSM60552: C-Line-C7R1dim-high-6h-GC GSM60553: C-Line-C7R1dim-high-24h-GC |
| 1234 | GSE7429 |
Profile | B cells produce important cytokines regulate bone metabolism. We comparison gene expression patterns of circulating B cells in blood from 20 postmenopausal females with low or high bone mineral density (BMD): 10 low BMD vs. 10 high BMD. In total 29 differentially expressed genes were identified including some novel genes to be relevant to bone metabolism. These results provide insight into the role of B cells in pathologic osteoporosis. Keywords: disease state analysis |
| 1235 | GSE7669 |
Profile | mRNA expression levels in synovial fibroblasts in 6 rheumatoid arthritis patients versus 6 osteoarthritis patients. Keywords: disease type comparison mRNA expression study |
| 1236 | GSE39136 |
Profile | Effect of FOXO knockdown on E2F1-mediated transcription |
| 1237 | GSE5116 |
Profile | The estrogen-dependence of breast cancer has long been recognized however, the role of 17β-estradiol (E2) in cancer initiation was not known until we demonstrated that it induces complete neoplastic transformation of the human breast epithelial cells MCF-10F. E2-treatment of MCF-10F cells progressively induced high colony efficiency and loss of ductulogenesis in early transformed (trMCF) cells and invasiveness in Matrigel invasion chambers. The cells that crossed the chamber membrane were collected and identified as bsMCF, and their subclones designated bcMCF, and the cells harvested from carcinoma formation in SCID mice designated caMCF. These phenotypes correlated with gene dysregulation during the progression of the transformation. The highest number of dysregulated genes was observed in caMCF, being slightly lower in bcMCF, and lowest in trMCF. This order was consistent with the extent of chromosome aberrations (caMCF > bcMCF >>> trMCF). Chromosomal amplifications were found in 1p36.12-pter, 5q21.1-qter and 13q21.31-qter. Losses of the complete chromosome 4 and 8p11.21-23.1 were found only in tumorigenic cells. In tumor-derived cell lines, additional losses were found in 3p12.1-14.1, 9p22.1-pter and 18q11.21-qter. Functional profiling of dysregulated genes revealed progressive changes in the integrin signaling pathway, inhibition of apoptosis, acquisition of tumorigenic cell surface markers and epithelial-mesenchymal transition. In tumorigenic cells, the levels of E-cadherin, EMA, and various keratins were low and CD44E/CD24 were negative, whereas SNAI2, vimentin, S100A4, FN1, HRAS, TGFβ1 and CD44H were high. The phenotypic and genomic changes triggered by estrogen exposure that lead normal cells to tumorigenesis confirm the role of this steroid hormone in cancer initiation. Keywords: Cell type comparison |
| 1238 | GSE15947 |
Profile | Background: Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D 1α,25 dihydroxyvitamin D3 (1,25(OH)2D) has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown. Results: We examined the effect of 1,25(OH)2D (+/- 100 nM, 6, 24, 48 h) on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH)2D (Affymetrix U133 Plus 2.0, n=4/treatment per time and dose). Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up), 24 h, 1816 (60 % up), 48 h, 3566 (38 % up). 288 transcripts were regulated similarly at all time points (182 up, 80 down) and many of the promoters for these transcripts contained putative vitamin D response elements. Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway) and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways). There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h. Conclusions: Our data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention. In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis. |
| 1239 | GSE9916 |
Profile | Direct comparison of the genome-level expression patterns of THP-1 cells exposed to either LPS or heat shock Peripheral blood mononuclear cells (PBMC) serve a sentinel role allowing the host to efficiently sense and adapt to the presence of danger signals. Herein we have directly compared the genome-level expression patterns (microarray) of human PBMC (THP-1 cells) subjected to one of two canonical danger signals heat shock and lipopolysaccharide (LPS). Based on sequential expression and statistical filters, and in comparison to control cells, we found that 3,988 genes were differentially regulated in THP-1 cells subjected to LPS stress, and 2,921 genes were differentially regulated in THP-1 cells subjected to heat shock stress. Venn analyses demonstrated that the majority of differentially regulated genes (greather than or equal to 70%) were uniquely expressed in response to one of the two danger signals. Functional analyses demonstrated that the two danger signals induced expression or repression of genes corresponding to unique pathways, molecular functions, biological processes, and gene networks. In contrast, there were 184 genes that were commonly upregulated by both stress signals, and 430 genes that were commonly downregulated by both stress signals. Interestingly, the 184 commonly upregulated genes corresponded to a gene network broadly related to inflammation, and more specifically to chemokine signaling. These data demonstrate that the mononuclear cell responses to the canonical stress signals, heat shock and LPS, are highly divergent. However, there is a heretofore unrecognized common pattern of gene network expression corresponding to chemokine-related biology. The data also serve as a reference database for investigators in the field of stress signaling. Keywords: treated vs non treated |
| 1240 | GSE18681 |
Profile | We present evidence for an autocrine cytokine network in human ovarian cancer that has paracrine actions on the tumour microenvironment. In experiments using bioinformatics analysis of large gene expression array datasets and ovarian cancer biopsies we found that the inflammatory cytokines TNF-α and IL-6, the chemokine receptor CXCR4 and its ligand CXCL12, are co-regulated in malignant cells. We named this co-regulation the TNF network. We had access to a unique set of ascites cell samples from patients with advanced ovarian cancer treated with the therapeutic anti-human TNF-α antibody infliximab. Serial samples pre and during treatment were obtained during paracentesis (drainage of ascites fluid for symptomatic relief). In nine of these patients there was sufficient mRNA available for gene expression profile analysis before treatment. |
| 1241 | GSE6802 |
Profile | Bronchial epithelial cells represent the first line of defense against invading airborne pathogens. They are important contributors to innate mucosal immunity and provide a variety of anti-microbial effectors. To investigate the role of epithelial cells upon infection of airway pathogens we stimulated BEAS-2B cells for 4 h with UV-inactivated bronchial pathogens including Staphylococcus aureus, Pseudomonas aeruginosa and Respiratory Syncitial Virus (RSV) that among other receptors can strongly activate TLR2, TLR4 and TLR3, respectively. Keywords: expression profiling, response to pathogens |
| 1242 | GSE12891 |
Profile | Gene expression profiles during the differentiation of EPCs into OECs were analyzed. |
| 1243 | GSE3325 |
Profile | An integrative analysis of this compendium of proteomic alterations and transcriptomic data was performed revealing only 48-64% concordance between protein and transcript levels. Importantly differential proteomic alterations between metastatic and clinically localized prostate cancer that mapped concordantly to gene transcripts served as predictors of clinical outcome in prostate cancer as well as other solid tumors. Keywords: prostate cancer progression |
| 1244 | GSE25332 |
Profile | Using a mimic miR-200c was restored to an aggressive Type 2 endometrial cancer cell line, Hec50 |
| 1245 | GSE35251 |
Profile | Compare the difference between pairwise NOF and iCAF (2d) tissues for one patient |
| 1246 | GSE29316 |
Profile | Canonical Hedgehog (Hh) signaling regulates the expression of genes that are critical to the patterning and development of a variety of organ systems. In adult both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligand, activation occurs within the stromal microenvironment (Yauch et al., 2009). In situ hybridization of the pathway target gene, Ptch1, shows that signaling is located at stromal perivascular fibroblast-like cells in xenograft tumor sections derived from Hh-expressing colorectal cancer cell lines. To study the downstream genes regulated by Hh signaling, we treated a primary human colon myofibroblast, CCD-18Co, with SHH (1 ug/ml) or no treatment (control) in serum-free medium supplemented with 0.1% BSA for 72 hrs and performed microarray analysis (Affymetrix U133P) on these samples. |
| 1247 | GSE49584 |
Profile | tumor-stroma crosstalk drives pancreatic carcinogenesis we used time-resolved genome-wide transcriptional profiling to analyse changes caused by co-exposure of pancreatic tumor and stellate cells |
| 1248 | GSE5809 |
Profile | During the invasive phase of implantation trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting immuno-acceptance of the fetal allograph. Global cross-talk between the trophoblast and the decidua has not been elucidated to date, and the current study used a functional genomics approach to investigate these paracrine interactions. Our data demonstrate a significant induction of pro-inflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune environment of the decidua to facilitate the process of implantation and assure an enriched cytokine/chemokine environment, while limiting mitotic activity of the stromal cells during the invasive phase of implantation. Keywords: Gene expression arrays in human stromal cells |
| 1249 | GSE18565 |
Profile | Human and mouse blood each contain two monocyte subsets. Here we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species’ subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPARγ signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse. Keywords: Expression profiling by array |
| 1250 | GSE20085 |
Profile | Since bone metastatic breast cancer is an incurable disease causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions. |
| 1251 | GSE31447 |
Profile | The ER stress inducing agent Thapsigargin (TG) and/or the cytoprotective agent Salubrinal were applied to lymphoblastoid cell lines. TG induced lytic replication as well as a distinct pattern of gene expression changes. This study was designed to identify host genes mediating lytic replication secondary to ER stress. |
| 1252 | GSE27034 |
Profile | Peripheral arterial disease (PAD) is a relatively common manifestation of systemic atherosclerosis that leads to progressive narrowing of the lumen of leg arteries. Circulating monocytes are in contact with the arterial wall and can serve as reporters of vascular pathology in the setting of PAD. We performed gene expression analysis of peripheral blood mononuclear cells (PBMC) in patients with PAD and controls without PAD to identify differentially regulated genes. We identified 87 genes differentially expressed in the setting of PAD; 40 genes were upregulated and 47 genes were downregulated. We employed an integrated bioinformatics pipeline coupled with literature curation to characterize the functional coherence of differentially regulated genes. Notably upregulated genes mediate immune response, inflammation, apoptosis, stress response, phosphorylation, hemostasis, platelet activation and platelet aggregation. Downregulated genes included several genes from the zinc finger family that are involved in transcriptional regulation. These results provide insights into molecular mechanisms relevant to the pathophysiology of PAD. |
| 1253 | GSE11755 |
Profile | Objective. Meningococcal sepsis remains an important cause of childhood morbidity and mortality. Largely due to logistic complexities of research in young children with acute life-threatening disease very little is known regarding differential expression kinetics and molecular regulation of immune response genes in leukocyte subsets. Materials and methods. In this prospective case-control study, six children with meningococcal sepsis were included. Blood was drawn at four time points (t=0, t=8, t=24 and t=72 h after admission to the paediatric intensive care unit). Blood was also collected from matched controls. Detailed immunophenotyping of leukocytes was performed; RNA isolated from whole blood, lymphocytes, monocytes, and granulocytes was used to perform Affymetrix micro-array gene expression analysis. Results and conclusion. There were no differences in total leukocyte count between patients and controls. In contrast to previous in vitro studies we observed an unexpected decrease in NK cell numbers, as well as downregulation of NK cell specific and cytotoxic T-cell related gene expression in patients with meningococcal septic shock. By contrast, expression of genes, involved in innate immunity and several other pathways, differed between the different leukocyte subpopulations in a dynamic fashion. Compared to previously reported gene expression profiles, it was possible to define a meningococcal sepsis specific expression profile. |
| 1254 | GSE28590 |
Profile | Smad2/3 are transcription factors that engage in TGF-beta-induced transcription. We determined and analyzed HepG2 and Hep3B-specific Smad2/3 binding sites by ChIP-chip. We used expression microarrays to compare the Smad2/3 and HNF4alpha binding sites identified by ChIP-chip or ChIP-seq respectively, to TGF-beta-induced gene expressions. |
| 1255 | GSE11185 |
Profile | To examine the differences between NOR1 and its fusion gene product EWS/NOR1 we compared the gene expression profiles of NOR1- and EWS/NOR1-overexpressing 293 cells. Keywords: gene comparison |
| 1256 | GSE12839 |
Profile | The cytokine interleukin-12 (IL-12) is known to play a central role in adaptive and innate immunity. We employed microarray analysis of IL-12 induced gene expression to provide further insights into its effects on immune response. Keywords: Paired study of expression levels: Treated vs. Control |
| 1257 | GSE6475 |
Profile | The pathogenesis of acne has been linked to multiple factors such as increased sebum production inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Keywords: acne lesion, normal skin |
| 1258 | GSE19240 |
Profile | Complete identification of the bone marrow niche remains one of the most progressing fields. Attempts to identify soluble factors involved in stem cell renewal have been less successful. We have previously shown that endothelial cells (EC) can induce the long-term proliferation of hematopoietic progenitor cells (HPC) especially when they had been subjected to an inflammatory stimulus like interleukins (IL) 1. To identify yet unknown growth factors, we compared the expression profile of IL-1 stimulated and non-stimulated endothelial cells. |
| 1259 | GSE3529 |
Profile | Three human ER+ breast cancer cell lines--MCF-7 T47-D, BT-474--grown with or without estradiol (E2). Keywords: Cell Line Comparison |
| 1260 | GSE17315 |
Profile | Micro RNAs (miRNAs) miR-130a miR-203 and miR-205 are jointly downregulated in prostate cancer and act as repressors of AR-signaling. MiRNAs are small non-coding RNAs that regulate the expression of specific mRNA targets mainly by translational repression, mRNA deadenylation or cleavage. Reconstitution of these lost miRNAs in the LNCaP PCa cell line cause morphology changes, growth arrest, and apoptosis, increasing when the miRNAs were co-expressed. Bioinformatic target prediction, mRNA expression and protein expression analysis upon overexpression of these miRNAs congruently identified targets known to be overexpressed in PCa and to be involved in AR trans-activation. This series profiles loss in mRNA expression in LNCaP cells transfected with one of the three miRNAs miR-130a, miR-203 and miR-205 compared to LNCaP cells transfected with a scramble miRNA. |
| 1261 | GSE36634 |
Profile | Glial progenitor cells comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for CNS remyelination and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function. |
| 1262 | GSE41315 |
Profile | Ezh2 protein is the enzymatic component of the Polycomb Repressive Complex (PRC)-2 which represses its target genes by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 have been identified in diffused large B cell lymphomas (DLBCLs) and follicular lymphomas (FLs). To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we have developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding and competing with the methyl group donor S-Adenosyl methionine (SAM). EI1-treated cells exhibit genome-wide loss of H3K27 methylation. Furthermore, inhibition of Ezh2 by EI1 in DLBCL cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer with the Ezh2 mutation. In this microarray experiment we examined the global gene expression changes in DLBCL cell line Karpas422 (Ezh2Y641N) after EI1 treatment for up to 6 days. |
| 1263 | GSE5563 |
Profile | In order to understand the molecular mechanism behind Vulvar Intraepithelial Neoplasia (VIN) we have analyzed the gene expression profile of VIN lesions in comparison to controls. Keywords: disease state analysis |
| 1264 | GSE40051 |
Profile | FOXM1 plays a key role in M phase in normal cells and is overexpressed in human glioma. We found that FOXM1 deprivation could sensitize the glioma cells to TMZ chemotherapy. To find out the mechanistic regulation of FOXM1 in chemo-resistant genes we used microarrays to select the potential genes regulated by FOXM1 which dominates in glioma chemo-resistance. |
| 1265 | GSE23935 |
Profile | TGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma. Differential gene expression analysis of patient-derived primary cultured glioblastoma cells treated with the TGF-beta receptor inhibitor LY2109761 |
| 1266 | GSE14825 |
Profile | Rhabdomyosarcomas (RMS) are characterized by expression of myogenic specification genes such as MyoD and/or Myf5, as well as their bHLH partners for heterodimerization, the E-proteins. We have shown that expression of a forced heterodimer of MyoD with one of the E2A proteins, E12, leads to differentiation in a RMS cell culture model when exposed to low serum conditions. Keywords: RD expressing Myod~E heterodimers and controls |
| 1267 | GSE32668 |
Profile | Estrogens have been reported to activate several processes via membrane binding to either classic estrogen receptors (ERs) or GPR30. We have used either estradiol or BSA-conjugated estradiol in order to initiate membrane-initiated actions and ICI 172780 (ICI) or G15 to explore ER- and GPR30-related transcription. Our results show that the majority of G15-inhibited transcription is depending on ERs, as it is also inhibited by ICI. However, a small number of transcripts, related to specific actions/pathways is either exclusively inhibited by G15, providing evidence about a specific GPR30 signature, or not inhibited by ICI or G15 suggesting the existence of another, yet unidentified estrogen receptor. |
| 1268 | GSE28998 |
Profile | The aim of this investigation was to evaluate the effect of training on the global transcriptional response of skeletal muscle to an acute bout of resistance exercise. |
| 1269 | GSE6233 |
Profile | Ezrin belongs to the ezrin¨Cradixin¨Cmoesin (ERM) family proteins which cross-link actin cytoskeleton and plasma membrane, and is actively involved in regulating the growth and metastatic capacity of cancer cells. Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies in the world and the expression of ezrin in ESCC has been described only recently, but its roles and mechanism still remained unclear. we have used the pSUPER RNAi system to stably suppress the expression of the ezrin gene in EC109, an esophageal squamous carcinoma cell line, and then cDNA microarray was performed to explore some changed genes with ezrin silence. Keywords: Gene expression after RNAi |
| 1270 | GSE22759 |
Profile | A predictive gene list for response to high dose melphalan therapy in patients diagnosed with multiple myeloma is generated by combining results from dose response experiments and microarray data using a B-cell line panel and the introduction of multivariate regression techniques. |
| 1271 | GSE6861 |
Profile | EORTC 10994 phase III breast cancer clinical trial comparing FEC (5-fluorouracil cyclophosphamide, epirubicin) with ET (epirubicin, docetaxel). 161 needle biopsies of locally advanced or large operable breast tumours were hybridised to Affymetrix X3P chips. The array data from the ER negative tumours (28/65 pathological CR in the FEC arm, 27/59 pathological CR in the ET arm) were used to validate the cell line-based chemotherapy response predictors developed by the Potti/Nevins group at Duke University (doi:10.1038/nm1491). Keywords: Tumour profiling |
| 1272 | GSE46925 |
Profile | Aberrant production and/or function of multiple host systemic factors (e.g. metabolic and immune-inflammatory mediators) act in concert to promote a ‘tumorigenic’ host milieu that directly promotes an aggressive malignant phenotype as well as drug resistance. Hence, strategies with the capacity to simultaneously act across multiple host systemic pathways may be required to optimize therapeutic outcomes in solid tumors. We hypothesized that chronic aerobic training, a pleiotropic whole-body intervention, modulates multiple systemic host pathways that, in turn, effectively alters cancer cell phenotype in vitro. Plasma samples from patients with solid tumors exposed to chronic aerobic training or sedentary control were comprehensively characterized for changes in immune, inflammatory, and metabolic pathways. Compared with sedentary control, aerobic training caused significant reductions in interleukin (IL)-4, macrophage inflammatory protein-1 beta (MIP1-β), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), and hepatocyte growth factor (HGF). There were no significant changes in leukocyte phenotype or any plasma metabolite signatures. Exposure of estrogen receptor (ER) distinct human breast cancer cell lines (MCF-7 and MDA-MB-231) to post-intervention serum from breast cancer patients exposed to aerobic training caused marked increases in proliferation, migration, and apoptosis, compared to control patient serum. Only the combination of cytokines significantly reduced in plasma following aerobic training recapitulated the phenotype observed with patient serum in MCF-7 cells whereas only the single addition of MIP-1β or HGF significantly increased apoptosis in MDA-MB-231 cells. Co-culturing of MDA-MB-231 cells with patient exercise serum and a HGF neutralizing antibody increased proliferation and completely abrogated exercise serum-induced apoptosis. Finally, whole-genome microarray of MDA-MB-231 cells exposed to exercise or control patient serum revealed differential modulation of 310 genes including PTEN, CDK3, and IGFBP1. Our findings indicate the widespread potential of chronic aerobic training to modulate host immune-inflammatory systemic factors in patients with solid tumors. Modulation of such pathways directly alters breast cancer phenotypes providing novel insight into the molecular pathways by which exercise may inhibit malignant progression. |
| 1273 | GSE13046 |
Profile | OSM increases the antiviral effect of IFNα in Huh7 cells infected with hepatitis A virus (HAV) or HCV replicon and synergizes with IFNα in the induction of antiviral genes |
| 1274 | GSE41883 |
Profile | The objective of this study was to determine how TNF-a an important proinflammatory cytokine, affects gene expression in the human annulus. Cells were grown in a 3D collagen construct for 14 days with TNF-a. mRNA was isolated and subjected to microarray. Fold changes in gene expression were determined via GeneSifer software. |
| 1275 | GSE28681 |
Profile | For gene expression profiling we used immortalized human mammary epithelial cells (HMLE) to isolate a pure epithelial fraction of cells by positive selection for CD24 expression using Magnetic Activated Cell Sorting (=24hi). We independently isolated 3 mesenchymal subpopulations (msp1-3) from HMLE cells by collecting floating cells from cultured monolayer HMLE cells. |
| 1276 | GSE7586 |
Profile | Chronic inflammation during placental malaria (PM) caused by Plasmodium falciparum is most frequent in first-time mothers and is associated with poor maternal and fetal outcomes. In the first genome wide analysis of the local human response to sequestered malaria parasites we identified genes associated with chronic PM, then localized the corresponding proteins and immune cell subsets in placental cryosections. Keywords: Disease state analysis |
| 1277 | GSE23493 |
Profile | Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases is not fully understood. The knowledge of global gene expression will help us to devlop early diagnostic biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB77 on human Kidney cells leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. Keywords: time course |
| 1278 | GSE16157 |
Profile | Cancer cells consume large amounts of glucose because of their specific metabolic pathway. However cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction. Cancer cells with dysfunctional mitochondria, such as mitochondrial DNA-deficient rho0 cells and electron transport chain blocker-treated cells, were highly sensitive to glucose deprivation. Our data demonstrated that this sensitization was caused by failure of the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER). This study suggests a link between mitochondria and the ER during the UPR under glucose deprivation conditions and that mitochondria govern cell fate, not only through ATP production and apoptosis regulation but also through modulating the UPR for cell survival. |
| 1279 | GSE6205 |
Profile | In order to investigate the patterns of genetic lesions in a panel of 23 Human Multiple Myeloma Cell Lines (HMCLs) we made a genomic integrative analysis involving FISH and both gene expression and genome-wide profiling approaches. The expression profiles of the genes targeted by the main IGH translocations showed that the WHSC1/MMSET gene involved in t(4;14)(p16;q32) was expressed at different levels in all of the HMCLs, and that the expression of the MAF gene was not restricted to the HMCLs carrying t(14;16)(q32;q23). Supervised analyses identified a limited number of genes specifically associated with t(4;14) and involved in different biological processes. The signature related to MAF/MAFB expression included the known MAF target genes CCND2 and ITGB7, as well as genes controlling cell shape and cell adhesion. Genome–wide DNA profiling allowed the identification of a gain on chromosome arm 1q in 88% of the analyzed cell lines, together with recurrent gains on 8q, 18q, 7q and 20q; the most frequent deletions affected 1p, 13q, 17p and 14q; and almost all of the cell lines presented LOH on chromosome 13. Two hundred and twenty-two genes were found to be simultaneously overexpressed and amplified in our panel, including the BCL2 locus at 18q21.33. Our data further support the evidence of the genomic complexity of multiple myeloma and reinforce the role of an integrated genomic approach in improving our understanding of the molecular pathogenesis of the disease. Keywords: cell line comparison |
| 1280 | GSE18946 |
Profile | Herpesviruses are known to encode micro (mi)RNAs and to use them to regulate the expression of both viral and cellular genes. The genome of Kaposi’s sarcoma herpesvirus (KSHV) encodes a cluster of twelve miRNAs which are abundantly expressed during both latency and lytic infection. Relatively few cellular targets of KSHV miRNAs are known. Here, we used a microarray expression profiling approach to analyze the transcriptome of both B lymphocytes and endothelial cells stably expressing KSHV miRNAs and monitor the changes induced by the presence of these miRNAs. We generated a list of potential cellular targets by looking for miRNA seed-match-containing transcripts that were significantly down regulated upon KSHV miRNAs expression. Interestingly, the overlap of putative targets identified in B lymphocytes and endothelial cells was minimal, suggesting a tissue-specific target-regulation by viral miRNAs. Among the putative targets, we identified caspase 3, a critical factor for the control of apoptosis, which we validated using luciferase reporter assays and western blotting. In functional assays we obtained further evidence that KSHV miRNAs indeed protect cells from apoptosis. |
| 1281 | GSE35330 |
Profile | Natural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy. |
| 1282 | GSE41499 |
Profile | Paired platinum-sensitive & platinum-resistant cell lines PEO1 and PEO4 (respectively) were derived from the same patient. Cell line cultures were profiled with the HT-HGU133a GeneChip to investigate chemotherapy resistance related expression of genes marked with different histone modifications in a primary ovarian tumour (clinical data for the primary ovarian tumour is available as Series supplementary file). |
| 1283 | GSE11440 |
Profile | A summary of the work associated to these microarrays is the following: Methotrexate (MTX) is one of the earliest cytotoxic drugs used in cancer therapy and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment with methotrexate is limited by the development of drug resistance, which may be acquired through different ways. To get insights into the mechanisms associated with drug resistance and sensitization we have performed a functional analysis of genes deregulated in methotrexate resistant cells, either due to its co-amplification with the DHFR gene or as a result of a transcriptome screening using microarrays. Genes adjacent to dhfr locus and included in the 5q14 amplicon were overexpressed in HT29 MTX-resistant cells. Treatment with siRNAs against those genes caused a slight reduction in cell viability in both HT29 sensitive and resistant cells. On the other hand, microarray analysis of HT29 and HT29 MTX resistant cells unveiled overexpression of caveolin 1, enolase 2 and PKCa genes in treated cells without concomitant copy number gain. siRNAs against these three genes effectively reduced cell viability and caused a decreased MTX resistance capacity. Moreover, overexpression of E-cadherin, which was found underexpressed in MTX-resistant cells, also sensitized the cells toward the chemotherapeutic agent. We provide functional evidences indicating that caveolin 1 and E-cadherin may play a critical role in cell survival and may constitute potential targets for coadjuvant therapy. Keywords: DHFR, Methotrexate, drug resistance |
| 1284 | GSE15792 |
Profile | To globally address the function of a novel ncRNA PCARNEQ located in chromosome 8q24 microarray analysis was performed on RNA isolated from prostate cancer cell line LNCaP cells treated with siRNA to PCARNEQ and the control siRNA to EGFP (siEGFP). |
| 1285 | GSE1650 |
Profile | Comparison of severely emphysematous tissue removed at lung volume reduction surgery to that of normal or mildly emphysematous lung tissue resected from smokers with nodules suspicious for lung cancer. Data obtained from the 18 patients with severe emphysema and 12 patients with mild/no emphysema. Research may provide insights into the pathogenetic mechanisms involved in chronic obstructive pulmonary disease (COPD). Keywords: other |
| 1286 | GSE31475 |
Profile | We used the microarray data to analyze host cells response on A549 cells infected with A/duck/Malaysia/F119/3/1997(H5N3) |
| 1287 | GSE19672 |
Profile | The MaxiK potassium channel is a key modulator of smooth muscle tone. Due to its calcium and voltage sensitivity MaxiK is activated following depolarization and Ca2+ mobilization, therefore relaxing the muscle. We investigate the effects of silencing MaxiK for 48h in corpus cavernosuml smooth muscle (CCSM) cells to identify possible mechanisms of compensation through molecular crosstalk between pathways regulating smooth muscle tone. |
| 1288 | GSE26672 |
Profile | global gene expression were compared among human blood iPSC human fibroblas iPSC, human embryonic stem cells, human bone marrow MNC and human forskin fibroblast Reprogramming blood cells to induced pluripotent stem cells (iPSCs) provides a novel tool for modeling blood diseases in vitro. we demonstrated that iPSCs free of transgene and vector sequences could be efficiently generated from human bone marrow and cord blood mononuclear cells using non-integrating episomal vectors. The reprogramming described here is up to 100 times more efficient, occurs 1 to 3 weeks faster as compared to the reprogramming of fibroblasts, and does not require isolation of progenitors or multiple rounds of transfection. This approach provides an opportunity to explore banked normal and diseased cord blood and bone marrow samples without the limitations associated with virus-based methods. |
| 1289 | GSE20051 |
Profile | Microarray expression analysis to identify global changes in transcription in response to RAF inhibition. Genes under RAF control were identified in a panel of BRAFV600E tumor cells following the short-term inhibition of RAF using a pan-RAF kinase inhibitor, PLX4032 (Plexxikon). For comparison with changes in gene expression in response to MEK inhibition using PD0325901 (Pfizer), the following array data was referenced: (http://www.ncbi.nlm.nih.gov/geo/ (accession no. GSE10086)). |
| 1290 | GSE7458 |
Profile | We hypothesized that broad-scale expression profiling would provide insight into the regulatory pathways that control gene expression in response to stress and potentially identify novel heat-responsive genes. HEp2 cells were heated at 37 to 43 °C for 60 min to gauge the heat shock response, using as a proxy inducible HSP-70 quantified by western blot analysis. Based on these results, microarray experiments were conducted at 37, 40, 41, 42 and 43°C (3 replicates/temperature x 5 groups = 15 U95Aver2 GeneChips). Using linear modeling, we compared the sets of microarrays at 40, 41, 42 and 43°C with the 37°C baseline temperature and took the union of the genes exhibiting differential gene expression signal to create two sets of “heat shock response” genes, each set reflecting either increased or decreased RNA abundance. Leveraging human and mouse orthologous alignments, we used the two lists of co-expressed genes to predict transcription factor binding sites in silico, including those for heat shock factor 1 (HSF1) and heat shock factor 2 (HSF2) transcription factors. We discovered HSF1 and HSF2 binding sites in 15 genes not previously associated with the heat shock response. We conclude that microarray experiments coupled with upstream promoter analysis can be used to identify novel genes that respond to heat shock. Additional experiments are required to validate these putative heat shock proteins and facilitate a deeper understanding of the mechanisms involved during the stress response. Keywords: stress response, temperature, human epithelial cells |
| 1291 | GSE45036 |
Profile | We studied alcohol's effect on human embryonic stem cell line H9. Our main objective was to delineate the molecular mechanisms that are involved in changing the differentiation potential of hESCs. |
| 1292 | GSE13396 |
Profile | Human Rhinovirus (HRV) infection can trigger exacerbations of asthma. Understanding of the mechanisms provoking airway inflammation and remodeling in asthma as well as the pathogenic mechanisms of HRV infection and its association with asthma exacerbations, may offer significant opportunities for improved disease management. Genome-wide expression analysis of HRV type 1A-infected primary bronchial epithelial (PBE) cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of gene expression after HRV infection in vitro. Keywords: response to rhinovirus infection |
| 1293 | GSE33892 |
Profile | Gene regulatory networks that govern hematopoietic stem cells (HSC) and leukemia–initiating cells (L-IC) are deeply entangled. Thus the discovery of compounds that target L-IC while sparing HSC is an attractive but difficult endeavor. Presently, most drug discovery approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPC) to assess therapeutic index. Here, we present a combined in vitro and in vivo strategy to identify compounds specific to L-IC in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which most were toxic to normal HSPC. Of the 10 compounds that passed this initial filter, we chose to characterize a single compound, kinetic riboside (KR), on AML L-IC and HSPC. KR demonstrated comparable efficacy to standard therapies against 63 primary AMLs. In vitro, KR effectively targeted the L-IC-enriched CD34+CD38- AML fraction, while sparing normal HSPC enriched fractions, although these effects were mitigated on HSC assayed in vivo, and highlights the importance of in vivo L-IC and HSC assays to measure function. Overall, we provide a novel approach to screen large drug libraries for the discovery of anti-L-IC compounds for human leukemias. The gene expression profile of TEX and M9-ENL1 cells were compared to HL-60 (Series GSE16160, GSE28185) and THP1 (Series GSE28185), to determine if TEX and M9-ENL1 cells were more enriched in stem cell (embryonic, adult, leukemia, and cancer) gene sets using Gene Set Enrichment Analysis (GSEA). |
| 1294 | GSE4183 |
Profile | Background and Aims: Gene expression analysis of colon biopsies using high-density oligonucleotide microarray can contribute to the understanding of local pathophysiological alterations and to functional classification of precancerous adenoma different stage colorectal carcinomas (CRC) and inflammatory bowel diseases (IBD). Results: Significant overexpression of collagen IV, lipocalin-2, caveolin-1, calumenin genes, and significant dowregulation of aquaporin-8, amnionless homolog, prostaglandin D2 receptor genes were detected in CRC patients compared to normal. Adenoma samples were characterized by upregulated CD44 antigen, met proto-oncogene and downregulated chemokine ligand-12, ADAM-like decysin-1 and ATP-binding casette A8 discriminatory genes. In IBD samples significantly increased lipocalin-2, interferon induced transmembrane protein 1 and 3 mRNA levels, decreased zinc finger protein 91 and transient receptor potential cation channel M6 mRNA levels were found. Ulcerative colitis and Crohn’s disease can be distinguished according to the top five genes: cyclin-G2; tripartite motif-containing-31; TNFR shedding aminopeptidase regulator-1; C-type lectin superfamily member-14 and AMICA. 88.3-97.8% of the cases was correctly classified according to discriminatory genes. Conclusions: Our whole genomic microarray analysis of biopsy samples provides discriminative signatures, and an insight into pathophysiological background of colonic diseases. The results afford a data warehouse which can be further mined for in-depth pathway analyses. Keywords: Colon biopsy specimens in diseased and normal state |
| 1295 | GSE5675 |
Profile | Pilocytic astrocytomas (PAs) are the most common glioma in children. While many PAs are slow growing or clinically indolent others exhibit more aggressive features with tumor recurrence and death. In order to identify genetic signatures that might predict PA clinical behavior, we performed gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type 1 (NF1). While no expression signature was found that could discriminate clinically-aggressive or recurrent tumors from more indolent cases, PAs arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we identified a gene expression signature that stratified PAs by location (supratentorial versus infratentorial). Keywords: Human, WHO grade I, Brain tumor, Pilocytic astrocytoma, NF1 |
| 1296 | GSE41194 |
Profile | We used gene expression profiling of human DCIS and IBC to discover uniquely expressed genes that may also regulate progression. |
| 1297 | GSE16020 |
Profile | We identified 18 patients with the distinct clinical phenotype of disseminated nontuberculous mycobacterial infections viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis and molds. This syndrome typically had its onset in adulthood and was characterized by profound circulating monocytopenia, B lymphocytopenia, and NK lymphocytopenia. T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels. This novel clinical syndrome links mycobacterial, viral, and fungal susceptibility with malignancy and is transmitted in an autosomal dominant pattern. In order to elucidate the possible genetic defect that results in this novel clinical syndrome, we performed microarray expression analysis on polymorphonuclear leukocytes (PMNs) isolated from affected patients and healthy controls. Keywords: healthy donor vs affected patient |
| 1298 | GSE43114 |
Profile | Background: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV |
| 1299 | GSE8749 |
Profile | We used the rhesus macaque model to study the effects of the cag pathogenicity island (cag PAI) on the H. pylori host-pathogen interaction. Specific pathogen free (SPF) monkeys with no prior exposure to H. pylori were experimentally challenged with wild type (WT) H. pylori strain J166 (N=4) or its cag PAI isogenic knockout (KO N=4). Animals underwent endoscopy before and 1, 4, 8, and 13 wks after challenge. Gastric biopsies were collected for quantitative culture, histopathology, and host gene expression. Quantitative cultures showed that all experimentally challenged animals were infected with WT H. pylori or its isogenic cag PAI KO. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with KO compared to WT. Microarray analysis was performed on challenged animals before and 1 and 13 wks after challenge, and on unchallenged control animals (N=4). Of the 119 up-regulated genes in the WT-infected animals, several encode innate antimicrobial effector proteins, including elafin, siderocalin, DMBT, DUOX2, and several novel paralogues of human defensin-2. Quantitative RT-PCR analysis showed that high level induction of each of these genes was dependent upon the presence of the cag PAI. Immunohistochemistry confirmed increased defensin epithelial cell staining in animals challenged with WT H. pylori compared to either KO-challenged or uninfected control animals. We propose that one function of the cag PAI is to induce an antimicrobial host response that serves to increase the competitive advantage of H. pylori in the gastric niche. Keywords: Transcript profiling , Wild type H. pylori, cag-PAI KO H. pylori |
| 1300 | GSE9832 |
Profile | Pluripotency the capacity of embryo-derived stem cells to generate all tissues in the organism, can be induced in somatic cells by nuclear transfer into oocyte, fusion with embryonic stem cells, and for male germ cells by cell culture alone. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4, and Myc) to yield induced Pluripotent Stem (iPS) cells. Using the same four factors, we have derived iPS cells from human embryonic stem cell-derived fibroblasts, primary human fetal cells, and diverse cells of neonatal and adult human origin. The human iPS cells manifest the colony morphology, gene expression patterns, and epigenetic characteristics of human Embryonic Stem (hES) cells, and form well-differentiated teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogram human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture. Biological replicates: GSM248201 and GSM248202; GSM248205 and GSM248206; GSM248207 and GSM248208; GSM248209 and GSM248210; GSM248211 and GSM248212; GSM248213 and GSM248214. Sample descriptions: H1-OGN: ES cells expressing GFP-NEO marker under OCT4 promoter dH1f: differentiated H1-OGN fibroblasts dHcf16: differentiated H1-OGN cloned fibroblasts MRC5: fetal lung fibroblasts BJ1: neonatal fibroblasts Keywords: cellular reprogramming |
| 1301 | GSE19697 |
Profile | A gene expression signature characterizes expression data from breast cancer samples of patients with pathological complete response (pCR) or residual disease (RD) following the neoadjuvant trial. Several gene expression profiles have been reported to predict breast cancer response to neoadjuvant chemotherapy. These studies often consider breast cancer as a homogeneous entity although higher rates of pathologic complete response (pCR) are known to occur within the basal-like subclass. We postulated that profiles with higher predictive accuracy could be derived from a subset analysis of basal-like tumors in isolation. Using a previously described ‘‘intrinsic’’ signature to differentiate breast tumor subclasses, we identified 50 basal-like tumors from two independent clinical trials associated with gene expression profile data. 24 tumor data sets (included in this GEO submission) were derived from a 119-patient neoadjuvant trial at our institution and an additional 26 tumor data sets were identified from a published data set (Hess et al. J Clin Oncol 24:4236–4244, 2006). The combined 50 basal-like tumors were partitioned to form a 37 sample training set with 13 sequestered for validation. Clinical surveillance occurred for a mean of 26 months. We identified a 23-gene profile which predicted pCR in basal-like breast cancers with 92% predictive accuracy in the sequestered validation data set. Furthermore, distinct cluster of patients with high rates of cancer recurrence was observed based on cluster analysis with the 23-gene signature. Disease-free survival analysis of these three clusters revealed significantly reduced survival in the patients of this high recurrence cluster. We identified a 23- gene signature which predicts response of basal-like breast cancer to neoadjuvant chemotherapy as well as disease-free survival. This signature is independent of tissue collection method and chemotherapeutic regimen. Keywords: Disease state analysis |
| 1302 | GSE22780 |
Profile | To identify genes in the chromosome 3p12 pathway to tumorigenesis in pancreatic cancer we screened two expression platforms and then as a third platform interrogated pancreatic cancer tumor/normal samples for differential expression. Data from the third expression platform experiments are shown herein. |
| 1303 | GSE20114 |
Profile | Previously published results from our double-blind placebo-controlled parallel study with docosahexaenoic acid (DHA) supplementation (3 g/d, 90 d) to hypertriglyceridemic men (39-66yr) showed that DHA reduced several risk factors for cardiovascular disease (CVD), including the plasma concentration of inflammatory markers. To determine the effect of DHA supplementation on the global gene expression pattern, we performed Affymetrix GeneChip microarray analysis of blood cells (treated with lipopolysaccharide (LPS) or vehicle) drawn before and after the supplementation from the hyperlipidemic men who participated in the previous study. Genes that were significantly differentially regulated by the LPS treatment and DHA supplementation were identified. Differential regulation of 18 genes was then confirmed by quantitative RT-PCR. Both microarray and qRT-PCR data showed that the expression of LDL receptor (LDLR), oxidized LDL receptor (OLR1), and cathepsin L1 (CTSL) was significantly suppressed by DHA supplementation; however, LPS stimulated the expression of LDLR and CTSL but not that of OLR1. LPS up-regulated and DHA suppressed the expression of prostaglandin E synthase (PTGES), PPAR delta, and various chemokines. Enrichment with Gene Ontology categories demonstrated that the genes related to transcription factor activity, immune responses, host defense responses, inflammatory responses, and apoptosis were inversely regulated by LPS and DHA. These results provide supporting evidence for the anti-inflammatory effects of DHA supplementation, and reveal previously unrecognized genes that are regulated by DHA, and are associated with risk factors of cardiovascular diseases. |
| 1304 | GSE23102 |
Profile | The functional activity of TRPM7 is essential for cell viability and growth and its expression is up-regulated in certain pathological conditions. In order to assess the effects of TRPM7 activity on cellular gene expression, inducible HEK293 cell-lines harboring the wild-type mouse TRPM7 and a mutant lacking the kinase domain were established. By using microarray analysis, we identified genetic profiles altered in transcription significantly and specifically by the expression of the functional TRPM7 channel. |
| 1305 | GSE22152 |
Profile | Gene expression data of glucocorticoid resistant and sensitive acute lymphoblastic leukemia cell lines for the article: Expression regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC. Generation of the GC sensitive and resistant clones is described in Parson et al. FASEB J 2005 (Pubmed id 15637111). In brief GC sensitive clones were generated by limiting dilution subcloning from the GC sensitive T-ALL cell line CCRF-CEM-C7H2. To generate GC resistant clones the CCRF-CEM-C7H2 cell line was clutured in the presence of 10E-7 M dexametasone. |
| 1306 | GSE25835 |
Profile | Microarrays were used to determine relative global gene expression changes in WT and BRCA1-mutation carrier breast epithelium as well as tumors created from WT and BRCA1-mutation carrier breast epithelial cells. |
| 1307 | GSE17546 |
Profile | Cellular senescence is a tumor suppressor mechanism and immortalization facilitates neoplastic transformation. Both mechanisms may be highly relevant to hepatocellular carcinoma (HCC) development and its molecular heterogeneity. Cellular senescence appears to play a major role in liver diseases. Chronic liver diseases are associated with progressive telomere shortening leading senescence that is observed highly in cirrhosis, but also in some HCC. We previously described the generation of immortal and senescence-programmed clones from HCC-derived Huh7 cell line. We used microarrays to detail the global programme of gene expression profiles of immortal and senescent-programmed clones. |
| 1308 | GSE37485 |
Profile | We have generated a large collection of normal human mammary epithelial cell strains from women aged 16 to 91 years derived from primary tissues, to enable functional and molecular interrogation of aging. We demonstrate in finite-lifespan cultured and uncultured epithelial cells that aging is associated with reduction of myoepithelial cells and with increases in luminal cells expressing keratin 14 and integrin α6, traits that are expressed exclusively in myoepithelial cells in women under 30. We find that changes to the luminal lineage result from age-dependent expansion of multipotent progenitors that bear defects resulting in incompletely differentiated luminal cells. These findings were verified in vivo in normal breast tissues. Myoepithelial cells have been suggested to act as tumor suppressors, and progenitor cells are implicated as the etiological roots of mammary carcinomas. Thus with aging there is a shift in the balance of luminal/myoepithelial lineages, and changes in the functional spectrum of multipotent progenitors, which presages increased potential for malignant transformation. |
| 1309 | GSE20300 |
Profile | Full title: Expression data from whole blood gene expression analysis of stable and acute rejection pediatric kidney transplant patients Tissues are often made up of multiple cell-types. Blood for example, contains many different cell-types, each with its own functional attributes and molecular signature. In humans, because of its accessibility and immune functionality, blood cells have been used as a source for RNA-based biomarkers for many diseases. Yet, the proportions of any given cell-type in the blood can vary markedly, even between normal individuals. This results in a significant loss of sensitivity in gene expression studies of blood cells and great difficulty in identifying the cellular source of any perturbations. Ideally, one would like to perform differential expression analysis between patient groups for each of the cell-types within a tissue but this is impractical and prohibitively expensive. This dataset is the validation dataset used to test the csSAM gene expression deconvolution algorithm as reported in the accompanying paper. |
| 1310 | GSE18842 |
Profile | PURPOSE The development of reliable gene expression profiling technology is having an increasing impact on our understanding of lung cancer biology. The present study aims to determine whether the phenotypic heterogeneity and genetic diversity of lung cancer are correlated. PATIENTS AND METHODS In this study microarray analysis was performed in a set of 91 non-small cell lung cancer (NSCLC) samples in order to: establish gene signatures in primary adenocarcinomas and squamous-cell carcinomas; determine differentially expressed gene sequences at different stages of the disease; and identify sequences with biological significance for tumor progression. After microarray analysis, the expression level of 92 selected genes was validated by qPCR in an independent set of 70 samples. RESULTS Gene sequences were differentially expressed as a function of tumor type, stage, and differentiation grade. High upregulation was observed for KRT15 and PKP1, which may be good markers to distinguish squamous cell carcinoma samples. High downregulation was observed for DSG3 in stage IA adenocarcinomas. CONCLUSION Expression signatures in NSCLC distinguish tumor type, stage, and differentiation grade. Keywords: Tumor vs control comparative genomics study |
| 1311 | GSE9764 |
Profile | Carcinoma associated fibroblasts (CAFs) have recently been implicated in important aspects of epithelial solid tumor biology such as neoplastic progression tumor growth, angiogenesis, and metastasis. However, neither the source of CAFs nor the differences between CAFs and fibroblasts from non-neoplastic tissue have been well defined. In this study we demonstrate that human bone marrow-derived mesenchymal stem cells (hMSCs) exposed to tumor-conditioned medium (TCM) over a prolonged period of time assume a CAF-like myofibroblastic phenotype. More importantly, these cells exhibit functional properties of CAFs including sustained expression of stromal derived factor 1 (SDF-1) and the ability to promote tumor cell growth both in vitro and in an in vivo co-implantation model and expression of myofibroblast markers including α-smooth muscle actin and fibroblast surface protein. hMSCs induced to differentiate to a myofibroblast-like phenotype using 5-azacytidine do not promote tumor cells growth as efficiently as hMSCs cultured in tumor-conditioned medium nor do they demonstrate increased SDF-1 expression. Furthermore, gene expression profiling revealed similarities between TCM exposed hMSCs and carcinoma associated fibroblasts. Taken together these data suggest that hMSCs are a source of carcinoma associated fibroblasts and can be used in the modeling of tumor-stroma interactions. To our knowledge this is the first report demonstrating that hMSCs become activated and resemble carcinoma associated myofibroblasts upon prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells. Keywords: differentiation |
| 1312 | GSE22619 |
Profile | Background and aims. The etiopathology of inflammatory bowel diseases is still poorly understood. To date only few little data are available on the microbiota composition in ulcerative colitis (UC), representing a major subform of inflammatory bowel diseases. Currently, one of the main challenges is to unravel the interactions between genetics and environmental factors in the onset or during the progression and maintenance of the disease. The aim of the present study was to analyse twin pairs discordant for UC for both gut microbiota dysbiosis and host expression profiles at a mucosal level and to get insight into the functional genomic crosstalk between microbiota and mucosal epithelium in vivo. Methods. Biopsies were sampled from the sigmoid colon of both healthy and diseased siblings from UC discordant twin pairs but also from healthy twins. Microbiota profiles were assessed by 16S rDNA libraries while mRNA expression profiles were analysed from the same volunteers using Affymetrix microarrays. Results. UC patients showed a dysbiotic microbiota with lower diversity and more species belonging to Actinobacteria and Proteobacteria phyla. On the contrary, their healthy siblings’ microbiota contained more bacteria from the Lachnospiracea and Ruminococcaceae family than did healthy individuals . Sixty-three host transcripts significantly correlated with bacterial genera in healthy individuals whereas only 43 and 32 correlated with bacteria in healthy and UC siblings from discordant pairs, respectively. Several transcripts related to oxidative and immune responses were differentially expressed between unaffected and UC siblings. Conclusion. A loss of crosstalk between gut microbiota and host was highlighted in UC patients. This defect was also striking in healthy siblings from discordant pairs, as was the lower biodiversity within the microbiota. Our results suggest disease-relevant interactions between host transcriptome and microbiota. Moreover, unusual aerobic bacteria were noticed in UC mucosal microbiota, whereas healthy siblings from discordant pairs had higher percentages of potentially beneficialusual commensal bacterial species. |
| 1313 | GSE41804 |
Profile | IL28B genotype was shown to be associated with treatment outcome of antiviral thearpy for HCV infection. We tried to clarify the molecular feature that was asocciated with IL2B genotype by comparing Hepatic gene expression of HCV related Hepatocellular carcinoma and non-cancerous tissue with Il28B rs8099917 TT genotype and TG/GG genotype. |
| 1314 | GSE42762 |
Profile | Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. |
| 1315 | GSE14386 |
Profile | IFNβ an effective therapy against relapsing-remitting (RR) multiple sclerosis (MS) is naturally secreted during the innate immune response against viral pathogens. The objective of this study was to characterize the immunomodulatory mechanisms of IFNβ targeting innate immune response and their effects on DC-mediated regulation of T-cell differentiation. We found that IFNβ−1a in-vitro treatment of human monocyte-derived dendritic cells (DCs) induced the expression of TLR7 and the members of its downstream signaling pathway, including myeloid differentiation factor 88 (MyD88), IL-1R-associated kinase (IRAK)4, and TNF receptor-associated factor (TRAF)6, while it inhibited the expression of IL-1R. Using siRNA TLR7 gene silencing, we confirmed that IFNβ-1a-induced changes in MyD88, IRAK4 and IL-1R expression were dependent on TLR7. TLR7 expression was also necessary for the IFNβ-1a-induced inhibition of IL-1β and IL-23, and the induction of IL-27 secretion by DCs. Supernatant (SN) transfer experiments confirmed that IFNβ-1a-induced changes in DCs’ cytokine secretion inhibit Th17 cell differentiation as evidenced by the inhibition of retinoic acid-related orphan nuclear hormone receptor C (RORC) and IL-17A gene expression and IL-17A secretion. Our study has identified a novel therapeutic mechanism of IFNβ−1a, that selectively targets the autoimmune response in MS. Keywords: The effect of IFN beta-1a on the gene expression in patients with clinically isolated syndrome suggestive of MS |
| 1316 | GSE11951 |
Profile | Metastasis is a complex process involving loss of adhesion migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell-cell and cell-matrix interactions. CD146 (MCAM) is associated with advanced tumor stage in melanoma, prostate and ovarian cancers. For this study, the MDA-MB-231 cell line was used as a prototypic mesenchymal and invasive cell line, spontaneously expressing high levels of CD146. Using whole-genome DNA microarrays, we investigated genes for which expression was modified by CD146 down-regulation, obtained by siRNA or shRNA technology |
| 1317 | GSE7377 |
Profile | Enlargement of normal terminal duct lobular units (TDLUs) by hyperplastic columnar epithelial cells is one of the most common abnormalities of growth in the adult female human breast. These hyperplastic enlarged lobular units (HELUs) are important clinically as the earliest histologically identifiable potential precursor of breast cancer. The causes of the hyperplasia are unknown but may include estrogen-simulated growth mediated by estrogen receptor alpha which is highly elevated in HELUs and may be fundamental to their development. This study used DNA microarray technology and RNA from microdissected pure epithelial cells to learn more about changes in gene expression and molecular pathways associated with the development of HELUs from TDLUs Keywords: Identification of early cancer precursors |
| 1318 | GSE24717 |
Profile | Given the very substantial heterogeneity of most human cancers it is likely that most cancer therapeutics will be active in only a small fraction of any population of patients. As such, the development of new therapeutics, coupled with methods to match a therapy with the individual patient, will be critical to achieving significant gains in disease outcome. One such opportunity is the use of expression signatures to identify key oncogenic phenotypes that can serve not only as biomarkers but also as a means of identifying therapeutic compounds that might specifically target these phenotypes. Given the potential importance of targeting tumors exhibiting a stem-like phenotype, we have developed an expression signature that reflects common biological aspects of various stem-like characteristics. The Consensus Stemness Ranking (CSR) signature is upregulated in cancer stem cell enriched samples, at advanced tumor stages and is associated with poor prognosis in multiple cancer types. Using two independent computational approaches we utilized the CSR signature to identify clinically useful compounds that could target the CSR phenotype. In vitro assays confirmed selectivity of several predicted compounds including topoisomerase inhibitors and resveratrol towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly, the CSR signature could predict clinical response of breast cancer patients to a neoadjuvant regimen that included a CSR-specific agent. Collectively, these results suggest therapeutic opportunities to target the CSR phenotype in a relevant cohort of cancer patients. This SuperSeries is composed of the SubSeries listed below. |
| 1319 | GSE30516 |
Profile | Crosstalk and complexity within signaling pathways has limited our ability to devise rational strategies for using network biology to treat human disease. This is particularly problematic in cancer where oncogenes that drive or maintain the tumorigenic state alter the normal flow of molecular information within signaling networks that control growth survival and death. Understanding the architecture of oncogenic signaling pathways, and how these networks are re-wired by ligands or drugs, could provide opportunities for the specific targeting of oncogene-driven tumors. Here we use a systems biology-based approach to explore synergistic therapeutic strategies to optimize the killing of triple negative breast cancer cells, an incompletely understood tumor type with a poor treatment outcome. Using targeted inhibition of oncogenic signaling pathways combined with DNA damaging chemotherapy, we report the surprising finding that time-staggered EGFR inhibition, but not simultaneous co-administration, can dramatically sensitize the apoptotic response of a subset of triple-negative cells to conventional DNA damaging agents. A systematic analysis of the order and timing of inhibitor/genotoxin presentation—using a combination of high-density time-dependent activity measurements of signaling networks, gene expression profiles, cell phenotypic responses, and mathematical modeling—revealed an approach for altering the intrinsic oncogenic state of the cell through dynamic re-wiring of oncogenic signaling pathways. This process converts these cells to a less tumorigenic state that is more susceptible to DNA damage-induced cell death, through re-activation of an extrinsic apoptotic pathway whose function is suppressed in the oncogene-addicted state. |
| 1320 | GSE48830 |
Profile | Transcriptional analysis was performed on pre and post excision human induced pluripotent stem cells the donor human dermal fibroblasts (HDFs) they were derived from and control human embryonic stem cells |
| 1321 | GSE8961 |
Profile | This experiment is designed to study the effects to HMPV on A549 over time Keywords: time course |
| 1322 | GSE10934 |
Profile | The sclera maintains and protects the eye ball which receives visual inputs. The aim of this study is to identify characteristics of the human sclera as one of the connective tissues derived from the neural crest and mesoderm. We have here demonstrated microarray data of cultured human scleral cells. Keywords: sclera, cartilage |
| 1323 | GSE15389 |
Profile | A genomics-based approach to identify pharmacodynamic biomarkers was used for a CDK (cyclin-dependent kinase) inhibitory drug. R547 is a potent CDK inhibitor with a potent anti-proliferative effect at pharmacologically relevant doses and is currently in Phase I clinical trials. Utilizing preclinical data derived from microarray experiments, we identified pharmacodynamic biomarkers to test in blood samples from patients in clinical trials. These candidate biomarkers were chosen based on several criteria: relevance to the mechanism of action of R547, dose responsiveness in preclinical models, and measurable expression in blood samples. We identified 26 potential biomarkers of R547 action and tested their clinical validity in patient blood samples by quantitative real-time PCR analysis. |
| 1324 | GSE12586 |
Profile | Little is known about alteration of the global gene expression by cigarette smoke (CS) and few biomarkers for smoking-related harm are available. We used Affymetrix HG-U133A GeneChips to measure the transcriptomes in eight cultured lymphocyte samples exposed to cigarette smoke condensate (CSC) in vitro . The in vitro exposure of lymphocytes to CSC significantly changed expression levels of 2266 genes many of which biologically interacted. They included genes encoding for xenobiotic metabolism and oxidative stress-response (e.g. Nrf2 and AhR signaling pathways), inflammation/immune response (e.g. cytokines), apoptosis, cell cycle and tumorigenesis. However, the magnitude of expression responses for some genes showed high inter-individual variability. Keywords: toxic effects on gene expression |
| 1325 | GSE1431 |
Profile | Human prostate cancer tissues analyses Keywords: other |
| 1326 | GSE41737 |
Profile | Gene expression profiling was carried out in Huh-7.5 cells in which miR-27a was over- or under-expressed. Transfection of cells with pre-miR-27a and pre-miR-control or anti-miR-27a and anti-miR-control enabled down- and up-regulated genes to be determined, respectively. Replication and infectivity of the lipotrophic hepatitis C virus (HCV) is regulated by cellular lipid status. Among differentially expressed micro (mi)RNAs, we found that miR-27a was preferentially expressed in HCV-infected compared with hepatitis B virus (HBV)-infected liver. Gene expression profiling of Huh-7.5 cells showed that miR-27a regulates lipid metabolism by targeting the lipid synthetic transcriptional factor, RXRα, and the lipid transporter, ABCA1 |
| 1327 | GSE17671 |
Profile | The purpose of the dataset is to analyze expression of genes induced by KRAS The proto-oncogene KRAS is mutated in a wide array of human cancers most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. An alternative strategy for targeting KRAS is to identify gene products that, when suppressed or inhibited, result in cell death only in the presence of an oncogenic allele. Here we have used systematic RNA interference (RNAi) to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IkB kinase, TBK1, was selectively essential in cells that harbor mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF- B anti-apoptotic signals involving cREL and BCL-XL that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations identify TBK1 as a potential therapeutic target in KRAS mutant tumors and establish a general approach for the rational identification of co-dependent pathways in cancer. |
| 1328 | GSE11626 |
Profile | The integral role of p53 in tumor suppression has promted many laboratories to perform extensive analyses of signaling pathways downstream of the p53 family of sequence-specific DNA binding transcription factors (p53 and its homologs p63 and p73). Despite the ability of p73 to regulate many p53 family target genes little is known about the specific pathways that modulate p73 during development, tumorigenesis and tumor therapy. In this study we present a gene signature-based approach for connecting signaling pathways to transcription factors, as exemplified by p73. We generated a p73 gene signature by integrating whole-genome chromatin immunoprecipitation and expression profiling. |
| 1329 | GSE5856 |
Profile | We and others have previously reported the paradoxical downregulation of endothelial nitric oxide synthase (eNOS NOS3) steady-state mRNA by pharmacological histone deacetylase (HDAC) inhibitors. This microarray experiment was designed to identify novel targets of an HDAC inhibitor (trichostatin A (TSA), 500 nM, 24h, Sigma) in primary human endothelial cells (human umbilical vein endothelial cells, HUVEC). Keywords: gene expression profiling, paired samples, dichotomous conditions |
| 1330 | GSE2729 |
Profile | Rotavirus infection is the single most important cause of severe diarrhea in young children worldwide. We used Affymetrix Human U95Av2 high density oligonucleotide arrays to compare gene expression profiles in peripheral blood mononuclear cells (PBMC) of 10 children with acute rotavirus diarrhea and 8 age-matched healthy children. We also examined patterns of gene expression in 5 convalescent-phase PBMC samples from rotavirus patients. For data analysis we imported .cel files generated by Affymetrix MAS5.0 into Genetraffic 3.1 software (Iobion) and performed robust multi-chip analysis. We considered a gene in patients differentially expressed if its level of expression was at least 1.5-fold higher or lower than the baseline (arithmetic mean) of the corresponding gene in 8 controls and if its pattern of elevated or repressed expression was observed in at least 7 of the 10 patients. Using these criteria, we identified ~1% up- and ~2% down-regulated genes in acute-phase PBMC of patients. Up-regulated genes included those involved in the differentiation, maturation, activation, and survival of B cells, as well as an array of genes with function in inflammatory and antiviral activities. We observed a pattern of repressed expression of a number of genes involved in the various stages of T-cell development and activation. On the basis of these results, we conclude that rotavirus infection induces robust inflammatory response and B-cell activation but represses T-cell response. Keywords: other |
| 1331 | GSE14474 |
Profile | This study provides a framework describing how magnetic exposure is transduced from the most-plausible molecular-level ‘biosensor’ (lipid membranes) to cell-level responses that include differentiation toward neural lineages. In addition SMF provided a stimulus that uncovered new relationships – that exist even in the absence of magnetic fields – between gangliosides, the time dependent regulation of IL-6 signaling by these glycolipids, and the fate of embryonic cells. |
| 1332 | GSE6434 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1333 | GSE15777 |
Profile | We describe 9 CLL patients who underwent a spontaneous clinical regression. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of VH3-30 gene in 2. The light chain variable region genes were mutated in 6/8 cases, with the usage of Vκ4-1 gene in 3. Microarray analysis of CLL cells revealed a distinctive genomic profile. The number of activated T lymphocytes expressing IFN-γ, TNF-α and IL-4 was similar between CLL in spontaneous regression and healthy individuals. |
| 1334 | GSE6804 |
Profile | Idiopathic pulmonary fibrosis (IPF) a chronic progressive lung disease of unknown etiology, is characterized by the expansion of myofibroblasts and abnormal deposition of extracellular matrix in the lung parenchyma. To elucidate the molecular mechanisms that lead to IPF, we analyzed myofibroblasts established from patients with IPF by oligonucleotide microarrays. Gene expression profiles revealed a novel pathophysiologic function of myofibroblasts as a generator of reactive oxygen species, and a self-defense mechanism against oxidative stress of their own generating. Keywords: cell type comparison, disease state analysis |
| 1335 | GSE44126 |
Profile | To assess the nature of CD8+CD40L+ memory Tcells we compared the gene expression to CD8+CD40L- and CD4+ counterparts, and found similarities in expression of genes encoding cytokines |
| 1336 | GSE31264 |
Profile | Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders. |
| 1337 | GSE45030 |
Profile | gene expression profiling of WT fibroblasts hiPSCs, and NPCs compared to the same cell types isolated from patients with Ataxia Telangiectasia gene expression profiling was carried out with Affymetrix Hg133 2.0 plus chips |
| 1338 | GSE37201 |
Profile | Specimens were collected from esophageal adenocarcinoma patients undergoing esophagectomy for adenocarcinoma at the University of Michigan Health System between 1991 and 2004. Written consent was obtained from each patient according to the approval and guidelines of the University of Michigan institutional review board. Patients receiving treatment with chemotherapy and/or radiotherapy prior to surgery were excluded. Tissue samples were fresh-frozen in liquid nitrogen and stored at −80 °C until use. |
| 1339 | GSE15893 |
Profile | The goal of this study was to identify signaling molecules downstream of CXCR4 in breast cancer cells. For this purpose we sorted CXCR4-positive and CXCR4-negative cells from MDA-MB-231 breast cancer cell line by flow cytometry and performed microarrays analysis. |
| 1340 | GSE21648 |
Profile | Wound healing within the oral mucosa results in minimal scar formation compared to wounds within the skin. We have recently demonstrated distinct differences in the ageing profiles of cells (oral mucosal and patient-matched skin fibroblasts) isolated from these tissues. We hypothesize that the increased replicative potential of oral mucosal fibroblasts may confer upon them preferential wound healing capacities. Passage-matched early cultures of oral mucosal fibroblasts and skin fibroblasts demonstrated distinct gene expression profiles with a number of genes linked to wound healing/tissue repair. We analyzed the gene expression profiles of oral mucosal and patient-matched skin fibroblasts for multiple patients both prior to (0h) and (6h) following a wounding stimulus. |
| 1341 | GSE14328 |
Profile | We integrated three transplant rejection microarray studies examining gene expression in samples from pediatric renal adult renal, and adult heart transplants. We performed one study ourselves and retrieved two others from the NCBI Gene Expression Omnibus (GEO)(GSE4470 and GSE1563). We identified 45 genes that were upregulated in common in acute rejection. Half were involved in one immune-related pathway. Among ten proteins we tested by serum ELISA, three successfully distinguished acute rejection from stable transplants. These were CXCL9, PECAM1, and CD44, with areas under the receiver operating characteristic curves of 0.844, 0.802, and 0.738, respectively. Immunohistochemistry showed that the PECAM1 protein was increased in acute rejection in renal, liver and heart transplants versus normal tissues. Our results show that integrating publicly-available gene expression data sets is a fast, powerful, and cost-effective way to identify serum-detectable diagnostic biomarkers. |
| 1342 | GSE24806 |
Profile | Ewing tumor cell line SBSR-AKS grows adherent to the culture vessel. A spontaneously derived sub-line of cell line SBSR-AKS shows growth in suspension. We used microarrays to analyse gene expression in these Ewing tumor cell lines |
| 1343 | GSE18773 |
Profile | Human solid tumors contain rare cancer side population (SP) cells which expel the fluorescencent dye H33342 and display cancer stem cell characteristics. Transcriptional profiling of cancer SP cells isolated by H33342 fluorescence analysis is a newly emerging approach to discover cancer stem cell markers and aberrant differentiation pathways. Using Affymetrix expression microarrays this study investigated differential gene expression between SP and non-SP (NSP) cells isolated from the CAL-51 human mammary carcinoma cell line. Keywords: cell type comparison |
| 1344 | GSE22301 |
Profile | The two most common melanoma histopathologic subtypes superficial spreading (SSM) and nodular melanoma (NM), are believed to represent sequential phases of linear progression from radial to vertical growth. Studies suggest, however, that SSM and NM are biologically distinct. We utilized an integrative genomic approach to examine the possibility that SSM and NM are the result of independent pathways characterized by unique molecular alterations. Cell lines including SSM, NM, metastatic melanoma, and melanocyte controls were evaluated for copy number changes and differential mRNA expression using single nucleotide polymorphism array (SNP 6.0, Affymetrix) and gene array (U133A 2.0, Affymetrix). Data sets were integrated to identify copy number alterations that correlated with gene expression, and array results were validated using immunohistochemistry on human tissue microarrays (TMAs) and an external data set. The functional effect of genomic deletion was assessed by lentiviral overexpression. Integrative genomics revealed 8 genes in which NM/SSM-specific copy number alterations were correlated with NM/SSM differential gene expression (P<0.05, Spearman’s rank). Pathways analysis of differentially expressed genes (N=114) showed enrichment for metabolic-related processes. SSM-specific genomic deletions (DIS3, MTAP, G3BP2, SEC23IP, USO1) were verified in an expanded panel of cell lines, and forced overexpression of MTAP in SSM resulted in reduced cell growth. Metabolism-related gene ALDH7A1 was verified as overexpressed in NM using human TMAs.The identification of recurrent genomic deletions in SSM not present in NM challenges the linear model of melanoma progression and supports the unique molecular classification of SSM and NM. |
| 1345 | GSE12155 |
Profile | Subjects underwent endothelial testing and blood sampling at baseline and after 3 months of exercise training. Microarray and flow cytometry-based characterization of cells from an endothelial progeniator colony assay was consistent with T lymphocytes but not endothelial cells. Keywords: expression analysis |
| 1346 | GSE22278 |
Profile | Fifteen human volunteer subjects (18-40 years of age) and 5 Trauma patients were studied. One volunteer group (saline + LPS [n = 8]) received a 12 hour infusion a second volunteer group (cortisol + LPS [n = 7]) received a 12 hour infusion of cortisol (3 µg/kg/min). After 6 hours of saline or cortisol infusion intravenous lipopolysaccharide (2 ng/kg) was administered to all subjects. Blood samples were collected at 0 hours, 6 hours and 24 hours relative to LPS administration at 0 hours. Blood samples were drawn from a grounp of Trauma patients shortly (day1-5) after admission and later in their ICU stay (day 5-7). Leukocytes were isolated from these blood samples, total RNA extracted, and microarray analyses performed using Affymetrix Focus GeneChips® on samples yeilding sufficent quantity and quality RNA for analysis. |
| 1347 | GSE11324 |
Profile | The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation,particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer. Keywords: estrogen effect, time course |
| 1348 | GSE21534 |
Profile | Literature suggests that the route of feeding may impact the immune system. This study examines changes in gene expression due to route of feeding in healthy volunteers. Healthy volunteers were fed contniuous parenteral diet or continuous enteral diet for 72 hours |
| 1349 | GSE22787 |
Profile | Expression .CEL files from Affymetrix HG-U133A 2.0 arrays using DNA from 14 human cell lines derived from metastasized melanoma |
| 1350 | GSE29384 |
Profile | Glioblastoma multiforme is the most common and aggressive form of brain cancer. The use of oncolytic HSV-1 (oHSV) to selectively target brain cancer cells leading to their lytic destruction has shown to be very promising in a preclinical setting but is lacking efficacy in clinical trials. Cyr61, a secreted extracellular matrix protein which functions to promote angiogenesis, migration, proliferation and tumorigenesis, was found to be upregulated rapidly following oHSV infection. Here we show, using microarray analysis, that Cyr61 expression leads to the induction of several genes with type 1 interferon function. We show that Cyr61 mediated type 1 IFN induction is through its interaction with integrin alpha6beta1 on the cell surface and results in oHSV inhibition, reducing the efficacy of this therapy. We used microarray to detail the global program of gene expression underlying Cyr61 mediated oncolytic HSV-1 inhibition and identified distinct classes of up-regulated genes during this process. |
| 1351 | GSE12253 |
Profile | the molecular mechanisms for the biphasic effect of alcohol are not fully understood. The goal of the study is to identify genes that are differentially expressed following alcohol exposure of 50mM and 100mM ethanol for 24 hours. |
| 1352 | GSE20163 |
Profile | Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD). |
| 1353 | GSE15132 |
Profile | Microarray analysis has been applied to the cell proliferation in a human colonic cel line Caco-2. We have shown previously that a moderate riboflavin depletion around weaning has a profound impact on the structure and function of the small intestine of the rat, which is not reversible following riboflavin repletion. In this study we have modelled riboflavin deficiency in a human cell line, shown irreversible loss of cell viability associated with impaired mitosis and identified candidate effectors of riboflavin depletion in the cell. The aim of the present study is to develop a cell culture model of riboflavin depletion and analyse its behaviour using a using a combination of cell biology approaches including microarray analysis. |
| 1354 | GSE6281 |
Profile | Genes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study we introduce the use of high density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal and nickel-exposed skin were obtained from 7 nickel-allergic patients and 5 non-allergic controls at four different time points during elicitation of eczema: 0h, 7h, 48h and 96h. Each gene expression profile was analysed by hybridization to high density oligonucletide arrays. Cluster analysis of 74 genes found to be differentially expressed in the patients over time revealed that the patient samples may be categorised into two groups: An early time point group (0h and 7h) and a late time point group (48h and 96h). Compared to the early time points, late time point skin samples were characterised by the up-regulation of inflammatory molecules including genes involved in the class I antigen presenting pathway and genes involved in lymphocyte adhesion and motility Correspondence analysis including both patients and controls revealed three distinct groups: i) the control group, ii) the early time point patient group (0h and 7h) and iii) the late time point patient group (48h and 96h). Keywords: time course, allergic response |
| 1355 | GSE25251 |
Profile | Cell lines play an important role for studying tumor biology and novel therapeutic agents. We demonstrated that cell lines represent a useful and reliable in vitro system for studying basic mechanisms in lung cancer. Moreover we presented 3 novel, comprehensively characterized SCC cell lines. |
| 1356 | GSE5764 |
Profile | The aim of our study was to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells. We examined ten mastectomy specimens from postmenopausal breast cancer patients. Ductal and lobular tumor and normal cells were microdissected from cryosections. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. GCOS pairwise comparison algorithm and rank products have identified multiple genes that are differentially expressed in comparisons between ductal and lobular tumor and normal cell types. The results suggest that these genes are involved in epithelial-mesenchymal transition TGFbeta and Wnt signaling. These changes are present in both tumor types but appear to be more prominent in lobular carcinomas. Keywords: cell type comparison |
| 1357 | GSE5741 |
Profile | LDL or Ox-LDL 200ug/ml which showed no loss of viability after a 48 hour exposure, induced a physiological and pathological transcriptional response, respectively. LDL induced a downregulation of genes associated with cholesterol biosynthesis while ox-LDL induced transcriptional alterations in genes related to inflammation, matrix expansion, lipid metabolism and processing, and apoptosis. Pentraxin-3 was secreted into the culture medium after RPE cells were stimulated with ox-LDL, and immunohistochemically evident in Bruch’s membrane of human macular samples with age-related macular degeneration. ARPE-19 cells exposed to 200?g/ml ox-LDL had a 38% apoptosis rate compared to less than 1% when exposed to LDL or untreated controls (p<0.0001). While LDL induced a physiologic response by RPE cells, a pathological phenotypic response was seen after treatment with oxidatively modified LDL. The transcriptional, biochemical, and functional data provide initial support of a role for the hypothesis that modified LDLs are one trigger for initiating events that contribute to the development of age-related macular degeneration. Keywords: treatment with non-treatment control |
| 1358 | GSE6364 |
Profile | The transition of regularly cycling endometrium from the proliferative or Estrogen-dominant phase of the menstrual cycle to the Progesterone-dominant Early and Mid Secretory phases requires wide-spread changes in gene expression that shift the endometrium from a proliferative capacity to a differentiated 'decidual' phenotype in preparation for implantation. This process appears delayed in women with severe endometriosis suggestive of a progesterone resistant endometrium in this disease. Keywords: disease state analysis |
| 1359 | GSE13292 |
Profile | Peripheral blood is an accessible and informative source of transcriptomal information for many human disease and pharmacogenomic studies. While there can be significant advantages to analyzing RNA isolated from whole blood particularly in clinical studies, the preparation of samples for microarray analysis is complicated by the need to minimize artifacts associated with highly abundant globin RNA transcripts. The impact of globin RNA transcripts on expression profiling data can potentially be reduced by using RNA preparation and labeling methods that remove or block globin RNA during the microarray assay. We compared four different methods for preparing microarray hybridization targets from human whole blood collected in PAXGene tubes. Three of the methods utilized the Affymetrix one-cycle cDNA synthesis/in vitro transcription protocol but varied treatment of input RNA as follows: i. no treatment; ii. treatment with GLOBINclear; or iii. treatment with globin PNA oligos. In the fourth method cDNA targets were prepared with the Ovation amplification and labeling system. Results: We find that microarray targets generated with labeling methods that reduce globin mRNA levels or minimize the impact of globin transcripts during hybridization detect more transcripts in the microarray assay compared with the standard Affymetrix method. Comparison of microarray results with quantitative PCR analysis of a panel of genes from the NF-kappa B pathway shows good correlation of transcript measurements produced with all four target preparation methods, although method-specific differences in overall correlation were observed. The impact of freezing blood collected in PAXGene tubes on data reproducibility was also examined. Expression profiles show little or no difference when RNA is extracted from either fresh or frozen blood samples. Conclusion: RNA preparation and labeling methods designed to reduce the impact of globin mRNA transcripts can significantly improve the sensitivity of the DNA microarray expression profiling assay for whole blood samples. While blockage of globin transcripts during first strand cDNA synthesis with globin PNAs resulted in the best overall performance in this study, we conclude that selection of a protocol for expression profiling studies in blood should depend on several factors, including implementation requirements of the method and study design. RNA isolated from either freshly collected or frozen blood samples stored in PAXGene tubes can be used without altering gene expression profiles. Keywords: Whole Blood, Protocol Variation, Expression Profiling, Microarray, globin, PAXGene, PNA |
| 1360 | GSE17046 |
Profile | Background: Infrared A radiation (IRA 760-1440 nm) is a major component of solar radiation and similar to ultraviolet (UV) radiation, causes photoaging of human skin by increasing the expression of matrixmetalloproteinase-1 (MMP-1) expression in human skin fibroblasts. This gene-regulatory effect resulted from the IRA induced activation of the pleiotropic MAPKinase ERK1/2 signaling pathway, indicating that the IRA response extends beyond MMP-1. In the present study we have therefore assessed the IRA-induced transcriptom in primary human skin fibroblasts. Results: Microarray analysis revealed 599 transcripts to be regulated by physiologically relevant doses of IRA in primary human skin fibroblasts. The IRA induced transcriptom differed from changes known to be induced by UVB or UVA radiation in the same cell type. IRA responsive genes include four categories: extracellular matrix, calcium homeostasis, stress signaling, and apoptosis. These results were confirmed by realtime PCR experiments analyzing thirteen of these genes representing these four categories. By means of chemical inhibitors of known signaling pathways we next show that besides ERK1/2, the p38-, JNK-, PI3K/AKT-, STAT3-, and IL-6 as well as calcium mediated signaling pathways are functionally involved in the IRA gene response and that a major part of it is triggered by mitochondrial, and to a lesser extent non-mitochondrial production of reactive oxygen species. Conclusion: This study identifies IRA radiation as a potent modulator of gene expression in human skin cells. The IRA response is specific and involves genes which are of critical importance for the homeostasis of human skin. Our data confirm the previous notion that IRA contributes to premature skin aging and indicate that further biological effects may result from IRA exposure of human skin. |
| 1361 | GSE42989 |
Profile | Sequencing studies from several model systems have suggested that diverse and abundant small RNAs may derive from tRNA but the function of these molecules remains undefined. Here we demonstrate that one such tRNA fragment, cloned from human B cells and designated CU1276, in fact possesses the functional characteristics of a microRNA, including a DICER1-dependent biogenesis, physical association with Argonaute proteins, and the ability to repress mRNA transcripts in a sequence-specific manner. The gene expression profiling undertaken for this study was done in order to assay mRNA-level changes in 293T cells upon modulation of CU1276 levels, and thereby to identify direct targets of this sequence. Ultimately, we fully validated the endogenous gene RPA1 as a CU1276 target. |
| 1362 | GSE45391 |
Profile | Gene expression profiling of gastric cancer cells MKN28 infected with Sox2 lentivirus comparing with MKN28 infected with control lentivirus |
| 1363 | GSE3769 |
Profile | Comparison of muscle stem cell preplates and myoblasts. Keywords: other |
| 1364 | GSE6207 |
Profile | This time course analysis is to study the targets and functions of miR-124. MiR-124 was overexpressed and the effect of miR-124 overexpression was compared to negative controls to identify downregulated genes and potential miRNA targets. Keywords: time course |
| 1365 | GSE30494 |
Profile | Microarray analysis to identify down-stream genes after treatment with siKDM3A |
| 1366 | GSE10281 |
Profile | Tumorigenic breast cancer cells characterized by high CD44 and low or undetectable CD24 levels (CD44+/CD24-/low) may be resistant to conventional therapies and responsible for cancer relapse. We defined a “signature” expression pattern of hundreds of genes associated with CD44+/CD24-/low mammosphere-forming cells. In a panel of patient breast tumors, this tumorigenic gene signature was found exclusively manifested in tumors of the recently identified “claudin-low” molecular profile subtype characterized by overexpression of many mesenchymal-associated genes, suggesting that these tumors have pre-existing higher levels of tumorigenic cells. Furthermore, when comparing the expression profiles of paired breast cancer core biopsies before versus after hormone therapy or chemotherapy, both the tumorigenic and “claudin-low” signatures were more active in about half of tumors after treatment, indicative of a greater enrichment of tumorigenic cells as a result of treatments targeting the bulk tumor cells. Keywords: two group comparison |
| 1367 | GSE28005 |
Profile | The adaptive mechanisms in response to excess energy supply are still poorly known in humans. Our aims were to define metabolic responses and changes in gene expression in adipose tissue of healthy volunteers during fat overfeeding. |
| 1368 | GSE29459 |
Profile | We used microarrays to observe the global gene expression in hematopoietic stem and projenitor cells during ex vivo culture with DMSO (Blank) or with Garcinol (GAR) and identified distinct classes of up or down-regulated genes. |
| 1369 | GSE33728 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1370 | GSE32607 |
Profile | Regulating the transition of T lymphocytes from quiescence into an activated proliferating state involves initiation of programmes that result in cell cycle entry (proliferation) and the growth cycle (blastogenesis). This study analyses the expression of mRNA regulsted during the transition from quiescence into the cell cycle. We used micro-arrays to monitor the dynamical behaviour of expression of genes expressed in primary human T cells stimulated with CD3/CD28 |
| 1371 | GSE30644 |
Profile | We have used an agnostic approach to identify drug combinations by using combination high throughput screening (cHTS) technology and make the surprising discovery that adenosine A2A and beta-2 adrenergic receptor agonists are highly synergistic selective and novel agents that enhance glucocorticoid activity in B-cell malignancies. We used the microarray study to understand the synergistic mechanism between dexamethasone and A2A receptor agonist or Beta-2 Adrenergic receptor agonist in a multiple myeloma cell line, MM1S. |
| 1372 | GSE14897 |
Profile | Reprogrammed somatic cells offer a valuable source of pluripotent cells that have the potential to differentiate into many cells types and provide a new tool for regenerative medicine. In the present study we differentiated induced pluripotent stem cells (iPS cells) into hepatic cells. We first showed that mouse iPS cells could from a complete liver in mouse embryo (E14.5) including hepatocytes endothelial cells, sinusoidal cells and resident macrophages. We then designed a highly efficient hepatocyte differentiation protocol using defined factors on human embryonic stem cells (ES cells). This protocol was found to generate more than 80% albumin expressing cells that show hepatic functions and express most of liver genes as shown by microarray analyses. Similar results were obtained when human iPS cells were induced to differentiate following the same procedure. |
| 1373 | GSE8658 |
Profile | In order to gain insights into how PPARg regulates different facets of dendritic cell (DC) differentiation we sought to identify PPARg regulated genes and gene networks in monocyte-derived dendritic cells using global gene expression profiling. We employed an exogenous ligand activation approach using a selective PPARg ligand (rosiglitazone abbreviated as RSG). In addition, we have defined culture conditions in which human serum (HS) induces PPARg activation via a yet uncharacterized endogenous mechanism. We also compared the gene expression profile of developing dendritic cells obtained from patients harboring dominant negative mutations of the PPARg receptor (C114R and C131Y). Keywords: ligand response |
| 1374 | GSE27444 |
Profile | Multiple gene expression studies have demonstrated that breast cancer biological diversity is associated with distinct transcriptional programs. Transcription factors because of their unique ability to coordinate the expression of multiple genes, are speculated to play a role in generating phenotypic plasticity associated with cancer progression including acquired drug resistance. Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust means for inducing and understanding various functional components of the cancer phenotype. Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to a fulvestrant, a clinically important anti-endocrine therapeutic agent. We isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor positive breast cancer cell lines. Comparative gene expression profile analysis of the ZF-TF-transduced breast cancer cell lines revealed a 72-gene cluster that constituted a common signature for the fulvestrant-resistance phenotype. Pathway enrichment-analysis of gene expression data revealed that the ZF-TF-induced fulvestrant resistance is associated with an estrogen receptor negative-like gene set and four unique myb-regulated gene sets. Furthermore, we identified a set of genes strongly expressed in the ZF-TF-induced fulvestrant-resistant cells that was correlated with a lower probability of distant metastasis-free or death-from-relapse-free survival of breast cancer patients. |
| 1375 | GSE10436 |
Profile | The effect of low RNA sample amount on amplification fidelity was investigated. Keywords: other |
| 1376 | GSE42066 |
Profile | To identify key biological pathways that define toxicity or biocompatibility after nanoparticle exposure three human cell types were exposed in vitro to two high aspect ratio nanoparticles for 1 hr or 24 hr and collected for global transcriptomics. Transcriptional responses were measured by global microarray analysis of cells in culture. |
| 1377 | GSE32057 |
Profile | Although anemia is common in Shwachman-Diamond syndrome (SDS) the underlying mechanism remains unclear. We asked whether SBDS, which is mutated in most SDS patients, is critical for erythroid development. We found that SBDS expression is high early during erythroid differentiation. Inhibition of SBDS in CD34+ hematopoietic stem cells and early progenitors (HSC/Ps) and K562 cells led to slow cell expansion during erythroid differentiation. Induction of erythroid differentiation resulted in markedly accelerated apoptosis in the knockdown cells; however, proliferation was only mildly reduced. The percentage of cells entering differentiation was not reduced. Differentiation also increased the oxidative stress in SBDS-knockdown K562 cells, and antioxidants enhanced the expansion capability of differentiating SBDS-knockdown K562 cells and colony production of SDS patient HSC/Ps. Erythroid differentiation also resulted in reduction of all ribosomal subunits and global translation. Furthermore, stimulation of global translation with leucine improved the erythroid cell expansion of SBDS-knockdown cells and colony production of SDS patient HSC/Ps. Leucine did not reduce the oxidative stress in SBDS-deficient K562 cells. These results demonstrate that SBDS is critical for normal erythropoiesis. Erythropoietic failure caused by SBDS-deficiency is at least in part related to elevated ROS levels and translation insufficiency since antioxidants and leucine improved cell expansion. |
| 1378 | GSE37416 |
Profile | We demonstrated recently that both constitutive and FAS-triggered apoptosis of human neutrophils are profoundly impaired by Francisella tularensis but how this is achieved is largely unknown. To test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, we used human oligonucleotide microarrays to identify differentially regulated genes in cells infected with F. tularensis strain LVS compared with uninfected controls. In order to examine the effect of F. tularensis on the neutrophil transcriptome, we performed microarray expression analysis on human neutrophils treated with F. tularensis subsp. holarctica live vaccine strain (LVS). |
| 1379 | GSE37132 |
Profile | Most cancer genomics papers to date have focused on aberrations in genomic DNA and protein-coding transcripts. However around 50% of transcripts have no coding potential and may exist as non-coding RNA. We performed RNA-seq in BRAFv600e melanoma skin cancer and on melanocytes over-expressing oncogenic BRAF to catalog transcriptome remodeling. We discovered that BRAF regulates expression of 1027 protein coding transcripts, 39 annotated lncRNAs and 70 novel transcripts. Many of the novel transcripts are lncRNAs. We used an indepenedent dataset to interrogate our novel transcripts and found that the novel lncRNA BANCR is a BRAF-regulated lncRNA recurrently upregulated in melanoma. Knockdown of BANCR impairs melanoma cell migration. |
| 1380 | GSE10086 |
Profile | This study used microarray expression analysis to identify global changes in transcript alteration in response to MEK inhibition. Genes under ERK control were identified in a panel of V600E BRAF and RTK-activated tumor cells and xenografts using short-term inhibition of ERK activity using the MEK inhibitor PD0325901 (Pfizer). This SuperSeries is composed of the SubSeries listed below. |
| 1381 | GSE40096 |
Profile | Analyzed the gene expression level in 5 pancreatic cell lines |
| 1382 | GSE23849 |
Profile | Protein homeostasis in the endoplasmic reticulum (ER) has recently emerged as a therapeutic target for cancer treatment. Disruption of ER homeostasis results in ER stress which is a major cause of cell death for cells exposed to the proteasome inhibitor Bortezomib, an anti-cancer drug approved for treatment of multiple myeloma and Mantle cell lymphoma. We recently reported that the ERAD inhibitor Eeyarestatin I (EerI) also disturbs ER homeostasis and has anti-cancer activities resembling that of Bortezomib. Our findings reveal a class of bifunctional chemical agents that can preferentially inhibit membrane-bound p97 to disrupt ER homeostasis and induce tumor cell death. These results also suggest that the AAA ATPase p97 may be a potential drug target for cancer therapy. |
| 1383 | GSE32701 |
Profile | Surgical samples have long been used as important subjects for cancer research. In accordance with an increase of neoadjuvant therapy biopsy samples have recently become imperative for cancer transcriptome. On the other hand, both biopsy and surgical samples are available for expression profiling for predicting clinical outcome by adjuvant therapy; however, it is still unclear whether surgical sample expression profiles are useful for the prediction by the use of biopsy samples because little has been done about comparative gene expression profiling between the two kinds of samples. When gene expression profiles were compared between biopsy and surgical samples, artificially induced epithelial-mesenchymal transition (aiEMT) was found in the surgical samples. This study will evoke the fundamental misinterpretation including underestimation of the prognostic evaluation power of markers by overestimation of EMT in past cancer research, and will furnish some advice for the near future as follows: 1) Understanding how long the tissues were under an ischemic condition; 2) Prevalence of biopsy samples for in vivo expression profiling with low biases on basic and clinical research; and 3) Checking cancer cell contents and normal- or necrotic-tissue contamination in biopsy samples for prevalence. |
| 1384 | GSE18462 |
Profile | Paired tissues (normal colon primary colorectal carcinoma, normal liver, liver metastasis of colorectal carcinoma) from 2 colorectal carcinoma patients in Taiwan were processed to generate total RNA, which was subsequently analyzed for gene expression using Affymetrix U133 plus 2.0 arrays. |
| 1385 | GSE29625 |
Profile | We have derived hESC from biopsied blastomeres of cleavage stage embryos under virtually the same conditions we used for the derivation of hESC lines from inner cell mass of blastocyst stage embryos. Blastomere-derived hESC lines exhibited all the standard characteristics of hESC including undifferentiated proliferation genomic stability, expression of pluripotency markers and the ability to differentiate into the cells of all three germ layers both in vitro and in vivo. To examine whether hESC lines derived from two developmental stages of the embryo differ in gene expression, we have subjected three blastomere-derived hESC lines and two ICM-derived hESC lines grown under identical culture conditions to transcriptome analysis using gene expression arrays. Unlike previously reported comparisons of hESC lines which demonstrated, apart from core hESC-associated pluripotency signature, significant variations in gene expression profiles of different lines, our data show that hESC lines derived and grown under well-controlled defined culture conditions adopt nearly identical gene expression profiles. Moreover, blastomere-derived and ICM-derived hESC exhibited very similar transcriptional profiles independent of the developmental stage of the embryo from which they originated. Furthermore, this profile was evident in very early passages of the cells and did not appear to be affected by extensive passaging. These results suggest that during derivation process cells which give rise to hESC acquire virtually identical stable phenotype and are not affected by the developmental stage of the starting cell population. |
| 1386 | GSE6049 |
Profile | Expression profiles of PTLD Keywords: Expression profiles of PTLD |
| 1387 | GSE13985 |
Profile | Atherosclerosis is characterized by thickening of the arterial wall and is the primary cause of the coronary artery disease and cerebrovascular disease two of the most common causes of illness and death worldwide. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia. Familial hypercholesterolemia is an autosomal dominant disorder, which is caused by mutations mainly located in the low-density lipoprotein receptor (LDLR) gene. It is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. Aim of this study was to find atherosclerotic markers in white blood cells of patients compared to healthy controls. None of these patients exhibited symptoms of atherosclerosis by standard diagnostic methods; however, transcriptome analysis of blood RNA indicated changes in ubiquitin proteolysis and cell adhesion system as expected in initiation steps of atherosclerosis. |
| 1388 | GSE32962 |
Profile | Acute Lymphoblastic Leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence of MLL translocations which is associated with a poor prognosis. Contributing to this poor prognosis is cellular drug resistance especially to glucocorticoids like prednisolone. Although in vitro prednisolone resistance mechanisms have been proposed in pediatric ALL, it has never been studied in MLL-rearranged infant ALL, which are highly resistant to glucocorticoids in vitro and in vivo. |
| 1389 | GSE45029 |
Profile | The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells -- including inhibition of the mitochondrial ribosome -- there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation and alter cell cycle progression in vitro. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism. |
| 1390 | GSE24128 |
Profile | CD138-selected marrow plasma cells from newly diagnosed AL patients were studied for cyclin D1 expression. We identified patients whose plasma cells overexpressed cyclin D1 and compared them to those whose cells did not. |
| 1391 | GSE15921 |
Profile | High metastatic nasopharyngeal carcinoma cell line 5-8F expression patterns. |
| 1392 | GSE7322 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1393 | GSE10584 |
Profile | In order to elucidate the molecular mechanism giving rise to the rare In(Lu) type of Lu(a-b-) blood group phenotype we compared the transcriptome of normal and In(Lu) erythroblasts at different stages of maturation. Many erythroid-specific genes had reduced transcript levels suggesting the phenotype resulted from a transcription factor abnormality. A search for mutations in erythroid transcription factors revealed mutations in the promoter or coding sequence of EKLF in 21 of 24 individuals with the In(Lu) phenotype. In all cases the mutant EKLF allele occurred in the presence of a normal EKLF allele. Individuals with the In(Lu) phenotype have no reported pathology indicating that one functional EKLF allele is sufficient to sustain human erythropoiesis. These data provide the first description of inactivating mutations in human EKLF and the first demonstration of a blood group phenotype resulting from mutations in a transcription factor. Keywords: Time course and cell type comparison. |
| 1394 | GSE8514 |
Profile | The source of aldosterone in 30 to 40 % of patients with primary hyperaldosteronism (PA) is unilateral aldosterone-producing adenoma (APA). The mechanisms causing elevated aldosterone production in APA are unknown. Herein we examined expression of G-protein coupled receptors (GPCR) in APA and demonstrate that compared to normal adrenals there is a general elevation of certain GPCR in many APA and/or ectopic expression of GPCR in others. RNA samples from normal adrenals (n = 5), APAs (n = 10), and cortisol-producing adenomas (CPAs) (n=13) were used on 15 genomic expression arrays, each of which included 223 GPCR transcripts presented in at least one out of 15 of the independent microarrays. The array results were confirmed using real-time RT-PCR (qPCR). Four GPCR transcripts exhibited a statistically significant increase that was greater than 3-fold compared to normal adrenals, suggesting a general increase in expression compared to normal adrenal glands. Four GPCR transcripts exhibited a greater than 15-fold increase of expression in one or more of the APA samples compared to normal adrenals. qPCR analysis confirmed array data and found the receptors with the highest fold increase in APA expression to be luteinizing hormone receptor (LH-R), serotonin receptor 4 (HTR4), gonadotropin-releasing hormone receptor (GnRHR), glutamate receptor metabotropic 3 (GRM3), endothelin receptor type B-like protein (GPR37), and ACTH receptor (MC2R). There are also sporadic increased expressions of these genes in the CPAs. Together, these findings suggest a potential role of altered GPCR expression in many cases of PA and provide candidate GPCR for further study. Keywords: disease state analysis |
| 1395 | GSE21105 |
Profile | This is an initial experiment which was performed in order to identify novel transcriptional targets of the tumor suppressor p53 |
| 1396 | GSE11151 |
Profile | Identification and evaluation of specific molecular markers is of great importance for reliable diagnostics and outcome prediction of renal neoplasms Using the Affymetrix microarray we established the gene expression signatures of normal kidneys and different types of renal tumors. Keywords: Several different biological groups, several samples per group |
| 1397 | GSE6321 |
Profile | CD38 expression is an important prognostic marker in CLL with high levels of CD38 associated with shorter overall survival. In this study we used gene expression profiling and protein analysis of highly purified cell-sorted CD38+ and CD38- chronic lymphocytic leukemia cells to elucidate a molecular basis for the association between CD38 expression and inferior clinical outcome. Paired CD38+ and CD38- CLL cells derived from the same patient were shown to be monoclonal by VH gene sequencing but despite this, CD38+ CLL cells possessed a distinct gene expression profile when compared with their CD38- sub-clones. Keywords: Sub-clonal analysis of CLL cells derived from the same leukemia sample |
| 1398 | GSE3062 |
Profile | Affymetrix U133 Plus 2.0 arrays were hybridized with varying amounts of starting material to determine whether different measurements of gene expression were observed. Keywords: Affymetrix starting material study |
| 1399 | GSE19383 |
Profile | Early genetic changes during cancer initiation may provide targets for agents that delay or even prevent, cancer. We hypothesized that cells bearing a single inherited “hit” in a tumor suppressor gene express an altered mRNA repertoire that may identify targets for measures that could delay or even prevent progression to carcinoma. Here, we report on the transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1 and BRCA2 mutation-carriers and controls. Our comparison analyses identified multiple changes in gene expression, in both tissues for both mutations that were independently validated by real-time RT-PCR analysis. Several of the differentially expressed genes had been previously proposed as cancer markers including, mammaglobin in breast cancer and serum amyloid in ovarian cancer. These findings demonstrate that heterozygosity for a mutant tumor suppressor gene can alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner, and that these detectable effects of “one-hit” represent early molecular changes in tumorigenesis that may serve as novel biomarkers of cancer risk and as targets for chemoprevention Using affymetrix U133 plus2 chips, we compare the transcriptome of primary breast and ovarian epithelial cultures derived from subjects predisposed to cancer, bearing monoallelic BRCA1 or BRCA2 mutations, with corresponding cultures from control individuals that do not have mutations. |
| 1400 | GSE31903 |
Profile | MX1 is a well-characterized interferon-induced antiviral gene. MX1 is activated by viral infection due to interferon production in cells. We treated non-permissive Huh7 cells and permissive HRP4 cells with interferon. We compared the expression of genes induced by interferon to determine host factors affecting HCV replication. |
| 1401 | GSE45022 |
Profile | The HIRA chaperone complex comprised of HIRA, UBN1 and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand its function and mechanism, we integrated HIRA, UBN1, ASF1a and histone H3.3 ChIP-seq and gene expression analyses. Most HIRA-binding sites co-localize with UBN1, ASF1a and H3.3 at active promoters and active and weak/poised enhancers. At promoters, binding of HIRA/UBN1/ASF1a correlates with the level of gene expression. HIRA is required for deposition of histone H3.3 at its binding sites. There are marked differences in nucleosome and co-regulator composition at different classes of HIRA-bound regulatory site. Underscoring this, we report novel physical interactions between the HIRA complex and transcription factors, a chromatin insulator and an ATP-dependent chromatin-remodelling complex. Our results map the distribution of the HIRA chaperone across the chromatin landscape and point to different interacting partners at functionally distinct regulatory sites. We used microarrays to detail the global programme of gene expression after knockdown of HIRA |
| 1402 | GSE39786 |
Profile | Estrogens(E2) are important steroid hormones that regulate differentiation proliferation, and apoptosis in hormone-dependent breast cancer.In order to detect the E2-dependent transcription program associated with the observed cell cycle response, we analyzed the effect of H2ac knockdown on MCF-7 gene expression using microarray. Interestingly, we noticed that 51% of the E2-upregulated genes are down-regulated by depletion of H2ac. The data also show that H2ac regulated E2-dependent genes through E2-induction signaling pathway. |
| 1403 | GSE41972 |
Profile | Numerous studies have described the altered expression and the causal role of miRNAs in human cancer. However to date efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here, we find that Nucleolin (NCL), a major nucleolar protein, post-transcriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, causally involved in breast cancer initiation, progression and drug-resistance. We also show that NCL is commonly overexpressed in human breast tumors, and its expression correlates with that of NCL-dependent miRNAs. Finally, this study indicates that NCL-binding guanosine-rich aptamers affect the levels of NCL-dependent miRNAs and their target genes, reducing breast cancer cell aggressiveness, both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. |
| 1404 | GSE4917 |
Profile | This series contain time course microarray data from MCF10A-Myc cells treated with either ethanol or Dexamethasone for 30 min 2 hr, 4 hr, and 24 hr. This series contains three biological replicates that were analyzed as independent replicate experiments (data were normalized within each replicate experiment, not across all samples). Keywords: time course |
| 1405 | GSE49910 |
Profile | The specialisation of mammalian cells in time and space requires genes associated with specific pathways and functions to be co-ordinately expressed. Here we have combined a large number of publically available microarray datasets (745 samples from over 100 separate studies) derived from human primary cells and analysed on the Affymetrix U133plus2.0 array. Using the network analysis tool BioLayout Express3D we have constructed and clustered large correlation graphs of these data in order to identify robust co-associations of genes expressed in a wide variety of cell lineages. We discuss the biological significance of a number of these associations, in particular the coexpression of key transcription factors with the genes that they are likely to control. We consider the regulation of genes in human primary cells and specifically in the human mononuclear phagocyte system. Of particular note is the fact that these data do not support the identity of putative markers of antigen-presenting dendritic cells, nor classification of M1 and M2 activation states, a current subject of debate within immunological field. We have provided this data resource on the BioGPS web site (www.biogps.org) and on macrophages.com (www.macrophages.com). |
| 1406 | GSE43177 |
Profile | MicroRNA are small non-coding RNA molecules that regulate gene expression. To investigate the role of microRNA in ITP we performed genome-wide expression analyses of mRNA and microRNA in T-cells from ITP patients and controls. We identified 1,915 regulated genes and 22 regulated microRNA that differed between ITP patients and controls. Seventeen of the 22 regulated microRNA were linked to changes in target gene expression; 57 of these target genes were associated with the immune system, e.g. T-cell activation and regulation of immunoglobulin production. CXCL13 and IL-21 were two microRNA target genes significantly increased in ITP. We could demonstrate increased plasma levels of CXCL13 and others have reported increased plasma levels of IL-21 in ITP. Thus, regulated microRNA were significantly associated with both gene and protein expression of molecules in immunological pathways. We suggest that microRNA may be important regulatory molecules involved in the loss of tolerance in ITP. |
| 1407 | GSE30391 |
Profile | Human umbilical cord Wharton’s jelly stem cells (WHJSC) are gaining attention as a possible clinical source of mesenchymal stem cells for use in cell therapy and tissue engineering due to their high accessibility expansion potential and plasticity. However, the cell viability changes that are associated to sequential cell passage of these cells are not known. In this analysis, we have identified the gene expression changes that are associated to cell passage in WHJSC. We used microarrays to detail the global programme of gene expression underlying cell passage on WHJSC. |
| 1408 | GSE22781 |
Profile | SN12C.19 is a renal carcinoma cell line with loss of heterozygosity in the 3p chromosomal region near the centromere. It is believed that a tumor suppressor gene is located in this region. In studies with athymic nude mice tumor formation followed injection of SN12C.19 cells. Tumor formation did not follow by injection of the hybrid cell line SN19(3i)YY, which includes a very small fragment insertion of the 3p chromosomal arm. The goal of this array experiment was to identify genes differentially expressed in SN12C.19 by the introduction of a normal copy of the chromosomal 3p arm. SN12C.19 and SN19(3i)YY cells were hybridized to Affymetrix U133 Plus 2.0 Chips. Array quality was inspected with output from dChip software. Gene expression was quantified with PDNN software. There were 57 probesets showing differential expression on the 3p arm, corresponding to 46 genes. |
| 1409 | GSE18239 |
Profile | Aberrant signal transduction contributes substantially to leukemogenesis. The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors and plays a nonredundant role in lymphoid cell precursor proliferation survival, and differentiation. Somatic mutations in JAK1 occur in individuals with acute lymphoblastic leukemia (ALL). JAK1 mutations were more prevalent among adult subjects with the T cell precursor ALL, where they accounted for 18% of cases, and were associated with advanced age at diagnosis, poor response to therapy, and overall prognosis We used microarray to compare the gene expression profile of JAK1 mutation positive or negative ALL blasts |
| 1410 | GSE11407 |
Profile | The purpose of this study was to characterize the gene expression profile of MDA-MB-231 breast cancer cells treated with various SCFA-hexosamine analogs to better understand the role of various modifications to this scaffold. Keywords: SCFA-hexosamine analog comparison |
| 1411 | GSE17300 |
Profile | Overexpression of USF1 in HEK293T cells in vitro to ascertain the genes downstream of USF1. Will identify direct targets as well as indirect targets of USF1. Keywords: Overexpression of transcription factor to determine downstream targets. |
| 1412 | GSE31474 |
Profile | We used the microarray data to analyze host cells response on A549 cells infected with A/duck/Malaysia/F189/07/2004(H5N2) |
| 1413 | GSE35659 |
Profile | The molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption. |
| 1414 | GSE6283 |
Profile | Background: Among full autosomal trisomies only trisomies of chromosome 21 (Down syndrome, DS), 18 (Edward syndrome, ES) and 13 (Patau syndrome, PS) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effects due to the trisomic chromosome, a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to define whether (1) overexpression of genes of the trisomic chromosome contributes solely to the phenotype, if (2) all genes of the trisomic chromosome are upregulated similarly and whether the ratio of gene expression is in agreement with the gene dosis, (3) whether the different trisomies behave similarly in the characteristics of transcriptional dysregulation, and (4) whether transcriptional pattern can be potentially used in prenatal diagnosis. Methods: Using oligonucleotide microarrays (Affymetrix, U133 Plus 2.0), we analyzed whole genome expression profiles representing 54.000 probe sets in cultured amniocytes (AC) and chorion villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 21, 18 and 13. Findings: We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional level of approximately 12-13 % of the supernumerary chromosome appeared similar to the respective chromosome pair in normal karyotypes. Expression values as well as the expression patterns of genes from the trisomic chromosome can distinguish the respective trisomic samples from euploid controls. A subset of chromosome 21-genes including the DSCR1-gene involved in fetal heart development was consistently up-regulated in different tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 13 and trisomy 18 vigorous downstream transcriptional changes were found. Interpretation: Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. As several transcriptional pathways are altered, complex regulatory mechanisms are involved in the pathogenesis of autosomal trisomies. A genome-wide transcriptional dysregulation was predominantly observed in trisomies 13 and 18, whereas a more to chromosome 21 restricted expression alteration was found in trisomy 21. Keywords: Trisomy, Down syndrome, Patau syndrome, Edward syndrome, microarray, gene expression, amniocytes, chorion villus cells, gene dosage effect, DSCR1 |
| 1415 | GSE12907 |
Profile | Juvenile pilocytic astrocytoma (JPA) is one of the most common brain tumors in children. The expression profiles of 21 JPAs determined using Affymetrix GeneChip U133A, were compared with subjects with normal cerebella. The genes involved in neurogenesis, cell adhesion, synaptic transmission, central nervous system development, potassium ion transport, protein dephosphorylation, and cell differentiation were found to be significantly deregulated in JPA. These 21 JPAs were further clustered into two major groups by unsupervised hierarchical clustering using a set of 848 genes with high covariance (0.5-10). Supervised analysis with Significance Analysis of Microarrays software between these two potential subgroups identified a list of significant differentially expressed genes involved in cell adhesion, regulation of cell growth, cell motility, nerve ensheathment, and angiogenesis. Immunostaining of myelin basic protein on paraffin sections derived from 18 incompletely resected JPAs suggests that JPA without myelin basic protein–positively stained tumor cells may have a higher tendency to progress. |
| 1416 | GSE40122 |
Profile | Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized; however potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7kb lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high mRNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a suite of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25 nucleotide “TINCR box” motif which is strongly enriched in interacting mRNAs \and required for TINCR binding. A high-throughput screen to analyze TINCR binding capacity to ~9,400 human recombinant proteins revealed direct binding of TINCR RNA to the Staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay (SMD), however, lacked differentiation impacts. Instead, the TINCR/STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through inducible lncRNA binding to differentiation mRNAs to ensure their expression. |
| 1417 | GSE32374 |
Profile | Congenital glioblastoma multiforme (cGBM) historically has been considered an aggressive tumor of infancy requiring extensive chemotherapy to achieve cure. We report on 4 patients at our institution with cGBMs who were treated with surgery and chemotherapy (carboplatin and etoposide every 21 days for 2-6 cycles). Four of four patients are progression free at a median time of 27.5 months (22-103 months). To characterize the molecular biology of cGBM we compared the gene expression profiles of 3 cGBMs to 12 pediatric and 6 primary adult glioblastomas collected at our institution. Unsupervised hierarchical clustering showed cGBMs grouped together with other high-grade gliomas. cGBMs demonstrated marked similarity to both pediatric and adult GBMs, with only a total of 31 differentially expressed genes identified (FDR < 0.05). Unique molecular features of congenital GBMs identified included over-expression of multiple genes involved in glucose metabolism and tissue hypoxia pathways. Four tyrosine kinases were also mong the up-regulated genes (RET, RASGRF2, EFNA5, ALK). Thus, at our institution congenital GBMs, while similar both histologically and molecularly to other GBMs, appear to have a good prognosis with surgery in combination with relatively moderate chemotherapy. Further study is needed to determine if the few gene expression differences that were identified may contribute to the better survival seen in these tumors compared to pediatric or adult GBMs. Key Words: glioblastoma; congenital; pediatric; gene expression; microarray |
| 1418 | GSE11181 |
Profile | Although evidence has shown that very small electric currents produce a beneficial therapeutic result for wounds non-invasive EMF therapy has consisted mostly of anecdotal clinical reports with very few well controlled laboratory mechanistic studies. In this study, we evaluated the effects and potential mechanisms of a non-invasive EMF device on skin wound repair. In vitro analyses with human skin keratinocyte cultures demonstrated that the non-invasive EMF has a very strong effect on accelerating keratinocyte migration and a relatively weaker effect on promoting keratinocyte proliferation. The positive effects of the non-invasive EMF on cell migration and proliferation seem keratinocyte specific without such effects seen on dermal fibroblasts. cDNA microarray and RT-PCR performed revealed increased expression of CRK7 and HOXC8 genes in treated keratinocytes. This study suggests that a non-invasive electric magnetic field accelerates wound reepithelialization through a mechanism of promoting keratinocyte migration and proliferation, possibly due to upregulation of CRK7 and HOXC8 genes. Keywords: Comparative Genomic Hybridization |
| 1419 | GSE17508 |
Profile | To examine the expression patterns of human miR-22-responsive transcripts in estrogen receptor alpha positive cell line MCF7 we transfected miR-22 duplex or negative control RNA duplex into MCF7 cells. Gene expression patterns were then evaluated using Affymetrix Human Genome U133 Plus 2.0 Array microarrays. Keywords: comparision of expression patterns in MCF7 cells with or without human miR-22 overexpression. |
| 1420 | GSE39227 |
Profile | miRNA-mediated gene expression silencing has previously been shown to be important for a variety of physiological and pathological processes. Here we have explored the role of one bona fide human-specific miRNA (miR-941) in evolution of the human-specific expression and function. Using combination of high-throughput sequencing (GSE26545), miRNA transfection and large-scale PCR of various human populations, we have shown that emergence and rapid expansion of miR-941 might take place on the human evolutionary linage between six and one million years ago. Functionally, miR-941 could be associated with hedgehog and insulin signaling pathways, and thus might potentially play a role in evolution of human longevity. Human-specific effects of miR-941 regulation are detectable in human brain and affect genes involved in neurotransmitter signaling. Furthermore, emergence of miR-941 on the human evolutionary linage was accompanied by the accelerated loss of its binding sites. Taken together, these results strongly implicate the contribution of miR-941 in evolution of the human-specific phenotype. |
| 1421 | GSE17763 |
Profile | Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways two functions generally assumed to be coordinately regulated. Here the regulation of these key functions was investigated in human blood-derived macrophages. IL-10 induced the phagocytic pathway, including CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxLDL. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of the spectrum of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form of the disease and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity in bacterial infections. |
| 1422 | GSE10096 |
Profile | Bone is a frequent target of lung cancer metastasis which is associated with significant morbidity and a dismal prognosis. To identify and functionally characterize genes involved in the mechanisms of osseous metastasis we developed a murine lung cancer model. Comparative transcriptomic analysis identified genes encoding signaling molecules (such as TCF4 and PRKD3), and cell anchorage related proteins (MCAM, and SUSD5), some of which were basally modulated by TGFbeta in tumor cells and in conditions mimicking tumor-stroma interactions. Triple gene combinations induced not only high osteoclastogenic activity but also a marked enhancement of global metalloproteolytic activities in vitro. These effects were strongly associated with robust bone colonization in vivo, whereas this gene subset was ineffective in promoting local tumor growth and cell homing activity to bone. Interestingly, global inhibition of metalloproteolytic activities and simultaneous TGFbeta blockade in vivo led to increased survival and a remarkable attenuation of bone tumor burden and osteolytic metastasis. Thus, this metastatic gene signature mediates bone-matrix degradation by a dual mechanism of induction of TGFbeta-dependent osteoclastogenic bone resorption and enhancement of stroma-dependent metalloproteolytic activities. Our findings suggest the cooperative contribution of host-derived and cell-autonomous effects directed by a small subset of genes in mediating aggressive osseous colonization. Keywords: disease state analysis of human metastatic cell lines |
| 1423 | GSE35642 |
Profile | The pesticide rotenone a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs. |
| 1424 | GSE28583 |
Profile | The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end an oligonucleotide microarray was performed (Affymetrix’s HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system. |
| 1425 | GSE18959 |
Profile | These arrays were conducted in order to confirm the generation of astrocytes from human embryonic stem cells and to determine expression differences between astrocyte subtypes. |
| 1426 | GSE21095 |
Profile | Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However a progenitor population for alveolar type II (ATII) cells in adult human lungs have not been identified. Here we isolated alveolar epithelial progenitor cells (AEPCs) from adult human lungs. AEPCs showed mesenchymal stem cell (MSC)-like characteristics combined with ATII cell-phenotypes. AEPCs had the capability for self-renewal and the potential to generate ATII cells in vitro. Furthermore, cells expressing similar markers were present within alveolar walls in normal lungs and these cells were significantly increased in ATII cell hyperplasias. These results suggest that adult human lungs contain a progenitor population for ATII cells. |
| 1427 | GSE12320 |
Profile | Our objective is to clarify the function of EWS-POU5F1 chimera. Specifially GBS6 cells were established from an undifferentiated bone sarcoma carrying translocation t(6;22)(p21;q12). The translocation resulted in a gene fusion between EWS and POU5F1. Gene expression analysis of t(6;22) undifferentiated sarcoma cell line GBS6 transfected with POU5F1 specific siRNA to investigate the function of EWS-POU5F1. |
| 1428 | GSE9241 |
Profile | The maturation of dendritic cells (DCs) after exposure to microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady state conditions triggered by alterations in E-cadherin-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the b-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These DCs induced tolerance in vivo and may thus contribute to the elusive steady state “tolerogenic DCs”. Keywords: time-course, dendritic cell maturation |
| 1429 | GSE27670 |
Profile | In this study we have investigated the effect of BLIMP1α on gene expression, cell differentiation and pathogenesis in normal human GC B cells using a non-viral vector based system |
| 1430 | GSE8685 |
Profile | In this study we compared the effects of IL-2 IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells. Keywords: 3 replicates in each of 4 conditions |
| 1431 | GSE13159 |
Profile | An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005 the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=2,096 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. |
| 1432 | GSE28810 |
Profile | Overexpression of miR-31 inhibits the migration and invasion ability of glioma cell. We sought to obtain the genes regulated by mir-31 in glioma cell line. |
| 1433 | GSE30169 |
Profile | Oxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin. These samples are an extention of samples of similar origin deposited in GSE20060 |
| 1434 | GSE3254 |
Profile | Considerable variation in gene expression data from different DNA microarray platforms has been demonstrated. However no characterization of the source of variation arising from labeling protocols has been performed. To analyze the variation associated with T7-based RNA amplification/labeling methods, aliquots of the Stratagene Human Universal Reference RNA were labeled using 3 eukaryotic target preparation methods and hybridized to a single array type (Affymetrix U95Av2). Variability was measured in yield and size distribution of labeled products, as well as in the gene expression results. All methods showed a shift in cRNA size distribution, when compared to un-amplified mRNA, with a significant increase in short transcripts for methods with long IVT reactions. Intra-method reproducibility showed correlation coefficients >0.99, while inter-method comparisons showed coefficients ranging from 0.94 to 0.98 and a nearly two-fold increase in coefficient of variation. Fold amplification for each method was positively correlated with the number of present genes. Two factors that introduced significant bias in gene expression data were observed: a) number of labeled nucleotides that introduces sequence dependent bias, and b) the length of the IVT reaction that introduces a transcript size dependent bias. This study provides evidence of amplification method dependent biases in gene expression data. Keywords: method validation study |
| 1435 | GSE18934 |
Profile | Human mesenchymal stem cells circulate in 1st and early 2nd trimester fetal blood but not in adults. Like other fetal cell types they cross the placenta, and can be found in maternal organs decades later. To determine potential ligands in human fetal mesenchymal stem cells not present in maternal blood, the gene expression of 1st trimester human fetal bone marrow, liver and blood derived mesenchymal stem cells will be compared to blood mononuclear cells from pregnant women using a Affymetrix human gene array system. |
| 1436 | GSE34750 |
Profile | Human T cell leukemia virus type 1 (HTLV-1) Tax is potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. In this study a large-scale host cell signaling events related to cellular proliferation were used to identify genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis. |
| 1437 | GSE17078 |
Profile | Protein C (PC) deficiency increases the risk of venous thrombosis (VT) among members of Kindred Vermont II but fails to fully account for the inheritance pattern. A genome scan of the pedigree supported the presence of a prothrombotic gene on chromosome 11q23 with weaker support on chromosomes 10p12 and 18p11.2-q11. Preliminary data from Affimetrix microarray expression analysis of Blood Outgrowth Endothelial Cells of 3 members of Kindred Vermont II compared to a well established normal control group indicated that IgsF4 was decreased in patients versus controls. In addition, both statistical and pathway analysis results suggested that these genes are associated protein C. Further studies indicated that Cell Adhesion Molecule 1 (CADM1), a member of the IgsF4 superfamily, may be associated with VT. |
| 1438 | GSE31469 |
Profile | We used the microarray data to analyze host cells response on A549 cells infected with A/WSN/33 (H1N1) |
| 1439 | GSE9349 |
Profile | Gene expression patterns of 11 metastazised tumors of the head and neck region were compared to 11 non-metastasized tumors Keywords: disease state analysis |
| 1440 | GSE12427 |
Profile | Epstein-Barr virus (EBV)- encoded RNAs (EBERs) are aboundance in all EBV lantency it was found that EBERs may contribute to the oncogenesis. To study the role of EBV-encoded small RNAs (EBERs) in Hodgkin lymphoma, we transfected Hodgkin lymphoma cell lines, KMH2 and L428, with EBER1 and screen with microarrays to verify what is the possible role of the EBER1 in Hodgkin lymphoma. |
| 1441 | GSE21989 |
Profile | Background: In diabetes chronic hyperinsulinemia is responsible for the instability of the atherosclerotic plaque and stimulates cellular proliferation through the activation of the MAP kinases which in turn regulate cellular proliferation. However, it is not known whether insulin itself could increase the transcription of specific genes for cellular proliferation in the endothelium. Hence, the characterization of transcriptional modifications in endothelium is an important step for a better understanding of the mechanism of insulin action and the relationship between endothelial cell dysfunction and insulin resistance. Methodology and principal findings: The transcriptional response of endothelial cells in the 440 minutes following insulin stimulation was monitored using microarrays and compared to a control condition. About 1700 genes were selected as differentially expressed based on their treated minus control profile, thus allowing the detection of even small but systematic changes in gene expression. Genes were clustered in 7 groups according to their time expression profile and classified into 15 functional categories that can support the biological effects of insulin, based on Gene Ontology enrichment analysis. In terms of endothelial function, the most prominent processes affected were NADH dehydrogenase activity, N-terminal myristoylation domain binding, nitric-oxide synthase regulator activity and growth factor binding. Pathway-based enrichment analysis revealed “Electron Transport Chain” significantly enriched. Results were validated on genes belonging to “Electron Transport Chain” pathway, using quantitative RT-PCR. Conclusions: As far as we know, this is the first systematic study in the literature monitoring transcriptional response to insulin in endothelial cells, in a time series microarray experiment. Since chronic hyperinsulinemia is responsible for the instability of the atherosclerotic plaque and stimulates cellular proliferation, some of the genes identified in the present work are potential novel candidates in diabetes complications related to endothelial dysfunction. |
| 1442 | GSE38190 |
Profile | To date there is no specific marker for limbal epithelial stem cells. The identification of a marker that is expressed in the limbal epithelium but not in the cornea or conjunctiva epithelium has been a growing need. To search for limbal-specific marker(s), we performed preferential gene profiling in the limbus in direct comparison to that in the cornea and conjunctiva using microarray technique. |
| 1443 | GSE27473 |
Profile | We propose the hypothesis that loss of estrogen receptor function which leads to endocrine resistance in breast cancer also results in de-differentiation from an epithelial to a mesenchymal phenotype that is responsible for increased aggressiveness and metastatic propensity. siRNA mediated silencing of the estrogen receptor in MCF7 breast cancer cells resulted in estrogen/tamoxifen resistant cells (pII) with altered morphology, increased motility with rearrangement and switch from an actin to a vimentin based cytoskeleton, and ability to invade simulated components of the extracellular matrix. Phenotypic profiling using an Affymetrix Human Genome U133 plus 2.0 GeneChip indicated fold changes ≥ 3 in approximately 2500 identifiable unique sequences, with about 1270 of these being up-regulated in pII cells. Changes were associated with genes whose products are involved in cell motility, loss of cellular adhesion and interaction with the extracellular matrix. Selective analysis of the data also showed a shift from luminal to basal cell markers and increased expression of a wide spectrum of genes normally associated with mesenchymal characteristics, with consequent loss of epithelial specific markers. Over-expression of several peptide growth factors and their receptors are indicative of an increased contribution to the higher proliferative rates of pII cells as well as aiding their potential for metastatic activity. Signalling molecules that have been identified as key transcriptional drivers of epithelial to mesenchymal transition were also found to be elevated in pII cells. We suggest that these data support our hypothesis that induced loss of estrogen receptor in previously antiestrogen sensitive cells is a trigger for the concomitant loss of endocrine dependence and onset of a series of possibly parallel events that changes the cell from an epithelial to a mesenchymal type. Inhibition of this transition through targeting of specific mediators may be a useful supplementary strategy to circumvent the effects of loss of endocrine sensitivity. We used microarrays to detail the global programme of gene expression underlying Epithelial to mesenchymal transition and identified distinct classes of regulated genes during this process. |
| 1444 | GSE25547 |
Profile | The transcription factor Peroxisome Proliferator-Activated Receptor α (PPARα) is an important regulator of hepatic lipid metabolism. While PPARα is known to activate transcription of numerous genes no comprehensive picture of PPARα binding to endogenous genes has yet been reported. To fill this gap, we performed ChIP-chip in combination with transcriptional profiling on HepG2 human hepatoma cells treated with the PPARα agonist GW7647. We found that GW7647 increased PPARα binding to 4220 binding regions. GW7647-induced binding regions showed a bias around the transcription start site and most contained a predicted PPAR binding motif. Several genes known to be regulated by PPARα, such as ACOX1, SULT2A1, ACADL, CD36, IGFBP1 and G0S2, showed GW7647-induced PPARα binding to their promoter. A GW7647-induced PPARα-binding region was also assigned to SREBP-targets HMGCS1, HMGCR, FDFT1, SC4MOL, and LPIN1, expression of which was induced by GW7647, suggesting cross-talk between PPARα and SREBP signaling. Our data furthermore demonstrate interaction between PPARα and STAT transcription factors in PPARα-mediated transcriptional repression, and suggest interaction between PPARα and TBP and C/EBPα in PPARα-mediated transcriptional activation. Overall, our analysis leads to important new insights into the mechanisms and impact of transcriptional regulation by PPARα in human liver and highlight the importance of cross-talk with other transcription factors. |
| 1445 | GSE15928 |
Profile | CD25 monoclonal antibody binding to the alpha-chain of the Interleukin-2 (IL-2) receptor blocks high affinity IL-2 binding thereby preventing complete T cell activation and being of ample importance in transplantation medicine and potentially the treatment of autoimmune disease. However, CD25 antibodies do not only block T cell activation but also prevent activation induced cell death (AICD) attributing a dual function to IL-2. In this study, the modulation of the genomic expression profile of human peripheral blood mononuclear cells (PBMC) with therapeutic concentrations of humanized anti-CD25 mAb was investigated. PBMC were stimulated with CD3 antibody OKT-3 together with recombinant IL-2 in the absence or presence of anti-CD25 mAb. RNA was extracted and subjected to microarray analysis on U133A microarrays (Affymetrix). The expression profile revealed the up-regulation of 62 genes and down-regulation of 38 genes by anti-CD25 mAb, respectively. |
| 1446 | GSE29060 |
Profile | Gene expression profiling for identification of genes regulated by DNA methylation |
| 1447 | GSE17636 |
Profile | NF1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing FoxF1. We used microarray to identify direct targets for NF1-C2. |
| 1448 | GSE13763 |
Profile | In the past three years the role of inflammatory cytokines and chemokines in tumour promotion and progression has been intensively studied. The chemokine receptor CXCR4 and its ligand CXCL12 are commonly expressed in malignant cells from primary tumours metastases and also in malignant cell lines. To investigate the biological significance of this receptor/ligand pair, we knocked-down CXCR4 expression in ovarian cancer cell line IGROV-1 using shRNA, and established stable cell lines. Using Affymetrix microarrays we compared in vitro gene expression in parental IGROV-1 and IGROV-Mock cells with two clones of IGROV-shCXCR4 cells. Gene Set Enrichment Analysis (GSEA) of those genes which were altered by RNA interference of CXCR4 revealed evidence for a cell autonomous signaling network involving CXCR4, TNF-a, IL6 and Notch pathways in ovarian cancer cells. Keywords: Affymetrix GeneChip Human Genome U133Plus 2.0 |
| 1449 | GSE28448 |
Profile | TGFβ is known to be a potent inducer of EMT a process involved in tumor invasion. TIF1γ has been reported to participate to TGFβ signaling. In order to understand the role of TIF1γ in TGFβ signaling and its requirement for EMT, we analyzed the TGFβ1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1γ-silenced cells after TGFβ1 treatment, whereas Smad4 inactivation completely blocked this process. In support of these observations, microarray data show that the functions of several TIF1γ target genes can be linked to EMT. As a negative regulator of Smad4, TIF1γ could be critical for the regulation of TGFβ signaling. This work highlights the molecular relationship between TIF1γ and Smad4 in TGFβ1 signaling and EMT. |
| 1450 | GSE24824 |
Profile | To identify genes differentially modulated by anti-miR-182 treatment in a liver melanoma metastasis mouse model. Targeting oncogenic microRNAs is emerging as a promising strategy for cancer therapy. Here we provide proof-of-principle for the safety and efficacy of miRNA targeting against metastatic tumors. We tested the effect of targeting miR-182 a pro-metastatic miRNA frequently overexpressed in melanoma, whose silencing represses invasion and induces apoptosis in vitro. In particular, we assessed the effect of anti-miR-182 oligonucleotides synthesized with 2’ sugar modifications and a phosphorothioate backbone in a mouse model of melanoma liver metastasis. Luciferase imaging showed that mice treated with anti-miR-182 had an appreciably lower burden of liver metastases compared to the control. We confirmed that miR-182 levels were effectively downregulated in the anti-miR treated tumors relative to the scrambled treated tumor both in the liver and in the spleen. This downregulation was accompanied by an upregulation of miR-182 direct targets. Transcriptome analysis of mouse tissues treated with anti-miR-182 or scramble oligonucleotides revealed an enrichment for genes controlling survival, adhesion and migration modulated in response to anti-miR-182 treatment. These data indicate that in vivo administration of anti-miRs allows for efficient miRNA targeting and concomitant upregulation of target levels. Our results suggest that the use of anti-miR-182 is a promising therapeutic strategy for metastatic melanoma and provide solid proof-of-principle for similar strategies against other metastatic tumors. Keywords: Differentially expressed genes (mRNAs) in response to miRNA inhibition |
| 1451 | GSE31681 |
Profile | Cumulus cells (CCs) are biologically distinct from other follicular cells and perform specialized roles transmitting signals within the ovary and supporting oocyte maturation during follicular development. The Affymetrix 3’ IVT express protocol was used to prepare cRNA (one-cycle amplification) with a starting concentration of 100 ng of total RNA To compare groups of CCs at different stages of oocyte nuclear maturation, a Significance Analysis of Microarrays (SAM) was performed. |
| 1452 | GSE33135 |
Profile | Glucocorticoids are part of the therapeutic armamentarium of chronic lymphocytic leukemia where it has been suggested that cells with unmutated IGHV genes exhibit higher sensitivity. The mechanisms by which glucorticoids are active in CLL are not well elucidated. We used microarrays to detail the global programme of gene expression underlying dexamethasone differential activity according to the prognostic subgroups mutated IGHV genes / low ZAP-70 expression and unmutated IGHV genes / high ZAP-70 expression. We aimed to ascertain the molecular mechanisms that are influencing the diffferential response to this drug. |
| 1453 | GSE18571 |
Profile | Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process of effects of a drug treatment. In this study we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer. Results: Colony formation and sulforhodamine B (IC50 < 1nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a signature, termed rapamycin metagene index (RMI), of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%). In the Miller dataset, RMI was significantly associated with tumor size or lymph node status. High (>75) percentile) RMI was significantly associated with longer survival (P = 0.015). On multivariate analysis, RMI (P = 0.029), tumor size (P = 0.015) and lymph node status (P = 0.01) were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (P = 0.41). In Wang dataset, RMI predicted time to disease relapse (P = 0.09). Conclusions: Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment. Mol Cancer. 2009 Sep 24;8(1):75. |
| 1454 | GSE26787 |
Profile | In order to identify pre-conceptional endometrial dysregulations we compared the endometrial expression between fertile and IF and RM patients |
| 1455 | GSE21657 |
Profile | This study was designed to identify genes that are differentially expressed when BP1 homeobox gene is overexpressed in MCF-7 breast cancer cells. The goal is to understand the functional role of BP1 in breast tumorigenesis. |
| 1456 | GSE6521 |
Profile | ErbB receptor ligands epidermal growth factor (EGF) and heregulin (HRG), induce dose-dependent transient and sustained intracellular signaling, proliferation and differentiation of MCF-7 breast cancer cells, respectively. In an effort to delineate the ligand-specific cell determination mechanism, we investigated time-course gene expressions induced by EGF and HRG that induce distinct cellular phenotypes in MCF-7 cells. To analyze the effects of ligand dosage and time for the gene expression independently, we developed a statistical method for decomposing the expression profiles into the two effects. Our results indicated that signal transduction pathways devotedly convey quantitative properties of the dose-dependent activation of ErbB receptor to early transcription. The results also implied that moderate changes in the expression levels of numbers of genes, not the predominant regulation of a few specific genes, might cooperatively work at the early stage of the transcription for determining the cell fate. However, the EGF- and HRG-induced distinct signal durations resulted in the ligand-oriented biphasic induction of proteins after 20 min. The selected gene list and HRG-induced prolonged signaling suggested that transcriptional feedback to the intracellular signaling results in a graded to biphasic response in the cell determination process, and that each ErbB receptor is inextricably responsible for the control of amplitude and duration of cellular biochemical reactions. Keywords: time course |
| 1457 | GSE42320 |
Profile | IKKe was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. In order to elucidate functional roles of IKKe we used microarray analysis to identify genes changed upon IKKe shRNA knockdown and compared with genes affected in ovarian cancers |
| 1458 | GSE21216 |
Profile | To elucidate whether or not a subtype of adenocarcinoma with neuroendocrine nature has poor prognosis we performed gene expression profiling of an achaete-scute complex homolog 1 (ASCL1) siRNA experiment. |
| 1459 | GSE9854 |
Profile | The tumor suppressor gene HIC1 (Hypermethylated in Cancer 1) is essential for mammalian development and is epigenetically silenced in many human tumors. Functionally HIC1 is involved in a complex pathway regulating P53 tumor-suppression activity. HIC1 encodes a sequence-specific transcriptional repressor containing five Krüppel-like C2H2 zinc fingers but only a few genes regulated by HIC1 have been reported, including SIRT1. Keywords: Time Series Design |
| 1460 | GSE16778 |
Profile | We used microarrays to examine gene expression levels from members of 45 CEPH-Utah pedigrees. Keywords: array-based gene expression |
| 1461 | GSE10410 |
Profile | The triazole antifungals myclobutanil (MYC) propiconazole (PPZ) and triadimefon (TDF) [Propiconazole CASNR 60207-90-1; Triadimefon CASNR 43121-43-3; Myclobutanil CASNR 88671-89-0] all disrupt steroid hormone homeostasis and cause varying degrees of hepatic toxicity. To identify biological pathways consistently activated across various study designs, gene expression profiling was conducted on livers from rats following acute, repeated dose, or prenatal to adult exposures. To explore conservation of responses across species, gene expression from these rat in vivo studies were also compared to in vitro data from rat and human primary hepatocytes exposed to MYC, PPZ, or TDF. Pathway and gene level analyses across time of exposure, dose, and species identified patterns of expression common to all three triazoles, which were also conserved between rodents and humans. Pathways affected included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Many of the differentially expressed genes are regulated by the nuclear receptors CAR, PPAR alpha and PXR, including ABC transporter genes (Abcb1 and MDR1), genes significant to xenobiotic, fatty acid, sterol and steroid metabolism (Cyp2b2 and CYP2B6; Cyp3a1 and CYP3A4; Cyp4a22 and CYP4A11) and xxx (Ugt1a1 and UGT1A1). Modulation of hepatic sterol and steroid metabolism is a plausible mechanism for triazole induced increases in serum testosterone. The gene expression changes caused by all three triazoles appear to focus on pathways regulating lipid and testosterone homeostasis, identifying potential common mechanisms of triazole hepatotoxicity that are conserved between rodents and humans. Keywords: dose response, time course, comparative toxicogenomics |
| 1462 | GSE15491 |
Profile | Pluripotent stem cells which are capable to generate any cell type of the human body, such as human embryonic stem cells (hESC) or human induced pluripotent stem cells (hiPS) are a very promising source of cells for regenerative medicine. However, the genesis, the in vitro amplification and the differentiation of these cells still need improvement before clinical use. This study aimed to improve our knowledge on these critical steps in pluripotent stem cell generation. We derived new hESC lines, generated hiPS and compared these cell types with human foreskin fibroblasts and partially reprogrammed fibroblasts. |
| 1463 | GSE20538 |
Profile | Thyroid hormone is crucial for normal brain development. Thyroid hormone transporters control thyroid hormone homeostatis in brain. Mutations in the thyroid hormone transporter MCT8 result in a complex endocrine and neurological phenotype. We investigated the mechanisms of disease by analyzing gene expression profiles in fibroblasts from patients with mutations in MCT8. Performing comparative transcriptome analysis we linked the genes differentially expressed in patient fibroblasts to the human brain transcriptome. |
| 1464 | GSE28792 |
Profile | Analysis of non-differentiated Caco-2 intestinal epithelial cell line treated with polydextrose fermentation metabolites fermented for 48 hours in 4-stage in vitro colon simulator in which the conditions mimic the human proximal, ascending, transverse and distal colon in sequence , as well as with medium, 100 mM NaCl and 5 mM butyrate. Polydextrose, a soluble fiber fermented in colon, was fermented with the in vitro colon simulator in three amounts of 0%, 1% and 2%. Results provide insight into the mechanisms underlying colon cancer cells and a comparison of a complex fiber metabolome to 5 mM butyrate and 100 mM NaCl. Furthermore, the results give insight of dosage effect of increasing the concentration of fiber. High level of dietary fiber has been epidemiologically linked to protection against the risk for developing colon cancer. The mechanisms of this protection are not clear. Fermentation of dietary fiber in the colon results in production of for example butyrate that has drawn attention as a chemopreventive agent. Polydextrose, a soluble fiber that is only partially fermented in colon, was fermented in an in vitro colon simulator, in which the conditions mimic the human proximal, ascending, transverse and distal colon in sequence. The subsequent fermentation metabolome were applied on colon cancer cells, and the gene expression changes studied. Polydextrose fermentation down-regulated classes linked with cell cycle, and affected number of metabolically active cells. Further, up-regulated effects on classes linked with apoptosis implicate that polydextrose fermentation plays a role in induction of apoptosis in colon cancer cells. The up-regulated genes involved also key regulators of lipid metabolism, such as PPARg and PGC-1α. These results offer hypotheses for the mechanisms of two health benefits linked with consumption of dietary fiber, reducing risk of development of colon cancer, and dyslipidemia. |
| 1465 | GSE17732 |
Profile | PFAPA the syndrome of periodic fever associated with aphthous stomatitis, pharyngitis and/or cervical adenitis, is the most common periodic fever disease in children. Cases are mostly sporadic; the etiopathogenesis is unknown. In order to shed more insights into pathogenesis, we performed microarray expression analysis on samples from patients with PFAPA during and between flares, healthy controls and patients with hereditary autoinflammatory diseases during flares. |
| 1466 | GSE28896 |
Profile | We explored the effects of dexamethasone and lenalidomide individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34+ cells and from CD34+ cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects on the production of erythroid progenitor colonies; dexamethasone selectively increased the number burst-forming units-erythroid (BFU-E), while lenalidomide specifically increased colony-forming units-erythroid (CFU-E). Use of the drugs in combination demonstrates that their effects are not redundant. |
| 1467 | GSE23741 |
Profile | PKC-δ inhibition with the selective inhibitor rottlerin, resulted in potent downregulation of type I collagen expression and production in normal human dermal fibroblasts and abrogated the exaggerated type I collagen production and expression in fibroblasts cultured from affected skin from patients with the fibrosing disorder, systemic sclerosis (SSc). To elucidate the mechanisms involved in the ability of PKC-δ to regulate collagen production in fibroblasts, we examined the effects of PKC-δ inhibition on the transcriptome of normal and SSc-derived human dermal fibroblasts. We used microarrays to detail the effects of PKC-δ inhibition with rottlerin on the transcriptome of normal and SSc-derived human dermal fibroblasts and to identify gene networks that might be involved in the regulation of extracellular matrix by PKC-δ. |
| 1468 | GSE35959 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1469 | GSE12764 |
Profile | MCF10A cells were then transfected with MEK1(S217S221) HRAS(G12V), and null control vectors Cells were lysed 24 hours post-transfection with collection of total RNA and protein Keywords: Oncogene inducation of gene expression changes |
| 1470 | GSE43881 |
Profile | The androgen receptor (AR) is a mediator of both androgen-dependent and castration- resistant prostate cancers. Identification of cellular factors affecting AR transcriptional activity could in principle yield new targets that reduce AR activity and combat prostate cancer yet a comprehensive analysis of the genes required for AR-dependent transcriptional activity has not been determined. Using an unbiased genetic approach that takes advantage of the evolutionary conservation of AR signaling, we have conducted a genome-wide RNAi screen in Drosophila cells for genes required for AR transcriptional activity and applied the results to human prostate cancer cells. We identified 45 AR-regulators, which include known pathway components and genes with functions not previously linked to AR regulation, such as HIPK2 (a protein kinase) and MED19 (a subunit of the Mediator complex). Depletion of HIPK2 and MED19 in human prostate cancer cells decreased AR target gene expression and, importantly, reduced the proliferation of androgen-dependent and castration-resistant prostate cancer cells. We also systematically analyzed additional Mediator subunits and uncovered a small subset of Mediator subunits that interpret AR signaling and affect AR-dependent transcription and prostate cancer cell proliferation. Importantly, targeting of HIPK2 by an FDA approved kinase inhibitor phenocopied the effect of depletion by RNAi and reduced the growth of AR-positive, but not AR negative, treatment-resistant prostate cancer cells. Thus, our screen has yielded new AR regulators including drugable targets that reduce the proliferation of castration-resistant prostate cancer cells. HIPK2 and MED19 were identified via a genome-wide RNAi screen as new androgen receptor (AR) reulators. Our goal in performing this microarray was to identify the gene regulated by HIPK2 and MED19 in a late stage prostate cancer cell line (LNCaP-abl), and to see what genes are in common with known genes to be regulated by AR, and what genes are unique to HIPK2 or MED19. |
| 1471 | GSE20578 |
Profile | One lung tumor and its adjacent normal were profiled for expression levels with the Affymetrix HGU133 plus 2.0 array. |
| 1472 | GSE36842 |
Profile | Atopic dermatitis (AD) is a common disease with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in lack of specific treatments. The prevailing view is that AD is a biphasic, T-cell polarized disease, with Th2 predominating acute AD, and a switch to Th1 characterizing chronic disease. Identification of factors that participate in onset of lesions and maintenance of chronic lesions is critical for development of targeted therapeutics. We performed global genomic, molecular and cellular profiling of paired non-lesional, acute, and chronic skin biopsies from ten AD patients. Onset of acute lesions is associated with a striking increase in a subset of terminal differentiation proteins, specifically the IL-22-modulated S100A7-9. Correspondingly, acute disease is associated with significant increases in gene expression levels of the major Th22- (IL-22) and Th2- (IL-4, IL-31) cytokines and Th17-regulated genes (CCL20, PI3/Elafin), without significant changes in IL-17. A lesser induction of Th1- (IFNγ, MX-1, CXCL9-11) associated genes was detected in acute disease. Chronic skin lesions are characterized by significantly intensified activation of Th22, Th2 and Th1. Our data establish increased expression of S100A7-9 and other epidermal genes at onset of acute AD, with parallel activation of Th2 and Th22 cytokines. Our findings suggest an absence of switch mechanism in chronic disease and instead indicate that progression to chronic lesions is associated with intensified activation of immune axes that initiate onset of acute lesions, particularly Th22 and Th2. This alters the prevailing view of pathogenesis, with important therapeutic implications. |
| 1473 | GSE30903 |
Profile | In the present study we investigated whether, and to what extent, P2Rs and their ligands are involved in the regulation of AML cells. Our findings show that AML blasts express several receptors belonging to the P2X and P2Y family. Although different samples respond differently to ATP and UTP stimulation (reflecting the variability intrinsic to the group of acute myeloid leukemias), all the tested samples appear to be responsive to purinergic signalling, as demonstrated by intracellular calcium mobilization. GEP analysis demonstrated that ATP induced the expression of cell cycle inhibitors and negative modulators of cell motility, such as inhibitors of GTPase activity. On the contrary, ATP inhibits the expression cell-cycle related genes (cyclins and CDKs), activators of cell motility (Rho GTPases regulators, matrix degradation enzyme and cytoskeleton proteins) and adhesion molecules involved in homing and engraftment. |
| 1474 | GSE25146 |
Profile | This study set out to identify global changes in gene expression in AGS gastric epithelial cells following 8 hours stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point. |
| 1475 | GSE36782 |
Profile | Gliomas are the most devastating of primary adult malignant brain tumors. These tumors are highly infiltrative and can arise from cells with extensive self-renewal capability and chemoresistance frequently termed glioma-propagating cells (GPCs). GPCs are thus the plausible culprits of tumor recurrence. Treatment strategies that eradicate GPCs will greatly improve disease outcome. Such findings support the use of GPCs as in vitro cellular systems for small molecule screening. However, the nuances in utilizing GPCs as a cellular screening platform are not trivial. These slow-growing cells are typically cultured as suspension, spheroid structures in serum-free condition supplemented with growth factors. Consequently, replenishment of growth factors throughout the screening period must occur to maintain cells in their undifferentiated state, as the more lineage-committed, differentiated cells are less tumorigenic. We will present a case study of a small molecule screen conducted with GPCs and explain how unique sphere activity assays were implemented to distinguish drug efficacies against the long-term, self-renewing fraction, as opposed to transient-amplifying progenitors, latter of which are detected in conventional viability assays. We identified Pololike kinase 1 as a regulator of GPC survival. Finally, we leveraged on public glioma databases to illustrate GPC contribution to disease progression and patient survival outcome. |
| 1476 | GSE14407 |
Profile | In contrast to epithelial derived carcinomas that arise in most human organs ovarian surface epithelial cells become more rather than less differentiated as the malignancy progresses. To test the hypothesis that ovarian surface epithelial cells retain properties of relatively uncommitted pluripotent cells until undergoing neoplastic transformation, we conducted gene expression profiling analysis (Affymetrix, U133 Plus 2.0) of 12 ovarian surface epithelial cells and 12 laser capture microdissected serous papillary ovarian cances. We find that over 2000 genes are significantly differentially expressed between the surface epithelial and cancer samples. Network analysis implicates key signaling pathways and pathway interactions in ovarian cancer development. Genes previously associated with adult stem cell maintenance are expressed in ovarian surface epithelial cells and significantly down-regulated in ovarian cancer cells. Our results indicate that the surface of the ovary is an adult stem cell niche and that deregulation of genes involved in maintaining the quiescence of ovarian surface epithelial cells is instrumental in the initiation and development of ovarian cancer. |
| 1477 | GSE33366 |
Profile | breast cancer. Combined IGF and estrogen-targeted therapy may improve the benefit of hormonal therapy alone. We employed a postmenopausal model of estrogen-dependent breast cancer in vitro and in vivo using the aromatase-expressing MCF-7/AC-1cells. Using this model we investigated the anti-tumor effects of the dual IGF-1R/InsR tyrosine kinase inhibitor, BMS-754807 alone and in combination with letrozole or tamoxifen in vivo. We used microarrays to compare gene expression changes of MCF7 breast xenograft treated with either BMS754807, or Tamoxifen or Letrozole alone; or Tamoxifen or Letrozole in combination with BMS754807 for 28 days |
| 1478 | GSE19314 |
Profile | We hypothesized that microarray analyses of whole blood gene expression would identify patterns of gene expression useful in the diagnosis for sacroidosis and identify inflammatory mediators relevant to the underlying pathophysiology. |
| 1479 | GSE19495 |
Profile | 1507 known genes have been identified differentially regulated during HisOH treatment by more than 2 fold. This includes 250 down-regulated genes and 1257 up-regulated genes. |
| 1480 | GSE41600 |
Profile | Microarray profiling using the Affymetrix GeneChip Human Genome U133 plus 2.0 arrays was performed to comprehensively determine global changes in transcript levels in bronchial epithelial cells following elastase treatment. Elastase caused a significant change in expression (P < 0.05 fold change 1.5) of 364 transcripts corresponding to 348 genes. Elastase affected the expression of signaling molecules including chemokines, cytokines, and receptors, as well as components of the spliceosome, transcription machinery, cell cycle and ubiquitin-mediated proteolysis. Importantly, the transcriptional response to elastase was attenuated by co-administration of 10 µM symplostatin 5. Comparison of the global heatmap of significantly modulated transcripts indicated that symplostatin 5 potently prevented the global effects of elastase. Symplostatin 5 caused a 20–68 % reduction in transcript levels of elastase-inducible genes including those involved in NOD- and MAPK- signaling pathways which are relevant to inflammation. |
| 1481 | GSE10799 |
Profile | We have investigated whether the early dissemination of tumor cells into bone marrow is associated with a specific molecular pattern in primary lung cancer Keywords: primary lung tumor tissue and normal bronchial epithelial tissue |
| 1482 | GSE28414 |
Profile | The second leading cause of cancer death for women in the U.S. is breast cancer moreover, a significant number of patients with breast tumors acquire resistance to drugs during therapy. To develop targeted therapeutic strategies to combat drug resistance it is essential to understand the basic molecular mechanisms through which cancer cells control sensitivity to chemotherapeutics. To identify new candidate genes and facilitate the discovery of novel drug resistance pathways, we have generated a resistance profile or ‘resistome’ of etoposide resitant MCF7 breast cancer cells. Differential expression of over 5000 genes (fold change > 2, P value < 0.05) indicate that several drug resistance mechanisms may be operating in these cells, including up-regulation of ABC transporter genes, down-regulation of the drug target and down-regulation of apoptotic genes. Several transcription factors such as RUNX2, SOX9, ETS1 and SMAD3 were up-regulated in the drug resistant cells. Targeted RUNX2 knockdown in the resistant cells using siRNA increased sensitivity to etoposide and also upregulated expression of pro-apoptotic genes indicating that RUNX2 could be a molecular target against etoposide resistance. Differential miRNA (microRNA) expression was observed among the drug resistant and sensitive cells suggesting that miRNA may also play a role in regulation of drug resistance. Hsa-miR-218, which targets ABCC6, was down-regulated in the drug resistant cell line. Transfection of a miR-218 mimic could down-regulate the expression of the efflux pump ABCC6 by 65% in drug resistant cells suggesting that regulation of miRNA may play an important role in etoposide resistance. |
| 1483 | GSE3467 |
Profile | We show that numerous miRNAs are transcriptionally up-regulated in papillary thyroid carcinoma (PTC) tumors compared with unaffected thyroid tissue. Among the predicted target genes of the three most upregulated miRNAs (miRs 221 222 and 146b), only less than 15% showed significant downexpression in transcript level between tumor and unaffected tissue. The KIT gene which is known to be downregulated by miRNAs 221 and 222 displayed dramatic loss of transcript and protein in those tumors that had abundant mir-221, mir-222, and mir-146b transcript. Keywords: Disease state analysis |
| 1484 | GSE21947 |
Profile | Background: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers. Methods: We examined gene expression in 46 cases of microdissected NlEpi from previously untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 ER+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9ER+, 7 ER-), we validated seven selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results: 216 probes (corresponding to 198 unique genes) distinguished the NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers themselves, (e.g., ESR1, GATA3, and CX3CL1, FABP7, respectively). QPCR validated the microarray results in both a sampling of the 30 original cases (84%) and all of the 16 independent cases (77%). Gene expression in NlEpiER+ and NlEPIERNlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 36%-53% of the genes or probes examined in each the 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions: Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. Thus, breast cancer subtypes may be detectable before histologic abnormalities. NlEpi gene expression may help define subtype-specific risk signatures, identify initial subtype specific genomic differences, and suggest new targets for subtype-specific prevention and therapy. We determined that 216 probesets significantly differed between histologically normal epithelium from ER+ breast cancer patients and from ER- breast cancer patients, and that gene expression in each type of histologically normal epithelium resembles expression of the corresponding subtype of invasive breast cancer (i.e., ER+ or ER-). These findings suggest that characteristic features of breast cancer subtypes are detectable prior to any histologic abnormality. This suggestion has implications for understanding breast cancer biology and devising new tools for assessing breast cancer risk. |
| 1485 | GSE31547 |
Profile | Develop an EGFR mutation gene expression signature to aid in predicting response and clinical outcome and to identify genes associated with the EGFR-dependent phenotype |
| 1486 | GSE45136 |
Profile | To discover novel growth factors for hematopoietic stem- and progenitor cells (HSPCs) we have assessed cytokine responses of cord blood (CB)-derived CD34+ cells in a high-content growth factor screen. We identify the immunoregulatory chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor that directly stimulates proliferation of primitive hematopoietic cells from different ontogenetic origins. Microarrays are used to compare the expression profiles of HSPCs expanded in SCF, TPO and CCL28 respectively. |
| 1487 | GSE41386 |
Profile | The loss of REST in uterine fibroids promotes aberrant gene expression and enables mTOR pathway activation |
| 1488 | GSE22601 |
Profile | T cells develop from progenitors that migrate from the bone marrow into the thymus. Thymocytes are subdivided roughly as being double negative (DN) double positive (DP), or single positive (SP), based on the expression of the CD4 and CD8 coreceptors. The DN stage is heterogeneous and can be subdivided into four distinct subsets in mice based on the expression of CD44 and CD25. In human, three distinct DN stages can be recognized: a CD34+CD38−CD1a− stage that represents the most immature thymic subset and the consecutive CD34+CD38+CD1a− and CD34+CD38+CD1a+ stages. Human DN thymocytes mature via an immature single positive (ISP CD4+) and a DP stage into CD4+ or CD8+ SP T cells that express functional T cell receptors (TCR) and that exit the thymus. In this study, gene expression was measured in each of these nine stages. |
| 1489 | GSE14500 |
Profile | Stimulation of HL60 progenitor cells with either DMSO (1.25% v/v) or atRA (10E-07M) resulted in their differentiation into neutrophils within six days. Gene expression profiles across 12 600 genes were measured for the differentiation processes induced by DMSO and atRA at 0 2, 4, 8, 12, and 18 h and daily thereafter until day 7 using oligonucleotide DNA microarrays. Keywords: time course, differentiation, cell fate transitions |
| 1490 | GSE30188 |
Profile | Analysis of serum starved PC-3 cells treated with CCG-1423 Latrunculin B, or the transcription elongation inhibitor DRB for 2 or 24 hours. Results provide insights to potential therapeutic approaches to cancer metastasis. |
| 1491 | GSE12336 |
Profile | Diffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)-β and thick stromal fibrosis. However detailed investigations on the roles of TGF-β signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF-β type II receptor expressing cells (2MLN-dnTβRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTβRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTβRII tumors. This results suggested disruption of TGF-β signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth. |
| 1492 | GSE15548 |
Profile | The scaffold attachment factors SAFB1 and SAFB2 are paralogs which are involved in cell cycle regulation, apoptosis, differentiation, and stress response. They have been shown to function as estrogen receptor co-repressors, and there is evidence for a role in breast tumorigenesis. To identify their endogenous target genes in MCF-7 breast cancer cells, we utilized gene expression array analysis, which was set up in a two-by-four design, with vehicle and estrogen treatment, and control, SAFB1, SAFB2, and SAFB1/SAFB2 siRNA as variables. Using custom chips containing 1.5 kb upstream regulatory region, we identified 541 SAFB1/SAFB2 binding sites in promoters of known genes, with significant enrichment on chromosome 1 and 6. Gene expression analysis revealed that the majority of target genes were induced in the absence of SAFB1 or SAFB2, and less were repressed. In contrast to SAFB2, which shared most of its target genes with SAFB1, SAFB1 had many unique target genes, most of them involved in regulation of the immune system. A subsequent analysis of the estrogen treatment group revealed that twelve percent of estrogen-regulated genes were dependent on SAFB1, with the majority being estrogen-repressed genes. These were primarily genes involved in apoptosis, such as BBC3, NEDD9, and OPG. Thus, this study confirms SAFB1/SAFB2’s primary role as co-repressors, and also uncovers a previously unknown role for SAFB1 in regulation of immune genes, and in estrogen-mediated repression of genes. |
| 1493 | GSE39907 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1494 | GSE17908 |
Profile | The genome of Epstein-Barr virus (EBV) encodes 86 proteins but only a limited set is expressed in EBV-growth transformed B cells termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell-cycle entry and proliferation of primary human B cells in contrast to an EBNA-2-deficient mutant virus. Surprisingly and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 upregulated and 167 downregulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A or might contribute to essential steps in the viral life cycle. In addition EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2. |
| 1495 | GSE34405 |
Profile | Gene expression profiling was carried out HeyA8 and SKOV3-ip1 ovarian cancer cell lines treated either with vehicle control or 10 uM norepinephrine. The primary research question is whether ovarian cancer cell gene expression differs as a function of norepinephrine exposure. |
| 1496 | GSE20081 |
Profile | The human steroid receptor RNA activator (SRA) gene encodes both non-coding RNAs (ncRNAs) and protein-generating isoforms. However the breadth of endogenous target genes that might be regulated by SRA RNAs remains largely unknown. To address this, we depleted SRA RNA in two human cancer cell lines (HeLa and MCF-7) with small interfering RNAs, then assayed for changes in gene expression by microarray analyses using Affymetrix HGU133+2 arrays. We also tested if SRA depletion affects estradiol-regulated genes in MCF-7 breast cancer cells. |
| 1497 | GSE7821 |
Profile | Whole genome expression profiling of 40 healthy human twins (20 monozygotic 20 dizygotic) Keywords: heritability test |
| 1498 | GSE29327 |
Profile | Analysis of gene expression of MCF10A to identify the targets of miR-221 and miR-222 Keywords: MCF10 miR-221, miR-222 |
| 1499 | GSE34268 |
Profile | CD34 positive cells of bone marrow samples from normal and MDS samples were cultured ex vivo into erythroid conditions. We used microarrays to detail the gene expression programm of erythroid cells between normal and pathological (MDS) samples |
| 1500 | GSE14330 |
Profile | The aim of this work was to identify functional features that are specific of human Treg cells through the identification of genes that are differentially expressed: 1/ in activated Treg clones versus activated Thelper clones; 2/ in Th clones activated in the presence versus the absence of TGFb; 3/ in suppressed Th clones, i.e. Th clones activated in the presence of Treg clones, versus controls. Keywords: TCR activation |
| 1501 | GSE4532 |
Profile | We used two RNA samples that differed only by a set of three hemoglobin transcripts to compare microarray cross-hybridization between two target preparation protocols. We found widespread cross-hybridization using standard cRNA target but substantially less cross-hybridization using cDNA target. Keywords: protocol comparison |
| 1502 | GSE34025 |
Profile | The mechanisms by which diesel exhaust particles act as an adjuvant are unknown. We hypothesized that these would be mediated through monocyte interactions with DEP. We sought to identify pathways with a role in inflammation or other signaling mechanisms that might demonstrate the mechanism of response to DEP. |
| 1503 | GSE37981 |
Profile | Gray matter volume in the cerebral cortex has been consistently found to be decreased in patients with schizophrenia. The superior temporal gyrus (STG) is one of the cortical regions that exhibit the most pronounced volumetric reduction. This reduction is generally thought to reflect at least in part, decreased number of synapses; the majority of these synapses are believed to be furnished by glutamatergic axon terminals onto the dendritic spines on pyramidal neurons. Pyramidal neurons in the cerebral cortex exhibit layer-specific connectional properties, providing neural circuit structures that support distinct aspects of higher cortical functions. For instance, dendritic spines on pyramidal neurons in layer 3 of the cerebral cortex are targeted by both local and long-range glutamatergic projections in a highly reciprocal fashion. Synchronized activities of pyramidal neuronal networks, especially in the gamma frequency band (i.e. 30-100 Hz), are critical for the integrity of higher cortical functions. Disturbances of these networks may contribute to the pathophysiology of schizophrenia by compromising gamma oscillation. This concept is supported by the following postmortem and clinical observations. First, the density of dendritic spines on pyramidal neurons in layer 3 of the cerebral cortex, including the STG, have been shown to be significantly decreased by 23-66% in subjects with schizophrenia. Second, consistent with these findings, the average somal area of these pyramidal cells is significantly smaller. Third, we have recently found that, in the prefrontal cortex, the density of glutamatergic axonal boutons, of which dendritic spines are their major targets, was significantly decreased by as much as 79% in layer 3 (but not layer 5) in subjects with schizophrenia. Finally, an increasing number of clinical studies have consistently demonstrated that gamma oscillatory synchrony is profoundly impaired in patients with schizophrenia. Furthermore, gamma impairment has been linked to the symptoms and cognitive deficits of the illness and the severity of these symptoms and deficits have in turn been associated with the magnitude of cortical gray matter reduction. Taken together, understanding the molecular underpinnings of pyramidal cell dysfunction will shed important light onto the pathophysiology of cortical dysfunction of schizophrenia. In order to gain insight into the molecular determinants of pyramidal cell dysfunction in schizophrenia, we combined LCM with Affymetrix microarray and high-throughput TaqMan®-based MegaPlex qRT-PCR approaches, respectively, to elucidate the alterations in messenger ribonucleic acid (mRNA) and microRNA (miRNA) expression profiles of these neurons in layer 3 of the STG. We found that transforming growth factor beta (TGFβ) and BMP (bone morphogenetic proteins) signaling pathways and many genes that regulate extracellular matrix (ECM), apoptosis and cytoskeleton were dysregulated in schizophrenia. In addition, we identified 10 miRNAs that were differentially expressed in this illness; interestingly, the predicted targets of these miRNAs included the dysregulated pathways and gene networks identified by microarray analysis. Together these findings provide a neurobiological framework within which we can begin to formulate and test specific hypotheses about the molecular mechanisms that underlie pyramidal cell dysfunction in schizophrenia. |
| 1504 | GSE14828 |
Profile | Fibroblast growth factor-2 delays the loss of chondrogenic potential in adult bone marrow-derived mesenchymal stem cells We compared human mesenchymal stem cells (hMSCs) expanded long-term with and without fibroblast growth factor (FGF) supplementation, with respect to their proliferation rate, and ability to differentiate along the chondrogenic pathway in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than those expanded under control conditions. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at passages 1 through 7, although, in some of the preparations, chondrogenic differentiation was somewhat diminished after seventh passage. Aggregates made with control cells differentiated along the chondrogenic lineage at first passage but exhibited only marginal chondrogenic differentiation after four passages and failed to form cartilage after seven passages. Microarray analysis of gene expression identified 334 transcripts that were differentially expressed in fourth passage control cells which had reduced chondrogenic potential compared to fourth passage FGF-treated cells which retained this differentiation capacity and 243 transcripts that were differentially expressed when comparing them to first passage control cells which were also capable of differentiating into chondrocytes. The intersection of these analyses yielded 49 transcripts that were differentially expressed in cells that exhibited chondrogenic differentiation in vitro compared to cells that did not. These preliminary data must now be validated to verify whether the different gene expression profiles translate into functional differences. These findings suggest that care should be exercised when extensively expanding these cells for cartilage tissue engineering applications. Keywords: time course and treatment |
| 1505 | GSE5787 |
Profile | Purpose: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. Experimental Design: A total of 33 biopsies were obtained from 11 patients sampling between two and five different areas for each tumor.The extracted RNAwas hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T =W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values. Results: In total, 448 ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to <0.15; if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed. Conclusion: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression. Keywords: disease state comparison |
| 1506 | GSE20559 |
Profile | A gene expression signature purporting to distinguish between telomerase and ALT immortalization has recently been described (Lafferty-Whyte et al. 2009). This was obtained as the intersection of two independent signatures, one obtained from cell lines and the other from a panel of liposarcomas, which utilize different telomere maintenance mechanisms (TMMs). To assess the utility of this signature we used Affymetrix U133plus2.0 arrays to undertake a similar analysis of an independent collection of liposarcomas of defined TMM. In our dataset, the 297 gene signature causes the liposarcomas to cluster not on the basis of TMM, but rather on the basis of tumor histological subtype [Figure 1], consistent with the signatures reported by others (Matushansky et al., 2008). |
| 1507 | GSE31311 |
Profile | In this study we investigated to which extend aberrant c Myc activity plays a functional role in other aNHL and whether it is independent from MYC translocations. Based on a combined microarray analysis of human germinal centre (GC) B cells transfected with c Myc and 220 aNHLs cases we developed a ‘c Myc index’. This data set contains expresssion profiles from Germinal center B-cells transfected with control or Myc expression vectors. The corresponding lymphoma gene expression profiles are included in the series with GEO accession GSE4475. |
| 1508 | GSE38749 |
Profile | Anatomical staging is a critical although imperfect, instrument to assess gastric cancer prognosis and define indication for surgery and adjuvant therapy. Despite recent advances, treatment results, as a whole, remain less than satisfactory. Thus, biomarkers are sorely needed to improve risk categorization and define new molecular targets for therapy. We used microarrays to identify genes differentially expressed according to prognosis of the patients. |
| 1509 | GSE8717 |
Profile | We used microarrays to identify genes regulated during oncolytic HSV infection. Oncolytic herpes simplex viruses (oHSV) are promising anticancer therapeutics. We sought to identify alterations in gene expression during oHSV infection of human cancer cells. Human malignant peripheral nerve sheath tumor (MPNST) cells were infected with G207 an ICP34.5-deleted oHSV previously evaluated in clinical trials. G207-infected cells demonstrated massive degradation of cellular mRNAs, while a subset were upregulated. A gene signature of 21 oHSV-induced genes contained 7 genes known to be HSV-induced. Go ontology classification revealed that a majority of upregulated genes are involved in Jak/STAT signaling, transcriptional regulation, nucleic acid metabolism, protein synthesis and apoptosis. Ingenuity-defined functional networks highlighted nodes for AP-1 subunits and interferon signaling via STAT1, SOCS1, SOCS3 and RANTES. Upregulation of SOCS1 correlated with sensitivity of MPNST lines to G207 and depletion of SOCS1 reduced virus replication >1-log. The transcriptome of oHSV-induced genes may predict oncolytic efficacy and provides rationale for next generation oncolytics. Keywords: treated vs non treated |
| 1510 | GSE6575 |
Profile | Gene expression in blood of children with autism spectrum disorder (ASD) was studied. Transcriptional profiles were compared with age and gender matched typically developing children from the general population (GP) or IQ matched children with mental retardation or developmental delay (MR/DD). Keywords: autism analysis |
| 1511 | GSE12846 |
Profile | Gene expression profiles of primary lymphatic endothelial cells (LECs) isolated from human foreskin were analyzed after siRNA-mediated knockdown of control (firefly luciferase) Prox1, NR2F2 or Prox1/NR2F2 for 48 hours. |
| 1512 | GSE36547 |
Profile | Transplantation with low numbers of hematopoietic stem cells (HSCs) found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the “effective” dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4°C, 10µM dmPGE2, 60 minutes). Incubation conditions were identified (37°C, 10µM dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells. |
| 1513 | GSE8596 |
Profile | For identification of candidate genes that is specifically expressed in Ewing family tumor (EFT) cells we performed DNA microarray-based global expression profiling using Affymetrix Human Genome U133 Plus 2.0 Array and analyxed expression profiles from EFT cell lines (7 lines), neuroblastoma (NB) cell lines (3 lines), a Rhabdomyosarcoma (RMS) cell line, and a human immortalized mesenchymal progenitor cells UET-13 cells. Keywords: Ewing family tumor |
| 1514 | GSE31243 |
Profile | Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies. |
| 1515 | GSE15520 |
Profile | Norwalk virus (NV) is a prototype strain of the noroviruses (family Caliciviridae) which have emerged as major causes of acute gastroenteritis worldwide. We have developed NV replicon systems using reporter proteins such as a neomycin resistant protein (NV replicon-bearing cells) and a green fluorescent protein (pNV-GFP) and demonstrated that these systems were excellent tools to study virus replication in cell culture. In this study, we first performed DNA microarray analysis of the replicon-bearing cells to identify cellular factors associated with NV replication. The analysis demonstrated that genes in lipid (cholesterol) or carbohydrate metabolic pathways were significantly (p< 0.001) changed by the gene ontology analysis. Among genes in the cholesterol pathways, we found that mRNA levels of hydroxymethylglutaryl-CoA (HMG-CoA) synthase, squalene epoxidase and acyl-CoA:cholesterol acyltransferase(ACAT) 1, ACAT 2, small heterodimer partner, and low density lipoprotein receptor (LDLR)-related proteins were significantly changed in the cells. |
| 1516 | GSE31245 |
Profile | PURPOSE: We investigated whether tumor tissue obtained at diagnosis expresses a specific gene profile that is predictive of findings at second-look surgery in patients with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Tumor tissue obtained at the time of diagnosis was profiled with oligonucleotide microarrays. Class prediction analysis was performed in a training set of 24 patients who had undergone a second-look procedure. The resultant predictive signature was then tested on an independent validation set comprised of 36 patients. RESULTS: A 93-gene signature referred to as the Chemotherapy Response Profile (CRP) was identified through its association with pathologic complete response. When applied to a separate validation set the CRP distinguished between patients with unfavorable versus favorable overall survival (median 41 months v not yet reached, respectively, log-rank P = .007), with a median follow-up of 52 months. The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. There was no genetic overlap between the CRP and our previously described Ovarian Cancer Prognostic Profile (OCPP), which demonstrated similar prognostic value. The combination of the CRP and OCPP yielded better prognostic discrimination then either profile alone. Genes present in the CRP include BAX, a proapoptotic protein previously associated with chemotherapy response in ovarian cancer. CONCLUSION: Identification of a gene expression profile based on pathologic response in EOC provides independent prognostic information and offers potential insights into the mechanism of drug resistance. Efforts to identify a more tailored profile using selected genes from both the CRP and OCPP are underway. keyword(s): Correlation with outcome |
| 1517 | GSE21750 |
Profile | Extracellular-regulated kinases (ERK1/2 and 5) are known to play important roles in growth and drug resistance of various cancers. Here we show roles of inhibition of ERK1 ERK2, or ERK5 on gene expression profiles of epithelioid malignant mesothelioma (MM) cells (HMESO). |
| 1518 | GSE14507 |
Profile | The epidermal growth factor receptor (EGFR) is frequently overexpressed in cancer and is an important therapeutic target. Aberrant expression and function of microRNAs has been associated with tumorigenesis. Bioinformatic predictions suggest that the human EGFR mRNA 3’-untranslated region contains three microRNA-7 (miR-7) target sites which are not conserved across mammals. We found that miR-7 down-regulates EGFR mRNA and protein expression in cancer cell lines (lung, breast, and glioblastoma) via two of the three sites, inducing cell cycle arrest and cell death. Because miR-7 was shown to decrease EGFR mRNA expression, we used microarray analysis to identify additional mRNA targets of miR-7. These included Raf1 and multiple other genes involved in EGFR signaling and tumorigenesis. Furthermore, miR-7 attenuated activation of protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2), two critical effectors of EGFR signaling, in different cancer cell lines. These data establish an important role for miR-7 in controlling mRNA expression and indicate that miR-7 has the ability to coordinately regulate EGFR signaling in multiple human cancer cell types. |
| 1519 | GSE12453 |
Profile | The pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly due to the technical challenge of analyzing its rare neoplastic L&H cells which are dispersed in an abundant non-neoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected lymphocytic and histiocytic (L&H) lymphoma cells in comparison to normal and other malignant B cells, which indicates a relationship of L&H cells to and/or origin from germinal center B cells at transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype and deregulation of many apoptosis-regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive NF-κB activity and aberrant ERK signaling. Thus, these findings shed new light on the nature of L&H cells, revealed several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies. |
| 1520 | GSE6044 |
Profile | Lung cancers are a heterogeneous group of diseases with respect to biology and clinical behavior. So far diagnosis and classification are based on histological morphology and immunohistological methods for discrimination between two main histologic groups: small cell lung cancer (SCLC) and non-small cell lung cancer which account for 20% and 80% of lung carcinomas, respectively. While SCLCs express properties of neuroendocrine cells, NSCLCs, which are divided into the three major subtypes adenocarcinoma, squamous cell carcinoma and dedifferentiated large cell carcinoma, show different characteristics such as the expression of certain keratins or production of mucin and lack neuroedocrine differentiation. The molecular pathogenesis of lung cancer involves the accumulation of genetic und epigenetic alterations including the activation of proto-oncogenes and inactivation of tumor suppressor genes which are different for lung cancer subgroups. The development of microarray technologies opened up the possibility to quantify the expression of a large number of genes simultaneously in a given sample. There are several recent reports on expression profiling on lung cancers but the analysis interpretation of the results might be difficult because of the heterogeneity of cellular components. A contamination of the tumor sample with normal epithelia, blood vessels, stromal cells, leucocytes and tumor necrosis may confound the true expression profile of the tumor. The use of laser capture microdissection (LCM) greatly improves the sample preparation for microarray expression analysis. Consequently, we used advanced technology including LCM and microarray analysis. In detail, we examined gene expression profiles of tumor cells from 29 previously untreated patients with lung cancer (10 adenocarcinomas (AC), 10 squamous cell carcinomas (SCC), 9 small cell lung cancer (SCLC)) in comparison to normal lung tissue (LT) of 5 control patients without tumor. Bronchoscopical biopsies from the primary lung tumor were taken before treatment. Biopsies were cut into 8µm sections and from each section cancer cells were isolated using laser capture microdissection in order to obtain pure samples of tumor cells. Total RNA was extracted, reversely transcribed, in-vitro transcribed, labelled and hybridized to the array. For expression analysis, microarrays covering 8793 defined genes (Human HG Focus Array, Affymetrix) were used. Following quality control, array data were normalized and analysed for significant differences using variance stabilizing transformation (VSN) and significance analysis of microarrays (SAM), respectively. Based on differentially expressed genes cancer samples could be clearly separated from non cancer samples using hierarchical clustering. Comparing AC, SCC and SCLC with normal lung tissue, we found 205, 335 and 404 genes, respectively, that were at least 2-fold differentially expressed with an estimated false discovery rate < 2.6%. Each histological subtype showed a distinct expression profile. Further, using a genetic programming approach we constructed a classificator to discriminate AC, SCC, NT and SCLC. To this end, the 50 genes with the greatest signal-to-noise ratio were selected to train the classificator. By leave-one-out cross validation all 34 samples were correctly classified in this training set. In order to validate the 50-gene-classificator on a test set, further 13 microdissected lung cancer samples were used and correctly classified in concordance to pathologic finding. In conclusion, the different lung cancer subtypes have distinct molecular phenotypes which reflect biological characteristics of the tumor cells and which might be the basis for development of targeted therapy. Moreover, gene expression profiling and genetic programming is a suitable tool for classification and discrimination of different histological subtypes in lung cancer in comparison to normal lung tissue. Keywords: ordered |
| 1521 | GSE48029 |
Profile | Human T-cell leukemia virus type 1 (HTLV-1) encodes HTLV-1 bZIP factor (HBZ) which is thought to be crucial for neoplastic and inflammatory diseases caused by HTLV-1. So, we analyzed the transcriptional profile of HBZ expressing cells and how HBZ affect the expression of apoptosis-related genes. We used microarrays to detail the effect of HTLV-1 bZIP factor (HBZ), which is encoded in the minus strand of HTLV-1 genome on gene expression. Especially how HBZ affect the expression of apoptosis-related genes. |
| 1522 | GSE19205 |
Profile | The human Werner and Bloom syndromes (WS and BS) are caused by deficiencies in the WRN and BLM RecQ helicases respectively. WRN, BLM and their S. cerevisiae homologue Sgs1, are particularly active in vitro in unwinding G-quadruplex DNA (G4-DNA), a family of non-canonical nucleic acid structures formed by certain G-rich sequences. Recently, mRNA levels from loci containing potential G-quadruplex-forming sequences (PQS) were found to be preferentially altered in sgs1 mutants, suggesting that G4-DNA targeting by Sgs1 directly affects gene expression. Here, we extend these findings to human cells. Using microarrays to measure mRNAs obtained from human fibroblasts deficient for various RecQ family helicases, we observe significant associations between loci that are upregulated in WS or BS cells and loci that have PQS. No such PQS associations were observed for control expression datasets, however. Furthermore, upregulated genes in WS and BS showed no or dramatically reduced associations with sequences similar to PQS but that have considerably reduced potential to form intramolecular G4-DNA. These findings indicate that, like Sgs1, WRN and BLM can regulate transcription globally by targeting G4-DNA. |
| 1523 | GSE21497 |
Profile | Following spinal cord injury skeletal muscle loss is rapid. This severe atrophy is attributed to declines in protein synthesis and increases in protein breakdown. However, the signaling mechanisms controlling these changes are not well understood. Nine male patients and one female patient with spinal cord injury (SCI) (Mean ± SEM = 43.9 ± 6.7 yrs) were recruited for this study. Six patients were quadriplegics and four patients were paraplegics. Inclusion criteria were as follows: patients above the age of 18 yrs, absence of severe brain injury (Glasgow Coma Scale > 13), absence of muscle-crush injury or compartment syndrome, absence of all of the following conditions: hypoxic injury, systemic sepsis, systemic inflammatory or autoimmune disease, and malignancy. Muscle biopsies were obtained from the vastus lateralis muscles of the SCI patients two days and five days post-SCI. Biopsies collected two days post-SCI were included in the current analysis. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Functional analysis found that 48h following SCI expression, gene expression changes were related to decreases in metabolic functions such as the tricarboxylic acid cycle and oxidative phosphorylation as well as increases in functions associated with protein degradation such as proteasome activity and ubiquitination. Furthermore, increases in expression of metallothioneins were found to be the most over-represented functional group in the DAVID analysis. Results from this study showed that functional categories of gene expression changes in human skeletal muscle are consistent with previous findings in animals. |
| 1524 | GSE42067 |
Profile | To identify key biological pathways that define toxicity or biocompatibility after nanoparticle exposure three human cell types were exposed in vitro to two high aspect ratio nanoparticles for 1 hr or 24 hr and collected for global transcriptomics. Transcriptional responses were measured by global microarray analysis of cells in culture. |
| 1525 | GSE12237 |
Profile | Brain metastasis is one of the most feared complications of cancer and the most common intracranial malignancy in adults. Its underlying mechanisms remain unknown. From breast cancer patients with metastatic disease we isolated cell populations that aggressively colonize the brain. Transcriptomic analysis of these cells yielded overlapping gene sets whose expression is selectively associated with brain metastasis. The expression of seventeen of these genes in primary breast tumors is associated with brain relapse in breast cancer patients. Some of these genes are also associated with metastasis to lung but not to liver bone or lymph nodes, providing a molecular basis for the long-observed clinical link between brain and lung metastasis. Among the functionally validated brain metastasis genes, the cyclooxygenase COX-2, the EGFR ligand HB-EGF, and the brain-specific α2-6 sialyltransferase ST6GALNAC5 mediate cancer cell passage through the blood-brain barrier. Other brain metastasis genes encode inflammatory factors and brain-specific proteolytic regulators, suggesting a multifaceted program for breast cancer colonization of the brain. |
| 1526 | GSE19567 |
Profile | Chronic myelogenous leukemia (CML) is a malignant stem cell disease characterized by a reciprocal translocation between chromosome 9 and 22. The selective bcr-abl tyrosine-kinase inhibitor Imatinib has become the therapy of choice for patients with newly diagnosed CML including those previously considered candidates for allogeneic haematopoietic stem cell transplantation. The tyrosine-kinase inhibitor Nilotinib is a derivate of Imatinib with higher potency. To examine the molecular and functional effects of Nilotinib and Imatinib in chronic myelogenous leukemia we performed gene expression and functional analyses in K562 cells following treatment with the two tyrosine kinase inhibitors. |
| 1527 | GSE37208 |
Profile | Collagen triple helix repeat containing 1 (CTHRC1) has been found to be up-regulated in many human solid tumors. In this study we investigated the changes of gene expression by comparing CTHRC1-siRNA and Scramble-siRNA control in hepatocellular carcinoma cell line HCCLM3, which has high expression levels of CTHRC1. |
| 1528 | GSE27924 |
Profile | Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment. |
| 1529 | GSE19816 |
Profile | Von Willebrand factor is a paracrine/autocrine regulator of human mesenchymal stem cell adhesion to distressed/apoptotic endothelial cells. This data set examines effect of vWF on gene expression in HUVECs. |
| 1530 | GSE28497 |
Profile | To identify new markers for minimal residual disease (MRD) detection in acute lymphoblastic leukemia (ALL) we compared genome-wide gene expression of lymphoblasts from 270 patients with newly diagnosed childhood ALL to that of normal CD19 CD10 B-cell progenitors (n=4). Expression of 30 genes differentially expressed by > 3-fold in at least 25% of cases of ALL (or 40% of ALL subtypes) was tested by flow cytometry in 200 B-lineage ALL and 61 nonleukemic BM samples, including samples containing hematogones. Of the 30 markers, 22 (CD44, BCL2, HSPB1, CD73, CD24, CD123, CD72, CD86, CD200, CD79b, CD164, CD304, CD97, CD102, CD99, CD300a, CD130, PBX1, CTNNA1, ITGB7, CD69, CD49f) were differentially expressed in up to 81.4% of ALL cases; expression of some markers was associated with the presence of genetic abnormalities. Results of MRD detection by flow cytometry with these markers correlated well with those of molecular testing (52 follow-up samples from 18 patients); sequential studies during treatment and diagnosis-relapse comparisons documented their stability. When incorporated in 6-marker combinations, the new markers afforded the detection of 1 leukemic cell among 105 BM cells. These new markers should allow MRD studies in all B-lineage ALL patients, and substantially improve their sensitivity. |
| 1531 | GSE16791 |
Profile | Thalidomide-dexamethasone (TD) combination is an effective induction therapy for newly diagnosed multiple myeloma patients candidates for subsequent autologous stem cell transplantation (ASCT). Since maximization of tumor response before ASCT may favorably affect the clinical outcomes, we designed a study to identify a gene expression profile (GEP) signature predictive of attainment of complete response to TD induction therapy. CD138+ bone marrow samples obtained at diagnosis from 112/311 patients were analyzed. Two subsequent time phases were planned. Firstly, a GEP supervised analysis, performed on a training set of 32 patients, allowed to identify 157 probe sets differentially expressed in complete responder + near complete responder (CR+nCR) versus ≤partial responder patients. Than, we generated an 8-gene GEP signature predicting at diagnosis the probability to achieve CR+nCR to TD induction therapy. The performance of this assay was subsequently validated in an 80 patients training set. The 8-gene signature provide a negative predictive value of 93% and a positive predictive value of 44%. The 8 genes were down-regulated in patients who achieved at least a nCR. These results could be an important first step to adopting a diagnostic assay, used to determine, at diagnosis, patients who will respond more favourably to a particular treatment strategy. |
| 1532 | GSE18866 |
Profile | Reexpression of microRNAs miR-15a/16-1 in a cell line deficient for these miRs (homozygous deletion of chromosomal region 13q14) results in the downregulation of certain mRNAs. |
| 1533 | GSE28715 |
Profile | Med26 is a subunit of the Human Mediator complex. The Mediator complex is an evolutionarily conserved coregulatory complex that interacts with RNA polymerase II to regulate gene expression. In metazoa Mediator is composed of some 30 distinct subunits. Mediator exists in multiple, functionally distinct forms that share a common core of subunits and can be distinguished by the presence or absence of a kinase module composed of Med12, Med13, Cdk8, and Cyclin C. In higher eukaryotes, a subset of Mediator complexes is associated with an additional subunit, Med26. This Med26-containing Mediator copurifies from cells with little or no kinase module, but near-stoichiometric Pol II. Evidence suggests that Med26-containing Mediator plays a key role in transcriptional activation however, the mechanism(s) by which Med26 contributes to this process are not known. To identify Med26 target genes, we used Affymetrix U133A plus 2.0 expression arrays to analyze mRNA expression in 293T cells from which Med26 had been depleted by transient transfection by each of three different siRNAs. |
| 1534 | GSE11919 |
Profile | The skin is a protective barrier against external insults and any lesion must be rapidly and efficiently repaired. Dermal fibroblasts are the major source of extracellular connective tissue matrix and play an important role in wound healing. Vitamin C is an important water-soluble free radical scavenger and an essential cofactor for collagen synthesis by dermal fibroblasts and consequently, may contribute to the maintenance of healthy skin. Using microarray analysis, we investigated the effects of long-term exposure to a stable vitamin C derivative, ascorbic acid 2-phosphate (AA2P), in contact-inhibited populations of primary human dermal fibroblasts. Compared with "scorbutic" cells, cells exposed to AA2P increased the expression of genes associated with DNA replication and repair and with the G(2)/M phase of the cell cycle. Consistent with the gene expression changes, AA2P increased the mitogenic stimulation of quiescent fibroblasts by serum factors and cell motility in the context of wound healing. Furthermore, AA2P-treated fibroblasts showed faster repair of oxidatively damaged DNA bases. We propose that vitamin C may protect the skin by promoting fibroblast proliferation, migration, and replication-associated base excision repair of potentially mutagenic DNA lesions, and we discuss the putative involvement of hypoxia-inducible transcription factor-1 and collagen receptor-related signaling pathways. |
| 1535 | GSE11428 |
Profile | Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in the onset and progression of prostate cancer. We investigated AR-induced gene expression in prostate cancer cells LNCaP and abl by transfecting siAR / siControl or treating cells with androgen (DHT) over a time course. Keywords: siRNA transfection and androgen stimulation time course |
| 1536 | GSE9691 |
Profile | Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts - an early step in metastatic dissemination. To further investigate the molecular basis of this notion we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. While the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness and anoikis-resistance. We find the E-cadherin binding partner beta-catenin to be necessary but not sufficient for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes. Keywords: E-cadherin knockdown, dominant-negative E-cadherin expression, E-cadherin and Beta-catenin double knockdown |
| 1537 | GSE11683 |
Profile | This study compares a cell line (MDA-MB-468GFP-LN) that aggressively metastasizes to lymph nodes to its parental line MDA-MB-468GFP. Derivation of the lines is described in Vantyghem et al Clinical & Experimental Metastasis (2005) 22: 351–361. The goal here was to compare the gene expression profile of MDA-MB-468GFP-LN to MDA-MB-468GFP, Compare differential expression to databases of genes known to be involved in either cancer stem cell identification or lymph node specific metastasis in large scale clinical studies, and to confirm genes by RT-PCR |
| 1538 | GSE7562 |
Profile | Although most of the oncogenic phenotypes of PTEN loss have been attributed to AKT activation AKT alone is not sufficient to induce all of the biological activities associated with PTEN inactivation. We searched for additional PTEN-regulated pathways through gene set enrichment analysis (GSEA) and found that PTEN inactivation causes an enrichment of genes associated with JNK activation. Biochemically, PTEN-null cells exhibit higher JNK activity, and genetic studies demonstrate that JNK functions parallel to and independently of AKT. Furthermore, PTEN deficiency sensitizes cells to JNK inhibition. We also found that negative feedback regulation of PI3K was impaired in PTEN-null cells. These findings implicate JNK in PI3K-driven cancers and demonstrate the utility of GSEA to identify functional pathways using genetically defined systems. Keywords: Genetic modification: PTEN RNAi |
| 1539 | GSE9593 |
Profile | To determine gene expression changes during in vitro senescence of MSC we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). There were global changes in the gene expression profile that were reproducible in three independent donor samples. Keywords: Replicative senescence time course |
| 1540 | GSE7268 |
Profile | Cryptosporidium hominis and parvum primarily infect intestinal epithelial cells which, in turn, play a key role in activating and communicating with the host immune system. To determinate which genes are regulated during early infection of non-transformed human epithelial cells, human ileal mucosa was removed (from surgical specimens), placed on collagen membranes, and cultured as explants. Explant cultures were infected with C. parvum, C. hominis, or control culture medium. After 24 hrs, RNA was extracted and analyzed using Affmetrix GeneChip microarrays. Among the more prominent genes with regulated expression was Osteoprotegerin (OPG), which was increased in all of the explants at 24 hrs and further up-regulated 1.58 fold by C. parvum and 2.54 fold by C. hominis infection compared with uninfected explants. Using real time PCR, we confirmed a 3.14 and 3.79 fold increase in OPG mRNA after infection with C. parvum and C. hominis respectively. Keywords: gene expression analysis via microarray |
| 1541 | GSE22563 |
Profile | Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4/RIL, REPRIMORPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) demonstrated frequent (>30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM, and SFRP1 suppressed the growth of RCC cell lines. Whereas, RNAi-knock-down of BNC1, SFRP1 and COL14A1 increased the growth potential of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC tumour suppressor genes can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection. |
| 1542 | GSE9715 |
Profile | Patients with tuberous sclerosis complex (TSC) develop hamartomas containing biallelic inactivating mutations in either TSC1 or TSC2 resulting in mammalian target of rapamycin (mTOR) activation. Hamartomas overgrow epithelial and mesenchymal cells in TSC skin. The pathogenetic mechanisms for these changes had not been investigated, and the existence or location of cells with biallelic mutations (“two-hit” cells) that resulted in mTOR activation was unclear. We compared TSC skin hamartomas (facial angiofibromas and periungual fibromas) to normal-appearing skin of the same patient, and observed more proliferation and mTOR activation in hamartoma epidermis. “Two-hit” cells were not detected in the epidermis. Fibroblast-like cells in the dermis, however, exhibited allelic deletion of TSC2, in both touch preparations of fresh tumor samples and cells grown from TSC skin tumors, suggesting that increased epidermal proliferation and mTOR activation were not caused by second-hit mutations in the keratinocytes but by mesenchymal-epithelial interactions. Gene expression arrays, used to identify potential paracrine factors released by mesenchymal cells, revealed more epiregulin mRNA in fibroblast-like angiofibroma and periungual fibroma cells than in fibroblasts from normal-appearing skin of the same patient. Elevation of epiregulin mRNA was confirmed using real-time PCR, and increased amounts of epiregulin protein were demonstrated using immunoprecipitation and ELISA. Epiregulin stimulated keratinocyte proliferation and phosphorylation of ribosomal protein S6 in vitro. These results suggest that hamartomatous TSC skin tumors are induced by paracrine factors released by “two-hit” cells in the dermis, and that proliferation with mTOR activation of the overlying epidermis is an effect of epiregulin. Keywords: Disease state analysis |
| 1543 | GSE24530 |
Profile | The Microarray study was designed to characterize the whole genome transcription profile of two subpopulations of H1 human embryonic stem cells we identified by size using flow cytometry.The heterogeneous nature of stem cells is an important issue in both research and therapeutic use in terms of directing cell lineage differentiation pathways as well as self-renewal properties. Using flow cytometry we have identified two distinct subpopulations by size within the H1 and BGN1 human embryonic stem (hES) cell lines. Both populations express stem the cell markers Oct-4, Nanog, Tra-1-60, Tra-1-80 and SSea-4 and express very low levels of differentiation markers common to the three germ layers. To investigate if the two populations possessed different transcription profiles, we performed whole genome microarray analysis, and identified approximately 400 genes with significant differential expression (p<0.01). Cloning experiments indicate that both populations are able to repopulate each other and maintain the parental population. The large cell population responds to retinoic acid (RA) differentiation as evidenced by greater than a 50% loss of gated cell number and loss of Oct-4 expression; while the small cell population number does not change and maintains Oct-4 protein expression. The presence of these two populations could be vitally important with respect to stem cell therapy and research as they respond differently to differentiation signals, which may be important in directing stem cell differentiation for disease therapy. |
| 1544 | GSE19098 |
Profile | Angiogenesis is tightly regulated by both soluble growth factors and cellular interactions with the extracellular matrix (ECM). While cell adhesion via integrins has been shown to be required for growth factor signaling and downstream angiogenesis the effects of quantitative changes in cell adhesion and spreading against the ECM remain less clear. Examining changes in global gene expression in limited versus high adhesion contexts in human umbilical vein endothelial cells, we demonstrated a VEGF-induced upregulation of genes associated with vascular invasion and remodeling when cell adhesion was restricted, whereas cells on highly adhesive surfaces upregulated genes associated with a proliferative response. |
| 1545 | GSE7874 |
Profile | Transcriptional profiles of human CD34+ cells cultured in EPO and EST conditions. |
| 1546 | GSE7095 |
Profile | Gene expression profiels in the human monocyte-derived dendritic cells (DCs) from 4 different donors (A B, C, and D) were studied. Cells were left untreated (Group 4), activated with LPS alone (Group 1) or activated in the presence cmv IL-10 (Group 2) or human IL-10 (Group 3) for 12 hours before subjected to RNA extraction. Keywords: IL-10, LPS, dendritic cells |
| 1547 | GSE22600 |
Profile | Menopausal estrogen (E2) replacement therapy increases the risk of estrogen receptor (ER)-positive epithelial ovarian cancers (EOC). Whether E2 is tumorigenic or promotes expansion of undiagnosed pre-existing disease is unknown. To determine E2 effects on tumor promotion we developed an intraperitoneal mouse xenograft model using ZsGreen fluorescent ER- 2008 and ER+ PEO4 human EOC cells. Tumor growth was quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly increased size, induced progesterone receptors, and promoted lymph node metastasis, confirming that ER are functional and foster aggressiveness. Laser captured human EOC cells from ER- and ER+ xenografted tumors were profiled for expression of E2-regulated genes. Three classes of E-regulated EOC genes were defined, but less than 10% were shared with E-regulated breast cancer genes. Since breast cancer selective ER modulators (SERM) are therapeutically ineffective in EOC, we suggest that our EOC-specific E-regulated genes can assist pharmacologic discovery of ovarian targeted SERM. |
| 1548 | GSE30792 |
Profile | A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent. |
| 1549 | GSE23332 |
Profile | Graft-versus-host disease (GvHD) is still one of the major complications following allogeneic stem cell transplantation (SCT) triggered by alloreactive donor T cells. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the development of GvHD data from the human system are rare mainly due to low cell numbers of circulating or organ-infiltrating Tregs in lymphopenic patients. Here, we present a comparative analysis of Tregs from patients with and without acute/ chronic GvHD designed as a dynamical approach studying the whole genome profile over the first 6 months after SCT. For this purpose, blood samples were collected monthly for FACS-based isolation of CD4+CD25highCD127low/- Tregs. The Treg transcriptome showed a high stability in the first half year representing the most sensitive time window for tolerance induction. However, the comparison of the Treg transcriptome from patients with and without GvHD uncovered regulated gene transcripts that point to a reduced suppressive function of Tregs with diminished migration capacity to the target organs likely contributing to the development of GvHD. These findings highlight the critical role of human Tregs in the pathophysiology of GvHD and identify novel targets for the manipulation of Tregs to optimize cellular immune intervention strategies. Keywords: cell type comparison |
| 1550 | GSE17119 |
Profile | We generated the transcriptional regulatory footprint of phthalimide neovascular factor 1 (PNF1)—a novel synthetic small molecule that exhibits significant in vitro endothelial potency and significant in vivo microvascular network expansion—by performing comparative microarray analysis on PNF1-stimulated (versus control) human microvascular endothelial cells (HMVEC) spanning 1-48 h post-supplementation. We subsequently applied network analysis tools (including substantial libraries of information regarding known associations among network components) to elucidate key signaling components and pathways involved in the PNF1 mechanism-of-action. We identified that PNF1 first induces function of the tumor necrosis factor-alpha (TNF-α) signaling pathway which in turn affects transforming growth factor-beta (TGF-β) signaling. |
| 1551 | GSE1420 |
Profile | Samples were obtained from 8 patients with Barrett's associated adenocarcinomas after transhiatal esophagectomy. Samples representative of the normal esophageal epithelium (N) Barrett’s esophagus (B) and esophageal adenocarcinomas (ADC) were obtained from every patient by experienced GI pathologists. RNA were extracted and samples were profiled for detection of genes differentially expressed in B and ADC relative to N and in ADC relative to B. Keywords: other |
| 1552 | GSE26213 |
Profile | The goal was to obtain expression data from the deep cones in early human hypertrophic scars to be used to confirm expression data obtained in a porcine model. |
| 1553 | GSE8066 |
Profile | Neuroblastomas are tumors of the developing peripheral sympathetic nervous system which originates from the neural crest. Twenty percent of neuroblastomas show amplification of the MYCN oncogene, which correlates with poor prognosis. The MYCN transcription factor can activate and repress gene expression. To broaden our insight in the spectrum of genes down-regulated by MYCN, we generated gene expression profiles of the neuroblastoma cell lines SHEP-21N and SKNAS-NmycER, in which MYCN activity can be regulated. In this study, we show that MYCN suppresses the expression of Dickkopf-1 (DKK1) in both cell lines. DKK1 is a potent inhibitor of the wnt/beta-catenin signalling cascade, which is known to function in neural crest cell migration. We generated a DKK1 inducible cell line, IMR32-DKK1, which showed impaired proliferation upon DKK1 expression. Surprisingly, DKK1 expression did not inhibit the canonical wnt/beta-catenin signalling, suggesting a role of DKK1 in an alternative route of the wnt pathway. Gene expression profiling of two IMR32-DKK1 clones showed that only a few genes, amongst which SYNPO2, were up-regulated by DKK1. SYNPO2 encodes an actin-binding protein and was previously found to inhibit proliferation and invasiveness of prostate cancer cells. These results suggest that MYCN might stimulate cell proliferation by inhibiting the expression of DKK1. DKK1 might exert part of its growth suppressive effect by induction of SYNPO2 expression. Keywords: DKK1, MYCN, neuroblastoma, Dickkopf |
| 1554 | GSE27702 |
Profile | Macrophages were infected with low (PR8) and high pathogenic influenza viruses (FPV and H5N1). To our surprise a genome-wide comparative systems biology approach revealed that in contrast PR8 infections with HPAIV H5N1 and FPV result in a reduced immune response of human macrophages contradicting a primary role of this cell type for the cytokine storm. Our data point to a viral strategy of HPAIV to bypass a major amplifier of the initial local inflammatory response thereby hampering antiviral effector mechanisms and facilitating virus spreading and systemic disease. |
| 1555 | GSE9768 |
Profile | The major aetiological risk factor for Barrett's oesophagus and oesophageal adenocarcinoma is gastroesophageal reflux. This study's aim was to identify genes involved in the celular response to reflux in vitro. The Barrett’s oesophagus cell line CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5; 152 genes were up-regulated at 2 hours (91 at 6 hours) and 10 down-regulated at 2 hours (34 at 6 hours). 12 genes were identified and were subsequently assessed in patients with non-erosive reflux disease, oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma Background and Aims: The major etiological risk factor for Barrett’s esophagus and esophageal adenocarcinoma is gastro-esophageal reflux. This study’s aim was to identify genes involved in the cellular response to components of reflux both in vitro and in patients with reflux-related disease. Methods: The Barrett’s cell line, CP-A hTERT, was exposed to media with acid, deoxycholic acid or a primary bile salt mixture. RNA expression was compared with controls on Affymetrix U133 Plus 2.0 arrays. 12 genes of interest were analysed by Real Time PCR both in cell line and biopsies from 110 patients with non-erosive reflux disease, esophagitis, Barrett’s esophagus and esophageal adenocarcinoma. Results: In CP-A hTERT, the greatest number of changes in gene expression was observed after treatment with deoxycholic acid, pH 4.5. Of 12 genes analysed in biopsies, 10 were significantly different between the 4 groups with the largest change for anterior gradient homolog 2, which may modulate p53 function. This had highest expression in biopsies from Barrett’s esophagus (median gene fold change for Barrett’s esophagus versus non-erosive reflux disease, 411.2 (95% CI 290.5-682.7; p<0.01); esophageal adenocarcinoma versus non-erosive reflux disease 68.1 (20.5-161.4; p<0.01)). In addition 4 genes associated with development/differentiation were upregulated in Barrett’s biopsies compared to those from non-erosive reflux disease (SEL1L, MFNG, CRIP1 and EFNA1). Conclusions: Novel genes have been identified, whose expression is altered after acid and bile exposure in vitro and in biopsies from patients with reflux related diseases. These genes may have utility as biomarkers of response to reflux and should be assessed in prospective studies. Keywords: Acid (pH 4.5) and bile (mixture of primary bile salts or the secondary bile salt deoxycholic acid, both at pH 4.5) challenge to a Barrett's oesophagus cell line. RNA extraction at 2 and 6 hours. Comparison of treatment RNA to control (non-treatment) RNA, |
| 1556 | GSE15744 |
Profile | Gene expression profiling has provided critical insights into the molecular pathways underlying development of model organisms however little information is available on regulated gene expression during human embryogenesis. We have now filled this important gap of knowledge by performing genome-wide microarray analysis of the Homo sapiens gene expression during the 4-9th week, a period when most organs develop. We analyzed individually 3 embryos for each of the 4th, 5th, 6th, 7th, 8th, and 9th week of human embryonic development by using the Affymetrix U133 plus 2.0 human GeneChip array.About half of all human genes are expressed and 18.6% of the expressed genes were significantly regulated during this important period. We further identified over 5000 regulated genes, most of which were previously not known to be associated with animal development. Our study also revealed that the genes involved here are distinct from those during early embryogenesis, which include three groups of maternal genes. Furthermore, we discovered that genes in a given developmental process are coordinately regulated. This led us to develop an easily searchable database of this entire collection of gene expression profiles, allowing for identification new genes important for a particular developmental process/pathway and deducing the potential function of a novel gene. The validity of the predictions from the database was demonstrated with two examples through spatiotemporal analyses of the two novel genes. Such a database should serve as a highly valuable resource for the molecular analysis of human development and pathogenesis. |
| 1557 | GSE17372 |
Profile | Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL. Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype. |
| 1558 | GSE4883 |
Profile | HMG-CoA reductase inhibitors statins, have beneficial vascular effects beyond their cholesterol-lowering action. These pleiotropic effects include an anti-inflammatory effect on macrophages. Since macrophages play a central role in atherogenesis, we further characterized the effects on peripheral blood monocyte-macrophages (HPBM). Using Affymetrix gene chip analysis of simvastatin-treated HPBM, we found that simvastatin treatment lead to the downregulation of the expression of many proinflammatory genes including several chemokines (e.g. MCP-1, MIP-1 alpha and β, RANTES, several other CC and CXC chemokines, IL-2 receptor-β, and leukemia inhibitory factor), members of the tumor necrosis factor family (e.g. lymphotoxin beta and TRAIL), VCAM-1, ICAM-3, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for the inflammatory response: simvastatin downregulated the expression of NF-kappaB relA/p65 subunit and ets-1 transcription factor, and upregulated the expression of a novel atheroprotective transcription factor, Kruppel-like factor 2 (KLF-2). The effects of simvastatin on KLF-2 and its target genes were dependent on protein prenylation, since inhibitors of protein prenylation had a similar inhibitory effect in THP-1 derived macrophages. Additionally, by lentiviral overexpression KLF-2 we showed that the effect of simvastatin on MCP-1 and TF were dependent on KLF-2. We concluded that simvastatin had a strong anti-inflammatory effect on macrophages, which includes upregulation of the atheroprotective transcription factor KLF-2. These findings further explain the beneficial pleiotropic effects of statins on cardiovascular diseases. Keywords: time-course, response to treatment |
| 1559 | GSE3894 |
Profile | By comparing the expression levels of genes between carriers of Nijmegen Breakage Syndrome and non-carriers we showed that NBS carriers have a distinct gene expression phenotype. Keywords: Cell Line Comparison |
| 1560 | GSE6604 |
Profile | Prostate cancer is characterized by heterogeneity in the clinical course that often does not to correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogeneous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodeling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer. Keywords: disease state analysis |
| 1561 | GSE7753 |
Profile | Systemic Juvenile Idiopathic Arthritis (sJIA) has been strongly associated with macrophage activation syndrome (MAS). To better understand the pathogenesid of sJIA and to facilitate the search for MAS biomarkers we examine gene expression profiles in untreated new onset sJIA. 17 new onset sJIA patients were included in the study. 5 of the 17 patients showed evidence of subclinical MAS and 2 eventually developed overt MAS. Keywords: disease versus control |
| 1562 | GSE10270 |
Profile | Breast cancer outcome is highly variable. Whether inadvertent exposure to environmental xenobiotics evokes a biological response promoting cancer aggressiveness and a higher probability of tumor recurrence remains unknown. To determine specific molecular alterations which arise in high-risk breast tissue in the presence of the ubiquitous xenoestrogen, bisphenol A (BPA), we employed non-malignant random periareolar fine needle aspirates (RPFNA) in a novel functional assay. Early events induced by BPA in epithelial-stromal cocultures derived from the contralateral tissue of breast cancer patients included gene expression patterns, which facilitate apoptosis evasion, endurance of microenvironmental stress, and cell cycle deregulation without a detectable increase in cell number. This BPA response profile was significantly associated with breast tumors characterized by high histologic grade (p<0.001), and large tumor size (p=0.002), resulting in decreased recurrence-free patient survival (p<0.001). Our assays demonstrate a biological “fingerprint” of probable prior exposure to endocrine disrupting agents, and suggest a scenario in which their presence in the microenvironmental milieu of high-risk breast tissue could play a deterministic role in establishing and maintaining tumor aggressiveness and poor patient outcome. Keywords: Gene expression, Epithelial, Breast cancer |
| 1563 | GSE14538 |
Profile | Several reports indicate that mesalazine (5-aminosalicylic acid or 5-ASA) is a promising candidate for the chemoprevention of Colo-Rectal Cancer (CRC) due to its ability to reach the purpose yet avoiding at the same time the side effects that are usually determined by prolonged administrations of Non Steroidal Anti-Inflammatory Drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colon cancer cells and consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints. A recent observation has suggested that these effects could be mediated by the capacity of 5-ASA to interfere with the nuclear translocation of beta-catenin, in turn responsible for the inhibition of its transcription activity. The aim of our study was to better characterize the molecular mechanism by which 5-ASA inhibits the beta-catenin signaling pathway. To address this issue we assessed, by means of the Affymetrix microarray methodology, the transcriptome changes determined on Caco2 cells by a 96 h treatment with 20 mM mesalazine. |
| 1564 | GSE26370 |
Profile | There are two major subtype of cells in breast cancer. These cancer cells response differently to glutamine deprivation here we use one luminal type of breast cancer cell (MCF7) and one basal type of breast cancer cell (MDAMB231) to compare the gene expression differences of these two types of cancer cells in glutamine deprivation. Many cancer cells depend on glutamine for survival and oncogenic transformation. Although targeting glutamine metabolism is proposed as novel therapies, their heterogeneity among different tumors is unknown. Here, we found only basal-type, but not luminal-type breast cancer cells, exhibited phenotypes of glutamine dependency and may benefit from glutamine-targeting therapeutics. The glutamine independence of luminal-type cells is caused by the specific expression of glutamine synthetase (GS), a pattern recapitulated in luminal breast cancers. The co-culture of luminal cells partially rescued the basal cells under glutamine deprivation, suggesting glutamine symbiosis. The luminal-specific expression of GS is directly induced GATA3 and down-regulates glutaminase expression to maintain subtype-specific glutamine metabolism. Collectively, these data indicate the distinct glutamine phenotypes among breast cells and enable the rational design of glutamine targeted therapies. |
| 1565 | GSE10791 |
Profile | Gene expression profiles were performed to compare the difference in sigmoid colon biopsies between from healthy control and patients with ulcerative colitis. Keywords: disease signature |
| 1566 | GSE32496 |
Profile | Epigenetic changes largely contribute to the regulation of gene expression in cancer cells. DNA methylation is part of the epigenetic gene regulation complex which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stage I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis using NimbleGen´s 385K Human CpG Island plus Promoter arrays. By testing for differences in methylation between tumors and corresponding non-malignant lung tissues we identified 298 tumor-specifically methylated genes. From many of these genes epigenetic regulation was unknown so far. Gene Ontology analysis revealed an over-representation of genes involved in regulation of gene expression and cell adhesion. Expression of 182 of 298 genes was found to be upregulated after 5-aza-2´-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) treatment of 3 NSCLC cell lines by Affymetrix microarray analysis. In addition, methylation of selected genes in primary NSCLCs and corresponding non-malignant lung tissue samples were analyzed by methylation-sensitive high resolution melting analysis (MS-HRM). Our results obtained by MS-HRM analysis confirmed our data obtained by MeDIP-chip analysis. Moreover, by comparing methylation results from MeDIP-chip analysis with clinico-pathological parameters of the patients we observed methylation of HOXA2 as potential parameter for shorter disease-free survival of NSCLC patients. In conclusion, using a genome-wide approach we identified a large number of tumor-specifically methylated genes in NSCLC patients. Our results stress the importance of DNA methylation for the pathogenesis of NSCLCs. |
| 1567 | GSE19060 |
Profile | Menisci play a vital role in load transmission shock absorption and joint stability. The current dogma is that the menisci simply protects the cartilage and play no role in osteoarthritis (OA) unless they are injured. However, there is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, 2) to examine gene expression in OA meniscal cells compared to normal control meniscal cells, and 3) to test the hypothesis that OA meniscal cells are different from normal meniscal cells. The grades of meniscal degeneration correlated in a positive fashion with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), integrin, beta 2 (ITGB2), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ankylosis, progressive homolog (ANKH) and fibroblast growth factor 7 (FGF7), were expressed at higher levels compared to normal control meniscal cells. In addition, many genes that were previously implicated in OA were also expressed at higher levels in OA meniscal cells, including ADAM metallopeptidase with thrombospondin type 1 motif, 5 (ADAMTS5). Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA. |
| 1568 | GSE25987 |
Profile | Description of differentially expressed genes between KMH2 CIITA-BX648577 knockdown cultures and non-silencing controls |
| 1569 | GSE7291 |
Profile | The possibility to deliver radioisotopes directly to tumor cells by using monoclonal antibodies has become a promising concept for the elimination of small tumor nodules or single disseminated tumor cells. The alpha-particle emitter Bismut-213 which has a high linear energy transfer and a very short path length appears to be able to kill cells by only few nuclear hits. Bismut-213 based alpha-immunotherapy treatment is currently proved in clinical trials for AML NHL and preclinically for CLL and multiple myeloma. Because little is known about the biological effects of alpha radiation we examined the molecular effects of the alpha emitter Bismut-213 in malignant and normal B-cells. In this study, we used the cell line Karpas 422 (K422) which had been derived from a malignant B-cell Non-Hodgkin’s lymphoma as well as normal primary CD19+ B-cells which had been selected immunomagnetically from peripheral blood. For the delivery and binding of the alpha emitter we used the monoclonal antibody rituximab which targets the CD20 receptor of malignant and normal B-cells. The lymphoma cell line K422 was incubated in vitro with Bismut-213-CD20 with 100 µCi and 200 µCi respectively, for 46 min (1 half life time of the alpha emitter) or 24 h. Immunomagnetically isolated CD19+ cells from healthy donors were incubated in vitro with Bismut-213-CD20 with 100 µCi or 200 µCi, for 46 min. Gene expression profiles of irradiated cells were analysed using cDNA oligonucleotide arrays (Affymetrix Human Genome Focus Arrays) comprising 8,793 genes and compared with those from untreated control cells. Following normalization significantly altered genes were identified by using the variance stabilization normalization (VSN) method and the significance analysis of microarrays (SAM) algorithm. Differentially expressed genes were defined to exhibit a fold change of 1,4 and higher or 0,7 and lower and a q-value of 5% or lower compared to the genes of the untreated control cells. Irradiated K422 cells with 100 µCi showed 42 differential expressed genes after 46 minutes (one half life time) and 451 deregulated genes after exposure of 24 hours. A similar response could be observed at an exposure of 200 µCi (50 differentially expressed genes after 46 min; 485 genes after 24 h). Hence, a severe radiation induced response could not be detected before 24 hours. 200 µCi irradiated CD19+ cells showed 67 differentially expressed genes after 46 minutes compared to the untreated CD19+ cells (for 100 µCi: 42 differentially expressed genes). By performing cluster analyses the irradiated cells exhibited a distinct homogenous molecular phenotype in comparison to not irradiated cells. Alpha irradiated cells showed transcriptional activation of DNA repair genes. Furthermore, both examined cell types showed up-regulated genes which are known to play a role in general and oxidative stress response. Surprisingly, up-regulation of interferon-stimulated genes in K422 cells could be observed. Because of the transcriptional activation of genes regulating the G1-S- cell cycle transition the supposition came up that the irradiated K422 do progress into the S-phase of the cell cycle and arrest in the S- or G2/M-phase. In contrast to the K422 cells the primary CD19+ B-cells revealed transcriptional activation of cell cycle inhibitors which is an already known reaction following ionizing radiation but no apoptosis associated genes could be observed. In spite of the massive cytotoxic damages which are assumed referring to the gene expression data the K422 cells appear to be able to activate several defense mechanisms in a precise manner. Hence, the malignant K422 cells exhibit a larger amount as well as more various responses than the CD19+ cells. This might be due to the tumorigenic transformation of the malignant cells that exhibit probably more effective defense strategies than the CD19+ cells. The balance between the therapeutic effect of alpha radiation on malignant cells and the damaging effect on normal cells is an essential issue and it is of important clinical relevance concerning radioimmunotherapy with alpha radiation. Keywords: time course and dose dependency |
| 1570 | GSE16674 |
Profile | miR-34a is strongly induced upon TPA-induced megakaryocyte differentiation of K562 cells. To investigate the gene networks regulated by this miRNA during the process of differentiation we performed gene microarray analysis in K562 cells overexpressing miR-34a or a control sequence. |
| 1571 | GSE40794 |
Profile | Cyclin D1b is a splice variant of the cell cycle regulator Cyclin D1 and is known to harbor divergent and highly oncogenic functions in human disease. While Cyclin D1b is induced during disease progression in many cancer types the mechanisms underlying Cyclin D1b function remain poorly understood. Herein, models of human disease were utilized to resolve the downstream pathways requisite for the pro-tumorigenic functions of Cyclin D1b. Specifically, it was shown that Cyclin D1b modulates the expression of a large transcriptional network that cooperates with AR signaling to enhance tumor cell growth and invasive potential. Notably, Cyclin D1b promoted AR-dependent activation of genes associated with metastatic phenotypes. Further exploration determined that transcriptional induction of SNAI2 (Slug) was essential for Cyclin D1b- mediated proliferative and invasive properties, implicating Slug as a critical driver of disease progression. Importantly, Cyclin D1b expression highly correlated with that of Slug in clinical samples of advanced disease. Further, in vivo analyses provided strong evidence that Slug enhances both tumor growth and homing to distal soft tissues. Collectively, these findings reveal the underpinning mechanisms behind the pro-tumorigenic functions of Cyclin D1b, and demonstrate that the convergence of the Cyclin D1b-AR and Slug pathways results in the activation of processes critical for the promotion of lethal tumor phenotypes. Analysis of transcriptomes under the control of individual D-type cyclin isoforms in the hormone dependent prostate cancer cell line LNCaP in the presence and absence of androgen. |
| 1572 | GSE10289 |
Profile | Effect of SDHB silencing using siRNA methodologies in the tumor phenotype We used microarrays to detail the global programme of gene expression when SDHB is silenced. Keywords: siRNA experiment (loss of function) |
| 1573 | GSE26725 |
Profile | Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In this study we present evidence that MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset of B-CLL patients. MYB physically associates with the promoter of MIR155 host gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates its transcription. This coincides with the hypermethylated histone H3K4 residue and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide evidence of oncogenic activities of MYB in B-CLL that include its stimulatory role in MIR155HG transcription. We have studied differentially expressed genes in the whole genome and also in the preselected groups of MYB target genes and miR-155 microRNA predicted targets. |
| 1574 | GSE17475 |
Profile | Affymetrix Human Genome U133A platform was used to obtain gene expression profiles of 28 pathologically and clinically well characterized adenocarcinomas of the lung. In addition EGFR status was determined by fluorescent in situ hybridization and immunohistochemistry. The classification of the cases using a clustering algorithm applied to the expression data correlated significantly with the histopathological tumor grades. In contrast, no correlation of gene expression data and EGFR status could be detected. |
| 1575 | GSE7101 |
Profile | Microarray data from G2-synchronized p53(+) and p53(-) fibroblasts before and after 3 h release from cell cycle blockade in the presence of 5 µM sodium arsenite. Keywords: Gene induction |
| 1576 | GSE24089 |
Profile | Oncogenic human papillomaviruses (HPVs) are associated with nearly all carcinomas of the uterine cervix and have also become an increasingly important factor in the etiology of a subset of oropharyngeal tumors. HPV-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. We analyzed the genome-wide expression patterns in two HPV(+) and two HPV(-) squamous cell carcinoma (SCC) cell lines. |
| 1577 | GSE11011 |
Profile | Translation initiation factors have complex functions in cells which are not yet understood. We show that depletion of initiation factor eIF4GI only modestly reduces overall protein synthesis in cells but phenocopies nutrient-starvation or inhibition of protein kinase mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation, bioenergetics and mitochondrial activity, thereby promoting autophagy. Translation of mRNAs involved in cell growth, proliferation and bioenergetics were selectively inhibited by reduction of eIF4GI, whereas mRNAs encoding proliferation inhibitors and catabolic pathway factors were increased. Depletion or over-expression of other eIF4G family members did not recapitulate these results. The majority of mRNAs that were translationally impaired with eIF4GI depletion were excluded from polyribosomes due to the presence of multiple upstream open reading frames and low mRNA abundance. These results suggest that the high levels of eIF4GI observed in many breast cancers might act to specifically increase proliferation, prevent autophagy and release tumor cells from control by nutrient sensing. Global regulation of transcription and polysomal association in eIF4GI-silenced cells. Keywords: Gene Silencing |
| 1578 | GSE45270 |
Profile | Profiling project of a panel of tubular adenoma and serrated adenoma patient material collected in the Academic Medical Center (AMC) in Amsterdam The Netherlands. The aim of the study was to compare the expression profiles of different types of colon cancer precursor lesions (tubular versus serrated adenomas) and determine their correspondence with a set of colon cancer patient-derived profiles that have distinct clinical outcomes. |
| 1579 | GSE10258 |
Profile | AML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a later onset a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p and 7q, as well as fast progression of the disease with extremely poor prognosis. We and other have shown that the MLL gene is over expressed in amplified cases, however, in most of the cases the amplified region is not restricted to the MLL locus. In the present study we investigated 19 patients with AML/MDS and MLL gain/amplification [15 AML (two secondary, following MDS and PV, and three therapy related) and 4 MDS cases (two therapy related)]. By means of array CGH performed in 12 patients (GSE9928) we were able to delineate the minimal deleted regions within 5q, 17p and 7q and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases were used to define the candidate genes within these regions. Interestingly, analysis of our data suggests an interdependency of genes influenced by losses of 5q and 17p and expression of genes present in 11q23-25. Additionally, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from all other types of AML, thus, indicating specific pathogenesis present in this entity. Keywords: AML patients, tumor stratification |
| 1580 | GSE39719 |
Profile | ERα17p is a synthetic peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially synthesized to mimic its calmodulin binding site. ERα17p was subsequently found to elicit estrogenic responses in E2-deprived ERα-positive breast cancer cells increasing proliferation and E2-dependent gene transcription. Surprisingly, in E2-supplemented media, ERα17p induced apoptosis and modified the actin network, influencing thereby cell motility. Here, we report that ERα17p induces a massive early (3h) transcriptional activity in breast cancer cell lines SKBR3). Remarkably, about 75% of the significantly modified transcripts were also modified by E2, confirming the pro-estrogenic profile of ERα17p. The different ER spectra of the used cell lines allowed us to extract a specific ERα17p signature related to ERα and its variant ERα36. With respect to ERα, the peptide activates nuclear (cell cycle, cell proliferation, nucleic acid and protein synthesis) and extranuclear signaling pathways. In contrast, through ERα36 it exerts inhibitory events on inflammation and cell cycle and inhibition of EGFR signaling. This is the first work reporting ERα36 specific transcriptional effects. The fact that a number ERα17p-induced transcripts is different from those activated by E2 revealed that the apoptosis and actin modifying effects of ERα17p are independent from the ER-related actions of the peptide. |
| 1581 | GSE14385 |
Profile | The study seeks to identify the epigenetic changes caused by exposure of to cigarette smoke condensate. To this goal human bronchial epithelial cells BEAS-2B, were treated with 5-aza-2’deoxycitidine and trychostatin A (5AzaC/TSA) subsequent to a chronic exposure (1 month) to cigarette smoke condensate (CSC). As negative control served BEAS-2B cells that were untreated or treated with CSC/DMSO for one month without the subsequent application of 5Aza/TSA. Keywords: stress response |
| 1582 | GSE13736 |
Profile | Gene expression in human umbilical vein endothelial cells (HUVEC) was investigated by microarray analysis after 4 h infection with S. aureus isolated from healthy nasal carriers (n=5) and from blood (n=5) of septic patients. All bacterial isolates were spa-typed and characterized with a DNA microarray to determine the presence of virulence genes. Keywords: infection studies pathogen, S. aureus |
| 1583 | GSE17483 |
Profile | Transcription factor Stat5 is constitutively active in human prostate cancer but not in normal prostate epithelium. Stat5 activation is associated with prostate cancer lesions of high histological grades and is present in the majority of castration-resistant recurrent human prostate cancers. The molecular mechnisms underlying constitutive activation of Stat5 in primary and recurrent human prostate cancer are currently unclear. We used microarrays to detail gene expression regulated by Stat5 in human prostate cancer cells. |
| 1584 | GSE18391 |
Profile | Adipose-derived stromal/stem cells (ASC) capable of multipotential differentiation can be isolated with high yield from human subcutaneous lipoaspirates. This study reports our recent experience isolating and immunophenotypically characterizing ASCs from >60 human subjects |
| 1585 | GSE11341 |
Profile | Pulmonary hypoxia is a common complication of chronic lung diseases leading to the development of pulmonary hypertension. The underlying sustained increase in vascular resistance in hypoxia is a response unique to the lung. Thus we hypothesised that there are genes whose expression is altered selectively in the lung in response to alveolar hypoxia. Using a novel subtractive array strategy, we compared gene responses to hypoxia in primary human pulmonary microvascular endothelial cells to those in cardiac microvascular endothelium and identified genes selectively differentially regulated in the lung endothelium. Keywords: Time course, cell type comparison |
| 1586 | GSE21270 |
Profile | The alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a direct mutagen and carcinogen causing DNA damage and other comprehensive alterations that lead to chromosomal aberrations, mutations, tumor initiation, and cell death. Our previous study revealed that MNNG at different concentrations could induce extensive changes in gene expression at an early stage of exposure. To further understand the dynamic cellular responses and hazardous effects caused by this environmental carcinogen, we used a whole-genome time-course screening methods to find out the gene expression changes induced by a low concentration of MNNG in human normal amnion epithelial FL cells. The cells were exposed to 1.0 µM MNNG, and differential gene expression profiles at 3, 12, and 24 h after MNNG treatment were obtained by use of Affymetrix HG-U133 Plus 2.0 oligonucleotide microarray technology, followed by quantitative real-time RT-PCR validation. The results showed that the low-dose MNNG exposure triggered extensive but moderate changes in gene expression at these three experiment time points after exposure. The responsive genes encode important proteins, including cell cycle regulators, transcription factors and signal transducers that determine cell cycle progression, cell fate and other activities associate with pro-oncogenic potentials. The differential gene expression profiles at the three time points varied greatly, and generally reflected a cellular responsive process from initiation to progression and to recovery after MNNG exposure. These results will aid our understanding of the complicated mechanisms of MNNG-induced cellular responses. Keywords：N-methyl-N'-nitro-N-nitrosoguanidine; Cellular response; Temporal gene expression change; Oligonucleotide microarray; Quantitative real-time RT-PCR |
| 1587 | GSE27494 |
Profile | Although the degenerating disc is considered to be the key source of pain in patients with low back pain the relationship between disc cells, nerves, and pain production is poorly understood. Neurotrophins are signaling molecules involved in the survival, differentiation, migration, and neurite outgrowth of central and peripheral neurons. Neurotrophins are now known to be expressed in non-neuronal tissues, including the intervertebral disc. We hypothesize that the inflammatory cytokine interleukin-1 (IL-1beta), which is produced by disc cells during degeneration, is a key element in the cascade of events involving neurotrophins. To test this, we used an in vitro experimental design which challenged 3D-cultured human annulus cells with IL-1beta and utilized microarray analysis to evaluate neurotrophin- and nerve-related gene expression profiles in treated vs. control cells. Analysis of nerve growth factor levels in conditioned media was also performed. Findings presented here support the hypothesis that proinflammatory cytokines (which are produced by disc cells during degeneration) are involved with a significant increase in the expression of neurotrophins and other nerve-related genes. Findings expand previous data on expression of neurotrophins in the degenerating disc, and provide the first documentation of expression of neurotrophin 3 and neuropilin 2. These results have direct translational relevance because they address the primary clinical issue with disc degeneration (low back pain) and open the possibility of novel analgesic therapies based on development of specific small-molecular antagonists to neurotrophins. |
| 1588 | GSE25518 |
Profile | Despite timely and successful surgery 32% of patients with bilateral and 10% with unilateral cryptorchidism will develop azoospermia. Cryptorchid boys at risk of azoospermia display a typical testicular histology of impaired mini-puberty at the time of the orchidopexy. During mini-puberty increased gonadotropin and testosterone secretion stimulate transformation of gonocytes into Ad spermatogonia. In azoospermia risk group this transformation is to a great extent impaired. This study aimed to analyze data on whole genome expression signatures of undescended testes at risk of developing azoospermia. |
| 1589 | GSE47920 |
Profile | T lymphocytes can be generated from T-cell-derived induced pluripotent stem cells (T-iPS). We used microarrays to better elucidate their phenotype and compare their gene expression profile to that of known lymhoid subsets from peripheral blood. |
| 1590 | GSE2600 |
Profile | THREE INDEPENDENT REPLICATES AND ARE THE CONTROL NON-INFECTED CELLS: GSM49939 GSM49940, GSM49941 THREE INFECTED INDEPEDENDENT REPLICATES: GSM49942, GSM49943, GSM49944 Keywords: ordered |
| 1591 | GSE16963 |
Profile | The expression of four transcription factors (OCT3/4 SOX2, KLF4, and c-MYC) can reprogram mouse as well as human somatic cells to induced pluripotent stem (iPS) cells. Expression of the c-MYC, also known as an oncogene, might induce carcinogenesis and thus, iPS cells produced with the use of c-MYC transduction cannot be used for human therapeutic applications. Furthermore, reprogramming efficiency was significantly reduced in the absence of c-MYC transduction. Here, we generated iPS cells from mesenchymal stromal cells (MSCs) derived from human third molars (wisdom teeth) by retroviral transduction of OCT3/4, SOX2, and KLF4 without c-MYC. Interestingly, clonally expanded MSCs, named 10F-15, could be used for iPS cell generation with 100-fold higher efficiency compared to that of other clonally expanded MSCs and human dermal fibroblasts. These iPS cells resembled human embryonic stem (ES) cells in many aspects, including morphology, ES markers expression, global gene expression, epigenetic states, and the ability to differentiate into the three germ layers in vitro and in vivo. Because human third molars are discarded as clinical waste, our data indicate that MSCs isolated from human third molars are a valuable cell source for the generation of iPS cells. |
| 1592 | GSE43115 |
Profile | Background: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV |
| 1593 | GSE12251 |
Profile | Infliximab an anti-TNFa monoclonal antibody, is an effective treatment for ulcerative colitis (UC) inducing over 60% of patients to respond to treatment. Consequently, about 40% of patients do not respond. This study analyzed mucosal gene expression from patients enrolled in ACT1 to provide a predictive response signature for infliximab treatment. Keywords: predictive response signature |
| 1594 | GSE16194 |
Profile | Snail is a zinc-finger transcription factor best known for its ability to down-regulate E-cadherin. Its established significance in embryology and organogenesis has been expanded to include a role in the tumor progression of a number of human cancers. In addition to E-cadherin it has more recently been associated with the down-regulation and up-regulation of a number of other genes that affect important malignant phenotypes. After establishing the presence of up-regulated Snail in human non-small cell lung cancer specimens, we used microarrays to detail the global programme of gene expression in non-small cell lung cancer cell lines stably transduced to over-express Snail as compared to vector control cell lines. |
| 1595 | GSE31548 |
Profile | Develop an EGFR mutation gene expression signature to aid in predicting response and clinical outcome and to identify genes associated with the EGFR-dependent phenotype |
| 1596 | GSE22435 |
Profile | Alternative mRNA splicing provides transcript diversity and has been proposed to contribute to several human diseases. Here we demonstrate that expression of genes regulating RNA processing is decreased in both liver and skeletal muscle of obese humans. To determine the metabolic impact of reduced splicing factor expression, we further evaluated the splicing factor, SFRS10, identified as down-regulated in obese human liver and skeletal muscle and in high fat fed rodents. siRNA-mediated reductions in SFRS10 expression induced lipogenesis and lipid accumulation in cultured hepatocytes. Moreover, SFRS10 heterozygous mice have both increased hepatic lipogenic gene expression and hypertriglyceridemia. We also demonstrate that LPIN1, a key regulator of lipid metabolism, is a splicing target of SFRS10, with reduced SFRS10 levels favoring the lipogenic β isoform of LPIN1. Importantly, LPIN1β-specific siRNA abolished the lipogenic effects of decreased SFRS10 expression. Together, our results indicate reduced expression of SFRS10 alters LPIN1 splicing and induces lipogenesis, demonstrating that reduced splicing factor expression observed in human tissues may contribute to metabolic phenotypes associated with human obesity. |
| 1597 | GSE10847 |
Profile | The transcription factors Smad2 and Smad3 mediate a large set of genes responses induced by the cytokine TGFβ but the extent to which their function depends on chromatin remodeling remains to be defined. We observed interactions between these two Smads and BRG1, BAF250b, BAF170 and BAF155, which are core components of the SWI/SNF chromatin-remodeling complex. Smad2 and Smad3 have a similar affinity for these components in vitro, and their interactions are primarily mediated by BRG1. In vivo, however, BRG1 predominantly interacts with Smad3, and this interaction is enhanced by TGFβ stimulation. Our results suggest that BRG1 is incorporated into transcriptional complexes that are formed by activated Smads in the nucleus, on target promoters. Using BRG1-deficient cell systems(H522 lung cancer cells), we defined the BRG1 dependence of the TGFβ transcriptional program genome-wide. Most TGFβ gene responses in human epithelial cells are dependent on BRG1 function. Remarkably, BRG1 is not required for the TGFβ-mediated induction of SMAD7 and SNON, which encode key mediators of negative feedback in this pathway. Our results provide a genome-wide scope of the participation of BRG1 in TGFβ action and suggest a widespread yet differential involvement of BRG1 SWI/SNF remodeler in the transcriptional response of many genes to this cytokine. Keywords: comparative genomic hybridization |
| 1598 | GSE19650 |
Profile | The host antitumor immunity changes drastically during carcinogenesis. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a precursor lesion of pancreatic cancer and progresses according to adenoma-carcinoma sequence. We found that the host antitumor immune reaction changes from an immune response to immune tolerance between intraductal papillary-mucinous adenoma (IPMA) and intraductal papillary-mucinous carcinoma (IPMC). In order to determine molecules affecting intraepithelial DC infiltration in IPMNs during multistep carcinogenesis we examined the gene-expression profiles of entire transcripts of neoplastic cells at different stages. |
| 1599 | GSE2723 |
Profile | This sample is part of a study that compares small sample amplification technologies. The analysis looks at differential gene expression when compared to one round of T7 amplification. A tumor cell line was used in comparison to a human reference RNA in this study. Keywords = amplification Keywords = small sample Keywords = Affymetrix Keywords: other |
| 1600 | GSE26869 |
Profile | Analysis of the transcriptome of mononuclear side population (SP) and main population (MP) cells of human fetal skeletal muscle from 12 human subjects of gestational age 14-18 weeks. |
| 1601 | GSE20950 |
Profile | Obesity is a risk factor for numerous metabolic disorders; however not all obese individuals are prone to insulin resistance. The central aim of this study was to identify molecular pathways directly related to insulin resistance independent of BMI in obesity. We sought to determine the gene expression signature of adipose tissue in a body mass index (BMI)-matched obese cohort of patients that are either insulin sensitive or insulin resistant. |
| 1602 | GSE6816 |
Profile | Melanoma tumor antigen p97 or melanotransferrin (MTf) is an iron (Fe)-binding protein with high homology to serum transferrin. MTf is expressed at very low levels in normal tissues and in high amounts in melanoma cells. The over-expression of MTf in tumor cells was hypothesized to assist rapidly proliferating neoplastic cells with their increased Fe requirements. However our recent characterization of the MTf knockout (MTf -/-) mouse demonstrated that MTf did not have an essential role in Fe metabolism. To understand the function of MTf, we utilized whole-genome microarray analysis to examine the gene expression profile of five models after modulating MTf expression. These models included two new stably transfected MTf hyper-expression models (SK-N-MC neuroepithelioma and LMTK- fibroblasts) and one cell type (SK-Mel-28 melanoma) where MTf was down-regulated by post-transcriptional gene silencing. These findings were compared to alterations in gene expression identified using the MTf -/- mouse. In addition, the changes identified from the gene array data were also assessed in a new model of MTf down-regulation in SK-Mel-2 melanoma cells. In the cell line models, MTf hyper-expression led to increased cellular proliferation, while MTf down-regulation resulted in decreased proliferation. Across all five models of MTf down- and up-regulation, we identified three genes modulated by MTf expression. These included ATP-binding cassette sub-family B member 5 (Abcb5), whose change in expression mirrored MTf down- or up-regulation. In addition, thiamine triphosphatase (Thtpa) and transcription factor 4 (Tcf4) were inversely expressed relative to MTf levels across all five models. The products of these three genes are involved in membrane transport, thiamine phosphorylation and cell proliferation/survival, respectively. This study identifies novel molecular targets directly or indirectly regulated by MTf and potential pathways involved in its function. These molecular targets could be involved, at least in part, to the role of MTf in modulating proliferation. Keywords: Melanotransferrin, hyperexpression cell lines, comparative genomic hybridization |
| 1603 | GSE4984 |
Profile | Human monocyte derived dendritic cells matured via galectin-1 or LPS. Keywords: dendritic cell maturation |
| 1604 | GSE20540 |
Profile | Conventional anti-cancer drug screening is typically performed in the absence of accessory cells (e.g. stromal cells) of the tumor microenvironment which can profoundly alter anti-tumor drug activity. To address this major limitation, we have developed assays (e.g. the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay) to selectively quantify tumor cell viability, in presence vs. absence of non-malignant stromal cells or drug treatment. These assays have allowed us to identify that neoplastic cells from diverse malignancies exhibit stroma-induced resistance to different anti-tumor agents. In this analysis, we evaluated the molecular changes triggered in myeloma cells by their in vitro interaction with stromal cells. The transcriptional profile of 3 human multiple myeloma (MM) cell lines (MM.1S, MM.1R, INA-6) co-cultured with stromal cells vs. when cultured alone was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip. |
| 1605 | GSE29375 |
Profile | APRIL (TNFSF13) is a ligand of the TNF superfamily which binds to two receptors BCMA and TACI. We have found that APRIL and its receptor BCMA are specifically enhanced in hepatocellular carcinoma, as compared to non-cancerous liver tissue. We further identified that HepG2 cells present the same ligand/receptor pattern as human hepatocellular carcinomas. We investigated the role of APRIL in HepG2 gene expression in a time course study. |
| 1606 | GSE9103 |
Profile | Aging is associated with mitochondrial dysfunction and insulin resistance. We conducted a study to determine the role of long-term vigorous endurance exercise on age-related changes in insulin sensitivity and various indices of mitochondrial functions. Keywords: The effect of excises in young and old human subjects by transcription profiling |
| 1607 | GSE20854 |
Profile | Microarrays were used to analyze differential gene expression and to help determine the efficacy of Iressa (gefitinib) a tyrosine kinase inhibitor, on endometrial cancer cells. Type I Ishikawa H and type II Hec50co endometrial carcinoma cells both express EGFR and sEGFR, but differ markedly in their responsiveness to the EGFR inhibitor gefitinib. This difference is paralleled by differences in the expression of sEGFR and EGFR, as well as in their transcriptional response following treatment with either EGFor gefitinib. The small cluster of differently regulated genes reported here in these type I vs. type II endometrial cancer-derived cell lines may identify candidate biomarkers useful for predicting sensitivity to EGFR blockade. |
| 1608 | GSE6146 |
Profile | Gene expression profiles of CD34+CD38- stem cells and more differentiated CD34+CD38+ progenitor cells were compared. Comparison of expression profiles of hematopoietic stem cells from fetal liver umbilical cord blood, bone marrow and mobilized pheripheral blood allowed us to identify a unique set of genes with conserved expression during ontogeny. Keywords: Cell type comparison |
| 1609 | GSE9350 |
Profile | Two pancreatic cancer cell lines with different metastatic and growth potential were compared under hypoxic conditions and under normal atmospheric oxygen pressure. The FG cell lines shows very few metastases and slow growth in mouse xenograft models. L3.6pl derived from FG by cycles re-implantation of metastatic cells obtained after orthotopic tumor growth in nude mice, shows high motility, aggressive growth and very high metastatic potential By comparison of the two cell lines under different oxygen concentration we tried to simulate in vivo conditions of tumors at different growth stages. Differentially expressed genes and transcription factor regulating coexpressed genes identified by SOTA clustering were used to identify key genes that define metastatic potential of pancreatic cancer cells Keywords: 2+2 factorial design |
| 1610 | GSE15645 |
Profile | Identify biomarkers to predict response to therapy in polyarticular juvenile idiopathic arthritis (JIA) using gene expression microarrays. |
| 1611 | GSE6631 |
Profile | Forty-four paired (from the same patient) samples of head and neck squamous cell carcinoma (HNSCC) and normal tissue were studied with Affymetrix U95A chips. A stringent multi-test approach combining 7 traditional and microarray-specific statistical tests, was used to analyze the resultant data. Candidate genes were assigned to tiers of significance based on the number of statistical tests that each gene satisfied. Representative genes (both up-regulated and down-regulated) from each of the 3 tiers would be quantified with RT-PCR on both microarray-tested and new samples of HNSCC. The goal of this study is to identify reliable differentially-expressed genes on HNSCC and to testify our hypothesis whether or not a combinatorial approach (multi-tests) to analyzing microarray data can really identify differentially-expressed genes with fewer false-positives. Keywords: disease state; tumor vs. normal |
| 1612 | GSE20168 |
Profile | Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects |
| 1613 | GSE18674 |
Profile | We performed microarray experiments to examine gene expression in human tissues. This data was used for comparison with our humanized mouse study (GEO ID GSE33846) and threshold determination of our tiling array data (GEO ID GSE18490 public in the near future). A total of 22 tissues (bone marrow, cerebellum, colon, cortex, fetal brain, heart, kidney, liver, lung, pancreas, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea and uterus) and 2 cell lines (HeLa and SH-SY5Y) were examined. |
| 1614 | GSE8002 |
Profile | In order to investigate the role of CD34 antigen in haematopoietic commitment we silenced the CD34 gene expression in CD34+ stem/progenitor cells using a siRNA approach. Keywords: treatment comparison |
| 1615 | GSE29410 |
Profile | The objective was to characterize differences in the secretome of human omental compared with subcutaneous adipose tissue using global gene expression profiling. Gene expression was measured using Affymetrix microarrays in subcutaneous and omental adipose tissue (n=3 independent subjects; 6 arrays). Predictive bioinformatic algorithms were employed to identify those differentially expressed genes that code for secreted proteins and to identify common pathways between these proteins. All patients provided informed written consent before inclusion in the study which was approved by the North of Scotland Research Ethics Committee (NOSREC). |
| 1616 | GSE42203 |
Profile | The multifunctional protein lipopolysaccharide-induced TNFalpha factor (LITAF) induces the secretion of inflammatory cytokines in monocytes and regulates protein degradation in neural cells. In B-cell lymphomas LITAF is frequently inactivated by epigenetic mechanisms, but beyond these data little is known about its regulation and function. Immunohistochemical and gene expression profiling analyses of normal and malignant B-cells revealed that LITAF and BCL6 exhibited opposite expression patterns. Accordingly, chromatin immunoprecipitation and luciferase experiments showed that LITAF is transcriptionally repressed by BCL6 in germinal center (GC) lymphocytes and in B-cell lymphoma cells. Gain- and-loss-of-function assays demonstrated that LITAF does not exert any of its previous roles. Conversely, LITAF co-localized with autophagosomes in B-cells whereby activated autophagic responses, which were abrogated upon LITAF silencing. Therefore, BCL6-mediated transcriptional repression of LITAF may contribute to an appropriate GC reaction by suppressing autophagy in GC lymphocytes, whereas constitutive repression of autophagic responses may promote B-cell lymphoma development. |
| 1617 | GSE29881 |
Profile | DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical artery endothelial cells (HUAECs) exposed to 1 nmol/L estradiol and/or 100 µg/ml oxidized low density lipoprotein (oxLDL) for 24 hours compared to control cells. |
| 1618 | GSE40885 |
Profile | Rationale: Lipopolysaccharide (LPS) is ubiquitous in the environment. Inhalation of LPS has been implicated in the pathogenesis and/or severity of several lung diseases including pneumonia, chronic obstructive pulmonary disease and asthma. Alveolar macrophages are the main resident leukocytes exposed to inhaled antigens. Objectives: To obtain insight into which innate immune pathways become activated within human alveolar macrophages upon exposure to LPS in vivo. |
| 1619 | GSE29618 |
Profile | Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology. Here we used the systems vaccinology approach to study the molecular mechanisms underlying the innate responses to the trivalent inactivated influenza (TIV) and live attenuated influenza (LAIV) vaccination in humans and to identify early gene signatures that predict the magnitude of the antibody responses to influenza vaccination. |
| 1620 | GSE1402 |
Profile | Biotinylated cRNA was synthesized from total RNA (Enzo; Farmingdale NY) and processed according to the Affymetrix GeneChip Expression Analysis Technical Manual (Affymetrix; Santa Clara, CA). 57 samples: 5 pauciarticular PBMC, 15 polyarticular PBMC, 11 control PMBC, 6 JSpA PBMC, 5 pauciarticular SFMC, 10 polyarticular PBMC, 5 JSpA SFMC classified by course. Keywords = juvenile rheumatoid arthritis (JRA) Keywords = peripheral blood mononuclear cells (PBMC) Keywords = synovial fluid mononuclear cells (SFMC) Keywords: other |
| 1621 | GSE23061 |
Profile | This dataset is part of the manuscript titled "The metabolic regulator ERRalpha a downstream target of HER2/IGF1, as a therapeutic target in breast cancer" (in review). The expression data obtained in human mammary epithelial cells were used to generate a list of ERRalpha-regulated genes that was later refined in clinical breast cancer datasets to generate a clinically relevant signature of ERalpha activity (referred to as Cluster 3 signature). Using this signature of the estrogen-related receptor alpha (ERRa) to profile more than eight-hundred breast tumors, we found that patients with tumors exhibiting higher ERRa activity were predicted to have shorter disease free survival. Further, the ability of an ERRa antagonist, XCT790, to inhibit breast cancer cell proliferation correlates with the cell’s intrinsic ERRa activity. These findings highlight the potential of using the ERRa signature and antagonists in targeted therapy for breast cancer. Using a chemical genomic approach we determined that activation of the HER2/IGF1 signaling pathways upregulates the expression of PGC-1b, an obligate cofactor for ERRa activity. Knockdown of PGC-1b in HER2 positive breast cancer cells impaired ERRa signaling and reduced cell proliferation, implicating a functional role of PGC1b/ERRa in the pathogenesis HER2 positive breast cancer. |
| 1622 | GSE42672 |
Profile | Transient pluripotency-factor-based signaling-directed (TPS) transdifferentiation approach could be further applied to generate functional induced endothelial (iEnd) cells from human fibroblasts with only two factors: Oct4 and Klf4 (OK). The iEnd cells exhibit characteristic endothelial cell phenotype in vitro and in vivo and are capable of functionally promoting vascular regeneration and blood perfusion in a murine model of PAD. |
| 1623 | GSE36700 |
Profile | Rheumatoid arthritis (RA) is an inflammatory joint disorder that results in progressive joint damage when insufficiently treated. In order to prevent joint destruction and functional disability in RA early diagnosis and initiation of appropriate treatment with Disease-Modifying Antirheumatic Drugs (DMARDs) is needed. However, in daily clinical practice, patients may initially display symptoms of arthritis that do not fulfil the classification criteria for a definite diagnosis of RA, or any other joint disease, a situation called “Undifferentiated Arthritis” (UA). Out of the patients with UA, 30 to 50% usually develop RA, and early identification of these remains a challenge. At the present time, although several risk factors associated with the development of RA have been identified (6-9), a model that reliably predicts the probability of evolution of UA into RA in individual patients is lacking. In order to better identify early RA patients, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration recently developed new classification criteria. Although these criteria are more sensitive, the risk of over-diagnosis is an important issue to consider, especially in very early disease. In this context, the present study explores the feasibility of a molecular diagnosis of arthritis, based on the identification of disease-specific transcriptomic profiles in synovial biopsies from patients with arthritis according to the underlying condition. In a previous study, we performed global analyses of gene expression in synovial biopsies from patients with RA, Systemic Lupus Erythematosus (SLE) and Osteoarthritis (OA), using high-density oligonucleotide spotted microarrays. We found that the gene expression profiles are strikingly different according to the underlying condition. Thus, the majority of the genes up-regulated in SLE are type I Interferon-inducible genes, as compared with the up-regulation genes involved in T cell and B cell activation in RA, and in extracellular matrix homeostasis in OA. Based on these results, similar analyses were performed in synovial biopsies from patients with seronegative arthritis (SA) and microcrystalline arthritis (MIC), in order to identify disease-specific molecular signatures. |
| 1624 | GSE37838 |
Profile | In deceased donor kidney transplantation acute kidney injury (AKI) prioir to surgery is a major determinant of delayed graft function (DGF), but AKI is histologically silent and difficult to assess. We hypothesized that a molecular measurement of AKI would add power to conventional risk assessments to predict the early poor allograft function at first week post transplantation. |
| 1625 | GSE15209 |
Profile | Gliomas have been proposed to be driven by a population of neural stem-like cells. We isolated a panel of novel human glioma cell lines using adherent neural stem cell conditions. The normal human foetal (hf) NS cells and the tumorigenic glioma NS cell lines were expanded using growth factors EGF and FGF in adherent culture conditions. In these conditions apoptosis and differentiation are suppressed resulting in more homogeneous populations of stem cells than has been reported previously. We included parallel primary biopsies of non-malignant brain tissue ('Normal Brain'). |
| 1626 | GSE22029 |
Profile | Fibroblasts are widely used cells for regenerative medicine in clinics such as gingival or facial skin treatment. In fact, fibroblasts are considered as a mixture of various types of cells with "spindle shape" and there is no available clear marker. Gingival and dermal fibroblasts are similar in their morphology and function; however it is considered that the cultured cells retain their original characteristics depending on the origin, which may contribute to the differential therapeutic effects. For example, gingival wounds are known to heal relatively quickly with less scar formation compared with skin, which may imply their higher capability for regeneration as a therapeutic effect. The reason for this phenomenon may be partly due to characteristic differences between gingival and dermal fibroblasts including the expression of migration stimulating factor and matrix formation but these differences remain largely unknown. Recently, the characteristics of dermal fibroblasts have been reported to be different depending on body sites, such as face, trunk and plamoplantar skin. Although the expression of fibronectin and their splicing variants were known to be different between trunk and oral mucosal fibroblasts, there is still no detailed report on the functional differences between gingival and dermal fibroblasts. In this study, we investigated differential gene expression in normal gingival and dermal fibroblasts using DNA microarray to investigate the difference between the vague fibroblast-type cells from different tissue origin to achieve higher therapeutic effect in cell therapy. |
| 1627 | GSE17187 |
Profile | Gastric cancer is one of the most common causes of cancer-related deaths worldwide. The lymph node status represents the strongest prognostic factor. Due to its extremely poor prognosis the identification of novel therapeutic targets is urgently needed. Therefore, we aimed to assess differentially expressed genes in nodal negative versus nodal positive intestinal type gastric carcinoma by GeneChip array technique. The transcriptional profile of 6 gastric cancers with and without lymphatic dissemination was analyzed. A total of 115 transcripts were found to be up- and 219 to be down-regulated in node positive compared with node negative gastric cancers. Next we searched for differentially expressed GPCRs. We identified 52 GPCRs and GPCR-related genes, which were up- or down-regulated with a fold change factor greater 1.5. |
| 1628 | GSE15013 |
Profile | In acute myeloid leukemia (AML) the mixed lineage leukemia (MLL) gene may be rearranged to generate a partial tandem duplication (PTD), or fused to partner genes through a chromosomal translocation (tMLL). In this study, we first explored the differentially expressed genes between MLL-PTD and tMLL using gene expression profiling of our cohort (15 MLL-PTD and 10 tMLL) and one published data set. The top 250 probes were chosen from each set, resulting in 29 common probes (21 unique genes) to both sets. The selected genes include four HOXB genes, HOXB2, B3, B5, and B6. The expression values of these HOXB genes significantly differ between MLL-PTD and tMLL cases. Clustering and classification analyses were thoroughly conducted to support our gene selection results. Second, as MLL-PTD, FLT3-ITD, and NPM1 mutations are identified in AML with normal karyotypes, we briefly studied their impact on the HOXB genes. Another contribution of this study is to demonstrate that using public data from other studies enriches samples for analysis and yields more conclusive results. |
| 1629 | GSE21252 |
Profile | Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. |
| 1630 | GSE32175 |
Profile | Affymetrix HG U133 Plus 2.0 Array (Affymetrix Santa Clara, CA) was used to profile transcriptomes and discover altered gene expression in saliva supernatant. Salivary transcriptomic biomarker discovery was performed on 10 lung cancer patients and 10 matched controls. Seven messenger RNA biomarkers were discovered and pre-validated |
| 1631 | GSE16625 |
Profile | Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. The patients with MDS chronic myelomonocytic leukemia (CMMoL), and high risk AML were treated with sequential administration of methylation inhibitor drugs (5AC and entinostat). To study gene expresion regulation in treated patients, microarray analysis was done on RNA samples extracted from CD34+ cells from 18 patients before and 15 days after treatment using Affymetrix U133Plus2.0. |
| 1632 | GSE25941 |
Profile | Global microarray (HG U133 Plus 2.0) was used to investigate the basal level skeletal muscle transcriptome profile of young and old adults. One vastus lateralis muscle biopsy was obtained in the basal state from 36 different subjects. |
| 1633 | GSE24468 |
Profile | Both pro- and anti-mitogenic activities have been ascribed to progesterone receptor (PR) agonists and antagonists in breast cancer cells however, the transcriptional responses that underlie these paradoxical functions are not apparent. Using non-transformed, normal human mammary epithelial cells (hMECs) engineered to express PR, and standard microarray technology, we defined 2,370 genes that were significantly regulated by the PR agonist R5020. Gene Ontology (GO) analysis revealed that GO-terms involved in inflammation and NF-κB signaling were among the most significantly regulated. Interestingly, on those NF-κB responsive genes that were inhibited by agonist-activated PR, antagonists either (a) mimicked the actions of agonists or (b) reversed the inhibitory actions of agonists. This difference in pharmacological response could be attributed to the fact that although agonist and antagonist-activated PR is recruited to the promoters of NF-κB responsive promoters, the physical presence of PR tethered to the promoter of some genes is sufficient for transcriptional inhibition whereas on others an agonist-activated PR conformation is required for inhibition of NF-κB signaling. Importantly, the actions of PR on the latter class of genes were reversed by an AF-2 inhibiting, LXXLL-containing peptide. Consideration of the relative activities of these distinct anti-inflammatory pathways in breast cancer may be instructive with respect to the likely therapeutic activity of PR agonists or antagonists in the treatment of breast cancer. |
| 1634 | GSE39763 |
Profile | Background: Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair yet EPCs from different anatomic locations possess unique biological properties. The underlying mechanisms are unclear. Method: We performed transcriptome analysis for EPCs isolated from 2 different sources: cord blood (CB) or adult peripheral blood (PB). Both gene expression microarray and small RNA sequencing (smRNA-seq) technologies were applied. Results: EPCs from CB expressed abundant genes involved in cell cycle, hypoxia signalling and blood vessel development, correlating with the phenotypes that CB-EPCs proliferated more rapidly, migrated faster, and formed tubule structure more efficiently. smRNA-seq further deciphered miRNome patterns in EPCs isolated from CB or PB: 54 miRNAs were enriched in CB-EPCs, while another 50 in PB-EPCs. Specifically, CB-EPCs expressed more angiogenic miRNAs such as miR-31, while PB-EPCs possessed more tumor suppressive miRNAs including miR-10a. Knocking down miR-31 levels in CB-EPCs suppressed cell migration and microtubule formation, while overexpressing miR-31 in PB-EPCs helped to recapitulate some of CB-EPC functions. Conclusion: Our results show the foundation for a more detailed understanding of EPCs from different anatomic sources. Stimulating the expression of angiogenic microRNAs or genes in EPCs of low activity (such as those from patients with cardiovascular diseases) might allow the development of novel therapeutic strategies. |
| 1635 | GSE22552 |
Profile | Understanding the pattern of gene expression and identifying the specific genes expressed during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here we have isolated four distinct populations of erythroblasts at successive erythropoietin-dependent stages of erythropoiesis including the terminal pyknotic stage. The transcriptome has been determined using Affymetrix arrays. First, we show that cells sorted by surface expression profile express not only significantly fewer genes than unsorted cells, but also significantly more differences in the expression levels of particular genes between stages than unsorted cells, demonstrating the importance of working with defined cell populations to identify lineage and temporally-specific patterns of gene expression. Second, using standard software and matched filtering we identify eleven differentially regulated genes and one continuously expressed gene previously undetected in erythroid expression studies with unknown roles in erythropoiesis (CA3, CALB1, CTSL2, FKBP1B, GSDMB, ITLN1, LIN7B, RRAD, RUNDC3A, UNQ1887, ZNF805, MYL12B). Finally, using transcription factor binding site analysis we identify potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts are a resource for functional studies of erythropoietic protein function and gene regulation. |
| 1636 | GSE12939 |
Profile | We found constitutive upregulation and higher degree induction of drug metabolism and disposition-related genes in a three-dimensional HepG2 culture. The upregulated genes are those believed to be regulated by different regulatory factors. The global gene expression analysis by Affymetrix GeneChip indicated that altered expressions of microtubule-related genes may change expressed levels of drug metabolism and disposition genes. Stabilization of the microtubule molecules with docetaxel a tubulin stabilizing agent, in the two-dimensional culture showed gene expression patterns similar to those in the three-dimensional culture, indicating that culture environment affects drug metabolism functions in HepG2 cells. Keywords: radial flow bioreactor cell culture system, three dimensional culture, HepG2, GeneChip U133A, |
| 1637 | GSE11327 |
Profile | Pro-inflammation triggered by microbial lipopolysaccharide (LPS) through Toll-like receptor (TLR) 4 in the presence of interferon (IFN)-g induces cytokine secretion in dendritic cells (DCs) tightly regulated by a defined differentiation program. This DC differentiation is characterized by a dynamic immune activating but also tolerance inducing phenotype associated with irreversible down-modulation of cytokines. CD40L on activated T cells further modifies DC differentiation. Using DNA micro arrays we showed down-regulated mRNA levels of TLR signaling molecules while CD40/CD40L signaling molecules were up-regulated at a time when LPS/IFN-g activated DCs have ceased cytokine expression. Accordingly we demonstrated that CD40/CD40L but not TLR4 or TLR3 signaling mediated by LPS or poly (cytidylic-inosinic) acid (poly I:C) and dsRNA re-established the capacity to secret interleukin (IL)-12 in LPS/IFN-g activated DCs which have exhausted their potential for cytokine secretion. This resulting TH1 polarizing DC phenotype – which lacked accompanying secretion of the crucial immune suppressive IL-10 - enhanced activation of cytotoxic T lymphocytes (CTLs). We therefore conclude that immune modulation is restricted to a secondary T-cell mediated stimulus at an exhausted DC state which prevents an immune tolerant DC phenotype. These findings impacts on the rational design of TLR activated DC-based cancer vaccines for the induction of anti-tumoral CTL responses. Keywords: time course |
| 1638 | GSE15176 |
Profile | Human induced pluripotent stem (iPS) cells have previously been derived from somatic cells using viral vectors that integrate transgenes into the genome. Genomic integration however, can allow persistent leaky expression of the transgenes and can create insertional mutations, thus limiting the utility of these cells for both research and clinical applications. Here, we describe the derivation of human iPS cells free of vector and transgene sequences using non-integrating oriP/EBNA1-based episomal vectors. The resulting iPS cells are similar to human embryonic stem (ES) cells in both proliferative and developmental potential. These results demonstrate that reprogramming of human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors, and removes one important obstacle to the clinical applications of these cells. |
| 1639 | GSE32887 |
Profile | Cutaneous sarcoidosis skin provides relatively non invasive access to granulomatous sarcoidosis tissue. |
| 1640 | GSE33950 |
Profile | Triple Negative Breast cancer accounts for some of the most aggressive types of breast cancer. By interrogating clinical datasets we found that the activities of p63 and Hypoxia-Inducible-Factors (HIFs), two master regulators of the invasive and metastatic cancer cell phenotype are linked in TNBC through the p63-target Sharp1. Mechanistically, Sharp1 promotes HIF-1α/HIF-2α proteasomal degradation by serving as HIFs presenting factor to the proteasome independently from oxygen levels and prior ubiquitination. To investigate unbiasedly if Sharp1 is a general inhibitor of HIF induced transcriptional program, we compared the transcriptomic profile of cells either overexpressing Sharp1 or depleted of HIF1a and HIF2a. |
| 1641 | GSE24244 |
Profile | GBM is a heterogenous brain tumor with hyperproliferation of endothelial cells. In order to understand the cellular mechanism of vasculogenesis in GBM four fractions of cells are seperated. Microarray assays was performed to examine the potential lineage relationship and the signal pathways involved in determining the cell identity and function. |
| 1642 | GSE22325 |
Profile | In the hematopoietic microenvironment endothelial cells (ECs) play an important role in the regulation of hematopoietic cell proliferation and trafficking. We previously demonstrated that EC stimulated with tumor necrosis factor alpha (TNF-α) induce the generation of dendritic cells from CD34(+) stem cells, whereas in contrast, interleukins were capable of inducing the proliferation of hematopoietic and myeloid progenitors. In order to identify potentially new soluble factors which greatly impact the self-renewal, proliferation and differentiation of CD34+ hematopoietic stem cells (HSC), we examined the expression profiles of IL-1ß, IL-3 and IL-6 stimulated human umbilical vein endothelial cells (HUVEC). |
| 1643 | GSE10393 |
Profile | Hepatocellular carcinoma (HCC) is a highly heterogeneous disease and prior attempts to develop genomic-based classification for HCC have yielded highly divergent results, indicating difficulty in identifying unified molecular anatomy. We performed a meta-analysis of gene expression profiles in data sets from eight independent patient cohorts across the world. In addition, aiming to establish the real world applicability of a classification system, we profiled 118 formalin-fixed, paraffin-embedded tissues from an additional patient cohort. A total of 603 patients were analyzed, representing the major etiologies of HCC (hepatitis B and C) collected from Western and Eastern countries. We observed three robust HCC subclasses (termed S1, S2, and S3), each correlated with clinical parameters such as tumor size, extent of cellular differentiation, and serum alpha-fetoprotein levels. An analysis of the components of the signatures indicated that S1 reflected aberrant activation of the WNT signaling pathway, S2 was characterized by proliferation as well as MYC and AKT activation, and S3 was associated with hepatocyte differentiation. Functional studies indicated that the WNT pathway activation signature characteristic of S1 tumors was not simply the result of beta-catenin mutation but rather was the result of transforming growth factor-beta activation, thus representing a new mechanism of WNT pathway activation in HCC. These experiments establish the first consensus classification framework for HCC based on gene expression profiles and highlight the power of integrating multiple data sets to define a robust molecular taxonomy of the disease. |
| 1644 | GSE6222 |
Profile | To investigate the mechanisms of liver cancer progression and metastasis we did expression profiling of human liver cancer and benign tissues. Keywords: gene expression array-based (RNA / in situ oligonucleotide) |
| 1645 | GSE14503 |
Profile | Type 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease and it is important to find new alternative source of the islet beta cells to replace the damaged cells. Human embryonic stem (hES) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into embryoid bodies and then induced to generate the pancreatic islet-like cell clusters, which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin. The expression profiles of microRNAs and mRNAs from the pancreatic islet-like cell clusters were further analyzed and compared with those of undifferentiated hES-T3 cells and differentiated embryoid bodies. MicroRNAs negatively regulate the expression of protein-coding mRNAs. The pancreatic islet-like cell clusters were found to exhibit very high expression of microRNAs miR-186, miR-199a and miR-339, which down-regulated the expression of LIN28, PRDM1, CALB1, GCNT2, RBM47, PLEKHH1, RBPMS2 and PAK6. Therefore, these microRNAs are very likely to play important regulatory roles in the differentiation of pancreatic islet cells and early embryonic development. |
| 1646 | GSE14858 |
Profile | Gene expression analysis identified a specific signature of differentially expressed genes discriminating good and poor responders in JMML patients. Gene expression signatures were analyzed on two EWOG patient cohorts of pediatric JMML patients. Keywords: Expression data |
| 1647 | GSE18015 |
Profile | Background: Gliomas are the most common type of primary brain tumours and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Methods: Eight fresh, primaries and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA. Results: Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders). Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups of samples: those discriminated by tumour location and, the most importantly, the group discriminated by their proliferative potential. Conclusions: Primary glioblastomas could be sub-classified according to the properties of their CD133+ cells. The molecular characterization of these potential stem cell populations could be critical to find new therapeutic targets and to develop an effective therapy for these tumours with very dismal prognosis. |
| 1648 | GSE38080 |
Profile | Hsp27 can regulate multiply signaling pathway and protect HCC cells apoptosis by mediating interaction with its cochaperones |
| 1649 | GSE41445 |
Profile | We profiled basal gene expressed levels of 21 cell lines (18 cancer and 3 non-tumorigenic) using Affymetrix HG-U133_plus2 GeneChip microarrays. Goal of the experiment was to benchmark a number of algorithms for biomarker detection all of which utilize gene expression data. |
| 1650 | GSE8687 |
Profile | In this study we compared the effects of IL-2 IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells. Keywords: 3 replicates in each of 4 conditions |
| 1651 | GSE12121 |
Profile | Transcriptional profiling was utilized to define the biological pathways of gingival epithelial cells modulated by mono- and complex co-culture with oral commensal S. gordonii and pathogenic P. gingivalis. We used microarrays to detail the global programme of gene expression underlying infection and identified distinct classes of up- and down-regulated genes during this process. Keywords: infection state |
| 1652 | GSE29133 |
Profile | Alveolar epithelial type II (ATII) cells play a critical role in homeostasis and repair process of the lungs. In lung diseases such as chronic obstructive pulmonary disease (COPD) ATII cells are damaged and fall into apoptosis or senescence. Until to date, global gene expression of ATII cells in COPD lungs has not been analyzed. We isolated ATII cells from three non-COPD and three COPD patients using a FACS method. Then, we performed microarray analysis to compare gene expression profiles of ATII cells between non-COPD and COPD patients. |
| 1653 | GSE28847 |
Profile | Smad1/5 are transcription factors that engage in BMP-induced transcription. We determined and analyzed Smad1/5 binding sites by ChIP-sequencing. We used expression microarrays to compare the Smad1/5 binding sites identified by ChIP-seq to BMP-induced gene expressions. |
| 1654 | GSE9762 |
Profile | Down syndrome (DS) is caused by an extra copy of chromosome 21. We are characterizing protein changes in human skin fibroblasts. We propose to study corresponding changes at the DNA level (by SNP analysis) and the RNA level (using Affymetrix chips). These studies will detail transcriptional and translational regulation in trisomy. The Specific Aim is to obtain data on RNA transcript levels using Affymetrix expression arrays in a group of trisomy 21 and euploid fibroblast cell lines. In parallel we will acquire SNP data to determine both genotype (call) and copy number changes for trisomic samples. The results will allow us to identify the patterns of change in a trisomic chromosome (relative to control). [1] We hypothesize that in genomic DNA samples derived from trisomy 21 (TS21) fibroblasts there will be an increased copy number on chr21 with additional microdeletions and microdeletions. [2] We hypothesize that the RNA transcripts derived from chr21 will be elevated relative to euploid controls. [3] We hypothesize that altered RNA transcript levels will be significantly correlated with altered protein levels from these same fibroblast cell lines. The experimental design is as follows. All samples are from deidentified individuals and were obtained from the Brain and Tissue Bank for Developmental Disorders at the University of Maryland, with Johns Hopkins IRB approval.[1] There are five trisomy 21 samples and five euploid samples (total n=10). Fibroblasts were grown in culture to comparable confluency and passage number. Cells were harvested. Total RNA was isolated with a Qiagen kit. The quantity and purity of the RNA was confirmed by spectrophotometry and by electrophoresing an aliquot on a 1% agarose gel. Approximately 10 micrograms of total RNA will be sent to TGen on dry ice for analysis on Affymetrix U133 PlusTwo arrays. Data analysis will be with Affymetrix and Partek software. Keywords: other |
| 1655 | GSE16745 |
Profile | Reintroduction of CEBPA in MN1-overexpressing hematopoietic cells prevents their hyper-proliferation and restores myeloid differentiation. Forced expression of MN1 in primitive mouse hematopoietic cells causes acute myeloid leukemia and impairs all-trans retinoic acid (ATRA) induced granulocytic differentiation. Here we studied the effects of MN1 on myeloid differentiation and proliferation using primary human CD34+ hematopoietic cells, lineage depleted mouse bone marrow cells, and bipotential (granulocytic/monocytic) human AML-cell lines. We show that exogenous MN1 stimulated the growth of CD34+ cells, which was accompanied by enhanced survival and increased cell cycle traverse in cultures supporting progenitor cell growth. Forced MN1 expression impaired both granulocytic and monocytic differentiation in vitro in primary hematopoietic cells and AML cell lines. Endogenous MN1 expression was higher in human CD34+ cells compared to both primary and in vitro differentiated monocytes and granulocytes. Microarray and real time RT-PCR analysis of MN1-overexpressing CD34+ cells showed down regulation of CEBPA and its downstream target genes. Re-introduction of conditional and constitutive CEBPA overcame the effects of MN1 on myeloid differentiation and inhibited MN1-induced proliferation in vitro. These results indicate that down regulation of CEBPA activity contributes to MN1-modulated proliferation and impaired myeloid differentiation of hematopoietic cells |
| 1656 | GSE18350 |
Profile | We describe Hi-C a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes. These expression data are used in the paper to show that there are marked differences in mRNA expression between loci in the open and closed chromatin compartments. |
| 1657 | GSE49583 |
Profile | tumor-stroma crosstalk drives pancreatic carcinogenesis we used time-resolved genome-wide transcriptional profiling to analyse changes caused by co-exposure of pancreatic tumor and stellate cells |
| 1658 | GSE30201 |
Profile | A role for reduced ribosomal protein gene dosage in both DBA and 5q- MDS suggests that other forms of MDS might also involve altered expression of ribosomal protein genes. We used microarrays to interrogate the expression of ribosomal proteins from purified hematopoietic stems cells from patients with low risk myelodysplastic syndrome and age-matched healthy controls. |
| 1659 | GSE15175 |
Profile | Human induced pluripotent stem (iPS) cells have previously been derived from somatic cells using viral vectors that integrate transgenes into the genome. Genomic integration however, can allow persistent leaky expression of the transgenes and can create insertional mutations, thus limiting the utility of these cells for both research and clinical applications. Here, we describe the derivation of human iPS cells free of vector and transgene sequences using non-integrating oriP/EBNA1-based episomal vectors. The resulting iPS cells are similar to human embryonic stem (ES) cells in both proliferative and developmental potential. These results demonstrate that reprogramming of human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors, and removes one important obstacle to the clinical applications of these cells. |
| 1660 | GSE26027 |
Profile | With a view to developing novel biomarkers of the efficacy of radiotherapy in patients with rectal cancer we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. Repeat biopsy did not increase toxicity. Radiotherapy induced the expression of genes involved in oxidative stress, signal transduction, apoptosis and immune response. |
| 1661 | GSE8049 |
Profile | Recent studies demonstrated that tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We established glioblastoma stem-like (GS-) cell cultures from 9 different glioblastomas 8 of which generated stably expandable cell lines. Analyzing GS-cell cultures, we discovered two clearly discernable phenotypes. Microarray analysis showed that the 4 GSf cell lines shared expression profiles dominated by genes involved in nervous system development and neuropeptide signaling, while the 5 GSr lines shared expression signatures enriched for extracellular matrix-proteins. Keywords: Cell line comparison |
| 1662 | GSE15227 |
Profile | Asporin also known as periodontal ligament-associated protein 1 (PLAP1), is a member of the family of small leucine-rich proteoglycan (SLRP) family. It is present within the cartilage extracellular matrix (ECM), and is reported have a genetic association with osteoarthritis. Its D14 allele has recently been found to be associated with lumbar disc degeneration in Asian subjects. There have been no studies, however, of this gene’s normal immunohistochemical localization within the human intervertebral disc, nor of expression levels in Caucasian individuals with disc degeneration. Studies were approved by our human subjects Institutional Review Board. Methods included immunohistochemical localization of asporin in the disc of humans and the sand rat (a small rodent with spontaneous age-related disc degeneration), and Affymetrix microarray analysis of asporin gene expression in vivo and in vitro. mmunohistochemical studies of human discs revealed that some, but not all, cells of the outer annulus expressed asporin. Fewer cells in the inner annulus contained asporin, and it was rarely present in cells in the nucleus pulposus. Similar patterns were found for the presence of asporin in lumbar discs of sand rats. Substantial relative gene expression levels were seen for asporin in both disc tissue and in annulus cells grown in three-dimensional culture. More degenerate human discs (Thompson grade 4) showed higher expression levels of asporin than did less degenerate (grade 1, 2 and 3) discs, p = 0.004. In the discs of Caucasian subjects studied here, and in the sand rat, greater immunolocalization levels were found in the outer compared to inner annulus. Localization was rare in the nucleus. Gene expression studies showed greatest expression of asporin in the more degenerate human discs in vivo. |
| 1663 | GSE15090 |
Profile | Muscle biopsies from biceps and deltoid were taken from 5 patients with FSHD 5 asymptomatic carriers and 5 normal controls. The genome-wide expression patterns were compared using Affymetrix U133 Plus 2.0 chips. Keywords: Facioscapulohumeral, FSHD, muscular dystrophy |
| 1664 | GSE32727 |
Profile | The newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation. |
| 1665 | GSE43862 |
Profile | Hyperthermia (HT) is widely used to treat patients with various cancers. In general HT elicits a wide spectrum of stress responses, such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown. The effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in human oral squamous cell carcinoma HSC-3 cells were investigated using an Affymetrix GeneChip system. |
| 1666 | GSE33585 |
Profile | The experiment aims to identify transcriptional effects of Infliximab (an anti-TNF antibody) and CDP870 on human cell lines Results were generated using 3 timepoints: 0h 6h, and 24h with each stimuli. |
| 1667 | GSE27018 |
Profile | Personalized biological insights into heterogeneous tumors such as breast cancer could improve clinical management. While genomic analysis has contributed significantly towards dissecting breast cancer heterogeneity, limitations in clinical application are partly rooted in the inter-tumor variability arising from a largely uncharacterized interactive exchange between diverse cell types in the tumor microenvironment. Here we first identified a common response signature to stromal coculture across breast cancer of varying clinicopathologic phenotypes. Proximity to fibroblasts resulted in gene transcript alterations of >2-fold for 107 probe sets, collectively designated as Fibroblast Triggered Gene Expression in Tumor (FTExT). Prominent features of tumor cell response included transcript repression related to biofunctions encompassing inflammatory signaling, cell movement, cell death, and cell growth and proliferation. In an evaluation of intertumor heterogeneity, the FTExT classifier stratified moderate and high histopathologic grade breast cancer according to clinical outcome (dataset 1, n=401, p=0.031; dataset 2, n=200, p=0.013), delineating a novel phenotype of stromal crosstalk underlying the prognostic potential of tumor grade. Extending correlative data through functional analysis of stromal-epithelial cocultures of both malignant and nonmalignant derivation, significant differences in cell cycle regulation, rate of proliferation, resistance to therapy-induced apoptosis, and growth arrest were observed in FTExT-based subgroups. Instead of a stromal impact that is uniformly cancer promoting, our data demonstrate striking variability in tumor cell response that directly contributes to contrasting functional aggressiveness of malignant breast tissue. Our findings uniquely reveal dynamically interacting paracrine components underlying the molecular and functional heterogeneity of breast cancer, thus presenting novel opportunities for tumor targeting. |
| 1668 | GSE9757 |
Profile | In addition to the estrogen responsive element (ERE)-dependent gene expression E2-ERalpha regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERalpha signaling is unclear. Our studies in infected ER-negative cell models with an ERalpha demonstrated that genomic responses assessed by microarrays from the alter cellular growth, death or motility. Keywords: MDA-MB-231 cells |
| 1669 | GSE12630 |
Profile | The tissue of origin form metastatic tumors is sometimes difficult to identify from clinical and histologic information. Gene expression signatures are one potential method for identifying the tissue of origin. In the development of algorithms to identify tissue of origin a collection of human tumor metastatic specimens with known primary sites or primary tumors with poor differentiation are very useful in identifying gene expressions signatures that can classify unknown specimens as to the tissue of origin. Here we describe a series of 276 such tumor specimens used for this purpose. The specimens are poorly differentiated, undifferentiated and metastatic specimens from tumors of the following types/tissues of origin: breast, liver, non-Hodgkin's lymphoma, non-small cell lung cancer, ovary, testicular germ cell, thyroid, kidney, pancreas, colorectal cancer, soft tissue sarcoma, bladder, gastric cancer, prostate and melanoma. This data combined with other series (GSE2109) was used to validate a proprietary tumor classification algorithm of Pathwork Diagnostics. The results of this validation set (N = 545 CEL files) showed that the algorithm correctly identified the tissue of origin for 89.4% of the specimens. Guidelines for commercial use: http://pathworkdx.com/GSE12630_request.html |
| 1670 | GSE18965 |
Profile | Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from asthmatic children fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n=36) healthy atopic (n=23) and healthy non-atopic controls (n=53) were investigated by microarray, gene expression and silencing, transcript regulation analysis and ability to close mechanical wounds. Results: Wound repair of AEC from healthy and atopic children were not significantly different and were both faster than AEC from asthmatics. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by qPCR and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in non-asthmatic AEC inhibited wound repair, while addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5’, 2’deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells. |
| 1671 | GSE38713 |
Profile | Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission. We performed a whole-genome transcriptional analysis of colonic biopsies from patients with histologically active and inactive UC as well as non-inflammatory controls. |
| 1672 | GSE30566 |
Profile | We identified 1700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples. |
| 1673 | GSE48521 |
Profile | To investigate fetal gene expression in obese compared to lean women in the second trimester by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA Analysis of paired data from obese cases and lean controls revealed differential expression of 205 genes. Functional analysis of differentially expressed genes suggested down-regulation of apoptosis in fetuses of obese women, particularly within nervous system pathways involving the cerebral cortex, and activation of pro-estrogenic, pro-inflammatory transcriptional regulators. |
| 1674 | GSE25634 |
Profile | To understand the molecular mechanisms underlying the congenital anomalies observed in patients with Trisomy 18 we compared gene expression in uncultured amniotic fluid supernatant samples from second trimester fetuses with Trisomy 18 and from euploid controls. Analysis of differential expression using both individual-gene and gene-set or pathway methods indicated disrupted function in ion transport, MHCII/T-cell mediated immunity, DNA repair, G-protein mediated signaling, kinases, and glycosylation. Significant down-regulation of genes involved in adrenal development was also identified in the trisomic fetuses, possibly explaining both the abnormal maternal serum estriols and the pre- and postnatal growth restriction found in this condition. |
| 1675 | GSE20677 |
Profile | A transcriptome-wide functional analysis of gene expression implicated multiple signaling pathways specific for Au-NP oligonucleotide complexes. Exposure to Au-NP oligonucleotide complexes is also accompanied by marked activation of immune cells. |
| 1676 | GSE9761 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1677 | GSE16715 |
Profile | Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by aa 1.5 Mb microdeletion on human chromosome 7. Although the molecular cause of the disorder is well-established little is known about the global impact of the deletion on gene expression. Here we profiled the transcriptomes of fibroblast cell lines from 8 young girls with WBS, and 9 sex- and age-matched control individuals Keywords: disease state analysis, gene expression profiling |
| 1678 | GSE12438 |
Profile | Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition. Keywords: Androgen receptor, histone deacetylase, prostate cancer, dose response |
| 1679 | GSE19643 |
Profile | Mesenchymal stem cells (MSCs) are a multipotent cell type that can differentiate into non-hematopoietic cells such as adipocytes. Adipocyte tissue is central to regulate energy balance. PGC-1 alpha controls several aspects of mitochondrial biogenesis. However, roles of PGC-1 alpha in brown fat differentiation of MSCs remain uncertain. To investigate roles of PGC-1 alpha in brown fat differentiation immortalized human MSCs were used for all experiments. The changes in genetic profiling between MSCs and PGC-1 alpha-expressing MSCs were analyzed by microarray analysis. The genetic profiling of PGC-1 alpha-expressing MSCs shows the significant increase of genes related to mitochondrial functions and lipid metabolism compared to that of MSCs. When expressed in MSCs, PGC-1 alpha activates a robust mitochondrial biogenesis and respiration. The expression of thermogenic markers, such as cytochrome C and complex II, was significantly increased in MSCs with treatment of adenovirus expressing PGC-1 alpha. Our microarray results also indicate that genetic pattern of PGC-1 alpha-expressing MSCs is very closed to that of adipose tissues. |
| 1680 | GSE17340 |
Profile | The human seminal plasma is a potential source of biomarkers for male reproductive disorders. A tissue-profiling analysis of the main organs participating in the secretion of this body fluid was conducted to identify tissue-specific genes along the male reproductive tract. |
| 1681 | GSE1786 |
Profile | Needle biopsies were obtained from the vastus lateralis muscle of 6 healthy sedentary, 67±2.5 year-old males before and after 3 months of training. Keywords: other |
| 1682 | GSE36179 |
Profile | Cytoplasmic RNA bound to eIF4E was pulled down from MDA-MB-231 cells to determine the influence of radiation on eIF4E mRNA binding |
| 1683 | GSE18043 |
Profile | Human adult mesenchymal stromal cells (hMSC) have the potential to differentiate into chondrogenic adipogenic or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptomic analysis, we found that integrin alpha5 (ITGA5) expression is upregulated during dexamethasone-induced hMSCs osteoblast differentiation. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers as well as in vitro osteogenesis in hMSCs. Downregulation of endogenous ITGA5 using shRNA blunted osteoblast marker expression and osteogenic differentiation. Pharmacological and molecular analyses showed that the enhanced hMSCs osteoblast differentiation induced by ITGA5 was mediated by activation of FAK/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of ITGA5 using a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. We also demonstrate that hMSCs engineered to over-express ITGA5 exhibited a marked increase in their osteogenic potential in vivo. These findings not only reveal that ITGA5 is required for osteoblast differentiation of adult human MSCs but also provide a novel targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs, which may be used for tissue regeneration in bone disorders where the recruitment or capacity of MSCs is compromised. Keywords: Time course of osteogenic differentiation processes |
| 1684 | GSE7708 |
Profile | Androgen Receptor (AR) is essential for the growth and progression of prostate cancer in both hormone-sensitive and hormone-refractory disease. We have designed a sequence-specific DNA binding polyamide (1) that targets the consensus androgen response element (ARE). This polyamide binds the PSA promoter ARE inhibits androgen-induced expression of PSA and several other AR-regulated genes in cultured prostate cancer cells, and reduces AR occupancy at the PSA promoter and enhancer. Down-regulation of PSA by this polyamide was comparable to that produced by the synthetic anti-androgen bicalutamide (Casodex) at the same concentration. Genome-wide expression analysis reveals that a similar number of transcripts are affected by treatment with the polyamide and with bicalutamide. Direct inhibition of AR-DNA binding by sequence-specific DNA binding small molecules could offer an alternative approach to antagonizing AR activity. A polyamide (2) that targets a different DNA sequence is included as a control. Keywords: Gene expression changes in cultured LNCaP cells after DHT-stimulation and various treatment conditions |
| 1685 | GSE6960 |
Profile | We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 μM) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Keywords: Dose response |
| 1686 | GSE30141 |
Profile | Transcriptional expression data for a bioactive small molecule for mechanism identification. |
| 1687 | GSE20060 |
Profile | Oxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin. |
| 1688 | GSE31172 |
Profile | In this study to obtain the biological impact of the mutated U2AF35, HeLa and TF-1 cells were retrovirally transduced with either mock, wild-type or S34F mutant of U2AF35, and Expression array was performed. |
| 1689 | GSE11670 |
Profile | Iron plays a central role in the regulation of many cellular functions. Dysregulation of its metabolism leads an iron overload situation and iron depletion leads to an inhibition of cell proliferation. Recent reports demonstrated that ICL670 (Novartis) acts as a potent NF-kappa-B inhibitor and improves hematological data in a subset of MDS patients (Cilloni et al Haematologica, s1: 238, 2007). However, the precise mechanism of anti-cancer effect of ICL670 is still uncertain. To evaluate the effect of ICL670, and to identify the moleclular pathways responsible for the observed reduced transfusion requirement during chelation therapy, we performed gene expression profiling to focus on the pathway involved in the anti-cancer effect of ICL670. |
| 1690 | GSE2004 |
Profile | Normal kidney liver, spleen, and Universal RNA from Stratagene were expression profiled across five centers (UCLA, Duke, TGen, Children's National Medical Center in Washington, DC, and University of Pennsylvania) using the Affymetrix, spotted Operon, Agilent, and Amersham arrays to identify differences in expression between microarray platforms as well as centers. To compare the four microarray platforms as well as the reproducibility across the centers. There will be expression differences between the five centers. The following array types were profiled at the centers: UCLA: Affymetrix, Amersham, Agilent TGen: Affymetrix (3000 scanner) Children's: Affymetrix (2500 scanner) Duke: Operon Oligo University of Penn.: Affymetrix Series_author: Consortium,,Cross Platform Keywords: other |
| 1691 | GSE12090 |
Profile | This study aims to compare gene expression profiles of chromophobe renal cell carcinoma (RCC) and benign oncocytoma aiming at identifying differentially expressed genes. |
| 1692 | GSE16179 |
Profile | These data provide scientific information to understand the mechanism of action of lapatinib resistance in HER2-positive patients and to test the combination of HER2-targeted agents and GSK1363089 (foretinib) in the clinic by using an acquired lapatinib-resistant cell line. |
| 1693 | GSE16118 |
Profile | Echo-contrast agents enhance the echogenicity of ultrasound and have been clinically used for diagonosis in current medical fields. Here the combined effects of Sonazoid, an echo-contrast agent, and ultrasound on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with Sonazoid (0.05%; Sonazoid only), ultrasound (0.3 W/cm2 for 1 min; ultrasound only) and the combination of Sonazoid and ultrasound (0.05% Sonazoid plus ultrasound 0.3 W/cm2 for 1 min; Sonazoid + Ultrasound) and followed by incubation for 3 h at 37°C. The percentage of DNA fragmentation 6 h after treatment was 5.8 ± 1.0 (mean ± SD, n = 3), 6.0 ± 0.4, 13.5 ± 1.0, and 18.3 ± 2.3 in cells treated with control, Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively. Of approximately 47,000 probe sets analyzed, probe sets that were differentially expressed by a factor 2.0 or greater were 40, 184 and 144 in cells treated with Sonazoid only, ultrasound only and Sonazoid + Ultrasound, respectively. |
| 1694 | GSE35830 |
Profile | In this study we examined the influence of seminal plasma on gene expression in human Ect1 ectocervical epithelial cells and the extent to which recombinant TGFβ3 elicits comparable changes. Ect1 cells were incubated with recombinant human TGFβ3 (5 ng/ml), 10% pooled human seminal plasma (v/v), or medium alone for 10h. RNA was reverse transcribed into cDNA and hybridized to Affymetrix GeneChip® Human Genome U133 plus 2.0 microarrays (Affymetrix, Santa Clara, CA). Exposure of Ect1 cells to seminal plasma resulted in differential expression of a total of 3955 probe sets, identified using high stringency criteria with MAS 5.0 analysis. These corresponded to 1338 genes up-regulated and 1343 genes down-regulated by seminal plasma. TGFβ3 treatment of Ect1 cells resulted in differential expression of 884 probe sets, corresponding to 346 up-regulated genes and 229 down-regulated genes. The genes differentially regulated by seminal plasma included several genes associated with cytokine–cytokine receptor interaction, TGFβ signalling, JAK/STAT signalling or VEGF signalling pathways, as specified by the KEGG database. Of 47 genes in these families, 17 (36.1%) were similarly regulated by both seminal plasma and TGFβ3. These data, together with additional experiments showing all three TGFβ isoforms can regulate inflammatory cytokine expression in Ect1 cells, identify TGFβ isoforms as key agents in seminal plasma that signal induction of pro-inflammatory cytokine synthesis in cervical cells. |
| 1695 | GSE48441 |
Profile | DNA microarray analysis revealed that the genes related to cell cycle regulation were significantly induced at non- and sub-lethal concentrations (i.e. 0.05-6 µM), while the common feature of heavy metal toxicity such as oxidative damage and following increase in glutathione, heat shock proteins, and metallothionein were confirmed at high concentrations (i.e., 6-40 µM). The concentration dependent modulation of gene expression (induction of cell cycle genes, induction of cell cycle arrest genes and apoptotic genes) following exposure to arsenic was further supported by acceleration of cell proliferation, ROS generation, and cytotoxicity. Furthermore, three cell cycle genes (i.e., CDC25B, UBE2C, and PTTG1) were proposed as marker genes of inorganic arsenic exposure. Those results indicated the potential pro-carcinogenic actions of inorganic arsenic occur in environmentally relevant exposures (as low as 0.07 µM). |
| 1696 | GSE4567 |
Profile | Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity however, the mechanism remains unknown. In this study, we hypothesized that the ultrafine fraction of ambient pollutant particles would cause endothelial cells dysfunction. We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine Chapel Hill particles (UFP) (100μg/ml) or vehicle for 4h with Affymetrix HG U133 Plus 2.0 chips (N = 4 each). Using an unpaired t-test (p <0.01, 5% false discovery rate) we found 426 unique genes to be differentially expressed with 320 upregulated genes and 106 downregulated genes. Among these genes, we noted upregulation of genes related to coagulation-inflammation circuitry including tissue factor (F3), coagulation factor II receptor-like 2 (F2RL2, PAR3), interleukin (IL)-6 and IL-8. Upregulation of these genes were independently confirmed by RT-PCR and/or protein release. Genes related to the CXC chemokine family that have been implicated in the pathogenesis of vascular disease were upregulated, including MCP-1 (2.60 fold), IL-8 (2.47 fold), CXCL1 (1.41 fold), CXCL2 (1.95 fold), CXCL3 (2.28 fold) and CXCR4 (1.30 fold). In addition, genes related to clotting independent signaling of F3 were also differentially expressed, including FOS, JUN and NFKBIA. Treatment of HPAEC with UFP for 16 hours increased the release of IL6 and IL8 by 1.9-fold and 1.8-fold respectively. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL6 and IL8 release by 30% and 70% respectively. Thus using gene profiling, we uncovered that UFP may induce vascular endothelial cells to express genes related to clotting and angiogenesis. These results provide a novel hypothesis that PM may cause cardiovascular adverse health effects via induction of tissue factor in vascular endothelial cells which then triggers clotting dependent and independent downstream signaling. Keywords: particle treatment |
| 1697 | GSE39843 |
Profile | CF's physiopathology is poorly explained by the mutation alone. The oxydative stress could be a major factor of this illness . Study its impact on transcriptome's CF cell line could be ameliorate our understanding of the evolution of cystic fibrosis. we used microarray technology to evaluate under oxydative stress the transcriptional state of an epithelial lung cell issued from a human with cystic fibrosis and to identify a set of modulated genes associated to survival cell processes. |
| 1698 | GSE17549 |
Profile | Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion. To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction) and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations. |
| 1699 | GSE6088 |
Profile | Atherosclerosis is the major cause of death in industrialized countries. This disease has initially been characterized as a lipid disorder but current concepts argue for an inflammatory disease, which develops in the background of hypercholesterolemia and other risk factors. In response to initial events of atherosclerosis formation, such as LDL-deposition in the subendothelial space, monocytes and T cells interact with the vessel wall. However, little is known about the properties and the behavior of these cells in this context. Using familial hypercholesterolemia (FH) as a model we demonstrate substantial differences in the gene expression of freshly isolated human monocytes and T lymphocytes. In FH monocytes we found an increased uptake of oxidized LDL, elevated amounts of scavenger receptors and adhesion molecules, and differences in the regulation of intracellular lipoprotein metabolism compared to monocytes from healthy individuals. Furthermore, the monocyte subpopulation of CD14+/CD16+ cells is less frequent in FH but exhibits significantly higher levels of CD11c and CD29 which increases the likelihood for their transmigration through the endothelial layer. The presence of increased amounts of CD69 in T lymphocytes from FH patients suggests that these cells are more activated than control cells. Our results indicate that some important steps of atherosclerosis formation already take place in circulating blood cells which extends current atherosclerosis models to the plasma compartment. Keywords: atherosclerosis, T cells, Familial Hypercholesterolemia |
| 1700 | GSE6004 |
Profile | Papillary thyroid cancers (PTC) that invade into local structures are associated with a poor prognosis but the mechanisms for PTC invasion are incompletely defined limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison to the central regions of primary PTCs, the invasive fronts overexpressed TGFbeta, NFkappaB and integrin pathway members, and regulators of small G-proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 35 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required for the development and maintenance of both a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is a common mechanism of PTC invasion and that vimentin regulates thyroid cancer EMT in vitro. Keywords: Genetic modification |
| 1701 | GSE7292 |
Profile | The possibility to deliver radioisotopes directly to tumor cells by using monoclonal antibodies has become a promising concept for the elimination of small tumor nodules or single disseminated tumor cells. The alpha-particle emitter Bismut-213 which has a high linear energy transfer and a very short path length appears to be able to kill cells by only few nuclear hits. Bismut-213 based alpha-immunotherapy treatment is currently proved in clinical trials for AML NHL and preclinically for CLL and multiple myeloma. Because little is known about the biological effects of alpha radiation we examined the molecular effects of the alpha emitter Bismut-213 in malignant and normal B-cells. In this study, we used the cell line Karpas 422 (K422) which had been derived from a malignant B-cell Non-Hodgkin’s lymphoma as well as normal primary CD19+ B-cells which had been selected immunomagnetically from peripheral blood. For the delivery and binding of the alpha emitter we used the monoclonal antibody rituximab which targets the CD20 receptor of malignant and normal B-cells. The lymphoma cell line K422 was incubated in vitro with Bismut-213-CD20 with 100 µCi and 200 µCi respectively, for 46 min (1 half life time of the alpha emitter) or 24 h. Immunomagnetically isolated CD19+ cells from healthy donors were incubated in vitro with Bismut-213-CD20 with 100 µCi or 200 µCi, for 46 min. Gene expression profiles of irradiated cells were analysed using cDNA oligonucleotide arrays (Affymetrix Human Genome Focus Arrays) comprising 8,793 genes and compared with those from untreated control cells. Following normalization significantly altered genes were identified by using the variance stabilization normalization (VSN) method and the significance analysis of microarrays (SAM) algorithm. Differentially expressed genes were defined to exhibit a fold change of 1,4 and higher or 0,7 and lower and a q-value of 5% or lower compared to the genes of the untreated control cells. Irradiated K422 cells with 100 µCi showed 42 differential expressed genes after 46 minutes (one half life time) and 451 deregulated genes after exposure of 24 hours. A similar response could be observed at an exposure of 200 µCi (50 differentially expressed genes after 46 min; 485 genes after 24 h). Hence, a severe radiation induced response could not be detected before 24 hours. 200 µCi irradiated CD19+ cells showed 67 differentially expressed genes after 46 minutes compared to the untreated CD19+ cells (for 100 µCi: 42 differentially expressed genes). By performing cluster analyses the irradiated cells exhibited a distinct homogenous molecular phenotype in comparison to not irradiated cells. Alpha irradiated cells showed transcriptional activation of DNA repair genes. Furthermore, both examined cell types showed up-regulated genes which are known to play a role in general and oxidative stress response. Surprisingly, up-regulation of interferon-stimulated genes in K422 cells could be observed. Because of the transcriptional activation of genes regulating the G1-S- cell cycle transition the supposition came up that the irradiated K422 do progress into the S-phase of the cell cycle and arrest in the S- or G2/M-phase. In contrast to the K422 cells the primary CD19+ B-cells revealed transcriptional activation of cell cycle inhibitors which is an already known reaction following ionizing radiation but no apoptosis associated genes could be observed. In spite of the massive cytotoxic damages which are assumed referring to the gene expression data the K422 cells appear to be able to activate several defense mechanisms in a precise manner. Hence, the malignant K422 cells exhibit a larger amount as well as more various responses than the CD19+ cells. This might be due to the tumorigenic transformation of the malignant cells that exhibit probably more effective defense strategies than the CD19+ cells. The balance between the therapeutic effect of alpha radiation on malignant cells and the damaging effect on normal cells is an essential issue and it is of important clinical relevance concerning radioimmunotherapy with alpha radiation. Keywords: time course and dose dependency |
| 1702 | GSE7216 |
Profile | Normal human epidermal keratinocytes (NHEK) from neonatal foreskin were cultured in serum-free EpiLife medium with human KC growth supplement (0.2% bovine pituitary extract (v/v) 5ug bovine insulin, 5ug/ml bovine transferrin, 0.5ng/ml human EGF, and 0.18 ug/ml hydrocortisone) from Cascade Biologics. Cultures were treated with recombinant cytokines from R&D Systems. J Immunol. 2007 Feb 15;178(4):2229-40. Keywords: cytokine response |
| 1703 | GSE11418 |
Profile | Human umbilical vein endothelial cells (HUVECs) formed capillary structures when co-cultured with normal human dermal fibroblasts (NHDFs). HUVEC competence and NHDF supportiveness of cord formation were found to be highly cell-passage dependent with the early passage cells forming more angiogenic cord structures. We thus profiled gene expression in NHDFs with different passages to understand the molecular mechanisms underlying the in vitro angiogenesis control. Keywords: Time course |
| 1704 | GSE19728 |
Profile | The aim of the study was to identify significant alterations in genes and molecular functional pathways in comparison with normal and ACM tissue and detect the marker genes to differentiate the different stage astrocytomas |
| 1705 | GSE16972 |
Profile | Rationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease. Objectives: Among inflammatory cell types alveolar macrophages appear to have a key role in initiating and/or sustaining disease progression. These cells are derived from peripheral monocytes. Identification of disease and cell type specific gene expression profiles can be revealing and also practically useful in order to diagnose and characterize disease progression and the effect of drug treatment. Methods: We used Affymetrix microarrays to obtain gene expression data of alveolar macrophages and circulating monocytes of COPD and healthy control patients. The microarray results were confirmed by quantitative real-time polymerase chain reaction in multiple patient collections. Measurements and Main Results: We have identified gene sets specifically associated with COPD in alveolar macrophages and also in monocytes. Immune function, responses to stimuli, and cell death related genes appear to be impacted in both cell types. Remarkably, there is an overlapping gene set between the two cell types. Conclusions: Taken together, our data show that COPD-specific gene signatures can be identified and validated, and that the disease also affects peripheral monocytes. Moreover, monocytes and alveolar macrophages carry overlapping gene expression signatures. Our findings further support the notion that altered responsiveness to stimuli is the key characteristic of alveolar macrophages and also of their precursors, peripheral monocytes. |
| 1706 | GSE22771 |
Profile | High anaplastic lymphoma kinase (ALK) protein levels may be correlated with an unfavorable prognosis in neuroblastoma (NBL) patients regardless of ALK mutation status. We therefore examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated (MUT) and wild type (WT) NBL cell lines. Six of the nineteen NBL cell lines had a point mutation and four an amplification of the ALK gene. ALK amplified cell lines showed similar ALK levels and ALK inhibitor sensitivity as WT cell lines and were therefore co-analyzed. The ALK mRNA (p=0.043), ALK 220 kDa (p=0.009) and ALK 140 kDa (p=0.025) protein levels were higher in ALK mutant (n=6) than WT cell lines (n=13). ALK mRNA and protein levels significantly correlated with ERK1 and ERK2 protein levels, and also with PHOX2B mRNA levels, a neural differentiation marker which is mutated in NBL. Response to ALK inhibitor TAE684 was also significantly correlated with ALK levels. ALK mutant cell lines (n=4) demonstrated a higher sensitivity towards ALK inhibitor TAE684 (14.9 fold more sensitive, p=0.004) than eight WT cell lines. These results underline the importance of ALK mutations but also ALK levels for response to ALK inhibitors in NBL cell lines. Furthermore, the strong correlation of PHOX2B and ALK suggests that neural differentiation stage may be correlated with ALK levels in neuroblastoma. These data will enhance understanding of ALK inhibitor response in future patient trials. |
| 1707 | GSE7959 |
Profile | The objective was to identify the molecular mechanisms responsible for in vitro and in vivo efficacy of an anti-MYCN peptide nucleic acid on a preclinical model of alveolar rhabdomyosarcoma. Cells treated with a anti-MYCN PNA exhibit growth arrest and apoptosis and in vivo tumor growth is blocked. Keywords: oncogene inhibition |
| 1708 | GSE23117 |
Profile | To study the gene expression profile of salivary glands with varying degrees of inflammation in Sjogren's and non Sjogren's patients |
| 1709 | GSE30501 |
Profile | PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation oncogenic transformation, cell lineage specification, migration, and survival. In our previous study, we found that PAX2 is highly expressed in low-grade ovarian serous carcinoma, but its expression in clear cell, endometrioid, and mucinous cell ovarian carcinomas have not been studied. More importantly, the functional role of PAX2 in ovarian cancer is not known. Downregulation of PAX2 in PAX2-expressing ovarian cancer cells inhibits cell proliferation and migration. This growth inhibition is due to the upregulation of the tumor suppressor gene G0S2 and subsequent induction of apoptosis. The PAX2 pathway thus represents a potential therapeutic target for PAX2-expressing ovarian carcinomas. |
| 1710 | GSE15156 |
Profile | To identify early processes in carcinogenesis we used an in vitro model, based on the initiating event in cervical cancer, human papillomavirus (HPV) transformation of keratinocytes. We compared gene expression in primary keratinocytes (K) and HPV16-transformed keratinocytes from early (E) and late (L) passages, and from benzo[a]pyrene treated L cells (BP). The transformed cells exhibit similar transcriptional changes to clinical cervical carcinoma. We revealed a contraction in expression of the apoptotic network during HF1 cell transformation, which affected the ability of L and BP cells to execute apoptosis, but did not lead to resistance to apoptotic stimuli. The contraction in the apoptotic machinery during the process of transformation was accompanied by a switch from apoptosis to necrosis in response to CDDP. The shrinkage of the pro- and anti-apoptotic networks appears to be part of a general contraction in the number of genes transcribed in L and BP cells. We also identified a large group of genes with induced expression, which are involved in cell metabolism and cell cycle, suggesting increased investment of the transformed cell in cellular proliferation. We hypothesize that the decrease in expression of many diverse pathways, including the pro- and anti-apoptotic networks, cuts the energy requirements for cell maintenance, allowing energy to be diverted towards rapid cell proliferation. This study supports the hypothesis that the process of cancer transformation may be accompanied by a shift from apoptosis to necrosis. |
| 1711 | GSE19888 |
Profile | We demonstrate that the G protein Gi3 is the cellular target of the adenosine A3 receptor (A3R). By using a cell permeable peptide comprising the C-terminal end of Gαi3 fused to an importation sequence (ALL1) as a selective inhibitor of Gi3 signaling we show that by coupling to Gi3, the A3R stimulates multiple signaling pathways in human mast cells, leading to upregulation of cytokines, chemokines and growth factors.Following contact with activated T cell membranes, endogenous adenosine binds to and activates the A3R, resulting in Gi3-mediated signaling. Specifically, the majority of ERK1/2 signaling initiated by contact with activated T cell membranes, is mediated by Gi3, giving rise to ALL1-inhibitable cellular responses. These results unveil the physiological GPCR that couples to Gi3 and establish the important role played by this G-protein in inflammatory conditions that involve adenosine-activated mast cells. We used microarrays to detail the effect of ALL1 on gene expression of HMC-1 cells activated directly by the A3 receptor, or by contact with activated T cell membranes. |
| 1712 | GSE42733 |
Profile | The study of the roles of macrophages in the microenvironment of cancer cells (tumor-associated macrophages TAM) has gained deep insight over the recent years. Here, we describe gene expression profile of chronic lymphocytic leukemia (CLL)-associated macrophages, also called nurse-like cells (NLC), derived from in vitro co-cultures system. We define these NLC as M2-oriented, TAM-like specific subset of macrophages, with very few inter-individual variations in gene expression profiles. |
| 1713 | GSE23368 |
Profile | C/EBPβ (CCAAT enhancer binding protein) is a transcription factor that plays a crucial role in survival and transformation of ALK+ anaplastic large cell lymphoma (ALCL). The aim of this study was to identify the downstream targets of C/EBPβ responsible for ALK-mediated oncogenesis. C/EBPβ was knocked down in ALK+ ALCL cell lines with a C/EBPβ-shRNA followed by gene expression profiling (GEP). GEP analysis revealed a reproducible signature of genes that were significantly regulated by C/EBPβ. Classification into biological categories revealed overrepresentation of genes involved in the immune response, apoptosis and cell proliferation. Transcriptional regulation by C/EBPβ was found in 6 of 11 (BCL2A1, G0S2, TRIB1, S100A9, DDX21 and DDIT4) genes investigated by chromatin immunoprecipitation. We demonstrated that BCL2A1, G0S2 and DDX21 play a crucial role in survival and proliferation of ALK+ ALCL cells. DDX21, a gene involved in rRNA biogenesis, was found differentially overexpressed in primary ALK+ ALCL cases. All three candidate genes were validated in primary ALCL cases by either immunohistochemistry or RT-qPCR. In conclusion, we identified and validated several key C/EBPβ-regulated genes with major impact on survival and cell growth in ALK+ ALCL, supporting the central role of C/EBPβ in ALK-mediated oncogenesis. |
| 1714 | GSE3307 |
Profile | Summary: Genetic disorders of muscle cause muscular dystrophy and are some of the most common inborn errors of metabolism. Muscle also rapidly remodels in response to training and innervation. Muscle weakness and wasting is important in such conditions as aging, critical care medicine, space flight, and diabetes. Finally, muscle can also be used to investigate systemic defects, and the compensatory mechansisms invoked by cells to overcome biochemical and genetic abnormalities. Here, we provide a 13 group data set for comparative profiling of human skeletal muscle. Groups studied are: Normal human skeletal muscle, Acute quadriplegic myopathy (AQM; critical care myopathy), Juvenile dermatomyositis (JDM), Amyotophic lateral sclerosis (ALS), spastic paraplegia (SPG4; spastin), Fascioscapulohumeral muscular dystrophy (FSHD), Emery Dreifuss muscular dystrophy (both X linked recessive emerin form; autosomal dominant Lamin A/C form), Becker muscular dystrophy (partial loss of dystrophin), Duchenne muscular dystrophy (complete loss of dystrophin), Calpain 3 (LGMD2A), dysferlin (LGMD2B), FKRP (glycosylation defect; homozygous for a missense mutation). U133A and U133B microarrays are both available. Hypothesis: This data set is able to define biochemical pathways that are either specific for a disease group, or shared between disease groups. For example, this data set has been used to determine the biochemical pathway perturbations that are shared between the two different types of Emery Dreifuss muscular dystrophy (lamin A/C, and emerin). Specific Aim: The specific aim of this study is to determine the disease-specific transcriptional profiles of these 13 patient groups, and to determine if these expression fingerprints provide either pathophysiology or diagnostic information for these diseases. Some of the groups in this large data set have been reported previously using U95A microarrays, as follows: Juvenile dermatomyositis (JDM): Tezak Z, Hoffman EP, Lutz JL, Fedczyna TO, Stephan D, Bremer EG, Krasnoselska-Riz I, Kumar A, Pachman LM. Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis: a novel model of pathogenesis. J Immunol. 2002 Apr 15;168(8):4154-63. PMID: 11937576 Duchenne muscular dystrophy (DMD) Chen YW, Zhao P, Borup R, Hoffman EP. Expression profiling in the muscular dystrophies: identification of novel aspects of molecular pathophysiology. J Cell Biol. 2000 Dec 11;151(6):1321-36. PMID: 11121445 Spastic paraplegia (SPG4, spastin): Molon A, Di Giovanni S, Chen YW, Clarkson PM, Angelini C, Pegoraro E, Hoffman EP. Large-scale disruption of microtubule pathways in morphologically normal human spastin muscle. Neurology. 2004 Apr 13;62(7):1097-104. PMID: 15079007 Acute quadriplegic myopathy (AQM): Di Giovanni S, Molon A, Broccolini A, Melcon G, Mirabella M, Hoffman EP, Servidei S. Constitutive activation of MAPK cascade in acute quadriplegic myopathy. Ann Neurol. 2004 Feb;55(2):195-206. PMID: 14755723 Fascioscapulohumeral muscular dystrophy (FSHD): Winokur ST, Chen YW, Masny PS, Martin JH, Ehmsen JT, Tapscott SJ, van der Maarel SM, Hayashi Y, Flanigan KM. Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet. 2003 Nov 15;12(22):2895-907. Epub 2003 Sep 30. PMID: 14519683 Keywords: muscle disease comparison |
| 1715 | GSE16447 |
Profile | We have analysed a family with an autosomal recessive type of tetraplegic cerebral palsy with mental retardation reduction of cerebral white matter, and atrophy of the cerebellum in an inbred sibship. Homozygosity mapping using SNPs was performed to identify the chromosomal locus for the disease. In the 14 Mb candidate region on chromosome 7q22, RNA expression profiling was used to select among the 203 genes in the area. |
| 1716 | GSE12868 |
Profile | ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T-cells, followed by extensive biochemical validation, reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind to several thousands target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC co-binds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs. |
| 1717 | GSE10196 |
Profile | YAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT). We used microarrays to detail the global program of gene expression to identify YAP target genes. PUBLICATION ABSTRACT: The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Since this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition (EMT), suggesting that this is a key feature of YAP signaling in mammalian cells. Keywords: vector vs. YAP comparison |
| 1718 | GSE17772 |
Profile | Conrad et al. Nature 456 344–349 (2008) have generated human adult germline stem cells (haGSCs) from human testicular tissue, which they claim have similar pluripotent properties to human embryonic stem cells (hESCs). Here we investigate the pluripotency of haGSCs by using global gene-expression analysis based on their gene array data and comparing the expression of pluripotency marker genes in haGSCs and hESCs, and in haGSCs and human fibroblast samples derived from different laboratories, including our own. We find that haGSCs and fibroblasts have a similar gene-expression profile, but that haGSCs and hESCs do not. The pluripotency of Conrad and colleagues’ haGSCs is therefore called into question. |
| 1719 | GSE21612 |
Profile | Current approaches to the preclinical investigation for novel cancer therapies rely heavily on the use of traditional cancer cell lines maintained in serum-containing conditions. The discrepancy between promising preclinical efficacy and clinical outcome of most novel anticancer agents emphasizes a need for developing predictive preclinical models that preserve the integrity of original patient tumors including cancer stem cell (CSC) compartment. In this study, we isolate and characterize CSCs from a non-small cell lung cancer cell line, NCI-H1299, by selectively propagating the cells in a stem-cell culture condition. Isolated CSCs proliferated as nonadherent spheroids, displayed capacity to differentiate and self-renew and exhibited higher tumorigenic potential compared to the parental cells. |
| 1720 | GSE26748 |
Profile | Cidofovir is an acyclic nucleoside phosphonate with strong antiviral activity against a broad spectrum of DNA viruses. Although it has previously been shown that cidofovir exerts an antiproliferative effect on HPV positive cells by the induction of apoptosis the exact mechanism of action remains to be unraveled. In order to study the activity of cidofovir against HPV, gene expression profiling was performed in cidofovir-treated and cidofovir-resistant SiHa cells by means of microarrays (HG-U133 Plus 2, Affymetrix). |
| 1721 | GSE31122 |
Profile | Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant CNS neoplasm whichprimarily occurs in children under three years of age. Due to poor outcomes with intense and toxicmultimodality treatment new therapies are urgently needed. Histone deacetylase inhibitors (HDIs)have been evaluated as novel agents for multiple malignancies and have been shown to function asradiosensitizers. They act as epigenetic modifiers and lead to re-expression of inappropriatelyrepressed genes, proteins, and cellular functions. Due to the underlying chromatin remodeling genemutation in ATRT, HDIs are ideal candidates for therapeutic evaluation. To evaluate the role of HDIsagainst ATRT in vitro, we assessed the effect of drug treatment on proliferation, apoptosis, and geneexpression. Additionally, we examined HDI pretreatment as a radiosensitization strategy for ATRT.MTS and clonogenic assays demonstrated that HDI treatment significantly reduces the proliferativecapacity of BT-12 and BT-16 ATRT cells. Also, the HDI SNDX-275 was able to induce apoptosis in bothcell lines and induced p21Waf1/Cip1 protein expression as measured by Western blot. Evaluation ofdifferential gene expression by microarray and pathway analysis after HDI treatment demonstratedalterations of several key ATRT cellular functions. Finally, we showed that HDI pretreatmenteffectively potentiates the effect of ionizing radiation on ATRT cells as measured by clonogenic assay.These findings suggest that the addition of HDIs to ATRT therapy may prove beneficial, especiallywhen administered in combination with current treatment modalities such as radiation. Keywords: ATRT; HDAC inhibitor; radiosensitization |
| 1722 | GSE9089 |
Profile | To understand the differentiation process of embryonic stem cells into hemangioblasts gene expression profiles of ES, EB and Blast cells (BL) were analyzed. Keywords: time course |
| 1723 | GSE20666 |
Profile | Chromosome 1 pericentric heterochromatin rearrangements : potent drivers of nuclear architecture perturbations and gene deregulation in human B cell lymphoma Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here we report the first evidence, that a distinct category of chromosomal translocation observed in human tumours – those targeting 1q12 satellite DNA - can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localised to the nuclear periphery and to arise as a consequence of long range ‘pairing’ between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localisation and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression by via long range epigenetic mechanisms. |
| 1724 | GSE6791 |
Profile | Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs) 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC. Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells. Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. Keywords: Gene expression ptofiles of primary cancers |
| 1725 | GSE23494 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1726 | GSE15575 |
Profile | Gene expression profiling of human embryonic kidney (HEK293) cells was performed to determine the effect of high and low glucose on gene expression. Microarrays were used to identify distinct classes of genes up-regulated in HEK293 cells during cultivation for 7 days in medium with physiological (low) glucose compared to high glucose. |
| 1727 | GSE27515 |
Profile | The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each other’s metastatic behavior. |
| 1728 | GSE20153 |
Profile | Genome-wide transcriptome analysis of expression changes in EBV transformed cell lines from the Coriell Cell Repository in Parkinson and Control subjects. |
| 1729 | GSE18486 |
Profile | The effects of the CDK inhibitors PHA-848125 and PHA-690509 on the A2780 cell line were analysed by gene expression profiling. |
| 1730 | GSE28335 |
Profile | Recent trials with MAPK inhibitors have shown promising results in many patients with metastatic melanoma; however nearly all responding patients experience disease relapse. We describe here how melanoma cells respond to MAPK inhibition in a phenotype-specific manner, suggesting that slow cycling invasive phenotype cells provide a treatment-resistant pool from which disease relapse may be derived. The implication is that while MAPK inhibition may successfully treat proliferating cells, another cell population needs to be addressed at the same time. |
| 1731 | GSE37812 |
Profile | RD induced DNA damage and suppressed DNA repair in PC-3 cells. Expression profiling of PC-3 cells treated with 10 umol/L RD for 24 hours. |
| 1732 | GSE2864 |
Profile | Nerve growth factor (NGF) is a neurotrophin that plays an important role in regulating the survival growth, and differentiation of sympathetic neurons. Many in vitro studies indicate that Egr transcription factors are coupled to NGF signaling and are essential signaling mediators of NGF-dependent differentiation of sympathetic neurons, such as neuroblastoma cells and pheochromocytoma cells. Mice that are deficient for both Egr1 and Egr3 have profound sympathetic nerve system defects, including abnormal neuron degeneration and impaired differentiation (unpublished observations). To further understand the role of Egr genes in sympathetic neuron development, it is necessary to examine the signal transduction pathways involved in NGF-mediated Egr-dependent gene regulation. The results will be helpful in understanding the pathobiology of those diseases related to aberrant sympathetic neuron differentiation, such as neuroblastoma and dysautonomias, and may provide new insights into therapies for these refractory diseases. To identify NGF-mediated Egr-dependent target genes in human SH-SY5Y/TrkA neuroblastoma cells: Many potential Egr target genes have been described over the years. However, very few have been characterized to be involved in NGF-mediated sympathetic neuron differentiation. In order to further understand the role of Egr genes in sympathetic neuron development, it is necessary to examine the signal transduction pathways involved in NGF-mediated Egr-dependent gene regulation. Egr1 and Egr3 are rapidly induced after NGF treatment and Egr1 is involved in activation of the differentiation marker gene NPY in SH-SY5Y/TrkA cells. Therefore, SH-SY5Y/TtrkA cells appear to be an excellent model system to study the role of Egr transcription factors in sympathetic neuron differentiation in vitro. A dominant negative Egr molecule that specifically blocks transcriptional activity mediated by Egr transcription factors will be used in this study to identify Egr-dependent target genes. Egr1 and Egr3 are rapidly induced after NGF treatment in human SH-SY5Y/TrkA neuroblastoma cells, which in turn differentiate into sympathetic-like neurons. We hypothesize that Egr transcription factors are involved in activating downstream signaling pathways during NGF mediated differentiation of SH-SY5Y/TrkA cells. Moreover, we hypothesize that by using a dominant negative Egr (dnEgr) molecule that blocks all Egr mediated gene transcription and Affymetrix microarray analysis, it will be possible to identify NGF-mediated Egr transcription dependent gene regulatory networks that may be involved in growth and differentiation of neuroblastoma. An unbiased approach to understanding these gene regulatory networks may lead to new insights relating to NGF signaling involved in neuronal growth and differentiation. Human neuroblastoma SH-SY5Y/TrkA cells will be infected with either dnEgr-expressing adenovirus (SH-SY5Y/TrkA-dnEgr) or with EGFP-expressing control adenovirus (SH-SY5Y/TrkA-EGFP). Equivalent infection efficiency and lack of viral toxicity will be verified by EGFP fluorescence microscopy 24 hours after infection and the cells will be treated with NGF (100 ng/ml). Total RNA will be extracted from SH-SY5Y/TrkA (uninfected), SH-SY5Y/TrkA-dnEgr, and SH-SY5Y/TrkA-EGFP cells treated with NGF for 0, 1 hour and 3 hours. Total RNA will be prepared from all of the samples and a portion subjected to real-time PCR analysis to ensure that NGF mediated Egr gene induction was not altered by the context of viral infection. Pilot experiments demonstrate that Egr genes are still induced in the context of viral infection greater than 100-fold. Egr1 mRNA peak expression is known to occur at 1 hour and decrease by 3 hours after NGF treatment in all of the samples. The peak expression of Egr target genes is expected to occur later than Egr1 peak expression since Egr1 proteins need to be expressed first to initiate the transcription of target promoters. Therefore, the RNA samples from SH-SY5Y/TrkA-dnEgr and SH-SY5Y/TrkA-EGFP treated with NGF for 3 hours will be used to probe Affymetrix high-density human genome U133 Plus 2.0 Arrays to identify differentially expressed genes. RNA amplification for probe synthesis should not be necessary since we will provide 10 ug of intact total RNA for each sample. We will provide three sets of samples to perform the comparative microarray analysis twice from different starting materials and a nine-way comparative analysis of the data will be performed. We expect that cells containing high levels of dnEgr will inhibit NGF mediated Egr-dependent target gene expression and that these gene networks should be identifiable when compared to EGFP infected cells that have normal Egr gene transcriptional activity. Keywords: time-course |
| 1733 | GSE25414 |
Profile | Genetic factors contribute to the development of ischemic stroke but their identity remains largely unknown. We tested the association with ischemic stroke of 210 single nucleotide polymorphisms (SNPs) associated with pathways functionally related to stroke. We observed an association between the rs7956957 SNP in LRP1 and next performed microarrays analysis in healthy individuals to investigate possible associations of LRP genotypes with the expression of other genes. Twelve blood samples were obtained from twelve different healthy subjects carrying different genotypes for the rs7956957 SNP of the LRP1 gene (GG CG or CC). |
| 1734 | GSE10316 |
Profile | The ubiquitin proteasome system (UPS) is known to possess important regulatory functions in the immune response. To gain a better and first comprehensive insight into the mechanisms underlying the conversion of immature to mature DC in terms of the expression of UPS related genes we undertook a comparative gene expression profiling during DC maturation in response to four different prototypic maturation stimuli. Keywords: time course |
| 1735 | GSE15237 |
Profile | The Eol1 cell line has been derived from a patient with chronic eosiniphilic leukemia. Eol1 cells express the FIP1L1-PDGFRalpha oncogene. Inhibition of FIP1L1-PDGFRalpha with imatinib mesylate (Glivec) blocks proliferation and survival of the cells. We performed microarray expression analysis to identify genes specifically regulated by FIP1L1-PDGFRalpha using imatinib-treated cells as baseline. The list of regulated genes was consistent with the activation of STAT trancription factors by FIP1L1-PDGFRA. Keywords: 4 hours treatment with Glivec |
| 1736 | GSE25619 |
Profile | To examine the effects of recombinant granulin on human mammary stromal fibroblasts we cultured normal human mammary fibroblasts in the presence of recombinant human granulin (1ug/ml) or PBS every 24h for 6 days. |
| 1737 | GSE26156 |
Profile | Gene expression of Double Positive and Single Positive CD4+ human thymocytes |
| 1738 | GSE7011 |
Profile | MLL-AF9 expression in normal human umbilical cord blood CD34+ cells leads to long-term proliferation of a myeloid progenitor cell with leukemogenic potential. Expression of a Core Binding Factor leukemia fusion (AML1-ETO or CBFbeta-SMMHC) in human CD34+ cells results in self-renewal of primitive progenitor cells with multilineage potential and stem cell ability but these cells do not induce leukemia in immunodeficient mice. This comparative microarray study was initiated to determine how faithful these cell cultures are to the transcriptome of patient samples expressing each of these different fusion proteins, and to analyze the signaling pathways that are unique to CBF cultures and MLL-fusion cultures, with the hope of determining why the MLL-fusion cells are leukemogenic while the CBF cells are not. Keywords: Disease state analysis; comparison of leukemia fusion gene expression in normal human hematopoietic progenitor cells |
| 1739 | GSE17009 |
Profile | Onconase represents a new class of RNA-damaging drugs. Mechanistically Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action. Microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 ug/ml Onconase for 24 h. |
| 1740 | GSE37430 |
Profile | Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5+ B lymphocytes in peripheral blood lymphoid organs and BM. The main feature of the disease is accumulation of the malignant cells due to decreased apoptosis. CD84 belongs to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors, and has an unknown function in CLL cells. Here, we show that the expression of CD84 is significantly elevated from the early stages of the disease, and is regulated by macrophage migration inhibitory factor (MIF) and its receptor, CD74. Activation of cell surface CD84 initiates a signaling cascade that enhances CLL cell survival. Both immune-mediated neutralization or blockade of CD84 induce cell death in vitro and in vivo. In addition, analysis of samples derived from an on-going clinical trial, in which human subjects were treated with humanized anti-CD74 milatuzumab shows a decrease in CD84 mRNA levels milatuzumab-treated cells. This downregulation was correlated with reduction of Bcl-2 and Mcl-1 message. Thus, our data show that overexpression of CD84 in CLL is an important survival mechanism that appears to be an early event in the pathogenesis of the disease. These findings suggest novel therapeutic strategies based on the blockade of this CD84-dependent survival pathway. |
| 1741 | GSE11791 |
Profile | Estrogen-responsive genes were identified by transcript profiling of estrogen-treated MCF-7 breast cancer cells. The gene expression profile generated after estrogen treatment was compared with that following inducible expression of c-Myc or c-Zip (a deletion mutant of c-Myc that lacks the N-terminal transactivation domains) in clonal MCF-7 cell lines. Keywords: Single time point |
| 1742 | GSE47436 |
Profile | In lung cancer progression p53 mutations are more often observed in invasive tumors than in non-invasive tumors, suggesting that p53 is involved in tumor invasion and metastasis. To understand the nature of p53 function as a tumor suppressor, it is crucial to elucidate the detailed mechanism of the alteration in epithelial cells, the main origin of solid tumors, following p53 inactivation. To elucidate the mechanism by which p53 loss enhances invasive and motile activities in human lung small airway epithelial cells (SAECs), we performed comprehensive expression profiling analyses between p53 knockdown and control cells using GeneChip Human Genome U133 plus 2.0 arrays. |
| 1743 | GSE24170 |
Profile | Ubiquitin-mediated proteolysis play a significant role in various biological processes including transcription DNA repair and cell cycle progression. The identification of Set8 and Set8b (a splice isoform) histone H4K20 methyl transferase as a substrate for the cullin-based ubiquitin ligase (CRL4-Cdt2) demonstrate that this pathway plays a significant role in promoting cell cycle progression, specifically promoting G2 progression. This study investigate the effect of failure to degrade Set8 in S-phase of the cell cycle via CRL4-Cdt2 on gene expression. |
| 1744 | GSE8702 |
Profile | Following androgen ablation therapy (AAT) the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics. Keywords: Time Course |
| 1745 | GSE40873 |
Profile | Background & Aims: The recurrence determines the postoperative prognosis of patients with hepatocellular carcinoma (HCC). It is unknown whether de novo HCCs derive from the liver with disability of an organic anion transport. This study was designed to elucidate the link between such transporters and the multicentric occurrence (MO) after radical hepatectomy. Results: SLC22A7 expression was the best predictor of metastasis-free survival (MFS) as judged by the GA (Fold 0.726; P=0.001). High SLC22A7 gene expression in noncancerous tissue prevent HCC occurrence after hepatectomy (Odds Ratio (OR), 0.2; 95%CI, 0.1-0.6; P=0.004). Multivariate analyses of MFS revealed the independent risk factor to be SLC22A7 expression (OR, 0.3; 95%CI, 0.1-1.0, P=0.043). Low SLC22A7 expression caused MO of HCC significantly (log-rank, P=0.001). In the validation study, multivariate analyses of MFS revealed the independent risk factor to be SLC22A7 expression (OR, 0.5; 95%CI, 0.3-0.8; P=0.012). As judged by Gene set-enrichment analysis, SLC22A7 down-regulation associated with mitochondrion (P=0.008; false discovery rate (FDR)=0.199; normalized enrichment score (NES) =1.804), oxidoreductase activity (P=0.006; FDR=0.157; NES=1.854) and fatty acid metabolic process (P=0.021; FDR=0.177; NES=1.723). Sirtuin3 also determined MFS (P= 0.018). Conclusions: These pathways involving SLC22A7 dysfunction may promote the occurrence of HCC. |
| 1746 | GSE22097 |
Profile | Islet transplantation exposes beta cells to mild hyperglycemia and to the abnormal environment of the transplant site. These conditions may affect beta cells and induce the expression of genes involved in beta cell damage. Gene expression profile of human beta cells exposed to mild hyperglycemia by transplantation into ICR-SCID mice was evaluated and compared with the gene profile of beta cells obtained from non-diabetic subjects. We found that the transplanted beta cells showed an unfolded protein response (UPR). There was upregulation of many genes of the IRE-1 pathway that provide protection against the deleterious effects of ER stress. Among them increased expression of genes coding XBP-1; the chaperone proteins PDIA4, Bip, and Grp94; and the ER degradation proteins EDEM1 and EDEM2. ERdj4 and DNA-JC3 were also upregulated. JUK had downregulated expression. The PERK and ATF-6 arms of the ER stress response had many downregulated genes in transplanted islets. The PERK's substrates, EIF2A and NRF2, showed markedly reduced expression, as downregulated was the expression of CReP. Other downregulated genes included HERP2, IRS-2, CHOP and C/EBP-beta. In the transplanted beta cells there was significantly decreased expression of ATF-6, as well as the downstream gene products CHOP and HERP2. There was increased expression of HRD1, which exerts an antiapoptotic effect by degrading unfolded proteins. In conclusion human beta cells in a transplant site had UPR changes in gene expression that protect against the proapoptotic effects of unfolded proteins. |
| 1747 | GSE42204 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1748 | GSE26884 |
Profile | Xenoestrogens are part of a group of agents termed endocrine disruptors because of their capacity to perturb normal hormonal actions. It has been suggested that xenoestrogens may contribute to the development of hormone-dependent cancers such as breast and endometrial cancers. Bisphenol A (BPA) is polymerized to manufacture polycarbonate plastic and epoxy resins. Human exposure occurs when BPA leaches from plastic-lined food and beverage cans. In the present work we are aiming to determine if BPA has carcinogenic properties by using an in vitro system. For this purpose, the human breast epithelial cells MCF-10F were treated with 10-3M to 10-9M BPA continuously for two weeks. The MCF-10F cells treated with 10-3M and 10-4M BPA died, indicating that these concentrations were toxic for the human breast epithelial cells. The cells treated with 10-5M to 10-9M BPA were evaluated for formation of solid masses in collagen and invasion capacity, both phenotypes that are indicators of cell transformation. MCF-10F treated with 10-5M, 10-6M, 10-7M, 10-8M and 10-9M BPA formed a high percentage of solid masses (34.6%, 20%, 42.4%, 31.8% and 32.2%, respectively). Ten passages after BPA treatments, the invasive capacities of the cells were evaluated using Boyden chambers. The invasion capacity was lower in the cells treated at high concentrations of BPA (10-5M and 10-6M), and there was an increased invasion for the cells treated at low BPA concentration (10-9M), although in all the cases the differences were not significant to the controls. Expression and DNA methylation analysis were performed with the cells treated with 10-5M and 10-6M BPA. We found that these cells showed an increased expression of BRCA1, BARD1, CtIP, RAD51 and BRCC3, all genes involved in DNA repair, and downregulation of PDCD5 and BCL2L11 (also known as BIM), both involved in apoptosis. The upregulation of CtIP was related to hypomethylation of the promoter/exon1 of this gene. Furthermore, BPA induced silencing of BCL2L11 by hypermethylation. This is the first demonstration that BPA induces neoplastic transformation of breast epithelial cells and that aberrant DNA methylation of genes involved in DNA repair and apoptosis could be involved in the initiation of the neoplastic process. |
| 1749 | GSE28502 |
Profile | Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus we scanned for possible candidate genes by using Affymetrix. |
| 1750 | GSE10804 |
Profile | Purpose: To identify the molecular phenotype of endothelial cells (EC) isolated from the unique vasculature of the corpus cavernosum. Methods: Human EC derived from corpus cavernosum (HCCEC n=5), coronary artery (HCAEC, n=4) and umbilical vein (HUVEC, n=3) were grown in culture and mRNA transcripts quantified by Affymetrix GeneChip microarrays. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. Several genes were verified by real-time PCR. The role of claudin 11 (CLDN11) in endothelial cell barrier function was examined by in vitro transendothelial electrical resistance assay. Results: Unsupervised hierarchical clustering of samples using all expressed genes yielded discrete groupings of EC lines according to their in vivo source of origin. 190 genes/transcripts were highly expressed only in cavernosal HCCEC. Gene Ontology classification indicated cavernosal enrichment in genes related to cell adhesion, extracellular matrix (ECM), pattern specification and organogenesis. KEGG pathway analysis showed high expression of gene relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine receptor interaction. Real-time PCR confirmed expression differences in cadherins 2 and 11, CLDN11, desmoplakin and versican. CLDN11, a component of tight junctions not previously described in ECs, was highly expressed only in HCCEC and its knockdown by siRNA significantly reduced transendothelial electrical resistance in HCCEC. Conclusions: HCCECs displayed expression of transcripts encoding matrix and adhesion proteins that regulate structural and functional characteristics of blood vessels. High expression of the tight junction protein CLDN11 is novel in endothelial cells and contributes to barrier function of cultured HCCEC. Keywords: penis, tight junctions, microarray, gene ontology, cell type comparison |
| 1751 | GSE31283 |
Profile | Histone deacetylase (HDAC) inhibitors are widely utilized in hematopoietic malignance therapy; nevertheless little is currently known concerning their effects on normal myelopoiesis. In order to investigate a putative interference of HDAC inhibitors in myeloid commitment of hematopoietic stem/progenitor cells (HSPCs) we treated CD34+ cells with valproic acid (VPA). Moreover, we investigate changes in gene expression induced by VPA treatment on HSPCs, by means of microarray analysis in VPA treated and untreated (CTR) CD34+ cells. VPA treatment induced H4 histone acetylation in CD34+ cells and blocked them in G0-G1 phase of cell cycle. CD34 expression is maintained for a longer time in VPA treated cells, while the physiological decrease of CD34 antigen occurred in CTR cells. Moreover, VPA favored erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage lineages, as demonstrated by immunophenotyping, morphological and clonogenic analysis. Finally, we demonstrated that VPA up-regulated master gene regulators of erythrocyte and megakaryocyte differentiation (GFI1B and MLLT3) through histone iper-acetylation of their promoters. These results indicate that VPA treatment enhances erythrocyte and megakaryocyte differentiation at the expense of granulocyte and mono-macrophage one. Microarray data provide for the first time a detailed molecular support for the biological effects promoted by VPA treatment in HSPCs. |
| 1752 | GSE13284 |
Profile | Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders. BCL11A siRNA label: B, NT siRNA label: N Keywords: cell type comparsion |
| 1753 | GSE32526 |
Profile | We have generated tumorigenic (S2N) and non-tumorigenic (S2) normal-like to basal-like breast cancer cell lines from primary tumors. At high in vivo inoculation cell numbers of 10^6 cells/mouse both S2N and S2 monolayer as well as sphere culture cells grew at similar rates. However, at low inoculation cell numbers down to 10^3 cells only S2N sphere cells generated xenograft tumors. mRNA profiling revealed a unique cluster pattern of the tumorigenic S2N sphere cells, but a detailed analysis of TIC relevant transcription factors like Oct3, Sox and Nanog family members, Myc, Slug or Twist1 revealed no consistently increased expression in the highly tumorigenic cell lines. Our data indicate that the intrinsic genetic and functional markers investigated are not solely indicative of the in vivo tumorigenicity of putative breast tumor-initiating cells. |
| 1754 | GSE39409 |
Profile | Adenocarcinomas of the ampulla of Vater are classified as biliary cancers though the exact epithelium of origin for these cancers is not known. We sought to molecularly classify ampullary adenocarcinomas in comparison to known adenocarcinomas of the pancreas, extrahepatic bile duct, and duodenum by gene expression analysis. |
| 1755 | GSE17718 |
Profile | We used microarrays to compare the global programme of gene expression in HTLV-positive ATL-derived and HTLV-positive in vitro-transformed cell lines with that of uninfected primary CD4 T cells. |
| 1756 | GSE18201 |
Profile | Background: Adipose tissue-derived stromal cells (ATSCs) hold great promises in regenerative medicine due to their easy retrieval, high proliferative capacity, and multi-lineage differentiation potential. In the last decade, several studies have reported the plasticity of ATSCs toward a hepatic fate. Nonetheless, the molecular mechanisms underlying the conversion from a mesenchymal to an epithelial phenotype remain poorly understood. Aim: In this study, we compared the full genome expression profiles of ATSCs cultured for 4 weeks under pro-hepatogenic conditions to undifferentiated ATSCs, in order to depict the molecular events involved in ATSC hepatic transdifferentiation. Methods: Molecular analysis was performed using the Affymetrix human focus arrays. Sets of differentially expressed genes were functionally categorized in order to understand which pathways drive the hepatic conversion and interesting target genes were validated by Q-PCR. Results: We showed that ATSC-derived hepatocyte-like cells activate several genes associated with specific liver functions, including protein metabolism, innate immune response regulation, and biodegradation of toxic compounds. Furthermore, microarray analysis highlighted the downregulation of several transcripts involved in stemness maintenance along with genes associated with a mesenchymal phenotype. Conclusion: Taken together, our data suggest that the in vitro system used in this study drove ATSCs toward a hepatic conversion through a subtle regulation of molecular pathways controlling stem cell properties and lineage commitment that promote mesenchymal-epithelial-transition. |
| 1757 | GSE10832 |
Profile | Self-renewing tumor initiating cells that are capable of differentiation and responsible for tumor growth have been isolated from cancers and cell lines. If such minor populations are associated with tumor progression understanding molecular pathways that are required for viability and maintenance of these populations will allow to target these pathways to eradicate tumors that are resistant to existing therapies. In this study we enriched for prostate cancer progenitors (Pr. CP’s) expressing cell surface markers CD44/CD133/alpha 2 beta 1 integrin in non-adherent serum-free growth conditions maintained as spheres. Cells grown in these conditions have increased in vivo clonogenic and in vivo tumorigenic potential. microarray analysis of cells grown in sphere conditions compared with long term monolayer culture conditions revealed preferential activation of PI3K/AKT pathway in prostate cancer progenitors. PI3K p110 alpha and beta protein levels were high in sphere condition cultured cells, and PTEN knockdown lead to an increase in Pr.CP’s, and to increased clonogenic and tumorigenic potential. Inhibition of Akt1 phosphorylation target FoxO3a lead to inhibition of tumorigenic capacity in vivo for prostate cancer cells. Inhibition of PI3K activity by PI3K inhibitor NVP-BEZ235 lead to a selective inhibition of Pr.CP’s, nuclear localization of FoxO3a and increase in GADD45a in prostate cancer cells. Taken together our data strongly suggest that PTEN and PI3K/Akt pathways are critical for prostate cancer stem-like cell maintenance and targeting the PI3K signaling by selective inhibitors may give an incredible advancement in prostate cancer treatment. Keywords: multiple tissues |
| 1758 | GSE16856 |
Profile | We used a modification of GINI analysis to identify genes containing premature translation termination codons (PTC) generated by nonsense or frameshift mutations in prostate cancer cell lines. The analysis was performed in two steps. In the first step nonsense mediated mRNA decay (NMD) was inhibited in prostate cancer cell lines using incubation with medium containing caffeine for 4 hours. Gene expression analysis of caffeine treated or untreated cells after this step detects mRNA accumulation that takes place for genes containing PTC and as well as for genes that show induction of transciption due to stress caused by NMD inhibition. In the second step either both transcription and NMD or transcription only are blocked by incubating cell in a medium containing either both actinomycin D and caffeine or actinomacin D only for 4 hours. Gene expression analysis after this second step detects mRNA degradation for genes containing PTC as well as for genes that show induction of transciption due to stress caused by NMD inhibition. The efficiency of mRNA degradation for genes containing PTC during this step depends on whether NMD is inhibited or not. The efficiency of mRNA degradation for stress response genes does not depend on whether NMD is inhibited or not. Our modified GINI protocol allows efficient separation of genes containing PTC from the genes that show mRNA increases due to stress response to NMD inhibition. |
| 1759 | GSE10824 |
Profile | Variation in gene expression is a fundamental aspect of human phenotypic variation. Several studies have analyzed gene expression levels in populations of different continental ancestry and concluded that there is variation across populations at a fraction of expressed genes. Here we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that samples from this population have variable proportions of continental ancestry. We show that for most genes examined, gene expression varies with genetic ancestry. Keywords: Human Gene Expression Study |
| 1760 | GSE8240 |
Profile | Transforming growth factor beta-1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFbeta activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFbeta-mediated epithelial to mesenchymal transition (EMT). Non-malignant HMEC (MCF10A, HMT3522 S1 and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture, or treated with a low concentration of TGFbeta (0.4 ng/ml), or double-treated. All double-treated (IR+TGFbeta) HMEC underwent a morphological shift from cuboidal to spindle-shaped. This phenotype was accompanied by decreased expression of epithelial markers E-cadherin, beta-catenin and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin and vimentin. Furthermore, double-treatment increased cell motility, promoted invasion and disrupted acinar morphogenesis of cells subsequently plated in Matrigel. Neither radiation nor TGFbeta alone elicited EMT, even though IR increased chronic TGFbeta signaling and activity. Gene expression profiling revealed that double treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes non-malignant HMEC to undergo TGFbeta-mediated EMT. Consistent with this, Erk phosphorylation were transiently induced by irradiation, persisted in irradiated cells treated with TGFbeta, and treatment with U0126, a Mek inhibitor, blocked the EMT phenotype. Together, these data demonstrate that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression. Keywords: response to ionizing radiation, response to transforming growth factor-beta, nonmalignant human mammary epithelial MCF10A cells, epithelial to mesenchymal transition |
| 1761 | GSE27041 |
Profile | Defective complex I (CI) is the most common type of oxidative phosphorylation (OXPHOS) disease in patients with an incidence of 1 in 5,000 live births. Complex I deficiency can present in infancy or early adulthood and shows a wide variety of clinical manifestations, including Leigh syndrome, (cardio)myopathy, hypotonia, stroke, ataxia and lactic acidosis. A number of critical processes and factors, like superoxide production, calcium homeostasis, mitochondrial membrane potential and mitochondrial morphology, are known to be involved in clinical CI deficiency, but not all factors are yet known and a complete picture is lacking. Therefore, whole genome gene expression profiling was performed in fibroblasts of CI deficient patients and controls, comparing glycolytic and oxidative conditions. Linear regression and pathway analysis identified a number of key adaptive processes. |
| 1762 | GSE15238 |
Profile | The liver is a multifunctional organ which undergoes rapid changes during the developmental period and relies on tightly-regulated gene expression. Little is known regarding the complex expression patterns of mRNAs during the early stages of human liver development in comparison to post-natal livers. We used microarrays to detail the global programme of gene expression during liver development following specification, at the stage of proliferation and differentiation when compared to post-natal livers, and identified distinct classes of up-regulated and downregulated genes during this process. |
| 1763 | GSE7832 |
Profile | Down-regulation of the Notch Differentiation Pathway in the Human Airway Epithelium in Normal Smokers and Smokers with Chronic Obstructive Lung Disease In cigarette smokers the toxic components of smoke place the epithelium under the constant stress of a variety of mechanisms of injury, with consequent modulation of airway epithelial regeneration and disordered differentiation. Based on the underlying hypothesis that these airway epithelial changes must involve quantitative changes in genes involved with the regulation of differentiation, we assessed the expression of the Notch pathway, a signaling pathway known to play a fundamental role in the embryonic lung as a gatekeeper for differentiation, in the small airway epithelium of non-smokers, normal smokers, and smokers with COPD. Microarray analysis demonstrated that 45 of the 55 Notch pathway-related genes are expressed in the human adult small airway epithelium and TaqMan quantitative PCR confirmed the expression of key genes in the pathway. TaqMan quantitative PCR analysis of the normal small airway epithelium demonstrated that Delta-like ligand 1 is the most highly expressed Notch ligand, Notch2 and 3 the most highly expressed receptor genes, and Hes1 the predominant downstream effector gene. TaqMan PCR was used to compare gene expression in nonsmokers vs healthy smokers vs smokers with COPD. The data show that some key genes in the ligands, receptors and downstream effectors in the Notch pathway are differentially expressed in smokers, with significant downregulation of a greater number of Notch-related genes in smokers with COPD compared to healthy smokers. These observations are consistent with the hypothesis that the Notch pathway, known to play an important role in lung morphogenesis, also likely plays a role in the adult human airway epithelium, with at least some of the Notch pathway gene expression dysregulated in association with smoking and its related disorder, COPD. Keywords: non-smokers, airway epithelial cells |
| 1764 | GSE12366 |
Profile | Sorted B cells using flow cytometry CD19 selected B cells were sorted using flow cytometry |
| 1765 | GSE24742 |
Profile | Objective: Rituximab displays therapeutic benefits in the treatment of rheumatoid arthritis (RA) patients resistant to TNF blockade. However the precise role of B cells in the pathogenesis of RA is still unknown. In this study we investigated the global molecular effects of rituximab in synovial biopsies obtained from anti-TNF resistant RA patients before and after administration of the drug. Methods: Paired synovial biopsies were obtained from the affected knee of anti-TNF resistant RA patients before (T0) and 12 weeks after initiation of rituximab therapy (T12). Total RNA was extracted, labeled according to standard Affymetrix procedures and hybridized on GeneChip HGU133 Plus 2.0 slides. Immunohistochemistry and quantitative real-time PCR experiments were performed to confirm the differential expression of selected transcripts. Results: According to paired Student’s t-tests, 549 out of 54,675 investigated probe sets were differentially expressed between T0 and T12. Pathway analysis revealed that genes down-regulated between T0 and T12 were significantly enriched in immunoglobulin genes, and genes involved in chemotaxis, leucocyte activation and immune responses (Gene Ontology annotations). By contrast, genes up-regulated between T0 and T12 were significantly enriched in transcripts involved in cell development (Gene Ontology annotation) and wound healing (GSEA). At baseline, higher synovial expression of immunoglobulin genes was associated with response to therapy. Conclusion: Rituximab displays unique effects on global gene expression profiles in synovial tissue of RA patients. These observations open new perspectives in the understanding of the biological effects of the drug and in the selection of patients likely to benefit from this therapy. |
| 1766 | GSE10240 |
Profile | Primary HBE cells were stimulated with IL-22 and IL-17 and gene expression was studied using an Affymetrix platform microarray, in order to investigate which genes may be upregulated or downregulated in response to these cytokines. Of particular interest was the host defense genes such as antimicrobial peptides, which have been shown to be upregulated by IL-22 and IL-17 in skin keratinocytes. Keywords: cytokine effect |
| 1767 | GSE9487 |
Profile | We performed genome-wide expression profiling of cells infected with control or RPS14 shRNAs. Keywords: controls vs. shRNA treated |
| 1768 | GSE9451 |
Profile | Background. The in vivo distribution status and molecular signature of bone marrow mesenchymal stem cells (MSC) remain unknown although ex vivo expanded MSC have been used in numerous studies. Methods/Results. To address these issues, we identified human MSC-characteristic genes, including 9 transcription factor genes - using DNA microarray analysis: Most (75 %) of the MSC-characteristic genes were down-regulated by knockdown of the transcription factors. Furthermore, we used an antibody set for the MSC-characteristic molecules in immunohistochemistry, which revealed that, in embryonic/neonatal mice, elongated MSC were abundant near the endosteum and in the interior of bone marrow, perichondrium and periosteum, whereas in adult mice round/compact MSC were found only in the interior of bone marrow: No MSC-like cells were found in any other skeletal or non-skeletal tissues using this antibody set. Conclusion. The identification of native MSC in developing and adult skeletal tissues should be useful in basic and clinical studies on MSC. Keywords: cell type comparison |
| 1769 | GSE12131 |
Profile | We have analyzed the variation of transcriptome of HUVECs intoxicated by the lethal toxin of Bacillus anthracis at 4 and 8 hours |
| 1770 | GSE41469 |
Profile | Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor gammat (RORgammat) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We identified a novel cell subset of CD56dimNKp46low cells that includes RORgammat+ILCs with a lineage-CD94-CD117brightCD127bright phenotype.We also included data regarding the genome-wide transcriptional profiles of human healthy colonic NK cells and RORgammat+ILCs.The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. |
| 1771 | GSE26603 |
Profile | ARHGAP8 was expressed at negligible levels in normal melanocytes but was ectopically activated in approximately 10% of melanoma specimens and melanoma cell lines. ARHGAP8 was ectopically expressed in ARHGAP8-negative M14 melanoma cells using the pIRES2 vector (Clontech) producing a bicistronic ARHGAP8-ires-eGFP mRNA. M14 cells stably transfected with vector control or N-terminally FLAG-tagged ARHGAP8 were cultured in 2D or 3D embedded growth conditions and then subjected to gene expression profiling using Affymetrix U133_Plus_2 gene chips. |
| 1772 | GSE12814 |
Profile | Uterine leiomyomata (UL) the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including del(7)(q22q32). To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t-tests demonstrates this matched design is critical to eliminate confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosacism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis. Keywords: uterine leiomyomata, fibroids, del(7)(q22q32), gene expression, aCGH, microarray |
| 1773 | GSE7893 |
Profile | Gene expression profiling was carried out on peripheral blood CD14+ leukocytes from 21 stressed caregivers and controls (all adult). The primary research question is whether gene expression differs in individuals from high stress vs low stress environments. Keywords: Risk prediction |
| 1774 | GSE9086 |
Profile | To understand the differentiation process of embryonic stem cells into hemangioblasts gene expression profiles of ES, EB and Blast cells (BL) were analyzed. Keywords: time course |
| 1775 | GSE32666 |
Profile | Estrogens have been reported to activate several processes via membrane binding to either classic estrogen receptors (ERs) or GPR30. We have used either estradiol or BSA-conjugated estradiol in order to initiate membrane-initiated actions and ICI 172780 (ICI) or G15 to explore ER- and GPR30-related transcription. Our results show that the majority of G15-inhibited transcription is depending on ERs, as it is also inhibited by ICI. However, a small number of transcripts, related to specific actions/pathways is either exclusively inhibited by G15, providing evidence about a specific GPR30 signature, or not inhibited by ICI or G15 suggesting the existence of another, yet unidentified estrogen receptor. |
| 1776 | GSE12086 |
Profile | Recessive retinitis pigmentosa (RP) is often caused by nonsense mutations that lead to low mRNA levels as a result of nonsense-mediated decay. Some RP genes are expressed at detectable levels in leukocytes as well as in the retina. We designed a microarray-based method to find recessive RP genes based on low lymphoblast mRNA expression levels Keywords: Recessive mutations; mRNA expression; nonsense mediated-decay; retinitis pigmentosa; lymphocyte; Affymetrix genechip Human Genome U133Plus2.0. |
| 1777 | GSE10696 |
Profile | A431 wild-type (wt) cancer cell line is sensitive to treatment with EGFR tyrosine kinase inhibitors (TKIs). By culturing it chronically under gefitinib it eventually becomes resistant (A431_GR cell). We know of a few proteins involved in this mechanism of drug resistance, but a cDNA exprssion array would add information to other genes that might be involved in this resistance mechanism. We used microarrays to identify the differences in the global gene expression between A431_wt (wild-type) cells and A431_GR cells. Keywords: comparison of two cell lines |
| 1778 | GSE15913 |
Profile | Thalidomide Exerts Distinct Molecular Antileukemic Effects and Combined Thalidomide/Fludarabine Therapy is Clinically Effective in High-Risk Chronic Lymphocytic Leukemia Background: Thalidomide represents a promising immunomodulatory drug that targets both leukemia cells and the tumor microenvironment. Methods: We treated chronic lymphocytic leukemia (CLL) patients with a combined thalidomide/fludarabine regimen and monitored cellular and molecular changes induced by thalidomide in-vivo prior to fludarabine treatment. Thalidomide was given daily (100mg p.o./day) and fludarabine was administered on days 7-11 (25 mg/m² i.v./day) within each 4-week cycle (maximum of 6 cycles). Twenty patients received thalidomide/fludarabine as first line therapy and 20 patients were previously treated. Unmutated IgVH mutation status was found in 36 cases and 13 had high-risk cytogenetic aberrations (deletion of 17p13 or 11q22-q23). Results: The overall response rate was 80% and 25% for untreated and previously treated patients respectively. While thalidomide effectively reduced the number of CLL cells, the number of CD3 lymphocytes showed no significant change, but the number of CD4+CD25hiFOXP3+ T-regulatory cells was significantly decreased. Gene expression profiling revealed a thalidomide induced signature containing both targets known to play a role in immunomodulatory drug action as well as novel candidate genes. Conclusions: Combined thalidomide/fludarabine therapy demonstrated efficacy in high-risk CLL patients. Furthermore, our study provides novel biological insights into thalidomide effect, which might act by enhancing apoptosis of CLL cells and reducing Tregs, thereby enabling T-cell dependent anti-tumor effect. |
| 1779 | GSE10820 |
Profile | The main goal of the research was to find some new biomarkers for the monitoring of the Minimal Residual Disease in Acute Lymphoblastic Leukemia patients. Keywords: Search for new Biomarkers |
| 1780 | GSE39720 |
Profile | ERα17p is a synthetic peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially synthesized to mimic its calmodulin binding site. ERα17p was subsequently found to elicit estrogenic responses in E2-deprived ERα-positive breast cancer cells increasing proliferation and E2-dependent gene transcription. Surprisingly, in E2-supplemented media, ERα17p induced apoptosis and modified the actin network, influencing thereby cell motility. Here, we report that ERα17p induces a massive early (3h) transcriptional activity in breast cancer cell line T47D. |
| 1781 | GSE46884 |
Profile | Human Polynucleotide Phosphorylase (hPNPaseold-35) is an evolutionarily conserved 3’→5’ exoribonuclease implicated in the regulation of numerous physiological processes like maintenance of mitochondrial homeostasis mtRNA import and aging-associated inflammation. From an RNase perspective, little is known about the RNA or miRNA species it targets for degradation or whose expression it regulates; except for c-myc and miR-221. |
| 1782 | GSE26511 |
Profile | Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early stage cervical cancer patients primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early stage cervical cancer. Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N0) and 19 with positive lymph nodes (N+), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early stage cervical cancer patients was performed for representatives of the identified pathways. Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-β, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N0, and two pathways (β-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N+ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N0 and N+ tumors (P<0.001) were involved in β-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3 and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-β and β-catenin) confirmed that the TGF-β pathway (positivity of Smad4) was related to N0 (OR:0.20, 95%CI:0.06-0.66) and the β-catenin pathway (p120 positivity) to N+ (OR:1.79, 95%CI:1.05-3.05). Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-β and p120-associated non-canonical β-catenin pathways are important in pelvic lymph node metastasis in early stage cervical cancer. |
| 1783 | GSE41914 |
Profile | We tested the hypothesis on the mechanisms responsible for the early control of NK cell function by identifying a discrete set of genes in circulating NK cells that were altered by exercise. Exercise leads to a rapid change in the profile of gene expression in NK cells. |
| 1784 | GSE22865 |
Profile | Extracellular cancer-specific methylated DNA has been shown to be a prognostic marker when detected in serum or plasma. In this study we investigated the effect of treating cancer cells with differentially methylated CpG DNA. When breast cancer cell lines were treated with methylated CpG DNA, a consistent upregulation of CHAC1 mRNA expression was observed. CHAC1 was recently described to be a novel component of the unfolded protein response pathway. To elucidate the role of CHAC1 mRNA expression in cancer in more detail, we analyzed expression of this gene in breast (n=107) and ovarian cancer (n=107) and found a strong correlation with tumor differentiation. Poorly differentiated tumors exhibited higher CHAC1 expression levels (p=0.004 for breast and p=0.031 for ovarian cancer). Additionally, hormone receptor (HR)-negative breast cancers (p<0.001) and advanced stage disease ovarian cancers (p=0.026) also demonstrated high CHAC1 mRNA levels. mRNA expression analysis of the two known CHAC1 isoforms showed a strong association of expression above the median with poor outcome in breast cancer patients in a multivariate analysis (isoform a: relative risk (RR) of death 3.2 (95% CI 1.6-6.5; p<0.01); RR of relapse 3.9 (95% CI 1.6-9.8; p<0.01); isoform b: relative risk (RR) of death 3.5 (95% CI 1.6-7.3; p<0.01); RR of relapse 6.6 (95% CI 2.4-18.5; p<0.01)). Univariate analysis in ovarian cancer showed that CHAC1 mRNA expression above the median was associated with a poor relapse free survival (p=0.03). In younger ovarian cancer patients (age < median age), a high CHAC1 mRNA expression was associated with overall survival (p=0.007) and relapse free survival (p=0.015). Finally, we show that downregulation of CHAC1 by small interfering RNA suppressed breast cancer cell migration and proliferation, whereas overexpression resulted in an observed increase in these cellular behaviours. This is the first report demonstrating that a gene (CHAC1) whose expression is triggered by methylated, but not unmethylated DNA, is involved in tumour biology. |
| 1785 | GSE42771 |
Profile | The ubiquitously expressed G-protein-coupled receptor kinase 2 (GRK2 ADRBK1) is an indispensable kinase involved in growth, differentiation and development. Exaggerated GRK2 activity plays a major pathophysiological role in the development of cardiovascular diseases such as heart failure and hypertension. GRK2 exerts its functions by kinase-dependent and kinase-independent effects. To assess the differential impact of GRK2 on cellular signalling we established HEK cell clones with over-expression of comparable protein levels of GRK2 or the kinase-deficient GRK2-K220R mutant, respectively. HEK cells were either cultured in vitro or expanded in vivo, in immunodeficient NOD.Scid mice to discriminate between in vitro and in vivo effects of GRK2. Whole genome microarray gene expression profiling was performed of cultured HEK cells and of NOD.Scid mouse-expanded HEK clones. As an additional control, cells were re-cultured in vitro after expansion in NOD.Scid mice. |
| 1786 | GSE6410 |
Profile | Affymetrix high-density oligonucleotide microarray analysis was performed to analyse cisplatin-induced gene expression changes in A549 NSCLC cells. Cells were treated with 50 µM of cisplatin for 1 hour and incubated for a further 10 hours in drug-free media before the gene expression changes were investigated. Results show that cisplatin induced changes in the expression of genes involved in apoptosis cell cycle control, DNA repair and transcription. Keywords: drug response |
| 1787 | GSE11686 |
Profile | Cerebral palsy is caused be an upper motor neuron lesion which casues spasticity as well as secondary effects on muscle . Muscle from cerebral palsy patients is has been shown to be smaller with more ECM and longer sarcomere lengths We used microarrays to globally investigate the transcriptional adaptations of cerebral palsy muscle and research which muscle pathways are altered in the diseased state Keywords: Disease state analysis |
| 1788 | GSE4885 |
Profile | This experiment series addresses the role of coactivator SRC-1/NcoA-1 for the induction of interleukin-6 (IL-6) target genes in HepG2 cells. For that purpose HepG2 human hepatocellular carcinoma cells were manipulated to stably express an shRNA that knocks down SRC-1 expression yielding the HepG2-∆Src1 cells. Either unmanipulated HepG2 or HepG2-∆Src1 cells were then treated for various periods with IL-6. Keywords: time course, genetic modification |
| 1789 | GSE26455 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1790 | GSE27928 |
Profile | It has been shown that tumor infiltrating immune cells have a profound impact on the outcome of FL. To find mechanisms whereby TILs are altered gene expession analysis of highly pure TILs were performed. |
| 1791 | GSE9758 |
Profile | In addition to the estrogen responsive element (ERE)-dependent gene expression E2-ERalpha regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERalpha signaling is unclear. Our studies in infected ER-negative cell models with an ERalpha mutant (ERalpha 203/204/211E) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERalpha are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERalpha signaling in model cell lines. Keywords: MDA-MB-231 cells |
| 1792 | GSE24897 |
Profile | Periodontitis is the most common human infection affecting tooth-supporting structures. It was shown to play a role in aggravating atherosclerosis. To deepen our understanding of the pathogenesis of this disease we exposed human macrophages to an oral bacteria Porphyromonas gingivalis (P. gingivalis) either as live bacteria, or its lipopolysaccharide (LPS) or fimbria. Microarray data from treated macrophages or control cells were analyzed to define molecular signatures. We focused our analysis on three important groups of genes. Group PG (genes differentially expressed by live bacteria only); Group LFG (genes differentially expressed in response to exposure to LPS and/or FimA); Group CG (core gene set jointly activated by all 3 stimulants). A total of 842 macrophage genes were differentially expressed in at least one of the three conditions compared to naïve cells. Using pathway analysis, we found that group CG activates the initial phagocytosis process and induces genes relevant to immune response, whereas group PG can de-activate the phagocytosis process associated with phagosome-lysosome fusion. LFG mostly affected RIG-I-like receptor signaling pathway. |
| 1793 | GSE40750 |
Profile | Neural stem cells can migrate towards tumors of both neural and non-neural origins which is crucial for the success in treating disseminated tumors. Although the understanding of the molecular mechanisms underlying NSC tumor tropism is limited, it has been noted that several cytokines, growth factors and receptors direct the migration in vitro. A proper understanding of the basic molecular mechanisms of NSC migration towards tumors, especially identification of key cellular regulators of the migration, will have important implications in improving the effectiveness of engineering and employing NSCs as tumor therapy agents. We compared gene expression profiles between migratory and non-migratory hiPSC-NSCs towards cancer cells using cDNA microarray profiling. |
| 1794 | GSE26077 |
Profile | Excessive MS is known to result in disappearance of the alveolar hard line enlargement of thePDL space, and destruction of alveolar bone, leading to occlusal traumatism. The regulatory role of MS is believed to play a critical role in the process of alveolar bone remodeling. However, little is known about the effect of excessive MS on expression of osteoclastogenesis-related genes in human PDL cells. |
| 1795 | GSE45899 |
Profile | Glioblastoma (GBM) is thought to be driven by a sub-population of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity yet remain poorly understood. Here we present a comparative epigenomic analysis of GBM CSCs that reveals widespread activation of genes normally held in check by Polycomb repressors. These activated targets include a large set of developmental transcription factors (TFs) whose coordinated activation is unique to the CSCs. We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. We show that ASCL1 is essential for maintenance and in vivo tumorigenicity of GBM CSCs. Genomewide binding profiles for ASCL1 and the Wnt effector LEF1 provide mechanistic insight and suggest widespread interactions between the TF module and the signaling pathway. Our findings demonstrate regulatory connections between ASCL1, Wnt signaling and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs. |
| 1796 | GSE18544 |
Profile | Gene Expression Profiling of a Mouse Xenograft Model of “Triple-Negative” Breast Cancer Brain Metastases With and Without Vorinostat Treatment. Purpose: As chemotherapy and molecular therapy improve the systemic survival of breast cancer patients the incidence of brain metastases increases. Few therapeutic strategies exist for the treatment of brain metastases because the blood-brain barrier severely limits drug access. We report the pharmacokinetic, efficacy, and mechanism of action studies for the histone deactylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in a preclinical model of brain metastasis of triple-negative breast cancer. Experimental Design: The 231-BR brain trophic subline of the MDA-MB-231 human breast cancer cell line was injected into immunocompromised mice for pharmacokinetic and metastasis studies. Pharmacodynamic studies compared histone acetylation, apoptosis, proliferation, and DNA damage in vitro and in vivo. Results: Following systemic administration, uptake of [14C]vorinostat was significant into normal rodent brain and accumulation was up to 3-fold higher in a proportion of metastases formed by 231-BR cells. Vorinostat prevented the development of 231-BR micrometastases by 28% (P = 0.017) and large metastases by 62% (P < 0.0001) compared with vehicle-treated mice when treatment was initiated on day 3 post-injection. The inhibitory activity of vorinostat as a single agent was linked to a novel function in vivo: induction of DNA double-strand breaks associated with the down-regulation of the DNA repair gene Rad52. Conclusions: We report the first preclinical data for the prevention of brain metastasis of triple-negative breast cancer. Vorinostat is brain permeable and can prevent the formation of brain metastases by 62%. Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation. |
| 1797 | GSE11092 |
Profile | CD34+ positively isolated from healthy donors (stimulated by G-CSF) with magnetic beads (after blood leukapheresis) CD34- obtained from 10dd cytokine cultured CD34+ Keywords: differentiation |
| 1798 | GSE5967 |
Profile | BACKGROUND: Assessment of gene expression in peripheral blood may provide a noninvasive screening test for allograft rejection. We hypothesized that changes in peripheral blood expression profiles would correlate with biopsy-proven rejection and would resolve after treatment of rejection episodes. METHODS AND RESULTS: We performed a case-control study nested within a cohort of 189 cardiac transplant patients who had blood samples obtained during endomyocardial biopsy (EMB). Using Affymetrix HU133A microarrays we analyzed whole-blood expression profiles from 3 groups: (1) control samples with negative EMB (n=7); (2) samples obtained during rejection (at least International Society for Heart and Lung Transplantation grade 3A; n=7); and (3) samples obtained after rejection, after treatment and normalization of the EMB (n=7). We identified 91 transcripts differentially expressed in rejection compared with control (false discovery rate <0.10). In postrejection samples, 98% of transcripts returned toward control levels, displaying an intermediate expression profile for patients with treated rejection (P<0.0001). Cluster analysis of the 40 transcripts with >25% change in expression levels during rejection demonstrated good discrimination between control and rejection samples and verified the intermediate expression profile of postrejection samples. Quantitative real-time polymerase chain reaction confirmed significant differential expression for the predictive markers CFLAR and SOD2 (UniGene ID No. 355724 and No. 384944). CONCLUSIONS: These data demonstrate that peripheral blood expression profiles correlate with biopsy-proven allograft rejection. Intermediate expression profiles of treated rejection suggest persistent immune activation despite normalization of the EMB. If validated in larger studies, expression profiling may prove to be a more sensitive screening test for allograft rejection than EMB. Keywords: human, peripheral blood, before and after therpay, untreated control |
| 1799 | GSE12305 |
Profile | Achievement of specific tumor cell targeting remains a challenge for glioma gene therapy. We report here the identification and characterization of a 5’ sequence of human HMGB2 gene for transcriptional targeting to glioblastoma. We performed microarray analysis and found HMGB2 as one of the genes that had a low level of expression in normal human astrocytes but was significantly up-regulated in glioblastoma cells. Real-time PCR quantification revealed increase in HMBG2 expression level in glioblastoma tissues and cells between 11 to 79 fold over that in normal human brain tissue. With progressive truncation of a 5’-upstream sequence of the HMGB2 gene, we identified a 500-bp fragment that displayed a high transcriptional activity in glioblastoma cells, but a low activity in normal brain cells. Using the sequence to drive the expression of the herpes simplex virus thymidine kinase gene in the context of a baculoviral vector, glioblastoma cells died in the presence of ganciclovir, whereas normal human astrocytes and neurons were not affected. We further confirmed that after intra-tumor injection, the baculoviral vector effectively suppressed the growth of human glioblastoma cells in a mouse xenograft model. Our results suggest that the 5’-upstream sequence of the HMGB2 gene can be used as an efficient, tumor-selective promoter in targeted vectors for glioblastoma gene therapy. |
| 1800 | GSE19864 |
Profile | The action of RB as a tumor suppressor has been difficult to define in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology to suppress RB, p107 or p130 with a genome wide analysis of gene expression in growing, quiescent or ras-senescent cells, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program. |
| 1801 | GSE43258 |
Profile | Purpose: In acute myeloid leukemia (AML) without retinoic acid receptor (RAR) rearrangement the effect of all-trans retinoic acid (ATRA) is still poorly understood despite an association of NPM1 mutation and ATRA response. Recently PRAME (preferentially expressed antigen in melanoma) has been shown to be a dominant repressor of RAR-signaling. Experimental design: Thus, we further investigated ATRA response mechanisms, especially the impact of PRAME expression on ATRA-responsiveness by profiling gene expression in K562 cell lines. Results: Our data revealed a PRAME-expression associated gene pattern to be significantly enriched for genes involved in the retinoic acid metabolic process. In leukemia cell line models we could demonstrate that retinoic acid-regulated cell proliferation and differentiation are impacted by PRAME expression. Conclusions: PRAME seems to impair differentiation and to increase proliferation likely via blocking RAR-signaling, which might be reversed by ATRA. |
| 1802 | GSE6377 |
Profile | Diagnosis of acute infection in the critically ill remains a challenge. Changes in physiologic parameters and existing molecular diagnostics are not specific and microbiologic confirmation of infection can take days. As cellular first responders preclinical studies indicate that circulating leukocytes are activated in response to bacterial infection, manifesting infection-specific transcriptional programs. We hypothesized that circulating leukocyte transcriptional profiles can be used to diagnose infection and monitor response to therapy in the critically ill. Keywords: ventilator associated pneumonia, predictor, microarray, timecourse, human, murine |
| 1803 | GSE2152 |
Profile | A series of gene expression measurements of uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene. Keywords: other |
| 1804 | GSE22293 |
Profile | Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration. |
| 1805 | GSE17987 |
Profile | Masitinib is a tyrosine kinase inhibitor of c-Kit PDGFRα and β, and to some extent Lyn of the Src kinase family. We evaluated the therapeutic potential of masitinib in vitro on human pancreatic tumour cell lines and in vivo in a mouse model of human pancreatic cancer. |
| 1806 | GSE41751 |
Profile | Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is frequently caused by a de novo point mutation at position 1824 in LMNA. This mutation activates a cryptic splice donor site in exon 11 and leads to an in-frame deletion within the prelamin A mRNA and the production of a dominant negative lamin A protein, known as progerin. Here we show that HGPS cells experience genome-wide alterations in patterns of H3K27me3 deposition, changes in the associations of genomic loci with nuclear lamin A/C, and, at late passages, genome-wide loss of spatial compartmentalization of active and inactive chromatin domains that characterizes chromosome folding in normal cells. We further demonstrate that the H3K27me3 changes associate with gene expression alterations in HGPS cells. Our results support a model that the accumulation of progerin in the nuclear lamina leads to altered H3K27me3 marks in heterochromatin, possibly through the down-regulation of EZH2, and disrupts heterochromatin-lamina interactions. These changes may then lead to the genomic disorganization and changes in transcriptional regulation we observe in HGPS fibroblasts. |
| 1807 | GSE20433 |
Profile | The Polycomb group (PcG) protein enhancer of zeste homolog 2 (EZH2) plays an essential role in histone methylation-mediated epigenetic gene silencing. We demonstrate that under physiological conditions cyclin-dependent kinase 1 (CDK1) and 2 (CDK2) bind to and phosphorylate EZH2 at threonine 350 (T350) in an evolutionally conserved motif. T350 phosphorylation is required for EZH2 function in silencing of genes that promote differentiation and inhibit proliferation and migration. Blockage of T350 phosphorylation by generating a T350A mutation largely diminishes the global effect of EZH2 on gene silencing. |
| 1808 | GSE21589 |
Profile | During HIV-1 infection there is a massive perturbation of host gene expression, but as yet, genome-wide studies have not identified host genes affecting HIV-1 replication in lymphatic tissue, the primary site of virus-host interactions. In this study, we isolated RNA from the inguinal lymph nodes of 22 HIV-1-infected individuals and utilized a microarray approach to identify host genes critically important for viral replication in lymphatic tissue by examining gene expression associated with viral load. Strikingly, ~95% of the transcripts (558) in this data set (592 transcripts total) were negatively associated with HIV-1 replication. Genes in this subset (1) inhibit cellular activation/proliferation (ex.: TCFL5, SOCS5 and SCOS7, KLF10), (2) promote heterochromatin formation (ex.: HIC2, CREBZF, ZNF148/ZBP-89), (3) increase collagen synthesis (ex.: PLOD2, POSTN, CRTAP), and (4) reduce cellular transcription and translation. Potential anti-HIV-1 restriction factors were also identified (ex.: NR3C1, HNRNPU, PACT). Only ~5% of the transcripts (34) were positively associated with HIV-1 replication. Paradoxically, nearly all these genes function in innate and adaptive immunity, particularly highlighting a heightened interferon system. The predominance of negative correlations as well as the disconnect between host defenses and viral load point to the importance of genes that regulate target cell activation and genes that code for potentially new restriction factors as determinants of viral load rather than conventional host defenses. |
| 1809 | GSE43010 |
Profile | The identification of recurrent somatic mutations in genes encoding epigenetic enzymes coupled with biochemical studies demonstrating aberrant recruitment of epigenetic enzymes such as histone deacetylases (HDACs) and histone methyltransferases (HMTs) to promoter regions through association with oncogenic fusion proteins such as PML-RARα and AML1-ETO has provided a strong rationale for the development compounds that target the epigenome for the treatment of cancer. HDAC inhibitors (HDACi) are potent inducers of tumor cell apoptosis but it remains unclear why tumor cells are selectively sensitive to HDACi-induced cell death. Herein we assessed the biological and molecular responses of normal and transformed cells to the FDA-approved HDACi vorinostat. Both HDACi selectively killed cells of diverse tissue origin that had been transformed through the serial introduction of different oncogenes. Time course microarray expression profiling revealed that normal and transformed cells transcriptionally responded to vorinostat treatment. Over 4200 genes responded differently to vorinostat in normal and transformed cells and gene ontology and pathway analyses identified a tumor-cell-selective pro-apoptotic gene-expression signature that consisted of BCL2 family genes. In particular, HDACi induced tumor cell-selective upregulation of the pro-apoptotic gene BMF and downregulation of the pro-survival gene BCL2A1 encoding BFL-1. Maintenance of BFL-1 levels in transformed cells through forced expression conferred vorinostat resistance indicating that specific and selective engagement of the intrinsic apoptosis pathways underlies the tumor cell-selective apoptotic activities of these agents. The ability of HDACi to affect the growth and survival of tumor cells whilst leaving normal cells relatively unharmed is fundamental to their successful clinical application. This study provides new insight into the transcriptional effects of HDACi in human donor-matched normal and transformed cells, and identifies molecules and pathways that could underpin the tumor-selective cytotoxic activity of these compounds. |
| 1810 | GSE30643 |
Profile | The familial or genetic Creutzfeldt-Jakob disease (fCJD or gCJD) is the inherent form of human prion diseases which accounts for approximately 10-15% of human prion diseases that are caused by mutations of the prion protein gene (PRNP). In this study, the global expression patterns of the parietal cortex from a patient with G114V gCJD were comparatively analyzed with the normal controls by using a commercial human genome expression chip. Totally 8774 genes showed differential expression, among them 2769 genes were upregulated and 6005 ones were downregulated. The reliability of the results was confirmed by the real-time RT-PCR assays for several specific genes. The most differentially expressed genes involved in the functions of regulation of transcription, ion transport, transcription, cell adhesion, signal transduction. The gene associated with gliosis was upregulated and the genes marked for neurons were downregulated, while the transcription of PRNP gene maintained unchanged. 169 different pathways showed significantly changed in the brain of G114V gCJD. The most significantly regulated pathways included that of Alzheimer’s and Parkinson’s disease, oxidative phosphorylation, regulation of actin cytoskeleton, MAPK signaling pathway and proteasome, which were described in prion diseases previously. In addition, some rarely addressed pathways in prion diseases, such as axon guidance, gap junction and purine metabolism, were also significantly changed in G114V gCJD. The transcriptional situations of the most genes in the top ten changed pathways were down-regulated. The extensive reductions of gene expressions in G114V gCJD showed the comparable profiles with sporadic CJD. The data here raised the useful clues for understanding the pathogenesis of the disease and selecting the potential biomarkers for diagnostic and therapeutic tools. |
| 1811 | GSE17386 |
Profile | To identify candidate downstream mRNA target for hsa-miR-130b |
| 1812 | GSE33874 |
Profile | To identify the potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma Microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP) isolated from fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma and the results were analyzed by paired T-test using BRB-ArrayTools |
| 1813 | GSE18226 |
Profile | DNA methylation is often inversely correlated with gene expression. We used expression microarrays to determine the relationship between DNA methylation and gene expression in 6 iPS cell lines and the fibroblasts from which they were derived. |
| 1814 | GSE9031 |
Profile | To identify genes more highly expressed in Myeloma celllines v.s lymphoma cell lines. Keywords: cell type comparison design |
| 1815 | GSE30442 |
Profile | Among acute myeloid leukemias (AML) with normal karyotype (CN-AML) NPM1 and CEBPA mutations define WHO provisional entities accounting for ~60% of cases, but the remaining ~40% remains poorly characterized. By whole exome-sequencing (WES) of one CN-AML patient lacking mutations in NPM1, CEBPA, FLT3, MLL-PTD and IDH1, we newly identified a clonal somatic mutation in BCOR (BCL6 co-repressor), a gene located in chromosome X. Further analyses showed that BCOR mutations occurred in 11/262 (4.2%) CN-AML cases and represented a substantial fraction (14/82, 17.1%) of CN-AML patients showing the same genetic background as the index patient subjected to WES. BCOR somatic mutations were: i) disruptive events similar to germline BCOR mutations causing the oculo-cranio-facial-dental (OCFD) genetic syndrome; ii) associated with markedly decreased BCOR mRNA levels, absence of full-length BCOR and absent or low expression of a truncated BCOR protein; iii) almost mutually exclusive with NPM1 mutations and frequently associated with DNMT3A and RUNX1 mutations, pointing to a cooperation between these events. Finally, BCOR mutations correlated with poor outcome among a cohort of 160 CN-AML patients (28% versus 66% overall survival at 2 yrs, P=0.024). Our results implicate for the first time BCOR in the pathogenesis of CN-AML without NPM1 mutations. |
| 1816 | GSE45046 |
Profile | NSC 59687 (oxyphenisatin acetate) is a novel anti-cancer agent with selectivity for breast and ovarian cell lines To elucidate the transcripts differentially regulated following treatment with Oxyphenisatin acetate (NSC 59687) |
| 1817 | GSE8157 |
Profile | Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZD) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZD in PCOS is in part mediated by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp. Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy control women. Treatment with pioglitazone improved insulin-stimulated total, oxidative and non-oxidative glucose metabolism, and reduced fasting serum insulin (all p < 0.05). Global pathway analysis using Gene Map Annotator and Pathway Profiler (GenMAPP 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1) revealed a significant upregulation of genes involved in mitochondrial oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome, translation factors, and proteasome complexes in PCOS patients after pioglitazone therapy. Quantitative real-time PCR suggested that upregulation of OXPHOS genes was mediated by an increase in PGC-1α expression (p < 0.05). Expression of genes involved in ribosomal proteins and OXPHOS was down-regulated in PCOS patients before treatment compared to matched healthy women using GenMAPP 2.1 and GSEA 2.1. These data indicate that pioglitazone therapy restores insulin sensitivity in part by a coordinated upregulation of genes involved in mitochondrial oxidative metabolism and protein biosynthesis in skeletal muscle of PCOS. These transcriptional effects of pioglitazone therapy may contribute to prevent the onset of type 2 diabetes in these women. Keywords: PCOS, microarray, global pathway analysis, insulin resistance, pioglitazone, protein metabolism, mitochondrial oxidative metabolism |
| 1818 | GSE3790 |
Profile | Post mortem human brain tissue comparison between HD patients and controls from 3 brain regions - cerebellum frontal cortex [BA4, BA9] and caudate nucleus. Gene expression analysed using linear models from LIMMA package in Bioconductor suite. Keywords: disease state analysis |
| 1819 | GSE5859 |
Profile | Expression level of genes in lymphoblasts from individuals in three HapMap populations (CEU CHB, JPT) were compared. More than 1,000 genes were found to be significantly different (Pc<0.05) in mean expression level between the CEU and CHB+JPT samples. Keywords: Comparison of Gene Expression Profiles from Lymphoblastoid cells |
| 1820 | GSE44807 |
Profile | The airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated p63+ Krt5+ progenitors. The integrity of this epithelium and its ability to act as a selective barrier are critical for normal lung function. In other epithelia there is evidence that transcription factors of the evolutionarily conserved grainyheadlike (GRHL) family play key roles in co-ordinating the expression of numerous proteins required for epithelial morphogenesis differentiation, remodeling and repair. However, little is known about their function in the adult lung. We used Affymetrix microarray analysis to compare transcripts in lentivirus transfected primary human bronchial epithelial (HBE) cells expressing either EGFP or DN-GRHL2 to help identify GRHL2 target genes and their functions in HBE cells. |
| 1821 | GSE7741 |
Profile | Introduction: Mechanisms that contribute to the pathogenesis of liver damage caused by hepatitis C virus (HCV) are not fully understood. Our previous work on liver biopsies from chronic HCV patients has shown modulation of the expression of certain cell cycle proteins indicating HCV-induced modifications of cell cycle events. We therefore hypothesize that HCV infection disrupts normal regulation of cell cycle that contributes to disease progression. Objective: To identify molecular disruptions during the course of HCV-associated disease progression using liver biopsy specimens of chronic hepatitis C patients. Methods: Liver biopsy samples classified on histological basis as early (fibrosis stage 0-1) or advanced (fibrosis stage 3-4) disease stage were studied using oligonucleotide array ( HG U133 Plus 2.0, Affymetrix GeneChip™ System). For comparison, liver specimens from patients with non-viral hepatitis were also analyzed by microarray. Expression data was analyzed using Genespring (GX 7.2) and Ingenuity Pathway analysis (3.0). The differential expression of selected cell cycle genes (cyclin D2, KPNA2, HERC5 and Bcl-2) identified after microarray analysis was confirmed by quantitative real-time RT-PCR. Results: Microarray analysis revealed two-fold or greater transcriptional change in 792 genes of the total 38,500 known human genes in HCV-advance disease stage (HCV-A) as compared to HCV-early disease stage (HCV-E). Most of the genes have a defined role in immune response, extracellular matrix and cell cycle and apoptosis. Keywords: HCV-advance disease state |
| 1822 | GSE6021 |
Profile | PTB is multifunctional RNA binding protein reported to be involved in splicing 3' -end processing, stability and translational regulation. Sample preparation methods (Gama-Carvalho et al, 2006, submitted) Suspension HeLa cells were grown in DMEM, 10% FCS, Pen/Strep and split 1:2 the day before harvesting. Post-nuclear cytoplasmic extracts were obtained as described (Herbert and Hecht 1999), using 5x107 cells/ml of lysis buffer. mRNAs were isolated by immunoprecipitation from 200ul of precleared HeLa cell extract, using the anti-U2AF65 MC3 mAb (Gama-Carvalho, Krauss et al. 1997) or the Bb7 anti-PTB mAb (ATCC) for 2h at 4ºC. Immune complexes were precipitated with a slurry with 50% of protein A/protein G agarose beads (Amersham), blocked with 100ug/ul of tRNA and RNAse free BSA (Ambion), by rotating for 1h at 4ºC and washed with lysis buffer. Complexes bound to the beads were eluted with TES buffer (10mM Tris, 0.5M EDTA, 0.5% SDS, pH 8.0) by heating at 65ºC for 10 minutes and Trizol extracted. Polyadenilated RNA in the cell extract (input) and in the immunoprecipitation sample was reverse transcribed, end-tagged and PCR amplified using the Super SMART PCR cDNA synthesis kit from Clontech, following manufacturer instructions. 1ug of input or precipitated RNA was used per RT-PCR reaction to produce samples for microarray hybridization. For each set of samples (input and immunoprecipitated) a 100ul test PCR reaction was performed according to manufacturer instructions and analyzed by agarose gel electrophoresis to select ideal conditions for amplification in the linear range. PCR reactions were pooled to obtain enough material for microarray hybridization. 15ug of PCR amplified cDNA from input and immunoprecipitated samples were fragmented, end labeled with biotin and hybridized to Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays as described (Brodsky, Meyer et al. 2005), following standard Affymetrix hybridization protocols. Brodsky, A. S., C. A. Meyer, et al. (2005). "Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells." Genome Biol 6(8): R64. Gama-Carvalho, M., R. D. Krauss, et al. (1997). "Targeting of U2AF65 to sites of active splicing in the nucleus." J Cell Biol 137(5): 975-87. Herbert, T. P. and N. B. Hecht (1999). "The mouse Y-box protein, MSY2, is associated with a kinase on non-polysomal mouse testicular mRNAs." Nucleic Acids Res 27(7): 1747-53. Keywords: RNA immunoprecipitation |
| 1823 | GSE41571 |
Profile | Objective: Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. A cell-specific approach has the potential to address the question of gene expression differences between particular cell types in stable and unstable plaques with greater precision than approaches based on the study of whole plaques. Using laser micro-dissection we isolated total RNA from macrophage-rich regions of stable and ruptured human atheromatous plaques derived from carotid endarterectomy samples which were comprehensively characterized using clinical, radiological and histological criteria, and carried out genome-wide gene expression profiling using microarrays. Results: The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences (p<0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques (p=5.4x10-7). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold (p=0.0086) and five-fold (p=0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions: We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential. |
| 1824 | GSE10072 |
Profile | Tobacco smoking is responsible for over 90% of lung cancer cases and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure. We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change>1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p=0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers. Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers. Keywords: comparative genomics |
| 1825 | GSE8633 |
Profile | Human conjunctival cell lines are useful tools for modeling ocular surface disease and evaluation of ocular drugs. Here we demonstrate that the IOBA-NHC and the ChWK conjunctival epithelial cell lines show using an unbiased gene microarray approach, unique gene expression signatures that differ from primary conjunctival epithelial cells (PCEC) and conjunctival tissue. Globally, the expression profile obtained with the Affymetrix U133A chip (>22000 genes) from PCEC was clustered more closely to conjunctival tissue than either of the 2 cell lines. However, when restricted to Gene Ontology sub-categories: cellular defense, viral replication/cycling, antigen presentation, anti-oxidant pathways and ubiquitin ligase complex, the cell lines correlated reasonably well to PCEC (r > 0.70). In the category response to inflammation, correlation of cell lines to PCEC was poor (r = -0.012 and –0.041 for IOBA-NHC and ChWK respectively). In general, the expression profile in IOBA-NHC cells was better correlated to PCEC than the ChWK cells. This was statistically significant (p<0.05) when one considers all the genes on the chip, or for proteins in the extracellular region, response to wounding, stress, lipid, protein and organic acid metabolism, development and differentiation. Our results are useful for the choice of conjunctival cell lines, if necessary, in future experiments, to increase validity of extrapolation to clinical scenarios. Keywords: Cell type comparison |
| 1826 | GSE7561 |
Profile | Substantial evidence implicates IGF-I signaling in the development and progression of breast cancer. To identify transcriptional targets of IGF action in breast cancer cells we performed gene expression profiling (>22,000 RNA transcripts) of IGF-I-stimulated MCF-7 cells, a well characterized breast cancer cell line that is highly responsive to IGFs. We defined an IGF-I gene signature pattern of hundreds of genes either up-regulated or down-regulated at both 3 and 24 hrs in vitro. After removing genes considered generic to cell proliferation, the signature was examined in four different public profile datasets of clinical breast tumors (representing close to 1000 patients), as well as in profile datasets of experimental models for various oncogenic signaling pathways. Genes with early and sustained regulation by IGF-I were highly enriched for transcriptional targets of the estrogen, Ras, and PI3K/Akt/mTOR pathways. The IGF-I signature appeared activated in most estrogen receptor-negative (ER-) clinical breast tumors and in a substantial subset (~25%) of ER+ breast tumors. Patients with tumors showing activation of the IGF-I signature tended to have a shorter time to disease recurrence (including patients not receiving adjuvant therapy), both when considering all patients and the subset of ER+ patients. We found evidence for cross-talk and common transcriptional endpoints between the IGF-I and estrogen systems. Our results support the idea that the IGF-I pathway is one mechanism by which breast tumors may acquire hormone independence and a more aggressive phenotype. Keywords: two group comparison |
| 1827 | GSE29326 |
Profile | Identification of relevant subgroups in childhood MDS patients by gene expression analysis and gene involve in progression into AML |
| 1828 | GSE44857 |
Profile | The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D). |
| 1829 | GSE46801 |
Profile | Melanocytes within benign human nevi are the paradigm for tumor suppressive senescent cells in a pre-malignant neoplasm. These cells typically contain mutations in either the BRAF or N-RAS oncogene and express markers of senescence including p16. However, a nevus can contain 10s to 100s of thousands of clonal melanocytes and approximately 20-30% of melanoma are thought to arise in association with a pre-existing nevus. Neither observation is indicative of fail-safe senescence-associated proliferation arrest and tumor suppression. We set out to better understand the status of nevus melanocytes. Proliferation-promoting Wnt target genes, such as cyclin D1 and c-myc, were repressed in oncogene-induced senescent melanocytes in vitro, and repression of Wnt signaling in these cells induced a senescent-like state. In contrast, cyclin D1 and c-myc were expressed in many melanocytes of human benign nevi. Specifically, activated Wnt signalling in nevi correlated inversely with nevus maturation, an established dermatopathological correlate of clinical benignancy. Single cell analyses of lone epidermal melanocytes and nevus melanocytes showed that expression of proliferation-promoting Wnt targets correlates with prior proliferative expansion of p16-expressing nevus melanocytes. In a mouse model, activation of Wnt signaling delayed, but did not bypass, senescence of oncogene-expressing melanocytes, leading to massive accumulation of proliferation-arrested, p16-positive non-malignant melanocytes. We conclude that clonal hyperproliferation of oncogene-expressing melanocytes to form a nevus is facilitated by transient delay of senescence due to activated Wnt signaling. The observation that activation of Wnt signaling correlates inversely with nevus maturation, an indicator of clinical benignancy, supports the notion that persistent destabilization of senescence by Wnt signaling contributes to the malignant potential of nevi. We used microarrays to detail the global programme of gene expression after lentiviral infection of BRAF in 3 replicates. |
| 1830 | GSE37964 |
Profile | The LEF/TCF family of transcription factors are downstream effectors of the WNT signaling pathway which drives colon tumorigenesis. LEF/TCFs have a DNA sequence-specific HMG box that binds Wnt Response Elements (WREs). The “E tail” isoforms of TCFs are alternatively spliced to include a second DNA binding domain called the C-clamp. We show that induction of a dominant negative C-clamp version of TCF1 (dnTCF1E) induces a p21-dependent stall in the growth of DLD1 colon cancer cells. Induction of a C-clamp mutant did not induce p21 or stall cell growth. Microarray analysis revealed that induction of p21 by dnTCF1EWT correlated with a decrease in expression of p21 suppressors that act at multiple levels from transcription (SP5, YAP1, RUNX1), to RNA stability (MSI2), and protein stability (CUL4A). We show that the C-clamp is a sequence specific DNA binding domain that can make contacts with 5’-RCCG-3’ elements upstream or downstream of WREs. The C-clamp-RCCG interaction was critical for TCF1E mediated transcriptional control of p21-connected target gene promoters. Our results indicate that a WNT/p21 circuit is driven by C-clamp target gene selection. Gene expression analysis of dnTCF and dnLEF induction in colon cancer cells. Dominant negative LEF/TCFs interferes with endogenous Wnt signaling by binding to Wnt Response Elements of target genes and displacing beta-catenin. Here we used induction of dnTCF-1 (wildtype and mutant forms of the C-clamp DNA binding domain) and dnLEF-1 to identify genes that change expression at 8 hours and 23 hours post-induction. |
| 1831 | GSE41328 |
Profile | Five colorectal adenocarcinomas and matched normal colonic tissues were analyzed with Affymetrix HG-U133-Plus-2.0 microarrays. Two labs independently generated microarray data with the same array platform on the same biological samples. |
| 1832 | GSE10174 |
Profile | This portion of the study evaluated the effects of topical 10% black raspberry gel application on gene expression profiles of premalignant oral lesions. Topical application of the bioadhesive black rasberry gel was observed to modulate gene expression and reduce proinflammatory proteins in human premalignant oral lesions. Keywords: Human oral tissues treated with 10% berry gfel |
| 1833 | GSE9750 |
Profile | This study is aimed in identification of gene expression profiles in cervical cancer and the role of specific genes in cervical carcinogenesis. Keywords: Gene expression in cervical cancer |
| 1834 | GSE18140 |
Profile | CONTEXT Nowadays the molecular mechanisms involved in endometrial receptivity and implantation are still not clear. OBJECTIVE The gene expression of human endometrium of patients undergoing an IVF treatment with GnRH antagonists/rec-FSH was studied. CONCLUSIONS COX-2 has been extensively studied as a crucial fertility element in both knock-out mice and human. It appears that increased expression of COX-2 and/or SCGB1D2 on the day of oocyte retrieval in GnRH antagonist/rec-FSH stimulated cycles coincides with a lower probability of achieving a clinical pregnancy in this cycle. Keywords: gene expression analysis, clinical pregnancy in IVF stimulated cycles |
| 1835 | GSE25014 |
Profile | Sickle cell disease is characterized by hemolysis vaso-occlusion and ischemia reperfusion injury. These events cause endothelial dysfunction and vasculopathies in multiple systems However, the lack of atherosclerotic lesions has led to the idea that there are adaptive mechanisms that protect the endothelium from major vascular insults in SCD patients. The molecular bases for this phenomenon are poorly defined. This study was designed to identify the global profile of genes induced by heme in the endothelium. |
| 1836 | GSE31595 |
Profile | Purpose: A 128-gene signature has been proposed to predict poor outcomes in patients with stage II and III colorectal cancer. In the present study we aimed to validate this previously published 128-gene signature on external and independent data from patients with stage II and III colon cancer. |
| 1837 | GSE35144 |
Profile | Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear if drug efficacy data obtained from xenograft models translate into clinically-relevant treatment modalities. In this study, we have generated a panel of 28 patient-derived colorectal cancer explants (PDCCEs), an extension of our previous work, by direct transplantation of human colorectal cancer (CRC) tissues into NOD-SCID mice. A comprehensive histological and molecular evaluation of PDCCEs and their corresponding patient tumor demonstrates that PDCCEs maintain histological features and global biology through multiple passages. Furthermore, we demonstrate that in vivo sensitivity of PDCCEs to oxaliplatin can predict patient outcomes. Our findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and can serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with CRC. |
| 1838 | GSE18676 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1839 | GSE39454 |
Profile | Immune cell infiltration in myositis were by examining microarray expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. |
| 1840 | GSE24081 |
Profile | CD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes – such as BATF – that inhibit T cell function. |
| 1841 | GSE16683 |
Profile | DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours compared to control cells. |
| 1842 | GSE2742 |
Profile | Total RNA was extracted from apratoxin A or vehicle treated HT29 cells using the RNeasy Mini Kit (Qiagen). Probe values from CEL files were condensed to probe sets using Rosetta Resolver software. Resolver ANOVA analysis was then performed between groups. Keywords: time course and dose |
| 1843 | GSE23618 |
Profile | In this study transcriptome profiling of dendritic cell subtypes was performed using various human dendritic cells. Monocyte-derived DC: CD14+ monocytes were obtained from buffy coats by Ficoll - gradient centrifugation and immunomagnetic cell separation using anti-CD14-conjugated microbeads. Monocytes were resuspended into 6-well culture dishes at a density of 1.5 x 10 million cells/ml and cultured in RPMI 1640 supplemented with 10% FBS containing 800 U/ml GM-CSF and 500 U/ml IL-4. Cells were cultured for 5 days and the IL-4 and GM-CSF addition was repeated at day 2. Dermal DC (DDC) and Langerhans Cells (LC) from skin: Human skin specimens were obtained from healthy donors undergoing corrective breast or abdominal plastic surgery after informed consent. Thick slices (3 mm) of skin containing the epidermis and the dermis were cut by use of a dermatome. Slices of skin were cut in pieces of 1 cm2 and incubated with Dispase II for 30–60 min at 37°C. The epidermis and dermis were separated with tweezers and washed with PBS. To isolate LC the epidermal sheets were incubated with PBS with 0.05% trypsin for 10 min at 37°C, and a single-cell suspension was prepared by pushing the tissue through 100 µm pore nylon cell strainers with a plunger of a 2-ml syringe. Epidermal cell suspension was enriched for LC by density centrifugation over Lymphoprep and CD1a-guided MACS (Miltenyi Biotec). To isolate DDC, the dermis was incubated with PBS containing Dispase and Collagenase A at 37°C for 2 h, after which, a single-cell suspension was prepared by pushing through 100 µm pore nylon cell strainers with a plunger of a 2-ml syringe. Cell suspension was enriched for DDC by CD1a-guided MACS. Blood Cd1c+ DC: Blood CD1c+ DC were isolated from periferal blood. BDCA1+ (CD1c) DCs were incubated with a lineage-specific PE-labeled Ab mixture, HLA-DR-allophycocyanin, and BDCA1-FITC. Lineage-negative and HLA-DRhigh DCs, positive for BDCA1 were sorted on a FACS and collected in tubes containing 1 ml of 100% FBS. A total of 40,000–100,000 cells was isolated (>98% pure). |
| 1844 | GSE10738 |
Profile | Cyclin T1-dependent genes in LPS-activated MM6 cells. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Keywords: cyclin T1 knockdown |
| 1845 | GSE9452 |
Profile | The samples are a part of a study aiming at diagnosing ulcerative colitis from genome-wide gene expression analysis of the colonic mucosa. Colonic mucosal samples were collected as endoscopic pinch biopsies from ulcerative colitis patients and from control subjects. Samples with and without macroscopic signs of inflammation were collected from the patients. Keywords: Disease state analysis |
| 1846 | GSE14378 |
Profile | The understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis like varying dormancy periods of Mets originating from the same primary tumor entity or the differing number of Mets in patients with the same primary tumor, are largely unknown. Knowing the molecular fundamentals of these phenomena would support the prognosis of patients´ outcome and facilitate the decision for an appropriate therapy regime. We analyzed the transcriptome-wide expression profiles of 20 pulmonary metastases of renal cell carcinoma in order to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval after nephrectomy (DFI) and the number of Mets per patient. Keywords: comparison of pulmonary metastases from patients with different clinical characteristics |
| 1847 | GSE40438 |
Profile | A consistent clinical feature of amyotrophic lateral sclerosis (ALS) is the sparing of eye movements. Pathological studies have confirmed that there is relative sparing of the cranial motor nuclei of the oculomotor trochlear and abducens nerves, although pathological changes resembling those seen in anterior horn cells are present to a lesser degree. The aim of the present study is to combine LCM and microarray analysis to study the differences between motor neurons that are selectively resistant (oculomotor neurons) and those that are vulnerable (lumbar spinal motor neurons) to the disease process in amyotrophic lateral sclerosis. |
| 1848 | GSE28476 |
Profile | Mutations of β-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and carcinomas (ACC). However the target genes of CTNNB1 have not yet been identified in adrenocortical tumors. Our objective was to identify genes de-regulated in adrenocortical tumors harbouring CTNNB1 genetic alterations. |
| 1849 | GSE34022 |
Profile | Hepatitis C virus (HCV) infection is primarily treated with a pegylated interferon alpha based therapy a regime that induces antiviral effects through the upregulation of many interferon-stimulated genes (ISGs). Whilst a number of anti-HCV ISGs have previously been identified, others may also be involved. Micorarrays were used to validate the presence of ISGs within subtracted libraries generated using the related techniques of suppression subtractive hybridisation and mirror orientation selection, which had initally been impllemented to isolate clones of ISGs following the interferon-alpha treatment of Huh-7 cells. |
| 1850 | GSE32547 |
Profile | 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors statins, are known to exert endothelial athero-protective effects through the induction of specific transcriptional factors and their downstream target genes besides lowering LDL-cholesterol. However its critical mechanism has not still been elucidated. Here we report the comprehensive change of transcripts induced by pitavastatin. We used repeated microarray analysis of HUVECs treated with pitavastatin for 4-hours, we identified a group of consistently up - or down - regulated genes. |
| 1851 | GSE11103 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1852 | GSE21550 |
Profile | Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR) the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent. Keywords: Time course |
| 1853 | GSE7845 |
Profile | Ricin is a potential bioweapon because of its toxicity availability, and ease of production. When delivered to the lungs, ricin causes severe pulmonary damage with symptoms that are similar to those observed in acute lung injury and adult respiratory distress syndrome. The airway epithelium plays an important role in the pathogenesis of many lung diseases, but its role in ricin intoxication has not been elucidated. Exposure of cultured primary human airway epithelial cells to ricin resulted in the activation of stress-activated protein kinases (SAPKs) and NF-κB and in the increased expression of multiple proinflammatory molecules. Among the genes upregulated by ricin and identified by microarray analysis were those associated with transcription, nucleosome assembly, inflammation, and response to stress. Sequence analysis of the promoters of these genes identified NF-κB as one of the transcription factors whose binding sites were over-represented. Although airway cells secrete TNF-α in response to ricin, blocking TNF-α did not prevent ricin-induced activation of NF-κB. Inhibition of p38 MAPK by a chemical inhibitor and NF-κB by short interfering RNA resulted in a marked reduction in the expression of proinflammatory genes, demonstrating the importance of these two pathways in ricin intoxication. Therefore, the p38 MAPK and NF-κB pathways are potential therapeutic targets for reducing the inflammatory consequences of ricin poisoning. Keywords: Comparative genomic hybridization |
| 1854 | GSE26928 |
Profile | Cells were isolated from healthy human donors (n=2). Unstimulated cells. Cells were stained with CD4 CD45RA, CCR7 and CXCR7. Using flow cytometry, 4 CD4+ T cell populations were sorted: (1) Naïve (CD45RA+CCR7+CXCR5-), (2) Central memory (CD45RA-CCR7+CXCR5-), (3) Effector memory (CD45RA-CCR7-CXCR5-) and (4) CXCR5+ cells (CD45RA-CCR7-CXCR5+) |
| 1855 | GSE14995 |
Profile | Background: JAG-1 is a ligand of Notch signaling and can regulate cell differentiation and proliferation in cancers. Recent studies indicated that JAG1 is a gene associated with cancer progression. Therefore we investigated the role of JAG1 in lung cancer progression. Methods: The expression of JAG1 was manipulated by overexpression or RNA silencing in several human lung cell lines. The effect of JAG1 on tumorigenesis and invasion was assessed by the cell anchorage-independent growth, cell proliferation, cell migration and invasion assays in vitro as well as metastasis in vivo. The potential downstream genes of JAG1 were identified by oligonucleotide microarrays and quantitative reverse transcription¡Vpolymerase chain reaction (RT-PCR). We further measured JAG1 expression in lung cancer specimens by RT-PCR. Correlation between JAG1 expression and overall survival of lung cancer patients was determined by using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: JAG1 enhanced anchorage-independent growth, cell migration, invasion in the lower invasive cells, CL1-0. JAG1 also increased the capability of migration and invasion in the other two lung cancer cell lines (A549 and NCI-H226). The silencing of JAG1 inhibited migration and invasion activities of the higher invasive cells, CL1-5, by siRNA technology. The invasion-promoting activity of JAG1 was also demonstrated in vivo by using a mouse metastasis model. By microarray analysis, we found that the expression of heat shock 70kDa protein 2 (HSPA2) was activated by JAG1 overexpression and eliminated by JAG1 silencing. Moreover, lung cancer patients with high JAG1 expressing tumors had shorter overall survival than those with low-expressing tumors. Conclusion: JAG1 might be an oncogene which promotes colonogenesis and metastasis, and high JAG1 expression is associated with shorten survival in lung cancer. |
| 1856 | GSE11227 |
Profile | Nocturnal home hemodialysis (NHD) [5 – 6 times a week 6-8 hours per session] augments uremia clearance and is associated with an increase in hemoglobin level. We have used microarray to have a global image of the changes at the gene expression. Keywords: Treatment |
| 1857 | GSE18373 |
Profile | Identification of signaling events contributing to the effect of recombinant MAGP2 on HUVECs and OVCA429. We used microarrays to identify the signaling events and up-regulated genes associated with MAGP2. |
| 1858 | GSE28444 |
Profile | Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus we scanned for possible candidate genes by using Affymetrix. |
| 1859 | GSE11942 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1860 | GSE10580 |
Profile | PRDM5 is a recently identified member of the PRDM family of proteins which functions as a transcriptional repressor by recruiting histone methyltransferase G9A to DNA, and behaves as a putative tumor suppressor in different types of cancer. We investigated PRDM5 function by identifying its target genes in U2OS cells at different time points after expression of PRDM5 protein. Keywords: Transcriptional regulation, time course |
| 1861 | GSE7806 |
Profile | The unfolded protein response (UPR) a signaling pathway triggered by endoplasmic reticulum (ER) stress, is induced by a range of environmental factors. Here we describe the identification and characterization of a synthetic small molecule, erstressin, which activates the UPR. Erstressin induced rapid phosphorylation of PERK and eIF2a and the alternative splicing of XBP-1, hallmark initiating events of the UPR. Further, erstressin activated the transcription of multiple genes involved in the UPR. Coincident with these effects, erstressin also downregulated the transcription of the inflammation-associated enzyme inducible nitric oxide synthase (iNOS) in cytokine-activated cells. A close analog of erstressin that failed to induce the UPR did not attenuate expression of iNOS, suggesting that both biological effects of erstressin were mediated by a common mechanism. Further, the structurally-distinct ER stressor thapsigargin also inhibited iNOS expression. Together these chemical genetic studies reveal an unanticipated anti-inflammatory role for the UPR. Keywords: Time course |
| 1862 | GSE24752 |
Profile | The polygenic nature of essential hypertension and its dependence on environmental factors pose a challenge for biomedical research. We hypothesized that microarray analysis of differential gene expression in peripheral blood cells would distinguish patients with hypertension from normotensive controls. We utilized microaaray analysis of differential gene expression in peripheral blood cells to identify differences in transcription profile of human essential hypertension compared with normotensive volunteers. |
| 1863 | GSE14245 |
Profile | Pancreatic cancer is the fourth leading cause of cancer death. Lack of early detection technology for pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. Oral fluid (saliva) meets the demand for non-invasive accessible, and highly efficient diagnostic medium. The level of salivary analytes, such as mRNA and microflora, vary upon disease onset; thus possess valuable signatures for early detection and screening. In this study, we evaluated the performance and translational utilities of the salivary transcriptomic and microbial biomarkers for non-invasive detection of early pancreatic cancer. Two biomarker discovery technologies were used to profile transcriptome in saliva supernatant and microflora in saliva pellet. The Affymetrix Human Genome U133 Plus 2.0 Array was used to discover altered gene expression in saliva supernatant. The Human Oral Microbe Identification Microarray (HOMIM) was used to investigate microflora shift in saliva pellet. Biomarkers selected from both studies were subjected to an independent clinical validation using a cohort of 30 early pancreatic cancer, 30 chronic pancreatitis and 30 healthy matched-control saliva samples. Two panels of salivary biomarkers, including eleven mRNA biomarkers and two microbial biomarkers were discovered and validated for pancreatic cancer detection. The logistic regression model with the combination of three mRNA biomarkers (ACRV1, DMXL2 and DPM1) yielded a ROC-plot AUC value of 0.974 (95% CI, 0.896 to 0.997; P < 0.0001) with 93.3% sensitivity and 90% specificity in distinguishing pancreatic cancer patients from healthy subjects. The logistic regression model with the combination of two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) yielded a ROC-plot AUC value of 0.895 (95% CI, 0.784 to 0.961; P < 0.0001) with 96.4% sensitivity and 82.1% specificity in distinguishing pancreatic cancer patients from healthy subjects. Importantly, the logistic regression model with the combination of four biomarkers (mRNA biomarkers, ACRV1, DMXL2 and DPM1; bacterial biomarker, S. mitis) could differentiate pancreatic cancer patients from all non-cancer subjects (chronic pancreatitis and healthy control), yielding a ROC-plot AUC value of 0.949 (95% CI, 0.877 to 0.985; P < 0.0001) with 92.9% sensitivity and 85.5% specificity. This study comprehensively compared the salivary transcriptome and microflora between pancreatic cancer and control subjects. We have discovered and validated eleven mRNA biomarkers and two microbial biomarkers for early detection of pancreatic cancer in saliva. The logistic regression model with four salivary biomarkers can detect pancreatic cancer specifically without the complication of chronic pancreatitis. This is the first report demonstrating the value of multiplex salivary biomarkers for the non-invasive detection of a high impact systemic cancer. Keywords: Salivary biomarker, pancreatic cancer, early detection, salivary transcriptome, salivary microflora |
| 1864 | GSE47873 |
Profile | Methylated DNA binding protein 2 (MBD2) has been shown to bind specific methylated promoters and suppress transcription. Here we systematically investigate MBD2 suppression by overexpressing MBD2 in MCF-10A cells and generating gene expression profiles of overexpressing cells and normal MCF-10A cells. |
| 1865 | GSE11057 |
Profile | Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. It has been applied to yeast and other systems but not to blood samples. Here we test the ability of this technique to determine the fractions of subsets of memory T cells in peripheral blood mononuclear cell (PBMC) samples. Keywords: cell type comparison |
| 1866 | GSE3744 |
Profile | Gene expression for 47 human breast tumor cases; (* normalized by GCRMA for global expression analysis) Keywords: Type |
| 1867 | GSE37317 |
Profile | Given the heterogeneity of disease evident from study of the presentation histomorphology, disease course, and molecular lesions of bladder cancer, a cohort of 8 non-muscle invasive and 11 muscle invasive bladder cancers were profiled for gene expression using the Affymetrix HG-U133A platform. |
| 1868 | GSE17195 |
Profile | We identified germline single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL) and its subtypes. Using the Affymetrix 500K Mapping array and publicly available genotypes we identified 18 SNPs whose allele frequency differed (P<1x10-5) between a pediatric ALL population (n=317) and non-ALL controls (n=17,958). Six of these SNPs differed (P≤0.05) in allele frequency among four ALL subtypes. Two SNPs in ARID5B not only differed between ALL and non-ALL groups (rs10821936, P=1.4x10-15, odds ratio[OR]=1.91; rs10994982, P=5.7x10-9, OR=1.62) but also distinguished B-hyperdiploid ALL from other subtypes (rs10821936, P=1.62 x10-5, OR=2.17; rs10994982, P=0.003, OR 1.72). These ARID5B SNPs also distinguished B-hyperdiploid ALL from other subtypes in an independent validation cohort (n=124 children with ALL) (P=0.003 and P=0.0008, OR 2.45 and 2.86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline genomic variations affect susceptibility to and characteristics of specific ALL subtypes. |
| 1869 | GSE10595 |
Profile | The hematopoietic microenvironment consists of non-hematopoietic derived stromal elements and hematopoietic derived monocytes and macrophages which interact and function together to control the proliferation and differentiation of early blood-forming cells. Two human stromal cell lines (HS-5 and HS-27a) representing distinct functional components of this microenvironment have been extensively characterized and shown to influence monocyte gene expression. This series of gene expression profiles is intended to extend the previous studies and identify which gene expression changes may require cell-cell contact or occur in the stromal cells as a result of monocyte influence;or in the monocytes as a result of stormal influences. Keywords: cellular response to cell contact and secreted factors |
| 1870 | GSE14956 |
Profile | To determine cardiac transcription profile in cyanotic Tetralogy of Fallot patients we collected myocardial samples immediately after institution of cardiopulmonary bypass from cyanotic Tetralogy of Fallot patients undergoing corrective surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology. |
| 1871 | GSE44239 |
Profile | To investigate the mechanism through which miR-203 inhibited the breast cancer cell invasion we overpression miR-203 in MDA-MB-231 cell line and performed a microarray to examine the genes which maybe targeted and down-regulated by miR-203. |
| 1872 | GSE15239 |
Profile | The liver has a remarkable ability to regenerate with the best experimental model for regeneration being partial hepatectomy (PHx), in which up to two-thirds of the liver may be removed, and the residual lobes enlarge to make up for the missing mass in a few days’ time. Liver regeneration has been extensively studied, mainly in rodent models, and characterized in terms of transcriptional regulation of gene expression. However, little is known regarding regulation of gene expression in a human model of regeneration following PHx. We used microarrays to follow gene expression changes shortly following PHx. |
| 1873 | GSE8823 |
Profile | Mononuclear phagocytes play an important role in the removal of apoptotic cells by expressing cell surface receptors that recognize and remove apoptotic cells. Based on the knowledge that cigarette smoking is associated with increased lung cell turnover we hypothesized that alveolar macrophages (AM) of normal cigarette smokers may exhibit enhanced expression of apoptotic cell removal receptor genes. AM obtained by bronchoalveolar lavage of normal non-smokers (n=11) and phenotypic normal smokers (n=13, 36 ± 6 pack-yr) were screened for mRNA expression of all known apoptotic cell removal receptors using Affymetrix HG-U133 Plus 2.0 chips with TaqMan RT-PCR confirmation. Of the 14 known apoptotic receptors expressed, only MER Tyrosine Kinase (MERTK), a transmembrane tyrosine kinase receptor, was significantly up-regulated in smokers. MERTK expression was then assessed in AM of smokers vs nonsmokers by TaqMan RT-PCR, immunohistochemistry, Western and flow analysis. Smoker AM had up-regulation of MERTK mRNA levels (smoker vs non-smoker, 3.6-fold by microarray, p<0.003; 9.5-fold by TaqMan RT-PCR, p<0.02). Immunohistochemistry demonstrated a qualitative increase in MERTK protein expression on AM of smokers. Increased protein expression of MERTK on AM of smokers was confirmed by Western and flow analyses (p< 0.007 and p< 0.0002, respectively). MERTK, a cell surface receptor that recognizes apoptotic cells, is expressed on human AM, and its expression is up-regulated in AM of cigarette smokers. This may reflect an increased demand for removal of apoptotic cells in smokers, an observation with implications for the development of chronic obstructive pulmonary disease (COPD), a disorder associated with dysregulated apoptosis of lung parenchymal cells. Keywords: Comparison of gene expression in alveolar macrophages of normal non-smokers and normal smokers. |
| 1874 | GSE18969 |
Profile | CD24 or heat stable antigen, is a cell surface sialoglycoprotein expressed on immature cells that disappears after the cells have reached their final differentiation stage. CD24 may be important in human embryonic kidney epithelial cell differentiation. In mice, CD24 expression is up-regulated in the early metanephros and localized to developing epithelial structures but the role and expression of CD24 in the developing human kidney has not been well described. In normal human fetal kidneys from 8 to 38 weeks gestation, CD24 expression was up-regulated and restricted to the early epithelial aggregates of the metanephric blastema and to the committed proliferating tubular epithelia of the S-shape nephron; however individual CD24+ cells were identified in the interstitium of later gestation and postnatal kidneys. In freshly isolated cells, FACS analysis demonstrated distinct CD24+ and CD24+133+ cell populations, constituting up to 16% and 14% respectively of the total cells analyzed. Isolated and expanded CD24+ clones displayed features of an epithelial progenitor cell line. Early fetal urinary tract obstruction resulted in an upregulation of CD24 expression, both in developing epithelial structures of early gestation kidneys and in the cells of the injured tubular epithelium of the later gestation kidneys. These results highlight the cell specific expression of CD24 in the developing human kidney and dysregulation in fetal urinary tract obstruction. We used microarrays to define the differences in global gene expression between obstructed and normal human fetal kidneys. |
| 1875 | GSE9865 |
Profile | Expression profile of dermal fibroblasts reprogrammed to a pluripotent state Keywords: cell-type comparison |
| 1876 | GSE1541 |
Profile | Alveolar epithalial cells (A549) were used as a model of pulmonary parenchymal cell activation to quiery gene expression profile of activation with either cyclic stretch (20% elongation) TNF (20 ng/ml), LPS (1 mcg/ml) or TNF+STRETCH at both 1 and 4 hrs. Keywords: time-course |
| 1877 | GSE15065 |
Profile | C/EBPbeta-2 results in EMT and ErbB indpendence this project investigated the gene changes in related genes upon C/EBPbeta-2 overexpression in MCF10A cells. We used microarray analysis to detail the global gene expression mediated by C/EBPbeta-2 and identified changes in known EMT genes however, known ErbB related genes were not altered. |
| 1878 | GSE10406 |
Profile | Our data demonstrates an increased number of submucosal glands in the sinus mucosa of pediatric patients with chronic rhinosinusitis (CRS). Additionally data in the literature indicates differentially altered expression of innate markers of immunity and of inflammatory mediators in the sinus mucosa of adult patients with cystic fibrosis, non-CF controls, and controls. Keywords: Differciation Study |
| 1879 | GSE17476 |
Profile | Over 180 LMNA gene mutations have been identified in human diseases including cardiac and skeletal myopathies lipodystrophies, and premature aging syndromes. Postulated mechanisms by which these mutations result in different phenotypes include perturbation of normal nuclear structure and chromosome organization, and gene activity. We investigated whether a cardiomyopathic LMNA mutation, E161K, displayed abnormal gene expression. We compared the gene expression profile in the E161K LMNA-mutant heart to that of an end stage LMNA-normal heart. |
| 1880 | GSE12767 |
Profile | 4 chorionic villus sampling specimens in pregnancies destined for preeclampsia and 8 matched controls were analyzed 36 genes were differentially expressed using J5 score and prediction modeling in caGEDA computer program Keywords: snap frozen banked CVS specimens with known pregnancy outcomes revealed genes differentially expressed in preeclampsia pregnancies |
| 1881 | GSE23554 |
Profile | Background. Genome-wide expression changes are associated with development of chemoresistance in patients with ovarian cancer (OVCA); the BCL2 antagonist of cell death (BAD) apoptosis pathway may play a role in clinical outcome. Methods. We analyzed specimens and/or genomic data from 1406 patients and 116 cancer cell lines. Genome-wide expression changes and cisplatin-resistance were evaluated in OVCA cell lines subjected to a total of 144 (cisplatin)-treatment/recovery cycles. Pathway analysis was performed on genes associated with increasing cisplatin-resistance. BAD protein phosphorylation was studied in patient samples and cell lines, and small interfering RNAs (siRNA) used to explore the pathway as a therapeutic target. We evaluated the influence of BAD-pathway expression on chemosensitivity and/or clinical outcome using genomic data from 60 human cancer cell lines and ovarian, breast, colon, and brain cancers from 1,258 patients. Results. The BAD pathway was associated with evolution of OVCA cell line cisplatin-resistance (P<0.001) and resistance of 7 human cancer cell types to 8 cytotoxic agents (P<0.05). OVCA chemoresistance was associated with BAD protein phosphorylation, and targeted siRNA modulation produced corresponding changes in chemosensitivity. Expression of a 47-gene BAD-pathway signature was associated with survival of 1,258 patients with ovarian, breast, colon, and brain cancer. The OVCA BAD-pathway signature survival advantage was independent of surgical cytoreductive status. Conclusions. The BAD apoptosis pathway influences the sensitivity of human cancers to a variety of chemotherapies, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a potential biomarker of therapeutic response, patient survival, and as a promising therapeutic target. |
| 1882 | GSE18498 |
Profile | The effects of the CDK inhibitor PHA-793887 on the A2780 human adenocarcinoma ovary cell line were analysed by gene expression profiling. |
| 1883 | GSE14886 |
Profile | HTETOP cells derived from the human fibrosarcoma cell line HT1080, express human topoisomearse II α (TOP2A) exclusively from a tetracycline (TET)-regulated transgene, we used HTETOP cells to differentiate between TOP2A-dependent and –independent apoptotic effects of doxorubicin and dexrazoxane. We used microarrays to detect global transcriptional changes in HTETOP cells following tetracycline doxycycline or dexrazoxane treatment. Keywords: Drug treatment comparison |
| 1884 | GSE20164 |
Profile | Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. |
| 1885 | GSE26523 |
Profile | Human epidermal keratinocytes were treated with 25 ng.ml EphB2 or EFNA4 both as-Fc conjugates (Sigma). |
| 1886 | GSE6022 |
Profile | U2AF65 is an essential splicing factor involved in the 3'splice site recognition dureing the first steps of spliceosome assembly. In addition this protein has nucleocytoplasmic shuttling activity and the Drosophila homologue has been implicated in mRNA export. We have used microarray hybridization coupled to RNA immunoprecipitation from HeLa cell cytoplasmic extracts using anti-U2AF65 antibodies to identify mRNA molecules associated with the U2AF65 splicing factor Sample preparation methods (Gama-Carvalho et al, 2006, submitted) Suspension HeLa cells were grown in DMEM, 10% FCS, Pen/Strep and split 1:2 the day before harvesting. Post-nuclear cytoplasmic extracts were obtained as described (Herbert and Hecht 1999), using 5x107 cells/ml of lysis buffer. mRNAs were isolated by immunoprecipitation from 200ul of precleared HeLa cell extract, using the anti-U2AF65 MC3 mAb (Gama-Carvalho, Krauss et al. 1997) or the Bb7 anti-PTB mAb (ATCC) for 2h at 4ºC. Immune complexes were precipitated with a slurry with 50% of protein A/protein G agarose beads (Amersham), blocked with 100ug/ul of tRNA and RNAse free BSA (Ambion), by rotating for 1h at 4ºC and washed with lysis buffer. Complexes bound to the beads were eluted with TES buffer (10mM Tris, 0.5M EDTA, 0.5% SDS, pH 8.0) by heating at 65ºC for 10 minutes and Trizol extracted. Polyadenilated RNA in the cell extract (input) and in the immunoprecipitation sample was reverse transcribed, end-tagged and PCR amplified using the Super SMART PCR cDNA synthesis kit from Clontech, following manufacturer instructions. 1ug of input or precipitated RNA was used per RT-PCR reaction to produce samples for microarray hybridization. For each set of samples (input and immunoprecipitated) a 100ul test PCR reaction was performed according to manufacturer instructions and analyzed by agarose gel electrophoresis to select ideal conditions for amplification in the linear range. PCR reactions were pooled to obtain enough material for microarray hybridization. 15ug of PCR amplified cDNA from input and immunoprecipitated samples were fragmented, end labeled with biotin and hybridized to Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays as described (Brodsky, Meyer et al. 2005), following standard Affymetrix hybridization protocols. Brodsky, A. S., C. A. Meyer, et al. (2005). "Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells." Genome Biol 6(8): R64. Gama-Carvalho, M., R. D. Krauss, et al. (1997). "Targeting of U2AF65 to sites of active splicing in the nucleus." J Cell Biol 137(5): 975-87. Herbert, T. P. and N. B. Hecht (1999). "The mouse Y-box protein, MSY2, is associated with a kinase on non-polysomal mouse testicular mRNAs." Nucleic Acids Res 27(7): 1747-53. Keywords: RNA immunoprecipitation |
| 1887 | GSE41414 |
Profile | Objective: to focus on the molecular mechanisms involved in the ALS related atrophy process that leads to selective wasting muscles . |
| 1888 | GSE38091 |
Profile | Hematopoietic stem cells (HSCs) are located in the bone marrow in a specific microenvironment referred as the hematopoietic stem cell niche where HSCs interact with a variety of stromal cells. Though several components of the stem cell niche have been identified, the regulatory mechanisms through which such components regulate the stem cell fate are still unknown. In order to address this issue, we investigated how osteoblasts (OBs) can affect the molecular and functional phenotype of HSCs and vice versa. Our data showed that CD34+ cells cultured with OBs give rise to higher total cell numbers, produce more CFU and maintain a higher percentage of CD34+CD38- cells compared to control culture. Moreover, clonogenic assay and long-term culture results showed that OBs enhance HSC differentiation towards the mono/macrophage lineage at the expense of the granulocytic and erythroid ones. Finally, GEP analysis allowed us to identify several cytokine-receptor networks, such as WNT pathway, and transcription factors, as TWIST1 and FOXC1, that could be activated by co-culture with OBs and could be responsible for the biological effects reported above. Altogether our results indicate that OBs are able to affect both HPC maintenance and differentiation capacity by modulating mono/macrophage and erythroid commitment. |
| 1889 | GSE34156 |
Profile | human blood monocytes were isolated activated and harvested at several timepoints In this study, we identified genes that were differentially expressed in human monocytes activated with eiter NOD2L and/or TLR2/1L. |
| 1890 | GSE14900 |
Profile | Mitochondrial biogenesis is under the control of two different genetic systems: the nuclear genome (nDNA) and the mitochondrial genome (mtDNA). mtDNA is a circular genome of 16.6 kb encoding 13 of the approximately 90 subunits that form the respiratory chain the remaining ones being encoded by the nuclear genome (nDNA). Eukaryotic cells are able to monitor and respond to changes in mitochondrial function through alterations in nuclear gene expression, a phenomenon first defined in yeast and known as retrograde regulation. With this experiment we aimed to identify the set of nuclear genes that significantly change their expression level in response to depletion of mtDNA. Keywords: case-control |
| 1891 | GSE3542 |
Profile | Profiling of MCF-7 cell lines stably overexpressing constitutively active Raf-1 constitutively active MEK, constitutively active c-erbB-2, or ligand-activatable EGFR as models of overexpressed growth factor signaling, as well as control vector transfected cells (coMCF-7) and control vector transfected cells long-term adapted for estrogen-independent growth (coMCF-7/lt-E2). Keywords: Cell Line Comparison |
| 1892 | GSE30985 |
Profile | Epigenetic changes accompany tumorigenesis and are required for tumor maintenance. Modulation of DNA methylation state histone acetylation, and histone methylation, as well as reversal of disease-associated epigenetic state aberrations, can be disruptive to malignant disease progression. We produced lipophilic prodrugs of decitabine, which is a DNA methyltransferase inhibitor and is efficacious in treatment of myelodysplastic syndromes when dosed subcutaneously. Comparison of parent and prodrug activities in vitro and in vivo revealed comparable effects and unveiled several novel features of nucleoside analog molecular activity in vitro. |
| 1893 | GSE18070 |
Profile | In this study we took advantage of a previously established breast cancer progression cell line model system, which consists of a parental MCF10A (MI) spontaneously immortalized mammary epithelial cell line and two of its derivatives: 1) MCF10ATk.cl2 (MII), a MCF10A H-Ras transformed cell line and 3) MCF10CA1h (MIII), derived from a xenograft of the MII cells in nude mice that progressed to carcinoma (1, 2). These cell lines were previously reported to exhibit distinct tumorigenic properties when re-implanted in nude mice; MI is non-tumorigenic, MII forms benign hyperplastic lesions and MIII forms low-grade, well differentiated carcinomas (2, 3). The advantage of this system is that these cell lines were derived from a common genetic background (MCF10A) and accumulated distinct genetic/epigenetic alterations in vivo enabling them to acquire a range of non-tumorigenic to carcinogenic properties. Our initial studies showed that MIII cells, but not MI or MII, exhibit an EMT phenotype, promoter DNA hypermethylation of epithelial genes and highly invasive properties in vitro. To investigate the role of TGFβ pathway in these processes, we disrupted the TGFβ downstream signaling events in MIII, by stably overexpressing the inhibitory Smad7, and analyzed the gene expression profiles of MII, MIII and MIIISmad7 cells using microarray analysis. Total RNA was isolated from three biological replicates corresponding to MIIpB, MIIIpB and MIIIpB-Smad7 cells using Trizol (Invitrogen) according to the manufacturer’s protocol, and the RNeasy mini-kit (Qiagen) was used to clean-up the RNA. Labeled cRNA fragments derived from the samples were hybridized onto human genome U133 plus 2.0 arrays (Affymetrix). Gene-expression estimates and a measure of sequence-specificity of the hybridization intensities were both determined using standard settings in MAS5 (Affymetrix). Probesets that did not exhibit sequence-specific hybridization in any sample were excluded from subsequent analysis. Differential expression between MIIpB and MIIIpB as well as between MIIIpB and MIIIpBSmad7 was assessed using Student’s t-test. Genes with a false discovery rate (FDR) < 0.05 and a greater than 2-fold difference in expression between the two cell lines were considered to be differentially expressed. |
| 1894 | GSE16728 |
Profile | Room temperature whole blood mRNA stabilization procedures such as the PAX gene system, are critical for the application of transcriptional analysis to population-based clinical studies. Global transcriptome analysis of whole blood RNA using microarrays has proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA in the blood. This is a particular problem in patients with sickle-cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation . In order to more accurately measure the steady state whole blood transcriptome in sickle-cell patients, we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA samples for genome-wide transcriptome analyses using oligonucleotide arrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle-cell disease patients. This led to an improvement in microarray data quality with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. The differentially modulated genes from the globin depleted samples had a higher correlation coefficient to the 112 genes identified to be significantly altered in our previous study on sickle-cell disease using PBMC preparations. Additionally, the analysis of differences between the whole blood transcriptome and PBMC transcriptome reveals important erythrocyte genes that participate in sickle-cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases and in multicenter clinical trials investigating a wide range of nonhematologic disorders where fractionation of cell types is impracticable. Keywords: Microarrays, PAXgene, globin reduction, whole blood, PBMC |
| 1895 | GSE22256 |
Profile | 786-0 is a cell line derived from a clear cell renal carcinoma. Previous studies have shown that the 786-O cell line harbors an inactivating mutation in the von-Hippel Lindau (VHL) gene. Mutations in the VHL gene occur in the majority of sporadic clear cell renal cell. To determine how inactivation of the VHL affects cellular functions we created a derivative of 786-0, which we call 786-VHL in which a functional allele of VHL has been introduced back into the 786-O cell line. |
| 1896 | GSE10650 |
Profile | The gain of Protocadherin LKC (PCDH24) expression in colon carcinoma cell line HCT116 has been shown to induce contact inhibition thereby completely abolishing tumor formation in vivo. To clarify the molecular mechanism, we performed DNA microarray analysis and compared gene-expression pattern between control and PCDH24-expressing HCT116 cells. Approximately 2000 genes were apparently changed their expression. Further proteomics analysis using 2-DE/MS confirmed the dramatic changes and provided additional information. We were aware that these changes are quite similar to the changes observed in epithelial-mesenchymal transition (EMT), most drastic changes in development and cancer metastasis. We thus further analyzed these changes using specific antibodies, and found distinct difference between these two phenomena. Among the differences, nuclear translocation of catenin beta 1 (CTNNB1) was inhibited by PCDH24-expression, subsequently some of the downstream nodes were suppressed. Although contact inhibition and cancer metastasis are completely opposite aspect of the cells, we expect that the identified differences will be key nodes to understand the relationship. We also expect that the nodes will be a target to modulate tumors arising stem cell transplantation (SCT), as well as a therapeutic target for cancer metastasis. Keywords: dose response |
| 1897 | GSE11618 |
Profile | X-linked inhibitor of apoptosis (XIAP) is the most potent endogenous caspase inhibitor preventing cell death via caspase-9 -7 and -3 (initiator and executioner caspase pathways). Using short hairpin RNA (shRNA) against XIAP, stably expressed in a parent HCT116 human colon cancer cell line, a series of clones have been developed. XIAP mRNA levels were established by RT-PCR, the four X (XIAP knockdown) clonal cell lines show 82-93% reduction in XIAP mRNA when compared to the four L (luciferase control) cell lines. Immunoblot analysis showed a 67-89% reduction in XIAP protein in X cell lines compared to L. RNA was analysed by microarray and XIAP knockdown was confirmed in 7 probe sets, there was no significant compensation of other IAP family members. XIAP knockdown induced a 2-fold increase in the basal level of apoptosis without modification of caspase 3/7 activity. Finally, XIAP knockdown sensitises cells to radiotherapy by 20%, to recombinant TRAIL by a 3-fold factor, and to paclitaxel and docetaxel by >2 fold factor. Future work should focus on targeted agents such as rhTRAIL in combination with strategies to down regulate XIAP. XIAP antisense is now in clinical development in oncology. |
| 1898 | GSE12113 |
Profile | Tumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis. These tumors were s.c. explanted in xenograft models for subsequent treatment experiments. This study aimed to assess the antitumor activity of the Hsp90 inhibitor IPI-504, in pancreatic cancer and to determine the biological effects of the agent. Keywords: Pharmacogenetics |
| 1899 | GSE8388 |
Profile | A unique feature of the tumour cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events especially promoter DNA-methylation, are involved in this silencing of many B-cell associated genes. Here we show that DNA-demethylation alone or in conjunction with histone-acetylation is not able to reconstitute the B-cell gene expression program in cultured HRS cells. Instead, combined DNA-demethylation and histone-acetylation of B cells induce a nearly complete extinction of their B-cell expression program and a tremendous up-regulation of numerous cHL characteristic genes including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the up-regulation of cHL characteristic genes and the extinction of the B-cell expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic up-regulation of cHL characteristic genes thus play - in addition to promoter DNA-hypermethylation of B-cell associated genes – a pivotal role for the reprogramming of HRS cells and explain why DNA-demethylation alone is unable to reconstitute the B-cell expression program in HRS cells. Keywords: Epigenetic modification |
| 1900 | GSE10575 |
Profile | The regeneration of diseased hyaline cartilage remains a great challenge mainly because degeneration activities after major injury or due to age-related processes overwhelm the self-renewal capacity of the tissue. We show that repair tissue from human articular cartilage of late stages of osteoarthritis harbor a unique progenitor cell population, termed chondrogenic progenitor cells exhibiting stem cell characteristics, such as multipotency, lack of immune system activation and, in particular, migratory activity. The isolated CPC exhibit a high chondrogenic potential and were able to populate diseased tissue in vivo. Moreover, down-regulation of the osteogenic transcription factor runx-2 enhanced the expression of the chondrogenic transcription factor sox-9 and consequently the matrix synthesis potential of chondrogenic progenitor cells. Our results, while offering new insight into the biology of progenitor cells from diseased cartilage tissue, might assist future strategies to treat late stages of osteoarthritis. Keywords: cell type comparison |
| 1901 | GSE24337 |
Profile | Background. The human airway epithelium consists of 4 major cell types: ciliated secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem / progenitor cells for the other airway cell types. The objective of this study is to better understand basal cell biology by defining the subset of expressed genes that characterize the signature of human airway epithelial basal cells. Methodology / Principal Findings. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium of healthy nonsmokers obtained by bronchial brushings in comparison to the transcriptome of the complete differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to the differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The human airway basal cell signature displayed extensive overlap with genes expressed in basal cells from other human tissues and murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the airway basal cell signature was characterized by genes encoding extracellular matrix components, and growth factors and growth factor receptors, including genes related to EGFR and VEGFR signaling. However, while human airway basal cells share similarity with basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, integrins, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion / Significance. The human airway epithelial basal cells signature identified in the present study provides novel insights into the ontogeny, molecular phenotype and biology of the stem / progenitor cells of the human airway epithelium. |
| 1902 | GSE47641 |
Profile | We recently identified recurrent mutations of cohesin complex in myeloid neoplasms through whole-exome sequencing analysis. RAD21 is one of the main components of the cohesin complex. In this study to investigate the biological impact of wild-type RAD21 on Kasumi1 cells harboring RAD21 mutation, Kasumi1 cells were retrovirally transduced with either mock or wild-type RAD21, and expression array was performed. |
| 1903 | GSE42114 |
Profile | We sought to understand the differences between the basal and suprabasal layers of normal human skin epidermis. |
| 1904 | GSE14701 |
Profile | We used microarray to look at the genes deregulated in PaTu8988s (adenovirus insensitive) and PaTu8988t (adenovirus sensitive) cell lines PaTu8988s and PaTu8988t are pancreatic cell lines derived from the same patient and show significant responses to oncolytic adenoviruses. The different response to adenovirus in these cell lines is not related to the previously known mechanisms that affect adenovirus infection. The two cell lines represent represent a "suitable" model to screen tumour-associated genes affecting the potency of aoncolytic adenovirus. |
| 1905 | GSE19665 |
Profile | Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors. |
| 1906 | GSE16219 |
Profile | We previously reported that human T cell lymphotropic virus 1 (HTLV-1) Tax oncoprotein constitutively activates TAK1. Here we established Tax-positive HuT-102 cells stably downregulated TAK1 expression by short-hairpin RNA (HuT-shTAK1 cells), and investigated the physiological function of TAK1. Microarray analysis demonstrated that several interferon (IFN)-inducible genes including chemokines such as CXCL10 and CCL5 were significantly downregulated in HuT-shTAK1 cells. In contrast, Tax-mediated constitutive activation of NF-kB was intact in HuT-shTAK1 cells. IRF3, a critical transcription factor in innate immunity to viral infection, was constitutively activated in a Tax-dependent manner. Activation of IRF3 and IRF3-dependent gene expression were dependent on TAK1 and TBK1. On the other hand, IRF4, another IRF family of transcription factor overexpressed in a Tax-independent manner, negatively regulated the TAK1-dependent IRF3 transcriptional activity. Together, HTLV-1 manipulates IFN signaling by regulating both positive and negative IRFs. |
| 1907 | GSE46170 |
Profile | Childhood T-ALL samples were compared with thymocyte subsets we compared key molecules of wnt signaling pathway in our cohort |
| 1908 | GSE26453 |
Profile | Assessing relevant differences between human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells is important given that such differences may impact their potential therapeutic use. We used microarray to profile the changes in global gene expression arising from the reprogramming of somatic cells to induced pluripotent stem cells. |
| 1909 | GSE5389 |
Profile | Bipolar affective disorder is a severe psychiatric disorder with a strong genetic component but unknown pathophysiology. We used microarray technology (Affymetrix HG-U133A GeneChips) to determine the expression of approximately 22 000 mRNA transcripts in post-mortem brain tissue (orbitofrontal cortex) from patients with bipolar disorder and matched healthy controls. Orbitofrontal cortex tissue from a cohort of 30 subjects was investigated and the final analysis included 10 bipolar and 11 control subjects. Differences between disease and control groups were identified using a rigorous statistical analysis with correction for confounding variables and multiple testing. Keywords: disease state analysis |
| 1910 | GSE14230 |
Profile | To determine a gene/molecular fingerprint of multiple myeloma (MM) endothelial cells (MMECs) also identifying some of the vascular mechanisms that govern the malignant progression from quiescent monoclonal gammopathy of undetermined significance (MGUS). A comparative gene expression profiling (GEP) was carried out on patient-derived MMECs and MGUS endothelial cells (MGECs) using the Affymetrix U133A Arrays. Expression of selective vascular markers were also validated by RT-PCR and immunoblotting analysis in primary cultures of ECs isolated from total bone marrow (BM)-mononuclear cells. Twenty-two genes were found differently expressed in MMECs compared to MGECs (with 14 down-regulated and 8 up-regulated), thus proving that molecular differences were maintained in vitro. Specific pathways analysis revealed transcriptional and protein expression changes for key regulators of extracellular matrix formation and bone remodeling, cell-adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Specifically, we focused on six of these genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3 and SEPW1), which were not previously functionally correlated to the overangiogenic phenotype of MMECs and disease activity. These data identified distinct EC gene expression profiles and some vascular phenotypes that could influence the remodeling of the BM-microenvironment in patients with active MM. A better understanding of the linkage between genetic and epigenetic events in MM tumor/ECs may contribute to the molecular classification of the disease, thereby identifying selective targets of more effective anti-vessel/stroma therapeutic strategies. Keywords: Gene expression profiling, endothelial cells, Multiple Myeloma. |
| 1911 | GSE22445 |
Profile | Here we report that piroxicam/cisplatin combined treatment exerts an apoptotic effect on mesothelioma cells. Genome-wide transcriptome analyses lead us to identify p21 as the possible apoptosis mediator acting as downstream target of the piroxicam/cisplatin treatment. |
| 1912 | GSE46528 |
Profile | Hepatitis C virus interacts extensively with host factors not only to establish productive infection but also to trigger unique pathological processes. Our recent genome-wide siRNA screen demonstrated that IKKα is a critical host factor for HCV. Here we describe a novel NF-κB-independent and kinase-mediated nuclear function of IKKα in HCV assembly. HCV infection through its 3’-untranslated region, interacts with DDX3X to activate IKKα, which translocates to the nucleus and induces a CBP/p300-mediated transcriptional program involving SREBPs. This novel innate pathway induces lipogenic genes and enhances core-associated lipid droplet formation to facilitate viral assembly. Chemical inhibitors of IKKα suppress HCV infection and IKKα-induced lipogenesis, offering a proof-of-concept approach for novel HCV therapeutic development. Our results show that HCV commands a novel mechanism to its advantage by exploiting intrinsic innate response and hijacking lipid metabolism, which likely contributes to a high chronicity rate and the pathological hallmark of steatosis in HCV infection. |
| 1913 | GSE7538 |
Profile | The effects of 7.5 micromolar parthenolide (PTL) were assessed on primary CD34+ acute myelogenous leukemia specimens obtained from 12 patients. Keywords: drug response gene expression search agent |
| 1914 | GSE30296 |
Profile | Follistatin is a folliculogenesis regulating protein that has been found in relatively high concentration in the female ovarian tissues. Follistatin acts as an antagonist to the function of Activin which is often found elevated in ovarian carcinogenesis and thus presents a possibility for therapeutic intervention in controlling ovarian cancer. Most of the ovarian cancer occurs in its ovarian surface epithelium (OSE) cells. Although breast cancer susceptibility gene 1 (BRCA1) is a known tumor suppressor for breast cancer but its role in ovarian cancer is beginning to unfold. We have shown that in ovarian carcinoma cells (SKOV3), stable overexpression of BRCA1 stimulates Follistatin secretion and simultaneously downregulates Activin expression. Moreover, knock down of BRCA1 in immortalized OSE (IOSE) cells from human ovarian tissue demonstrates downregulation of Follistatin secretion with simultaneous up regulation of Activin expression. IOSE cells generated from an ovarian cancer patient with BRCA1 mutation failed to secrete Follistatin in the medium. Our results indicate a novel function for BRCA1 in the form of regulation of the expression of Follistatin in the ovarian cells. |
| 1915 | GSE24522 |
Profile | Multiple myeloma is characterized by frequent chromosomal alterations. Deletion of chr 13 especially band 13q14, is commonly observed in early stages of MM, suggesting the presence of tumor suppressor genes (TSG) within this region. We sought to functionally validate the role of the microRNAs-15a/16 cluster, centered at the deleted region, as TSGs and delineate their downstream target genes in MM. Using “sponge” lentiviral vectors to competitive stably inhibit mature microRNAs in vitro and in vivo, we have documented enhanced proliferative and invasive capacity of cells with stably inhibition of miR-16. Expression profiling analysis of miR-16-deficient cells identified a large number of downstream target genes. This loss-of-function system, which mimics the 13q chromosomal deletion, provides a valuable tool to investigate their function in MM pathogenesis and their potential use as therapeutic targets. |
| 1916 | GSE18198 |
Profile | NOTCH proteins regulate signaling pathways involved in cellular differentiation proliferation and death. Overactive Notch signaling as been observed in numerous cancers and has been extensively studied in the context of T-cell acute lymphoblastic leukemia (T-ALL) where more than 50% of pateints harbour mutant NOTCH1. Small molecule modulators of these proteins would be important for understanding the role of NOTCH proteins in malignant and normal biological processes. We were interested to measure the global changes in gene expression upon treatment of the human T-ALL cell lines HPB-ALL and KOPT-K1 with either vehicle alone (DMSO) or SAHM1, an alpha-helical hydrocarbon stapled peptide derived from the MAML1 co-activator protein. |
| 1917 | GSE14934 |
Profile | Gene expression profiles were collected from HEK-HT cells expressing H-Ras with Ras-activating (G12V) Raf-activating (G12V,T35S), RalGEF-activating (G12V,E37G), or PI3K-activating (G12V,Y40C) mutations. Keywords: Comparison of Ras pathway components. |
| 1918 | GSE31518 |
Profile | We used the microarray data to analyze host cells response on A549 cells infected with Influenza A virus (A/Singapore/478/2009 (pH1N1)) |
| 1919 | GSE16238 |
Profile | The EVI1 gene codes for a transcription factor with important roles in development and leukemogenesis. Overexpression of EVI1 in acute myeloid leukemia (AML) is one of the worst prognostic factors in patients with and without 3q26 rearrangements. Evi1 acts in several pathways through the interaction with proteins with important functions in hematopoiesis; however the role of Evi1 as a transcription factor is not well known, and only some Evi1 target genes have been identified in mice. Our aim was to investigate the pathways and direct target genes of EVI1. Differential expression profiles after EVI1 knockdown allowed us to identify 125 genes involved in cell growth, differentiation and signal transduction that could be related to EVI1. Moreover, we looked for potential EVI1 binding sites within the region 1000 bp upstream of the transcription start sites of all human genes. We selected a total of 70 genes from the bioinformatics search, genes related to EVI1 by literature, and genes differentially expressed in the expression array. ChIP in the TF1 and HEL cell lines with two EVI1 antibodies demonstrated that EVI1 binds to the proximal promoter regions of 18 of these genes, most of them involved in important differentiation and proliferation pathways, confirming the important role of EVI1. Interestingly, EVI1 binds to the proximal region of its promoter, suggesting that it could be regulating its own transcription. Further functional studies are in progress. These data provide a starting point for further studies aimed at uncovering the mechanism for EVI1-induced transformation leukemias. Keywords: Gene expression analysis after transient knockdown of EVI1. |
| 1920 | GSE28503 |
Profile | Transcription of mRNA in mammalian is mainly performed by RNA polymerase II (PolII). POLRMT is responsible for the production of cytoplasmic and nuclear form of mitochondrial RNA polymerase. The former (mtRNAP) participates in transcription of RNA in the mitochondria while the latter (spRNAP-IV) is responsible for some mRNA transcription in the nucleus. The nature and amount of genes transcribed by spRNAP-IV still remains unclear. Thus we scanned for possible candidate genes by using Affymetrix. |
| 1921 | GSE11394 |
Profile | Highly purified subpopulations of primitive bipotent and committed luminal progenitor cells as well as mature luminal and myoepithelial cells from normal human mammary tissue were isolated and compared their transcriptomes obtained using the Affymetrix GeneChip Human X3P Array. Keywords: human mammary progenitors stem cells, transcriptomes, Notch signaling, gene expression |
| 1922 | GSE4646 |
Profile | We examined the adherence-mediated signaling of meningococci to human cells by comparing gene expression profiles of primary human umbilical vein endothelial cells (HUVEC) infected by piliated and adherent wild-type (WT) frpC/frpA-deficient mutant, or the non-adherent (ΔpilD) N. meningitidis MC58 bacteria defective in production of the type IV pilus, respectively. Surprisingly, no significant difference was found between the transcriptomes of HUVECs infected by bacteria producing, or not the RTX FrpC and FrpA proteins, thus failing to provide any hints on their biological activity. In contrast, pili-mediated adhesion of meningococci resulted in alterations of expression levels of human genes known to regulate apoptosis, cell proliferation, inflammatory response or adhesion. In particular, genes for signaling pathway proteins involved in early embryonic development, such as transforming growth factor-β (TGF-β)/Smad, Wnt/β-catenin, and Notch/Jagged were found to be upregulated upon adhesion of N. meningitidis together with genes for a number of transcription factors. This reveals that adhering piliated meningocci manipulate signaling pathways controlling human cell proliferation, survival and defense mechanisms, while establishing a commensal relationship with the host. Keywords: time course, infection response, genetic modification |
| 1923 | GSE18877 |
Profile | Dosage compensation restores a balanced network of gene expression between autosomes and sex chromosomes in males (XY) and females (XX). In mammals this is achieved by doubling the expression of X-linked genes in both sexes, together with X inactivation in females. X up-regulation may be controlled by DNA sequence based and/or epigenetic mechanisms that double the X output potentially in response to an autosomal counting factor. Human triploids with either one or two active X chromosomes (Xa) provide a mean to test X chromosome expression in the presence of three sets of autosomes, which will help understand the underlying mechanisms of X up-regulation. We measured whole genome gene expression in human triploid cell cultures with either one or two active X. We found that overall X-linked gene expression is not tripled in the presence of three sets of autosomes. However, in triploid cells with a single active X chromosome, its expression is adjusted upward, presumably by an epigenetic mechanism that senses the active X-autosome ratio. |
| 1924 | GSE21477 |
Profile | Using various exposure conditions we studied the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in primary human nasal epithelial cells (HNEC). DPX were indirectly measured by the alkaline comet assay as the reduction of gamma ray – induced DNA migration. DPX are the most relevant primary DNA alterations induced by FA and the comet assay is a very sensitive method for the detection of FA-induced DPX. In parallel experiments, we investigated changes in gene expression by using a full genome human microarray. After a single treatment with FA (50 to 200 µM), concentration – and time-dependent changes in gene expression were seen under conditions that also induced genotoxicity. Repeated treatments with low FA concentrations (20 and 50 µM) did not lead to a significant induction of DPX but repeated treatments with 50 µM FA changed the expression of more than 100 genes. Interestingly, the expression of genes involved in the main pathway for FA detoxification and the repair of DPX were not specifically enhanced. A high degree of overlap was seen among the pattern of gene changes induced by FA in HNEC in comparison to recently published array studies for nasal epithelial cells from rats exposed to FA in vivo. Our results suggest that HNEC are a suited in vitro model for the characterization of FA-induced toxicity and the relationship between genotoxic and other cytotoxic effects. |
| 1925 | GSE47874 |
Profile | The overall objective of the heritage project is to study the role of the genotype in cardiovascularmetabolic and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in several cardiovascular disease and diabetes risk factors. |
| 1926 | GSE11142 |
Profile | The long-term objective of this project is to establish roles played in development and function of the immune system by nicotinic acetylcholine receptors (nAChR) and exposure to the tobacco alkaloid nicotine. The planned gene chip studies will allow us to assess effects of nicotine exposure on gene expression in a model T cell line, and the findings are expected to help direct further efforts. One of the biomedically-relevant hypotheses of this project is that tobacco use and nicotine exposure affect immune system development. To establish effects of nicotine exposure on gene expression in the CEM model T cell line. Immune system nAChR acting as ion channels or via novel signaling cascades mediate their effects on T cell development by altering expression of genes involved in T cell receptor rearrangements, cytokine expression, and cell death/survival decisions. CEM cells will be treated for one hour or one day with an effective dose of nicotine or with the same medium change but in the absence of nicotine. Keywords: nicotine, T cell line |
| 1927 | GSE11499 |
Profile | The whole-genome oligonucleotide microarray analysis of peripheral blood samples can contribute to the determination of distant blood markers of local pathophysiological alterations in colorectal diseases. These markers can lead to alternative screening procedures. |
| 1928 | GSE19982 |
Profile | [original title] Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma. Background : Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods : Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n=15) and oncocytoma specimens (n=15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. Immunohistochemical validation was performed in an independent set of tumors. Results : A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusion : Gene expression profiles and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. We have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma. |
| 1929 | GSE14807 |
Profile | The therapeutic potential of pro-resolution factors in determining the outcome of inflammatory events has gained ground over the past decade. However the attention has been focused on the non-genomic effects of these endogenous, anti-inflammatory substances. In this study, we have focused our attention on identifying specific annexin 1 (AnxA1) protein/ALX receptor mediated gene activation, in an effort to identify down-stream genomic targets of this well-known, glucocorticoid induced, pro-resolution factor. |
| 1930 | GSE14827 |
Profile | Osteosarcoma patients with development of pulmonary metastasis have still poorer prognosis in spite of aggressive treatment. However molecular mechanism of metastasis is still unknown. We analysed the expression levels of 54,613 probe sets in surgical 27 samples of osteosarcoma with GeneChip Human Genome U133 Plus 2.0 arrays. Keywords: gene expression array-based, count |
| 1931 | GSE31455 |
Profile | Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders. |
| 1932 | GSE12606 |
Profile | In recent years several approaches have been taken in the peptide-based immunotherapy of metastatic renal cell carcinoma (RCC), although little is known about HLA presentation on metastases compared to primary tumor and normal tissue of RCC. In this study we compared primary tumor, normal tissue and metastases with the aim of identifying similarities and differences between these tissues. We performed this comparison for two RCC patients on the level of the HLA ligandome using mass spectrometry and for three patients on the level of the transcriptome using oligonucleotide microarrays. The quantitative results show that primary tumor is more similar to metastasis than to normal tissue, both on the level of HLA ligand presentation and mRNA. We were able to characterize a total of 142 peptides in the qualitative analysis of HLA-presented peptides. Six of them were significantly overpresented on metastasis, among them a peptide derived from CD151; fourteen were overpresented on both primary tumor and metastasis compared to normal tissue, among them an HLA ligand derived from tumor protein p53. Thus, we could demonstrate that peptide-based immunotherapy might affect tumor as well as metastasis of RCC, but not healthy kidney tissue. Furthermore we were able to identify several peptides derived from tumor-associated antigens that are suitable for vaccination of metastatic RCC. |
| 1933 | GSE14479 |
Profile | Acute Myeloid Leukemia (AML) is a heterogeneous disease from the molecular and biological standpoints and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients that shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, while the rest presented with silencing of this gene and co-expression of certain T cell markers. DNA methylation studies revealed that these two groups of patients could be readily segregated in an unsupervised fashion based on their DNA methylation profiles alone. Furthermore, CEBPA silencing was associated with the presence of an aberrant DNA hypermethylation signature, which was not present in the CEBPA mutant group. This aberrant hypermethylation occurred more frequently at sites within CpG islands. CEBPA silenced leukemias also displayed marked hypermethylation when compared with normal CD34+ hematopoietic cells, while CEBPA mutant cases showed only mild changes in DNA methylation when compared to these normal progenitors. Biologically, CEBPA silenced leukemias presented with a decreased response to myeloid growth factors in vitro. Keywords: Gene expression profiling using arrays |
| 1934 | GSE43489 |
Profile | To study the mechanisms of the epithelial-mesenchymal transition (EMT) in prostate cancer metastasis we first generated an epithelial model cell line derived from prostate cancer epithelial PC3 cells. We isolated a subpopulation of cells that showed a stable epithelial phenotype in culture and designated them PC3-Epi. We next developed mesenchymal cell lines from PC3-Epi cells, through interactions with macrophages. These mesenchymal cell lines were designated PC3-EMT1, PC3-EMT12 and PC3-EMT14. We transfected two of these mesenchymal lines (PC3-EMT1 and PC3-EMT14) with lentiviral ZEB1-shRNA vector (sh4) or the scrambled control (Scr). Consistent with ZEB1's role in EMT and maintenance of the mesenchymal state, silencing of ZEB1 induced the mesenchymal-epithelial transition (MET) in PC3-EMT1 and PC3-EMT14. |
| 1935 | GSE24187 |
Profile | With particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR. Expression profiling with Affymetrix whole genome arrays shows that statins induce extensive transcriptome changes. |
| 1936 | GSE30242 |
Profile | The effect of mometasone furoate on the proliferation of 2 patients of human lung fibroblasts was investigated at 8 different time points |
| 1937 | GSE15583 |
Profile | Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 9 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. The clustering analysis of the expression profiles based on different clustering methods consistently revealed that hypoxia was not the major factor characterizing the data set. T-test analysis with multiple testing correction fails to identify significantly differentially expressed genes. Conversely the l1-l2 regularization selects 11 significant probesets while building an effective classification rule. The algorithm is cast within a cross-validation framework in order to achieve an unbiased analysis. The estimated cross-validation error is 17% (3 out of 18). We show that the use of l1-l2 regularization allowed us to model the effect of hypoxia, which was not detected by conventional t-test based approaches and we find a panel of genes able to properly discriminate the normoxic versus the hypoxic status of neuroblastoma cell lines. |
| 1938 | GSE41226 |
Profile | G9a depleted SKCO3 cells were used to identify genes regulated by G9a-dependent epigenetic regulations We used microarrays to detail the global programme of gene expression underlying paritoneal dissemination and identified distinct classes of G9a-regulated genes during this process. |
| 1939 | GSE46924 |
Profile | The cholesterol metabolite and SERM 27HC, is the signaling molecule that links cholesterol to breast cancer pathophysiology Hypercholesterolemia is a risk factor for breast cancer, and patients taking statins demonstrate lower breast cancer incidence and decreased breast cancer recurrence, data that highlights the potential importance of the recent finding that 27-Hydroxycholesterol (27HC), a primary metabolite of cholesterol, acts as a selective estrogen receptor modulator (SERM). The goal of this study was to evaluate the impact of 27HC on breast cancer pathophysiology. Elevation of 27HC in murine models increased tumor growth in an estrogen receptor dependent manner. Importantly, a high cholesterol diet decreased the time to tumor onset and increased tumor growth, and this response required presence of CYP27A1. Within human breast cancer samples, CYP27A1 expression increasesd with grade, in addition to being highly expressed in tumor associated macrophages. Finally 27HC increases metastasis to the lung. The findings herein strongly support a role for 27HC in breast cancer pathophysiology, providing support for the exploration of potential chemopreventative benefits of lower cholesterol diets, and pharmacological inhibitors of HMG-CoA reductase or CYP27A1. |
| 1940 | GSE24592 |
Profile | The nuclear hormone receptor estrogen receptor-alpha (ERα), and MAP kinases both play key roles in hormone-dependent cancers, yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ERα activates and interacts with ERK2, a downstream effector in the MAPK pathway, resulting in ERK2 and ERα colocalization at chromatin binding sites across the genome of breast cancer cells. KEYWORDS: siRNA knock-down, ligand treatment |
| 1941 | GSE38987 |
Profile | Acute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted-resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (~3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were non-recurrent, we observed a number of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2 and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the non-classical regulators of mRNA-processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a significant enrichment of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML. |
| 1942 | GSE24578 |
Profile | Given the very substantial heterogeneity of most human cancers it is likely that most cancer therapeutics will be active in only a small fraction of any population of patients. As such, the development of new therapeutics, coupled with methods to match a therapy with the individual patient, will be critical to achieving significant gains in disease outcome. One such opportunity is the use of expression signatures to identify key oncogenic phenotypes that can serve not only as biomarkers but also as a means of identifying therapeutic compounds that might specifically target these phenotypes. Given the potential importance of targeting tumors exhibiting a stem-like phenotype, we have developed an expression signature that reflects common biological aspects of various stem-like characteristics. The Consensus Stemness Ranking (CSR) signature is upregulated in cancer stem cell enriched samples, at advanced tumor stages and is associated with poor prognosis in multiple cancer types. Using two independent computational approaches we utilized the CSR signature to identify clinically useful compounds that could target the CSR phenotype. In vitro assays confirmed selectivity of several predicted compounds including topoisomerase inhibitors and resveratrol towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly, the CSR signature could predict clinical response of breast cancer patients to a neoadjuvant regimen that included a CSR-specific agent. Collectively, these results suggest therapeutic opportunities to target the CSR phenotype in a relevant cohort of cancer patients. |
| 1943 | GSE7307 |
Profile | Normal and diseased human tissues were profiled for gene expression using the Affymetrix U133 plus 2.0 array In total 677 samples were processed representing over 90 distinct tissue types Some tissue samples were purchased from Stratagene (SG), Ambion (AB), and Becton-Dickinson (BD) Keywords: Human body index of gene expression |
| 1944 | GSE31323 |
Profile | To identify the genes differently expressed in the epithelium and the stromal of Benign Prostatic Hyperplasia (BPH) we collect the epithelium and the stromal from the patients with benign prostatic hyperplasia by laser micro-dissection. And then, Affymetrix HG-U133_Plus_2 gene-chip was used to detect and compare the expression level of genes. To find which genes are most abundantly expressed in epithelium and stromal and what is the role of these genes in the pathogenesis of BPH. |
| 1945 | GSE22038 |
Profile | MCL cell lines were treated with aza and aza in combination with TSA. |
| 1946 | GSE27186 |
Profile | Transcription factor-mediated reprogramming yields induced pluripotent stem cells (iPSC) by erasing tissue specific methylation and re-setting DNA methylation status to an embryonic stage. We compared bona fide human iPSC derived from umbilical cord blood (CB) and neonatal keratinocytes (K). Through both incomplete erasure of tissue specific methylation and de novo tissue specific methylation CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles. Functionally, CB-iPSC displayed better blood formation in vitro, whereas K-iPSC differentiated better to a keratinocyte fate, implying that the tissue of origin needs to be considered in future therapeutic applications of human iPSCs. We performed gene expression and global DNA methylation profiling on iPS and the source somatic cell types to search for evidence of epigenetic memory. |
| 1947 | GSE23994 |
Profile | Specific changes in gene expression during cancer initiation should enable discovery of biomarkers for risk assessment early detection and targets for chemoprevention. It has been previously demonstrated that altered mRNA and proteome signatures of morphologically normal cells bearing a single inherited “hit” in a tumor suppressor gene parallel many changes observed in the corresponding sporadic cancer. Here, we report on the global gene expression profile of morphologically normal, cultured primary breast epithelial and stromal cells from Li-Fraumeni syndrome (LFS) TP53 mutation carriers. Our analyses identified multiple changes in gene expression in both morphologically normal breast epithelial and stromal cells associated with TP53 haploinsufficiency, as well as interlocking pathways. Notably, a dysregulated p53 signaling pathway was readily detectable. Pharmacological intervention with the p53 rescue compounds CP-31398 and PRIMA-1 provided further evidence in support of the central role of p53 in affecting these changes in LFS cells and treatment for this cancer. Because loss of signaling mediated by TP53 is associated with the development and survival of many human tumors, identification of gene expression profiles in morphologically normal cells that carry “one-hit” p53 mutations may reveal novel biomarkers, enabling the discovery of potential targets for chemoprevention of sporadic tumors as well. |
| 1948 | GSE4779 |
Profile | The goal of the study was to identify a gene expression signature capable of predicting a pathological complete response following neoadjuvant anthracycline-based chemotherapy of breast cancer. The samples were taken from the FEC arm (5-fluorouracil epirubicin, cyclophosphamide) of the EORTC 10994 trial. EORTC 10994 is a phase III clinical trial comparing FEC with ET (epirubicin, docetaxel) in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 200 ng total RNA per chip was amplified using the Affymetrix small sample protocol (IVT then Enzo). 102 tumours were tested on Affymetrix X3P chips. Single biopsies were tested per tumour. The CEL files were quantile normalised using rma. The clinical response measure was pathological complete response (pCR, disappearance of the tumour after chemotherapy with at most scattered invasive cells detected by histology). |
| 1949 | GSE1418 |
Profile | purified CD34+ cells from bone marrow of imatinib-treated patients were compared to those of healthy donors Keywords = CML Keywords = CD34+ cells Keywords = imatinib Keywords: ordered |
| 1950 | GSE24868 |
Profile | Malignant progression in cancer has been associated with the emergence of populations of tumor-initiating cells (TIC) endowed with capabilities for unlimited self-renewal survival under stress and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by the genetic program known as epithelialmesenchymal transition (EMT) may be an essential step in the evolution of neoplastic cells into fully metastatic populations. A widely accepted paradigm is that EMT potentiates tumor cell self-renewal and metastatic behaviour. Here we describe a cellular model in which a clonal population enriched in TIC expresses a genetic program distinct from a second population with traits of stable EMT, and in which both populations cooperate for enhanced local invasiveness and metastasis. Induction of the TIC-enriched population to undergo EMT by several stimuli or by constitutive overexpression of the transcription factor SNAI1 engaged a mesenchymal program while suppressing the CSC program. This suggests that TIC and EMT, contrary to current paradigms, correspond to alternative states. Furthermore, diffusible factors secreted by the population with EMT traits also induced mesenchymal reprogramming of the population enriched in CSCs. Local invasiveness in vitro and lung colonization in vivo of the TIC-enriched population was enhanced by co-injection with the EMT-trait population, and expanded the range of organs to which it metastasized. Thus, in our model, relatively stable TIC and EMT phenotypes reflect alternative genetic programs expressed by distinct clonal populations. We also suggest that dynamic cooperation between tumor subpopulations displaying either TIC or EMT traits may be a general mechanism driving local invasiveness and metastasis. |
| 1951 | GSE14317 |
Profile | Abstract: Adult T-cell leukemia/lymphoma (ATL) is an aggressive and fatal disease. We have examined 18 ATL patient samples using Affymetrix HG-U133A2.0 arrays. Using the BRB array program we identified genes differentially expressed in leukemia cells compared to normal lymphocytes. Several unique genes were identified that were overexpressed in leukemia cells including TNFSF11, RGS13, MAFb, CSPG2, C/EBPalpha and TCF4. 200 of the most highly overexpressed ATL genes were analyzed by the PathwayStudio 4.0 program. ATL leukemia cells were characterized by an increase in genes linked to "central" genes CDC2/cyclin B1, SYK/LYN, PCNA and BIRC5. Because of its potential therapeutic importance, we focused our studies on the regulation and function of BIRC5, whose expression was increased in 13 of 14 leukemia samples. TCF4 reporter assays and transfection of DN-TCF4 demonstrated that TCF4 regulates BIRC5 gene expression. Functionally, transfection of ATL cells wi BIRC5 shRNA decreased BIRC5 exprression and cell viability 80%. Clinical treatment of ATL patients with Zenapax or bortezomib decreased BIRC5 expression and cell viability. These experiments represent the first direct experimental evidence that BIRC5 plays an important role in ATL cell viability and provides important insight into ATL genesis and potential targeted therapies. Keywords: disease state analysis |
| 1952 | GSE49891 |
Profile | The second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected rank-order gene expression, and functional genomic analysis. Fewer gene transcripts were observed using RNA-Seq than microarray (4,135 v 8,841). Correlation of total expression within each sample ranged from R=0.43 to R=0.57. On average, there was 59% concordance in gene identity among the top 10% of genes ranked by expression. The RNA-Seq data yielded more significant pathways enrichment within the “Physiological Systems Development and Function” categories of IPA. Alternative splicing of many well-known genes, including those previously studied in fetal development, such as H19 and IGF2 is detected by RNA-Seq. Also included in this paper is discussion of the technical challenges inherent to working with cell-free fetal RNA and possible solutions. |
| 1953 | GSE17449 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 1954 | GSE40404 |
Profile | We compared the transcriptomes of isogenic diploid fibroblasts expressing progerin or elevated levels of wild-type prelamin A with that of wild-type fibroblasts. We subsequently used the reversion towards normal of two phenotypes reduced cell growth and dismorphic nuclei, by treatment with farnesyltransferase inhibitor (FTI) or overexpression of ZMPSTE24, as a filtering strategy to identify genes linked to the onset of these two phenotypes. |
| 1955 | GSE35218 |
Profile | Abstract: Epigenetic alterations are a fundamental aspect of cancer cells and epigenetic drugs are currently used in clinical practice for hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and show epigenetic defects of apoptotic pathways, which makes the introduction of epigenetic drugs in this patient category logical. However, the young age of these patients is accompanied by ongoing developmental processes which are regulated epigenetic mechanisms, and prompted us to study molecular effects of nanomolar dosage epigenetic drugs in neuro-ectodermal tumor cell lines. Combination treatment of 5-aza-2`-deoxicytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages resulted in wide-spread demethylating effects in 17 NBL and 5 PNET cell lines in vitro. This widespread demethylation had large effects on gene-expression profiles. In NBL cell lines, almost every cellular pathway (193/200) investigated demonstrated altered expression upon treatment, and resulted in upregulation of known epigenetically regulated genes such as X-chromosomal, tissue-specific, and a few imprinted genes. Integration analysis of CpG island methylation array data and whole genome gene expression data identified 30 genes potentially upregulated by gene promoter demethylation. Homeobox genes frequently showed demethylation in both short term (72 hours) and long term cultures (3 months) of NBL lines. Continuous treatment with epigenetic drugs resulted in low rates of proliferation. The low rate of proliferation that might explain limited consecutive demethylation upon prolonged exposure. In conclusion, genome-wide methylation and gene expression changes are induced DAC and TSA treatment at nanomolar dosages. These effects affected more than 97% of cellular pathways investigated. Further studies towards the effects of epigenetic drug combinations are advised before being applied in clinical trials for pediatric patients. |
| 1956 | GSE17269 |
Profile | The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. Since these circulating atypical B cells in the blood of CVID patients could not be assigned to any certain B cell differentiation stage in the periphery, they were designated as CD21low B cells. Although, CD21low B cells are polyclonal and unmutated IgM+IgD+ B cells like naive B cells in the peripheral blood, they reveal several distinct phenotypic and functional features. In order to uncover the the global programme of gene expression underlying these differences and changes in CD21low B cells we have performed microarray hybridization experiments and identified differentially expressed genes which define a distinct gene expression profile in CD21low B cells compared to naive B cells. |
| 1957 | GSE17948 |
Profile | Human cytomegalovirus (HCMV) induces pro-inflammatory monocytes following infection and we have evidence that EGFR is a key mediator in this early activation. To begin to address how this signalling pathway is responsible for the rapid activation of infected monocytes we examined the role this pathway played in the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of genes, including inflammatory genes, were regulated in a EGFR-dependent manner, identifying this pathway as a key cellular control point in the conversion of monocytes to an activated pro-inflammatory state following HCMV infection. Keywords: Disease state |
| 1958 | GSE30159 |
Profile | Glucose intolerance and diabetes mellitus are classical parts of endogenous Cushing’s syndrome (CS) and insulin resistance is a feature of cortisol excess. CS patients display characteristics including hyperglycemia, abdominal obesity, reduced high-density lipoprotein cholesterol levels and elevated triglycerides, and arterial hypertension. Hypercortisolism is a well known cause of bone loss, and patients with CS frequently display low bone mass and fragility fractures. Cortisol excess inhibits bone formation, increases bone resorption, impairs calcium absorption from the gut, and affects the secretion of several hormones, cytokines, and growth factors with potential influence on bone metabolism. Bone biopsies from nine CS patients, before and mean 3 months after surgery, were screened for expressional candidate genes using Affymetrix human Gene Plus 2.0 Arrays. Analyses were performed to identify genes in glucocorticoid-induced osteoporosis and genes in glucose metabolism and energy homeostasis. |
| 1959 | GSE13475 |
Profile | Background Mutations in STOX1 were proposed as causal for predisposing to preeclampsia a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation. Methodology and Principal Findings In the present study, we have developed a choriocarcinoma cell line overexpressing STOX1. This overexpression results in the transcriptional modification of 12.5% of the genes, some of them being direct targets as shown by chromatin immunoprecipitation. STOX1 overexpression correlates strongly and specifically with transcriptomic alterations in preeclamptic placentas (r=0.30, p=9.10-7). Numerous known key modulators of preeclampsia (such as Endoglin, Syncytin, human chrionic gonadotrophin-hCG-, and Glial Cell Missing Homolog -GCM1-) were modified in these transformed choriocarcinoma cells. Conclusions Our results contribute to reconcile contradictory data about the involvement of STOX1 in preeclampsia. In addition, they strongly suggest that anomalies in STOX1 expression are associated with the onset of preeclampsia, thus indicating that this gene should be the target of future studies. Furthermore, our cellular model could constitute an invaluable resource for studying specific aspects of this human disease. |
| 1960 | GSE32280 |
Profile | Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and healthy controls. We used microarrays to detail the global programme of gene expression to develop blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder |
| 1961 | GSE34748 |
Profile | We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR for 30 transcripts were performed on RNA from protocol renal allograft biopsies in 3 groups: 1) +XM/TG+ biopsies before and after TG; 2) +XM/NoTG; and 3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups significantly altered expression was seen for 2,447 genes (18%) and 3,200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3,718 probe sets were differentially expressed but these were over-represented in only 4 pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to control biopsies and to +XM/NoTG biopsies. In conclusion, pre-transplant DSA results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of XM+ grafts are exposed to chronic injury. |
| 1962 | GSE28406 |
Profile | Pluripotent stem cells including human embryonic stem (hES) and human induced pluripotent stem (hiPS) cells, have been regarded as potential sources for cell-based transplantation therapy. However, the immunogenicity of these cells remains the major determinant for successful clinical application. We therefore studied multiple hES and hiPS cell lines for MHC expression, HLA haplotyping, expression of immune-related genes and T cell activation. The data showed lower levels of MHC class I (MHC-I), b2-microglobulin and HLA-E in undifferentiated stem cells, but the levels were increased to near the levels of somatic cells after co-treatment with interferon gamma. However, the percentages of cells expressing antigen presenting cell markers and MHC-II molecules remained consistently low. Activation of responder lymphocytes by the pluripotent stem cells was significantly lower than by allogeneic lymphocytes in mixed lymphocyte reactions. Finally, the data showed significant differential expression of immune privilege genes (TGF-beta2, Arginase 2, Indo1, GATA3, POMC, VIP, CACLA, CACLB, IL-1RN, CD95L, CR1L, Serpine 1, HMOX1, IL6, LGALS3, HEBP1, THBS1, CD59 and LGALS1) between pluripotent stem cells/derivatives and somatic cells. We concluded that pluripotent stem cell progeny may retain some level of immune privilege and will likely behave in a way different from those of somatic cells after transplantation. |
| 1963 | GSE14526 |
Profile | Aberrant DNA methylation one of the major epigenetic alterations in cancer, has been reported to accumulate in a subset of colorectal cancer (CRC), so-called CpG island methylator phenotype (CIMP), which was known to correlate with microsatellite instability (MSI)-high CRC. To select new methylation markers genome-widely and epigenotype CRC by DNA methylation comprehensively, we performed methylated DNA immunoprecipitation-on-chip analysis using MSI-high CRC cell line HCT116 and microsatellite-stable SW480, and re-expression array analysis by 5-aza-2-deoxycytidine/Trichostatin A. Methylation levels of 44 new markers selected and 16 previously reported markers were analyzed quantitatively in 149 clinical CRC samples using MALDI-TOF mass spectrometry. By unsupervised two-way hierarchical clustering, CRC was clustered into high-, intermediate-, and low-methylation epigenotypes. Methylation markers were clustered into two groups: Group-1 showing methylation in high-methylation epigenotype and including all the 11 CIMP-related markers except NEUROG1, and Group-2 showing methylation in high- and intermediate-methylation epigenotypes. Marker panel deciding methylation epigenotypes with the highest accuracy was developed: 1st-Panel consisting of Group-1 genes (CACNA1G, LOX, SLC30A10) to extract high-methylation epigenotype, and 2nd-Panel consisting of Group-2 genes (ELMO1, FBN2, THBD, HAND1) and SLC30A10 again to divide the remains into intermediate- and low-methylation epigenotypes. High-methylation epigenotype correlated significantly with BRAF mutation, MSI, proximal tumor location, and mucinous component, in concordance with reported CIMP. Intermediate- and low-methylation epigenotypes significantly correlated with KRAS-mutation(+) and KRAS-mutation(-), respectively. KRAS-mutation(+) intermediate-methylation epigenotype showed worse prognosis than KRAS-mutation(-) low-methylation epigenotype (p=0.030). These three epigenotypes with different genetic characteristics suggested different molecular CRC genesis, and the markers might be useful to predict prognosis. |
| 1964 | GSE20986 |
Profile | To compare the gene expression profiles of unpassaged proliferating HUVEC and human iris, retinal and choroidal microvascular endothelial cells. Gene expression profiling revealed significant differences between HUVEC and ocular microvascular endothelial cells suggesting that HUVE cells may not be a suitable surrogate when studying pathophysiological mechanisms of ocular disorders. There were significant differences in the gene expression of important cell signalling pathways in human retinal and choroidal ECs. These differences may be important in the mechanisms and treatment of choroidal and retinal neovascularisation. |
| 1965 | GSE48444 |
Profile | The gene expression of 6 different mouse xenografts initiated by BPLER cells analyzed by microarray. Basal-like triple negative breast cancers (TNBC) have poor prognosis. To study the basal-like transcriptional profile of tumors transformed by defined genetic elements the human breast epithelial cell line BPLER was injected into NOD/SCID mice. The resulting tumors were excised for expression analysis. Keywords: breast cancer, BPLER, metastasis, tumor stem cells, tumor initiating cells, breast adenocarcinoma |
| 1966 | GSE10685 |
Profile | Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6 a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. Keywords: Human skeletal muscle time course response to IL-6 infusion |
| 1967 | GSE12992 |
Profile | Medulloblastoma is the most frequent malignant pediatric brain tumor. Considerable efforts are dedicated to identify markers that help to refine treatment strategies. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favorable patient outcome. We report a series of 72 pediatric medulloblastomas evaluated for beta-catenin immunostaining CTNNB1 mutations, and studied by comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumor cells) in 6 cases and focal nuclear staining (<10% of cells) in 3 cases. The other cases exhibited either a signal strictly limited to the cytoplasm (58 cases) or were negative (5 cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented a strong activation of the Wnt/beta-catenin pathway. Remarkably, 5 out of these 6 tumors showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumors with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2) from diagnosis. All three patients with a focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumors represent a distinct molecular subgroup of medulloblastomas with favorable outcome, indicating that therapy de-escalation should be considered. Yet, international consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved. |
| 1968 | GSE26656 |
Profile | We aimed to analyze the effects of Wnt-1 overexpression on the mRNA expression profile of human melanoma in a mouse xenograft model and correlated the results with then presence or absence of lymphangiogenesis and metastasis. Affymetrix gene expression analysis revealed activation of canonical and non-canonical targets genes in response to Wnt-1 as compared with controls. In regard to lymphangiogenic factors the amount of VEGF-C was the single best marker to correlate with the amount of lymph-angiogenesis. |
| 1969 | GSE2125 |
Profile | This series represents isolated alveolar macrophages from human subjects. Keywords: parallel sample |
| 1970 | GSE18997 |
Profile | The aim of the study was to identify in vivo spermatogonial gene expression within the context of their biological niche. Identification of spermatogonial genes was done by t-testing on the replicates of Score 3 (Spermatogonia) and Score 2 (SCO) testicular biopsies. |
| 1971 | GSE15368 |
Profile | Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of p53 mutant-expressing cells Saos2-His273. |
| 1972 | GSE30884 |
Profile | By using high-density DNA microarrays we analyzed the gene-expression profile of Hodgkin's lymphoma cell line L-540 after tretament with the histone deactelyse inhibitor vorinostat. Kewitz et al., submitted |
| 1973 | GSE39902 |
Profile | To investigate the role of TAZ downstream of APC and beta-catenin in mammary epithelial cells cells we compared the expression profiles of MCF10-T1k (MII) cells transfected with siControl, siAPC, siAPC+siTAZ, sibeta-catenin, or sibeta-catenin+siTAZ. Keywords: expression profiling by array |
| 1974 | GSE19735 |
Profile | The pathways involved in hierarchical differentiation of human embryonic stem cells (hESC) into abundant and durable endothelial cells (EC) are unknown. We employed an EC-specific VE-cadherin promoter driving GFP (hVPr-GFP) to screen for factors that augmented yields of vascular-committed ECs from hESCs. In phase 1 of our approach inhibition of TGFb, precisely at day 7 of hESC differentiation, enhanced emergence of hVPr-GFP+ ECs by 10-fold. In the second phase, TGFb-inhibition preserved proliferation and vascular identity of purified ECs, resulting in net 36-fold expansion of homogenous EC-monolayers, and allowing transcriptional profiling that revealed a unique angiogenic signature defined by the VEGFR2highId1highVE-cadherin+EphrinB2+CD133+HoxA9- phenotype. Using an Id1-YFP hESC reporter line, we showed that TGFb-inhibition sustained Id1 expression in hESC-derived ECs, which was required for increased proliferation and preservation of EC commitment. These data provide a multiphasic method for serum-free differentiation and long-term maintenance of authentic hESC-derived ECs, establishing clinical-scale generation of transplantable human ECs. |
| 1975 | GSE31652 |
Profile | In psoriasis inflammation and epidermal hyperplasia are thought to be controlled by T cell-derived cytokines. Evidence now suggests that Th17 and Th22 cells infiltrate psoriasis lesions and by secreting IL-17 and IL-22, respectively, may drive disease-specific gene or cell responses. While studies in model systems indicate that IL-22 has a dominant pathogenic role, there is evolving evidence that IL-17 contributes to features of psoriasis. To more fully understand the role of IL-17 in human disease pathogenesis, we examined psoriatic skin lesions obtained from patients treated with an anti-IL-17 (IL-17 A) monoclonal antibody, LY2439821. In a phase 1, randomized, double-blind, placebo-controlled dose escalation trial, patients with chronic psoriasis were randomized to receive 3 doses of subcutaneous LY2439821 at 5 mg (n=8), 15 mg (n=8), 50 mg (n=8), 150 mg (n=8) or placebo (n=8) at weeks 0, 2 and 4. Repeat biopsies were taken from the same lesional area at baseline, week 2 and 6. At week 6, a PASI75 was observed in 0/8, 2/8, 5/7 and 8/8 patients receiving 5 mg, 15 mg, 50 mg or 150 mg LY2439821 respectively and 0/8 patients receiving placebo. The antibody was well-tolerated. In patients receiving the two highest doses, histological and immunohistochemical analyses of biopsies revealed significant reductions from baseline in keratinocyte proliferation, hyperplasia and epidermal thickness after 2 weeks, as well as reduced infiltration into the dermis and epidermis by T-cells (CD3+) and dendritic cells (CD11c and DC-LAMP). Keratinocyte expression of innate defense proteins, S100A7, S100A8, beta-defensin2 and LL37/cathelicidin was also reduced. By week 6, the skin appeared normal with a reversal of disease defining pathological features. Quantitative RT-PCR revealed decreased expression of interferon gamma (IFN-gamma), IL-22 and IL-17, key cytokines from T cell subsets Th1, Th22 and Th17, respectively. In order to explore the extent to which IL-17 blockade influences an even broader set of inflammatory or psoriatic disease related genes, mRNA levels from skin biopsy samples were evaluated using whole genome microarrays. At week 2, the highest dose of LY2439821 modulated over 1500 genes significantly (>1.5 fold change [FC], p<0.05). Of these, 51 genes were strongly suppressed (>7-fold) including IL-19, lipocalin, amphiregulin, granzyme B, and several chemokines. In a separate analysis, those genes known to be synergistically regulated by both IL-17 and TNF-alpha showed the greatest normalization in expression compared to genes known to be regulated by TNF-alpha alone, IFN-gamma or Interferon alpha. Our data suggest that Th17 cells, through the expression of IL-17, mediate psoriasis pathogenesis, and that neutralization of IL-17 with LY2439821 suppresses signaling through multiple inflammatory circuits by inhibiting expression of cytokines from multiple T cell subsets, as well as chemokines, and antimicrobial proteins from keratinocytes. |
| 1976 | GSE30529 |
Profile | We identified 1700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli; 330 probesets were commonly differentially expressed in both compartments. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in an additional set of DKD samples. |
| 1977 | GSE9946 |
Profile | Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 23-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype. In summary, regulatory myeloid DC and macrophages may play a dual role during life-threatening granulomatous infections, such as tuberculosis: on one hand, regulatory myeloid cells promote pathogen containment by efficiently killing intracellular bacteria, on the other hand these cells inhibit granuloma-associated T cells and thereby might be involved in the retention of TNF-controlled granuloma integrity protecting the host from granuloma break-down and pathogen dissemination. Keywords: Cell type comparison, response to infection |
| 1978 | GSE32197 |
Profile | Purpose: In this study we try to investigate the possible signaling pathways involved in the tumorigenesis of fibroblastic and anaplastic meningiomas. We also attempt to investigate EGFL6 gene expression in brain arachnoidal tissues and various tumors and to measure EGFL6 levels in serum samples from healthy people and patients with various tumors by using ELISA. Experimental Design: Differential gene expression profiles between meningiomas and brain arachnoidal tissues were established by using Affymetrix GeneChip Human U133 Plus 2.0 Array. KEGG pathway analysis was performed to identify potential gene pathways that may be involved in the pathogenesis of meningiomas. Quantitative real-time PCR (qRT-PCR) was performed to validate the differentially expressed genes in the KEGG pathways. EGFL6 mRNA levels were also determined in brain arachnoidal tissues, meningiomas, and other tumors by qRT-PCR. EGFL6 levels were measured in serum samples from healthy people and patients with various tumors by using ELISA. Results: Fibroblastic meningioma exhibited upregulated PI3K/Akt and TGFβ signaling pathways, and accelerated G1/S progression cell cycle. KEGG analysis also demonstrated that focal adhesion and ECM-receptor interaction pathways were activated in anaplastic meningioma. Benign meningiomas had significantly higher levels of EGFL6 mRNA than brain arachnoidal tissues and atypical and anaplastic meningiomas (P<0.001). EGFL6 gene was also highly expressed in ovarian cancer, but expressed lowly in all other investigated tumors. EGFL6 was hardly detectable in serum samples of healthy people. The mean serum EGFL6 concentration was 675, 118, and 126 pg/ml in patients with benign, atypical, and anaplastic meningiomas respectively. Patients with ovarian cancers also had high serum EGFL6 levels (mean concentration: 617 pg/ml). Patients with all other investigated tumors, however, had low levels of serum EGFL6 with mean concentration less than 240 pg/ml. Conclusion: We proposed that deregulation of cell cycle and PI3K/Akt pathways might play important roles in the tumorigenesis of fibroblastic meningioma. It was also suggested that the activated integrin-mediated signaling pathways were involved in the pathogenesis of anaplastic meningioma. We presented evidence that EGFL6 might serve as a novel serum biomarker for benign meningioma and ovarian cancer. It was also suggested that EGFL6 could help discriminate benignancy or malignancy of meningiomas before surgery or at early time points. |
| 1979 | GSE22779 |
Profile | Article title: Expression regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells. Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as a GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC. |
| 1980 | GSE1937 |
Profile | All mRNA was isolated after 8 hours of culture time in each of three culture conditions. (1) TCPS Plate (2) Collagen-GAG 2 dimensional coated plate and (3) collagen-GAG three dimensional mesh. Keywords: ordered |
| 1981 | GSE16870 |
Profile | Expression data from HeLa cells treated with V-ATPase inhibitors or with desoxyferramine compared to HeLa treated with DMSO or medium with low LDL To determine which genes respond first to low concentrations of V-ATPase inhibition we treated HeLa cells with two different V-ATPase inhibitors, bafilomycin and phenylsalicylihalamide (LX1077) at concentrations that slow cell growth by only 20%. To identify genes responding to expected effects of inhibiting the V-ATPase, expression data from inhibiting the V-ATPase was compared to that of chelating iron or incubating cells in medium with low LDL. |
| 1982 | GSE27414 |
Profile | screening of signature deterimes the individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells There is paucity of information whether human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from separate donors might have different effects on improving myocardial repair after myocardial infarction (MI). |
| 1983 | GSE19278 |
Profile | We and others have shown that S100P is highly upregulated during the progression of pancreatic cancer. We used microarrays to look at the target genes regulated by S100P in the pancreatic cancer cell line Panc1. Keywords: Gene overexpression |
| 1984 | GSE29220 |
Profile | Ovarian cancer is the leading cause of death in gynecological diseases and has been considered as one of the most fatal cancers due to lack of reliable detection strategy in the early stage. Therefore the capability to detect the morbidity initiation with an sensitive and effective approach is one of the most desirable goals for curing ovarian cancer. In this study, we used microarray technology for salivary mRNA biomarkers discovery, and evaluated the performance and translational utilities of discovered markers from a clinical study using an independent sample cohort . We used microarrays to profile and compare the gene expressions between ovairan cancer patient and matched controls, and identified seven down-regulated genes after the validation study. |
| 1985 | GSE10061 |
Profile | To investigate the oxidant sensitivity of E/ER regulated gene expression E/ER regulated genes are identified using E deprivation or ER-alpha siRNA knockdown; and oxidative stress responsive is determined by 8hr exposure to diamide, hydrogen peroxide and menadione Keywords: biomarker identification |
| 1986 | GSE35696 |
Profile | Tyrosine phosphorylation is a hallmark for activation of Signal Transducer and Activator of Transcription (STAT) proteins but their transcriptional activity also depends on other secondary modifications. Type I interferons (IFNs) can activate both the ISGF3 (STAT1:STAT2:IRF9) complex and STAT3, but with cell-specific, selective triggering of only the ISGF3 transcriptional program. Following a genome-wide RNAi screen, we identified the Sin3a complex as an important mediator of this STAT3 transcriptional repression. Sin3a directly interacts with the DNA-binding domain of STAT3 and alters its acetylation status. SIN3A silencing enhances recruitment of STAT3 and enhanceosome components to the SOCS3 promoter, resulting in histone hyperacetylation and enhanced transcription. Conversely, Sin3a is required for ISGF3-dependent gene transcription and for an efficient IFN-mediated antiviral protection against Influenza A and hepatitis C viruses. The Sin3a complex therefore acts as a context-dependent STAT1/3 transcriptional switch. |
| 1987 | GSE18903 |
Profile | We investigated the differentially expressed genes between MCF-7 and MCF-7-14 and estimated the similarities of expression profiles between MCF-7-14 and MDA-MB-231. We identified genes differentially expressed between non-invasive/non-metastatic and invasive/metastatic breast cancer cells. |
| 1988 | GSE7392 |
Profile | Introduction. Factors contributing to kidney transplant fibrosis remain incompletely understood—particularly in the absence of acute complications. Methods. Baseline and one-year surveillance biopsies from 15 uncomplicated living donor kidney transplants were subjected to microarray and quantitative RT-PCR (qRT-PCR) analyses in order to examine changes in gene expression patterns over time. Biopsy pairs were purposefully selected from allografts with no history of acute complications and were divided into those that were histologically normal (n = 7) and those that had developed subclinical interstitial fibrosis (n = 8) at 1 year. Results. Compared to the paired baseline specimens expression levels of 3578 probesets were found altered in all the one-year biopsies studied. A large proportion of the upregulated genes in this transplant-associated profile were functionally linked with inflammation, immunity or response to injury. These included components of inflammation-related signaling pathways (integrin, interferon and TLR) as well as individual mediators of inflammatory and immune responses. An additional 2884 probesets demonstrated altered expression in fibrotic grafts only at 1 year. The gene products in this fibrosis-associated profile were also predominantly linked with inflammation and immune function, suggesting exaggerated inflammatory activity within the fibrotic grafts. qRT-PCR analyses confirmed the predicted expression patterns for selected transcripts from the microarray profiles. Conclusions. Transcriptional profiles of histologically normal living donor renal allografts indicate that there is ongoing injury response and inflammation at 1 year compared to the immediate post-transplant period. Subclinical development of interstitial fibrosis during the first post-transplant year is associated with additional upregulation of inflammation-related genes. Keywords: time course, comparative expression |
| 1989 | GSE44971 |
Profile | Pilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and can cause significant morbidity including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase (MAPK) pathway, but little else is known about their development. To further define their molecular development, we analysed the global DNA methylation profiles of 61 PAs and 6 normal cerebellum samples and integrated this data with transcriptome profiling. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups. Significant expression differences were identified for the majority of differentially methylated genes, and these were unexpectedly associated with a strong positive correlation between methylation and expression. We also identified a large number of differentially methylated/expressed genes between cerebellar PAs and normal cerebellum, which included additional developmental genes. |
| 1990 | GSE6494 |
Profile | Exposure to Polychlorobiphenyls (PCBs) is known to cause serious health effects in human but the gene expression profiles leading to development of differnet diseases is not fully understood. The knowledge of global gene expression will help us to devlop early diagnostic biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of PCB153 on human liver cells leading to identification of distinct classes of up-regulated and down-regulated genes and cellular processes. Keywords: time course |
| 1991 | GSE19404 |
Profile | Central nervous system primitive neuroectodermal tumors (CNS PNET) and medulloblastomas are both embryonal tumors that predominantly occur in children. We used microarrays to analyse a cohort of CNS PNETs and medulloblastomas to identify gene expression related to tumor subgroups. |
| 1992 | GSE10317 |
Profile | A investigation of the gene expression of one parathyroid tumour compared to its adjacent normal tissue Keywords: differentially expressed gene profile |
| 1993 | GSE9662 |
Profile | To identify a group of genes characteristic of a single neoplasia and determinant for the risk to relapse, we have performed gene expression analysis of ductal breast carcinoma samples using Affymetrix oligonucletide microarray (HU133A). Biopses from 60 patients, 30 good prognosis (desease free from six to ten years after surgical treatment) and 30 poor prognosis, have been analyzed. From each group we have created six homogeneous pools to show, during the analysis, only genes expressed in a greatly different way. A reduced number of cases has been used to avoid dilution of genes expressed only in few samples. Analysis have identified 77 candidate genes with a specific ontological distribution that contained some genes that were linked to breast cancer by previous studies. Microarray results validation has been performed by real-time PCR analysis on 127 single cases of breast cancer. Gene function study and literature data allow to define our candidate genes as potential markers of prognosis. Keywords: Breast cancer gene expression analysis |
| 1994 | GSE16054 |
Profile | Mutations in the SFTPC gene associated with interstitial lung disease in human patients result in misfolding endoplasmic reticulum (ER) retention, and degradation of the encoded surfactant protein C (SP-C) proprotein. To identify candidate genes involved in ER quality control of SP-C, HEK293 cells were transiently transfected with mutant SP-C (SP-CΔexon4 or SP-CL188Q), SP-CWT, or vector cDNAs, and global changes in gene expression were assessed by microarray analyses. Microarray analysis demonstrated that the SPC exon 4 deletion and SPC L188Q mutations invoke very similar transcriptional profiles including the activation of major players mediating ER response and unfolding protein response (UPR) in transient transfection system. In combination with promoter scan (UPRE, ERSE, XBP1 sites) and protein domain analysis (Finding ER Lumen, ER Membrane retention signal, J-Domain and Leucine Zipper domain), we were able to not only verify the known ERAD components (XBP1, Bip, Erdj4&5), but also identify multiple ER components which may play critical roles in the detection and /or degradation of mutant SPC, which in turn will help us to gain better understanding of the entire mammalian ERAD machinery. |
| 1995 | GSE6710 |
Profile | Biopsies from uninvolved and from lesional skin of 13 patients with plaque-type psoriasis. Based on paired samples 179 genes were more than 2-fold differentially expressed in lesional skin. Keywords: Comparison of uninvolved and lesional skin |
| 1996 | GSE26673 |
Profile | Burkitt lymphoma is the commonest cancer in children in Africa. We compared the gene expression profiles of African Burkitt lymphoma patients with those of cases presented in Western countries in both immunocompetent (sporadic Burkitt lymphoma) and HIV-infected patients (immunodeficiency associated Burkitt lymphoma). We used microarrays to detail the global programme of gene expression in different subtypes of Burkitt lymphoma. |
| 1997 | GSE1317 |
Profile | This data set was generated as part of Biogen Community Lab's science fair mentorship program. In brief human basal cells (ATCC: CRL-7761, designation TE 353.Sk) were cultured to 80% confluence. After removing media, cells were treated with a titration of ultraviolet light (Biorad GS GeneLinker, 254 nm energy maximum). Media was then added and cells were grown for 24 hours. Total RNA was harvested using RLT buffer and Qiagen RNeasy kit. 5 ug of total RNA was labeled using standard Affymetrix protocols for Eukaryotic target preparation (GeneChip Expression Analysis Technical Manual Revision 4). GeneChip intensity values were scaled to 2500 RFU. Keywords = UV Keywords = ultraviolet Keywords = basal cell Keywords: dose response |
| 1998 | GSE42363 |
Profile | The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With an extremely poor five-year survival rate of only 15% identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutation spectra from the whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a novel mutational signature in EACs defined by a high prevalence of A to C transversions at Ap*A dinucleotides. Statistical analysis of the exome data identified 26 genes that are mutated at a significant frequency. Of these 26 genes, only four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include several chromatin modifying factors and candidate contributors to EAC: SPG20, TLR4, ELMO1, and DOCK2. Notably, functional analyses of EAC-derived mutations in ELMO1 increase cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis. |
| 1999 | GSE11504 |
Profile | Human bone marrow is a complex diversified and well-organized hematopoietic network changing composition with age. The purpose of this study was to analyze variations in relative precursor B cell abundance in bone marrow with age by means of global gene expression profiling. RNA was isolated from composite bone marrow from 25 healthy children, adolescents and adults age 2 months to 28 years. As reference transcript for precursor B cells we used recombination activating gene RAG1 exploring the data for other transcripts showing the same profile as RAG1 with age. We identified 54 genes with correlated expression profiles to RAG1 (r ≥ 0.9, p = 0), characterized by high expression at 3 - 20 months followed by a fast decline to lower signal levels maintained until early adulthood. Immunophenotyping from a similar healthy age-matched cohort (n = 37) showed a comparable decrease of precursor B cells. Of the 54 genes 15 were characteristically B cell associated representing cell surface molecules (CD19, CD72, CD79A, CD79B, CD180, IGL@, IGLL1, VPREB1, VPREB3), a signal transduction molecule (BLNK) and transcription factors (DNTT, EBF1, PAX5, POU2AF1, RAG2). Of the remaining transcripts some may represent novel B cell transcripts or genes involved in control of B cells. Bone marrow was obtained from healthy children eligible for elective minor surgery and voluntary health care workers. The bone marrow samples (2.5ml) were immediately after aspiration transferred to PAXgene tubes for mRNA stabilization before RNA extraction and hybridization on Affymetrix microarrays. To that end, the study presents a picture of the total marrow activity with minimal manipulation that would otherwise influence gene expression results. |
| 2000 | GSE21943 |
Profile | The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define the role of c-Myb during the terminal differentiation of hematopoietic precursors we studied the effects of its silencing in human primary CD14-myeloblasts, which maintain a granulo-monocyte differentiation bipotentiality. c-Myb-silenced myeloblasts were blocked in the G1 phase of the cell cycle at 24 hours post-nucleofection and subsequently were forced towards macrophage differentiation, as demonstrated by immunophenotypic and morphological analysis. Indeed, c-Myb-silenced CD14- cells differentiate to macrophage even after the treatment with ATRA 10-6 M, demonstrating that the c-Myb knockdown strongly impairs the ability of myeloblasts to differentiate to granulocytes. Gene expression profiling of c-Myb-silenced CD14- cells identified some potential c-Myb targets that can account for these effects. |
| 2001 | GSE19639 |
Profile | Hyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer. A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. We used gene expression microarrays to identify genes and pathways that are commonly dysregulated in ER+ cell lines with acquired hormone-independent growth. MCF-7 ZR75-1, MDA-361, and HCC-1428 ER+, estrogen-responsive breast cancer cells were cultured under hormone-depleted conditions (10% DCC-FBS) for several months until sustainable hormone-independent cell populations emerged. |
| 2002 | GSE37580 |
Profile | Identification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells. HL60 cells were untreated or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS |
| 2003 | GSE23629 |
Profile | This study investigates the molecular signatures that drive Renal Cell Carcinoma (RCC) metastatic conversion using the 16 paired Human tumor samples. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. |
| 2004 | GSE5281 |
Profile | Information about the genes that are preferentially expressed during the course of Alzheimer’s disease (AD) could improve our understanding of the molecular mechanisms involved in the pathogenesis of this common cause of cognitive impairment in older persons provide new opportunities in the diagnosis, early detection, and tracking of this disorder, and provide novel targets for the discovery of interventions to treat and prevent this disorder. Information about the genes that are preferentially expressed in relationship to normal neurological aging could provide new information about the molecular mechanisms that are involved in normal age-related cognitive decline and a host of age-related neurological disorders, and they could provide novel targets for the discovery of interventions to mitigate some of these deleterious effects. Aim 1. Collect brain samples from three Alzheimer’s Disease Centers (ADCs) for subsequent gene expression profiling. Individuals will be stratified with respect to diagnostic groups (using both clinical and neuropathological criteria), age groups, and APOE genotype. 150 individual brains will be sampled from the Arizona ADC, the Duke University ADC, and the Washington University ADC. Miniscule sample sizes (200 um of sectioned tissue) from six brain regions that are histopathologically or metabolically relevant to AD and aging will be collected, ensuring that this proposal does not deplete the national resource. Frozen and fixed samples will be sent to Phoenix, sectioned in a standardized fashion, and then returned. Aim 2. Tissue heterogeneity will be eliminated prior to expression profiling by performing laser capture microscopy on all brain regions. Aim 3. Expression profile LCM-captured cells on the Affymetrix U133 Plus 2.0 array (~55,000 transcripts), and quickly provide these data to the community at large. Aim 4. Identify pathogenic cascades related to each of the clinico-pathologic correlates using unsupervised and supervised analyses coupled with a hypothesis-driven approach. Aim 5. Validation of the expression correlates at the protein and functional levels. Scientific progress in the last few years has improved our understanding of AD and raised the hope of identifying treatments to halt the progression and prevent the onset of this disorder. For instance, researchers have begun to characterize the cascade of molecular events which lead to the major histopathological features of the disorder: neuritic plaques, which contain extra-cellular deposits of amyloid beta-peptides (Abeta); neurofibrillary tangles, which contain the hyperphosphorylated form of the intracellular, microtubule-associated protein, tau; and a loss of neurons and synapses. These molecular events provide targets for the development of promising new treatments. For example, A-beta has been postulated to trigger a cascade of events that are involved in the pathogenesis of AD. This proposal hopes to provide new information about the genes that are preferentially expressed in the development of AD histopathology, including the over-expression of APP, amyloid-induced neurotoxicity, and hyperphosphorylation of tau, as well as bring clarity to the metabolic abnormalities that seem to play a role in dementia and AD development and pathology. We will perform LCM on 6 brain regions with about 14 biological replicates per brain region. The brain regions are as follows: 1) entorhinal cortex 2) hippocampus 3) medial temporal gyrus 4) posterior cingulate 5) superior frontal gyrus and 6) primary visual cortex. We will collect layer III pyramidal cells from the white matter in each region, isolate total RNA from LCMed cell lysates, and perform double round amplification of each sample for array analysis. Keywords: other |
| 2005 | GSE18146 |
Profile | The role of androgen in breast cancer development is not fully understood although androgen receptors (AR) have been identified in breast cancer clinical samples and cell lines. However the whole spectra of androgen actions cannot be accounted to the classic AR mode of action and the possible existence of a cell surface AR has been suggested. Indeed androgens like all steroids have been reported to trigger membrane initiated signaling activity and exert specific actions. Androgens acting on the membrane can rapidly activate kinase signaling pathways and ultimately could affect gene expression. However the molecular nature of membrane androgen binding sites represents another major persisting question. In the present study, we investigated early transcriptional effects of testosterone and the impermeable testosterone-BSA conjugate, in two breast cancer cell lines, in an attempt to decipher specific genes modified in each case, providing evidences about specific membrane initiating actions. Our data indicate that the two agents tested affect the expression of several genes. A group of genes were commonly affected while others were uniquely modified by each agent. In MDA-MB-231 cells, that are AR negative, the majority of genes affected by testosterone were also affected by testosterone-BSA indicating a membrane action. Subsequent analysis revealed that the two agents trigger different molecular pathways and cellular/molecular functions, suggestive of a molecular heterogeneity of membrane and intracellular AR. In addition, the phenotypic interactions of membrane-acting androgen with growth factor were verified at the transcriptomic level. Finally an interesting interplay between membrane-acting androgen with inflammation-related molecules, with potential clinical implications was revealed. |
| 2006 | GSE33984 |
Profile | KSHV promotes endothelia to mesenchymal transformation (EntMT) in EAHY cells We have used Affymetrix Gene Arrays to investigate the patterns of regulation of gene expression in EAHY cells infected with KSHV in comparison to uninfected EAHY cells |
| 2007 | GSE4127 |
Profile | Anticancer drug clustering in lung cancer based on gene expression profiles. We performed gene expression analysis in lung cancer cell lines. (used: Affymetrix GeneChip Human Genome U133 Array Set HG-U133A). We also examines the sensitivity of these cell lines to commonly used anti-cancer agents (docetaxel paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin, and carboplatin) via MTT assay. We related the cytoxic activity of each of these agents to corresponding expression pattern in each of the cell lines using modified NCI program. Keywords: cytotoxicity, lung cancer, anticancer drugs |
| 2008 | GSE41443 |
Profile | To identify genes whose expression was affected by RBP2 we performed gene expression microarray analysis in control and RBP2 depletion human lung cancer cell line. Two individual shRNA (RBP2 KD1 and RBP2 KD2) were used to limit potential off-target effects. |
| 2009 | GSE29630 |
Profile | Although galectin-3 is known to modulate the cell proliferation RNA processing, tumorigenesis, metastasis and apoptosis and also, which is highly expressed in human cancers, the function of galectin-3 is still controversy in gastric cancer. Here, we demonstrated the function of galectin-3 on gastric cancers by silencing with synthetic double-stranded small interfering RNA (siRNA). After silencing of galectin-3, cell numbers decreased and cell shapes changed in round. To determine the mechanism, microarray analysis was used to detect the changes in gene expression by galectin-3 silencing. |
| 2010 | GSE15400 |
Profile | Conditioned media from a human embryonic germ cell-derived line called SDEC was found to be supportive of human embryonic stem cell growth in the absence of feeder layers on a simple type I collagen matrix. We performed gene expression studies comparing this line to non-supportive cell lines (WI-38 and Detroit 551) to try to identify gene targets responsible for this phenomenon. We used Affymetrix microarrays to identify genes that are differentially regulated in SDEC vs. non-supportive cell lines. The goal is to determine which genes maybe be contributing to human embryonic stem cell growth in the absence of a mouse fibroblast feeder layer. |
| 2011 | GSE28146 |
Profile | Alzheimer's disease (AD) is a devastating neurodegenerative disorder that threatens to reach epidemic proportions as our population ages. Although much research has examined molecular pathways associated with AD relatively few studies have focused on critical early stages. Our prior microarray study correlated gene expression in human hippocampus with AD markers. Results suggested a new model of early-stage AD in which pathology spreads along myelinated axons, orchestrated by upregulated transcription and epigenetic factors related to growth and tumor suppression (Blalock et al., 2004). However, the microarray analyses were performed on RNA from fresh frozen hippocampal tissue blocks containing both gray and white matter, potentially obscuring region-specific changes. In the present study, we used laser capture microdissection to exclude major white matter tracts and selectively collect CA1 hippocampal gray matter from formalin-fixed, paraffin-embedded (FFPE) hippoc ampal sections of the same subjects assessed in our prior study. Microarray analyses of this gray matter-enriched tissue revealed many correlations similar to those seen in our prior study, particularly for neuron-related genes. Nonetheless, in the laser-captured tissue, we found a striking paucity of the AD-associated epigenetic and transcription factor genes that had been strongly overrepresented in the prior tissue block study. In addition, we identified novel pathway alterations that may have considerable mechanistic implications, including downregulation of genes stabilizing ryanodine receptor Ca2+ release and upregulation of vascular development genes. We conclude that FFPE tissue can be a reliable resource for microarray studies, that upregulation of growth-related epigenetic/ transcription factors with incipient AD is predominantly localized to white matter, further supporting our prior findings and model, and that alterations in vascular and ryanodine receptor-relat ed pathways in gray matter are closely associated with incipient AD. |
| 2012 | GSE40830 |
Profile | The cellular composition of heterogeneous samples can be predicted from reference gene expression profiles that represent the homogeneous constituent populations of the heterogeneous samples. However, existing methods fail when the reference profiles are not representative of the constituent populations. We developed PERT, a new probabilistic expression deconvolution method, to address this limitation. PERT was used to deconvolve cellular composition of variably sourced and treated heterogeneous human blood samples. Our results indicate that even after correcting batch effects, cells presenting the same cell surface antigens display different transcriptional programs when they are uncultured versus culture-derived. Given gene expression profiles of culture-derived heterogeneous samples and profiles of uncultured reference populations, PERT was able to accurately recover proportions of pure populations composing the heterogeneous samples. We anticipate that PERT will be widely applicable to expression deconvolution problems using profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular identity. Gene expression microarray to examine transcriptome variations between uncultured and culture-deried blood cells of the same phenotype as defined by the on and off expression of antigens. |
| 2013 | GSE16149 |
Profile | A tissue like buccal mucosa (from cheek swabs) would be an ideal sample material for rapid easy collection for testing of biomarkers as an alternative to blood. A limited number of studies, primarily in the smoker/oral cancer literature, address this tissue's efficacy for quantitative PCR or microarray gene expression analysis. In this study both qPCR and microarray analyses were used to evaluate gene expression in buccal cells. An initial study comparing blood and buccal cells from the same individuals looked at relative amounts of four genes. The RNA isolated from buccal cells was degraded but was of sufficient quality to be used with RT-qPCR to detect expression of specific genes. Second, buccal cell RNA was used for microarray-based differential gene expression studies by comparing gene expression between smokers and nonsmokers. The isolation and amplification protocol allowed use of 150-fold less buccal cell RNA than had been reported previously with human microarrays. We report here the finding of a small number of significant gene expression differences between smokers and nonsmokers, using buccal cells as target material. Additionally, Gene Set Enrichment Analysis confirmed that these genes were changing expression in the same pattern as seen in an earlier buccal cell study performed by another group. Our results suggest that in spite of a high degree of RNA degradation, buccal cells from cheek mucosa could be used to detect differential gene expression between smokers and nonsmokers. However the RNA degradation, increase in sample variability and microarray failure rate show that buccal samples should be used with caution as source material in expression studies. |
| 2014 | GSE10433 |
Profile | The pathogenesis of acne has been linked to multiple factors such as increased sebum production inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. 13-cis Retinoic Acid (13-cis RA, isotretinoin) is the most potent agent in acne treatment. Surprisingly, its mechanism of action in acne is still unknown. Gene expression profiling of skin from 6 patients treated with isotretinoin was performed to gain insights into its mechanism of action. Skin biopsies were obtained from the patients at baseline and at one-week isotretinoin treatment. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays in order to examine changes in gene expression as a result of treatment. After treatment, 43 genes were significantly changed: 38 up-regulated and 5 down-regulated. A significant proportion of these genes are involved in pathways that regulate differentiation, tumor suppression, serine proteases, serine protease inhibitors and solute transfer. These studies are the first describing the initial changes in gene expression associated with isotretinoin therapy and are valuable in identifying potential therapeutic targets in acne. Keywords: drug treatment effects |
| 2015 | GSE12710 |
Profile | RNA isolation and purification steps greatly influence the results of gene expression profiling. There are two commercially available products for whole blood RNA collection PAXgene and Tempus blood collection tubes, and each comes with their own RNA purification method. We examined the impact of RNA isolation methods on gene expression profiles. We demonstrated that peripheral blood RNA isoaltion can critically impact differential expression results, particularly in the clinical setting where fold-change differences are typically small and there is inherent variability within biological corhorts Keywords: micorarray quality assurance |
| 2016 | GSE30385 |
Profile | Objective: Identify genes that are differentially expressed between critically ill trauma patients who go on to develop ventilator-associated pneumonia (VAP) compared to similar patients who do not develop VAP Using gene expression differences develop a model that predicts which patients are at greater risk of developing VAP. |
| 2017 | GSE25127 |
Profile | The study aims to define gene expression changes associated with mithramycin treatment of Ewing Sarcoma cell lines. |
| 2018 | GSE16155 |
Profile | Ependymoma the 3rd most common brain tumor in children, recurs in approximately 50% of patients. There is currently no robust marker that predicts for recurrence, which is a significant clinical problem We used global gene expression profiling of 19 patient surgical samples obtained at initial diagnosis and with known clinical outcomes to discover novel prognostic markers. |
| 2019 | GSE14231 |
Profile | The development of chemo-resistance has dramatically limited the clinical efficiency of platinum-based therapy. Although many resistant mechanisms have been demonstrated genetic/molecular alterations responsible for drug resistance in the majority of clinical cases has not been identified. We analyzed three pairs of testicular germ cell tumor (TGCT) cell lines using Affymetrix expression microarrays to identify differential expressed genes. Then the expression of CCND1/CyclinD1, selected from the microarray analysis, was determined in cisplatin sensitive and resistance cancer samples including TGCTs, ovarian and prostate cancers by quantitative reverse transcription PCR analysis (qRT-PCR). Finally, we determined the gene knocked-down effect of CyclinD1. Expression microarray study revealed a limited number of differentially expressed genes across all three cell lines when comparing the parental and resistant cells. Among them, CyclinD1 was the most significantly differentially expressed gene. Importantly, we found that, in clinical TGCT samples, the overall expression level of cyclinD1 is higher in resistant cases compared to those sensitive samples (9/12 in the resistant group and only 3/8 in the sensitive group). We also found that cyclinD1 expressed dozens of fold higher in the resistant than in the sensitive ovarian cancer cell lines and dramatically overexpressed in prostate cancer. We re-sensitized the resistant cells by knocking-down cyclinD1. We demonstrated that deregulation of cyclinD1 is the major cause of TGCT cisplatin resistance and it may also be commonly involved in other human cancers. Combined cyclinD1 inhibition and cisplatin chemotherapy may be used clinically to treat the large number of cyclinD1 deregulated resistant tumors. |
| 2020 | GSE29981 |
Profile | The purpose of this study was to compare and contrast the expression of mRNA sequences in samples of endometrial glandular epithelium taken at discrete points in the menstrual cycle of healthy female subjects. This study was approved by the Erasme Hospital Ethics Committee and was conducted at the Pfizer Clinical Research Unit at the Erasme hospital Brussels. The study was conducted in accordance with the Declaration of Helsinki on Ethical Principals for Medical Research Involving Human Subjects, adopted by the General Assembly of the World Medical Association (1996). In addition, the study was conducted in accordance with the protocol, the principles of the International Conference on Harmonization guideline on Good Clinical Practice and applicable local regulatory requirements and laws. Written informed consent was obtained from all participants in this study prior to screen. Female healthy subjects were between 20 and 39 years of age and had a regular menstrual cycle. A total of 23 endometrial biopsies were taken from women at different stages of their menstrual cycle (mid & late follicular; early & mid luteal phases) by pipelle catheter. Glandular epithelium was laser capture microdissected and total RNA was purified, labelled and hybridized to Affymetrix HG-U133 Plus 2 chips using standard protocols. The resulting data were subjected to a principal component analysis and assessment by a proprietary methodology, the causal reasoning engine. Using this analysis we describe new progesterone marker genes and a robust methodology which may be useful for identifying endometrial pharmacological response genes or diagnostic disease markers. |
| 2021 | GSE35252 |
Profile | Compare the difference between pairwise NOF and iCAF (4d) tissues for one patient |
| 2022 | GSE8515 |
Profile | Using whole-genome Affymetrix microarrays (HG-U133A) we characterized the transcriptome profile of cultured human macrophages stimulated for 4 h with interleukin 1 (IL-1) or interleukin 6 (IL-6). We found that, in distinction to liver cells, IL-1 is much more potent than IL-6 in modifying macrophage gene expression, although considerable heterogeneity in response of macrophages deriving from individual blood donors was observed. The obtained results permitted to identify a large number of cytokine-responsive genes. coding for proteins of unknown function that are now being studied in our laboratory. They may represent novel targets in the anti-inflammatory therapy. Keywords: Cytokine response |
| 2023 | GSE11581 |
Profile | Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in proliferation motility, adhesion, invasion, angiogenesis, and survival signaling. Focal adhesion kinase has been shown to be overexpressed in many types of tumors, including breast cancer at early stages of tumorigenesis. To study the biological role of FAK in breast tumorigenesis, we used FAKsiRNA to down-regulate FAK in MCF-7 cell lines. |
| 2024 | GSE28815 |
Profile | The undifferentiated state of pluripotent stem cells depends heavily on the culture conditions. We show that a unique combination of small molecules SMC4, added to culture conditions converts primed pluripotent stem cells to a more naïve state. By conducting Affymetix analysis we show of majority of lineage markers are repressed in SMC4 culture. |
| 2025 | GSE13378 |
Profile | The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barrett’s metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisions with data derived from gene expression studies of Barrett’s esophagus and associated adenocarcinoma. Additionally this study may be used to assess divergence in response to bile acids by comparisons with similar study performed in SKGT4 barrett''s assocaited adenocarcinoma cell line. |
| 2026 | GSE44245 |
Profile | Baseline gene expression of human lymphocytes 24 hours after 5 Gy gamma irradiation We used microarrays to detail the global gene expression of human lymphocytes after irradiation |
| 2027 | GSE18476 |
Profile | The PLZF-RARa fusion oncoprotein is overexpressed in the t(11;17) subtype of acute promyelocytic leukemia. Gene expression microarrays were used to identify genes involved in leukemic transformation. We used microarray to detect gene expression changes induced by the PLZF-RARa fusion oncoprotein in the U937 cell line |
| 2028 | GSE12837 |
Profile | Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions. The RMA normalized data, analyzed using Bioconductor packages and RMA pre-processing procedure are available as a supplementary file on the Series record. |
| 2029 | GSE6280 |
Profile | End stage renal disease (ESRD) is associated with hyperplastic-cystic remodelling of the kidneys (ARCD) and increased rate of kidney tumours. Using the Affymetrix oligoarray we have established the gene expression signature of ESRD/ARCD kidneys and compared to those of normal kidneys and of distinct types of renal tumours. Keywords: normal and different tumor tissues |
| 2030 | GSE6015 |
Profile | The Polycomb group (PcG) proteins form chromatin-modifying complexes that are essential for embryonic development and stem cell renewal and are commonly deregulated in cancer. Here we identify their target genes using genome-wide location analysis in human embryonic fibroblasts. We find that Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27 co-occupy >1000 silenced genes with a strong functional bias for embryonic development and cell fate decisions. We functionally identify 40 genes derepressed in human embryonic fibroblasts depleted of the PRC2 components (EZH2, EED, SUZ12) and the PRC1 component, BMI-1. Interestingly, several markers of osteogenesis, adipogenesis, and chrondrogenesis are among these genes, consistent with the mesenchymal origin of fibroblasts. Using a neuronal model of differentiation, we delineate two different mechanisms for regulating PcG target genes. For genes activated during differentiation, PcGs are displaced. However, for genes repressed during differentiation, we paradoxically find that they are already bound by the PcGs in nondifferentiated cells despite being actively transcribed. Our results are consistent with the hypothesis that PcGs are part of a preprogrammed memory system established during embryogenesis marking certain key genes for repressive signals during subsequent developmental and differentiation processes. Keywords: polycomb, development, differentiation, cell fate, stem cells, siRNA |
| 2031 | GSE32375 |
Profile | We are currently studying the mechanisms that confer tumour initiating potential upon SP and as part of this work, we undertook gene profiling studies comparing expression between SP and non-SP cells, initially focusing on the most common soft tissue sarcoma, malignant fibrous histiocytoma (or MFH) Sarcomas contain a subpopulation of cells which exclude Hoechst dye (SP cells) and are enriched for tumor initiating potential. The persistence of SP cells could be responsible for relapse or a failed response to therapy. Expression profiles were compared between the SP and non-SP cells from malignant fibrous histiocytoma (MFH) tumors using microarray. The Hedgehog and Notch pathways were activated in SP cells. Blocking these pathways in MFH xenografts established in NOD-SCID mice depleted the abundance of SP cells and reduced tumor growth. Intriguingly, treatment also substantially inhibited the potential for successful secondary transplantation. The data provides support that SP cells act as tumor initiating cells in sarcomas and suggests targeting the SP as an enticing approach for sarcoma therapy. |
| 2032 | GSE17215 |
Profile | Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs |
| 2033 | GSE46286 |
Profile | The objective of this study was to identify the tissue expression patterns and biological pathways enriched in term amniotic fluid cell-free fetal RNA by comparing functional genomic analyses of term and second-trimester amniotic fluid supernatants. There were 2871 significantly differentially regulated genes. In term amniotic fluid, tissue expression analysis showed enrichment of salivary gland, tracheal, and renal transcripts as compared with brain and embryonic neural cells in the second trimester. Functional analysis of genes upregulated at term revealed pathways that were highly specific for postnatal adaptation such as immune function, digestion, respiration, carbohydrate metabolism, and adipogenesis. Inflammation and prostaglandin synthesis, two key processes involved in normal labor, were also activated in term amniotic fluid. |
| 2034 | GSE11208 |
Profile | The long-term goal of this project is to establish whether and how chronic nicotine exposure affects nervous system function. The biological targets of nicotine action are diverse members of the superfamily of neurotransmitter-gated ion channels called nicotinic acetylcholine receptors (nAChR). nAChR play multiple critical roles in chemical signaling throughout the brain and body. They also must be involved in nicotine dependence, which drives tobacco product use responsible for tremendous economic and personal costs. To define changes in gene expression induced by nicotine exposure in a model neuronal cell lines expressing at least two nicotinic receptor subtypes. Nicotine exposure exerst at least some of its effects on nervous system function by altering gene expression. Cells of the SH-SY5Y human neuroblastoma will be exposed to an efficacious dose of nicotine or to control medium for two different periods. Keywords: time-course |
| 2035 | GSE22533 |
Profile | A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. To model resistance to aromatase inhibitor (AI) therapy long-term estrogen-deprived (LTED) derivatives of MCF-7 and HCC-1428 cells were generated through culture for 3 and 7 months under hormone-depleted conditions, respectively. These LTED cells showed sensitivity to the ER downregulator fulvestrant under hormone-depleted conditions, suggesting continued dependence upon ER signaling for hormone-independent growth. To evaluate the role of ER in hormone-independent growth, LTED cells were treated +/- 1 uM fulvestrant x 48 h before RNA was harvested for gene expression analysis. |
| 2036 | GSE26594 |
Profile | Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation including resistance to apoptosis. In previous work, we showed that exposure to the pro-inflammatory cytokines, TNF-α and IFN-γ reverses fibroblast resistance to apoptosis. The goal of this study was to investigate the underlying mechanism. Based on an initial interrogation of the transcriptomes of unstimulated and TNF-α and IFN-γ-stimulated primary lung fibroblasts and the lung fibroblast cell line, MRC5, we show here that among Fas-signaling pathway molecules, Fas expression was increased ~6-fold in an NF-κB and p38mapk-dependent fashion. Prevention of the increase in Fas expression using Fas siRNAs blocked the ability of TNF-α and IFN-γ to sensitize fibroblasts to Fas ligation induced-apoptosis; while enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. They also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant. |
| 2037 | GSE36895 |
Profile | Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC) the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. |
| 2038 | GSE48567 |
Profile | We have identified the overexpression of FGF18 as an independent predictive marker for poor clinical outcome in patients with advanced stage high-grade serous ovarian cancer. Functional studies have demonstrated that FGF18 promotes migration, invasion and tumorigenicity of ovarian cancer cells in vitro and in vivo. To identify the FGF18 responsive genes contributing its biologic effects on ovarian tumorigenesis, we performed gene expression profiling in ovarian cancer cell line A224 with ectopic overexpression of FGF18 or RFP (as control). |
| 2039 | GSE40326 |
Profile | In multiple myeloma (MM) hypoxia-inducible transcription factor-1 (HIF-1) is overexpressed in the MM cells of the hypoxic bone marrow (BM) microenvironment. Herein, we explored in MM cells the in vitro and in vivo effects of persistent HIF-1 inhibition by expression of a lentivirus shRNA pool on proliferation, survival and transcriptional and pro-angiogenic profiles. Among the significantly modulated genes (326 and 361 genes in hypoxic and normoxic condition, respectively), we found that HIF-1 inhibition in the human myeloma cell line JJN3 downregulates the pro-angiogenic molecules VEGF, IL8, IL10, CCL2, CCL5, and MMP9. Interestingly, several pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1. The effect of HIF-1 inhibition was assessed in vivo in NOD/SCID mice both in subcutaneous and intratibial models, indicating in either case a dramatic reduction of weight and volume of the tumor burden as a consequence of HIF-1 knockdown. Moreover, a significant reduction of the number of vessels per field and VEGF immunostaining were observed. Finally, in the intra-tibial experiments, HIF-1 inhibition significantly blocks JJN3-induced bone destruction. Overall, our data indicate that HIF-1 suppression in MM cells significantly blocks MM-induced angiogenesis and reduces both tumor burden and bone destruction in vivo, strongly indicating HIF-1 as an emerging therapeutic target in MM. |
| 2040 | GSE28327 |
Profile | In multiple myeloma (MM) endothelial progenitor cells (EPCs) regulate tumor angiogenesis and disease progression. They share a common bone marrow microenvironment with myeloma tumor cells. CD138+ tumor plasma cells from 12 newly diagnosed patients with advanced MM were examined for genomic instability by RNA microarrays to assess changes in gene expression. |
| 2041 | GSE11237 |
Profile | Pharmacological inhibition of cyclooxygenase-2 (COX-2) is being explored as a chemotherapeutic option because COX-2 protein expression is often elevated in many cancers. Cancer cells treated with COX-2 inhibitors such as the selective COX-2 inhibitor celecoxib, show growth inhibition and the induction of apoptosis, through alterations in inflammatory processes, angiogenesis, cell adhesion and transforming growth factor-β signaling. This study was conducted to determine if the same processes are relevant to celecoxib’s effects on human colorectal adenocarcinomas treated in vivo. A cohort of 23 patients with primary colorectal adenocarcinomas was randomized to receive a 7-day course of celecoxib (400 mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from patients with and without celecoxib pre-treatment. Using fold change (>1.5) and p-value (<0.05) cut-offs, 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not. Of the differentially expressed genes, multiple genes involved in cellular lipid and glutathione metabolism showed decreased expression levels in celecoxib pre-treated samples; changes associated with diminished cellular proliferation. Other observed gene expression changes consistent with reduced proliferation include: altered expression of genes involved in cell adhesion (including collagen, laminin, von Willebrand factor and tenascin C), increased expression of inflammatory modulators (including inerleukin-6, S100 calcium binding protein A8, and several chemokines) and decreased expression of the pro-angiogenic gene, angiogenin. Celecoxib pre-treatment for 7 days in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation. Keywords: treatment outcome |
| 2042 | GSE35809 |
Profile | Genome-wide mRNA expression profiles of 70 primary gastric tumors from the Australian patient cohort. Like many cancers gastric adenocarcinomas (gastric cancers) show considerable heterogeneity between patients. Thus, there is intense interest in using gene expression profiles to discover subtypes of gastric cancers with particular biological properties or therapeutic vulnerabilities. Identification of such subtypes could generate insights into the mechanisms of cancer progression or lay the foundation for personalized treatments. Here we report a robust gene-xpression-based clustering of a large collection of gastric adenocarcinomas from Singaporean patients [GSE34942 and GSE15459]. We developed and validated a classifier for the three subtypes in Australian patient cohort. |
| 2043 | GSE18313 |
Profile | T cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+TCRVβ+ restricted cytotoxic T cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report the presence of CTL clones with varying TCRVβ repertoire in 70% of patients with Waldenstrom’s Macroglobulinaemia (WM) (n=20). Previous nucleoside analogue (NA) therapy associated with an increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRVβ expansions (X2=11.6; P<0.001) as 83% of patients without (n=6) and only 7% with TCRVβ expansions (n=14) had received NA. Clonality of CD3+CD8+CD57+TCRVβ+ restricted CTLs were confirmed by TCRVβ CDR3 size analysis and direct sequencing. To characterize CTL clones, samples of CD3+CD8+CD57+TCRVβ+ cells were profiled using DNA microarrays and the results were validated on both gene and protein level. By gene set enrichment analysis, CTL clones not only expressed genes (GZMB, PRF1, FGFBP2) from cytotoxic pathways but also genes which suppress apoptosis, inhibit proliferation, arrest cell cycle G1/S transition and activate T cells (RAS, CSK and TOB pathways). Proliferation tracking confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity and anergic nature of clonal T cells in a B cell tumor. We used microarrays to detail the global programme of gene expression underlying T cell clonal expansion and identified distinct classes of up-regulated genes during this process. |
| 2044 | GSE13738 |
Profile | There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this the question of whether such forms of ‘bystander’ T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyse bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander activated T cells. Here, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially amongst CD4+ memory T cells. Furthermore, bystander activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses. |
| 2045 | GSE20146 |
Profile | Genome-wide transcriptome analysis of expression changes in Globus Pallidus interna (GPi) from Parkinson's disease brain tissue versus control brain tissue. |
| 2046 | GSE12644 |
Profile | We explored gene expression profile of human aortic valves in patients with or without aortic stenosis. The dataset that we generated constitutes a large-scale quantitative measurements of gene expression in normal and stenotic human valves. The goal was to compare gene expression levels between the two groups and identified a list of genes that are up- or down-regulated in aortic stenosis. Keywords: disease state analysis |
| 2047 | GSE26834 |
Profile | Although estrogen receptor (ER) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer cross-talk between these pathways, particularly at the level of gene transcription, remains poorly understood. We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3hr or 24hr. IGF-I regulated mRNA of 5-10-fold more genes than estradiol, and many genes were co-regulated by both ligands. Importantly, expression of these co-regulated genes correlated with poor prognosis of human breast cancer. Closer examination revealed enrichment of repressed transcripts. Interestingly, a number of potential tumor suppressors were down-regulated by IGF-I and estradiol. In fact, BLNK, one of the top repressed genes, is a potential growth suppressor in breast cancer cells. Analysis of three down-regulated genes showed that E2-mediated repression occurred independently of IGF-IR, and IGF-I-mediated repression occurred independently of ER. However, repression by IGF-I or estradiol required common downstream kinases. In conclusion, E2 and IGF-I co-regulate a set of genes that affect breast cancer outcome. There is enrichment of repressed transcripts, and the down-regulation is independent at the receptor level. This may be important clinically, as tumors with active ER and IGF-IR signaling may require co-targeting of both pathways. KEYWORDS: multiple group comparison |
| 2048 | GSE28619 |
Profile | Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease and occurs in patients with excessive alcohol intake It is characterized by marked hepatocellular damage steatosis and pericellular fibrosis. Patients with severe AH have a poor short-term prognosis. Unfortunately, current therapies (i.e. corticosteroids and pentoxyphylline) are not effective in many patients and novel targeted therapies are urgently needed. The development of such therapies is hampered by a poor knowledge of the underlying molecular mechanisms. Based on studies from animal models, TNF alfa was proposed to play a pivotal role in the mechanisms of AH. Consequently, drugs interfering TNF alfa were tested in these patients. The results were disappointing due to an increased incidence of severe infections. Unluckily, there are not experimental models that mimic the main findings of AH in humans. To overcome this limitation, translational studies with human samples are required. We previously analyzed samples from patients with biopsy-proven AH. In these previous studies, we identified CXC chemokines as a potential therapeutic target for these patients. We expanded these previous observations by performing a high-throughout transcriptome analysis. |
| 2049 | GSE32054 |
Profile | CD34+ fraction of cord blood (CB) cells can be reprogrammed on pronectinF-coated dish in serum free medium using Sendai virus (SeV) vector carrying reprogramming factors OCT3/4 SOX2, KLF4 and c-MYC. human ES cell-like colonies came to merge around 18 days after SeV infection on pronectin-coated dish in human ES cell medium supplemented with bFGF under normoxic culture (20% O2). After passages, dish like-shape colonies were seeded on pronectinF-coated 96 well-plate in a single cell and cultured in N2B27 based medium supplemented with LIF, FK, MAPKi, GSKi in hypoxic culture condition (5% O2) for cloning purpose. Emerged dome shape colonies were collected and cultured in human ES cell medium supplemented with bFGF under normoxic culture (20% O2) again. Dish shape and human ES cell-like colonies derived from single cell were picked up for further appraisal of reprogrammed cells such as expression of pluriotency–related molecules. Reprogrammed cells can be maintained for more than 20 passages without differentiation. |
| 2050 | GSE2665 |
Profile | Lymph node vs. tonsil Keywords: repeat sample |
| 2051 | GSE28415 |
Profile | The second leading cause of cancer death for women in the U.S. is breast cancer. Moreover a significant number of patients with breast tumors acquire resistance to drugs during therapy. To develop targeted therapeutic strategies to combat drug resistance it is essential to understand the basic molecular mechanisms through which cancer cells control sensitivity to chemotherapeutics. To identify new candidate genes and facilitate the discovery of novel drug resistance pathways, we have generated a resistance profile or ?resistome? of etoposide resistant MCF7 breast cancer cells. Differential expression of over 5000 genes (fold change > 2, P value < 0.05) indicate that several drug resistance mechanisms may be operating in these cells, including up-regulation of ABC transporter genes, down-regulation of the drug target and down-regulation of apoptotic genes. Several transcription factors such as RUNX2, SOX9, ETS1 and SMAD3 were up-regulated in the drug resistant cells. Targeted RUNX2 knockdown in the resistant cells using siRNA increased sensitivity to etoposide and also upregulated expression of pro-apoptotic genes indicating that RUNX2 could be a molecular target against etoposide resistance. Differential miRNA (microRNA) expression was observed among the drug resistant and sensitive cells suggesting that miRNA may also play a role in regulation of drug resistance. Hsa-miR-218, which targets ABCC6, was down-regulated in the drug resistant cell line. Transfection of a miR-218 mimic could down-regulate the expression of the efflux pump ABCC6 by 65% in drug resistant cells suggesting that regulation of miRNA may play an important role in etoposide resistance. This SuperSeries is composed of the SubSeries listed below. |
| 2052 | GSE31315 |
Profile | Targeted therapies against cancer stem cells which are enriched in side populations (SP) involves interruption of Wnt-signalling. Furthermore EpCAM is a SP marker and modulator of Wnt-signalling. Therefore, the effects of an anti-EpCAM treatment on SP-cells and WNT/β-catenin signalling was studied. SP of the human lung adenocarcinoma cell line A549 was obtained by fluorescence activated cell sorting and whole genome scans helped to define their molecular phenotype after anti-EpCAM antibody treatment. |
| 2053 | GSE39452 |
Profile | EZH2 is frequently over-expressed in aggressive and metastatic solid tumors including castration resistant prostate cancer (CRPC). We sought to determine EZH2-dependent gene expression programmes in prostate cancer progression, and found an intriguing functional switch of EZH2 from a repressor to an activator during CRPC development. We used microarrays to detail the global profiling of gene expression that are differentially regulated upon EZH2 depletion in two different prostate cancer cell lines. |
| 2054 | GSE37595 |
Profile | T-bet is pivotal for initiation and perpetuation of Th1 immunity. Identification of novel T-bet regulated genes is crucial for further understanding the biology of this transcription factor. By combining siRNA technology with genome-wide mRNA analysis we sought to identify new T-bet regulated genes in IL-18-activated KG1 cells. |
| 2055 | GSE11552 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 2056 | GSE12854 |
Profile | The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Keywords: genetic modification |
| 2057 | GSE26910 |
Profile | Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value. |
| 2058 | GSE24155 |
Profile | Absent in Melanoma 2 (AIM2) is a member of the HIN-200 family of hematopoietic IFN-inducible nuclear proteins associated with infection defense and tumor pathology. Recently, AIM2 was found to act as a DNA sensor in innate immunity. In addition, a high frequency of AIM2-alterations was observed in microsatellite unstable tumors. To elucidate AIM2 function in colorectal tumors, we here addressed AIM2-responsive genes by microarray. Among genes up-regulated by AIM2, there were a number of interferon-stimulated genes (ISGs: IFIT1, IFIT2, IFIT3, IFI6, IRF7, ISG15, HLA-DRA, HLA-DRB, TLR3 and CIITA) as well as genes involved in intercellular adhesion and matrix remodeling. Expression of ISGs correlated with expression of AIM2 in ten different IFN-γ treated colorectal cancer cell lines. Moreover, knock-down of AIM2 resulted in reduced expression of HLA-DRA, HLA-DRB, and CIITA in IFN-γ treated cells. IFN-γ independent induction of HLA-DR genes and their encoded proteins was also demonstrated upon transient induction of AIM2. STAT-signaling was not involved in IFN-γ independent induction of ISGs, arguing against participation of cytokines released in an autocrine manner. Our data indicate that AIM2 mediates IFN-γ dependent and independent induction of several Interferon stimulated genes (ISGs) including genes encoding the MHC II antigens HLA-DRα and β. we used microarray techniques to define genes responsive to AIM2 expression in colorectal tumor cells. |
| 2059 | GSE1614 |
Profile | This is an analysis of Caco-2 BBe cell spontaneous differentiation. JF2dR1-JF2dR4 = proliferating cells; JF8dR1-JF8dR4 = 4 d post-confluent; JF15dR1-JF15dR4 = 11 d pc differentiated Keywords: time-course |
| 2060 | GSE34112 |
Profile | The hypoxia response contributes to radio and chemo-resistance in cancer cells. Our previous work has shown that the nitric oxide donating non-steroidal anti-inflammatory drug (NO-NSAID) NO-sulindac is a potent inhibitor of the hypoxia response in prostate cancer cells and leads to increased susceptibilty to radiation. In this study we used microarrays to investigated the global impact of NO-sulindac on the hypoxia response in prostate cancer cells with a view to determining the mechanism of action. |
| 2061 | GSE24547 |
Profile | Treatment with Aurora inhibitors has been shown to induce diverse biological responses in different tumor cell lines in part depending on their p53 status. To characterize at the transcriptional level the effects of Danusertib we analyzed by microarray different tumor cell lines, with WT or mutant p53 status, that showed differential cell cycle response upon drug treatment. |
| 2062 | GSE43591 |
Profile | MicroRNAs are small noncoding RNA molecules that are involved in the control of gene expression. To investigate the role of microRNA in multiple sclerosis (MS) we performed global microarray analyses of mRNA and microRNA in peripheral blood T-cells from relapsing-remitting MS patients and controls. We identified 2,452 regulated genes and 21 regulated microRNA that differed between MS patients and controls. By Kolmogorov-Smirnov test, 20 of 21 regulated microRNA were shown to affect the expression of their target genes, many of which are involved in the immune system. LIGHT (TNFSF14) was a microRNA target gene significantly decreased in MS. The down-regulation of mir-494 and predicted mRNA-target LIGHT was verified by real-time PCR and we could demonstrate decreased serum levels of LIGHT in MS. Thus, regulated microRNA were significantly associated with both gene and protein expression of a molecule in immunological pathways. These findings indicate that microRNA may be important regulatory molecules in T-cells in MS. |
| 2063 | GSE7890 |
Profile | Keloids are benign tumors of the dermis that form during a protracted wound healing process. Susceptibility to keloid formation occurs predominantly in people of African and Asian descent. The key alteration(s) responsible for keloid formation has not been identified and there is no satisfactory treatment for this disorder. The altered regulatory mechanism is limited to dermal wound healing although several diseases characterized by an exaggerated response to injury are prevalent in individuals of African ancestry. We have observed a complex pattern of phenotypic differences in keloid fibroblasts grown in standard culture medium or induced by hydrocortisone. In this study Affymetrix-based microarray was performed on RNA obtained from fibroblasts cultured from normal scars and keloids grown in the absence and presence of hydrocortisone. We observed differential regulation of approximately 500 genes of the 38,000 represented on the Affymetrix chip. Of particular interest was increased expression of several IGF-binding and IGF-binding related proteins and decreased expression of a subset of Wnt pathway inhibitors and multiple IL-1-inducible genes. Increased expression of CTGF and IGFBP-3 was observed in keloid fibroblasts only in the presence of hydrocortisone. These findings support a role for multiple fibrosis-related pathways in the pathogenesis of keloids Keywords: cell-type comparison, drug treatment comparison |
| 2064 | GSE25613 |
Profile | The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL) an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. |
| 2065 | GSE17543 |
Profile | Transcription factor FoxM1 is expressed in proliferating cells and its expression is critical for cell proliferation in embryos and tumors. FoxM1 regulates a multi-gene transcriptional network for cell cycle regulation. We used microarrays to detail the global program of gene expression either directly or indirectly regulated by FoxM1, and distinct classes of up- and down-regulated genes. |
| 2066 | GSE9091 |
Profile | To understand the differentiation process of embryonic stem cells into hemangioblasts gene expression profiles of ES, EB and Blast cells (BL) were analyzed. Keywords: time course |
| 2067 | GSE41851 |
Profile | Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and performed a pan-genomic comparative analysis between MALC and classical suspension cultures. We used microarrays to detail the global gene expression profile induced by aggregated growth of lymphoma cells. |
| 2068 | GSE17299 |
Profile | IFNα-mediated gene expression pattern. Direct effects of IFNα on human CD8 T cells without any other concomitant signal. This analysis examined the direct effects of IFNa on human CD8 T cells without any other concomitant signal. Total human CD8 T cells were magnetically sorted from peripheral blood by negative selection. In order to minimize the presence of antigen-experienced cells total human CD8 T cells were depleted of CD45RO+ cells by labelling with anti-CD45RO magnetic bead. In both steps of cellular sorting, negative selection were preferred to positive selection to avoid direct labelling of CD8 T cell surface molecules could interfere with downstream IFNa-mediated signalling. Magnetically sorted untouched human CD8+CD45R0- T cells from three different donors were unstimulated or stimulated with IFNa2b or IFNa5 and cells were harvested 7 hours later. mRNAs from the 3 subjects were pooled and analyzed using Affymetrix human HG-U133A 2.0 array gene chips Fold-change ≥ 2 criterion was used to identify genes which expression differed between treatment and control (unstimulated cells). Keywords: Gene expression pattern analysis |
| 2069 | GSE25119 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 2070 | GSE26101 |
Profile | A characteristic feature of anaplastic large cell lymphoma (ALCL) is the significant reduction of the T-cell expression program despite its T-cell origin a finding very similar to the loss of B-cell identity of classical Hodgkin lymphoma (cHL). Previously we demonstrated that epigenetic mechanisms are active in cHL to induce this peculiar phenotype. The results show that combined DNA demethylation and histone acetylation of T-cell lines induce an almost complete extinction of the T-cell phenotype, including the down-regulation of essential T-cell receptor signalling pathway genes such as CD3, LCK and ZAP70, as well as an up-regulation of ALCL-characteristic genes. In contrast, combined DNA demethylation and histone acetylation of ALCL cells is not able to reconstitute their T-cell phenotype. This clearly demonstrates that similar epigenetic mechanisms are active in ALCL and cHL which are responsible for the extinction of their cell type characteristic phenotype. |
| 2071 | GSE16236 |
Profile | Myelodysplastic Syndromes (MDSs) are a heterogeneous family of clonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis and frequently leukemia progression. To exlore how MDS develop into leukemia we performed the transcriptional profiling of lesional cells and normal lymphoid cells from the MDS patients. |
| 2072 | GSE34789 |
Profile | Ventilator induced lung injury can lead to serious conditions like ARDS which are associated with a high mortality (around 30% Stapleton et al., Chest, 2005). We hypothesized that changes of expression levels of different genes would lead us to the identification of critical target genes, which might influence the inflammation and outcome associated with this condition. We used human whole genome U133 Plus 2.0 microarrays to detail the changes of gene expression and identified distinct classes of up-regulated genes during this process. |
| 2073 | GSE2888 |
Profile | The use of peripheral blood mononuclear cells (PBMC) for transcriptome analysis has already been proven valuable for assessing disease-associated and drug response related gene signatures. While these proof-of-principle studies have been critically important the instability of RNA within PBMC prohibits their use in large scale multi-center trials for which samples have to be transported for a prolonged time prior RNA isolation. Therefore, a prerequisite for transcriptome analysis of peripheral blood in clinical trials will be a standardized and valid method to immediately stabilize the RNA profile after blood withdrawal. We demonstrate that the globin mRNA reduction method results in significantly improved data quality of stabilized RNA samples resulting in low intra-group variance and a detection rate of expressed genes similar to PBMC. More important, even small differences in gene expression such as observed between females and males were detected and sufficient to predict gender in whole blood samples. Keywords: biological replicates |
| 2074 | GSE32676 |
Profile | To perform an integrative profile of human pancreatic cancer (PDAC) to identify prognosis-significant genes and their related pathways. A concordant survival-based whole genome in silico array analysis of DNA copy number and mRNA & micro RNA (miRNA) expression in 25 early stage PDAC was performed. A novel composite score simultaneously integrated gene expression with regulatory mechanisms to identify the signature genes with the most levels of prognosis-significant evidence. The predominant signaling pathways were determined via a pathway-based approach. Independent patient cohorts (n= 150 and 42) were then used as in vitro validation of the array findings. We find that EGFR, SRC signaling, and PI3K/AKT pathway activation are strongly linked to clinical disease progression. Furthermore, we identify two discrete subsets of pancreatic tumors characterized by either SRC or PI3K/AKT signaling that may dictate variable responses to targeted therapy. |
| 2075 | GSE6885 |
Profile | The gene expression of two different tumorigenic human breast epithelial cell types (HMLER and BPLER) is compared with their immortalized parental cell-of-origin (HME and BPE). Keywords: breast cancer cell-of-origin, HMEC, BPEC,metastasis, tumor stem cells, tumor initiating cells, breast adenocarcinoma |
| 2076 | GSE26966 |
Profile | Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options. To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples. Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45β, GADD45γ and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1. PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45β was performed. Overexpression of GADD45β in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45γ, methylation interference assays showed no evidence of epigenetic modification of the GADD45β promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45β is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45γ, GADD45β is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression. |
| 2077 | GSE6324 |
Profile | We used human Affymetrix microarrays to identify the up- or down-regulated gene expressions from MDA-MB-231 cells infected with control vector or Flag-SR-IkBa Keywords: microarray |
| 2078 | GSE48466 |
Profile | We used microarrays to compare the gene expression profiles of different H1N1 isolates (seasonal and pandemic) in lung epithelial cells in vitro. |
| 2079 | GSE9712 |
Profile | Nu61 a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Keywords: Pair-wise comparison of radiosensitive vs radioresistant tumors |
| 2080 | GSE16093 |
Profile | To date all methods to generate induced pluripotent stem (iPS) cells require the use of genetic materials and/or potentially mutagenic chemicals. Here we report the generation of stable human iPS cells from human fibroblasts by directly delivering defined reprogramming proteins. This system eliminates the potential risks associated with genetic and/or chemical manipulation, and could provide a safe and physiologically intact source of cells for regenerative medicine. |
| 2081 | GSE17906 |
Profile | The prostate stroma is a key mediator of epithelial differentiation and development and potentially plays a role in the initiation and progression of prostate cancer. Isolation and characterization of viable populations of the constituent cell types of prostate tumors could provide valuable insight into the biology of cancer. The CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between normal and tumor-associated reactive stromal cells. Reactive stroma is characterized by smooth muscle differentiation, prostate down-regulation of SPOCK3, MSMB, CXCL13, and PAGE4, bladder down-regulation of TRPA1, HSD17B2, IL24, and SALL1, and an up-regulation of CXC-chemokines. This study identified a group of differentially expressed genes in CD90+ reactive stromal cells that are potentially involved in organ development and smooth muscle cell differentiation. |
| 2082 | GSE42586 |
Profile | The multifunctional protein tyrosine phosphatase PRL-1 (Gene Symbol: PTP4A1) has been identified as an important oncogene with roles in promoting cell proliferation survival, migration, invasion, and metastasis. However, little is currently known about the signaling pathways through which it mediates its effects. We used Affymetrix Human Genome U133 Plus 2.0 arrays to examine the global molecular changes of gene expression occurring in response to stable PRL-1 overexpression in human embryonic kidney 293 (HEK293) cells. |
| 2083 | GSE6596 |
Profile | The aim of our work was the comparison of human and mouse gene expression data and to identify a conserved breast tumor gene set. The results encourage the usefulness of transgenic mice as a model for human breast cancer formation and therapy. Keywords: Comparison of gene expression data |
| 2084 | GSE18150 |
Profile | Overexpression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) occurs in diverse malignancies including prostate cancer, breast cancer, and glioblastoma multiforme (GBM) (1). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep), or its specific down-regulation by shRNA, strongly impairs GBM cancer stem cell self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM cancer stem cells, we found the expression of c-myc, recently reported to be essential for GBM cancer stem cells, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated down-regulation of EZH2 in combination with chromatin immunoprecipitation (ChIP) experiments revealed that c-myc is a direct target of EZH2 in GBM cancer stem cells. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM cancer stem cell maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management. |
| 2085 | GSE29652 |
Profile | Astrocyte dysfunction impacts their normal function including neuronal support, thereby contributing to neurodegenerative pathologies including Alzheimer's disease (AD). Therefore to understand the role of astrocytes in the pathogenesis of age-related disorders we analysed the gene expression profile of astrocytes with respect to Alzheimer-type pathology. The aim of the present study was to combine immuno-LCM and microarray analysis to characterise the astrocyte transcriptome at different Braak stages, and with respect to ApoE genotype, in post-mortem human temporal cortex sampled dervied from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS). |
| 2086 | GSE4757 |
Profile | Alzheimer's Disease (AD) is a devastating neurodegenerative disorder affecting approximately 4 million people in the U.S. alone. AD is characterized by the presence of senile plaques and neurofibrillary tangles in cortical regions of the brain. These pathological markers are thought to be responsible for the massive cortical neurodegeneration and concomitant loss of memory reasoning, and often aberrant behaviors that are seen in patients with AD. Understanding the molecular mechanisms whereby these histopathological markers develop will greatly enhance our understanding of AD development and progression. A clearer understanding of the mechanisms underlying neurofibrillary tangle formation specifically may help to clarify the basis for dementia of AD as well as the dementias associated with other diseases that are collectively referred to as "tauopathies." To expression profile both neurons containing neurofibrillary tangles and normal neurons from the entorhinal cortex of 10 mid-stage AD cases. The gene expression profile of neurons that contain neurofibrillary tangles will differ from the expression profile of histopathologically normal neurons from the same patient and from the same brain region. Some of these differences will be informative as to the mechanisms of tangle formation. Keywords: disease-state analysis |
| 2087 | GSE30676 |
Profile | T lymphocytes are orchestrators of adaptive immunity. Naïve T cells may differentiate into the Th1 Th2, Th17 or iTreg phenotype, depending on environmental co-stimulatory signals. In order to identify the genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli an pathway inhibitors |
| 2088 | GSE18180 |
Profile | Background and aim: Human Induced pluripotent stem (iPS) cells have been derived from dermal fibroblasts keratinocytes and blood cells by ectopic expression of defined transcription factors.1–5 Application of this approach in human cells would have enormous potential and generate patient-specific pluripotent stem cells to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. In the present study, we investigated whether genetically marked human mesenchymal cells of gut mesentery may give rise to iPS cells. Methods: We used lentiviruses to express Oct4, Sox2, Nanog in mesenchymal cells of gut mesentery, then generated iPS cells were identified in many aspects including morphology, pluripotent markers, global gene expression profile, DNA methylation status at pluripotent cell-specific genes, embryoid bodies and terotomas formation. Results: The resulting iPS cells from mesenchymal cells of gut mesentery were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, and epigenetic status of pluripotent cell-specific genes. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. DNA fingerprinting showed that the human iPS cells were derived from the donor cells and are not a result of contamination. |
| 2089 | GSE34771 |
Profile | This study aimed to define the genes associated with PCNSL patient survival. Expression profiling was performed on 34 PCNSLs. A gene classifier was developed. |
| 2090 | GSE2724 |
Profile | A series of gene expression measurements of uterine fibroids with mutated fumarate hydratase (FH) gene and normal myometrium. Keywords: other |
| 2091 | GSE25970 |
Profile | The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research. However substantial variation has been reported among pluripotent cell lines, which could affect their utility and clinical safety. Such cell-line specific differences must be better understood before one can confidently use embryonic stem (ES) or induced pluripotent stem (iPS) cells in translational research. Towards this goal we have established genome-wide reference maps of DNA methylation and gene expression for 20 previously derived human ES lines and 12 human iPS cell lines, and we have measured the in vitro differentiation propensity of these cell lines. This resource enabled us to assess the epigenetic and transcriptional similarity of ES and iPS cells and to predict the differentiation efficiency of individual cell lines. The combination of assays yields a scorecard for quick and comprehensive characterization of pluripotent cell lines. We used microarrays to compare the gene expression profiles between human ES cell lines, iPS cell lines, fibroblasts and embryoid bodies, and to identify cell-line specific outlier genes. |
| 2092 | GSE19811 |
Profile | We used microarrays to detail the global gene expression profile in subcutaneous adipose tissue between controls and HIV-infected patients under antiretroviral treatment. |
| 2093 | GSE28799 |
Profile | Increasing evidence supports the existence of a subpopulation of cancer cells capable of self-renewal and differentiation into diverse cell lineages. These cancer stem-like or cancer-initiating cells (CICs) also demonstrate resistance to chemo- and radiotherapy and may function as a primary source of cancer recurrence. We report here on the isolation and in vitro propagation of multicellular ovarian cancer spheroids from a well-established ovarian cancer cell line (OVCAR-3). The spheroid-derived cells (SDCs) display self-renewal potential the ability to produce differentiated progeny, and increased expression of genes previously associated with CICs. SDCs also demonstrate higher invasiveness, migration potential, and enhanced resistance to standard anticancer agents relative to parental OVCAR-3 cells. Furthermore, SDCs display up-regulation of genes associated with epithelial-to-mesenchymal transition (EMT), anticancer drug resistance and/or decreased susceptibility to apoptosis, as well as, down-regulation of genes typically associated with the epithelial cell phenotype and pro-apoptotic genes. Pathway and biological process enrichment analyses indicate significant differences between the SDCs and precursor OVCAR-3 cells in TGF-beta-dependent induction of EMT, regulation of lipid metabolism, NOTCH and Hedgehog signaling. Collectively, our results indicate that these SDCs will be a useful model for the study of ovarian CICs and for the development of novel CIC-targeted therapies. |
| 2094 | GSE22377 |
Profile | Gastric cancer can be divided in two major histological subtypes: diffuse and intestinal-type adenocarcinomas. Since both types diverge in many clinical and molecular characteristics is widely accepted that both represent distinct disease entities that may benefit from different therapeutic approaches. The diffuse type is explicitly more invasive and affected patients possess extremely poor prognosis. Gene expression profiling studies identified numerous genes with differences in mRNA expression between the two types. However, little overlap of published gene lists exists forcing the need for further and more comprehensive analyses. We used microarray-based whole-transcriptome expression profiling to characterize the gene expression profile of both histologiocal types and to identify differentially expressed genes. |
| 2095 | GSE19128 |
Profile | Using herbogenomics this study provides novel insight into putative genes which may be involved in physiological responses. |
| 2096 | GSE14103 |
Profile | Analysis of synchronized HCT116 cells at various time points up to 10 hours following treatment with DMSO or Nocodazole. |
| 2097 | GSE12027 |
Profile | Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by smooth muscle-like LAM cells which have mutations in the tumor suppressor genes Tuberous Sclerosis Complex (TSC) 1 or 2, and the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of MCP-1/CCL2, GROa/CXCL1 and ENA-78/CXCL5 were significantly higher in samples from LAM patients than healthy volunteers. In this transcript analysis, expression of chemokine and chemokine receptor mRNA in LAM cells differed from those in melanoma and smooth muscle cells. Subsequent immunohistochemistry of lung sections from 30 LAM patients confirmed protein expression of chemokines and these receptors varied among LAM patient and differed from that seen in breast cancer and melanoma cells. . In vitro, MCP-1/CCL2 induced selective migration of cells showing loss of heterozygosity of TSC2 from a heterogeneous populations of cells grown from explanted LAM lungs. In addition, the frequencies of single-nucleotide polymorphisms in the MCP-1 gene promoter region differed significantly in LAM patients and healthy volunteers (p=0.018), and one polymorphism was associated significantly more frequently with the decline of lung function. These observations are consistent with the notion that chemokines such as MCP-1 may serve to specify site of LAM cell metastasis. Keywords: Human patient sample comparison with cell lines |
| 2098 | GSE25147 |
Profile | This study set out to identify global changes in gene expression in MKN45 gastric epithelial cells following 8 hours stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point. |
| 2099 | GSE35165 |
Profile | Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis except during the early stages of cancer development. Using mammary glandular structures (acini) produced in a three-dimensional cell culture system we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity. In order to identify the genes dependent on apical polarity that could control cell quiescence, and possibly other aspects of tissue homeostasis, we have used Affymetrix technology microarray analysis of the 22,277 features/genes of the Human Genome U133A 2.0 array Chip in apically polarized and non-polarized breast epithelial acinar cells in three-dimensional culture. Genes commonly down-regulated in two treatments that altered apical polarity compared to control were considered to be dependent on apical polarity status for their transcription. |
| 2100 | GSE16119 |
Profile | Little is known about the immune performance and interactions of CNS microglia/macrophages in glioma patients. Microglia/macrophages were found to be the predominant immune cell infiltrating gliomas (approximately 1% of total cells); others identified are myeloid dendritic cells (DCs) plasmacytoid DCs, and T cells. Using a procedure enriching for CD11b/c+CD45+ glioma-infiltrating microglia/macrophages (GIMs) from postoperative tissue specimens of glioma patients (Hussain et al. Neuro Oncol. 2006 J;8(3):261-79) gene expression profiles were obtained form paired samples. The expression profiles are used to identify expression signatures contributed by GIMs in glioblastoma data sets (Murat et al, submitted). |
| 2101 | GSE14773 |
Profile | Isolation and enrichment of cancer stem cells in colorectal carcinoma to study role of epithelial-mesenchymal transition regilators in tumor malignancy. |
| 2102 | GSE5081 |
Profile | The whole-genome oligonucleotide microarray analysis gives an opportunity for studying the unidentified gene expression background of the idiopathic and H.pylori related gastric erosive alterations. Using microarrays we compared the whole genome gene expression profile of HP+ and HP- gastric erosions and normal adjacent mucosa to explain the possible role and response to HP infection and to get morphology related mRNA expression patterns. Keywords: whole genomic expression |
| 2103 | GSE23183 |
Profile | Goal: To compare the gene expression profiles from pediatric patients with each other with those reported in adults and in those related to exosomes. Background: Suppression of human immunodeficiency virus (HIV) replication by CD8+ T-cells (CD8 suppression) contributes to survival in adults and children < 1 year. Soluble CD8 suppression can also be seen in some older children with AIDS. The factor responsible, CD8-derived antiviral factor (CAF), acts at the level of HIV RNA transcription. Differential gene expression techniques have been used to define the gene(s) mediating this phenomenon in adults. Recently, CAF has been linked to exosomes secreted by CD8+ T-cells. Objective: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those reportedly related to exosomes. Design/Methods: We used differential gene expression to study 3 older children with HIV infection, 1 who did demonstrate soluble CD-8 suppression and 2 who did not, and compared our results with those reported in 2 previous studies in adults and their relatedness to exosome components secreted by CD8+ T-cells. Results: 18 differentially expressed genes were also seen in 1 adult study (p=0.002, χ2 test), and 38 such genes (p < 0.0001, χ2 test) in a second adult study. In addition, two exosome components and some RNA’s related to exosomal proteins were also differentially expressed. Conclusions: In children with HIV infection, we found significant differentially expressed genes that correlated to those previously reported in 2 studies in adults. Our data also lends some support to the recent identification of CAF with exosomes secreted by CD8+ T-cells. |
| 2104 | GSE17939 |
Profile | We expressed a constitutively active mutant of MEK5 (MEK5D) in human primary endothelial cells (EC) to study the transcriptional and functional responses to Erk5 activation under static conditions. |
| 2105 | GSE24259 |
Profile | PAR-1 is known to be involved in the transition from non-metastatic to metastatic melanoma. We sought to determine the downstream target genes regulated by PAR-1 to determine how PAR-1 is contributing to the metastatic melanoma phenotype. |
| 2106 | GSE21887 |
Profile | More effective therapeutic approaches for castration-resistant prostate cancer (CRPC) are urgently needed thus reinforcing the need to understand how prostate tumors progress to castration resistance. We have established a novel mouse xenograft model of prostate cancer, KUCaP-2, which expresses the wild-type androgen receptor (AR) and which produces the prostate-specific antigen (PSA). In this model, tumors regress soon after castration, but then reproducibly restore their ability to proliferate after 1 to 2 months without AR mutation, mimicking the clinical behavior of CRPC. In the present study, we used this model to identify novel therapeutic targets for CRPC. Evaluating tumor tissues at various stages by gene expression profiling, we discovered that the prostaglandin E receptor EP4 subtype (EP4) was significantly upregulated during progression to castration resistance. Immunohistochemical results of human prostate cancer tissues confirmed that EP4 expression was higher in CRPC compared with hormone-naïve prostate cancer. Ectopic overexpression of EP4 in LNCaP cells (LNCaP-EP4 cells) drove proliferation and PSA production in the absence of androgen supplementation in vitro and in vivo. Androgen-independent proliferation of LNCaP-EP4 cells was suppressed when AR expression was attenuated by RNA interference. Treatment of LNCaP-EP4 cells with a specific EP4 antagonist, ONO-AE3-208, decreased intracellular cyclic AMP levels, suppressed PSA production in vitro, and inhibited castration-resistant growth of LNCaP-EP4 or KUCaP-2 tumors in vivo. Our findings reveal that EP4 overexpression, via AR activation, supports an important mechanism for castration-resistant progression of prostate cancer. Furthermore, they prompt further evaluation of EP4 antagonists as a novel therapeutic modality to treat CRPC. |
| 2107 | GSE647 |
Profile | primary ALL cells (B- and T-lineage) resistant to prednisolone by the MTT in vitro sensitivity assay Keywords = ALL Keywords: other |
| 2108 | GSE11630 |
Profile | In inflammatory diseases of the airway a high level (estimated to be as high as 8 mM) of HOCl can be generated through a reaction catalyzed by the leukocyte granule enzyme myeloperoxidase (MPO). HOCl, a potent oxidative agent, causes extensive tissue injury through its reaction with various cellular substances, including thiols, nucleotides, and amines. In addition to its physiological source, HOCl can also be generated by chlorine gas inhalation from an accident or a potential terrorist attack. Despite the important role of HOCl-induced airway epithelial injury, the underlying molecular mechanism is largely unknown. In the present study, we found that HOCl induced dose-dependent toxicity in airway epithelial cells. By transcription profiling using GeneChip, we identified a battery of HOCl-inducible antioxidant genes, all of which have been reported previously to be regulated by nuclear factor erythroid-related factor 2 (Nrf2), a transcription factor that is critical to the lung antioxidant response. Consistent with this finding, Nrf2 was found to be activated time and dose dependently by HOCl. Although the epidermal growth factor receptor-MAPK pathway was also highly activated by HOCl, it was not involved in Nrf2 activation and Nrf2-dependent gene expression. Instead, HOCl-induced cellular oxidative stress appeared to lead directly to Nrf2 activation. To further understand the functional significance of Nrf2 activation, small interference RNA was used to knock down Nrf2 level by targeting Nrf2 or enhance nuclear accumulation of Nrf2 by targeting its endogenous inhibitor Keap1. By both methods, we conclude that Nrf2 directly protects airway epithelial cells from HOCl-induced toxicity. |
| 2109 | GSE10710 |
Profile | Overexpression of a caspase-resistant form of Bcl-2 (D34A) in human umbilical vein endothelial cells (EC) implanted into immunodeficient mice promotes the maturation of human EC-lined microvessels invested by vascular smooth muscle cells (VSMC) of mouse origin. In contrast EC implants not overexpressing Bcl-2 form only simple, uncoated EC tubes. Here we compare the phenotypes of vessels formed in vivo and the transcriptomes in vitro of EC expressing different forms of Bcl-2. Wild type Bcl-2, like the caspase resistant D34A Bcl-2 mutant, is anti-apoptotic in vitro and promotes VSMC recruitment in vivo, whereas a G145E mutant that has diminished anti-apoptotic activity in vitro does not promote vessel maturation in vivo. The D34A and wild type forms of Bcl-2, but not the G145E mutant form of Bcl-2 significantly regulate RNA transcripts previously associated with EC-VSMC interactions and VSMC biology, including matrix Gla protein, insulin like growth factor binding protein (IGFBP)-2, matrix metaloproteinase-14 (MMP14), ADAM17 and Stanniocalcin-1. These effects of Bcl-2 on the transcriptome are detected in EC cultured as angiogenic 3-D tubes but are attenuated in EC cultured as 2-D monolayers. Bcl-2-regulated transcription in EC may contribute to vascular maturation, and support design of tissue engineering strategies using EC. Keywords: genetic modification, growth condition modification. |
| 2110 | GSE12548 |
Profile | The purpose of this study is to determine the changes in gene expression by a human retinal pigment epithelium (RPE) cell line (ARPE-19) in response to combination treatment of TGF and TNF which induces phenotypic changes in vitro that mimic the EMT (Epithelial-to-Mesenchymal Transition). For this purpose, total RNA was extracted from TGF and TNF-treated ARPE-19 cells and differential gene expression between each time point (0, 1, 6, 16, 24, 42, and 60 hours) was determined using genechip arrays (Affymetrix, Human Genome U133). Keywords: time course |
| 2111 | GSE25428 |
Profile | Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. Diagnosis usually occurs after metastatic spread largely reflecting vague symptoms of early disease combined with lack of an effective screening strategy. Epigenetic mechanisms of gene regulation, including DNA methylation, are fundamental to normal cellular function and also play a major role in carcinogenesis. To elucidate the biological and clinical relevance of DNA methylation in ovarian cancer, we conducted expression microarray analysis of 39 cell lines and 17 primary culture specimens grown in the presence or absence of DNA methyltransferase (DNMT) inhibitors. Two parameters, induction of expression and standard deviation among untreated samples, identified 378 candidate methylated genes, many relevant to TGF-beta signaling. We analyzed 43 of these genes and they all exhibited methylation. Treatment with DNMT inhibitors increased TGF-beta pathway activity. Hierarchical clustering of ovarian cancers using the 378 genes reproducibly generated a distinct gene cluster strongly correlated with TGF-beta pathway activity that discriminates patients based on age. These data suggest that accumulation of age-related epigenetic modifications leads to suppression of TGF-beta signaling and contributes to ovarian carcinogenesis. The cancer stem cell hypothesis posits that malignant growth arises from a rare population of progenitor cells within a tumor that provide it with unlimited regenerative capacity. Such cells also possess increased resistance to chemotherapeutic agents. Resurgence of chemoresistant disease following primary therapy typifies epithelial ovarian cancer and may be attributable to residual cancer stem cells, or cancer initiating cells, that survive initial treatment. As the cell surface marker CD133 identifies cancer initiating cells in a number of other malignancies, we sought to determine the potential role of CD133+ cells in epithelial ovarian cancer. We detected CD133 on ovarian cancer cell lines, in primary cancers, and on purified epithelial cells from ascitic fluid of ovarian cancer patients. We found CD133+ ovarian cancer cells generate both CD133+ and CD133- daughter cells, whereas CD133- cells divide symmetrically. CD133+ cells exhibit enhanced resistance to platinum-based therapy, drugs commonly used as first line agents for treatment of ovarian cancer. Sorted CD133+ ovarian cancer cells also form more aggressive tumor xenografts at a lower inoculum than their CD133- progeny. Epigenetic changes may be integral to the behavior of cancer progenitor cells and their progeny. In this regard, we found that CD133 transcription is controlled by both histone modifications and promoter methylation. Sorted CD133- ovarian cancer cells treated with DNA methyltransferase and histone deacetylase inhibitors show a synergistic increase in cell surface CD133 expression. Moreover, DNA methylation at the ovarian tissue active P2 promoter is inversely correlated with CD133 transcription. We also found that promoter methylation increases in CD133- progeny of CD133+ cells, with CD133+ cells retaining a less methylated or unmethylated state. Taken together, our results show that CD133 expression in ovarian cancer is directly regulated by epigenetic modifications and support the idea that CD133 demarcates an ovarian cancer initiating cell population. The activity of these cells may be epigenetically detected and such cells might serve as pertinent chemotherapeutic targets for reducing disease recurrence. |
| 2112 | GSE45921 |
Profile | Gliomas are aggressive lethal solid brain tumors arising from support cells in the central nervous system. Despite intense efforts to optimize the treatment of gliomas the outcomes of high grade glioma patients are still frustrating. The causes and progress of gliomas have been investigated extensively; however, the genetic factors involved in the development of this disease remain poorly understood. We used microarrays to detail the global program of gene expression in different grade glioma tissues and try to find out some genes associated with the tumorigenesis of gliomas. |
| 2113 | GSE17410 |
Profile | Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a MS signature comparing female MS specimens before pregnancy with respect to female MS specimens at ninth month pregnancy. |
| 2114 | GSE38816 |
Profile | Follicular lymphoma (FL) shows heterogenous expression of the cell surface B-cell marker CD20. In order to investigate whether this heterogeneity also marks underlying transcriptional heterogeneity, we sorted tumor B-cells from 8 FL specimens based upon their intermediate or high expression of CD20 and transcriptionally profiled them. |
| 2115 | GSE6047 |
Profile | To characterize the molecular origin of primary lymphomas of the central nervous system (PCNSL) 21 PCNSL of immunocompetent patients were investigated by microarray-based gene expression profiling. Comparison of the transcriptional profile of PCNSL with various normal and neoplastic B cell subsets demonstrated PCNSL (i) to display gene expression patterns most closely related to late germinal center B cells, (ii) to display a gene expression profile similar to systemic diffuse large B cell lymphomas (DLBCL), and (iii) to be in part assigned to the activated B cell-like (ABC) or the germinal center B cell-like (GCB) subtype of DLBCL. Keywords: PCNSL – DLBCL – gene expression profiling |
| 2116 | GSE22298 |
Profile | Targets of Retinoic Acid (RA) were identified in primary human epidermal keratinocytes grown in the presence or absence of all-trans retinoic acid for 1 4, 24, 48 and 72 hours. Targets of Thyroid Hormone (T3) were identified in primary human epidermal keratinocytes grown in the presence or absence of the hormone; same controls as for RA. |
| 2117 | GSE8218 |
Profile | Prostate cancer gene expression profiles were studied in this project. A total RNA from 148 prostate sample with various amount of different cell types were hybridized to Affymetrix U133A arrays. The percentage of different cell types vary considerably among samples and were determined by pathologist. Cell type specific genes can be determined by linear regression using the methods of Stuart et al PNAS, 2004. Keywords: disease state analysis |
| 2118 | GSE1140 |
Profile | Analysis of peripheral blood mononuclear cells (PBMCs) separated from whole blood of healthy male subjects - prior to onset of exercise - immediately following the end of exercise and - immediately following 1 hour of recovery from exercise Keywords: other |
| 2119 | GSE9648 |
Profile | CoMet a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. Nine metabolites predicted to be lowered in Jurkat cells with respect to normal lymphoblasts were examined: riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, α-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole. All, alone or in combination, exhibited antiproliferative activity. Of eleven metabolites predicted to be increased or unchanged in Jurkat cells, only two (bilirubin and androsterone) exhibited significant antiproliferative activity. These results suggest that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, resulting in uninhibited cellular growth and have the implication that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery. Keywords: cell type |
| 2120 | GSE12246 |
Profile | Tumor hypoxia is not a stable phenomenon but cycles between periods of deep hypoxia and reoxygenation. Cyclic hypoxia originates from heterogeneities in red blood cell flux and from the permanent remodelling of the angiogenic vascular network. Endothelial cells lining tumor blood vessels are therefore also influenced by cyclic hypoxia. The gene expression pattern promoted by cyclic hypoxia differs from those observed under normoxia and even continuous hypoxia. PTGS2 is one gene exquisitely up-regulated in endothelial cells (and tumor cells) in response to cyclic hypoxia. Elevated COX-2 (the PTGS2 gene product) expression and activity account for cyclic hypoxia-driven increase in endothelial cell survival and angiogenesis. |
| 2121 | GSE30660 |
Profile | Airway epithelial cells are the first cells of the lungs to be exposed to the toxic agents contained within cigarette smoke. Accordingly the response of these cells to this challenge is of considerable interest in the context of diseases in which cigarette smoke is a major aetiological factor. We used Affymetrix microarrays to study the effects of repeated cigarette smoke challenge on three-dimensional human lung airway epithelial cultures. |
| 2122 | GSE27071 |
Profile | Background and aim: Analysis of data obtained from genome wide gene expression experiments is challenging due to the huge amount of variables, management of the data and the need for multivariate analysis. We here present the R package: pcaGoPromoter that facilitates the interpretation of genome wide expression data to overcome these problems. In a first step principal component analysis is applied to overview any differences between the observations and possible groupings. The next step is interpretation of the principal components with respect to both biological function and involvement of predicted transcription factor binding sites. The robustness of the results is evaluated using cross validation. Illustrative plots of PCA score plots and Gene Ontology terms are available. To illustrate the functionality of the R package, we designed a serum stimulation experiment, where the main biological outcome is well documented. Results: Samples from the serum stimulation experiment were analyzed using the Affymetrix Human Genome U133 Plus 2.0 chip. The array data were analyzed by the tools of the pcaGoPromoter package, which resulted in a clear separation of the observations into the three experimental groups - controls, serum only and serum with inhibitor. The functional annotation of the axes in the PCA score plot showed the expected serum promoted biological processes such as cell cycle progression and the predicted involvement of the expected transcription factors including E2F. In addition unexpected results, e.g. the cholesterol synthesis in serum depleted cells and NF-κB activation in inhibitor treated cells were uncovered. Conclusion: The pcaGoPromoter R package provides a collection of tools for analyzing gene expression data. It works with any platform using gene symbols or Entrez Ids as probe identifiers. In addition support for several popular Affymetrix GeneChip platforms is provided. The tools give an overview of the data via principal component analysis, functional interpretation by Gene Ontology terms (biological processes), and indication of involvement of possible transcription factors. Thus, pcaGoPromoter structures the high-dimensional data of gene expression experiments and can be applied to generate hypotheses for further exploration. |
| 2123 | GSE2435 |
Profile | Assessment of mRNA expression changes in the B-lymphoblastoid cell line Awells after 6 h and 24 h of starvation-induced autophagy Keywords: ordered |
| 2124 | GSE37868 |
Profile | FDFT1 catalyzes the first reaction in the mevalonate/isoprenoid pathway we demonstrated that FDFT1 down-regulation by two shRNAs significantly reduced cell migration and invasion in highly invasive lung cancer cell lines in vitro, as well as in lung metastases in vivo. We used microarrays to detail the FDFT1 regulated gene expression underlying invasion-metastasis cascade and identified distinct classes of up-regulated genes during this process. |
| 2125 | GSE29807 |
Profile | Low Birth Weight (LBW) newborns (with weight less than 2500g) suffer a higher frequency and severity of microbial infection than normal birth weight (NBW) newborns. Morbidity and mortality of LBW infants due to infectious diseases are known to be high and it has been associated with compromised immune functions however, the complete understanding of the cause is lacking. We, therefore, conducted a gene expression study to identify all the defective pathways and functions in the LBW newborns using DNA microarray. RNA were isolated from the umbilical cord blood of the NBW and LBW newborns and processed for chip hybridisation. Our results suggest down-regulation of genes participating in several canonical pathways vital in the defense response against microbes and perpetuation of immune responses. Pattern recognition receptors (PRRs) and Interferon signaling appear to be most significantly impacted pathways. The information generated from this study may help in depth understanding of the cause of higher frequency of infections in LBW and thus, in turn help devise better therapeutic interventions. |
| 2126 | GSE20543 |
Profile | To identify candidate downstream mRNA target(s) for hsa-miR-616 Affymetrix Human Genome U133 Plus GeneChip 2.0 |
| 2127 | GSE28694 |
Profile | The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end an oligonucleotide microarray was performed (Affymetrix’s HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system. |
| 2128 | GSE47206 |
Profile | Highlighting the gene expression characteristics of a large panel of lung cancer cell lines. Microarrays were used to explore and detail the global gene expression profile of 56 lung cancer cell lines |
| 2129 | GSE40400 |
Profile | Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that is characterized by increased circulating androgen levels anovulatory infertility, and frequently, insulin resistance and hyperinsulinemia.The abnormity of oocyte nuclear maturity is the main reason for anovulatory infertility and pregnancy loss in PCOS patients.The bidirectional exchanges between oocyte and contiguous CCs are important for oocyte competence acquisition, early embryonic development and CC expansion.Gene expression profiles of CCs has been suggested to predict embryo development and pregnancy outcome. We used microarrays to detail the global programme of gene expression of CCs isolated from oocytes at metaphase I (CCMI) and metaphase II (CCMII) stage under controlled ovarian stimulation (COS) cycle in PCOS patients. |
| 2130 | GSE28796 |
Profile | The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant dose-dense docetaxel treatment using gene expression profiling on pretreatment biopsies. Patients with high-risk operable breast cancer were treated with 75 mg/m2 IV of docetaxel on day 1 of each cycle every 2 weeks x 4 cycles . Tumor tissue from pretreatment biopsies was obtained from 12 patients enrolled in the study. Gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR). |
| 2131 | GSE8646 |
Profile | p63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation. Keywords: Hay Wells syndrome, TAp63alpha, genetic alteration, pp63 Q540L |
| 2132 | GSE23655 |
Profile | Inappropriate activation of developmental pathways is a well-recognized tumor-promoting mechanism. Here we show that overexpression of the homeoprotein Six1 normally a developmentally restricted transcriptional regulator, increases Transforming Growth Factor-beta (TGF-beta) signaling in mammary carcinoma cells and induces an epithelial to mesenchymal transition (EMT) that is in part dependent on its ability to increase TGF-beta signaling. TGF-beta signaling and EMT have been implicated in metastatic dissemination of carcinoma. Using spontaneous and experimental metastasis mouse models, we demonstrate that Six1 overexpression promotes breast cancer metastasis. In addition, we show that, like its induction of EMT, Six1-induced experimental metastasis is dependent on its ability to activate TGF-beta signaling. Importantly, in human breast cancers Six1 significantly correlates with nuclear Smad3, and thus increased TGF-beta signaling. Further, breast cancer patients whose tumors overexpress Six1 have a shortened time to relapse and metastasis, and an overall decrease in survival. Finally, we show that the effects of Six1 on tumor progression likely extend beyond breast cancer, since its overexpression correlates with adverse outcomes in numerous other cancers, including brain, cervical, prostate, colon, kidney, and liver, amongst others. Our findings argue that Six1, acting through TGF-beta signaling and EMT, is a powerful and global promoter of cancer metastasis. |
| 2133 | GSE20347 |
Profile | To characterize gene expression in esophageal squamous cell carcinoma we examined gene expression in tumor and matched normal adjacent tissue from 17 ESCC patients from a high-risk region of China. |
| 2134 | GSE34800 |
Profile | The identification of subtype-specific translocations has revolutionized diagnostics of sarcoma and provided new insight into oncogenesis. We used RNA-Seq to investigate samples diagnosed as small round cell tumors of bone possibly Ewing sarcoma, but lacking the canonical EWSR1-ETS translocation. A new fusion was observed between the BCL6 co-repressor (BCOR) and the testis specific cyclin B3 (CCNB3) genes on chromosome X. RNA-Seq results were confirmed by RT-PCR and cloning the tumor-specific genomic translocation breakpoints. 24 BCOR-CCNB3-positive tumors were identified among a series of 594 sarcomas. Gene profiling experiments indicate that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas, particularly Ewing’s sarcoma. Finally, we show that CCNB3 immunohistochemistry is a powerful diagnostic marker for this group of sarcoma and that over-expression of BCOR-CCNB3 or of a truncated CCNB3 activates S-phase in NIH3T3 cells. Thus the intrachromosomal X fusion described here represents a new subtype of bone sarcoma caused by a novel gene fusion mechanism. |
| 2135 | GSE42068 |
Profile | To identify key biological pathways that define toxicity or biocompatibility after nanoparticle exposure three human cell types were exposed in vitro to two high aspect ratio nanoparticles for 1 hr or 24 hr and collected for global transcriptomics. Transcriptional responses were measured by global microarray analysis of cells in culture. |
| 2136 | GSE17477 |
Profile | Investigation of interacting effects of TB and IFN-g on gene expression regulation within human macrophage-like THP-1 cells |
| 2137 | GSE40057 |
Profile | In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the aggressiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in aggressive cell lines when compared to normal and less aggressive cell lines. Transient overexpression of miR-200c, miR-205, and miR-375 in MDA-MB-231 cells led to the inhibition of cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that it plays a more important role in regulating the aggressiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. To our knowledge, this study is the first systematic screening of functional miRNA target genes in aggressive breast cancer cells. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer aggressiveness and ultimately lead to the identification of novel biomarkers associated with prognosis. |
| 2138 | GSE11266 |
Profile | Orphan nuclear receptor estrogen-related receptor alpha (ERRα) has recently been shown to carry negative prognostic significance in breast and ovarian cancers. The specific role of ERRα in tumor growth and progression however, is yet to be fully understood. The significant homology between estrogen receptor alpha (ERα) and ERRα initially suggested that these receptors may share similar transcriptional targets. Using the well-characterized ERα-positive MCF-7 breast cancer cell line, we sought to gain a genome-wide picture of ERα-ERRα cross-talk using an unbiased microarray approach. Since a small molecule ligand has not been identified for ERRα, its transcriptional activity in these studies was induced using its known coactivator PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) as a protein ligand. Both wild-type PGC1, as well as ERRa-specific variant (PGC1 2x9) were used to activate ERRa. Non-NR-dependent activities of PGC-1α were controlled for using a variant PGC-1α in which the leucines within the NR-interacting domain had been mutated to alanines (L2L3M). Beta-galactosidase (BGAL) overexpression was used as a non-specific background control. Activation of endogenous ER was achieved by treatment with 10 nM estadiol. Keywords: Response to stimulus |
| 2139 | GSE7894 |
Profile | Gene expression profiling was carried out on peripheral blood CD2+ leukocytes from 29 children with asthma. The primary research question is whether gene expression differs in individuals from high socioeconomic status environments vs low socioeconomic status environments. Keywords: Risk prediction |
| 2140 | GSE38583 |
Profile | The tumor microenvironment is characterized by low glucose and hypoxia. It is well known that changes in the tumor microenvironment such as hypoxia and low glucose, can increase the production of VEGF. Although the role of hypoxia in the regulation of VEGF production is well understood, the mechanism linking glucose deprivation (GD) to tumor growth and angiogenesis is unclear. Here, GD (a physiological stimulus) was used to treat human tumor cells. The transcriptional reprogramming of tumor cells by GD was measured with microarray technology to provide a comprehensive analysis of the gene expression profile underlying the GD treatment. Our study suggested that GD initiates an angiogenic switch by increasing the expression of proangiogenic mediators (VEGF, FGF2, IL6, etc.) and decreasing the expression of angiogenesis inhibitors (THBS1, CXCL14 and CXCL10). The markers of Unfolded Protein Response (UPR) (Grp78/Bip, CHOP, ATF4, etc.) were significantly increased. The above results suggest GD may regulate angiogenesis through activation of the UPR. |
| 2141 | GSE22539 |
Profile | Microarray was used to study global gene expression of a cell culture model based on SV40-immortalized human corneal epithelial (iHCE) cells. The gene expression profile of the cell line was compared to the normal human corneal epithelium. Affymetrix HG-U133A GeneChips® were used for microarray experiments and results were validated by performing RT-qPCR for selected genes. iHCE was found to over- and under-express 22 % and 14 % of the annotated genes respectively. The results of this study suggest that differences between iHCE cells and normal corneal epithelium are substantial and therefore the use of these cells in corneal research should be considered with caution. |
| 2142 | GSE8003 |
Profile | In order to investigate the role of CD34 antigen in haematopoietic commitment we overexpressed the human CD34 cDNA in human CD34+ cells by retroviral gene transfer. Keywords: treatment comparison |
| 2143 | GSE30195 |
Profile | Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders characterized by dysplastic blood cell formation and peripheral blood cytopenias. Up to 30% of patients with MDS will progress to a highly chemotherapy-resistant secondary acute myeloid leukemia (sAML). We identified mutations in U2AF1 in MDS patients and patients with U2AF1 mutations are at an increased risk of developing sAML. |
| 2144 | GSE27372 |
Profile | The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast formation and the occurrence of bone lesions are still unknown. Osteocytes regulate bone remodeling at least in part through the cell death and apoptosis triggering osteoclast recruitment and formation. In this study firstly we shown that MM cells increased osteocyte death and affect their transcriptional profile evaluated by microarray analysis up-regulating osteoclastogenic cytokines as interleukin (IL)-11. Consistently we show that the conditioned media of human pre-osteocytes co-cultured with MM cells significantly increased osteoclastogenesis. To translate into a clinical perspective such in vitro evidences, we then performed histological analysis on bone biopsies obtained from MM patients, MGUS and healthy controls. We found a significant reduction in the number of viable osteocytes in MM patients as compared to controls. A significant negative correlation between the number of viable osteocytes and that of osteoclasts was also demonstrated. Moreover, as regards the skeletal involvement, we found that MM patients with bone lesions have a significant lower number of viable osteocyte than those without. Overall, our data suggest a role of osteocytic cell death in MM-induced osteoclast formation in vitro and MM bone disease in vivo in MM patients. |
| 2145 | GSE25090 |
Profile | We investigated that gene expression profile of generated human iPS cells from cord blood cells using temperature sensitive sendai-virus vector. |
| 2146 | GSE3183 |
Profile | The purpose of this project is to gain a better understanding of the early cytokine-mediated mechanisms that lead to asthma. Keywords: time series IL13 |
| 2147 | GSE10046 |
Profile | Abstract The interplay between histone modifications and promoter hypermethylation provides a causative explanation for epigenetic gene silencing in cancer. Less is known about the upstream initiators that direct this process. Here we report that the Cystatin M (CST6) tumor suppressor gene is concurrently down-regulated with other loci in breast epithelial cells co-cultured with cancer-associated fibroblasts (CAFs). Promoter hypermethylation of CST6 is associated with aberrant AKT1 activation in epithelial cells, as well as the disabled INNP4B regulator resulted from the suppression by CAFs. Repressive chromatin, marked by trimethyl-H3K27 and dimethyl-H3K9, and de novo DNA methylation is established at the promoter. The findings suggest that microenvironmental stimuli are triggers in this epigenetic cascade, leading to the long-term silencing of CST6 in breast tumors. Our present findings implicate a causal mechanism defining how tumor stromal fibroblasts support neoplastic progression by manipulating the epigenome of mammary epithelial cells. The result also highlights the importance of direct cell-cell contract between epithelial cells and the surrounding fibroblasts that confer this epigenetic perturbation. Since this two-way interaction is anticipated, the described co-culture system can be used to determine the effect of epithelial factors on fibroblasts in future studies. |
| 2148 | GSE35493 |
Profile | Rhabdoid tumors (RTs) are aggressive tumors of early childhood that occur most often in brain (AT/RTs) or kidney (KRTs). Regardless of location they are characterized by loss of functional SMARCB1 protein, a component of the SWI/SNF chromatin remodeling complex. The aim of this study was to determine genes and biological process dysregulated in common to both AT/RTs and KRTs. Gene expression for AT/RTs was compared to that of other brain tumors and normal brain using microarray data from our lab. Similar analysis was performed for KRTs and other kidney tumors and normal kidney using data from GEO. Dysregulated genes common to both analyses were analyzed for functional significance. Unsupervised hierarchical clustering of RTs identified 3 major subsets: 2 comprised of AT/RTs, and 1 of KRTs. Compared to other tumors, 1187, 663 and 539 genes were dysregulated in each subset, respectively. Only 14 dysregulated genes were common to all 3 subsets. Compared to normal tissue, 5209, 4275 and 2841 genes were dysregulated in each subset, with an overlap of 610 dysregulated genes. Among these genes, processes associated with cell proliferation, MYC activation, and epigenetic dysregulation were common to all 3 RT subsets. The low overlap of dysregulated genes in AT/RTs and KRTs suggests that factors in addition to SMARCB1 loss play a role in determining subsequent gene expression. Drugs which target cell cycle or epigenetic genes may be useful in all RTs. Additionally, targeted therapies tailored to specific RT subset molecular profiles should be considered. |
| 2149 | GSE41459 |
Profile | Proline rich 15 (PRR15) is a small nuclear protein required for normal conceptus development in the sheep. We used microarrays to assess the changes in the trophoblast transcriptome when PRR15 expression was diminished. |
| 2150 | GSE39042 |
Profile | Hypoxia protects cancer cells from chemotherapeutic drug-induced cell death. We used microarrays to detail the changes in gene expression underlying hypoxia-induced chemoresistance in cancer cells. |
| 2151 | GSE47934 |
Profile | Demonstration of hematopoietic stem cells (HSCs) was first shown in the mouse and was dependent on recipient bone marrow (BM) to support in vivo multilineage hematopoietic reconstitution thereby illustrating non-cell-autonomous requirements for HSC functions. Murine studies have defined microanatomic compartments in the BM comprised of osteoblasts, mesenchymal cells, subsets of vasculature, and innervating neural cells functioning as an HSC-supportive niche. Despite the potential clinical applications, analyses of putative HSCs in the BM of humans has not been examined. Here, using human bone biopsies, we provide evidence of HSC propensity to endosteal regions of Trabecular Bone Area (TBA). Independent of phenotypic definitions based on prospective isolation, functional studies indicate that human HSCs residing in the TBA of human and transplanted recipients had superior regenerative and self-renewal capacity and are molecularly distinct to those repopulating the Long Bone Area (LBA). Consistent with the non-cell-autonomous nature of HSC function, osteoblasts in the TBA possess unique characteristics and expressed a key network of factors including those involving Notch activity which could regulate TBA vs. LBA location of human HSCs in vivo. Our study illustrates that human-mouse xenografts provide a surrogate to indigenous human HSC in the BM, and demonstrates that BM architecture plays a critical role in defining functional properties of human HSCs. |
| 2152 | GSE15218 |
Profile | The human neuroblastoma cell line Lan5 cells were cultured in complete DMEM till 80% confluence then placed at 60000 cells per squared cm. Cells were then plated in 24-well plates for cell viability assay and in T75 flasks for RNA isolation. Medium was replaced with serum-free fresh medium for 12 hours prior to s100b treatment. Gene expression patterns were then analysed using the Human Focus Genechip array. |
| 2153 | GSE36820 |
Profile | Adenoid cystic carcinoma (ACC) is an uncommon malignant neoplasm (incidence of 0.35 per 100000) that occurs in different body sites. It most often arises in salivary glands and other secretory glands in the head and neck region. To find the gene expression signatures of ACC, we performed microarray experiments to compare ACC xenograft tumor models and normal tissue samples. We used microarrays to detail the global program of gene expression underlying adenoid cystic carcinoma and identified distinct classes of up- and down-regulated genes compared to non-neoplastic salivary tissue. |
| 2154 | GSE22544 |
Profile | Introduction: A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine complementary analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions that demonstrate copy number alterations providing a mechanistic approach to identify the 'driver genes’. Methods: We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs). Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Twelve IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from LOH analysis to identify genes showing loss of expression in LOH regions. Results: Copy number analysis results demarcated smaller boundaries for many previously reported CNAs, and in some cases, the CNAs were defined as more than a single contiguous event. Additionally, we were able to assign driver genes to these commonly reported regions using a rigorous methodology. For example, RAB25 showed a large increased expression in the tumors and mapped to the commonly reported amplification at 1q22. We also identified 5 genes in the 8q24 amplicon and TSEN4 in the 17q25 amplified region. LOH analysis confirmed some previously reported regions, and integration with copy number data determined that the detected LOH were copy neutral events. Finally, we have identified several RXR pathways that demonstrated down-regulation in IDC whose members may represent further targets of therapeutic intervention. Conclusion: We have demonstrated the utility of the application of integrated analysis using high-resolution CGH and whole genome transcript analysis for detecting driver genes in IDC. The high resolution platform allowed a refined demarcation of CNAs, and gene expression profiling provided a mechanism to detect genes directly impacted by the CNA. This is the first report of LOH in IDC using a high resolution platform. |
| 2155 | GSE26862 |
Profile | Using homologous recombination in human ESC we inserted an enhanced green fluorescent protein (eGFP) transgene into a locus encoding a postulated marker of human endoderm, SOX17 in H9 human embryonic stem cells. This allowed purification of SOX17+ hESC endodermal progeny by fluorescence activated cell sorting (FACS) to generate microarray gene expression profile. |
| 2156 | GSE19587 |
Profile | The full complement of molecular pathways contributing to Parkinson’s disease (PD) pathogenesis remains unknown. Here to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and α-synuclein toxicity, we investigated a yeast model expressing α-synuclein. Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing α-synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis. |
| 2157 | GSE13601 |
Profile | Background: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. Methods: The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). The 20 patients were then grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients by quantitative real-time RT-PCR. Results: Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.0467). In survival studies, only GLUT3 showed a prognostic value with disease-specific (P=0.049), relapse-free (P-0.0042) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. Conclusions: The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma. Keywords: gene expression profiling |
| 2158 | GSE46054 |
Profile | In order to clarify the downstream target genes of SPAG4 we performed knockdown of SPAG4 using siRNA both under normoxia and hypoxia. |
| 2159 | GSE7138 |
Profile | Foam cell formation from monocyte-derived macrophages is a hallmark of atheroscle-rotic lesions. Aspects of this process can be recapitulated in vitro by exposing MCSF-induced or platelet factor4 (CXCL4)-induced macrophages to oxidized (ox) or minimally modified (mm) low density lipoprotein (LDL). We measured gene expression in periph-eral blood mononuclear cells (PBMCs) monocytes and macrophages treated with CXCL1 (GRO-α) or CCL2 (MCP-1) as well as foam cells induced by native LDL, mmLDL or oxLDL using 22 Affymetrix gene chips. Using an advanced Bayesian error-pooling approach and a heterogeneous error model (HEM) with a false discovery rate (FDR) <0.05, we found 5,303 of 22,215 probe sets to be significantly regulated in at least one of the conditions. Among a subset of 917 candidate genes that were preselected for their known biological functions in macrophage foamcell differentiation, we found that 290 genes met the above statistical criteria for significant differential expression patterns. While many expected genes were found to be upregulated by LDL and oxLDL, very few were induced by mmLDL. We also found induction of unexpected genes, most strikingly MHC-II and other dendritic cell markers such as CD11c. The gene expression patterns in response to oxLDL were similar in MCSF-induced and CXCL4-induced macrophages. Our findings suggest that LDL and oxLDL, but not mmLDL, induce a dendritic cell-like phenotype in macrophages, suggesting that these cells may be able to present antigens and support an immune response. Keywords: PBMC, monocytes, macrophages, foam cells, chemokines |
| 2160 | GSE12198 |
Profile | Transcriptional profiling of NKAES-derived NK cells after 7 days of culture compared to primary human NK cells and NK cells stimulated by low or high dose IL2 after 7 days of culture. |
| 2161 | GSE7568 |
Profile | The goal of the study was to identify the effects of TGF-beta on primary human macrophages maturated under different conditions. Keywords: time course differentiation conditions, alternative activation |
| 2162 | GSE14566 |
Profile | Nucleotides triphosphates are extracellular messengers binding to specific plasma membrane receptors (P2Rs) that modulate responses as different as proliferation differentiation, migration or cell death on several cell types including hematopoietic stem cells. Little and controversial information is available on the role of extracellular nucleotides in human mesenchimal stem cells (hMSCs). In this study, we assessed whether P2Rs are expressed and functional in bone marrow-derived hMSCs. Our results demonstrated, at the mRNA and protein level, the expression of all P2X and P2Y receptor subtypes identified so far. P2R activation by their natural ligands adenosine triphosphate (ATP) and uridine triphosphate (UTP) induced in hMSCs, intracellular Ca2+ concentration changes, plasma membrane depolarization and permeabilization. hMSCs were resistant to the cytotoxic effects of high dose ATP despite the expression of permeabilizing P2Rs as demonstrated by the lack of morphological changes, significant release of intracellular markers of cell death or modification of the mitochondrial network. Gene expression profiling revealed the down-regulation of cell proliferation genes whereas genes involved in cell migration and cytokine production were strongly up-regulated by ATP. Functional studies confirmed the inhibitory activity of ATP on proliferation of hMSCs and clonogenic progenitors. Moreover, ATP exerted a chemotactic effect on hMSCs and increased their migration in response to the chemokine CXCL12. Finally, whereas ATP did not affect T-cell inhibitory activity of hMSCs, the nucleotide increased the production of pro-inflammatory cytokines by hMSCs. Thus, our data show that purinergic signaling modulates hMSC functions and point to a role for extracellular nucleotides on hMSCs biology. |
| 2163 | GSE2535 |
Profile | This is a class prediction experiment where the class is the response status to imatinib (also called Gleevec), a drug used to treat patients with chronic myelogenous leukemia (CML). There are two data sets, a training set (from Leipzig, 8 Responders and 5 Non-Responders) and a validation set (from Mannheim, 8 Responders and 7 Non-Responders). The objective is to identify differentially regulated genes between CML patients who respond and those who do not respond to imatinib and confirm the results in the validation data set. The samples from blood or bone marrow of CML patients were hybridized to Affymetrix HG-U95Av2 chip and RMA was used to generate the normalized signal values. Keywords = chronic myelogenous leukemia Keywords = imatinib Keywords = cytogenetic responses Keywords = Gleevec Keywords = Affymetrix Keywords: other |
| 2164 | GSE10309 |
Profile | Background: Claudin-1(CLDN1) one of the key components of tight junction proteins, was found to be down-regulated in human lung adenocarcinomas. This study we investigated the clinical significance of CLDN1 expression in lung adenocarcinoma patients and its role in cancer progression. Method: CLDN1 mRNA expression was measured in tumor specimens from 51 patients with lung adenocarcinoma. CLDN1 protein expression was also examined by immunohistochemistry on specimens from an independent cohort of 67 lung adenocarcinoma patients. CLDN1 and cancer cell migration, invasion, and in vivo metastasis were studied by compared CLDN1 overexpressed, specific shRNA knockdown cells and controls. The Affymetrix oligonucleotide microarray analysis was performed to identify CLDN1 downstream genes. Results: Lung adenocarcinoma patients with low expression of CLDN1 mRNA had shorter overall survival (p = 0.032, log-rank test). This result was further confirmed by immunohistochemistry of CLDN1 protein expression in an independent cohort of lung adenocarcinoma patients (p=0.024). Over-expression of CLDN1 inhibited lung adenocarcinoma cell migration, invasion, and in vivo metastasis. Knockdown of the exogenous CLDN1 expression in CLDN1 transfectants can restore the cancer cell invasive and metastatic ability. By using Affymetrix microarray we have identified panel of genes altered by CLDN1 over-expression. CLDN1 can up-regulate several cancer invasion/metastasis suppressors such as CTGF, THBS1, DLC1, OCLN, ZO-1, and also down-regulate invasion/metastasis enhancers such as SPP1, CUTL1, TGF-α, SLC2A3, PGF, which support that CLDN1 may behave as an invasion and metastasis suppressor. Conclusions: CLDN is a cancer invasion and metastasis suppressor. CLDN1 expression is a useful prognostic predictor and a potential drug treatment target for lung adenocarcinoma patients. Keywords: genetic modification |
| 2165 | GSE37715 |
Profile | Human hepatocyte chimeric mice were prepared and treated with hepatitis C virus (HCV) and/or interferon-alpha (IFN-α). To analyze the changes in gene expression cDNA microarray analysis was performed with the collected human hepatocytes from the chimeric mouse livers. We consider that these results provide molecular insights into possible mechanisms used by HCV to evade innate immune responses, as well as novel therapeutic targets and a potential new indication for interferon therapy. |
| 2166 | GSE28662 |
Profile | Expression data from treatment of actinomycin D (2.5uM) and triptolide (500 nM) on MCF7 cells for 2 4 and 6 hours. We used microarrays to explore the mechanism of triptolide action. |
| 2167 | GSE26622 |
Profile | In clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation. |
| 2168 | GSE9397 |
Profile | Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contractions of the D4Z4 repeat array in the subtelomeric region of chromosome 4q. By comparing genome-wide gene expression data from muscle biopsies of patients with FSHD to those of 11 other neuromuscular disorders we intend to identify disease-specific changes which are more likely to be involved in the early stages of the disease progression. The data will help to identify pathological mechanisms involved in FSHD. Keywords: Differentiation design |
| 2169 | GSE41559 |
Profile | Limitless reproductive potential is one of the hallmarks of cancer cells1. This ability is accomplished by maintaining telomeres which erosion otherwise causes cellular senescence or death. Human cancer cells often maintain shorter telomeres than do cells in surrounding normal tissues2-5. While most cancer cells activate telomerase, which can elongate telomeres6, it remains elusive why cancer cells keep telomeres short. Here we show that forced elongation of telomeres in cancer cells promotes their differentiation in a tumor microenvironment in vivo. We elongated telomeres of human prostate cancer PC-3 cells, which possess short telomeres7, by enhancing their telomerase activity. The resulting cells with long telomeres retain an ability to form tumors in a mouse xenograft model. Strikingly, these tumors exhibit many duct-like structures and reduced N-cadherin expression, reminiscent of well-differentiated adenocarcinoma. These phenotypic changes are caused by telomere elongation per se but not enhanced telomerase activity. Gene expression profiling revealed that telomere elongation correlates with inhibition of cell-cycle processes. Together, our results suggest a functional contribution of short telomeres to tumor malignancy by regulating cancer cell differentiation. |
| 2170 | GSE29237 |
Profile | Microarray anlaysis was performed to investigate gene expression patterns of other transcription factors involved in early retinal and/or forebrain development using human embryonic stem cell-derived retinal and forebrain progenitor cells. After 20 days of differentiation vesicular neurospheres selectively expressed multiple retinal transcription factor genes appropriate for the OV stage of retinogenesis, whereas nonvesicular neurospheres expressed transcription factors indicative of the embryonic forebrain. Many transcription factor genes associated with retinal development were present at higher levels in vesicular vs. nonvesicular neurospheres. Nonvesicular neurospheres, on the other hand, expressed higher levels of transcription factors implicated in early forebrain development. Taken together, results indicated that the vesicular and nonvesicular neurospheres harbored retinal progenitor cells and early forebrain populations, respectively. |
| 2171 | GSE31472 |
Profile | We used the microarray data to analyze host cells response on A549 cells infected with A/duck/Malaysia/F118/08/2004(H5N2) |
| 2172 | GSE29986 |
Profile | T-cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) share common morphologic and immunophenotypic features and are treated with similar therapeutic approaches. Nonetheless they show distinct clinical presentations suggesting that they may represent two different biological entities. In order to investigate T-LBL and T-ALL biological characteristics we used transcriptional profiling approache. Genome-wide gene expression profiling, performed on 20 T-LBL and 10 T-ALL diagnostic specimens, showed that the two malignancies shared a large fraction of their transcriptional profile while a subset of genes appeared to be differentially expressed in T-LBL versus T-ALL. This gene signature included genes involved in chemotactic responses and angiogenesis which might play a role in the different tumor cell localization suggesting that T-LBL and T-ALL could be two distinct diseases with unique transcriptional characteristics. |
| 2173 | GSE31193 |
Profile | Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders. |
| 2174 | GSE23968 |
Profile | Gene expression profiles of human embryonic stem cells fibroblasts, and fibroblast-derived induced pluripotent stem cells |
| 2175 | GSE19348 |
Profile | Intracranial pediatric germ cell tumors (GCTs) have different histological differentiations prognosis and clinical behaviors. Prognosis of patients with germinoma and mature teratoma is good, while patients with other types of GCTs, termed as nongerminomatous malignant germ cell tumors (NGMGCTs), require more extensive drug and irradiation treatment regimen. The mechanisms underlying different prognosis of various GCT subgroups remain elusive. We presented a distinct mRNA profile correlating with GCT histological differentiation and prognosis. |
| 2176 | GSE9894 |
Profile | We have studied the plasma membrane protein phenotype of human culture-amplified and native Bone Marrow Mesenchymal Stem Cells (BM MSCs). We have found using microarrays and flow cytometry, that cultured cells express specifically 113 transcripts and 17 proteins that were not detected in hematopoietic cells. These antigens define a lineage-homogenous cell population of mesenchymal cells, clearly distinct from the hematopoietic lineages, and distinguishable from other cultured skeletal mesenchymal cells (periosteal cells and synovial fibroblasts). Among the specific membrane proteins present on cultured MSCs, 9 allowed the isolation from BM mononuclear cells of a minute population of native MSCs. The enrichment in Colony-Forming Units-Fibroblasts was low for CD49b, CD90 and CD105, but high for CD73, CD130, CD146, CD200 and integrin alphaV/beta5. Additionally, the expression of CD73, CD146 and CD200 was down-regulated in differentiated cells. The new marker CD200, because of its specificity and immunomodulatory properties, deserves further in depth studies. Keywords: cell type comparison |
| 2177 | GSE16906 |
Profile | The goal is to investigate gene regulation in endometrial stromal cells expressing the Notch ligand Jag1. |
| 2178 | GSE5224 |
Profile | To identify genes that influence resistance to mastitis we scanned a whole genome of 181 susceptible and 297 resistant cows and revealed significant linkage to Bos taurus autosomal chromosome (BTA) 21 with a likelihood of odds (LOD) score of 28. Because FEZL is a transcription factor that influences resistance to mastitis, we compared LOD scores of BTA21 among cows carrying 12G/12G, 12G/13G, and 12G/13GFEZL to evaluate whether FEZL affects linkage in this chromosome. Cows carrying 13G/13GFEZL had the most significant linkage with a LOD score of 35, despite a decrease in the number of samples from 478 to 224. This finding suggested that the gene influencing resistance to mastitis on BTA21 might be controlled by FEZL. To investigate genes that might influence resistance to mastitis through FEZL, we screened human breast cancer-derived OCUB-M cells transfected with expression vector encoding 12GFEZL using microarray analysis. Keywords: overexpression comparison |
| 2179 | GSE40268 |
Profile | Type I interferon (IFN) is a family of 15 cytokines (in human 13α 1β,1ω) which exert several cellular functions through the binding to a common receptor. Despite the initial activation of the same Jak/Stat signalling pathway, the cellular response may be different depending on the type I IFN subtype. We investigated the activity of different type I IFN subtypes - IFNα1, α2, α8, α21, ω and β- on the differentiation of DC. Transcriptome analyses identified two distinct groups, the IFNα/ω-DC and the IFNβ-DC. 78 genes, 7 chemokines and expression levels of cell surface markers characteristic of DC distinguished IFNα-DC and IFNβ-DC. These differences are unlikely to impact the efficacy of T cell functional response since IFNα2-DC and IFNβ-DC were equipotent in inducing the proliferation and the polarization of allogenic naïve CD4 T cells into Th1 cells and in stimulating autologous memory CD4 or CD8 T cells. In contrast, IFNα2-DC were found to be more efficient than IFNβ-DC in the phagocytic uptake of dead cells. |
| 2180 | GSE492 |
Profile | The purpose of this study is to discover genes that might increase aqueous humor outflow when human ciliary muscle or human trabecular meshwork cells are treated with the prostaglandin analogues latanoprost free acid or prostaglandin F2alpha. Five tissue donors were pooled on each chip. Keywords: other |
| 2181 | GSE48792 |
Profile | Two ELK-1 overexpressing cells were generated from CSES7 cell line and compared to WT CSES7. We used microarrays to study the gene expression profiles of the ELK-1 overexpressing cells in order to identify ELK-1 target genes that might be involve in the processes of apoptosis and differentiation |
| 2182 | GSE16089 |
Profile | A summary of the work associated to these microarrays is the following: The need for an integrated view of all data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize phenomena in terms of how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance we constructed Biological Association Networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). Seven cell lines representative of different types of cancer including colon cancer (HT29 and Caco2), breast cancer (MCF7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by microarrays covering the whole human genome and analyzed with the GeneSpring GX software package, v.7.3.1. Genes deregulated in common in the two colon cancer cell lines studied, were subject of Biological Association Networks construction. Dikkopf homolog-1 (DKK1) was a clear node of this network, and functional validations of this target using a siRNA showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of differentially expressed genes in the two breast cancer cell lines studied. siRNA treatment against UGT1A showed also an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was a gene overexpressed in common among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. Biological Association Networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using iRNA technology against these three genes show chemosensitization toward MTX. |
| 2183 | GSE16200 |
Profile | Loss of Syk in normal breast cells in vivo and in vitro: gene expression and phenotypic switch to stem-cell like with induction of invadopodia Morphological and gene microarray analysis following Syk knockdown in MCF10A reveals a loss of luminal and differentiated epithelial features with epithelial to mesenchymal transition and a gain in invadopodia and stem/ progenitor cell marker expression. These results support the role of Syk in limiting normal stem/progenitor proliferation and invasion during morphogenesis and support the role of Syk as a critical tumor suppressor for breast cancer. |
| 2184 | GSE16524 |
Profile | Setleis Syndrome is a rare type of facial ectodermal dysplasia characterized by an aged leonine appearance with puckered skin about the eyes absent eyelashes on both lids or multiple rows on the upper lids and none on the lower lids, eyebrows that slant sharply upward laterally, and a rubbery feel of the nose and chin. Some of the patients showed bilateral temporal marks superficially like forceps marks and like the lesions seen in focal facial dermal dysplasia. We have evidence that Setleis Syndrome is caused by nonsense mutations in the gene coding for the small bHLH transcription factor known as TWIST2 in Puerto Rican and Omani patients. We performed expression microarray analysis of RNA samples derived from skin fibroblasts grown from skin biopsies of Setleis Syndrome patients and normal controls in order to identify genes potentially involved in facial development and the pathogenesis of Setleis Syndrome. |
| 2185 | GSE33903 |
Profile | To study differentially expressed genes in neuro-ectodermal cell lines MYCN amplification (NMA) is the most important prognostic factor in neuroblastoma (NBL) patients however 70% of advanced stage NBL are non-NMA and lack known driving oncogenic events. Gene expression profiles (HU133plus2.0 arrays, Affymetrix) of 17 NBL and 5 peripheral neuro-ectodermal cell lines were used to identify potential subgroups of NBL cell lines with a distinct gene signature. One group of non-NMA NBL cell lines was identified with a distinct gene expression profile and characterized by high expression of AXL. AXL is a tyrosine kinase receptor which plays a role in the metastatic process of cancer. We hypothesized that AXL contributes to the metastasizing potential of non-NMA NBL and tested if AXL silencing diminishes malignant properties of high AXL expressing cell lines. AXL was silenced in two non-NMA NBL cell lines by using a lentiviral shRNA construct that was able to transduce these cell lines with >90% infection efficiency. AXL mRNA expression level was efficiently knocked-down resulting in a severe decrease of migration of AXL positive cell lines GI-M-EN and SH-EP-2, and decreased invasion of GI-M-EN. Morphologically, AXL knockdown induced more rounded cells with a loss of contact. Intracellularly, we observed induction of stress fibers (immunofluorescence F-actin) in GI-M-EN. These changes in cytoskelet were associated with decreased migration. No effects were observed for cell proliferation, apoptosis or downstream pathways. In conclusion, AXL is identified as a possible mediator of NBL metastasis. |
| 2186 | GSE21899 |
Profile | This work presents the discovery of genes that are dysregulated in patients with Type I and Type III Gaucher Disease. It provides insight into the unique pathogenesis of these phenotypes improved diagnostic accuracy and potential novel therapies for these patients. |
| 2187 | GSE22342 |
Profile | Decidual macrophage populations CD11cHI and CD11cLO cells were analyzed for expression profiles and unique characteristics. We used microarrays to detail the global program of gene expression and to determine differences between these two unique decidual macrophage populations. |
| 2188 | GSE30781 |
Profile | Human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na+- and K+-dependent ATPase (Na+/K+-ATPase). Because HCEC proliferative activity is low in vivo,we tried to activate proliferation of HCEC by inhibiting cyclin-dependent kinase inhibitors.We have here demonstrated microarray data of transduced human corneal endothelial cell lines. |
| 2189 | GSE28044 |
Profile | Microarrays were used to examine gene expression changes that may be present in the fallopian tube epithelium of morphologically normal BRCA1 mutation positive and negative subjects. Fallopian tube epithelia has been implicated as an early point of origin for serous carcninoma. By examining the early events present in the microenvironment of this tissue between BRCA1 mutation carriers and non-carriers we hoped to elucidate mechanisms that may lead to the development of epithelial ovarian cancer. |
| 2190 | GSE15743 |
Profile | NK cells are believed to contribute to the control of hepatitis C virus infection and pathogenesis of liver disease. Standard treatment of both acute and chronic hepatitis C is based on the administration of interferon alpha however, the effects of type I interferons on human NK cells have not been studied in the context of hepatitis C. We therefore first performed a microarray screen for genes differentially regulated in human NK cells after stimulation of PBMC with recombinant interferon alpha-2b. One of the genes upregulated was TRAIL which was confirmed in vitro on the protein level. Keywords: Interferon alpha; human NK cells; stimulation for 6 hours; cells sorted after stimulation of whole PBMC |
| 2191 | GSE25012 |
Profile | phenotypic reprogramming ability of teh zebtafish brain microenviroment on GBM derived cells controlled by the activation of endogenous Wnt pathway |
| 2192 | GSE38408 |
Profile | TIMP-2 is an endogenous angiogenesis inhibitor i.e. inhibits endothelial cell proliferation and tumor angiogenesis. As a result, TIMP-2 inhibits tumor growth and progression to metastasis. Understanding, therefore, the mechanisms of TIMP-2-mediated tumor growth inhibition would provide further support on the use of TIMP-2 as a novel biological agent for cancer therapy. We used microarray analysis to determine the TIMP-2 and Ala+TIMP-2 transcriptional profiles of A549 cancer cells in order to understand how TIMP-2 inhibits tumor growth and angiogenesis. |
| 2193 | GSE1364 |
Profile | This series represents the complete series of the human 293h media depleted storage on agarose / rehydration condition course analysis. Samples include Control monolayer; Control, monolayer/full recovery, antibiotics; Spheroid, no storage; two week storage/0hr recovery; two week storage/full recovery; four week storage/0hr recovery; six week storage/0hr recovery. Keywords = 293h cells Keywords = desiccation Keywords = rehydration Keywords = spheroid Keywords = stabilization Keywords = ambient temperature Keywords: other |
| 2194 | GSE36766 |
Profile | CD4+ helper T (Th) cells are critical regulators of immune responses but their role in breast cancer is currently unknown. This work aims to characterize Th cells infiltrating invasive primary human breast tumors analyze the influence by the tumor microenvironment and identify Th cell specific prognostic gene signatures. CD4+ T cells isolated from the tumor (TIL), axillary lymph node (LN) and blood (PB) of 10 patients were analyzed on Affymetrix U133 Plus 2.0 arrays. A confirmation set of 60 patients were studied by flow cytometry, qRT-PCR or immunohistochemistry and analyzed according to the extent of the tumor immune infiltrate. Gene expression profiles of freshly isolated TIL were also compared with TIL that had been rested overnight or with CD4+ T cells [non-stimulated (NS) or stimulated (S)] from healthy donor PB treated with tumor supernatant (SN). Comparing gene expression profiles of donor blood derived memory CD4+ T cells [non-stimulated (NS) or stimulated (S)] with and without tumor supernatant (SN) treatment |
| 2195 | GSE22183 |
Profile | Genome-wide mRNA expression profiles of 37 unique gastric cancer cell lines (GCCLs). Keywords: gastric cancer cell culture |
| 2196 | GSE7862 |
Profile | Normal and two transformed buccal keratinocyte lines were cultured under a standardized condition to explore mechanisms of carcinogenesis and tumor marker expression at transcript and protein level. An approach combining three bioinformatic programs allowed coupling of abundant proteins and large-scale transcript data to low-abundance transcriptional regulators. The analysis identified previously proposed and suggested novel, protein biomarkers, Gene Ontology categories and molecular networks including functionally impaired key regulator genes for buccal/oral carcinoma. Keywords: Cell type comparison |
| 2197 | GSE37267 |
Profile | Age-related transcriptome changes can contribute to better understanding of gastrointestinal disorders such as colorectal cancer in older population |
| 2198 | GSE30304 |
Profile | To conduct comparative transcriptomic analyses on normal or malignant prostate epithelial cells in response to tissue contextual changes we cultured immortalized prostate epithelial cells or prostate cancer cells as cell monolayers or three-dimensional organoids and profiled their transcriptomes in respective culture contexts. |
| 2199 | GSE29605 |
Profile | MicroRNA-155 is frequently over-expressed in CLL and is associated with worse clinical prognosis. To understand the role of miR-155 in CLL pathogenesis we used microarrays to identify genes that are expressed at significantly lower levels in CLLs that harbor higher levels of miR-155 expression in an attempt to determine the relevant gene targets of miR-155 in CLL. |
| 2200 | GSE14986 |
Profile | Emergence of antiestrogen-resistant cells in MCF-7 cells during suppression of estrogen signaling is a widely accepted model of acquired breast cancer resistance to endocrine therapy. To obtain insight into the genomic basis of endocrine therapy resistance we characterized MCF-7 monoclonal sublines that survived 21-day exposure to tamoxifen (T-series sublines) or fulvestrant (F-series sublines) and sublines unselected by drugs (U-series). All T/F-sublines were resistant to the cytocidal effects of both tamoxifen and fulvestrant. However, their responses to the cytostatic effects of fulvestrant varied greatly, and their remarkably diversified morphology showed no correlation with drug resistance. mRNA expression profiles of the U-sublines differed significantly from those of the T/F-sublines, whose transcriptomal responsiveness to fulvestrant was largely lost. A set of genes strongly expressed in the U-sublines successfully predicted metastasis-free survival of breast cancer patients. Most T/F-sublines shared highly homogeneous genomic DNA aberration patterns that were distinct from those of the U-sublines. Genomic DNA of the U-sublines harbored many aberrations that were not found in the T/F-sublines. These results suggest that the T/F-sublines are derived from a common monoclonal progenitor that lost transcriptomal responsiveness to antiestrogens as a consequence of genetic abnormalities many population doublings ago, not from the antiestrogen-sensitive cells in the same culture during the exposure to antiestrogens. Thus, the apparent acquisition of antiestrogen resistance by MCF-7 cells reflects selection of preexisting drug-resistant subpopulations without involving changes in individual cells. Our results suggest the importance of clonal selection in endocrine therapy resistance of breast cancer. |
| 2201 | GSE19638 |
Profile | The effects of several compounds on the MCF7 human adenocarcinoma mammary cell line were analysed by gene expression profiling. |
| 2202 | GSE18973 |
Profile | Hepatocyte nuclear factor-4α (HNF4α NR2A1) is a nuclear receptor which has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver. However, a detailed understanding of native HNF4α in the steady state remains to be elucidated. Here we report the native HNF4α isoforms, phosphorylation status and complexes in the steady state, as shown by shotgun proteomics in HepG2 hepatocarcinoma cells. Shotgun proteomic analysis revealed the complexity of native HNF4α, including multiple phosphorylation sites and inter-isoform heterodimerization. The associating complexes identified by label-free semi-quantitative proteomic analysis include the following: the DNA-dependent protein kinase catalytic subunit, histone acetyltransferase complexes, mRNA splicing complex, other nuclear receptor coactivator complexes, the chromatin remodeling complex, and the nucleosome remodeling and histone deacetylation complex. Among the associating proteins, GRB10 interacting GYF protein 2 (GIGYF2, PERQ2) is a new candidate cofactor in metabolic regulation. Moreover, an unexpected heterodimerization of HNF4α and Hepatocyte nuclear factor-4γ was found. A biochemical and genome-wide analysis of transcriptional regulation showed that this heterodimerization activates gene transcription. The genes thus transcribed include the cell death-inducing DEF45-like effector b (CIDEB) gene, which is an important regulator of lipid metabolism in the liver. This suggests that the analysis of the distinctive stoichiometric balance of native HNF4α and its cofactor complexes described here is important for an accurate understanding of transcriptional regulation. |
| 2203 | GSE8952 |
Profile | Study of Sox18 regulated genes: Human umbilical vein endothelial cells (HUVEC) were either transduced with adenoviral vectors expressing SOX18 from an IRES-EGFP casette or IRES-EGFP alone, or left untreated. After 16 hours, mRNA was isolated and analyzed by hybridization to Affymetrix HG-U133A arrays. |
| 2204 | GSE39840 |
Profile | Introduction: Increasing evidence now supports the association between the fetal inflammatory response syndrome (FIRS) with the pathogenesis of preterm labor intraventricular hemorrhage and bronchopulmonary dysplasia. These disorders are among the most important causes of mortality and morbidity in the perinatal period. During the fetal inflammatory response syndrome (FIRS) polymorphonuclear leukocytes (PMNs) and monocytes (MONOs) are sequentially recruited into the placenta; the same process occurs in the lung of the newborn during the development of bronchopulmonary dysplasia (BPD). The aim of the study was to reveal cell-specific differences in gene expression and cytokine release in response to endotoxin that would elucidate inflammatory control mechanisms in the newly born. Results: Compared to PMNs, MONOs had a greater diversity and more robust expression of pro-inflammatory (PI) gene expression at 4h. Only MONOs had genes changing expression in the JAK/STAT pathway including interleukin-10. |
| 2205 | GSE12971 |
Profile | Affymetrix expression arrays were used to compare expression patterns upon knockdown of PARP-1 PARG, SIRT1, or macroH2A in comparison to Luciferase control. |
| 2206 | GSE9429 |
Profile | Diffuse large B-cell lymphoma (DLBCL) has striking clinical and molecular variability. Although a more precise identification of the multiple determinants of this variability is still under investigation there is a consensus that high-clinical-risk DLBCL cases require a risk-adapted therapy, since intensification of chemotherapy with autologous stem-cell transplantation (ASCT) has been shown to improve the prognosis for high-risk patients in randomised clinical trials. In spite of this, the protocols used for these patients have a high morbidity, associated with ASCT and the use of multiple drugs. This makes it important to identify patients that may take benefit from risk-adapted therapies, through the recognition of biological markers that provide information about both the tumoral cells and the microenvironment. Unfortunately, many of the studies so far performed have relied on heterogeneous series of patients, staged or treated with different protocols. For instance, some of the variability in DLBCL arises from the fact that this diagnosis is applied to de novo and secondary tumours, nodal and extranodal, irrespective of clinical stage, patient age and associated infections. Additionally, DLBCL includes some specific variants, such as mediastinal DLBCL and T/HRBCL, with specific prognostic parameters. This could prevent the identification of potential predictive biomarkers, because the results of many studies show that the search for predictive biomarkers should be promoted in the context of samples of clinically homogeneous patients enrolled in clinical trials. A further source of variability is the dependence of some predictive markers on specific therapeutic approaches, as is the case for the Bcl6 expression in DLBCL, since Bcl-6+ cases have been shown not to benefit from the addition of R to CHOP. Here we have analysed a series of high-clinical-risk DLBCLs by a two-stage approach, first identifying functional signatures by expression analysis, then analysing surrogate biomarkers using tissue microarrays (TMAs). This eclectic approach could reveal new aspects of the relationship between the neoplastic cells and the microenvironment, leading to the identification of previously unknown prognostic markers. At the same time, the use of functional signatures to analyse expression-profiling data avoids the poor reproducibility of the data obtained from gene-by-gene analysis, and benefits from the existence of a growing body of data concerning the major pathways deregulated in DLBCL. To avoid the bias of semiquantitative scoring, in this study we have quantified the markers included in the multivariate analysis. Keywords: new biological variables, risk-adapted therapies |
| 2207 | GSE14844 |
Profile | Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However this is yet to be established. We examined 4-hour test-retest reliability and 10 month test-retest stability of individual differences in gene expression in 10 12-year-old children. |
| 2208 | GSE30478 |
Profile | Histone methylation occurs on both lysine and arginine residues and its dynamic regulation plays a critical role in chromatin biology. Here we identify the UHRF1 PHD domain (PHDUHRF1) an important regulator of DNA CpG methylation, as an unanticipated histone H3 unmodified arginine 2 (H3R2)-recognition modality. This conclusion is based on binding studies and co-crystal structures of the PHDUHRF1 bound to histone H3 peptides, where the guanidinium group of unmodified R2 forms an extensive intermolecular hydrogen bond network, with methylation of H3R2, but not H3K4 or H3K9, disrupting complex formation. We have identified direct target genes of UHRF1 from microarray and ChIP studies. Importantly, we show that UHRF1’s ability to repress its direct target gene expression is dependent on PHDUHRF1 binding to unmodified H3R2, thereby demonstrating the functional importance of this recognition event and supporting the potential for crosstalk between histone arginine methylation and UHRF1 function. |
| 2209 | GSE20708 |
Profile | In addition to KIT and PDGFRA mutations sequential accumulation of other genetic events is involved in the development and progression of gastrointestinal stromal tumors (GISTs). Until recently, the significance of these other alterations has not been thoroughly investigated. The combination of gene expression profiling and high-resolution genomic copy number analysis offers a detailed molecular portrait of GISTs, providing an essential comprehensive knowledge necessary to guide the discovery of novel target genes involved in tumor development and progression. Fresh tissue specimens from 25 patients with GIST were collected and gene expression profiling was performed using Affymetrix U133Plus array. |
| 2210 | GSE32959 |
Profile | The aim of this dataset was to study in detail the transcription kinetics initiated by cytokines IL-12 and IL-4 in early differentiation of Th1 and Th2 cells respectively. |
| 2211 | GSE29828 |
Profile | Cell lines bearing MLL translocations (MV4-11 and MOLM-13) were treated with a potent selective inhibitor of the DOT1L histone methyl transferase. Treatment of MLL-rearranged cell lines with the DOT1L inhibitor selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes. Here we provide expression profiling data of cells treated with DOT1L inhibitor or vehicle control. |
| 2212 | GSE8441 |
Profile | Inadequate dietary protein intake causes adverse changes in the morphology and function of skeletal muscle. These changes may be reflected in early alterations in muscle mRNA levels. Microarray analysis was used to assess whether inadequate protein intake differentially affects skeletal muscle transcript levels and expression profiles in older adults. Keywords: dietary intake response |
| 2213 | GSE10856 |
Profile | Decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily and is up-regulated in tumors that originate from a diversity of lineages. DcR3 is capable of promoting angiogenesis inducing dendritic cell apoptosis, and modulating macrophage differentiation. Since tumor-associated macrophages (TAMs) are the major infiltrating leukocytes in most malignant tumors, we used microarray technology to investigate whether DcR3 contributes to the development of TAMs. Among the DcR3-modulated genes expressed by TAMs, those that encode proteins involved in MHC class II (MHC-II)-dependent antigen presentation were down-regulated substantially, together with the master regulator of MHC-II expression (the class II transactivator, CIITA). The ERK- and JNK-induced deacetylation of histones associated with the CIITA promoters was responsible for DcR3-mediated down-regulation of MHC-II expression. Furthermore, the expression level of DcR3 in cancer cells correlated inversely with HLA-DR levels on TAMs and with the overall survival time of pancreatic cancer patients. The role of DcR3 in the development of TAMs was further confirmed using transgenic mice over-expressing DcR3. This elucidates the molecular mechanism of impaired MHC-II-mediated antigen presentation by TAMs, and raises the possibility that subversion of TAM-induced immunosuppression via inhibition of DcR3 expression might represent a target for the design of new therapeutics. Keywords: time-dose response |
| 2214 | GSE39186 |
Profile | We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes. |
| 2215 | GSE9927 |
Profile | The mechanism of CD4(+) T cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T cell activation. We assumed that the pathogenic process of excessive CD4(+) T cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo activated CD4(+) T cells from untreated HIV(+) individuals are clearly different from those activated CD4(+) T cells from HIV(-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV(+) individuals. Furthermore we find an enrichment of proliferative and Type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV(+) individuals compared to HIV(-) individuals. We confirm these findings by examination of in vivo activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a hyper-proliferative state that is modulated by Type I interferons. From these results, we propose a new model for CD4(+) T cell depletion during chronic HIV-1 infection. Keywords: disease state analysis |
| 2216 | GSE42924 |
Profile | HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFN’s. The three alleles and mutants with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFN’s. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. We investigated the effect of various Tat alleles and mutants on host cell gene expression in immature dendritic cells (iDC). The cells were infected with adenoviruses expressing the Tat constructs. |
| 2217 | GSE651 |
Profile | primary ALL cells (B- and T-lineage) resistant to daunorubicin by the MTT in vitro sensitivity assay Keywords = ALL Keywords: other |
| 2218 | GSE16451 |
Profile | Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections. We used microarrays to examine the transcriptional responses of the human BE(2)-C neuroblastoma cell line to infection with western equine encephalitis virus (WEEV). |
| 2219 | GSE3419 |
Profile | The human hair follicle bulge is an important niche for keratinocyte stem cells (KSC). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSC. In this study we determined the distribution of label-retaining cells to carefully define the human anagen bulge. Using navigated-laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and Activin/BMP signaling were over-represented in the bulge while genes responsible for cell proliferation were under-represented, consistent with quiescent non-cycling KSC in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1 while CD24, 34, 71 and 146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hi24lo34lo71lo146lo) obtained from hair follicle suspensions demonstrated high colony forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. Keywords: Affymetrix micrarray analysis of human hair follicles |
| 2220 | GSE15537 |
Profile | Genome-wide mRNA expression profiles of normal skin fibroblasts used as one of the (normal) references in the study. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Keywords: normal skin fibroblasts, cell culture |
| 2221 | GSE7305 |
Profile | Normal and diseased human tissues were profiled for gene expression using the Affymetrix U133 plus 2.0 array In total 20 samples were processed Keywords: Human tissue transcriptional profiling |
| 2222 | GSE35230 |
Profile | In an effort to understand the mechanisms of acquired resistance to BRAF inhibitors we isolated clones that acquired resistance to the BRAF inhibitor GSK2118436 derived from the A375 BRAF V600E mutant melanoma cell line. This resistance clones acquired mutations in NRAS and MEK1. One clones, 16R6-4, acquired two mutations in NRAS – Q61K and A146T. Proliferation and western blot analyses demonstrated that these clones were insensitive to single agent GSK2118436 or GSK1120212 (an allosteric MEK inhibitor) but were sensitive to the combination of GSK2118436 and GSK1120212. To further characterize this combination, global transcriptomic analysis was performed in A375 and 16R6-4 after 24 hour treatment with GSK2118436, GSK1120212 or the combination of GSK2118436 and GSK1120212. This data set was published in Molecular Cancer Therapeutics with the title “Combined inhibition of BRAF and MEK, BRAF and PI3K/mTOR, or MEK and PI3K/mTOR overcomes acquired resistance to the BRAF inhibitor GSK2118436, mediated by NRAS or MEK mutations” by Greger, J.G., et.al. |
| 2223 | GSE40215 |
Profile | NF-Y a trimeric transcription factor (TF) composed of two histone-like subunits (NF-YB (NFYB) and NF-YC (NFYC)) and a sequence-specific subunit (NF-YA), binds to the CCAAT motif, a common promoter element. Genome-wide mapping reveals 5,000-15,000 NF-Y binding sites depending on the cell type, with the NF-YA and NF-YB subunits binding asymmetrically with respect to the CCAAT motif. Despite being characterized as a proximal promoter TF, only 25% of NF-Y sites map to promoters. A comparable number of NF-Y sites are located at enhancers, many of which are tissue specific, and nearly half of NF-Y sites are in select subclasses of HERV LTR repeats. Unlike most TFs, NF-Y can access its target DNA motif in inactive (non-modified) or polycomb-repressed chromatin domains. Unexpectedly, NF-Y extensively co-localizes with FOS in all genomic contexts, and at promoters and enhancers this often occurs in the absence of JUN and the AP-1 motif. NF-Y also co-associates with a select cluster of growth-controlling and oncogenic TFs, consistent with the abundance of CCAAT motifs in the promoters of genes overexpressed in cancer. Interestingly, NF-Y and several growth-controlling TFs bind in a stereo-specific manner, suggesting a mechanism for cooperative action at promoters and enhancers. Our results indicate that NF-Y is not merely a commonly-used, proximal promoter TF, but rather performs a more diverse set of biological functions, many of which are likely to involve co-association with FOS. Scrambled control (shSCM) and NF-YA pLKO.1-shRNAs were designed by Sigma-Aldrich. The puromycin resistance cassette was replaced with an EGFP cassette. Viral production and transduction were carried out as previously described (Benatti et al. 2011). HeLaS3 cells were transduced with shSCM or shNF-YA viral supernatants, in triplicate, and cells collected after 48 hr of incubation. Total RNA was prepared by Trizol extraction and Qiagen RNeasy kit purification, converted to biotinylated aRNA and hybridized to U133 Plus 2.0 GeneChip expression arrays using the 3’ IVT Express Kit (Affymetrix, USA) following the manufacturer’s protocol. Arrays were RMA normalized (Irizarry et al. 2003), gene expression levels calculated, differential expression determined using the following R packages from the Bioconductor project: affy (Gautier et al. 2004), limma (Smyth 2004). |
| 2224 | GSE17307 |
Profile | Analysis of dexamethasone-stimulated A549 lung adenocarcinoma epithelial cells treated with a glucocorticoid response (GR) element (GRE) specific DNA binding polyamide. Polyamide designed to target the sequence 5'-WGWWCW-3' and disrupt GR-mediated gene expression. Effects of the GR antagonist mifepristone also examined. |
| 2225 | GSE11352 |
Profile | Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy we mapped estrogen receptor alpha (ERalpha) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERalpha binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5' and 3' ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERalpha binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERalpha-positive from ERalpha-negative breast tumors. The expression dynamics of the genes adjacent to ERalpha binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERalpha appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERalpha target genes. Unexpectedly, we found that only 22%-24% of the bona fide human ERalpha binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERalpha binding and gene regulation. Keywords: time course |
| 2226 | GSE3960 |
Profile | The specific genes that influence neuroblastoma biology and are targeted by genomic alterations remain largely unknown. We quantified mRNA expression in a highly annotated series of 101 prospectively collected diagnostic neuroblastoma primary tumors and the expression profiles were determined using Affymetrix U95Av2 arrays. Comparisons between the sample groups allow the identification of genes with localized expression patterns. This study demonstrates that the genomic data can be used to subcategorize the disease into molecular subsets and the regional copy number alterations are correlated with a broad number of transcriptional alterations genome wide. This data also suggests that multiple genes from several discrete regions of the human genome co-operate to supress neuroblastoma tumorigenesis and progression. Keywords: Disease state analysis genetic modification |
| 2227 | GSE4086 |
Profile | Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia. We found that HIF-1 also actively suppresses glucose metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1α-null cells increases ATP levels, attenuates hypoxic ROS generation and rescues these cells from hypoxia-induced apoptosis. These studies reveal a novel hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production. Keywords: Hypoxia responsive, case control |
| 2228 | GSE28603 |
Profile | Hypoxia in adipose tissue is suggested to be involved in the development of a chronic mild inflammation which in obesity can further lead to insulin-resistance. The effect of hypoxia on gene expression in adipocytes seems to play a central role in this inflammatory response observed in obesity. However, the global impact of hypoxia on transcriptional changes in human adipocytes is unclear. Therefore, we compared gene expression profiles of human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes under normoxic or hypoxic conditions to detect hypoxia-responsive genes in adipocytes by using whole human genome microarrays. |
| 2229 | GSE13715 |
Profile | A genomic expression comparison was done among neural progenitor cells cultured on 2D substrates 3D porous polystyrene scaffolds, and as 3D neural spheres (in vivo surrogate), with the goal of assessing the feasibility of establishing the meaning of 3D and associated physiological relevance at the molecular level |
| 2230 | GSE8471 |
Profile | Heregulin beta-1 (HRG) is an extracellular ligand that activates mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI3K)/Akt signaling pathways through ErbB receptors. MAPK and Akt have been shown to phosphorylate the estrogen receptor (ER) at Ser-118 and Ser-167 respectively, thereby mimicking the effects of estrogenic activity such as estrogen responsive element (ERE)-dependent transcription. In the current study, integrative analysis was performed using two tiling array platforms, comprising histone H3 lysine 9 (H3K9) acetylation and RNA mapping, together with array comparative genomic hybridization (CGH) analysis in an effort to identify HRG-regulated genes in ER-positive MCF-7 breast cancer cells. Through application of various threshold settings, 333 (326 up-regulated and 7 down-regulated) HRG-regulated genes were detected. Prediction of upstream transcription factors (TFs) and pathway analysis indicated that 21% of HRG-induced gene regulation may be controlled by the MAPK cascade, while only 0.6% of the gene expression is controlled by ERE. A comparison with previously reported estrogen (E2)-regulated gene expression data revealed that only 12 common genes were identified between the 333 HRG-regulated (3.6%) and 239 E2-regulated (5.0%) gene groups. However, with respect to enriched upstream TFs, 4 common TFs were identified in the 14 HRG-regulated (28.6%) and 13 E2-regulated (30.8%) gene groups. These results indicated that while E2 and HRG may induce common TFs, the regulatory mechanisms that govern HRG- and E2-induced gene expression differ. Keywords: growth hormone response |
| 2231 | GSE7869 |
Profile | To elucidate the molecular pathways that modulate renal cyst growth in autosomal dominant polycystic kidney disease (ADPKD) Keywords: Disease state analysis |
| 2232 | GSE10234 |
Profile | Cyclin T1-dependent genes in LPS-activated MM6 cells. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Keywords: shrna knockdown |
| 2233 | GSE1676 |
Profile | Response to treatment with the radiomimetic drug NCS in cells knocked-down for ATM p53, and the Rel_A subunit of NFkB; and in control un-infected cells and cells infected with siRNA against LacZ Keywords = DNA damage Keywords = ATM Keywords = p53 Keywords = RelA Keywords: other |
| 2234 | GSE39718 |
Profile | ERα17p is a synthetic peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially synthesized to mimic its calmodulin binding site. ERα17p was subsequently found to elicit estrogenic responses in E2-deprived ERα-positive breast cancer cells increasing proliferation and E2-dependent gene transcription. Surprisingly, in E2-supplemented media, ERα17p induced apoptosis and modified the actin network, influencing thereby cell motility. Here, we report that ERα17p induces a massive early (3h) transcriptional activity in breast cancer cell line MDA-MB-231. |
| 2235 | GSE22103 |
Profile | Neutrophils play critical roles in modulating the immune response. However neutrophils have a short circulating half life, are readily stimulated in vitro, and have low levels of cellular mRNA when compared to other blood leukocyte populations. All of these factors have made it difficult to evaluate neutrophils from clinical populations for molecular and functional studies. Here we present a robust methodology for rapidly isolating neutrophils directly from whole blood and develop ‘on- chip’ processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and demonstrate the ability of the device to discriminate subtle differences in the genomic and proteomic response of peripheral blood neutrophils to direct and indirect stimulation. Lastly, we implement this tool as part of a near patient blood processing system within a multi-center clinical study of the immune response to severe trauma and burn injury and demonstrate that this technique is easy to use by nurses and technical staff yielding excellent quality and sufficient quantity of mRNA for sensitive genomic readout of the host response to injury |
| 2236 | GSE6367 |
Profile | Hormones and growth factors accelerate cell proliferation of breast cancer cells and these molecules are well investigated targets for drug development and application. The mechanisms of cell proliferation of breast cancers lacking estrogen receptor (ER) and HER2 have not been fully understood. The purpose of the present study is to find genes that are differentially expressed in breast cancers and that might significantly contribute to cell proliferation in these cancers. Forty tumor samples, consisting of ten each of immunohistochemically ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) cancer were analyzed using oligonucleotide microarrays. Both genes and tumor samples were subjected to hierarchical clustering. ER(+)/HER2(-) breast cancers and ER(-)/HER2(-) cancers tended to form a tumor cluster, but HER2 positive breast cancers were split into different tumor clusters. Significant differential expression between IHC-ER(-)/HER2(-) and other tumors was defined as having an expression level at least 2-fold higher or 2-fold lower, and analyzed by multi-step two-way ANOVA. Genes overexpressed differently in IHC-ER(-)/HER2(-) breast cancers compared to other all three types were 8 genes (FABP7, GABRP, GAL, CXCL13, CDC42EP4, C2F, FOXM1, CSDA), and underexpressed genes were nine including ITGB5, KIAA0310, MAGED2, PRSS11, SORL1, TGFB3, KRT18, CPE, BCAS1. No gene was directly related to cell proliferation such as cyclins, cyclin-dependent kinase, p53, p16, and the pRb and p21 families. We had a particular focus on a transcriptional factor E2F-5 from a list of genes overexpressed in ER negative breast cancers compared to ER positive breast cancers, and further examined. Gene amplification of E2F-5 was detected in 5/57 (8.8%) in breast cancers by FISH. No point mutation was found at the binding domain with DNA or dimerization partner of E2F-5. Immunohistochemically E2F-5 positive cancers were more frequent in ER(-)/HER2(-) cancer (14/27, 51.9%) than in other types of cancer (5/30, 16.7%) (p=0.05). E2F-5 positive cancers had higher Ki-67 labeling index (59.5%) than E2F-5 negative cancers (36.3%). E2F-5 positive cancers showed higher histological grade including metaplastic carcinoma, and worse clinical outcome with shorter disease free survival in node negative patients. In conclusion, we demonstrated that there is a population of breast cancer with overexpression of a cell cycle related transcriptional factor E2F-5. E2F-5 positive breast cancers were frequent in ER(-)/HER2(-) group with high Ki-67 labeling index, high histological grade and worse clinical outcome. Keywords: immunohistochemical phenotype |
| 2237 | GSE5231 |
Profile | This SuperSeries is composed of the SubSeries listed below. |
| 2238 | GSE5109 |
Profile | Obesity results from a chronic imbalance between energy intake and energy expenditure with excess calories stored as fat. As such, weight loss has long been considered as a primary goal of treatment for obesity. A surgical treatment of severe obesity such as gastric bypass provides the most dramatic reductions in body weight, and a well-known effect of weight loss is an improvement in insulin sensitivity. However, the molecular mechanism underlying this association remains unclear. Thus, we profiled skeletal muscle of morbidly obese patients before and after gastric bypass surgery. Results from this project will provide global patterns of gene expression with weight loss, which help to understand the pathogenesis of obesity at the molecular level. Keywords: Time-Series |
| 2239 | GSE11199 |
Profile | Although host genetics influences susceptibility to tuberculosis few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of tuberculosis infection would have distinct gene expression profiles, and that polymorphisms in these genes may also be associated with susceptibility to TB. We measured gene expression levels of >38,500 genes from ex vivo Mtb- stimulated macrophages in 12 subjects with 3 clinical phenotypes: latent, pulmonary and meningeal tuberculosis (n=4 per group). After identifying differentially expressed genes, we confirmed these results in 34 additional subjects by real-time PCR. We also used a case-control study design to examine whether polymorphisms in differentially regulated genes were associated with susceptibility to these different clinical forms of TB. We compared gene expression profiles in Mtb-stimulated and unstimulated macrophages and identified 1608 and 199 genes that were differentially expressed by >2 and >5-fold, respectively. Using cluster analysis, we identified gene expression patterns that distinguished the different clinical forms of tuberculosis. In an independent sample set of 34 individuals and a subset of highly regulated genes, 90% of the microarray results were confirmed by RT-PCR, including expression levels of CCL1, which distinguished the 3 clinical groups. Furthermore, 6 single nucleotide polymorphisms (SNPs) in CCL1 were found to be associated with TB in a case-control genetic association study with 273 TB cases and 188 controls. To our knowledge, this is the first identification of CCL1 as a gene involved in host susceptibility to TB and the first study to combine microarray and DNA polymorphism studies to identify genes associated with TB susceptibility. These results suggest that genome-wide studies can provide an unbiased method to identify critical macrophage response genes that are associated with different clinical outcomes and that variation in innate immune response genes regulate susceptibility to tuberculosis. Keywords: tuberculosis, tuberculous meningitis, macrophage, gene expression, microarray |
| 2240 | GSE18047 |
Profile | Mutations involving the NFKB pathway are present in at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCL). These mutations which are thought to be progression events, enable MM tumors to become less dependent on extrinsic bone marrow signals that activate NFKB. Studies on a panel of 50 MMCL provide some clarification of the mechanisms through which these mutations act and the significance of classical vs alternative activation of NFKB. First, only one mutation (NFKB2) selectively activates the alternative pathway, whereas several mutations (CYLD, NFKB1, TACI) selectively activate the classical pathway. However, most mutations affecting NIK level (NIK, TRAF2, TRAF3, cIAP1&2, CD40) activate the alternative but often both pathways. Second, we confirm the critical role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated proteosomal degradation of NIK in MM. Third, using transfection to selectively activate the classical or alternative NFKB pathways, we show virtually identical changes in gene expression in one MMCL, whereas the changes are similar albeit non-identical in a second MMCL. Together, our results suggest that MM tumors can achieve increased autonomy from the bone marrow microenvironment by mutations that activate either NFKB pathway. |
| 2241 | GSE43608 |
Profile | To identify genes involved in survival to prolonged hypoxia we exposed HCT116 to hypoxia for 3 days. Control cells were exposed to normoxic conditions. |
| 2242 | GSE38680 |
Profile | Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease. |
| 2243 | GSE5486 |
Profile | Inhibition of the nonsense mediated decay (NMD) mechanism in cells results in stabilization of transcripts carrying premature translation termination codons. A strategy referred to as gene indentification by NMD inhibition (GINI) has been proposed to identify genes carrying nonsense mutations (Noensie & Dietz 2001). Genes containing frameshift mutations in colon cancer cell line have been identifying mutatnt genes using GINI, we have now further improved the strategy. In this approach, inhibition of NMD with emetine is complemented with inhibiting NMD by blocking the phosphorylation of the hUpf1 protein with caffeine. In addition, to enhance the GINI strategy, comparing mRNA level alterations produced by inhibiting transcription alone or inhbiiting transcription together with NMD following caffeine pretreatment were used for the efficient identification of false positives produced as a result of stress response to NMD inhibition. To demonstrate the improved efficiency of this approach, we analyzed colon cancer cell lines showing microstellite instability. Bi-allelic inactivating mutations were found in the FXR1, SEC1L1, NCOR1, BAT3, PHD14, ZNF294, C190ORF5 genes as well as genes coding for proteins with yet unknown functions. Keywords: microarray, gene expression, Affymetrix, drug treatment, emetine, caffeine, actinomycin D, novel tumor suppressor gene candidates |
| 2244 | GSE12056 |
Profile | Background. The cAMP Response Element Binding Protein CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution. Therefore, we propose CREB to be a potential target for therapy. To understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line. Results. By combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. The transcription factor Elk-1 was upregulated in response to CREB deletion. Conclusions. We have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. In particular, we speculate that the regulation of histone genes may play an important role in this process, by possibly altering the regulation of DNA replication during the cell cycle. |
| 2245 | GSE18370 |
Profile | Pathologic and epidemiologic evidence has led to a histologic model of breast cancer progression that involves advancement through specific morphologic stages including atypical ductal hyperplasia (ADH) ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (IMC), although not necessarily always in a linear fashion. Numerous observational studies have examined genetic, epigenetic and gene expression differences in breast tissues representing these different stages of progression, but model systems which would allow for experimental testing of specific factors influencing transition through these stages are scarce. The 21T series cell lines, all originally derived from the same patient with metastatic breast cancer, have been proposed to represent a mammary tumor progression series. We report here that three of the 21T cell lines indeed mimic specific stages of human breast cancer progression (21PT-derived cells, ADH; 21NT-derived cells, DCIS; 21MT-1 cells, IMC) when grown in the mammary fat pad of nude mice, albeit after up to a year post-injection. In order to develop a more rapid, readily manipulatable in vitro assay for examining the biologic differences between these cell lines, we have made use of a 3D Matrigel system. When grown in 3D Matrigel, we have found characteristic morphologies of the three cell lines in which quantifiable aspects of the stage-specific in vivo behaviors (i.e. differences in acinar structure formation, cell polarization, cell cohesiveness, cell proliferation, cell invasion) are re-capitulated in a reproducible fashion. Gene expression profiling has revealed a characteristic pattern for each of the three cell lines. Interestingly, WNT pathway alterations are particularly predominant in the early transition from 21PTci (ADH) to 21NTci (DCIS), whereas alterations in expression of genes associated with control of cell motility and invasiveness phenomena are more prominent in the later transition of 21NTci (DCIS) to 21MT-1 (IMC). This system thus reveals potential therapeutic targets and will provide a means of testing the influences of identified genes on transitions between these stages of pre-malignant to malignant growth. Keywords: DCIS or IDC vs ADH |
| 2246 | GSE37949 |
Profile | To identify candidate genes involved in enhanced tumorigenicity and metastasis of CD90+ esophageal tumor-initiating cells. |
| 2247 | GSE12098 |
Profile | To compare the gene expression profile of MSCs harvested from bone marrow in the context of cell migration. |
| 2248 | GSE16589 |
Profile | Despite the importance of inter-cellular communication networks in regulating stem cell fate decisions very little is known about the topology, dynamics, or functional significance. Using human blood stem cell cultures as an experimental paradigm, we present a novel bioinformatic approach to integrate genome-scale molecular profiles (transcriptome and secretome) and publicly available databases to reconstruct soluble factor-mediated inter-cellular signalling networks regulating blood stem cell fate decisions. |
| 2249 | GSE26526 |
Profile | Purpose: The chromosomal deletion 11q affects biology and clinical outcome in CLL but del11q-deregulated genes remain incompletely characterized. Results: We have identified differential expression of the insulin receptor (INSR) in CLL including high-level INSR expression in the majority of CLL with del11q. High INSR mRNA expression in 11q CLL (~10-fold higher mean levels than other genomic categories) was confirmed by Q-PCR in 247 CLL cases. INSR protein measurements in 257 CLL cases through FACS, compared with measurements in normal CD19+ B-cells and monocytes, confirmed that a subset of CLL aberrantly expresses high INSR levels. |
| 2250 | GSE11578 |
Profile | Since its discovery as a tumour suppressor some fifteen years ago the transcription factor p53 has attracted paramount attention for its role as “the guardian of the genome”. TP53 mutations occur so frequently in cancer, regardless of patient age or tumour type, that they appear to be part of the life history of at least 50% of human tumours. In most tumours that retain wild-type p53, its function is inactivated due to deregulated HDM2, a protein which binds to p53 and which can inhibit the transcriptional activity of p53 and induce its degradation. RITA is a low-molecular-weight compound which addresses the second group of tumours retaining functionally reactive wt p53. It was found in a screening of the National Cancer Institute (NCI) library of low-molecular-weight compounds based on its ability to selectively kill wtp53-containing cells. RITA binds directly to p53 and diplaces its main destructor Mdm2, as well as inducing a shift in the conformation of p53. This is in contrast to the wtp53-reactivating compound Nutlin3a, which targets Mdm2, inhibiting its ability to degrade p53. Using microarray technology we have explored the effect of RITA on the transcriptome of isogenic cell-lines with knocked-out (KO) or intact (WT) TP53. While the effects on KO cells are below detection limit, the effects on WT cells are profound. The known p53 targets induced are predominately apoptotic, in contrast to the genes affected by Nutlin3a, which are exclusively growth-arrest genes. Keywords: Antitumor agent |
| 2251 | GSE9090 |
Profile | To understand the differentiation process of embryonic stem cells into hemangioblasts gene expression profiles of ES, EB and Blast cells (BL) were analyzed. Keywords: time course |
| 2252 | GSE39293 |
Profile | Cidofovir is an acyclic nucleoside phosphonate with strong antiviral activity against a broad spectrum of DNA viruses. Although it has previously been shown that cidofovir exerts an antiproliferative effect on HPV positive cells by the induction of apoptosis the exact mechanism of action remains to be unraveled. In order to study the activity of cidofovir against HPV, gene expression profiling was performed in cidofovir-treated and cidofovir-resistant HeLa, HaCaT, and PHK cells by means of microarrays (HG-U133 Plus 2, Affymetrix). |
| 2253 | GSE27716 |
Profile | The World Health Organization has subclassified adenocarcinoma based upon predominant cell morphology and growth pattern such as bronchioloalveolar carcinoma (BAC) adenocarcinoma with mixed subtypes (AC-mixed), and homogenously invasive tumors with a variety of histological patterns Pure invasive adenocarcinomas are often devoid of bronchioloalveolar morphology. The clinical importance of lung adenocarcinoma invasion is supported by several recent studies indicating that the risk of death in non-mucinous BAC is significantly lower than that of pure invasive tumors and in tumors with greater than 0.6 cm of fibrosis or linear invasion (J Thorac Oncol 6:244-285) To identify human tumor cell signatures associated with lung adenocarcinoma subtype and invasion, we performed microarray gene expression profiling of microdissected tumor cells noninvasive AC and AC-Mixed invasive tumors. |
| 2254 | GSE16088 |
Profile | Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy. |
| 2255 | GSE43032 |
Profile | SF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed. We studied gene expression profiles using Affymetrix microarrays in the H295R/TR SF-1 adrenocortical cancer cell line where SF-1 expression can be increased in a doxycycline-dependent manner (Mol. Endocrinol. 21: 2968–2987, 2007) |
| 2256 | GSE31864 |
Profile | To gain a more depth knowledge of repressive epigenetic gene regulation in UCC we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium. We identified a panel of genes with cancer specific epigenetic mediated aberrant expression. |
| 2257 | GSE11345 |
Profile | The effects of stimulating intestinal epithelial cells with Th17 cytokines IL17 and IL22, was investigated Keywords: dose response |
| 2258 | GSE15659 |
Profile | Gene expression profiles of subsets of CD4+ T cells according to their expression of FoxP3 and CD45RA were compared. Abstract: FoxP3 is a key transcription factor for the development and function of natural CD4+ regulatory T cells (Tregs). Here we show that human FoxP3+CD4+ T cells are composed of three phenotypically and functionally distinct subpopulations: CD45RA+FoxP3low resting Tregs (rTregs) and CD45RA-FoxP3high activated Tregs (aTregs) both of which are suppressive in vitro, and cytokine-secreting CD45RA-FoxP3low non-suppressive T cells. The proportion of the three subpopulations characteristically altered in cord blood, aged individuals, and patients with immunological diseases. Terminally differentiated aTregs rapidly die while rTregs proliferate and convert into aTregs in vitro and in vivo as shown by the transfer of rTregs into NOD-scid-common gamma-chain-knockout mice and by TCR sequence-based T cell clonotype tracing in peripheral blood of normal individuals. Taken together, the dissection of FoxP3+ cells into subsets enables one to analyze Treg differentiation dynamics and interactions in normal and disease states, and to control immune responses through manipulating particular FoxP3+ subpopulations. |
| 2259 | GSE33658 |
Profile | Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors. |
| 2260 | GSE19471 |
Profile | Gene expression profiles of human BM-MSC isolated form normal donor to elucidate potential molecular network for clinical application |
| 2261 | GSE11285 |
Profile | We identified GSK3 as a regulator of GBM cell survival using microarray analysis small molecule and genetic inhibitors of GSK3 activity. Various molecular and genetic approaches were then employed to dissect out the molecular mechanisms responsible for GSK3 inhibition-induced cytotoxicity. Keywords: time course |
| 2262 | GSE12199 |
Profile | We used microarrays to detail the global programme of gene expression for MCF-7 and MDA-MB-231 and revealed the correlation between the methylation state of various genomic components and gene expression level. The expression analyses of the two breast cancer cell lines are a part of the whole study. The summary of our study is as follows: We establish a technique called modified methylation-specific digital karyotyping (MMSDK) based on methylation-specific digital karyotyping (MSDK) with a novel sequencing approach. Briefly, after a tandem digestion of genomic DNA with a methylation-sensitive mapping enzyme and a fragmenting enzyme, short sequence tags are obtained. These tags are amplified, followed by direct, massively parallel sequencing (Solexa 1G Genome Analyzer). This method allows high-throughput and low-cost genome-wide DNA methylation mapping. We applied this method to investigate global DNA methylation profiles for widely used breast cancer cell lines, MCF-7 and MDA-MB-231, which are representatives for luminal-like and mesenchymal-like cancer types, respectively. By comparison, a highly similar overall DNA methylation pattern was revealed for the two cell lines. However a cohort of individual genomic loci with significantly different DNA methylation profile between two cell lines was identified. Furthermore, we revealed a genome-wide significant correlation between gene expression and the methylation status of gene promoters with CpG islands (CGIs) in the two cancer cell lines, and a correlation of gene expression and the methylation status of promoters without CGIs in MCF-7 cells. Keywords: genetic modification |
| 2263 | GSE34607 |
Profile | Background: In classrooms high concentrations of particulate matter PM10 were measured. It is unknown whether the hazard of indoor particles is similar to that of the better studied outdoor particles. This study therefore analyzed adverse biological effects of classroom in comparison to outdoor PM10. Methods: Samples were taken from six schools during teaching hours. Genome-wide gene expression in human bronchial BEAS-2B epithelial cells was analyzed and regulated genes were verified by quantitative PCR. Polycyclic aromatic hydrocarbons (PAH), endotoxin, and cat allergen Fel d 1 were analyzed with standard methods. Enhancement of allergic reactivity by PM10 was confirmed with CD63 upregulation in human primary basophils. Acceleration of human blood coagulation was determined with supernatants of PM10-exposed human peripheral blood monocytes. Results: Indoor PM10 induced SERPINB2 (involved in blood coagulation) and inflammatory genes (like CXCL6, CXCL1, IL6, IL8, all p<0.001). Outdoor PM10 induced xenobiotic metabolizing enzymes (CYP1A1, CYP1B1, TIPARP, all p<0.001). The induction of inflammatory genes by indoor PM10 could be explained by endotoxin (indoor 128.5±42.2EU/mg versus outdoor 13.4±21.5EU/mg, p<0.001), the induction of CYP by outdoor PAH (indoor 8.3±4.9ng/mg versus outdoor 16.7±15.2ng/mg, p<0.01). The induction of SERPINB2 was confirmed by a more rapid human blood coagulation (p<0.05). Indoor PM10 had no effect on the allergic reactivity from human primary basophils, except in cat allergic individuals. This was explained by varying Fel d 1 concentrations in indoor PM10 (p<0.001). Conclusions: Indoor PM10, compared to outdoor PM10, was 6 times higher, had a different composition, and on an equal weight basis induced more inflammatory and allergenic reactions, and accelerated blood coagulation. Outdoor PM10 had significantly lower effects, but induced detoxifying enzymes. Therefore, preliminary interventions for the reduction of classroom PM10 seem reasonable, perhaps by intensified ventilation. |
| 2264 | GSE12860 |
Profile | Rheumatoid arthritis (RA) leads to progressive destruction of articular structures. Despite recent progress in controlling inflammation and pain little cartilage repair has yet been observed. This in vitro study aims to determine the role of chondrocytes in RA-related cartilage destruction and antirheumatic drug-related regenerative processes. Human chondrocytes were three-dimensionally cultured in alginate beads. To determine the RA-induced gene expression pattern, human chondrocytes were stimulated with supernatant of RA synovial fibroblasts (RASF) and normal donor synovial fibroblasts (NDSF), respectively. To examine antirheumatic drug response signatures, human chondrocytes were stimulated with supernatant of RASF that have been treated with disease-modifying antirheumatic drugs (DMARD; azathioprine, sodium aurothiomalate, chloroquine phosphate, methotrexate), non-steroidal anti-inflammatory drugs (NSAID; piroxicam, diclofenac) or steroidal anti-inflammatory drugs (SAID; methylprednisolone, prednisolone). Genome-wide expression profiling with oligonucleotide microarrays was used to determine differentially expressed genes. Real-time RT-PCR and ELISA were performed for validation of microarray data. Following antirheumatic treatment, microarray analysis disclosed a reverted expression of 94 RA-induced chondrocyte genes involved in inflammation/NF-κB signalling, cytokine/chemokine activity, immune response, proliferation/differentiation and matrix remodelling. Hierarchical clustering analysis showed that treatment of RASF with the DMARD azathioprine, gold sodium thiomalate and methotrexate resulted in chondrocyte gene expression signatures that were closely related to the “healthy” pattern. Treatment with the SAID methylprednisolone and prednisolone strongly reverted the RA-related chondrocyte gene expression, in particular the expression of genes involved in inflammation/NF-κB and cytokine/chemokine activity. The NSAID piroxicam and diclofenac and the DMARD chloroquine phosphate had only moderate to marginal effects. Pathway analysis determined major mechanisms of drug action, for example pathways of cytokine-cytokine receptor interaction, TGF-β/TLR/Jak-STAT signalling and ECM-receptor interaction were targeted. This in vitro study provides a comprehensive molecular insight into the antirheumatic drug response signatures in human chondrocytes, thereby revealing potential molecular targets, pathways and mechanisms of drug action involved in chondrocyte regeneration. Thus, the present study may contribute to the development of novel therapeutic chondro-protective compounds and strategies. Keywords: drug response |
| 2265 | GSE27887 |
Profile | Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/“T22” immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate to severe AD. In psoriasis NB-UVB has been found to suppress the Th1/Th17 immune polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Our study evaluates the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods: 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results: All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, T22, and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation also normalized after phototherapy. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/“T22”-associated cytokines and chemokines, and normalized expression of barrier proteins. Conclusions: Our study shows reversal of both the epidermal defects and underlying immune activation in AD. By determining the correlation of variables with therapeutic response, we have defined a set of biomarkers of disease response that associate resolved Th2 and T22 inflammation with reversal of barrier pathology. This data supports the “inside-out” hypothesis of AD, suggesting that it is a disease primarily driven by an immune stimulus. |
| 2266 | GSE44968 |
Profile | We used microarrays to develop gene signatures for XBP1 and IRE1 in myeloma cells to explore the role of this UPR/differentiation pathway in proteasome inhibitor resistance. |
| 2267 | GSE7848 |
Profile | Previous studies indicate that the triterpene glycoside actein from the herb black cohosh inhibits growth of human breast cancer cells. This study seeks to identify genes altered in human breast cancer cells by treatment with actein using gene expression analysis. We treated MDA-MB-453 human breast cancer cells with actein at 2 doses, 20 or 40 μg/mL, for 6 or 24 h. We identified 5 genes that were activated after each of the treatments that are known to play a role in cellular responses to diverse stresses, including the DNA damage and unfolded protein responses. In addition, four genes that mediate the integrated stress response (ISR), including activating transcription factor 4, were induced under at least one of the 4 treatment conditions. We used hierarchical clustering to define clusters comprising patterns of gene expression. Two ISR genes, activating transcription factor 3 (ATF3) and DNA damage- inducible transcript 3, and lipid biosynthetic genes were activated after exposure to actein at 40 μg/mL for 6 h, whereas the cell cycle genes cyclin E2 and cell division cycle 25A were repressed. Our results suggest that actein induces 2 phases of the ISR, the survival phase and the apoptotic phase, depending on the dose and duration of treatment. We confirmed the results of gene expression analysis with real-time RT-PCR for 18 selected genes and Western blot analysis for ATF3. Since actein activated transcription factors that enhance apoptosis, and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer. Keywords: expression,time course, dose response |
| 2268 | GSE18139 |
Profile | Title: Array-based gene expression CGH and tissue data define a 12q24 gain in neuroblastic tumors with prognostic implication. Background: Neuroblastoma has successfully served as a model system for the identification of neuroectoderm-derived oncogenes. However, in spite of various efforts, only a few clinically useful prognostic markers have been found. Here, we present a framework, which integrates DNA, RNA and tissue data to identify and prioritize genetic events that represent clinically relevant new therapeutic targets and prognostic biomarkers for neuroblastoma. Methods: A single-gene resolution aCGH profiling was integrated with microarray-based gene expression profiling data to distinguish genetic copy number alterations that were strongly associated with transcriptional changes in two neuroblastoma cell lines. FISH analysis using a hotspot tumour tissue microarray of 37 paraffin-embedded neuroblastoma samples and in silico data mining for gene expression information obtained from previously published studies including up to 445 healthy nervous system samples and 123 neuroblastoma samples were used to evaluate the clinical significance and transcriptional consequences of the detected alterations and to identify subsequently activated gene(s). Results: In addition to the anticipated high-level amplification and subsequent overexpression of MYCN, MEIS1, CDK4 and MDM2 oncogenes, the aCGH analysis revealed numerous other genetic alterations, including microamplifications at 2p and 12q24.11. Most interestingly, we identified and investigated the clinical relevance of a previously poorly characterized amplicon at 12q24.31. FISH analysis showed low-level gain of 12q24.31 in 14 of 33 (42%) neuroblastomas. Patients with the low-level gain had an intermediate prognosis in comparison to patients with MYCN amplification (poor prognosis) and to those with no MYCN amplification or 12q24.31 gain (good prognosis) (P = 0.001). Using the in silico data mining approach, we identified elevated expression of five genes located at the 12q24.31 amplicon in neuroblastoma (DIABLO, ZCCHC8, RSRC2, KNTC1 and MPHOSPH9). Among these, DIABLO showed the strongest activation suggesting a putative role in neuroblastoma progression. Conclusions: The presented systematic and rapid framework, which integrates aCGH, gene expression and tissue data to obtain novel targets and biomarkers for cancer, identified a low-level gain of the 12q24.31 as a potential new biomarker for neuroblastoma progression. Furthermore, results of in silico data mining suggest a new neuroblastoma target gene, DIABLO, within this region, whose functional and therapeutic role remains to be elucidated in follow-up studies. |
| 2269 | GSE31546 |
Profile | Develop an EGFR mutation gene expression signature to aid in predicting response and clinical outcome and to identify genes associated with the EGFR-dependent phenotype |
| 2270 | GSE11350 |
Profile | Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and derive embryonic stem cell properties. Here we report the successful establishment of stable pluripotent human adult germline stem cells (haGSCs) derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of haGSCs revealed many similarities to human embryonic stem (hES) cells and haGSCs produced teratomas after subcutaneous transplantation into immunodeficient mice. The haGSCs differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of hES cells. We conclude that the generation of haGSCs from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with hES cells. Keywords: pluripotent stem cells characterisation |
| 2271 | GSE44867 |
Profile | A375 cells with inducible knockdown HSF1 with and without HSP90 inhibitor treatment |
| 2272 | GSE42660 |
Profile | Expression data of BL2 Burkitt Lymphoma cell line (controls and samples treated with different B cell specific stimuli) |
| 2273 | GSE33504 |
Profile | Systemic mastocytosis (SM) is an incurable neoplasm characterized by abnormal accumulation of neoplastic mast cells (MC) in vascularized organs. In indolent SM MC express several different adhesion-molecules including CD2 and CD58, and form focal tissue-aggregates, whereas in advanced SM, MC often lack CD2 and produce a more diffuse infiltration-pattern. To explore the functional role of CD2 in the pathology of SM, stable CD2+ and CD2− subclones of the human MC-leukemia cell line HMC-1 were generated and injected intraperitoneally into pfp/rag2 mice. CD2+ HMC-1 cells formed solid mastocytomas in the peritoneum and lungs, whereas CD2− cells produced diffuse infiltration. CD2+ and CD2− HMC-1 subclones all displayed the driver-mutant KIT D816V, exhibited the same growth-kinetics, and displayed identical adhesion-receptors including CD44 and selectin-ligands. To explore the mechanism of organ invasion, E- and P-selectin-deficient scid mice (scid-select) were employed. While massive HMC-1 infiltrates were detected in the lungs of control mice, infiltration was markedly reduced or absent in scid-select mice. The invasion-receptor CD44 was detectable in all MC infiltrates, with most abundant expression in the invasion-front. Together, our data show that selectins mediate organ-invasion of MC and CD2-CD58 interactions contribute to a more focal infiltration-pattern which is lost during progression to MC leukemia. |
| 2274 | GSE7578 |
Profile | Bmi-1 and Mel-18 are close structural homologues that belong to the polycomb group (PcG) of transcriptional regulators of homeotic gene expression in development. They are believed to stably maintain repression of gene expression by altering the state of chromatin at specific promoters. A number of clinical and experimental observations have also implicated Bmi-1 in tumorigenesis and stem cell maintenance. Bmi-1 overexpression or amplification has been observed in a number of human malignancies particularly in B-cell lymphomas, medulloblastomas and breast cancer. We report here that shRNA-mediated knock-down of either Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of proliferation, loss of clonogenic survival and anchorage-independent growth, and suppression of xenograft tumor formation in nude mice. Furthermore, overexpression of both Bmi-1 and Mel-18 significantly increased clonogenic survival of Rat1 fibroblasts. In contrast, stable downregulation of Bmi-1 or Mel-18 alone did not affect the growth of SK-OV-3 or U2OS cancer cell lines or normal human WI38 fibroblasts. Gene expression analysis of shRNA-expressing DAOY cells has demonstrated a significant overlap in the Bmi-1- and Mel-18-regulated genes and revealed novel gene targets under their control. Taken together, these results suggest that Bmi-1 and Mel-18 might have overlapping functions in human tumorigenesis. Keywords: shRNA knock-down |
| 2275 | GSE22356 |
Profile | Rationale: Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial. Objective: To identify genes that are differentially expressed in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension which could be used as biomarkers of disease for early diagnosis and provide insight into pathogenesis of pulmonary hypertension in at-risk populations. Methods and Results: Gene expression analysis was performed on a carefully characterized Microarray Cohort of scleroderma patients with (n=10) and without (n=10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a separate Validation Cohort of scleroderma patients with (n=15) and without (n=19) pulmonary hypertension by RT-qPCR. We identified inflammatory and immune-related genes including interleukin-7 receptor (IL-7R) and chemokine receptor 7 (CCR7) as differentially expressed in patients with scleroderma-associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL-7R on circulating CD4+ T cells from scleroderma patients with pulmonary hypertension. Conclusions: Differences exist in the expression of inflammatory and immune-related genes in peripheral blood cells derived from patients with scleroderma-related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at-risk populations to facilitate early diagnosis and provide insight into inflammatory and autoimmune mechanisms of scleroderma-related pulmonary hypertension. |
| 2276 | GSE12917 |
Profile | Rho family small GTPases serve as molecular switches in the regulation of diverse cellular functions including actin cytoskeleton remodeling cell migration, gene transcription, and cell proliferation. Importantly, Rho overexpression is frequently seen in many carcinomas. However, published studies have almost invariably utilized immortal or tumorigenic cell lines to study Rho GTPase functions and there are no studies on the potential of Rho small GTPase to overcome senescence checkpoints and induce preneoplastic transformation of human mammary epithelial cells (hMECs). We found that ectopic expression of wild-type RhoA as well as a constitutively-active RhoA mutant (G14V) in primary hMEC strains led to their immortalization and preneoplastic transformation. Significantly, RhoA-T37A mutant, known to be incapable of interacting with many well known Rho-effectors ,was also capable of immortalizing hMECs.Our results demonstrate that RhoA can induce the preneoplastic transformation of hMECs by altering multiple pathways linked cellular transformation and breast cancer. Through microarray analysis, we want to identify genes and pathways linked to RhoA induced hMECs immortalization. |
| 2277 | GSE658 |
Profile | primary ALL cells (B-lineage) resistant to vincristine by the MTT in vitro sensitivity assay Keywords = ALL Keywords: other |
| 2278 | GSE17073 |
Profile | Genes differentially expressed among cells constituting an in vitro human lung carcinogenesis model consisting of normal immortalized, transformed and tumorigenic bronchial epithelial cells were identified. The differentially expressed genes were then analyzed to determine their relevance to the gene expression patterns of clinical non-small cell lung cancer (NSCLC) samples as well as the clinical outcome of patients with this disease. |
| 2279 | GSE46873 |
Profile | Immuno-chemotherapy regimens elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumors in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that drives aggressive tumor growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma. We have identified CYCLON has a nuclear factor involved in tumor progression and treatment resistance in aggressive lymphoma. In order to get further insights into the molecular mechanisms related to the expression of this factor, we used Raji cells to compared gene expression profiles of control and CYCLON knock-down cell lines. |
| 2280 | GSE9055 |
Profile | The many steps involved in the production of a mature mammalian mRNA are extensively coupled and levels of both precursors and products can be measured using expression and genomic tiling microarrays. Different probes in these arrays targeting the same transcript often give different signals; then, precursor (nascent) RNA – which is present transiently at low concentrations – is difficult to detect. Keywords: TNFa stimulation time course of HUVEC |
| 2281 | GSE15991 |
Profile | To obtain a genomic view of hepatocyte nuclear factor-4α (HNF-4α) in the regulation of the inflammatory response microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokines in a model of knock-down HNF-4α HepG2 cells. The results indicate an extensive role for HNF-4α plays in the regulation of a large number of the liver-specific genes. Majority of genes (71%) affected by cytokine treatment are also affected by HNF-4α knock-down. This significant overlap suggests that HNF-4α may play a role in regulating the cytokine-induced inflammatory response. |
| 2282 | GSE9526 |
Profile | Besides the established selection criteria based on embryo morphology and blastomere number new parameters for embryo viability are needed to improve the clinical outcome of in vitro fertilization (IVF) and more particular of elective single embryo transfer (eSET). The aim of the study was to analyse genome-wide whether the embryo viability was reflected by the expression of genes in the oocyte surrounding cumulus cells. Early cleavage (EC) was chosen as a parameter for embryo viability. Keywords: class comparison |
| 2283 | GSE10021 |
Profile | We performed a global analysis of both miRNAs and mRNAs expression across sixteen human cell lines and extracted negatively correlated pairs of miRNA and mRNA which indicate miRNA-target relationship. The many of known-target of miR-124a showed negative correlation suggesting our analysis were valid. We further extracted physically relevant miRNA-target gene pairs, applying computational target prediction algorism with inverse correlations of miRNA and mRNA expression. Furthermore, Gene Ontology-based annotation and functional enrichment analysis of the extracted miRNA-target gene pairs indicated putative functions of miRNAs. Keywords: Cell type comparison |
| 2284 | GSE22639 |
Profile | Irradiated cell lines exposed to 1-10 Gy |
| 2285 | GSE14491 |
Profile | TGFβ ligands act as tumor suppressors in early stage tumors but are paradoxically diverted into potent prometastatic factors in advanced cancers. The molecular nature of this switch remains enigmatic. We now show that TGFβ-dependent cell migration invasion and metastasis are empowered by mutant-p53. To investigate the specific gene expression program by which mutant-p53 and TGFβ control invasion and metastasis in breast cancer cells, we compared the TGFβ transcriptomic profile of control and mutant-p53 depleted MDA-MB-231 cells. Keywords: expression profiling by array |
| 2286 | GSE37573 |
Profile | In this report we applied standard and original methods of analysis of gene expression microarray data to delineate differences in the molecular pathways impacted by stimulation of Epstein-Barr virus (EBV) transformed B cells derived from patients with systemic lupus erythematosus (SLE) and normal unrelated controls. In order to understand the dynamics and interconnections the B cell molecular pathways the system was perturbed with a biologically relevant signal, co-crosslinking of the B cell antigen receptor (BCR) and FcγR2b and global gene expression changes were assessed at various timepoints post-stimulation. Both traditional analysis of differential gene expression and analysis of the dynamics of gene expression variations were performed. Combining these two methods in an analysis process we call Pathway Dysregulation Analysis allows us to establish model networks of functional gene expression important for B cell signaling responses and elucidate gene expression regulatory interconnections disrupted in B cells from individuals with lupus. Through this technique, we found two main groups of gene associations changed significantly with the disease phenotype, which included genes with established controlling function of the B cell activation, and genes involved in apoptosis initiation or prevention. |
| 2287 | GSE41035 |
Profile | Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood. In this study with a bladder carcinoma cell line expressing inducible FGFR3 shRNAs, we sought to identiy transcriptional targets of FGFR3 and investigate their contribution to bladder cancer development. |
| 2288 | GSE43210 |
Profile | Store operated calcium entry (SOCE) downstream of T cell receptor (TCR) activation in T lymphocytes has been shown to be mediated mainly through the Calcium Release Activated Calcium (CRAC) channel. Here we compared the effects of a novel, potent and selective CRAC inhibitor, 2,6-Difluoro-N-{5-[4-methyl-1-(5-methyl-thiazol-2-yl)-1,2,5,6-tetrahydro-pyridin-3-yl]-pyrazin-2-yl}-benzamide (RO2959), on T cell effector functions with that of a previously reported CRAC channel inhibitor, YM-58483, and a calcineurin inhibitor Cyclosporin A (CsA). Using both electrophysiological and calcium-based fluorescence measurements, we showed that RO2959 is a potent SOCE inhibitor that blocked an IP3-dependent current in CRAC-expressing RBL-2H3 cells and CHO cells stably expressing human Orai1 and Stim1, as well as SOCE in human primary CD4+ T cells triggered by either TCR stimulation or thapsigargin treatment. Furthermore, we demonstrated that RO2959 completely inhibited cytokine production as well as T cell proliferation mediated by TCR stimulation or MLR (Mixed Lymphocyte Reaction). Lastly, we showed by gene expression array analysis that RO2959 potently blocked TCR triggered gene expression and T cell functional pathways similar to CsA and FK506. Thus, both from a functional and transcriptional level, our data provide evidence that RO2959 is a novel and selective CRAC inhibitor that potently inhibits human T cell functions. |
| 2289 | GSE11279 |
Profile | Analysis of SW480 cells following knockdown of Ezrin using RNAi. Ezrin is a protein that regulate the organization of cytoskeleton. Ezrin KD SW480 was used to study the role of ezrin in colon cancer. Keywords: ezrin colon cancer, migration |
| 2290 | GSE9759 |
Profile | In addition to the estrogen responsive element (ERE)-dependent gene expression E2-ERbeta regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERbeta signaling is unclear. Our studies in infected ER-negative cell models with an ERbeta mutant (ERbetaDBD) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERbeta are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERbeta signaling in model cell lines. Keywords: MDA-MB-231 cells |
| 2291 | GSE28050 |
Profile | BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements (MAREs) at low intracellular heme levels. Upon heme binding BACH1 is released from the MAREs, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we performed knock-down of BACH1 in HEK 293T cells using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays. |
| 2292 | GSE40564 |
Profile | Purpose: The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell proliferation and survival and is frequently altered and activated in neoplasia including carcinomas of the lung. In this study we investigated the potential of targeting the catalytic class IA PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types. Experimental Design: The expression of PI3K isoforms in patient specimens was analyzed. The effects on SCLC cell survival and downstream signaling were determined following PI3K isoform inhibition by selective inhibitors or down-regulation by small interfering RNA. Results: Over-expression of the PI3K isoforms p110α and p110β was shown by immunohistochemistry in primary SCLC tissue samples. Targeting the PI3K p110α with RNA interference (RNAi) or selective pharmacological inhibitors resulted in strongly affected cell proliferation of SCLC cells in vitro and in vivo, while targeting p110β was less effective. Inhibition of p110α also resulted in increased apoptosis and autophagy, which was accompanied by decreased phosphorylation of Akt and components of the mammalian target of rapamycin (mTOR) pathway, such as the ribosomal S6 protein, and the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). A DNA microarray analysis revealed that p110α inhibition profoundly affected the balance of pro- and anti-apoptotic Bcl-2 family proteins. Finally, p110α inhibition led to impaired SCLC tumor formation and vascularization in vivo. Conclusion: Together our data demonstrate the key involvement of the PI3K isoform p110α in multiple tumor-promoting processes in SCLC. |
| 2293 | GSE10961 |
Profile | At present medical treatments of synchronous and metachronous liver metastases from colorectal cancer are not differentiated. The aim of the study was to analyze the gene expression profiling of synchronous and metachronous lesions in order to identify molecular signatures as possible basis for choice of systemic therapies. Fresh tissues specimens from metastases of 18 patients undergone liver surgery were collected (10 synchronous and 8 metachronous lesions). Gene expression profiling was studied using Affymetrix platform. Two different profiles were identified. Pathway related to the Epidermal Growth Factor receptor (EGFr) was upregulated in metachronous lesions whereas pathways mainly related to inflammation in synchronous lesions. Real Time-PCR, Western Blotting and ELISA confirmed that the metachronous lesions had the overexpression of EGFr, but the synchronous ones had the overexpression of Cyclo-oxygenase 2 (COX-2). These results suggest that synchronous or metachronous liver metastases from colorectal cancer could be differently treated on the basis of different molecular pathways. Keywords: disease state analysis |
| 2294 | GSE33727 |
Profile | These samples are part of a study that tries to find melanoma subgroups by the mean of gene expression analysis. Recent trials with MAPK inhibitors have shown promising results in many patients with metastatic melanoma; however nearly all responding patients experience disease relapse. We describe here how melanoma cells respond to MAPK inhibition in a phenotype-specific manner, suggesting that slow cycling invasive phenotype cells provide a treatment-resistant pool from which disease relapse may be derived. The implication is that while MAPK inhibition may successfully treat proliferating cells, another cell population needs to be addressed at the same time. |
| 2295 | GSE30522 |
Profile | Characterization of the gene expression profiles of specific cell populations of the human urinary bladder provides an important set of research tools for the study of cellular differentiation and the cancer process. The transcriptome is a definitive identifier of each individual cell types. Surgically resected tissue was digested by collagenase and the different cell types were sorted by antibodies to cluster designation (CD) cell surface antigens. The sorted cells were analyzed by DNA microarrays. The transcriptome datasets were analyzed for differentially expressed genes and plotted on a principal components analysis space for cell lineage relationship. The following bladder cell types were analyzed: CD9+ urothelial CD104+ basal, CD13+ stromal of lamina propria, CD9+ urothelial carcinoma cancer, and CD13+ urothelial carcinoma-associated stromal. Gene expression differences between the cell types of tumor and their respective non-cancer counterpart provide biomarker candidates. Basal cells of the bladder and prostate, although sharing CD cell surface markers, are quite different in overall gene expression. Furthermore, these cells lack transcript features of stem cell signature of embryonic stem or embryonal carcinoma cells. Cell type-specific transcriptomes are more informative than bulk tissue transcriptomes. The relatedness of different cell types can be determined by transcriptome dataset comparison. |
| 2296 | GSE20667 |
Profile | The NF-κB pathway is a critical regulator of the immune system and has been implicated in cellular transformation and tumorigenesis. NF-κB response is regulated by the activation state of the IκB kinase (IKK) complex and triggered by a wide spectrum of stimuli. We previously reported that NF-κB is downstream of Notch1 in T cell acute lymphoblastic leukaemia (T-ALL) however both the mechanisms involving Notch1-induced NF-κB activation and the potential importance of NF-κB in the maintenance of the disease are unknown. Here we visualize Notch-induced NF-κB activation using both human T-ALL cell lines and animal models of this type of leukemia. We show that it is not Notch1 itself but Hes1, a canonical Notch target, the responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by a direct transcriptional repression of the deubiquitinating enzyme CYLD, a well-characterized IKK inhibitor. Consistently, CYLD expression is significantly reduced in primary T-ALL leukemias. Finally, we demonstrate that IKK complex inhibition is a promising option for the targeted therapy of T-ALL as suppression of IKK function affected both the survival of human T-ALL cells in vitro and the maintenance of the disease in vivo. Transcriptional consequences of NF-kB inactivation in human T-ALL1 cell line |