| 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 | 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. |
| 5 | 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. |
| 6 | 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. |
| 7 | 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 |
| 8 | 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. |
| 9 | 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 |
| 10 | 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 |
| 11 | 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. |
| 12 | GSE44335 |
Profile | We used microarrays to investigate the transcription profile of FOXC2 expression in a human mammary epithelial cell line. |
| 13 | 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. |
| 14 | 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. |
| 15 | 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 |
| 16 | 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. |
| 17 | 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. |
| 18 | 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. |
| 19 | 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. |
| 20 | 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 |
| 21 | 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 |
| 22 | 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 |
| 23 | 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. |
| 24 | 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. |
| 25 | 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. |
| 26 | GSE35414 |
Profile | Evaluation of specific coordinated pattern of transcriptional events consistent with anti-myeloma activity of FK866 (chemical Nampt inhibitor) |
| 27 | 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 |
| 28 | 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. |
| 29 | 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 |
| 30 | 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. |
| 31 | GSE41198 |
Profile | We used gene expression profiling of human DCIS and IBC to discover uniquely expressed genes that may also regulate progression. |
| 32 | 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 |
| 33 | 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 |
| 34 | 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 |
| 35 | 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 |
| 36 | GSE41227 |
Profile | We used gene expression profiling of human DCIS and IBC to discover uniquely expressed genes that may also regulate progression. |
| 37 | 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 |
| 38 | 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 |
| 39 | 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. |
| 40 | 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. |
| 41 | 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. |
| 42 | 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 |
| 43 | 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. |
| 44 | 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 |
| 45 | 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. |
| 46 | 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. |
| 47 | 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. |
| 48 | GSE7621 |
Profile | We used microarrays to detail the global program of gene expression underlying Parkinson's disease Keywords: normal versus diseased |
| 49 | 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. |
| 50 | 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. |
| 51 | GSE25724 |
Profile | We performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples. |
| 52 | 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 |
| 53 | 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. |
| 54 | 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 |
| 55 | 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 heterochromatin |