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GSE51373
Homo sapiens
25 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. Methods: The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with the same standard platinum-based chemotherapy. Twelve patient tumors demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumors from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using a Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumors from the resistant group and the sensitive group. Results: Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels, which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NFB/ERK gene signalling networks. Conclusions: This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. Future studies to validate these markers are necessary to apply this knowledge to biomarker-based clinical trials.
Publication Title
Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We profiled and quantitated miRNAs in two skin tumors (Basal cell carcinoma and Merkel cell carcinoma) and identified tumor-specific miRNAs. We used these tumor-specific miRNAs to guide development of miRNA fluorescence in situ hybridization. Overall design: 2 barcoded sequencing runs, including 40 unique samples (36 used in manuscript). The details of each sample can be found in Supplementary Tables S1 and S2.
Publication Title
Multicolor microRNA FISH effectively differentiates tumor types.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Molecular distinctions between the stasis and telomere attrition senescence barriers in cultured human mammary epithelial cells
Publication Title
Molecular distinctions between stasis and telomere attrition senescence barriers shown by long-term culture of normal human mammary epithelial cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Mapping 50K Xba240 SNP Array (mapping50kxba240), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 26 Downloadable Samples
Affymetrix Human Mapping 50K Xba240 SNP Array (mapping50kxba240), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
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.
Publication Title
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus, Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
Publication Title
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global transcriptome patterns were obtained from ATAF1-IOE seedlings at 1 h, 2 h and 5 h after estradiol induction or mock treatment, and from mature ATAF1-IOE leaves at 5 h after estradiol induction or mock treatment.
Publication Title
Transcription Factor Arabidopsis Activating Factor1 Integrates Carbon Starvation Responses with Trehalose Metabolism.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We have previously demonstrated that bone marrow-derived DC can prevent diabetes development and halt progression of insulitis in NOD mice, the mouse model of type 1 diabetes (T1D). The DC population that was most effective in this therapy had a mature phenotype, expressed high levels of costimulatory molecules and secreted low levels of IL-12p70. The protective DC therapy induced regulatory Th2 cells that shifted the dominant Th1 environment, present in NOD mice, to a mixed Th1/Th2 milieu. Microarray analysis of therapeutic and non-therapeutic DC populations revealed several novel molecules that could play important roles in the observed DC-mediated therapy. The therapeutic DC population expressed a unique pattern of costimulatory molecules and chemokines, which were confirmed by flow cytometry and ELISA assays. We have performed in vitro chemotaxis assays that demonstrated the therapeutic DC preferentially attracted Th2 cells, as compared to Th1, Treg or nave T cells. In addition we quantified the in vivo migration of activated islet-specific T cells to the pancreas using novel cell labeling techniques and 19F nuclear magnetic resonance. A subcutaenous injection of therapeutic DC alters the migration of both Th1 and Th2 cells to the pancreas, and Th1 cells appeared in the lymph node draining the site of DC injection. These results suggest that the therapeutic function of DC is mediated in part by the chemoattractive properties of these DC for diabetogenic Th1 cells.
Publication Title
Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of gene expression in WT and ATRX KO Cast x 129 Mouse ES cells Overall design: Paired end RNA-seq analysis of PolyA selected RNA and PolyA depeleted RNA from in both wildtype nd ATRX knocked out Castx129 Mouse ES Cells
Publication Title
ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Non-symbiotic hemoglobins are ubiquitously expressed proteins known to interact with nitric oxide, an inhibitor of mitochondrial respiration and an important signalling component. We evaluated the underlying molecular mechanisms of AtHb1 (also referred as AtGLB1 or AHb1) function, its effects on stress response and the interplay with nitric oxide. For this purpose, AtHb1 was overexpressed in Arabidopsis thaliana under control of the seed-specific promoter LeB4.
Publication Title
Seed-specific elevation of non-symbiotic hemoglobin AtHb1: beneficial effects and underlying molecular networks in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part, Treatment
View Samples