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GSE8928
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Eicosanoids are potent regulators of gene expression of inflammatory cells. Pro- (leukotrienes B4 and C4) and anti-indflammatory (lipoxins A4 and B4) eicosanoids have been described in the literature but the detailed impact of these lipid mediators on the gene expression pattern of monocytic cells has not been studied in detail. We cultured the permanent monocytic cell line MonoMac 6 for 12 h in the absence (solvent control) and presence of these eicosanoids and quantified the differential gene expression patterns using the microarray technology.
Publication Title
Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and -13.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 98 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Formaldehyde, an important industrial chemical, is used for multiple commercial purposes throughout the industrialized world. This simple, one carbon aldehyde is a natural metabolite formed in cells throughput the body. However, it is also a rodent nasal carcinogen, when inhaled by rats every day for two-years at irritant concentrations. High tumor incidences occur at concentration of 10 ppm and above; no tumors are observed at concentrations below 6.0 ppm. The US Environmental Protection Agency (US EPA) is now (2007) conducting a risk assessment to try to evaluate possible cancer risks for much lower levels of human exposure. Sensitive methods are needed to evaluate tissue responses below those concentrations that are clearly irritant or carcinogenic. This microarray study was undertaken to evaluate the mode of action for nasal responses to inhaled formaldehyde in Fisher 344 rats over a range of exposure concentrations. The range of concentrations used spanned those at which virtually no tissue responses were observed (0.7 ppm) to those that represent the highest concentration in the cancer studies (15 ppm) that produced nasal tumors in half the exposed group of rats. The study identified doses at which there were no statistically significant changes in gene expression; intermediate doses with changes in a small number of genes not easily grouped by function; and then concentrations where changes were consistent with irritation and cell stress responses.
Publication Title
A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure.
Sample Metadata Fields
Sex, Subject
View Samples- Rattus norvegicus
- 72 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Formaldehyde (FA), an endogenous cellular aldehyde, is a rat nasal carcinogen. In this study, concentration- and exposure-duration transitions in FA mode of action (MOA) were examined with pharmacokinetic (PK) modeling for tissue formaldehyde acetal (FAcetal) and glutathione (GSH) and with histopathology and gene expression studies for tissue responses in nasal epithelium from rats exposed to 0, 0.7, 2, 6, 10 or 15 ppm FA 6 hr/day for 1, 4 or 13 weeks. The study had two goals. The first goal was to develop a basic PK model to estimate various forms of tissue formaldehyde and tissue glutathione (GSH). The second goal was to compare histopathology and gene expression changes in nasal tissues caused by inhalation of FA with changes in tissue FAcetal and free GSH calculated from the PK model. Patterns of gene expression varied with concentration and with duration. At 0.7 and 2 ppm, sensitive response genes (SRGs) - associated with cellular stress, thiol transport/reduction, inflammation, and cell proliferation - were similarly upregulated at all exposure durations. At 6 ppm and greater, gene expression changes showed enrichment of pathways involved in cell cycle, DNA repair, and apoptosis processes. ERBB, EGFR, WNT, TGF-, Hedgehog, and Notch signaling were also enriched in differentially expressed genes. Benchmark doses (BMDs) for genes in significantly enriched pathways were lower at 13 weeks than at 1 or 4-week. The transcriptional and histological changes corresponded to PK model-predicted changes in free GSH at 0.7 and 2 ppm and in FAcetal at 6 ppm. DNA-replication stress, enhanced proliferation, metaplasia, and stem cell-niche activation appear to be associated with FA carcinogenesis at 6 ppm and above. Dose dependencies in MOA, the presence of high physiological FAcetal, and non-linear FAcetal/GSH tissue kinetics indicate that FA concentrations below 150 ppb (and probably any concentrations below irritant levels, i.e., ~ 1 ppm) would not increase cancer risks of inhaled FA in the nose or any other tissue. Closer examination of dose response relationships for endogenous compound toxicity could help guide biologically relevant approaches for chemical risk assessment.
Publication Title
Formaldehyde: integrating dosimetry, cytotoxicity, and genomics to understand dose-dependent transitions for an endogenous compound.
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 66 Downloadable Samples
Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The contribution of copy number (CN)-altered genes in cervical carcinogenesis is unknown owing to a lack of correlation with gene expression. We mapped CN-altered genes in 31 cervical cancers (CCs), and investigated the expression of 21,000 genes in 55 CCs using microarrays. Biological processes associated with genes deregulated by gene dosage and the relationship between gene dosage and patient survival were investigated. CN-altered genome (CN-AG) percentages varied widely among tumors from 0% to 32.2% (mean = 8.1 8.9). Tumors were classified as low (mean = 0.5 0.6, n = 11), medium (mean = 5.4 2.4, n = 10), or high (mean = 19.2 6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated by gene dosage; by contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.6% of deregulated genes in whole tumors (r2 = 0.236, p = 0.006; analysis of variance), including those in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This result suggests that the remaining genes are not deregulated directly by gene dosage but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profiles of APC/C-proteasome-dependent proteolysis and glycolysis were associated with poor patient survival, although only the first 2 correlations were statistically significant (p < 0.05, log-rank test). The data suggest that inhibitors of APC/C-dependent proteasome proteolysis and glycolysis may be useful treatments in these patients.
Publication Title
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However, most patients eventually develop resistance to this treatment.
Publication Title
Identification of docetaxel resistance genes in castration-resistant prostate cancer.
Sample Metadata Fields
Disease, Disease stage, Cell line, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- (ffymetrixhumanexon1.0starray[cdf:huex10stv2,corer3,a20071112,ep)
Description
Although many genes have been proposed to be involved in prostate carcinogenesis, no single gene or gene profile has shown to have prognostic value. The main challenge for clinical management is to distinguish slowly growing tumors from those that will relapse. In this study, we compared expression profiles of 18 prostate samples (7 with Gleason 6, 8 with Gleason 7 and 3 with Gleason score equal or higher than 8) and 5 non-neoplastic prostate samples, using the GeneChip Human Exon Array 1.0 ST of Affymetrix. Microarray analysis revealed 99 genes showing statistically significant differences among tumors with Gleason score 6, 7 and 8. In addition, mRNA expression of 29 selected genes was analyzed by qRT-PCR with microfluidic cards in an extended series of 30 prostate tumors. From these, 29 were selected to be validated and the differential expression of 18 of them (62%) was independently confirmed by quantitative real-time RT-PCR (14 upregulated and 4 downregulated in higher Gleason scores) in the extended series. This list was further narrowed down to 12 genes that were differentially expressed in tumors with Gleason score of 6-7 vs 8. Finally, the protein levels of two genes from the 12-gene signature (SEC14L1 and TCEB1) were additionally validated by immunohistochemistry. Strong protein levels of both genes were correlated with Gleason score, stage, and PSA progression.
Publication Title
A 12-gene expression signature is associated with aggressive histological in prostate cancer: SEC14L1 and TCEB1 genes are potential markers of progression.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 18 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Sexual dimorphism in mammals is mostly attributable to sex-related hormonal differences in fetal and adult tissues; however, this may not be the sole determinant. Though genetically-identical for autosomal chromosomes, male and female preimplantation embryos could display sex-specific transcriptional regulation which can only be attributted to the differences in sexual chromosome dosage.
Publication Title
Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
THO/TREX is a conserved nuclear complex that functions in mRNP biogenesis at the interface of transcription-RNA export with a key role in preventing transcription-associated genome instability.
Publication Title
Genome-wide function of THO/TREX in active genes prevents R-loop-dependent replication obstacles.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
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.
Publication Title
Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells.
Sample Metadata Fields
Cell line
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