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GSE65198
Rattus norvegicus
59 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.
Publication Title
Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profiles in blasts from three APL patients expressing PML/RAR were assessed before and after treatment with 1 uM retinoic acid (RA) in vitro for four hours. We then studied a U937 clone conditionally expressing PML/RAR (U937-PR), (Grignani et al. 1993) (Alcalay et al. 2003), and compared the gene expression profile prior to and after 4 hours of treatment with 1 uM RA, to that obtained from a cell line bearing an empty vector (U937-MT). For each sample, biotinylated cRNA targets were synthesized starting from 5ug of total RNA, and hybridized to the complete set of HG-U133 Affymetrix oligonucleotide chips, which explores the expression of approximately 45,000 human transcripts. Results were analyzed using MASv5 and further elaborated with the GenePicker software. GeneChip probe sets regulated by RA in each sample were clustered into non-redundant regulated genes according to UniGene release Hs.166.
Publication Title
Molecular signature of retinoic acid treatment in acute promyelocytic leukemia.
Sample Metadata Fields
Specimen part, Disease, Cell line, Subject, Compound
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
AML1/ETO oncoprotein is directed to AML1 binding regions and co-localizes with AML1 and HEB on its targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 17 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Pheochromocytomas (PCC) are mostly benign tumors, amenable to complete surgical resection. However, 1017% of cases can become malignant, and once metastasized, there is no curative treatment for this disease. Given the need to identify effective therapeutic approaches for PCC, we evaluated the antitumor potential of the dual PI3K/mTOR inhibitor BEZ235 against these tumors. We employed an in vivo model of endogenous PCCs (MENX mutant rats), which closely recapitulate the human tumors. Mutant rats with PCCs were treated with 2 doses of BEZ235 (20 and 30 mg/kg), or with placebo, for 2 weeks. Treatment with BEZ235 induced cytostatic and cytotoxic effects on rat PCCs, which could be appreciated by both staining the tumors ex vivo with appropriate markers, and non-invasively by functional imaging (diffusion weighted-DW-MRI) in vivo.
Publication Title
Targeting PI3K/mTOR signaling exerts potent antitumor activity in pheochromocytoma in vivo.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
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.
Publication Title
AML1/ETO oncoprotein is directed to AML1 binding regions and co-localizes with AML1 and HEB on its targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle.
Publication Title
Direct link between metabolic regulation and the heat-shock response through the transcriptional regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood.
Publication Title
Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1 down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1 on expression of genes encoding secreted proteins. Interestingly, PGC-1 requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1 modulates the secretome of mouse embryonic fibroblasts (MEFs).
Publication Title
Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
ERG activity was blocked using YK-4-279 in three subcutaneously implanted ERG+ (LuCaP 23.1, 86.2, and 35) and one ERG- (LuCaP 96) PDX. Tumor volume (TV), body weight (BW), serum prostate specific antigen (PSA), and overall survival (OS) were compared to vehicle treated controls. Changes in gene expression were assessed by RNASeq and tissue microarrays were constructed to assess necrosis, proliferation, apoptosis, microvessel density, and ERG expression. Overall design: RNA sequencing of tumors from from 16 animals (2 control, 2 treated from each of four patient derived xenograft lines) using Illumina HiSeq 2500.
Publication Title
Inhibition of ERG Activity in Patient-derived Prostate Cancer Xenografts by YK-4-279.
Sample Metadata Fields
Sex, Treatment, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Medial HOXA genes demarcate haematopoietic stem cell fate during human development.
Sample Metadata Fields
Specimen part
View Samples