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GSE56740
Rattus norvegicus
139 Downloadable Samples
Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Background: The in vivo gene response associated with hyperthermia and subsequent return to homeostasis or development of heat illness is poorly understood. Early activation of gene networks in the heat stress response is likely to lead to the systemic inflammation, multi-organ functional impairment, and other pathophysiological states characteristic of heat illness. Here, we perform an unbiased global characterization of the multi-organ gene response using an in vivo model of heat stress in the conscious rat.
Publication Title
Patterns of gene expression associated with recovery and injury in heat-stressed rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 94 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Predicting liver injury after exposure to toxic industrial chemicals is complicated by the large number of potential environmental contaminants, mixtures, and exposure dose and route scenarios. Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be fibrogenic by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male Sprague-Dawley rats dosed with varying concentrations of three fibrogenic compounds (allyl alcohol, carbon tetrachloride, and 4,4-methylenedianiline) and two non-fibrogenic compounds (bromobenzene and dexamethasone) were conducted. Fibrosis was definitively diagnosed by histopathology. Transcriptomics data matched the predictions made using the DrugMatrix data with greater than 90% accuracy. Microarray data were verified using a 67-plex panel Bioplex assay, confirming that the 67-plex panel constituted a biomolecular signature of hepatic fibrosis (Figure). Necrosis and inflammatory infiltration were comorbid with fibrosis. Interaction analysis identified 24 genes specific for the fibrosis phenotype. The protein product of the gene most strongly correlated with the fibrosis phenotype (Pcolce) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (p<0.05). PCOLCE is a novel biomarker candidate of fibrotic injury. These results support the development of gene panels for liver injury and may suggest bridging biomarkers for molecular mediators linked to histopathology.
Publication Title
Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 60 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 60 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Chlorpyrifos (CPF) is an organophosphorus pesticide (OP), and one of the most widely used pesticides in the world. Metabolites of CPF and other OPs continue to be identified in the majority of human samples, even in countries such as the United States where OP use is declining (Arcury et al., 2010). The effects of repeated occupational and environmental exposures to OPs are poorly understood, although human and animal studies consistently identify neurotoxicity as the primary endpoint of concern. Thus, occupational exposures to sublethal doses of CPF are consistently associated with problems in cognitive abilities, such as learning and memory but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of CPF neurotoxicity, we employed a rat model that simulated documented CPF exposures in Egyptian agricultural workers. We quantified mRNA expression profiles in the CA1 region of the hippocampus of adult male Long Evans (LE) rats administered CPF at 3 or 10 mg/kg/d (s.c.) for 21 days. Despite significant inhibition of cholinesterase activity by the end of the 21 d exposure period, the CPF-exposed rats displayed minimal signs of cholinergic toxicity. Distinct hippocampal mRNA and miRNA signatures were associated with CPF exposure. Toxicogenomics-based evidence identified increased expression of neuropeptide genes in the hippocampi of CPF-exposed rats, which have been shown to activate receptor-mediated signaling pathways involved in cell survival. The analysis of small non-coding RNA profiles suggested the possibility that miR132/212-mediated homeostatic regulatory pathways may also be activated by repeated exposures to CPF. These findings identify potential molecular effects that may contribute to neurobehavioral deficits.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 45 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Introduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Methods: Left renal ischemia was induced in rats by clamping renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) intraperitoneally. Animals were sacrificed at 3h, 24h or 120h post- IR and blood, urine and kidney were collected. Results: Serum creatinine (mg/dL) at 24 h IR in VPA (2.71.8) and Dex (2.31.2) was reduced (P<0.05) compared to Vehicle (3.80.5). At 3h post-IR, urine albumin (mg/ml) was higher in Vehicle (1.470.10), VPA (0.840.62) and Dex (1.040.73) compared to uninjured/untreated control (0.140.26) group. At 24h post-IR urine Lipocalin-2 (g/ml) was significantly higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to uninjured/untreated control (0.67o.29); also, Kidney Injury Molecule-1 (KIM-1; ng/ml) was significantly higher in VPA, Dex and Vehicle groups (13.7-18.7) compared uninjured/untreated control (1.71.9). KIM-1 levels were significantly (P<0.05) higher in all groups compared to uninjured/untreated control levels. Histopathology at 3h post IR demonstrated (P<0.05) reduction in ischemic injury in the renal cortex in VPA (Grade 1.6 1.5) compared to Vehicle (Grade 2.91.1) group. Inflammatory cytokines IL1 and IL6 were down-regulated in VPA and Dex groups. BCL2 was higher in VPA group. DNA microarray analysis demonstrated reduced stress response and injury, and improved recovery related gene expression in the kidneys of VPA treated animals. Conclusions: VPA administration reduced kidney IR injury and improved regeneration. KIM-1 and Lipocalin-2 appear to be promising early urine biomarkers of acute ischemic kidney injury.
Publication Title
Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Oxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability to toxic agents and carcinogenic exposures. In order to provide a basis for tissue-specific difference, we examined the tissue-specific transcriptional features of 101 oxidative stress-associated genes in 10 different tissues and organs of healthy mice under physiological conditions.
Publication Title
Tissue-Specific Profiling of Oxidative Stress-Associated Transcriptome in a Healthy Mouse Model.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 678 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
BACKGROUND: In patients with suspicious pulmonary lesions, bronchoscopy is frequently non-diagnostic. This often results in additional invasive testing, including surgical biopsy, although many patients have benign disease. We sought to validate an airway gene-expression classifier for lung cancer in patients undergoing diagnostic bronchoscopy. METHODS: Two multicenter prospective studies (AEGIS 1 and 2) enrolled 1357 current or former smokers undergoing bronchoscopy for suspected lung cancer. Bronchial epithelial cells were collected from normal appearing mucosa in the mainstem bronchus during bronchoscopy. Patients without a definitive diagnosis from bronchoscopy were followed for 12 months. A gene-expression classifier was used to assess the risk of lung cancer, and its performance was evaluated. RESULTS: A total of 298 patients from AEGIS 1 and 341 from AEGIS 2 met criteria for analysis. Bronchoscopy was non-diagnostic for cancer in 272 of 639 patients (43%; 95%CI, 39-46%). The gene expression classifier correctly identified 431 of 487 patients with cancer (89% sensitivity; 95%CI, 85-91%), and 72 of 152 patients without cancer (47% specificity; 95%CI, 40-55%). The combination of the classifier and bronchoscopy had a sensitivity of 97% (95%CI, 95-98%), which was independent of size, location, stage, and histological subtype of lung cancer. In patients with an intermediate pre-test risk (10-60%) of lung cancer, the NPV of the classifier was 91% (95%CI 75-98%). CONCLUSIONS: In patients with an intermediate risk of lung cancer and a non-diagnostic bronchoscopy, a gene-expression classification of low-risk warrants consideration of a more conservative diagnostic approach that could reduce unnecessary invasive testing in patients with benign disease.
Publication Title
A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 594 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 150 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics. Here we report the identification of 2,576 somatic mutations across approximately 1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. Additionally, 373 tumors were assayed for copy number alterations via Agilent 244A CGH arrays and 153 breast, lung, and colon samples were assayed for mRNA abundance with Affymetrix HuEx1 Exon Arrays.
Publication Title
Diverse somatic mutation patterns and pathway alterations in human cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 294 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancer, a leading cause of cancer related deaths, is a heterogeneous disease, with little consensus on molecular subclasses and their clinical relevance. We describe four molecular subtypes linked with distinct patterns of molecular alterations, disease progression and prognosis viz. a) Microsatellite Instable: hypermutated intestinal subtype tumors occurring in antrum, best overall prognosis, lower frequency of recurrence (22%), with liver metastasis in 23% of recurred cases b) Mesenchymal-like: diffuse tumors with worst prognosis, a tendency to occur at an earlier age and highest recurrence (63%) with peritoneal seeding in 64% of recurred cases, low frequency of molecular alterations c) TP53-inactive with TP53 loss, presence of focal amplifications and chromosomal instability d) TP53-active marked by EBV infection and PIK3CA mutations. The key molecular mechanisms and associated survival patterns are validated in multiple independent cohorts, to provide a consistent and unified framework for further preclinical and clinical research.
Publication Title
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.
Sample Metadata Fields
Specimen part, Subject
View Samples