Genome-wide analysis of gene expression in liver after insulin receptor antagonist S961 treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Peng Yi
PROVIDER: E-GEOD-45694 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Insulin receptor antagonist S961 induces pancreatic beta cell replication. Microarray anaysis was performed in liver to find genes that may mediate beta cell replication.
2013-04-02 | GSE45694 | GEO
Project description:We have previously identified a prognostic 31-gene expression signature in locally advanced cervical cancer that is associated with tumor hypoxia and reflected by the dynamic contrast enhanced magnetic resonance (DCE-MR) image parameter ABrix. To bring the signature closer to clinical use, we here aimed to construct a classifier with key signature genes that retained an association to ABrix and separated the patients into groups with different hypoxia status and chemoradiotherapy outcome. A training cohort of 42 patients and two independent cohorts of 108 and 131 patients were included. Gene expression data were generated from tumor biopsies by two Illumina array generations (WG6, HT12), and for a subset of 74 patients, by the RT-qPCR platform. The amplitude ABrix in the Brix pharmacokinetic model was extracted from DCE-MR images of 64 patients and used as a measure of hypoxia. Different classifiers were constructed in the training cohort. By evaluating their ability to separate the patients correctly according to ABrix, a 6-gene classifier with strong correlation to ABrix was identified. In validation analyses, the classifier separated the patients into two groups with 5-years progression-free survival probabilities of 85% and 60%. Both the prognostic value and ABrix-association were confirmed in an independent cohort, and robustness across array generations and assay platforms was demonstrated. The prognostic value was independent of existing clinical markers. A robust, prognostic hypoxia classifier has been constructed, and might be used alone or combined with DCE-MR imaging to achieve an early indication of a patientâs risk of failure and allocate high risk patients to adjuvant hypoxia-targeted therapy. Total 150 patient and 2 cell line samples were analysed with Illumina WG-6, while 136 patient and 6 cell line samples were analyzied with Illumina HT-12.
2016-03-29 | E-GEOD-72723 | biostudies-arrayexpress
Project description:The present work aimed to identify reference genes for RT-qPCR studies of hypoxia in cervical cancer. From 422 candidate reference genes selected from the literature, we used Illumina array-based expression profiles to identify 182 genes not affected by hypoxia treatment in eight cervical cancer cell lines or correlated with the hypoxia-associated dynamic contrast-enhanced magnetic resonance imaging parameter ABrix in 42 patients. Among these genes, we selected nine candidates (CHCHD1, GNB2L1, IPO8, LASP1, RPL27A, RPS12, SOD1, SRSF9, TMBIM6) that were not associated with tumor volume, stage, lymph node involvement or disease progression in array data of 150 patients, for further testing by RT-qPCR. geNorm and NormFinder analyses of RT-qPCR data of 74 patients identified CHCHD1, SRSF9 and TMBIM6 as the most suitable set of reference genes, with stable expression both overall and across patient subgroups with different hypoxia status (ABrix) and clinical parameters. The suitability of the three candidates as reference genes were validated in studies of the hypoxia-induced genes DDIT3, ERO1A, and STC2. After normalizing with CHCHD1, SRSF9 and TMBIM6, the RT-qPCR data of these genes showed a significant correlation with Illumina expression (P<0.001, n=74) and ABrix (P<0.05, n=32), and the STC2 data were associated with clinical outcome, in accordance with the Illumina data. Thus, CHCHD1, SRSF9 and TMBIM6 seem to be suitable reference genes for studying hypoxia-related gene expression in cervical cancer samples by RT-qPCR. STC2 might be a useful prognostic hypoxia biomarker in cervical cancer that warrants further investigation. Totally 150 tumor samples and 12 cell line samples were analysed with Illumina WG-6 and 4 cell line samples were analysed with Illumina HT-12
2016-03-29 | E-GEOD-75034 | biostudies-arrayexpress
Project description:We aimed to investigate the transcriptional program associated with pimonidazole staining in prostate cancer. A pimonidazole gene signature was identified that showed positive correlation to Ki67 labeling index, indicating increased proliferation in pimonidazole positive tumors. A positive correlation to clinical tumor stage and presence of lymph node metastasis was also found, consistent with associations between pimonidazole staining and clinico-pathological parameters. Moreover, the gene signature was associated with high Gleason score in a validation cohort of 59 patients and showed prognostic impact independent of Gleason score and other clinical markers in a watchful waiting validation cohort of 281 patients. Our work reveals the molecular basis of an aggressive prostate cancer phenotype reflected by pimonidazole staining, and suggests that genes involved in proliferation, DNA repair and hypoxia response contribute to this phenotype. We combined pimonidazole immunohistochemistry data and expression profiles to identify transcriptional program activated in pimonidazole positive tumors. Whole-genome gene expression profiles were determined in tumor biopsies from an investigation cohort of 46 patients, where 39 patients had received pimonidazole prior to surgery. Gene ontology analysis of 1046 genes upregulated in pimonidazole positive tumors, as defined by a staining fraction above 10%, showed significant enrichment of the biologic processes cell cycle, translation and cellular response to stress. Gene set analysis based on this result identified gene expressions in proliferation, DNA repair and hypoxia response as major parts of the transcriptional program associated with pimonidazole staining. Gene expression data of four prostate cancer cell lines were used to generate hypoxia response gene sets for this analysis. A signature of the 32 most essential genes in the program was constructed and shown to be associated with prostate cancer aggressiveness in two independent validation cohorts.
2015-01-05 | E-GEOD-55935 | biostudies-arrayexpress
Project description:Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer’s disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury. Male ICR mice weighing 30–40 g were kept five per cage under a constant 12-h light/dark cycle, at room temperature (23°C). Food (Purina rodent chow) and water were available ad libitum. Each mouse was used for one experiment and for one time point only. The Ethics Committee of the Sackler Faculty of Medicine approved the experimental protocol (M-09-055), in compliance with the guidelines for animal experimentation of the National Institutes of Health (DHEW publication 85–23, revised, 1995). A minimal number of mice were used for the study and all efforts were made to minimize suffering. All experimental manipulations were conducted during the light phase of the cycle. Experimental mTBI was induced using the concussive head trauma device described previously (Milman et al. 2005; Zohar et al. 2003). Briefly, mice were lightly anesthetized (Isoflurane) and placed under the weight-drop concussive head trauma instrument. The device consists of a metal tube (inner diameter 13 mm), placed vertically over the mouse head. A metal weight (30 g) was dropped from the top of the tube (80 cm) and struck the skull at the temporal right side between the corner of the eye and the ear. A sponge supported the head, allowing some antero-posterior motion without any rotational head movement at the moment of the impact. Immediately after the injury, mice were placed back in their cages for recovery. The effect of the injury upon behavior and cognition was studied from 7 days following the trauma. Sham treated mouse groups were treated identically only the weight was not dropped. The peptide Ex-4 was obtained from Bachem (Torrance, CA). In order to obtain a constant steady-state concentration of Ex-4 in mice prior to injury; Ex-4 was delivered by use of micro-osmotic pumps (7 day infusion duration), 2 days prior to the induction of mTBI. For the Ex-4 treated animals the peptide was dissolved in an equal volume of saline and dimethyl sulfoxide (DMSO) mixture and delivered from a subcutaneously implanted ALZET Micro-osmotic pump (Model 1007D, Alzet, Cupertino, CA) at a rate of 3.5 pM/kg/min. In drug treatment control groups, saline and DMSO pumps were implanted in each animal following the same surgical procedure as used for the Ex-4 treatment animals. In all animals, pumps were placed, posterior to the scapulae. Pump implantation was performed under anesthesia (ketamine/xylazine) utilizing sterile procedures. Mini pumps were implanted 48 hours prior to the weight drop injury. The number of animals from each treatment group that went on to microarray analysis were as follows, Sham, n = 5; mTBI, n = 4; Ex-4, n = 5; Ex-4/ mTBI, n = 4. Mouse cognition was assessed using the novel object recognition paradigm. After the completion of the novel object behavioral assessment, animals were euthanized and the hippocampus dissected for total RNA isolation. Total RNA was prepared using the Qiagen RNeasy Mini Kit (Qiagen, Inc. Valencia CA) following the manufacturer's specifications. Quantity and quality of the RNA was assessed using the Agilent 2100 Bioanalyzer with RNA 6000 Nano Chips. The total RNA (500 ng) was used to generate biotin-labeled cRNA using the Illumina TotalPrep RNA Amplification Kit (Ambion; Austin, TX, cat # IL1791). In short, 500 ng of total RNA was first converted into single-stranded cDNA with reverse transcriptase using an oligo-dT primer containing the T7 RNA polymerase promoter site and then copied to produce double-stranded cDNA molecules. The double stranded cDNA was cleaned and concentrated with the supplied columns and used in an overnight in vitro transcription reaction where single-stranded RNA (cRNA) was generated and labeled by incorporation of biotin-16-UTP. This cRNA was used in the hybridization reaction. Briefly, a total of 750 ng of biotin-labeled cRNA was hybridized at 58oC for 16 hours to Illumina's SentrixMouse Ref-8, v2 Expression BeadChips (Illumina, San Diego, CA). Each BeadChip has ~24,000 well-annotated RefSeq transcripts with an approximately 30-fold redundancy. The arrays were washed, blocked and the biotin labeled cRNA was detected by staining with streptavidin-Cy3. Arrays were scanned at a resolution of 0.8 m using the Beadstation 500 X from Illumina, data was extracted from the image using Illumina BeadStudio software, v3.4.0.
2012-10-17 | E-GEOD-41345 | biostudies-arrayexpress
Project description:Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, in addition to DNA repair, genome stability is also controlled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can alter the DNA damage cell cycle checkpoints. Here, we show that hypoxia (24h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting of U2OS cells. While some of the changes reflected hypoxia-induced inhibition of cell cycle progression, flow cytometric bar-coding analysis of individual cells showed that the levels of several G2 checkpoint regulators were reduced in G2 phase cells after hypoxic exposure, in particular cyclin B1. These effects were accompanied by decreased Cyclin dependent kinase (CDK) activity in G2 phase cells after hypoxia. Furthermore, cells pre-exposed to hypoxia showed a longer G2 checkpoint arrest upon treatment with ionizing radiation. Similar results were found following other hypoxic conditions (~0.03 % O2 20h and 0.2% O2 72h). These results demonstrate that the DNA damage G2 checkpoint can be altered as a consequence of hypoxia, and we propose that such alterations may influence the genome stability of hypoxic tumors. We measured gene expression changes in U2OS cells after treatment with 0.2% hypoxia for 24 hours. The data were used in the exploration of hyopxia induced alterations in the G2 checkpoint.
2016-01-04 | E-GEOD-70530 | biostudies-arrayexpress
Project description:Analysis of effect of S-phase arrest and replication checkpoint activation on differentiating hESCs at the gene expression level. The hypothesis tested in the present study was that replication checkpoint activation prevents the exit from pluripotency in hESCs. Results provide important information of the response of hESCs to replication arrest, such as upregulation of genes involved in the TGF-beta signaling pathway, and subsequent maintenance of pluripotency marker expression. Total RNA obtained from hESCs incubated in medium without bFGF and TGF-beta supplemented with either DMSO, Aphidicolin or Aphidicolin+AZD7762 for 0, 48 and 96 hours.
2015-07-28 | E-GEOD-62062 | biostudies-arrayexpress
Project description:The liver plays a central role in metabolism and is important in maintaining homeostasis throughout the body. This study integrated transcriptomic and metabolomic data to understand how the liver responds under chronic heat stress. Chickens from a rapidly growing broiler line were heat stressed for 8 hours per day for one week and liver samples were collected at 28 days post hatch. Transcriptome analysis reveals changes in genes responsible for cell cycle regulation, DNA replication, and DNA repair along with immune function. Integrating the metabolome and transcriptome data highlighted multiple pathways affected by heat stress including glucose, amino acid, and lipid metabolism along with glutathione production and beta- oxidation.
2017-02-21 | GSE95088 | GEO
Project description:Hypoxia inducible factor 1 (HIF1) has been shown to cooperate with the androgen receptor (AR) in activation of oncogenic pathways in prostate cancer (PCa). Here we hypothesized that HIF1 also plays a role in PCa response to androgen deprivation therapy (ADT). Comparison of gene expression profiles of androgen exposed (AE) and androgen deprived (AD) CWR22 PCa xenografts identified 596 upregulated and 748 downregulated genes after ADT. Gene ontology (GO) analysis of the differentially expressed genes showed significant enrichment of the biological processes cell proliferation, cell cycle and metabolism and suggested suppression of these processes after ADT. A set of 80 hypoxia-inducible genes were identified in 22Rv1 and LNCaP cell lines treated with hypoxia and showed considerable overlap (53%) with the downregulated genes. Immunostaining of the hypoxia marker pimonidazole showed no difference between AE- and AD-tumors. Comparison of the differentially expressed genes with lists of 1115 direct AR- and 276 direct HIF1-target genes identified 138 AR- and 40 HIF1-targets that were regulated after ADT, including six shared AR- and HIF1-targets for which downregulation was confirmed with RT-PCR. Most HIF1-targets were downregulated and included in the significant biological processes and the set of hypoxia-inducible genes. The downregulation of HIF1-targets was consistent with decreased HIF1A immunostaining in AD- compared to AE-tumors (p=0.002). A decrease in HIF1A immunostaining after ADT was also demonstrated in a cohort of 35 PCa patients (p<0.001). These data suggest suppressed HIF1-signaling after ADT and a shared role of HIF1 and AR in the regressive phase of PCa after ADT. Prostate cancer xenografts were subjected to adrogen deprivation therapy and analysed with regard to changes in gene expressions. Cell culture experiments were performed to generate prostate cancer specific gene lists associated with hypoxia.
2013-10-02 | E-GEOD-42868 | biostudies-arrayexpress
Project description:miRNA analysis of breast epithelial cell line with stem cell properties before and after undergoing endothelial induced epithelial to mesenchymal transition (EMT). miRNA expression anlysis was done on breast epithelial cells before and after endothelial induced EMT. D492 is a breast epithelial cell line with stem cell properties that undergoes EMT in 3D rBM coculture with endothelial cells. Total RNA was isolated from D492 and D492M (a mesenchymal derivative) at 50% and 90% confluency in monolayer.
2015-07-02 | E-GEOD-60524 | biostudies-arrayexpress