Gene-expression analysis of Oncostatin-M (OSM) signalling in cervical squamous cell carcinomas over-expressing the Oncostatin-M receptor (OSMR)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Julien Bauer
PROVIDER: E-GEOD-27480 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:PPARδ is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle and liver. The aim of our study was to assess the effect of either the well-validated PPARδ agonist GW501516, or a novel PPARδ agonist KD3010 in mouse models of liver fibrosis. KD3010, but not GW501516, treated mice had markedly less liver injury induced by carbon tetrachloride (CCl4) injections. Deposition of extracellular matrix proteins was lower in the KD3010 group as compared to the vehicle or GW501516 treated group. Interestingly, profibrogenic CTGF was significantly induced by GW501516, but not KD3010, following CCl4 treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for three weeks. Hepatocytes were identified as targets for PPARδ agonist, and primary hepatocytes treated with KD3010 showed decreased serum starvation or CCl4-induced cell death, while GW501516 treated hepatocytes were not protected. KD3010 treatment of hepatocytes decreased reactive oxygen species (ROS) production after CCl4 exposure. In conclusion, our data demonstrate that a novel PPARδ agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis. Given the oral availability and the favorable pharmacologic profile of KD3010, ligand activation of PPARδ represents an attractive and promising target for patients with chronic liver diseases. Total RNA was extracted from primary mouse hepatocytes treated with DMSO or PPARd agonists (KD3010, GW1516)
2012-04-18 | E-GEOD-32121 | biostudies-arrayexpress
Project description:The gene expression profile of vaginal cells isolated from MRKHS patients, compared with those without MRKHS, presented alterations of developmental genes such as HOXB family, the Notch ligands JAG1 and DLL1 and MUC1, which can represent key elements in the pathogenesis of MRKHS, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract. This study included sixteen MRKHS patients, diagnosed by clinical examination, trans abdominal and pelvic ultrasonography, nuclear magnetic resonance (NMR) and/or vaginoscopy, that underwent reconstruction of neovagina in the Department of Gynecologic-Obstetrical and Urologic Sciences of Sapienza University of Rome between 2007 and 2011, and five control subjects with no known reproductive tract defects or developmental malformations. 8 patients and 5 controls were analyzed using Illumina beadarray.
2013-11-22 | E-GEOD-52609 | biostudies-arrayexpress
Project description:Analysis of the genes involved in the metastasis of head and neck squamous cell carcinoma (HNSCC). We hypothesized that there would be overexpression of certain genes in the highly metastatic USC-HN1-GFP-G1 and USC-HN1-GFP-G2 cell lines compared to the parental USC-HN1-GFP cell line. We used the USC-HN1 cell line stably transfected with H2B-GFP and developed an immortal cell line (USC-HN1-GFP), which was injected into the tongues of SCID/nude mice. The metastatic cells were collected at the LN, separated and cultured, forming an immortal USC-HN1-GFP-G1 cell line. These cells were reinjected into the tongues of mice and the USC-HN1-GFP-G2 cell line was formed by the same LN collection method. The gene expression in these three cell lines were compared using Illumina microarray chips.
2012-10-29 | E-GEOD-41893 | biostudies-arrayexpress
Project description:Background: Measurement of genome-wide DNA methylation (DNAm) has become an important avenue for investigating potentially functional changes in various pathological conditions. Illumina Infinium is a relatively inexpensive and user-friendly DNAm microarray platform used by many researchers to measure DNAm on a large scale. However it has been suggested that a subset of probes may give rise to misleading results due to issues related to probe design. To facilitate biologically significant data interpretation, we set out to enhance probe annotation of the newest HumanMethylation450 BeadChip array (with >485,000 probes covering 99% of RefSeq genes). Results: Annotation that was added or expanded on includes 1) SNPs documented in the probe target, 2) probe binding specificity, 3) CpG classification of target sites and 4) gene feature classification of target sites. Probes with documented SNPs within 10bp of the target site and especially those with documented SNPs at the target CpG, were associated with increased within-tissue variation in DNAm. An example of a probe with a SNP at the target CpG was used to demonstrate how sample genotype can confound the measurement of DNAm. 8.6% of probes were identified as non-specific, in other words, these probes map to multiple locations in silico. DNAm measured from these non-specific probes likely represents a combination of DNAm from multiple genomic sites. The expanded biological annotation demonstrated that based on DNAm, grouping probes by alternative CpG classes rather than UCSC islands provides a more distinctive classification system of CpG sites. Finally variable enrichment for tissue-specific differentially methylated probes was noted across CpG classes and gene feature groups, depending on the tissues that were compared. Conclusion: Probes containing SNPs and non-specific probes may affect the assessment of DNAm using the 450k array. Additionally CpG enrichment classes and to a lesser extent gene feature groups were associated with distinct patterns of DNAm. Thus, we recommend that confounded probes be removed from analyses and that genomic trends be considered in analyses of the Illumina HumanMethylation450 BeadChip. DNAm arrays offer a powerful approach for which thoughtful use of probe content can be utilized to better understand the biological processes affected. Bisulfite converted DNA from 4 buccal, 4 blood and 4 chorionic villus samples was hybridized to the Illumina Infinium HumanMethylation450 BeadChip array.
2013-03-04 | E-GEOD-42409 | biostudies-arrayexpress
Project description:The downstream events and target genes of p53 in senescence responses are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, a key player in mediating T cell inhibitory function, in p53-mediated cellular senescence. Overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistently, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued Foxp3 expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through p21 induction and subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression and ROS production and is necessary for p53-mediated senescence. control and treated samples (human), young passage (p3) or old passage (p7) samples (mouse)
2015-08-13 | E-GEOD-71980 | biostudies-arrayexpress
Project description:The purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response. This first comprehensive study of the molecular response to trastuzumab, pertuzumab and combination therapy in vivo highlights that there are both common and distinct downstream effects to different HER2 antibodies and that pathways may be invoked more strongly or in a different manner by a combination of agents. Some of the in vivo results for ovarian tumors differ from previous in vitro studies in breast cancer cells, emphasizing that the molecular response to anti-cancer agents involves variable and complex disease-specific interactions of signaling mechanisms. SCOV3 Ovarian cell line xenografts treated with Trastuzumab, pertuzumab or combination after 4 days
2012-05-02 | E-GEOD-31432 | biostudies-arrayexpress
Project description:This study aimed at investigating the impact of chronic ingestion of sebacic acid (SA), a 10 carbons medium-chain dicarboxylic acid, on glycemic control in a mouse model of type 2 diabetes (db/db mice). Three groups of 15 mice were fed for 6 weeks either a chow diet (Ctrl), or a chow diet supplemented with 1.5% or 15% (SA1.5% and SA15% resp.) energy from SA. Fasting glycemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results-After 42 days of supplementation, fasting glycemia and HbA1c were ~70% and ~25% lower in the SA15% group compared to other groups showing a beneficial effect of SA on hyperglycemia. During OGTT, blood glucose area under the curve (AUC) was reduced after SA15% compared to other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared to Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusions-Dietary supplementation of SA largely improves glycemic control in a mouse model of type 2 diabetes. This beneficial effect may be due (1) to a reduced hepatic glucose output resulting from transcriptional down regulation of key gluconeogenesis genes and (2) to an improved glucose induced-insulin secretion. Microarray analysis of 6-8 wk old male BKS.Cg-m+/+Leprdb/J 000642 db/db mice. 2 groups. n=15/group: 1) Control group. 2) Sebacic acid high dose group - 15% (77.6g/kg food, â??9g/kg body weight per day).
2010-10-29 | E-GEOD-21083 | biostudies-arrayexpress
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2011-04-30 | E-GEOD-24352 | biostudies-arrayexpress
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2010-10-22 | E-GEOD-24821 | biostudies-arrayexpress