The STAT-ROC feasibility study
Ontology highlight
ABSTRACT:
DISEASE(S): Oesophagus,Upper Gastro-intestinal Cancer
PROVIDER: 2426916 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Statins reduce cardiovascular disease risk by lowering plasma low density lipoprotein (LDL)-cholesterol. To identify novel pathways that modulate statin response, we assessed the influence of simvastatin exposure on expression quantitative trait locus (eQTL) associations across the genome in 480 lymphoblastoid cell lines (LCLs). Cell lines were derived blood samples collected ant entry visit from participants in the Cholesterol and Pharmacogenomics (CAP) trial, who underwent a 6 week 40mg/day simvastatin trial. We identified 4590 cis-eQTLS that were independent of treatment status (FDR=1%) and six cis-eQTLS for which there was evidence of an interaction with treatment (FDR=20%). Genotypes and Phenotypes derived from these indivudals are available through dbGaP (Accession Number). eQTL results are available at: http://eqtl.uchicago.edu/cgi=bin/gbrowse/eqtl/ Dataset consists of 960 expression beadarrays (Illumina HumanRef-8v3) representing paired samples derived from 24-hour exposures of 480 lymphoblastoid cell lines (LCLs) to 2 micromolar simvastatin acid or control buffer.
2012-06-30 | E-GEOD-36868 | biostudies-arrayexpress
Project description:Statins reduce cardiovascular disease risk by lowering plasma low density lipoprotein (LDL)-cholesterol. To identify novel pathways that modulate statin response, we assessed the influence of simvastatin exposure on expression quantitative trait locus (eQTL) associations across the genome in 480 lymphoblastoid cell lines (LCLs). Cell lines were derived blood samples collected ant entry visit from participants in the Cholesterol and Pharmacogenomics (CAP) trial, who underwent a 6 week 40mg/day simvastatin trial. We identified 4590 cis-eQTLS that were independent of treatment status (FDR=1%) and six cis-eQTLS for which there was evidence of an interaction with treatment (FDR=20%). Genotypes and Phenotypes derived from these indivudals are available through dbGaP (Accession Number). eQTL results are available at: http://eqtl.uchicago.edu/cgi=bin/gbrowse/eqtl/
2012-07-01 | GSE36868 | GEO
Project description:Statin-induced gene expression differences observed in LCLs may be influenced by their transformation, and thus differ from those observed in native B-cells. To assess this possibility, we prepared LCLs and purified B-cells from the same donors, and compared mRNA profiles after 24hr incubation with simvastatin (2M-BM-5M) or sham buffer. We prepared LCLs and purified B-cells from the same donors, and compared mRNA profiles after 24hr incubation with simvastatin (2M-BM-5M) or sham buffer. Genes involved in cholesterol metabolism were similarly regulated between the two cell types under both the statin and sham treated conditions, and the statin-induced changes were significantly correlated.
2013-11-12 | E-GEOD-51444 | biostudies-arrayexpress
Project description:To compare early life exposures to see if they are associated with persistent molecular changes at the transcriptional level. Subjects were drawn from the Newcastle Pre-Term Birth Growth Study. A randomised, controlled trial to look at the effect on growth of dietary manipulation after hospital discharge.
2012-03-14 | GSE22013 | GEO
Project description:To compare early life exposures to see if they are associated with persistent molecular changes at the transcriptional level. Subjects were drawn from the Newcastle Pre-Term Birth Growth Study. A randomised, controlled trial to look at the effect on growth of dietary manipulation after hospital discharge. 23 chips with 4 conditions with factors sex and growth status (slow/rapid). Each condition has 6 replicates except for {male, rapid growth} which has 5 replicates.
2012-03-14 | E-GEOD-22013 | biostudies-arrayexpress
Project description:HMG-CoA reductase inhibitors, statins, have beneficial vascular effects beyond their cholesterol-lowering action. These pleiotropic effects include an anti-inflammatory effect on macrophages. Since macrophages play a central role in atherogenesis, we further characterized the effects on peripheral blood monocyte-macrophages (HPBM). Using Affymetrix gene chip analysis of simvastatin-treated HPBM, we found that simvastatin treatment lead to the downregulation of the expression of many proinflammatory genes including several chemokines (e.g. MCP-1, MIP-1 alpha and β, RANTES, several other CC and CXC chemokines, IL-2 receptor-β, and leukemia inhibitory factor), members of the tumor necrosis factor family (e.g. lymphotoxin beta and TRAIL), VCAM-1, ICAM-3, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for the inflammatory response: simvastatin downregulated the expression of NF-kappaB relA/p65 subunit and ets-1 transcription factor, and upregulated the expression of a novel atheroprotective transcription factor, Kruppel-like factor 2 (KLF-2). The effects of simvastatin on KLF-2 and its target genes were dependent on protein prenylation, since inhibitors of protein prenylation had a similar inhibitory effect in THP-1 derived macrophages. Additionally, by lentiviral overexpression KLF-2 we showed that the effect of simvastatin on MCP-1 and TF were dependent on KLF-2. We concluded that simvastatin had a strong anti-inflammatory effect on macrophages, which includes upregulation of the atheroprotective transcription factor KLF-2. These findings further explain the beneficial pleiotropic effects of statins on cardiovascular diseases. Experiment Overall Design: Cell culture studies. Experiment Overall Design: Human peripheral blood monocytes (HPBM) were isolated from buffy coats from healthy blood-donor volunteers (Finnish Red Cross, Helsinki, Finland) using Ficoll-Paque gradient centrifugation. None of the blood donors were on statin therapy. During isolation, monocytes from 3 individuals were pooled. Adherent cells were cultured in standard medium (20% human serum, Cambrex for differentiation into macrophages. The macrophage-phenotype at day 7 after isolation was confirmed with the typical shape of macrophages and also by macrophage-immunostaining (mAB CD68, DAKO, Denmark, dilution 1:200), where macrophages presented >95% of the cell population. The study protocol has been accepted by the Ethical Committee of the University of Kuopio. Experiment Overall Design: Simvastatin treatment. Experiment Overall Design: Simvastatin was a generous gift from Merck & Co. The inactive lactone form of simvastatin was hydrolyzed to the corresponding β-hydroxy acid. The HPBM-macrophages were treated with statin at day 7 after the isolation. 12 hours prior to statin treatment the cell growth media were changed to serum-free media. The statin-treated (10 uM simvastatin in serum-free media) cells were collected at 12 h and 24 h for Affymetrix analyses. The toxicity of simvastatin was assessed in cell culture: 5x concentration of simvastatin (50 uM) had no effect on cell viability. Experiment Overall Design: RNA isolation. Experiment Overall Design: Total RNA was isolated from the cells using Trizol reagent (Gibco BRL, USA) according to manufacturersâ?? instructions. The quality and amount of RNA was assessed by spectrophotometry (NanoDrop, USA) and by agarose gel electrophoresis. Experiment Overall Design: Microarray analyses. Experiment Overall Design: For Affymetrix analyses three separate HPBM cell isolation and simvastatin experiments were performed (HPBMs from 3 individuals at each time, total n=9). Cells were collected at 12 h and 24 h after the statin treatment. Total RNA was isolated as above. cDNAs were prepared from RNAs (5 ug of RNA) with reverse transcriptase (Superscript II primed by a poly (T) oligomer/T7 promoter). cDNAs were subsequently used as a template to make biotin-labeled cRNA with an in vitro transcription reaction. cRNAs (15 ug) were hybridized to Affymetrix HGU133 Plus 2.0 oligonucleotide arrays, which was processed and scanned according to manufacturerâ??s instructions. Each array quantifies the expression of over 47 000 transcripts (including full-length mRNA sequences and expressed sequence tags) derived from build 133 of the UniGene database (available at www.affymetrix.com). Experiment Overall Design: Microarray data analysis. Experiment Overall Design: Affymetrix GeneChip® Operating Software (GCOS) was used to generate .CEL files which were then converted into .DCP files using dChip (http://www.dchip.org) V1.3 software 28. The arrays were normalized to baseline array with median probe intensity, and gene expression data were generated calculating model-based expression values. In this study, genes were considered differentially expressed if they changed more than 1.5-fold (90% confidence bound of the fold change), absolute difference of signals was >100, at least 40% of the samples were called present in both groups and False Discovery Rate (FDR) was less than 1%. Hierarchical clustering was performed by dChip using Pearson correlation with a centroid-linkage method. Gene function analysis was performed by using the gene ontology mining tool GoSurfer incorporated in dChip program.
2008-06-13 | E-GEOD-4883 | biostudies-arrayexpress
Project description:Clinical data of patients suffering from COVID-19 have indicated that statin therapy, used to treat hypercholesterolemia, is associated with a better clinical outcome. We therefore investigated the effect of statins on SARS-CoV-2 infection in human lung cells and found that fluvastatin inhibited coronavirus infection, while other tested statins did not. Fluvastatin inhibited high and low pathogenic coronaviruses in vitro and ex vivo in a dose-dependent manner. Proteomic analyses of infected versus uninfected lung epithelial cells treated with fluvastatin, simvastatin, or rosuvastatin revealed that all tested statins modulated the cholesterol synthesis pathways without compromising the innate antiviral immune response. Strikingly, fluvastatin treatment uniquely affected the proteome of SARS CoV 2 infected cells, specifically downregulating proteins that modulate protein translation and viral replication. These results suggest that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that fluvastatin may have a moderate beneficial effect on SARS CoV-2 infection by modulating protein translation.
2021-12-07 | PXD023422 | Pride
Project description:Persistent symptoms after COVID-19 infection can affect almost half of COVID-19 survivors, leading to poor quality of life. Despite its prevalence, the pathophysiology of this phenomenon is poorly understood. We analyzed differences in gene expression between patients with and without post-COVID symptoms in hospital, at follow-up, and longitudinally. As part of the Banque Québécoise de la COVID-19 biobank, 24 adult patients who were hospitalized due to respiratory COVID-19 were enrolled. Whole blood was collected within the first 10 days in hospital and 4-12 weeks after discharge. K-medoids clustering was performed to further separate patients into clusters/endotypes for DE analysis and pathway enrichment. We found that high rates of post-COVID symptoms in hospitalized patients were associated with an inability to mount, and subsequently resolve by 4-12 weeks after discharge, a robust early response involving immune and hemostatic pathways, which was seen in two of three endotypes.
2023-08-15 | GSE222253 | GEO
Project description:The statin family of cholesterol-lowering drugs was shown to influence the risk of multiple types of cancers. However, the anti-tumor effects of statins in pancreatic cancer and their efficacy differs among the individual statins, are not currently well-defined. Thus, the aim of the present study was to identify the biological pathways affected by individual statins in human pancreatic cancer. The study was performed on human pancreatic cancer cell linesMiaPaCa-2 and PANC-1, exposed to three statins (Lovastatin, Fluvastatin and Simvastatin). mRNA-seq were performed (Sequenced with PE150, and 20M reads were generated.)
2020-04-30 | GSE149566 | GEO
Project description:The aim of our study was to assess the impact of simvastatin on the amount of cytosolic lipid droplets (LDs), which are implicated in many biological processes including proliferation, inflammation, carcinogenesis, apoptosis, necrosis or growth arrest. Human pancreatic cancer cells MiaPaCa-2 were treated with simvastatin (6 and 12 _M) for 24 hours. Changes in expression of genes related to lipid metabolism in the simvastatin-treated cells were examined by DNA microarray analysis. The treatment of the cells with simvastatin increased their intracellular content of LDs, partially due to the uptake of cholesterol and triacylglycerides from medium; but in particular, due to enhanced synthesis of triacylglycerides as proved by detection of significant overexpression of genes related to de novo synthesis of triacylglycerides and phospholipids. Further, simvastatin markedly influenced expression of genes directly affecting cell proliferation and signaling.
2013-11-21 | E-MTAB-1501 | biostudies-arrayexpress