Project description:Blood from 17 patients taking enteric-coated low-dose aspirin (LDA) and with suspected bleeding from small intestine and 18 control patients taking aspirin were analyzed. Results provide insight into the risk for aspirin-induced small bowel bleeding.
Project description:Blood from 17 patients taking enteric-coated low-dose aspirin (LDA) and with suspected bleeding from small intestine and 18 control patients taking aspirin were analyzed. Results provide insight into the risk for aspirin-induced small bowel bleeding. 35 samples; 1 array per sample.
Project description:Aspirin use has been associated with reduced ovarian cancer risk. However, the underlying biological mechanisms are not fully understood We examined the association between gene expression profiles in ovarian tumors and current low and regular dose aspirin use in the 1-2 years prior to diagnosis
Project description:<p>The causal mechanisms of common diseases and their therapies have been only marginally illuminated by genetic variants identified in genome wide association studies (GWAS) utilizing single nucleotide polymorphism (SNPs). Platelet activation pathways reflecting hemostasis and thrombosis are the underlying substrate for many cardiovascular diseases and related acute events. To overcome GWAS limitations, genomic studies are needed that integrate molecular surrogates for platelet-related phenotypes assayed in cell-based models derived from individuals of known genotypes and phenotypes. In our GWAS study of native platelet aggregation phenotypes and aggregation in response to low dose aspirin in 2200 subjects (GeneSTAR, Genetic Study of Aspirin Responsiveness), important genome wide "signals" (p<5x10-8) associated with native platelet aggregation and important "signals" associated with platelet responsiveness to aspirin were identified and replicated. Although we are currently performing functional genomics studies to elucidate our most promising findings in known genes (PEAR1, MET, PIKC3G), most "signals" occurred in intergenic regions or in introns. Mechanistic interpretation is limited by uncertainty as to which gene(s) are up- or down-regulated in the presence of most SNP modifications. In this 3 phase proposal, we will (1) create pluripotent stem cells (iPS) from peripheral blood mononuclear cells, and then differentiate these stem cells into megakaryocytes (2) develop an efficient strategy to produce iPS and megakaryocytes using a novel pooling method, and (3) produce iPS and megakaryocytes from 250 subjects in GeneSTAR (European Americans and African Americans), selected based on specific hypotheses derived from GWAS signals in native and post aspirin platelet function; characterize genetic mRNA transcripts using a comprehensive Affymetrix array; measure protein expression for transcripts of interest using mass spectrometry; examine mRNA and protein expression patterns for each GWAS signal to determine the functional pathway(s) involved in native platelet phenotypes; and examine the functional genomics of variations in responsiveness to aspirin using our prior genotyped and phenotyped population. Precise information about the exact functional processes in megakaryocytes and platelets may lead to innovative and tailored approaches to risk assessment and novel therapeutic targets to prevent first and recurrent cardiovascular and related thrombotic events.</p>
Project description:Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. In WT mice, Hsp70 inducers (TRC051384, or tubastatin A) delayed thrombus formation. Remarkably, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression, higher circulating levels of activated protein C (APC) upon thrombotic stimulus and increased protection against endothelial apoptosis. Thus, Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, being especially promising in situations where there is a major bleeding hazard. Microarray analysis in peripheral blood cells includes eight patients with AF and stroke and eight AF subjects without stroke
Project description:The identification of surrogate single nucleotide polymorphism (SNP) markers that can predict responses to preoperative chemoradiotherapy (CRT) in rectal cancer patients. Genome-wide association studies in clinical populations are theoretically capable of identifying markers that are capable of tumor regression after CRT. We used Affymetrix’s SNP Array 6.0 to detail genetic polymorphism of patient’s group showing differential responsiveness to preoperative CRT and profiled SNP biomarkers.
Project description:Research shows that low-dose Aspirin prevents diseases of heart and blood vessels as well as cancer of the colon and rectum and it is also associated with risk of bleeding. In this study, they want to learn how patients regard the benefits and risks of low-dose Aspirin for the prevention of these diseases. The researchers also want to learn how patients balance these risks and benefits.
Project description:The identification of surrogate single nucleotide polymorphism (SNP) markers that can predict responses to chemotherapy could enable the efficient selection of patients for various regimens. Genome-wide association studies in clinical populations are theoretically capable of identifying markers that are capable of influencing drug responses. We used Affymetrix’s SNP Array 6.0 to detail genetic polymorphism of patient’s group showing differential responsiveness to various regimens and profiled SNP biomarkers for various regimens.
2011-12-31 | GSE26853 | GEO
Project description:Multiple nucleotide polymorphism DNA markers for the accurate evaluation of genetic variations
Project description:Whole genome gene expression and single nucleotide polymorphism microarrays were used to characterise a novel immunodeficiency disorder, Herbert's Syndrome.