Although corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy.
Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis.
Specimen part
View SamplesWe derived a transcriptional signature of oncogenic KRAS by using the KF508 murine pancreatic ductal cell line with an inducible Lox-Stop-Lox (LSL) cassette in front of the KRASG12D oncogene to regulate transcription. This dataset allowed us to study the differential expression profile after oncogenic KRAS induction in mouse.
Master Regulators of Oncogenic KRAS Response in Pancreatic Cancer: An Integrative Network Biology Analysis.
Cell line, Treatment
View SamplesThe objectives of this study were to measure effects of an aspirin intervention on gene expression in normal colonic epithelial and stromal tissue in healthy humans and to determine whether response differed by UGT1A6*2 genotype. We also sought to characterize gene expression differences within colonic tissue microenvironments by identifying genes that were differentially expressed between epithelial and stromal tissue.
Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.
Sex, Specimen part
View SamplesTumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by non-epithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin (IL)-33 as an epithelial cell-derived regulator of stromal cell activation and mediator of intestinal polyposis. IL-33 expression was elevated in the tumors and serum of colorectal cancer patients and induced in the adenomatous polyps of ApcMin/+ mutant mice. Genetic and antibody suppression of IL-33 signaling in ApcMin/+ mice inhibited proliferation, induced apoptosis, and suppressed angiogenesis in polyps, which reduced both tumor number and size. In ApcMin/+ polyps, IL-33 expression localized to tumor epithelial cells and expression of the IL-33 receptor, IL1RL1, associated with two stromal cell types, namely subepithelial myofibroblasts (SEMFs) and mast cells, whose activation was previously associated with polyposis. In vitro IL-33 stimulation of human SEMFs induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and expression of mast cell-derived proteases and cytokines known to promote polyposis. Together, our results suggest that IL-33 is a tumor epithelial cell-derived paracrine signal that promotes polyposis through the coordinated activation of stromal cells and the formation of a reactive stroma microenvironment. Overall design: Six T-75 flasks of CCD-18Co cells were grown to 80% confluency; three were treated with rhIL-33, three were given vehicle control; cells were trypsinized and split in two--half of each flask used for sequencing and half for qPCR validation post-sequencing
IL-33 activates tumor stroma to promote intestinal polyposis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenomic enhancer profiling defines a signature of colon cancer.
Specimen part
View SamplesCancer is characterized by gene expression aberrations. Studies have largely focused on coding sequences and promoters, despite the fact that distal regulatory elements play a central role in controlling transcription patterns. Here we utilize the histone mark H3K4me1 to analyze gain and loss of enhancer activity genome wide in primary colon cancer lines relative to normal colon crypts. We identified thousands of variant enhancer loci (VELs) that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome. Furthermore, VELs are enriched in haplotype blocks containing colon cancer genetic risk variants, implicating these genomic regions in colon cancer pathogenesis. We propose that reproducible changes in the epigenome at enhancer elements drive a unique transcriptional program to promote colon carcinogenesis.
Epigenomic enhancer profiling defines a signature of colon cancer.
Specimen part
View SamplesVitamin D deficiency has been associated with increased esophageal cancer risk. Vitamin D controls many downstream regulators of cellular processes including proliferation, apoptosis, and differentiation. We evaluated the effects of vitamin D supplementation on global gene expression in patients with Barrett's esophagus.
A nonrandomized trial of vitamin D supplementation for Barrett's esophagus.
Specimen part
View SamplesWe report ileal gene expression at diagnosis in a cohort of 210 treatment-naïve patients of pediatric Crohn''s disease and 35 non-IBD controls from the RISK study. After three years of follow-up after diagnosis, 27 of the CD patients progressed to complicated disease (B2 and/or B3). We aim to test whether Transcriptional Risk Scores helps to distinguish between patient subgroups, improving the predictive power gained from Genetic Risk Scores. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents (<17 years) who presented with symptoms of IBD. Non-IBD control label corresponds to those with suspected IBD, but without inflammation and normal endoscopic findings. Biopsies were stored at -80 degrees.
Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.
No sample metadata fields
View SamplesWe used human gene expression microarray to interrogate how glutamine deprivation differentially impact gene expession in isogenic PIK3CA mutant and WT cells.
5-Fluorouracil Enhances the Antitumor Activity of the Glutaminase Inhibitor CB-839 against <i>PIK3CA</i>-Mutant Colorectal Cancers.
Specimen part, Cell line, Treatment
View SamplesGenome-wide association studies have identified a locus within the second intron of the FGFR2 gene that is consistently the most strongly associated with estrogen receptor-poisive breast cancer risk. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Previously, a systems biology approach was adopted to elucidate the regulatory networks operating in MCF-7 breast cancer cells in order to examine the role of FGFR2 in mediating risk. Here, the same approach has been employed using a number of different estrogen receptor-positive breast cancer cell lines in order to see if the previous findings are reproducible and consistent in estrogen receptor-positive disease.
Regulators of genetic risk of breast cancer identified by integrative network analysis.
Specimen part, Cell line, Treatment
View Samples