Intestinal Cell News Volume 3.05 | Feb 10 2017

TOP STORY

Molecular Dissection of Colorectal Cancer in Pre-Clinical Models Identifies Biomarkers Predicting Sensitivity to EGFR Inhibitors

The OncoTrack consortium recruited 106 colorectal carcinoma (CRC) patients and developed a pre-clinical platform generating a compendium of drug sensitivity data totaling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumors, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumors and derived models provides a resource for advancing researchers’ understanding of CRC. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Intestinal NCoR1, a Regulator of Epithelial Cell Maturation, Controls Neonatal Hyperbilirubinemia

Investigators report that deletion of intestinal nuclear receptor corepressor 1 (NCoR1) completely diminishes hyperbilirubinemia in hUGT1 neonates because of intestinal UGT1A1 gene derepression. Transcriptomic studies and immunohistochemistry analysis demonstrate that NCoR1 plays a major role in repressing developmental maturation of the intestines. [Proc Natl Acad Sci USA] Abstract

Transcriptional Repression of miR-200 Family Members by Nanog in Colon Cancer Cells Induces Epithelial-Mesenchymal Transition

The authors found that Nanog mRNA expression level was inversely correlated with miR-200c and miR-200b expression levels in colon cancer cell lines and human colorectal cancer tissues. Forced Nanog expression in low-Nanog colon cancer cells inhibited miR-200c and miR-200b expression, and interfered Nanog expression in high-Nanog colon cancer cells promoted miR-200c and miR-200b expression. [Cancer Lett] Abstract

Intestinal Cancer Stem Cells Marked by Bmi1 or Lgr5 Expression Contribute to Tumor Propagation via Clonal Expansion

Scientists showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. At tumor initiation and during tumor propagation in the colon, the descendants of Lgr5-positive cells clonally proliferated to form clusters. [Sci Rep] Full Article

Relation between NOD2 Genotype and Changes in Innate Signaling in Crohn’s Disease on mRNA and miRNA Levels

The authors characterized the link between NOD2 genotype and inflammatory-mediated changes in innate signaling by studying transcriptional and post-transcriptional activity in response to NOD2-agonist muramyl dipeptide in monocytes from healthy controls, and Crohn’s disease patients with and without NOD2 loss-of-function polymorphisms. [Sci Rep] Full Article

Erythropoietin-Induced Cytoprotection in Intestinal Epithelial Cells Is Linked to System Xc

Investigators hypothesize that erythropoietin could be protective against cell necrosis by increasing the levels of glutathione. This was demonstrated using intestinal epithelial cells as a model system. S4-CPG and sulfasalazine pharmacologically inhibited xCT, which induced cell death. [Exp Cell Res] Abstract

Chloride Channel ClC- 2 Enhances Intestinal Epithelial Tight Junction Barrier Function via Regulation of Caveolin-1 and Caveolar Trafficking of Occludin

To study the mechanism of ClC-2-mediated tight junction (TJ) barrier function and intracellular trafficking of occludin, scientists established ClC-2 over-expressing Caco-2 cell line by full length ClC-2 ORF transfection. ClC-2 over-expression significantly enhanced TJ barrier compared to control Caco-2^pEZ cells. [Exp Cell Res] Abstract

Collagen Peptides Ameliorate Intestinal Epithelial Barrier Dysfunction in Immunostimulatory Caco-2 Cell Monolayers via Enhancing Tight Junctions

The effect of Alaska pollock skin-derived collagen and its three tryptic hydrolytic fractions, HCP, MCP and LCP on TNF-α induced barrier dysfunction was investigated in Caco-2 cell monolayers. TNF-α induced barrier dysfunction was significantly attenuated by the collagen and its peptide fractions, especially LCP, compared to TNF-α treated controls. [Food Funct] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

A Process Engineering Approach to Increase Organoid Yield

The authors discovered that populations of spheroids with a diameter greater than 75 µm and an inner mass are enriched 1.5- and 3.8-fold for pre-organoids, respectively, thus providing rational guidelines towards establishing a robust protocol for high quality intestinal organoids. [Development] Abstract

Clonal Evolution of Colorectal Cancer in IBD

The authors review the biological drivers of mutant clone selection in inflammatory bowel disease (IBD) with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and colorectal cancer. [Nat Rev Gastroenterol Hepatol] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Dr. Glenn Eisen Now Leads GIQuIC National Endoscopy Quality Registry

Glenn M. Eisen, MD, MPH, FACG, FASGE, is now the President and Chair of the Board of Directors of the GI Quality Improvement Consortium (GIQuIC), a national endoscopic registry and clinical benchmarking tool for gastroenterologists. [American College of Gastroenterology (PR Newswire Association LLC.)] Press Release

Cancer Research UK Announces Inaugural Grand Challenge Teams to Answer the Biggest Questions in Cancer

Cancer Research UK announces that four international teams are the first recipients of its global £100 million Grand Challenge competition, which aims to overcome the biggest challenges facing cancer researchers in a global effort to beat cancer sooner. [Cancer Research UK] Press Release

Senate Confirms Price to Lead HHS

Former Representative Tom Price was confirmed as secretary of the Department of Health and Human Services (HHS) by the U.S. Senate. Price now takes the helm of a $1 trillion government department that includes the National Institutes of Health, the Centers for Disease Control and Prevention, and the Food and Drug Administration. [ScienceInsider] Editorial

French Auditors Criticize €5-Billion Science Super-Campus Near Paris

France’s government auditor has taken a sharp swipe at efforts to develop a science super-campus near Paris that, by 2020, was supposed to rival the world’s top campus universities, such as the US Massachusetts Institute of Technology. [Nature News] Editorial

NEW Innovations in Cancer Research and Regenerative Medicine
September 10-17, 2017
Ho Chi Minh City, Viet Nam

Visit our events page to see a complete list of events in the community.

NEW Faculty Position – Intestinal Stem Cell Research (Duke University Division of Gastroenterology)

Postdoctoral Fellowship – Cellular Mechanisms by Which Fatty Acids Are Absorbed in the Gut (UCSF – Cardiovascular Research Institute)

Research Associate – Colorectal Cancer (University of Virginia)

Postdoctoral Research Scientist – Epithelial Homeostasis and Cancer (Medical Research Council)

Gastroenterologist(s) – General and Interventional (Temple University)

Postdoctoral Fellow – Translational Intestinal Models (Johnson & Johnson Group)

Postdoctoral Fellowship – Neuro-Immune Regulation of Mucosal Barrier Function (Linköping University)

Postdoctoral Research Fellow – Intestinal Disease (Children’s Hospital Los Angeles)

Research Fellow – Cross Talk between Immune Cells, Microbes and the Intestinal Barrier (University of Michigan Ann Arbor)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Assistant or Associate Member – Stem Cell/Gene Therapy (Fred Hutchinson Cancer Research Center)

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