Intestinal Cell News Volume 3.04 | Feb 3 2017

TOP STORY

Feedback Control of AHR Signaling Regulates Intestinal Immunity

Investigators showed that dysregulated expression of Cyp1a1 in mice depletes the reservoir of natural aryl hydrocarbon receptor (AHR) ligands, generating a quasi AHR-deficient state. Constitutive expression of Cyp1a1 throughout the body or restricted specifically to intestinal epithelial cells resulted in loss of AHR-dependent type 3 innate lymphoid cells and T helper 17 cells and increased susceptibility to enteric infection. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Creatine Maintains Intestinal Homeostasis and Protects against Colitis

CRISPR/Cas9-targeted (Gatm^c/c) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm^c/c mice displayed increased cell death and decreased proliferation during dextran sodium sulfate (DSS) treatment. In addition, Gatm^c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin. [Proc Natl Acad Sci USA] Abstract | Press Rlease

Similarities and Differences in the Transcriptional Control of Expression of the Mouse TSLP Gene in Skin Epidermis and Intestinal Epithelium

Scientists demonstrated that in epidermal keratinocytes, unliganded heterodimers of vitamin D receptor/retinoid X receptor (RXR)-α and retinoic acid receptor-γ/RXR-β are bound as repressing complexes to their cognate DNA-binding sequence(s) in the thymic stromal lymphopoietin (TSLP) promoter regulatory region. [Proc Natl Acad Sci USA] Abstract

Adipocytes Activate Mitochondrial Fatty Acid Oxidation and Autophagy to Promote Tumor Growth in Colon Cancer

The authors showed that adipocytes isolated from adipose tissues of colon cancer patients have an important role in modulating cellular metabolism to support tumor growth and survival. Abundant adipocytes were found in close association with invasive tumor cells in colon cancer patients. [Cell Death Dis] Full Article

miR-155-5p Positively Regulates CCL17-Induced Colon Cancer Cell Migration by Targeting RhoA

Researchers found that miR-155-5p knockdown in serum starved colon cancer cells decreased CCL17-induced cell chemotaxis. Moreover, knocking down miR-155-5p markedly decreased CCL17-provoked activation of RhoA in colon cancer cells. Bioinformatics analysis predicted two putative binding sites in the AU-rich element at the 3′ untranslated region of RhoA mRNA. [Oncotarget] Full Article

The Heparanase Inhibitor PG545 Attenuates Colon Cancer Initiation and Growth, Associating with Increased p21 Expression

The authors provide evidence that heparanase down regulates the expression of p21, a cyclin-dependent kinase inhibitor that attenuates the cell cycle. Notably, a reciprocal effect was noted for PG545, a potent heparanase inhibitor. This compound efficiently reduced cell proliferation, colony formation, and tumor xenograft growth, associating with a marked increase in p21 expression. [Neoplasia] Full Article

VSL#3 Probiotic Differently Influence IEC-6 Intestinal Epithelial Cell Status and Function

Researchers compared the in vitro effects of two multi-strain high concentration formulations both commercialized under the same brand VSL#3 but sourced from different production sites on a non-transformed small-intestinal epithelial cell line, IEC-6. The effects on cellular morphology, viability, migration, and H₂O₂-induced damage were assessed before and after the treatment with both VSL#3 formulations. [J Cell Physiol] Abstract

Translationally Controlled Tumor Protein TCTP Is Induced Early in Human Colorectal Tumors and Contributes to the Resistance of HCT116 Colon Cancer Cells to 5-FU and Oxaliplatin

Investigators studied the early increase of TCTP levels in human colorectal cancer and the regulation of TCTP expression in HCT116 colon cancer cells, in response to treatment with the anti-cancer drugs 5-fluorouracil (5-FU) and oxaliplatin. [Cell Commun Signal] Full Article

TFF3-Dependent Resistance of Human Colorectal Adenocarcinoma Cells HT-29/B6 to Apoptosis Is Mediated by miR-491-5p Regulation of lncRNA PRINS

Researchers hypothesized that trefoil factor 3 (TFF3) rescues intestinal epithelial cancer cells from tumor necrosis factor-α-induced apoptosis by involving regulatory RNA networks. In silico-based expression analysis revealed TFF3-mediated regulation of selected microRNAs as well as long non-coding RNAs, whereas miR-491-5p was identified to target the lncRNA ‘psoriasis susceptibility-related RNA gene induced by stress’ (PRINS). [Cell Death Discov] Full Article

Current and Emerging Therapeutic Targets for IBD

The author aims to provide a comprehensive overview about current and future therapeutic approaches for IBD therapy. Furthermore, potential mechanisms of action of these therapeutic approaches and their implications for clinical therapy in IBD are discussed. [Nat Rev Gastroenterol Hepatol] Abstract

Evolutionary and Ecological Forces That Shape the Bacterial Communities of the Human Gut

The authors discuss how factors lead to formation of the gut bacterial community and influence its interactions with the host. They also address how gut bacteria contribute to disease and how they could potentially be targeted to prevent and treat a variety of human ailments. [Mucosal Immunol] Abstract

Stem Cell Treatment in Crohn’s Disease

Several studies suggest that mesenchymal stem cells improve Crohn’s disease and Crohn’s fistula. In the recent years, a lot of studies of mesenchymal stem cell transplantation or local rejection with bone marrow-derived stem cells and adipose tissue-derived stem cells have been reported in the treatment of refractory Crohn’s disease and many of which are in remission. [Hum Gene Ther] Abstract

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

Astellas and Ironwood Report Positive Top-Line Results from Phase III Linaclotide Trial for Patients with Chronic Constipation Conducted in Japan

Astellas Pharma Inc. and Ironwood Pharmaceuticals, Inc. announced top-line results indicating that the Phase III clinical trial of linaclotide conducted in Japan in adults with chronic constipation met its primary endpoint. Linaclotide is approved in Japan as the first prescription treatment for adults with irritable bowel syndrome with constipation. [Astellas Pharma Inc.] Press Release

U.S. Food and Drug Administration Approves 72 mcg Dose of LINZESS^® (Linaclotide) for Adults with Chronic Idiopathic Constipation

Ironwood Pharmaceuticals, Inc. and Allergan plc announced that the U.S. Food and Drug Administration has approved a 72 mcg dose of LINZESS^® for the treatment of chronic idiopathic constipation in adult patients. [Ironwood Pharmaceuticals, Inc.] Press Release

Seattle Biotech Neovia Begins Clinical Trial for Immunotherapy Enhancing Cancer Drug

Neovia Oncology has enrolled its first patient into a Phase I clinical trial for its lead cancer drug NEV-801, a novel, multi-inhibitor drug able to enhance immunotherapy response in patients with advanced drug-resistant cancers. [Neovia Oncology] Press Release

Emmaus Life Sciences, Inc. Receives Notice of Allowance for U.S. Patent for Use of L-Glutamine in Treatment of Diverticulosis

Emmaus announced the allowance by the US Patent & Trade Office of patent application number 13/694,592 covering the use of its lead investigative product, pharmaceutical grade L-glutamine, for the treatment of diverticulosis. [Emmaus Life Sciences, Inc. (PR Newswire Association LLC.)] Press Release

The £6 Billion Man: New Top Job in U.K. Science Goes to Mark Walport

The government announced the selection of Mark Walport, currently the chief science adviser to the U.K. government, as head of UK Research and Innovation. The umbrella organization for the existing research councils will serve as the strategic command center of government research funding. [ScienceInsider] Editorial

Trump Immigration Ban Upends International Work on Disease

Efforts to combat diseases rely on networks of scientists to detect outbreaks early, understand how the diseases operate and then intervene. Researchers say that President Donald Trump’s travel ban challenges that process, putting the United States at risk. [Nature News] Editorial

NEW Epigenetic Regulation of Stem Cell Differentiation
March 1, 2017
Amsterdam, The Netherlands

NEW 19^th International AEK Cancer Congress
March 1-3, 2017
Heidelberg, Germany

NEW Intestinal Organoid In-Person Training
May 9-10, 2017
Vancouver, Canada

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

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

Postdoctoral Researcher – Organoid Technology (Hubrecht Organoid Technology)

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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