Intestinal Cell News Volume 5.27 | Jul 26 2019

TOP STORY

Intra- and Inter-Cellular Rewiring of the Human Colon during Ulcerative Colitis

Researchers generated an atlas of 366,650 cells from the colon mucosa of 18 ulcerative colitis patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST₄ + enterocytes, microfold-like cells, and IL13RA₂ + IL₁₁ + inflammatory fibroblasts, which they associated with resistance to anti-TNF treatment. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Distinct CRC-Associated APC Mutations Dictate Response to Tankyrase Inhibition

Using new animal models, human cell lines, and ex vivo organoid cultures, scientists showed that Tankyrase inhibition could control WNT hyperactivation and provided long-term tumor control in vivo, but that effective responses were critically dependent on how APC was disrupted. [Cancer Discov] Abstract

MiR-135b Delivered by Gastric Tumor Exosomes Inhibits FOXO1 Expression in Endothelial Cells and Promotes Angiogenesis

Investigators found that exosome-delivered miRNA contributed greatly to angiogenesis in gastric cancer (GC). The downregulation of FOXO1 was observed in GC. After measurement of miR-135b levels, they found that miR-135b and FOXO1 were negatively correlated. [Mol Ther] Abstract

Ubiquitin Ligase TRIM65 Promotes Colorectal Cancer Metastasis by Targeting ARHGAP35 for Protein Degradation

High expression of TRIM65 is associated with colorectal cancer (CRC) metastasis and recurrence. Ectopic overexpression of TRIM65 in CRC cell lines enhanced proliferation, invasion, and migration, while knockdown of TRIM65 expression had the opposite effects. [Oncogene] Full Article

DGAT2 Partially Compensates for Lipid-Induced ER Stress in Human DGAT1-Deficient Intestinal Stem Cells

The authors showed an unexpected role for diacylglycerol acyltransferase (DGAT)2 in lipid metabolism as DGAT2 partially compensated for lipid droplet formation and lipotoxicity in DGAT1-deficient intestinal stem cells. Furthermore, they showed that (un)saturated fatty acids-induced lipotoxicity was mediated by endoplasmic reticulum stress. [J Lipid Res] Abstract

MicroRNA-95 Knockdown Inhibits Epithelial-Mesenchymal Transition and Cancer Stem Cell Phenotype in Gastric Cancer Cells through MAPK Pathway by Upregulating DUSP5

MiR-95 and DUSP5 expression was altered in a gastric cancer (GC) cell line to evaluate their respective effects on the epithelial-mesenchymal transition process, cellular processes, cancer stem cell phenotype, as well as tumor growth ability. It was further predicted in bioinformatic prediction and verified in GC tissue and cell line experiments that miR-95 was highly expressed in GC. [J Cell Physiol] Abstract

MicroRNA 32 Promotes Cell Proliferation, Migration, and Suppresses Apoptosis in Colon Cancer Cells by Targeting OTU Domain Containing 3

The experiment revealed the obvious upregulation of miR-32 in colorectal cancer tissues and six cancer cell lines, compared with normal tissues and cells. Moreover, miR-32 upregulation reduced cell apoptosis and promoted cell proliferation and migration, while its downregulation displayed opposite effects. [J Cell Biochem] Abstract

Investigating the Proteomic Profile of HT-29 Colon Cancer Cells after Lactobacillus kefiri SGL 13 Exposure Using the SWATH Method

Proteomic analysis was combined with determination of kefir characteristics in order to confirm kefir’s use as a probiotic. Therefore, a label-free strategy based on SWATH-MS was applied to investigate the proteomic profile of HT-29 cells after exposure for 24 hours to a specific strain of Lactobacillus kefiri named SGL 13. [J Am Soc Mass Spectrom] Abstract | Graphical Abastract

A More Physiological Approach to Lipid Metabolism Alterations in Cancer: CRC-Like Organoids Assessment

Investigators checked the Acyl-CoA synthetases/Stearoyl-CoA desaturase (ACSLs/SCD) axis status, its regulatory miRNAs and the effect of metformin treatment in intestinal organoids with the most common acquired mutations in a sporadic colorectal cancer (CRC) as a model for specific and personalized treatment. Despite ACSL4 expression being upregulated progressively in CRC-like organoids, metformin was able to downregulate its expression, especially in the first two stages. [PLoS One] Full Article

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Innate Immune Cell-Epithelial Crosstalk during Wound Repair

The authors focus on epithelial and innate immune cell interactions that mediate wound healing and restoration of tissue homeostasis in the skin and intestine. [J Clin Invest] Abstract

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Bayer, Bristol-Myers Squibb and Ono Pharmaceutical Enter into a Clinical Collaboration Agreement to Investigate Stivarga^® (Regorafenib) and Opdivo^® (Nivolumab) as Combination Therapy in Patients with Metastatic Colorectal Cancer

Bayer, Bristol-Myers Squibb Company and Ono Pharmaceutical Co., Ltd. announced the three companies have entered into a clinical collaboration agreement to evaluate the combination of Bayer’s kinase inhibitor Stivarga^® and Bristol-Myers Squibb’s/Ono’s anti-PD-1 immune checkpoint inhibitor, Opdivo^® in patients with micro-satellite stable metastatic colorectal cancer (mCRC), the most common form of mCRC. [Bristol-Myers Squibb Company] Press Release

Innovation Pharmaceuticals Announces License Agreement with Alfasigma S.p.A. for the Development and Commercialization of Brilacidin in Ulcerative Proctitis/Ulcerative Proctosigmoiditis

Innovation Pharmaceuticals reported that the company has executed a license agreement with Alfasigma S.p.A to develop and commercialize locally-administered Brilacidin, on a worldwide basis, for the treatment of ulcerative proctitis/ulcerative proctosigmoiditis. [Innovation Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

Stero Biotechs to Commence Phase IIa Clinical Trial of Cannabidiol-Based Formulation for Patients with Crohn’s Disease

Stero Biotechs received its second Helsinki approval to move forward with a second Phase IIa clinical trial. The trial will be a randomized, double-blind, placebo-controlled, multicenter study of ST-SDCD-01, a cannabidiol based solution in an effort to lower the steroid dosage in patients with steroid dependent Crohn’s disease. [Stereo Biotechs, Ltd. (PR Newswire, LLC.)] Press Release

Investigational Subcutaneous Formulation of Vedolizumab Meets Primary Endpoint in Achieving Clinical Remission at Week 52 in Patients with Moderately to Severely Active Crohn’s Disease

Takeda Pharmaceutical Company Limited announced top-line results from the VISIBLE 2 clinical trial evaluating the efficacy and safety of an investigational subcutaneous formulation of the gut-selective biologic vedolizumab as maintenance therapy in adult patients with moderately to severely active Crohn’s disease who achieved clinical response at week six following two doses of open-label vedolizumab intravenous therapy at weeks zero and two. [Takeda Pharmaceutical Company Limited] Press Release

Arena Pharmaceuticals Announces First Subject Dosed in CAPTIVATE Phase II Trial Evaluating Olorinab in Abdominal Pain Associated with Irritable Bowel Syndrome

Arena Pharmaceuticals, Inc. announced that the first subject has been dosed in the Phase II CAPTIVATE trial evaluating olorinab, an investigational, oral, highly-selective, full agonist of the cannabinoid type 2 receptor in development for the treatment of visceral pain associated with gastrointestinal disorders. [Arena Pharmaceuticals, Inc.] Press Release

Blueprint Medicines Announces European Medicines Agency Validation of Marketing Authorization Application for Avapritinib for the Treatment of PDGFRα D842V Mutant GIST and Fourth-Line GIST

Blueprint Medicines Corporation announced that the European Medicines Agency has validated the company’s Marketing Authorization Application for avapritinib for the treatment of adult patients with PDGFRα D842V mutant gastrointestinal stromal tumors (GIST), regardless of prior therapy, and fourth-line GIST. [Blueprint Medicines Corporation] Press Release

LONSURF^® (Trifluridine/Tipiracil) Receives Positive Opinion from CHMP in the EU for Patients with Previously Treated Metastatic Gastric Cancer

Servier and its partner Taiho Pharmaceutical Co., Ltd announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion for LONSURF as monotherapy for the treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction, who have been previously treated with at least two prior systemic treatment regimens for advanced disease. [Servier (Business Wire, Inc.)] Press Release

Mark Frey, PhD, Receives $1.7M Grant to Study How the GI Tract Repairs Itself after Injury

Chemotherapy and radiation target cancer cells but these treatments produce unwanted side effects on healthy tissue. The intestines are particularly sensitive to this toxicity. A better understanding of how intestinal tissue repairs itself in response to injury could help medicine develop ways to minimize these and other off-target effects. [Children’s Hospital Los Angeles] Press Release

Dr. James Wells presents his group’s work on hPSC-derived GI organoids and their use for studying disease. Watch Now

Former UK Science Minister Returns as Brexit Government Assembles

The prime minister shake-up sees a return to the Conservative government for Jo Johnson, the prime minister’s brother and a former minister for universities and science. Johnson, who was generally popular with scientists, is back as a minister straddling the Department for Business, Energy and Industrial Strategy — which oversees research — and the Department for Education. [Nature News] Editorial

Scientists Doing Basic Studies of Human Brain Win Longer Reprieve from Clinical Trials Reporting Rule

US scientists who challenged a new rule that would require them to register their basic studies of the human brain and behavior in a federal database of clinical trials have won another reprieve. The National Institutes of Health in Bethesda, Maryland, says it now understands why some of that kind of research won’t easily fit the format of ClinicalTrials.gov, and the agency has delayed the reporting requirements for another two years. [Science Magazine] Editorial

NEW 2019 National Cancer Research Institute Cancer Conference
November 3-5, 2019
Glasgow, United Kingdom

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

NEW Scientific Communications Coordinator (STEMCELL Technologies Inc.)

NEW Postdoctoral Fellow – Multi-Omics in Intra-Tumor Heteregenity (The Institute of Cancer Research)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Postdoctoral Researcher – Microbiome Interactions in IBD (Quadram Institute Bioscience)

Postdoctoral Fellow – Single Cell Genomics of IBD (Wellcome Sanger Institute)

Postdoctoral Fellowship – Cancer Biology (Ninewells Hospital and Medical School)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Immunometabolism of IBD (Luxembourg Institute of Health)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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