Intestinal Cell News Volume 5.23 | Jun 28 2019

TOP STORY

V211D Mutation in MEK1 Causes Resistance to MEK Inhibitors in Colon Cancer

Researchers report the emergence of the novel MEK1 V211D gatekeeper mutation in a patient with BRAF K601E colon cancer treated with the allosteric MEK inhibitor binimetinib and the anti-epidermal growth factor receptor antibody panitumumab. The MEK1 V211D mutation concurrently occurred in the same cell with BRAF K601E and led to RAF-independent activity but remained regulated by RAF. [Cancer Discov] Abstract

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R-Spondin-3 Induces Secretory, Antimicrobial Lgr5⁺ Cells in the Stomach

Investigators demonstrated that R-spondin (Rspo)3 induced differentiation of basal Lgr5⁺ cells into secretory cells that express and secrete antimicrobial factors, such as intelectin-1, into the lumen. The depletion of Lgr5⁺ cells or the knockout of Rspo3 in myofibroblasts led to hypercolonization of the gastric glands with H. pylori, including the stem cell compartment. [Nat Cell Biol] Abstract

A Stem-Cell-Derived Platform Enables Complete Cryptosporidium Development In Vitro and Genetic Tractability

Investigators describe a platform for complete life cycle development and long-term growth of Cryptosporidium parvum in vitro using “air-liquid interface” (ALI) cultures derived from intestinal epithelial stem cells. Transcriptomic profiling revealed that differentiating epithelial cells grown under ALI conditions underwent profound changes in metabolism and development that enabled completion of the parasite life cycle in vitro. [Cell Host Microbe] Abstract | Graphical Abstract

Activation of IGF1R by DARPP-32 Promotes STAT3 Signaling in Gastric Cancer Cells

Scientists utilized in vitro assays, 3D gastric gland organoid cultures, mouse models, and human tissue samples to investigate the biological and molecular impact of Mr 32000 (DARPP-32) on activation of IGF1R and STAT3 signaling and gastric tumorigenesis. DARPP-32 enhanced phosphorylation of IGF1R, a step that was critical for STAT3 phosphorylation at Y705, nuclear localization, and transcription activation. [Oncogene] Abstract

The Protein Secretion Modulator TMED9 DrivesCNIH4/TGFα/GLI Signaling Opposing TMED3-WNT-TCF to Promote Colon Cancer Metastases

Analyses in three colon cancer cell types highlighted a TMED9-dependent gene set that included CNIH4, a member of the CORNICHON family of TGFα exporters. Data indicated that TGFA and CNIH4, which displayed predictive value for disease-free survival, promoted colon cancer cell metastatic behavior, and suggested that TMED9 pro-metastatic function involved the modulation of the secretion of TGFα ligand. [Oncogene] Full Article

Long Non-Coding RNA GAS5 Inhibits Cell Migration, Invasion and Promotes Autophagy by Targeting MicroRNA-222-3p via the GAS5/PTEN Signaling Pathway in Colorectal Cancer

The authors investigated the role of long non-coding (lnc)RNA growth arrest-specific 5 (GAS5) in colorectal cancer cells via mediation of the microRNA-222-3p (miR-222-3p)/GAS5/phosphatase and tensin homolog (PTEN) signaling pathway. HCT116 and SW480 cells were collected and treated with si-lncRNA GAS5, oe-lncRNA GAS5, miR-222-3p mimic, miR-222-3p inhibitor or si-lncRNA GAS5 + miR-222-3p mimic. [Mol Ther Nucleic Acids] Abstract

Intestinal Stem Cells Acquire Premature Senescence and Senescence Associated Secretory Phenotype Concurrent with Persistent DNA Damage after Heavy Ion Radiation in Mice

Reactive oxygen species and mitochondrial superoxide were measured using fluorescent probes. Since DNA damage was linked to senescence and senescent cells acquired senescence-associated secretory phenotype, researchers stained intestinal stem cells for both senescence markers p16, p21, and p19 as well as SASP markers IL6, IL8, and VEGF. [Aging (Albany NY)] Full Article

Influences of Simulated Gastrointestinal Environment on Physicochemical Properties of Gold Nanoparticles and Their Implications on Intestinal Epithelial Permeability

Scientists investigated the influence of gastrointestinal tract fluids on the physicochemical properties of gold nanoparticals (Au NPs) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂H₂. [J Environ Sci Health C Environ Carcinog Ecotoxicol Rev] Abstract

New Lectins from Mediterranean Flora. Activity against HT29 Colon Cancer Cells

A screening of antitumoral activity on HT29 colon cancer cells, based on polypeptide characterization and specific lectin binding to HT29 cells membrane receptors, was performed in order to assess the bioactivities present in four Mediterranean plant species: Juniperus oxycedrus subsp. oxycedrus, Juniperus oxycedrus subsp. badia, Arbutus unedo and Corema album. [Int J Mol Sci] Full Article

Distinct Localization of Mature HGF from Its Precursor Form in Developing and Repairing the Stomach

Hepatocyte growth factor (HGF) promoted organoid formation similar to EGF, indicating the potential for HGF to promote the survival and growth of gastric stem cells. Phosphorylated MET and proteolytically processed two-chain HGF localizations changed during regeneration following gastric injury. [Int J Mol Sci] Full Article

(-)-Epicatechin Mitigates Radiation-Induced Intestinal Injury and Promotes Intestinal Regeneration via Suppressing Oxidative Stress

Investigators set up an injured model of “minigut” ex-vivo, which mimicked the process of intestinal regeneration in vivo. They found that (-)-epicatechin could repress oxidative stress by regulating SOD and MDA levels in serum and intestine tissue. [Free Radic Res] Abstract

Vitamin K3 (Menadione) Suppresses Epithelial-Mesenchymal-Transition and Wnt Signaling Pathway in Human Colorectal Cancer Cells

Menadione showed cytotoxicity against human colorectal cancer cells and human primary colon cancer cells but was relatively ineffective against the cells from human normal colon and human primary colon epithelial cells. [Chem Biol Interact] Abstract

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Targeting Immune Cell Circuits and Trafficking in Inflammatory Bowel Disease

The author discusses pathogenic cytokine responses of immune cells as well as immune cell trafficking as a rational basis for new translational therapies in IBD. [Nat Immunol] Abstract

Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer Chemoprevention

Investigators review data related to patents involving nobiletin (NOB) to illustrate the extensiveness of each research area and its direction of commercialization. Furthermore, they also provide suggested directions for future research to advance NOB as the next promising candidate in colorectal cancer chemoprevention. [Cancers] Full Article

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Zealand Pharma Doses First Subject in Phase I Clinical Trial with Potential Next Generation Dual-Acting Peptide Therapeutic for Short Bowel Syndrome

Zealand Pharma A/S announced the dosing of the first subject in a Phase I clinical trial to evaluate the safety and tolerability of ZP7570 as a potential first-in-class next generation treatment of short bowel syndrome. [Zealand Pharma A/S (GlobeNewswire, Inc.)] Press Release

Pfizer Receives US FDA Approval for Its Oncology Biosimilar, ZIRABEV™ (Bevacizumab-Bvzr)

Pfizer Inc. announced the FDA has approved ZIRABEV™, a biosimilar to Avastin^®, for the treatment of five types of cancer: metastatic colorectal cancer; unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma; and persistent, recurrent or metastatic cervical cancer. [Pfizer Inc.] Press Release

NORD Awards Ten New Grants in Eight Disease States for Rare Disease Research

The National Organization for Rare Disorders^® (NORD) has announced ten new grants as part of its Rare Disease Research Grant Program, which celebrates its 30^th anniversary in 2019. [The National Organization for Rare Disorders] Press Release

MU Receives $8.6 Million Federal Grant for New Biomedical Research Center

The University of Missouri (MU) announced that researchers in the College of Agriculture, Food and Natural Resources have received an $8.6 million grant from the National Institutes of Health to establish a new national research center. The Swine Somatic Cell Genome Editing Center will focus on aiding the development of biomedical treatments for human diseases such as cystic fibrosis. [The University of Missouri] Press Release

Meet Dr. Caroline Lindemans and explore her work using organoids to study intestinal repair. Read the Full Profile

More Scientists Dismissed for Undisclosed Foreign Ties, Says NIH

The US National Institutes of Health (NIH) says that universities have fired scientists and refunded grant money as a result of the agency’s efforts to enforce a requirement that grantees report foreign ties, reports Science. The agency says these actions have occurred more than has been publicly reported so far. [The Scientist] Editorial

Discrimination Drives LGBT+ Scientists to Think About Quitting

Nearly one-third of physical scientists from sexual and gender minorities in the United Kingdom have considered leaving their jobs because of their workplace climate, suggests a survey. And 18% who are lesbian, gay, bisexual, transgender or from other sexual and gender minorities (LGBT+) said they had experienced harassment, bullying or exclusionary behavior in the workplace. [Nature News] Editorial

Proposal to Close UK Mouse-Research Center Is ‘Major Threat’

Leaders and senior scientists at a national mouse-genetics center in the United Kingdom have written an open letter decrying a recommendation to close the facility’s on-site academic research unit. The closure of the MRC Harwell Institute’s Mammalian Genetics Unit – where scientists study disease using animal models – would be “a major threat to mouse genetics in the UK”, says the letter, organized by 14 senior Harwell scientists. [Nature News] Editorial

NEW Barrier Immunity
September 18, 2019
London, United Kingdom

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NEW Research Program Manager – IBS Clinical Trials (University of North Carolina at Chapel Hill)

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

Professor – Microbiomes of the Human Body (The University of South Florida)

Postdoctoral Research – Lipoproteins in IBD (University of Connecticut)

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

Principle Investigator – Gut Physiology (Nestlé Research Center)

Postdoctoral Researcher – Mucosal Immunology and Inflammation (Gilead Sciences, Inc.)

Postdoctoral Fellow – Intestinal and Pulmonary Stem Cell Biology (Stanford School of Medicine)

Postdoctoral Researcher – Intestinal Immunology (KU Leuven)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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