Intestinal Cell News Volume 4.17 | May 11 2018

TOP STORY

Cell-Specific Imd-NF-κB Responses Enable Simultaneous Antibacterial Immunity and Intestinal Epithelial Cell Shedding upon Bacterial Infection

Investigators found that in Drosophila, the Imd-NF-κB pathway controlled enterocyte shedding upon infection, via a mechanism independent of reactive oxygen species-associated apoptosis. Mechanistically, the Imd pathway synergized with JNK signaling to induce epithelial cell shedding specifically in the context of bacterial infection, requiring also the reduced expression of the transcription factor GATAe. [Immunity] Abstract | Graphical Abstract

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Activation of Intestinal Tuft Cell-Expressed Sucnr1 Triggers Type 2 Immunity in the Mouse Small Intestine

Scientists confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. [Proc Natl Acad Sci USA] Abstract

A Chemical Genetics Approach Identifies PTP4A3 as a Regulator of Colon Cancer Cell Adhesion

To interrogate the role of PTP4A3 in colorectal cancer cell migration and invasion, investigators deleted the Ptp4a3 gene from murine colorectal tumor cells. The resulting PTP4A3^−/− cells exhibited impaired colony formation, spheroid formation, migration, and adherence compared with the paired PTP4A3^fl/fl cells [FASEB J] Abstract

miR-338-3p Functions as a Tumor Suppressor in Gastric Cancer by Targeting PTP1B

Scientists found that protein-tyrosine phosphatase 1B (PTP1B) was upregulated in gastric cancer tissues and overexpression of PTP1B in vitro promoted cell migration and prevented apoptosis. [Cell Death Dis] Full Article

Tumor Suppressive Role of ARHGAP17 in Colon Cancer through Wnt/β-Catenin Signaling

Researchers found that ARHGAP17 expression was obviously lower in colon cancer specimens than in normal colonic mucosa. ARHGAP17 expression was associated with tumor stage, size and differentiation. [Cell Physiol Biochem] Full Article

Released Mitochondrial DNA following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction

Using in vitro models, hypoxia/reoxygenation (H/R) up-regulated oxidative stress, disrupted mitochondrial activity and the mitochondrial membrane potential, induced apoptosis and elevated the mtDNA levels in the supernatant of intestinal epithelial cells, and the co-culture of mtDNA with human primary dendritic cells significantly elevated TLR9-MyD88 expression and enhanced the production of inflammatory cytokines and chemokines. [Sci Rep] Full Article

Modulation of Gene Transcription and Epigenetics of Colon Carcinoma Cells by Bacterial Membrane Vesicles

The authors revealed that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of colon-carcinoma cells. The changes in gene expression correlated positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. [Sci Rep] Full Article

Phytosomal Curcumin Inhibits Tumor Growth in Colitis-Associated Colorectal Cancer

Researchers explored the therapeutic potential of novel phytosomal curcumin as well as its application in combination with 5-flurouracil in a mouse-model of colitis-associated colon-cancer. [J Cell Physiol] Abstract

Efficient Generation of Cynomolgus Monkey Induced Pluripotent Stem Cell-Derived Intestinal Organoids with Pharmacokinetic Functions

Scientists generated intestinal organoids from cynomolgus monkey induced pluripotent stem (CMiPS) cells and analyzed their pharmacokinetic functions. CMiPS cells were induced into the hindgut; then, the cells were seeded on microfabricated culture vessel plates to form spheroids. The resulting floating spheroids were differentiated into intestinal organoids in a medium containing small-molecule compounds. [Stem Cells Dev] Abstract

Walnut Phenolic Extract Inhibits Nuclear Factor KappaB Signaling in Intestinal Epithelial Cells, and Ameliorates Experimental Colitis and Colitis-Associated Colon Cancer in Mice

Walnut phenolic extract (WPE) significantly inhibited interleukin (IL)-8 and IL-1α expression in COLO205 cells. WPE attenuated both the TNF-α-induced IκB phosphorylation/degradation and NF-κB DNA binding activity. The administration of oral WPE significantly reduced the severity of colitis in both acute and chronic colitis models, including the IL-10^-/- mice. [Eur J Nutr] Abstract

Knockdown of Beclin-1 Impairs Epithelial-Mesenchymal Transition of Colon Cancer Cells

Researchers investigated the effects of beclin-1, a key molecule involved in activation of autophagy, on epithelial-to-mesenchymal transition of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of beclin-1 were used in this study. [J Cell Biochem] Abstract

NADPH Oxidases and ROS Signaling in the Gastrointestinal Tract

The authors discuss new insights of how NADPH oxidases act via reactive oxygen species (ROS) as multifaceted regulators of the intestinal barrier in homeostasis, infectious disease and intestinal inflammation. [Mucosal Immunol] Abstract

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RedHill Announces Last Patient Assessed for Primary Endpoint in RHB-104 Phase III Study for Crohn’s Disease

RedHill Biopharma Ltd. announced that the last patient enrolled in the first Phase III study with RHB-104 for Crohn’s disease has completed 26 weeks of treatment for primary endpoint evaluation. [RedHill Biopharma Ltd.] Press Release

Taiho Oncology Announces Positive Topline Results from Pivotal Phase III Trial of LONSURF^® (Trifluridine/Tipiracil) in Metastatic Gastric Cancer

Taiho Oncology, Inc. and Servier, announced that the pivotal Phase III trial evaluating LONSURF^® plus best supportive care (BSC) versus placebo plus BSC in patients with previously treated metastatic gastric cancer, met its primary endpoint of prolonged overall survival. [Taiho Oncology, Inc. (PR Newswire Association LLC.)] Press Release

Genentech Provides Update on Phase III Study of TECENTRIQ (Atezolizumab) and COTELLIC (Cobimetinib) in People with Heavily Pre-Treated Locally Advanced or Metastatic Colorectal Cancer

Genentech announced that the Phase III IMblaze370 study evaluating the combination of TECENTRIQ^® and COTELLIC^® did not meet its primary endpoint of overall survival compared to regorafenib. [Genentech] Press Release

Exelixis Provides Update on IMblaze370 Phase III Pivotal Trial of Atezolizumab and Cobimetinib in Patients with Heavily Pretreated Locally Advanced or Metastatic Colorectal Cancer

Exelixis, Inc. announced that IMblaze370, the Phase III pivotal trial of atezolizumab, an anti-PDL1 antibody discovered and developed by Genentech and cobimetinib, an Exelixis-discovered MEK inhibitor, did not meet its primary endpoint. [Exelixis, Inc.] Press Release

Dr. Sylvia Boj details the use of organoids as model systems in drug screening and personalized medicine. Watch Now

FDA Seeks Permanent Injunctions against Two Stem Cell Clinics

The FDA, in two complaints filed in federal court, is seeking permanent injunctions to stop two stem cell clinics from marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements. [U.S. Food and Drug Administration] Press Release

Hungarian Scientists Are on Edge As Country Is Poised to Force Out Top University

In early April, several days after Viktor Orbán secured his third consecutive term—and fourth overall—as Hungarian prime minister with a landslide victory for his conservative party, the pro-government paper Figyelő; published a list of more than 200 people it called “mercenaries” of George Soros, the American-Hungarian billionaire philanthropist. The list included investigative journalists and human rights advocates—and 30 academics from the Soros-founded, Budapest-based Central European University. [ScienceInsider] Editorial

Release of Three Americans by North Korea Bolsters Hopes for Academic Diplomacy

The release of three Americans by North Korea is being welcomed in the United States. Leaders of the Pyongyang University of Science and Technology in North Korea also see the move as good news, and are hoping it might ultimately lead to the end of a travel ban that has prevented its U.S. instructors from teaching classes. [ScienceInsider] Editorial

NEW Goodbye Flat Biology: In Vivo Inspired Cancer Biology and Therapy
September 9-12, 2018
Berlin, Germany

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NEW Postdoctoral Positions – Colon Stem Cells and Carcinogenesis (Johns Hopkins University School of Medicine)

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

Postdoctoral Fellowship – Inflammatory Bowel Disease (European Molecular Biology Laboratory)

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Academic Position – Cancer Research (Cedars-Sinai Medical Center)

Tenure-Track Faculty Position – Cancer Research (University of Ottawa)

PhD Student – Endocrine Cells in the Gut (Helmholtz Zentrum München)

Postdoctoral Scholar – Colorectal Cancer (Medical University of South Carolina)

Postdoctoral Training Fellow – Intestinal Research (The Francis Crick Institute)

Postdoctoral Position – Digestive Health (University of California, Irvine)

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