Intestinal Cell News Volume 2.43 | Nov 25 2016

TOP STORY

Engineered Human Pluripotent-Stem-Cell-Derived Intestinal Tissues with a Functional Enteric Nervous System

Scientists recapitulated normal intestinal enteric nervous system development by combining human-pluripotent stem cells-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. [Nat Med] Abstract | Press Release

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack

Investigators report a rapid epithelial response that alleviates infection stress and protects enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. [Cell Host Microbe] Abstract | Graphical Abstract

Soluble IL-33 Receptor sST2 Inhibits Colorectal Cancer Malignant Growth by Modifying the Tumor Microenvironment

The authors report that the expression level of sST2, a soluble form of the IL-33 receptor, is inversely associated with the malignant growth of colorectal cancer (CRC). sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumor growth, metastasis and tumor angiogenesis, whereas its overexpression in high-metastatic cells suppresses these processes. [Nat Commun] Full Article

Melatonin Synergizes the Chemotherapeutic Effect of 5-Fluorouracil in Colon Cancer by Suppressing PI3K/AKT and NF-κB/INOS Signaling Pathway

Melatonin exerts anti-tumor activity in various cancers, but it has never been combined with 5-FU as an anti-colon cancer treatment to improve the chemotherapeutic effect of 5-FU. Researchers assessed such combinational use in colon cancer and investigated if melatonin could synergize the anti-tumor effect of 5-FU. They found that melatonin significantly enhanced the 5-FU-mediated inhibition of cell proliferation, colony formation, cell migration and invasion in colon cancer cells. [J Pineal Res] Abstract

Direct Regulation of FOXK1 by C-Jun Promotes Proliferation, Invasion and Metastasis in Gastric Cancer Cells

Scientists found that Forkhead box (FOX) K1 protein expression was higher in 8/10 fresh cancer tissues compared with that in adjacent normal tissues. FOXK1 overexpression enhanced the proliferation, migration and invasion of gastric cancer (GC) cells. Moreover, FOXK1 expression was stimulated by transforming growth factor-β1. [Cell Death Dis] Full Article

EZH2 Mediates Lidamycin-Induced Cellular Senescence through Regulating p21 Expression in Human Colon Cancer Cells

Scientists studied the role of enhancer of zeste homolog 2 (EZH2) in lidamycin (LDM)-induced senescence, as well as in the cytotoxicity of LDM in human colon cancer cells. LDM was found to be relatively more potent in inhibiting the colon cancer cells harboring high EZH2 level and induces irreversible cellular senescence at IC₅₀ dose range, as evidenced by senescence-associated β-galactosidase staining, cell cycle arrest and molecular changes of senescence regulators including p21 in HCT116 and SW620 cells. [Cell Death Dis] Full Article

An Amino Acid-Based Oral Rehydration Solution (AA-ORS) Enhanced Intestinal Epithelial Proliferation in Mice Exposed to Radiation

Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that amino acid-based oral rehydration solution increased proliferation, maturation, and differentiation and improved electrolyte and nutrient absorption in irradiated mice. A single-hit, multi-target crypt survival curve showed a significant increase in crypt progenitors in irradiated mice treated with AA-ORS for six days compared to the saline-treated group without a change in D₀. [Sci Rep] Full Article

Intestinal Tuft Cells Regulate the ATM Mediated DNA Damage Response via Dclk1 Dependent Mechanism for Crypt Restitution following Radiation Injury

Intestinal epithelial cells were isolated and purified and utilized for experimental analysis. The authors found that small intestinal crypts of Villin^Cre;Dclk1^f/f mice were hypoplastic and more apoptotic 24 hours post-total body irradiation, a time when stem cell survival is p53-independent. [Sci Rep] Full Article

Classic IL-6R Signaling Is Dispensable for Intestinal Epithelial Proliferation and Repair

Scientists tested the influence of interleukin (IL)-6 classic signaling on intestinal repair and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic cancer cell lines, primary non-malignant intestinal organoids did not respond to IL-6 classic signaling. Mice deficient in intestinal IL-6R did not display increased susceptibility to acute dextran sulfate sodium-induced colitis. [Oncogenesis] Full Article

INTESTINAL STEM CELL & ORGANOID RESEARCH

Thyroid Hormone-Induced Activation of Notch Signaling Is Required for Adult Intestinal Stem Cell Development during Xenopus laevis Metamorphosis

To study the role of Notch signaling, investigators analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch) and targets (Hairy), in the metamorphosing intestine by real-time RT-PCR and in situ hybridization or immunohistochemistry. They showed that they are up-regulated during both natural and thyroid hormone-induced metamorphosis in a tissue-specific manner. [Stem Cells] Abstract

Mesenchymal Stromal Cell Therapy for Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair. The authors review the current data on mesenchymal stromal cell therapy in IBD. [Aliment Pharmacol Ther] Abstract

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Tillotts Pharma AG Introduces the New Technology OPTICORE^™ (OPTImized COlonic RElease) for Colonic Targeting of Active Molecules for the Treatment of Any Colon Disease

Tillotts Pharma AG introduced a new advanced enteric coating for solid dosage forms. The OPTICORE™ coating technology comprises two trigger systems and an accelerator to allow targeted drug release in the large intestine to improve local and/or systemic drug bioavailability. [Press release from Tillotts Pharma AG (PR Newswire Association LLC.) discussing research presented at the 2016 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting, Denver] Press Release

RedHill Biopharma Announces YELIVA™ (ABC294640) Poster Presentation

RedHill Biopharma Ltd. announced the presentation of a poster relating to YELIVA^™ (ABC294640), the company’s proprietary, first-in-class, orally-administered sphingosine kinase-2 selective inhibitor. [Press release from RedHill Biopharma Ltd. discussing research presented at 2016 EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium, Munich] Press Release

Athenex and Lilly Enter Clinical Collaboration Agreement

Athenex, Inc. announced a new collaboration to conduct a Phase Ib study that will evaluate the safety and tolerability of oraxol, Athenex’s oral form of paclitaxel, in combination with Eli Lilly and company’s CYRAMZA^® (ramucirumab), a vascular endothelial growth factor receptor 2 antagonist, in patients with advanced gastric and esophageal cancer. [Athenex, Inc.] Press Release

CPRIT Advances Cancer Research at UT Southwestern with New Awards

UT Southwestern Medical Center researchers recently received $5.8 million in support from the Cancer Prevention and Research Institute of Texas (CPRIT). This amount also includes $2 million in recruitment grants to help UT Southwestern attract new cancer researchers. [UT Southwestern Medical Center] Press Release

UK Scientists Excited by Surprise £2-Billion Government Windfall

UK Chancellor of the Exchequer Philip Hammond has announced a large boost in funding for research and development (R&D). The government is expecting to spend an extra £4.7 billion on R&D between now and 2020–21, and the final year’s £2-billion boost will represent a rise of around 20% in total government R&D spending. [Nature News] Editorial

NgAgo Gene-Editing Controversy Escalates in Peer-Reviewed Papers

A heated dispute over gene-editing that began online is now playing out in the scientific literature. Six months ago, Chinese researchers reported that an enzyme called NgAgo could be used to edit mammalian genes – and that it might be more accurate and more versatile than the popular CRISPR-Cas9 gene-editing technique. [Nature News] Editorial

Canadian Researcher in Legal Battle to Keep Her Interviews Confidential

When Canadian graduate student Marie-Ève ​​Maillé held interviews with 93 people in 2010 about a massive wind farm being built in the Arthabaska region of Quebec, she made a promise that social scientists routinely make: that her respondents would remain anonymous, and that nobody would be able to trace quotes in her thesis back to them. [ScienceInsider] Editorial

Conservatives, Liberals Team Up against Animal Research

“Painful, bizarre, and wasteful experiments.” Buying dogs “just to cut them apart … and kill them.” These statements might sound like the rhetoric used by extreme animal rights groups, but they come from White Coat Waste—a new, unlikely coalition of fiscal conservatives and liberal activists that aims to end federal funding for research involving dogs and other animals by targeting people’s pocketbooks in addition to their heartstrings. [ScienceInsider] Editorial

NEW Challenges, Solutions and Progress in Stem Cell Medicine
February 18-21, 2017
Carlsbad, United States

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NEW Research Officer – Transcriptional and Epigenetic Regulation in Colon Cancer and Intestinal Development (Hudson Institute of Medical Research)

PhD Studentship – Self-Renewal and Differentiation in Intestinal Stem Cells (University of East Anglia)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

PhD Studentships – Cancer Research (University of Cambridge)

Academic Gastrointestinal Pathologist – Faculty Position (University of Utah)

Research Technician III IV – Gastrointestinal Cancer (Fred Hutchinson Cancer Research Center)

Portfolio Manager – Material and Recipe Manager (Nestle Institute of Health Sciences)

Postdoctoral Fellow – Molecular Infection Biology (Umeå University)

Postdoctoral Research Fellow – Intestinal Stem Cell Repair Mechanisms after Injury and Inflammation (Children’s Hospital Los Angeles)

Postdoctoral Fellow – Mucosal immunology / Neuro-immune interaction (KU Leuven)

Postdoctoral Research Fellow – Cancer Epidemiology (Fred Hutchinson Cancer Research Center)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

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