Intestinal Cell News Volume 2.44 | Dec 2 2016

TOP STORY

Inhibitor of Apoptosis Protein-1 Regulates Tumor Necrosis Factor-Mediated Destruction of Intestinal Epithelial Cells

The authors investigated the roles of inhibitor of apoptosis proteins in the regulation of tumor necrosis factor-induced cell death in the intestinal epithelium of mice and intestinal organoids. [Gastroenterology] Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Protective Effects of Ginsenoside Rg1 on Intestinal Ischemia/Reperfusion Injury-Induced Oxidative Stress and Apoptosis via Activation of the Wnt/β-Catenin Pathway

Ginsenoside Rg1 (Rg1) treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation in the in vitro study. [Sci Rep] Full Article

A Polysaccharide from Lentinus edodes Inhibits Human Colon Cancer Cell Proliferation and Suppresses Tumor Growth in Athymic Nude Mice

Scientists investigated the direct antitumor activity of SLNT (a water-extracted polysaccharide from L. edodes) and its probable mechanism. They showed that SLNT significantly inhibited proliferation of HT-29 colon cancer cells and suppressed tumor growth in nude mice. [Oncotarget] Full Article

TRIM11, a Direct Target of miR-24-3p, Promotes Cell Proliferation and Inhibits Apoptosis in Colon Cancer

Researchers showed that miR-24-3p downregulation contributes to TRIM11 (tripartite motif-containing protein 11) upregulation in colon cancer (CC). They also demonstrated that TRIM11 overexpression promotes cell proliferation and colony formation and inhibits apoptosis in CC, while knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited cell proliferation and induced apoptosis. [Oncotarget] Full Article

Peroxiredoxin 2 Is Essential for Maintaining Cancer Stem Cell-Like Phenotype through Activation of Hedgehog Signaling Pathway in Colon Cancer

The authors used short-hairpin RNAs and a peroxiredoxin 2 (Prdx2)-overexpression vector to determine the effects of Prdx2. They demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon cancer stem cells. [Oncotarget] Full Article

Drosophila Sulf1 Is Required for the Termination of Intestinal Stem Cell Division during Regeneration

Scientists showed that a specific modification of heparan sulfate (HS) is critical in regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular HS endosulfatase Sulf1 results in increased ISC division during normal homeostasis, which is caused by upregulation of mitogenic signaling including the JAK/STAT, EGFR, and Hedgehog pathways. [J Cell Sci] Abstract

MICU1 May Be a Promising Intervention Target for Gut-Derived Sepsis Induced by Intra-Abdominal Hypertension

Investigators detected changes in the expression of MICU1 during the development of increased intestinal permeability in rats with intra-abdominal hypertension, and they explored the related mechanism regulating epithelial-barrier functions by knocking-down micu1 in Caco-2 cells. [Cell Death Discov] Full Article

Severe Changes in Colon Epithelium in the Mecp2-Null Mouse Model of Rett Syndrome

Patients affected by Rett presented with intestinal affections whose origin is still not known. Researchers have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice. [Mol Cell Pediatr] Full Article

INTESTINAL STEM CELL & ORGANOID RESEARCH

A SILAC-Based Method for Quantitative Proteomic Analysis of Intestinal Organoids

Scientists described how to apply a stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic approach to measure protein expression changes in intestinal organoids under different experimental conditions. They generated SILAC organoid media that allow organoids to grow and differentiate normally, and confirmed the incorporation of isotopically labelled amino acids. [Sci Rep] Full Article

Novel Therapies in Inflammatory Bowel Disease: An Evaluation of the Evidence

Many new and effective therapies are in development for inflammatory bowel diseases (IBD) and, if positive in late phase trials, are anticipated to be available within the next decade. Having a number of different agents available will allow the clinician to offer the best therapies for an individual patient. This will likely have huge implications not only for patients and clinicians, but for society as a whole. [Am J Gastroenterol Suppl] Full Article

Therapeutic Targets in Inflammatory Bowel Disease: Current and Future

In addition to a “failure of mechanism,” other reasons for drug failure may include issues with the drug itself—for example, insufficient activity, or lack of targeting, inadequate trial design or dosing, or potentially our inability to characterize patients who may be more (or less) responsive to a specific therapy. The authors summarize some of the successes and failures and evaluate therapies currently under investigation for inflammatory bowel disease. [Am J Gastroenterol Suppl] Full Article

Intestinal Stem Cell Transplantation

The authors present a brief overview of the studies that have succeeded in generating new epithelial tissues in the surface of native intestines in mice by organoid transplantation. They also discuss possible applications of this experimental approach in basic research on the intestinal epithelium as well as in regenerative medicine for various types of intestinal diseases in humans. [J Gastroenterol] Abstract

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Blueprint Medicines Announces Proof-of-Concept Data from Phase I Clinical Trial of BLU-285 in Patients with Advanced Gastrointestinal Stromal Tumors

Blueprint Medicines Corporation announced data from its ongoing Phase I clinical trial evaluating BLU-285, an investigational medicine for the treatment of patients with advanced gastrointestinal stromal tumors. These data provide proof-of-concept for BLU-285, a potent, highly selective inhibitor of D842V mutant PDGFRα and Exon 17 mutant KIT. [Press release from Blueprint Medicines Corporation discussing research presented at 28^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Munich] Press Release

Biostage Receives FDA Orphan Drug Designation for Cellspan^™ Esophageal Implant

Biostage, Inc. announced that its Cellspan^™ Esophageal Implant was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) to restore the structure and function of the esophagus subsequent to esophageal damage due to cancer, injury or congenital abnormalities. [Biostage, Inc.] Press Release

First Two Patients at SurgOne Foregut Institute Implanted in EndoStim’s LESS GERD Clinical Trial for Gastroesophageal Reflux Disease (GERD)

SurgOne Foregut Institute and EndoStim, Inc., announced that the first two patients in Englewood, CO have been implanted with the EndoStim device in the Lower Esophageal Sphincter Stimulation for GERD trial, at SurgOne Foregut Institute. The EndoStim system is a minimally-invasive implantable device designed to provide long-term reflux control by restoring normal function to the esophagus through neurostimulation. [EndoStim, Inc.] Press Release

Valeant Announces the Initiation of a Primary Care Sales Force for Xifaxan^® and Relistor^®

Valeant Pharmaceuticals International, Inc. announced that it has initiated a significant sales force expansion to focus on potential primary care physician prescribers of Xifaxan for irritable bowel syndrome with diarrhea and Relistor for opioid induced constipation. [Valeant Pharmaceuticals International, Inc.] Press Release

US Health-Reform Legislation Clears Big Hurdle

Legislation that would streamline research and development at the US National Institutes of Health and drug regulation at the Food and Drug Administration is one step closer to becoming law. The US House of Representatives approved the nearly 1,000-page bill — known as the 21st Century Cures Act — on 30 November. The Senate is expected to take up the controversial US$6.3-billion measure as early as next week. [Nature News] Editorial

Battle over US Overtime Pay Rules Leaves Many Postdocs in Limbo

Institutions struggle to respond after court blocks regulations that would have increased wages for junior researchers. Some universities are proceeding with planned salary increases for postdocs, but others have cancelled — or at least, temporarily halted — changes to researchers’ pay. The uncertainty over how the legal battle will play out is already affecting some postdocs’ career and family plans. [Nature News] Editorial

FDA Chief Pushes Back against Criticism of Stem Cell Treatment Regulations

The country’s top drug regulators pushed back on claims they move too slowly in approving new stem cell treatments and sought to temper expectations for the field’s potential to benefit patients, emphasizing the hazards and the unknowns that persist with developing such therapies. [STAT News] Editorial

Congress Poised to Pass Sweeping Biomedical Innovation Bill

Congress is poised to approve a massive piece of legislation that would provide the National Institutes of Health with $4.8 billion over the next decade for a set of research initiatives, including brain and cancer research and efforts to develop so-called precision medicine treatments that are tailored to an individual’s genetic makeup. [ScienceInsider] Editorial

Spanish Military Flies Lab Animals to Canary Islands after Airlines Refuse to Take Them on Board

Twenty-nine transgenic mice that two Spanish airlines had refused to transport hitched a ride to the Canary Islands on a military plane Friday and are now at their final destination, the University of La Laguna on Tenerife in Spain. The mice, bred in the United States, had been stranded in Madrid for two months because Iberia and Air Europa have stopped shipping laboratory animals. [ScienceInsider] Editorial

NEW Translational Opportunities in Stem Cell Research
February 27-March 1, 2017
Basel, Switzerland

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NEW Tenure-Track Position – Various Projects (University Medical Center Utrecht)

NEW Project Manager I – Clinical Trials (Fred Hutchinson Cancer Research Center)

NEW Molecular and Cellular Biology – Scientist(s) (Immunocore)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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)

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

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