Intestinal Cell News Volume 4.31 | Aug 17 2018

TOP STORY

Generation of Tumor-Reactive T Cells by Co-Culture of Peripheral Blood Lymphocytes and Tumor Organoids

Researchers demonstrated that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. They showed that these T cells can be used to assess the efficiency of killing of matched tumor organoids. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Therapeutic Ablation of Gain-of-Function Mutant p53 in Colorectal Cancer Inhibits Stat3-Mediated Tumor Growth and Invasion

Over half of colorectal cancers (CRCs) harbor TP53 missense mutations (mutp53). Investigators showed that the most common mutp53 allele R248Q exerted gain of function and created tumor dependence in mouse CRC models. [Cancer Cell] Abstract | Graphical Abstract

The Environmental Sensor AHR Protects from Inflammatory Damage by Maintaining Intestinal Stem Cell Homeostasis and Barrier Integrity

Scientists found that regeneration of intestinal epithelial cells (IECs) upon injury through infection or chemical insults was profoundly influenced by the environmental sensor aryl hydrocarbon receptor (AHR). IEC-specific deletion of Ahr resulted in failure to control C. rodentium infection due to unrestricted intestinal stem cell proliferation and impaired differentiation, culminating in malignant transformation. [Immunity] Full Article | Press Release | Graphical Abstract

Temporal Regulation of the Bacterial Metabolite Deoxycholate during Colonic Repair Is Critical for Crypt Regeneration

Altering bacterial metabolite deoxycholate (DCA) levels via antibiotic treatment enhanced prostaglandin E2 (PGE2) levels but impaired wound repair, which was rescued with DCA treatment. DCA acted via its receptor, farnesoid X receptor, to inhibit the enzyme cPLA2 required for PGE2 synthesis. Thus, colonic wound repair required temporally regulated signals from microbial metabolites to coordinate host-associated signaling cascades. [Cell Host Microbe] Abstract

Intestinal P-Glycoprotein Exports Endocannabinoids to Prevent Inflammation and Maintain Homeostasis

Scientists identified endocannabinoids as the first known endogenous substrates of the apically restricted multidrug resistance transporter P-glycoprotein (P-gp) and revealed a mechanism, which they believe is novel, for endocannabinoid secretion into the intestinal lumen. Knockdown or inhibition of P-gp reduced luminal secretion levels of N-acyl ethanolamine-type endocannabinoids, which correlated with increased neutrophil transmigration in vitro and in vivo. [J Clin Invest] Full Article | Press Release 1 | Press Release 2

PRSS8 Suppresses Colorectal Carcinogenesis and Metastasis

Investigators found that genetic deficiency of the Prss8 gene caused spontaneous colitis and an inflamed rectum at an early age and caused intestinal tumors at a late age, which were linked to increased intestinal cell proliferation and migration but decreased cell differentiation. [Oncogene] Abstract

Chronic Intestinal Inflammation in Mice Expressing Viral Flip in Epithelial Cells

Scientists analyzed the consequences of constitutive expression of HHV8-viral FLIP in intestinal epithelial cells in mice. Expression of vFlip disrupted tissue homeostasis and induces severe intestinal inflammation. [Mucosal Immunol] Abstract

Two Novel SHP-1 Agonists, SC-43 and SC-78, Are More Potent Than Regorafenib in Suppressing the In Vitro Stemness of Human Colorectal Cancer Cells

Investigators found that SC-43 and SC-78 but not regorafenib inhibited constitutive and IL-6-induced STAT3 phosphorylation in HCT-116 and HT-29 cells, respectively. Moreover, SC-43 and SC-78 were more potent than regorafenib in suppressing the stemness properties of these cells. [Cell Death Discov] Full Article

Wnt Pathway Is Involved in 5-FU Drug Resistance of Colorectal Cancer Cells

To investigate the detailed mechanism of 5-FU resistance, the authors developed a model of 5-FU-resistant cells from HCT-8 cells, a well-established colorectal cancer cell line. They found that the drug-resistant cells demonstrated high expression of TCF4 and β-catenin, indicating an upregulated Wnt pathway. [Exp Mol Med] Full Article

Cancer Stem Cells as Targets for DC-Based Immunotherapy of Colorectal Cancer

Researchers found that the detailed configuration of cancer stem cell (CSC)-like markers significantly influenced the maturation and activation of dendritic cells (DCs) after stimulation with cancer cells lysates or culture supernatants. This basic stimulatory effect was enhanced by LPS that is normally present in colorectal cancer CSCs niche. [Sci Rep] Full Article

Rhamnogalacturonan, a Chemically-Defined Polysaccharide, Improves Intestinal Barrier Function in DSS-Induced Colitis in Mice and Human Caco-2 Cells

Scientists investigated the protective and healing effects of rhamnogalacturonan isolated from Acmella oleracea (L.) R.K. Jansen leaves in an experimental model of intestinal inflammation in mice and in heterogeneous human epithelial colorectal adenocarcinoma cells. [Sci Rep] Full Article

Generation of Renewable Mouse Intestinal Epithelial Cell Monolayers and Organoids for Functional Analyses

Conditional reprogramming has enabled the development of long-lived, normal epithelial cell lines from mice and humans by in vitro culture with ROCK inhibitor on a feeder layer. The authors applied this technology to mouse small intestine to create 2D mouse intestinal epithelial monolayers from genetic mouse models for functional analysis. [BMC Cell Biol] Full Article

Dynamic Formation of Microvillus Inclusions during Enterocyte Differentiation in Munc18-2 Deficient Intestinal Organoids

Scientists discovered that the microvillus inclusion disease phenotype was correlated with the degree of enterocyte differentiation: secretory vesicles accumulated already in crypt progenitors, while differentiated enterocytes displayed an apical tubulovesicular network and enlarged lysosomes. Upon prolonged enterocyte differentiation, cytoplasmic F-Actin-positive foci were observed that further progressed into classical microvillus inclusions. [Cell Mol Gastroenterol Hepatol] Abstract | Full Article

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Organoids for Drug Discovery and Personalized Medicine

The author provides an update on current organoid technology and summarizes the application of organoids in basic research, disease modeling, drug development, personalized treatment, and regenerative medicine. [Annu Rev Pharmacol Toxicol] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.

Celltrion Begins Global Phase III Clinical Trial for Its Bevacizumab Biosimilar ‘CT-P16’

Celltrion, Inc. is set to launch global Phase III clinical trial for its bevacizumab biosimilar ‘CT-P16’ for the treatment of cancer. [Celltrion, Inc.] Press Release

RedHill Biopharma Receives Allowance for New U.S. Patent Covering RHB-104 for Crohn’s Disease and RHB-204 for NTM Infections

RedHill Biopharma Ltd. announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office for a new formulation patent, expected to be valid until at least 2029, that further expands the company’s intellectual property portfolio covering RHB-104 for Crohn’s disease and RHB-204 for pulmonary nontuberculous mycobacteria (NTM) infections. [RedHill Biopharma Ltd.] Press Release

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

Researcher at the Center of an Epic Fraud Remains an Enigma to Those Who Exposed Him

The first thing that went through Alison Avenell’s head when she heard Yoshihiro Sato had died was that it might be a trick. It was March 2017, and in the previous years, Avenell, a clinical nutritionist at the University of Aberdeen in the United Kingdom, had spent thousands of hours combing through Sato’s papers, together with three colleagues in New Zealand. They had discovered that Sato, a bone researcher at a hospital in southern Japan, had fabricated data for dozens of clinical trials published in international journals. [ScienceInsider] Editorial

Top Geneticist Loses £3.5-Million Grant in First Test of Landmark Bullying Policy

One of the world’s largest research-funding charities has revoked a £3.5-million (US$4.5-million) grant awarded to a top cancer geneticist, Nazneen Rahman, following allegations that she bullied scientists and other staff when she worked at the Institute of Cancer Research in London. [Nature News] Editorial

How Unpaywall Is Transforming Open Science

Unpaywall has become indispensable to many academics, and tie-ins with established scientific search engines could broaden its reach. On 26 July, Elsevier announced plans to integrate Unpaywall into its Scopus database searches, allowing it to deliver millions more free-to-read papers to users than it does currently. [Nature News] Editorial

Hundreds of Researchers from Harvard, Yale and Stanford Were Published in Fake Academic Journals

In the so-called “post-truth era”, science seems like one of the last bastions of objective knowledge, but what if science itself were to succumb to fake news? Over the past year, German journalist Svea Eckert and a small team of journalists went undercover to investigate a massive underground network of fake science journals and conferences. [Vice Media LLC] Editorial

NEW Cancer Stem Cells: Impact on Treatment 2018
December 11-15, 2018
Seefeld, Austria

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NEW Postdoctoral Scholar – Intestinal Research (Penn State College of Medicine)

Postdoctoral Position – Host-Microbiome Interactions in the Gastrointestinal Tract (University of Gothenburg)

Postdoctoral Associate – Functional Genomics of Inflammatory Bowel Disease (Center for Computational and Integrative Biology)

Postdoctoral Fellow – Signal Transduction of Intestinal Cells (Mornell Chemical Senses Center)

Postdoctoral Fellow – Colon Cancer (Vanderbilt University Medical Center)

Senior Research Scientist – Cancer Research (Memorial Sloan Kettering Cancer Center)

Assistant/Associate Research Professor – Inflammatory Bowel Disease (Cedars-Sinai Inflammatory Bowel & Immunobiology Research Institute)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

Postdoctoral Scholar – Molecular and Cell Biology (University of California, Berkeley)

Assistant Professor – Cancer Biology (Université de Genève)

Postdoctoral Fellow – Colorectal Cancer (Dalhousie University)

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