Intestinal Cell News 4.18 May 17, 2018 | |
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TOP STORYChance Discovery Links Inflammatory Bowel Disease with Common Bacterial Gut Toxin Researchers helped establish a connection between microcin B17, a well-known toxin produced by E. coli bacteria, and inflammatory bowel disease. [Press release from the John Innes Centre discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium Scientists investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. [Cell Stem Cell] Full Article | Graphical Abstract Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection Wnt induction activated the epithelial canonical Wnt pathway, resulting in the expression of C-type lectin and lysozyme genes that enhanced host defense. [Immunity] Abstract | Graphical Abstract Targeting Tumor Cell Plasticity by Combined Inhibition of NOTCH and MAPK Signaling in Colon Cancer Scientists demonstrated that high NOTCH activity marks a distinct colon cancer cell subpopulation with low levels of WNT and MAPK activity and with a pronounced epithelial phenotype. Therapeutic targeting of MAPK signaling had limited effects on tumor growth and caused expansion of tumor cells with high NOTCH activity, whereas upon targeting NOTCH signaling, tumor cells with high MAPK activity prevailed. [J Exp Med] Abstract | Press Release PRDM1 Silences Stem Cell-Related Genes and Inhibits Proliferation of Human Colon Tumor Organoids Investigators showed that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. [Proc Natl Acad Sci USA] Abstract The authors defined a critical interleukin (IL)-36/IL-23/IL-22 cytokine network that is instrumental for antimicrobial peptide production and host defense. Using a murine model of intestinal damage and repair, they showed that IL-36γ is a potent inducer of IL-23 both in vitro and in vivo. [Proc Natl Acad Sci USA] Abstract | Press Release Researchers generated cell-specific conditional argininosuccinate lyase knockout mice in combination with genetic and chemical colitis models. They demonstrated that nitric oxide (NO) derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation. [Cell Rep] Full Article | Graphical Abstract The authors demonstrated that clinically used anti-EGFR antibodies, including cetuximab and panitumumab, induce killing of sensitive colorectal cancer cells through p73-dependent transcriptional activation of the pro-apoptotic Bcl-2 family protein PUMA. [Oncogene] Abstract To elucidate the roles of saturated fatty acids in endoplasmic reticulum (ER) stress and inflammation in intestinal epithelial cells, scientists examined myristate and palmitate. Myristate, but not palmitate, induced ER stress signaling, including activation of inositol-requiring enzyme 1 and X-box binding protein 1 signaling. [FASEB J] Abstract Investigators generated Rnf43 knock‐out mice in a C57BL/6N background using the CRISPR‐Cas9 system. Although intestinal organoids from the Rnf43 knock‐out mice did not show continuous growth compared with those from the wild‐type mice in the absence of R‐spondin, an azoxymethane/dextran sodium sulfate mouse model demonstrated that the tumors were markedly larger in the Rnf43 knock‐out mice than in the wild‐type mice. [Cell Physiol Biochem] Abstract Knockdown of lincDUSP in patient-derived colon tumor cell lines resulted in significantly decreased cell proliferation and clonogenic potential, and increased susceptibility to apoptosis. [Sci Rep] Full Article | Press Release Difructose Dianhydride Improves Intestinal Calcium Absorption, Wound Healing, and Barrier Function In vitro experiments revealed that difructose anhydride (DFA)-IV treatment improved intestinal wound-healing after lipopolysaccharide challenge in small intestinal epithelial cells. [Sci Rep] Full Article Knockdown of TP53-induced glycolysis and apoptosis regulator (TIGAR) enhanced the anticancer effects of aescin in vitro and in vivo, whereas overexpression of TIGAR or replenishing TIGAR downstream products, NADPH and ribose, attenuated aescin-induced apoptosis. [Acta Pharmacol Sin] Abstract | |
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REVIEWSCurrent Status of 3D Organoids as Pre‐Clinical Models The authors expand organoid applications to the study disease progression and drug response in different cancers. They also discuss shortcomings, limitations, and advantages of developed 3D cultures, with the rationale behind the methodology. [Stem Cells] Abstract Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
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SCIENCE NEWSSyndax Pharmaceuticals, Inc. announced updated results from multiple cohorts of the ongoing Phase II ENCORE 601 trial of entinostat in combination with KEYTRUDA®, Merck’s anti-PD-1 therapy. ENCORE 601 is a Phase Ib/II trial evaluating the efficacy and safety of entinostat in combination with pembrolizumab across multiple cohorts of PD-(L)1 treatment-naïve and pre-treated cancers, including non-small cell lung cancer, melanoma and microsatellite stable colorectal cancer. [Press release from Syndax Pharmaceuticals, Inc. discussing research to be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release | |
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INDUSTRY NEWSeFFECTOR Therapeutics, Inc. announced that it has dosed the first patient in the randomized portion of its Phase II clinical trial of eFT508, the company’s lead product candidate, in combination with avelumab, an anti-PD-L1 checkpoint inhibitor, for the treatment of microsatellite stable colorectal cancer. [eFFECTOR Therapeutics, Inc.] Press Release ABIVAX announced the completion of enrollment of its Phase IIA clinical trial ABX464-101 in 30 patients with moderate-to-severe ulcerative colitis. [ABIVAX] Press Release Roche 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. [Roche] Press Release | |
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POLICY NEWSUK’s Powerful Funding Body Takes Shape The United Kingdom’s newly minted unified funding agency has released the first outline of its strategy. The long-awaited document gives the nation’s researchers an insight into how the mega-funding agency — which will command a budget of £6 billion (US$8 billion) — will work. [Nature News] Editorial Chief Academic Officer Accused in Ongoing Research Scandal at UCL Prominent geneticist David Latchman, the chief academic and administrative officer of Birkbeck, University of London, has been accused of “recklessness” for his role in an ongoing research scandal, according to a report described by The Telegraph. [The Scientist] Editorial Europe’s Open-Access Drive Escalates As University Stand-Offs Spread Bold efforts to push academic publishing towards an open-access model are gaining steam. Negotiators from libraries and university consortia across Europe are sharing tactics on how to broker new kinds of contracts that could see more articles appear outside paywalls. [Nature News] Editorial Patient Registries to Bolster Cell- and Gene-Therapy Clinical Trial Data As the first personalized cell and gene therapies are approved from small clinical trials, researchers propose the creation of publicly accessible databases to pull together real-world results. [The Scientist] Editorial
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EVENTSNEW 6th Annual German Stem Cell Network (GSCN) Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESResearch Technologist – Stem Cell Biology (STEMCELL Technologies Inc.) Postdoctoral Fellowship – Inflammatory Bowel Disease (European Molecular Biology Laboratory) 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 Position – Digestive Health (University of California, Irvine) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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