Intestinal Cell News 5.16 May 10, 2019 | |
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TOP STORYInvestigators demonstrated effective immunotherapy of colorectal cancer via systemic delivery of an immunostimulatory chemotherapeutic combination in nanoscale coordination polymer core-shell particles. Oxaliplatin and dihydroartemesinin had contrasting physicochemical properties but strong synergy in reactive oxygen species generation and anticancer activity. [Nat Commun] Full Article | |
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PUBLICATIONS(Ranked by impact factor of the journal)Researchers analyzed structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 gastric cancers. Their data demonstrated diverse models of complex SVs operative in gastric cancer, which led to high-level amplification of oncogenes. [Nat Commun] Full Article 3D Model for CAR-Mediated Cytotoxicity Using Patient-Derived Colorectal Cancer Organoids Scientists developed a platform to study CAR cell cytotoxicity against 3-dimensional patient-derived colon organoids. Luciferase-based measurement served as a quantitative read-out for target cell viability. Additionally, they set up a confocal live imaging protocol to monitor effector cell recruitment and cytolytic activity at a single organoid level. [EMBO J] Abstract | Graphical Abstract The authors identified a protein called FAM64A, which promoted STAT3 activity through modulating the DNA-binding activity of STAT3. Consequently, FAM64A also promoted Th17 differentiation and development of colitis and colitis-associated cancer. This study revealed a previously unreported function of FAM64A in the regulation of inflammation and tumorigenesis and provided a potential therapeutic target for inflammatory diseases and cancer. [Proc Natl Acad Sci USA] Abstract Posttranscriptional Regulation of Colonic Epithelial Repair by RNA Binding Protein IMP1/IGF2BP1 Scientists demonstrated that Imp1ΔIEC mice exhibit enhanced recovery following dextran sodium sulfate-mediated colonic injury. Imp1ΔIEC mice exhibited Paneth cell granule changes, increased autophagy flux, and upregulation of Atg5.) [EMBO Rep] Abstract | Graphical Abstract The authors constructed a single-cell atlas for 32,332 high-quality cells from gastric antral mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer using single-cell RNA sequencing. They then constructed a single-cell network underlying cellular and molecular characteristics of gastric epithelial cells across different lesions. [Cell Rep] Full Article | Graphical Abstract Selecting the First Chemical Molecule Inhibitor of HSP110 for Colorectal Cancer Therapy Investigators combined crystallographic studies on human HSP110 and in silico modeling to identify HSP110 inhibitors that could be used in colorectal cancer therapy. Two molecules, binding to the same cleft of HSP110 nucleotide-binding domain, were selected from a chemical library. These molecules blocked HSP110 chaperone anti-aggregation activity and HSP110 association to its client protein STAT3, thereby inhibiting STAT3 phosphorylation and colorectal cancer cell growth. [Cell Death Differ] Full Article Cancer associated fibroblasts and NFs were obtained from fresh colorectal cancer (CRC) and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. [Mol Cancer] Full Article Oct1/Pou2f1 Is Selectively Required for Colon Regeneration and Regulates Colon Malignancy To determine the effect of Oct1 loss on stem cell maintenance and malignancy, researchers deleted Oct1 in two different mouse gut stem cell compartments. Oct1 deletion preserved homeostasis in vivo and the ability to establish organoids in vitro, but blocked the ability to recover from treatment with dextran sodium sulfate, and the ability to maintain organoids after passage. [PLoS Genet] Full Article Scientists applied a kinome-wide CRISPR/Cas9 screen to systematically identify kinases that were determinants of sensitivity to a potent FGFR inhibitor AZD4547 in KatoIII cells, a gastric cancer cell line with FGFR2 amplification. In total, they identified 20 kinases, involved in ILK, SRC, and EGFR signaling pathways, as determinants that alter cell sensitivity to FGFR inhibition. [Oncogenesis] Full Article Using intestinal organoids developed from duodenal biopsies from both non-celiac (NC) and celiac (CD) patients, researchers explored the contribution of gut epithelium to CD pathogenesis and the role of microbiota-derived molecules in modulating the epithelium’s response to gluten. When compared to NC, RNA sequencing of CD organoids revealed significantly altered expression of genes associated with gut barrier, innate immune response, and stem cell functions. [Sci Rep] Full Article To investigate global DNA methylation changes, human colon carcinoma HCT116 cells, which were hypomorphic for DNA methyltransferase 1, therefore showing a lower global DNA methylation, were compared to HCT116 wildtype cells. As a model system for early embryogenesis, murine embryonic stem cells were adapted to serum-free 2i medium, leading to a significant decrease in DNA methylation. [Sci Rep] Full Article Subscribe to one of our other 19 science newsletters such as Pulmonary Cell News & ESC & iPSC News. | |
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REVIEWSTreatment With Indigo Naturalis for Inflammatory Bowel Disease and Other Immune Diseases Recently, indigo naturalis (IN) was reported to be effective for treating ulcerative colitis (UC) and psoriasis. The mechanisms of IN for UC is not clear, but aryl hydrocarbon receptor ligand, the active components of IN, can promote mucosal healing by inducing the production of interleukin-22 from type-3 innate lymphocytes. [Immunol Med] Full Article Visit our reviews page to see a complete list of reviews in the intestinal cell research field. | |
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SCIENCE NEWSProgenity to Showcase New Data Progenity, Inc. announced three upcoming poster presentations. Alongside their women’s health products, Progenity has an extensive and innovative pipeline of ingestible molecular diagnostics and therapeutic products in development for gastrointestinal disorders, such as inflammatory bowel disease and small intestinal bacterial overgrowth. [Press release from Progenity, Inc. (Business Wire, Inc.) discussing research to be presented at Digestive Disease Week®, San Diego] Press Release Ironwood Pharmaceuticals to Highlight IW-3718 and Linaclotide Data Ironwood Pharmaceuticals, Inc. announced that the company and its collaborators will present clinical data for IW-3718, and both clinical and non-clinical data for linaclotide. During an oral presentation, Michael Vaezi, MD, PhD, of Vanderbilt University will share Phase IIb data on the effect of IW-3718 on a spectrum of symptoms associated with persistent gastroesophageal reflux disease despite treatment with proton pump inhibitors. [Press release from Ironwood Pharmaceuticals, Inc. discussing research to be presented at Digestive Disease Week®, San Diego] Press Release | |
Dr. Jason Spence shares his insights on the derivation of organoids from hPSCs. Listen Now | |
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INDUSTRY NEWSPfizer Acquires Clinical-Stage Biotech Therachon Pfizer announced that it has entered into a definitive agreement to acquire all the shares of Therachon Holding AG, a privately-held clinical-stage biotechnology company focused on rare diseases, with assets in development for the treatment of achondroplasia and short bowel syndrome. [Pfizer (Business Wire, Inc.)] Press Release Zealand Pharma A/S has enrolled the first patient in a Phase III extension trial to evaluate the long-term safety and efficacy of glepaglutide treatment in patients with short bowel syndrome (SBS). Patients who have completed either of the preceding Phase II and Phase III trials for glepaglutide as treatment for SBS may be eligible to participate in the Phase III extension trial. [Zealand Pharma A/S (Globe Newswire, Inc.)] Press Release Ritter Pharmaceuticals, Inc. announced that the final patient in its first pivotal Phase III clinical trial of RP-G28 for the potential treatment of lactose intolerance, a study known as the “Liberatus” study, has completed the 30-day treatment dosing period. [Ritter Pharmaceuticals, Inc.] Press Release Abivax announced that Canada is the first country to have fully authorized its Phase IIb clinical trial design for ABX464 to treat ulcerative colitis. The first patient is expected to be enrolled in the study in Q2 2019. In addition to Canada, the clinical trial will largely be conducted in Europe. [Abivax] Press Release CStone Pharmaceuticals announce that the National Medical Products Administration recently approved the initiation of a Phase I/II clinical trial in China evaluating avapritinib, a drug candidate discovered by the company’s partner Blueprint Medicines, in patients with unresectable or metastatic gastrointestinal stromal tumors. [CStone Pharmaceuticals] Press Release Teva Pharmaceutical Industries Ltd. announced the launch of a generic version of Delzicol® delayed-release capsules, 400 mg, in the US. Mesalamine Delayed-Release Capsules are an aminosalicylate indicated for the treatment of mildly to moderately active ulcerative colitis in patients five years of age and older, and for the maintenance of remission of ulcerative colitis in adults. [Teva Pharmaceutical Industries Ltd.] Press Release Takeda Pharmaceutical Company Limited announced that the FDA has accepted for review a Biologics License Application for a subcutaneous (SC) formulation of vedolizumab for maintenance therapy in adults with moderately to severely active ulcerative colitis. Takeda proposes to make vedolizumab SC available in both pre-filled syringe and pen options. [Takeda Pharmaceutical Company Limited (Business Wire, Inc.)] Press Release The AGA Research Foundation Funds 52 Promising Research Projects The American Gastroenterological Association (AGA) is announced the 52 researchers selected to receive funding through the AGA Research Foundation Awards Program. The AGA Research Foundation will provide more than $3 million in research funding in the 2019 award year. [American Gastroenterological Association] Press Release | |
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POLICY NEWSIntolerance and Funding Concern Indian Scientists Ahead of Election A rising intolerance towards intellectuals and minority groups in India has prompted scientists there to speak out ahead of the country’s mammoth general election. More than 200 scientists have signed an open letter appealing to citizens to reject the discrimination and violence being promoted by some extremist groups. [Nature News] Editorial Brazilian Biomedical Science Faces Reproducibility Test An ambitious project to test the reproducibility of biomedical experiments by Brazilian scientists is about to get under way. The Brazilian Reproducibility Initiative was launched last year by researchers at the Federal University of Rio de Janeiro. Now, the first wave of reproducibility testing is set to begin in August, with help from more than 60 laboratories scattered over 43 Brazilian research centers. [Nature News] Editorial US Lawmakers Propose Plan to Reduce Primate Research at National Institutes of Health The US National Institutes of Health (NIH) would be required to reduce its use of non-human primates in research, under a spending bill approved on 8 May by a committee in the US House of Representatives. The bill would direct the NIH “to accelerate efforts to reduce and replace the use of nonhuman primates with alternative research models” in its laboratories. [Nature News] Editorial
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EVENTSNEW Australian Gastroenterology Week (AGW) 2019 Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Functional Genomics of IBS (Wellcome Sanger Institute) Postdoctoral Researcher – Intestinal Immunology (KU Leuven) Postdoctoral Director – mRNA Treatment for Rare Diseases (Moderna) Postdoctoral Researcher – Gastrointestinal Cancer & IBD (Case Western Reserve University) Postdoctoral Position – Functional Genomics of IBS (Wellcome Sanger Institute) Postdoctoral Position – Oesophago-Gastric Cancer Research (University of Cambridge) Postdoctoral Position – IBS and Autoimmune Disease (National Research Council of Canada) Postdoctoral Position – Animal Genomics & IBD (University of Liège) Graduate Student Position – Breast & Colorectal Cancer Research (Dalhousie University) Associate Professor – Oncology (University of California, Davis) Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute) 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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