Intestinal Cell News Volume 4.14 | Apr 20 2018

TOP STORY

Genetic Editing of Colonic Organoids Provides a Molecularly Distinct and Orthotopic Preclinical Model of Serrated Carcinogenesis

Investigators used organoid culture combined with CRISPR/Cas9 genome engineering to sequentially introduce genetic alterations associated with serrated colorectal cancer and which regulate the stem cell niche, senescence and DNA mismatch repair. [Gut] Abstract | Press Release

(Ranked by impact factor of the journal)

STAG2 Deficiency Induces Interferon Responses via cGAS-STING Pathway and Restricts Virus Infection

Using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, scientists demonstrated that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids. [Nat Commun] Full Article

AKT as a Key Target for Growth Promoting Functions of Neutral Ceramidase in Colon Cancer Cells

Investigators demonstrated that AKT is a key target for the growth suppressing functions of ceramide. They showed that inhibition of ceramidase activates GSK3β through dephosphorylation, and thus is required for the subsequent phosphorylation and degradation of β-catenin [Oncogene] Abstract

The POU/Oct Transcription Factor Nubbin Controls the Balance of Intestinal Stem Cell Maintenance and Differentiation by Isoform-Specific Regulation

Scientists demonstrated that the nubbin (nub)-encoded protein isoforms, Nub-PB and Nub-PD, play opposite roles in the regulation of intestinal stem cell (ISC) maintenance and differentiation. Depletion of Nub-PB in progenitor cells increased ISC proliferation by derepression of escargot expression. Conversely, loss of Nub-PD reduced ISC proliferation, suggesting that this isoform is necessary for ISC maintenance, analogous to mammalian OCT4/POU5F1 functions. [Stem Cell Reports] Full Article | Press Release | Graphical Abstract

Heat Shock Factor 1 Epigenetically Stimulates Glutaminase 1-Dependent mTOR Activation to Promote Colorectal Carcinogenesis

Researchers found that heat shock factor 1 (HSF1) was increased in colorectal cancer (CRC) and had a positive correlation with shorter disease-free-survival. Knockdown of HSF1 in CRC cells attenuated their growth, while inhibiting mTOR activation and glutamine metabolism. [Mol Ther] Abstract

Dietary Fat and Fiber Interact to Uniquely Modify Global Histone Post-Translational Epigenetic Programming in a Rat Colon Cancer Progression Model

The combinatorial diet (fish oil + pectin) uniquely affected transcriptional profiles in the intestinal epithelium, e.g., upregulating lipid catabolism and beta‐oxidation associated genes. These genes were linked to activated ligand-dependent nuclear receptors associated with n‐3 polyunsaturated fatty acids and were also correlated with the mitochondrial L-carnitine shuttle and the inhibition of lipogenesis. [Int J Cancer] Abstract

Surface Engineered Lipid Nanoparticle-Mediated Site-Specific Drug Delivery System for the Treatment of Inflammatory Bowel Disease

The authors proposed development of mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting and site-specific delivery of budesonide to the inflamed tissues. The in vitro cytotoxicity studies using J774A.1 cell line revealed that Mn-NLCs were non-toxic as compared to pure drug. [Artif Cells Nanomed Biotechnol] Abstract | Graphical Abstract

Enteric Nervous System Regulation of Intestinal Stem Cell Differentiation and Epithelial Monolayer Function

Researchers investigated the role of the enteric nervous system and intestinal myofibroblasts in the maintenance of a primary intestinal epithelial barrier through regulation of monolayer permeability, cytokine production, and differentiation of intestinal stem cells. [Sci Rep] Full Article

Tea Polysaccharides Inhibit Colitis-Associated Colorectal Cancer via Interleukin-6/STAT3 Pathway

Scientists investigated the antitumor activities of tea polysaccharides (TPS) on colitis-associated cancer using the azoxymethane/dextran sulfate sodium mouse model and interleukin (IL)-6-induced colorectal cancer cell line and determined whether TPS exerted its antitumor effects through the IL-6/STAT3 pathway. [J Agric Food Chem] Abstract | Graphical Abstract

Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions

Using bioprinting, the authors generated 3D intestinal tissue composed of human primary intestinal epithelial cells and myofibroblasts with architecture and function to model the native intestine. The 3D intestinal tissue demonstrated a polarized epithelium with tight junctions and specialized epithelial cell types and expresses functional and inducible CYP450 enzymes. [iScience] Full Article

Th9 Cells: Probable Players in Ulcerative Colitis Pathogenesis

Recently, infiltration of Th9 cells, overexpression of interleukin (IL)-9, and certain genes associated with Th9 differentiation have been demonstrated in inflammatory microenvironment of ulcerative colitis. Intestinal oversecretion of IL-9 protein is likely to break down epithelial barriers and compromise tolerance to certain commensal microorganisms which leads to inflammation. [Int Rev Immunol] Abstract

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

Qu Biologics Begins Phase II Clinical Trial in Crohn’s Disease

Qu Biologics Inc. announced the receipt of a ‘No Objection Letter’ from Health Canada and the initiation of their follow-on Phase II clinical trial to study QBECO SSI for treatment of Crohn’s disease. [Qu Biologics Inc. (GlobeNewswire)] Press Release

Bioatla Announces FDA Clearance of Investigational New Drug Application for CAB-ROR2-ADC Therapeutic

BioAtla, LLC announced the FDA has cleared BioAtla’s Investigational New Drug application for BA3021, a first-in-class conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC), in patients with solid tumors. [BioAtla, LLC (PR Newswire Association LLC.)] Press Release

Learn the basics of culturing mouse intestinal organoids with an instructional video series. Watch the Video Now

Global Cancer Scheme Lets People Share Data across the World

People with cancer will soon be able to donate their medical information to a global database aimed at discovering new treatments. When the database becomes fully functional later this year, any individual with cancer will have access to a document – the “Universal Patient Consent Form” – that will allow them to make their medical and genetic data freely accessible to all cancer researchers. [New Scientist Ltd.] Editorial

Women Less Successful When Applying for Patents

Women inventors have less success than men at each step of the patent application process in the U.S., according to a study published this month in Nature Biotechnology. [The Scientist] Editorial

Dutch Universities, Journal Publishers Agree on Open-Access Deals

Despite some difficult negotiations, academic institutions in the Netherlands have been securing subscriptions that combine publishing and reading into one fee. [The Scientist] Editorial

African Scientists Call for More Control of Their Continent’s Genomic Data

Africa-based researchers issued guidelines for the ethical handling of samples for genomic studies. The voluntary rules are an effort to combat ‘helicopter’ research, in which foreign scientists take samples and data from communities and then return to their home institutions. [Nature News] Editorial

NEW 12^th Colorectal Cancer Conference
August 16-17, 2018
Melbourne, Australia

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Scholar – Colorectal Cancer (Medical University of South Carolina)

NEW Postdoctoral Position – Regulation of Immunity in Intestinal Cancer (University of Gothenburg)

NEW Research Associate – Intestinal Cell (King’s College London)

Postdoctoral Training Fellow – Intestinal Research (The Francis Crick Institute)

Postdoctoral Position – Digestive Health (University of California, Irvine)

Postdoctoral Fellowship – Intestinal Cancer (University of Gothenburg)

Postdoctoral Research Fellow – Colon Cancer (Health Sciences North Research Institute)

Postdoctoral Research Fellow – Lysosomes in Neonatal Enterocytes and Their Pathologies (Northwestern University)

Director Position – Immune Intestinal Homeostasis (Institute for Basic Science)

Postdoctoral Position – Molecular Biology/Signal Transduction/Cancer/Inflammation (Universite de Liege)

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