Intestinal Cell News Volume 7.02 | Jan 22 2021

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    2020-22-01 | ICN 7.02


    Intestinal Cell News by STEMCELL Technologies
    Vol. 7.02 – 22 January, 2021
    TOP STORY

    A
    CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Non-Essential Modes of Oncogenic Transformation

    CRISPR/Cas9-mediated ARID1A knockout in primary TP53-/- human gastric organoids induced morphologic dysplasia, tumorigenicity and mucinous differentiation.
    [Cancer Discovery]

    Abstract


    Immunofluorescence image of adult stem cell-derived intestinal organoids.
    PUBLICATIONSRanked by the impact factor of the journal

    NTPDase8
    Protects Mice from Intestinal Inflammation by Limiting P2Y6 Receptor Activation: Identification of a New Pathway of Inflammation for the Potential Treatment of IBD

    Scientists investigated the role of nucleoside triphosphate diphosphohydrolase-8 (NTPDase8) in intestinal inflammation. Human intestinal epithelial cells expressed NTPDase8 and P2Y6 similarly as in mice.
    [Gut]

    Abstract

    Model Complexity as Determining Factor for In Vitro
    Nanosafety Studies: Effects of Silver and Titanium Dioxide Nanomaterials in Intestinal Models

    Researchers studied the cytotoxic, proinflammatory, and DNA damaging properties of polyvinylpyrrolidone‐capped silver and titanium dioxide engineered nanomaterials in four in vitro models of increasing complexity—from proliferating Caco‐2 and HT29‐MTX‐E12 monocultures to long‐term transwell triple cultures including THP‐1 macrophages to reproduce the human intestine in healthy versus inflamed‐like state.
    [Small]

    Full Article

    HAND1
    and BARX1 Act as Transcriptional and Anatomic Determinants of Malignancy in Gastrointestinal Stromal Tumor

    The authors showed that HAND1 was expressed in aggressive gastrointestinal stromal tumor, modulating KIT and core transcription factor expression and supporting proliferative cellular programs.
    [Clinical Cancer Research]

    Abstract

    Transit-Amplifying
    Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition

    Using a high-throughput approach that combined enteroid monolayers and quantitative imaging, scientists identified conditions that enriched for specific cell types as well as interactions between pathways.
    [Developmental Cell]

    Full Article

    Goblet Cell LRRC26 Regulates BK Channel Activation and Protects against Colitis in Mice

    Utilizing a mouse model in which MUC2 was fluorescently tagged, thereby allowing visualization of single goblet cells (GCs) in intact colonic crypts, the authors showed that murine colonic GCs had functional LRRC26-associated BK channels.
    [Proceedings of the National Academy of Sciences of the United States of America]

    Abstract

    AMP-Activated
    Protein Kinase-Induced β-Catenin Degradation through Parkin Phosphorylation Reverses Chemotherapy Resistance of Colon Cancer Cells

    Scientists explored the mechanism regarding AMP-activated protein kinase-mediated β-catenin degradation in chemotherapy resistance in colon cancer. β-catenin was upregulated in colon cancer tissues and cells, as it was positively correlated with the malignancy and poor prognosis, and chemotherapy resistance of colon cancer.
    [Molecular Therapy-Nucleic Acids]

    AbstractGraphical Abstract

    MicroRNA-194:
    A Novel Regulator of Glucagon-Like Peptide-1 Synthesis in Intestinal L Cells

    Researchers investigated the intracellular mechanism of glucagon-like peptide-1 (GLP-1) synthesis in L cells from the perspective of miRNA. They found that GLP-1 level was down-regulated in the plasma and ileum tissues of obese mice, while the ileac miR-194 expression was up-regulated.
    [Cell Death & Disease]

    Full Article

    Proteomics
    Analysis of Human Intestinal Organoids during Hypoxia and Reoxygenation as a Model to Study Ischemia-Reperfusion Injury

    Investigators demonstrated the use of human small intestinal organoids to model ischemia-reperfusion injury by exposing organoids to hypoxia and reoxygenation.
    [Cell Death & Disease]

    Full Article

    Enhancer
    of Zeste Homolog 2-Mediated Paired Box 8 Methylation Promotes Gastrointestinal Stromal Tumor Progression through Wnt4 Downregulation

    The authors explored whether enhancer of zeste homolog 2-mediated paired box 8 methylation affects gastrointestinal stromal tumor (GIST) development through regulation of Wnt4. A total of 50 cases of GIST tissues were collected and the human GIST cell lines were cultured.
    [Cancer Gene Therapy]

    Abstract

    Vinblastine
    Treatment Decreases the Undifferentiated Cell Contamination of Human iPS Cell-Derived Intestinal Epithelial-Like Cells

    Investigators examined whether vinblastine could remove residual undifferentiated human induced pluripotent stem cells in human induced pluripotent stem cells-derived intestinal epithelial cells (hiPSC-IECs), and attempted to generate hiPSC-IECs applicable to transplantation medicine.
    [Molecular Therapy-Methods & Clinical Development]

    AbstractGraphical Abstract

    Targeting
    the m6A-Reader Protein YTHDF1 Effectively Re-Sensitizes Cisplatin Resistant Colon Cancer Cells through Modulating the Glutaminase (GLS)-Mediated Glutamine Metabolism

    Researchers report YTHDF1 was significantly upregulated in human colon tumors and cell lines. Overexpression of YTHDF1 decreased the cisplatin sensitivity of colon cancer cells.
    [Molecular Therapy-Oncolytics]

    AbstractGraphical Abstract


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    REVIEWS

    Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium—A Review

    Scientists assessed the current literature detailing the effects of ω-3 polyunsaturated fatty acids (PUFAs) on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentanoic acid and docosahexanoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids.
    [Foods]

    Full Article

    INDUSTRY AND POLICY NEWS

    US Food and Drug Administration Accepts for Priority Review Application for Opdivo® (Nivolumab) Combined with Chemotherapy as First-Line Treatment in Metastatic Gastric Cancer, Gastroesophageal Junction Cancer and Esophageal Adenocarcinoma

    Bristol Myers Squibb announced that the FDA has accepted its supplemental Biologics License Application for Opdivo®, in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, based on results from the CheckMate-649 trial.
    [Bristol Myers Squibb]

    Press Release

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    Medical University of Gdańsk – Gdańsk, Poland


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    Karolinska Institutet – Huddinge, Sweden

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    Aichi Cancer Center – Nagoya, Japan

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    GMA Oncology – Multi-Tumor Strategy

    Daiichi Sankyo, Inc. – Basking Ridge, New Jersey, United States

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