Intestinal Cell News Volume 3.25 | Jul 7 2017

TOP STORY

Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity

Researchers explored inter-relationships between putative mouse intestinal stem cell (ISC) populations by comparative RNA-sequencing. The transcriptomes of multiple cycling ISC populations closely resembled Lgr5⁺ ISCs, the most well-defined ISC pool, but Bmi1-GFP⁺ cells were distinct and enriched for enteroendocrine markers, including Prox1. [Cell Stem Cell] Abstract | Graphical Abstract

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INTESTINAL CANCERS & DISEASES

Synergy between Prkdc and Trp53 Regulates Stem Cell Proliferation and GI-ARS after Irradiation

The authors used mouse models to explore the relative roles of DNA repair, apoptosis, and cell cycle arrest in radiation response. Ionizing radiation (IR) induced DNA double strand breaks and DNA-PK mutant Prkdc^scid/scid mice were sensitive to gastrointestinal acute radiation syndrome (GI-ARS) due to an inability to repair these breaks. IR also activated the tumor suppressor p53 to trigger apoptotic cell death within intestinal crypt cells and p53 deficient mice were resistant to apoptosis. [Cell Death Differ] Abstract

Continuous In Vitro Exposure of Intestinal Epithelial Cells to E171 Food Additive Causes Oxidative Stress, Inducing Oxidation of DNA Bases but No Endoplasmic Reticulum Stress

Investigators shed some light on the mechanisms behind the potential toxicity of E171 on epithelial intestinal cells, using two in vitro models: i) a monoculture of differentiated Caco-2 cells, and ii) a coculture of Caco-2 with HT29-MTX mucus-secreting cells. Cells were exposed to E171 and two different types of TiO₂-nanoparticles, either acutely or repeatedly. [Nanotoxicology] Abstract

RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis

Scientists showed that retinol binding protein 4 (RBP4) and STRA6 expression is associated with poor oncologic prognosis. Downregulating STRA6 or RBP4 in colon cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency. [Stem Cell Reports] Full Article

MicroRNA 375 Regulates Proliferation and Migration of Colon Cancer Cells by Suppressing the CTGF-EGFR Signaling Pathway

Investigators found that the connective tissue growth factor (CTGF) is a direct target gene of MIR375. Expression of CTGF, a ligand of epidermal growth factor receptor (EGFR), was markedly enhanced in human colorectal cancer tissues in comparison with the corresponding normal colon tissues. [Int J Cancer] Abstract

Chronic Stress and Intestinal Barrier Dysfunction: Glucocorticoid Receptor and Transcription Repressor HES1 Regulate Tight Junction Protein Claudin-1 Promoter

Researchers employed the 21-day Caco-2/BBe cell model to replicate cell differentiation along the crypt axis. HES1 siRNA treatment early in differentiation increased claudin-1 (CLDN1). In contrast, stress levels of cortisol decreased CLDN1 in late differentiation stage but not in the early stage. [Sci Rep] Full Article

Novel Gold(I) Thiolate Derivatives Synergistic with 5-Fluorouracil as Potential Selective Anticancer Agents in Colon Cancer

New gold(I) thiolate complexes were synthesized and characterized, and their physicochemical properties and anticancer activity were tested. The complexes showed high anticancer activity against Caco-2 cells, comparable to that of auranofin, and very low cytotoxic activity against enterocyte-like differentiated cells. [Inorg Chem] Abstract | Graphical Abstract

Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

Scientists investigated the anticancer effect of levistolide A (LA) in HCT116 and its isogenic p53^-/- colon cancer cells, as well as the underlying mechanisms. They showed that LA inhibited viability and caused apoptosis of both wild-type and p53^-/- HCT116 cells. [Cell Physiol Biochem] Full Article

Nicotinamide Adenine Dinucleotide Replenishment Rescues Colon Degeneration in Aged Mice

Investigators discovered the correlation between colon degeneration and altered nicotinamide adenine dinucleotide level in aged mice. Despite upregulated colonic tryptophan hydroxylases expression, serotonin release and expression of colon-predominant type IV serotonin receptor, reduced viability of interstitial cells of Cajal while enhanced aquaporins led to a less colonic motility and increased luminal dehydration in aged mice. [Signal Transduct Target Ther] Full Article

INTESTINAL STEM CELL & ORGANOID RESEARCH

Pink1 and Parkin Regulate Drosophila Intestinal Stem Cell Proliferation during Stress and Aging

Researchers investigated how alterations in mitochondrial homeostasis modulate stem cell behavior in vivo via RNA interference–mediated knockdown of factors involved in mitochondrial dynamics. Intestinal stem cell (ISC)/enteroblast (EB)-specific knockdown of the mitophagy-related genes Pink1 or Parkin suppresses the age-related loss of tissue homeostasis, despite dramatic changes in mitochondrial ultrastructure and mitochondrial damage in ISCs/EBs. [J Cell Biol] Abstract

Multifaceted Interpretation of Colon Cancer Stem Cells

The authors review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. They also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype. [Int J Mol Sci] Full Article

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

FOXFIRE Combined Analysis Results in First-Line Treatment of Metastatic Colorectal Cancer Presented

Results of the FOXFIRE Combined Analysis, a study of 1,103 patients randomized to receive either standard first-line chemotherapy for colorectal cancer that has spread to the liver, or the same chemotherapy plus a treatment procedure called selective internal radiation (SIR) therapy using SIR-Spheres^® Y-90 resin microspheres, were presented. [Press release from Sirtex Medical Limited discussing research presented at the 2017 American Society of Clinical Oncology (ASCO) meeting, Chicago] Press Release

NOXXON Announces First Patients Treated in Phase I/II Clinical Trial of NOX-A12 Combined with Keytruda^® in Metastatic Pancreatic and Colorectal Cancer

NOXXON Pharma N.V. announced that the first patients were treated in its Phase I/II clinical trial in patients with metastatic colorectal and pancreatic cancer at the National Center for Tumor Diseases in Heidelberg, Germany. [NOXXON Pharma N.V.] Press Release

Promega Intends to Seek FDA Approval for Microsatellite Instability Assay to Assist in Strategic Cancer Decisions

Promega Corporation intends to seek US FDA approval and CE-IVD marking for a commercially available Microsatellite Instability assay to assist oncologists and pathologists in determining colorectal cancer decisions. [Promega Corporation] Press Release

Fight CRC and Cancer Research Institute Award $400,000 to Support Cutting-Edge Immunotherapy Research in Colorectal Cancer

Fight Colorectal Cancer (CRC) and the Cancer Research Institute announced that they have awarded a $400,000 research grant to Cynthia L. Sears, M.D., professor of medicine, oncology and molecular microbiology and immunology at Johns Hopkins University School of Medicine. Dr. Sears was awarded the grant for her project, “Gut microbiome and the immune microenvironment of human primary and metastatic colorectal cancer.” [Cancer Research Institute] Press Release

Trump Administration Chooses Georgia Physician to Lead US Public-Health Agency

Obstetrician and gynecologist Brenda Fitzgerald will direct the US Centers for Disease Control and Prevention, Secretary of Health and Human Services, Tom Price announced. [Nature News] Editorial

French Scientist Fined for Failure to Disclose Industry Ties

In an unprecedented court case in Paris, an eminent French lung specialist has been fined €50,000 and given a six-month suspended jail sentence because he didn’t disclose his ties to the oil industry during a Senate air-pollution inquiry. [Nature News] Editorial

NEW VII InterAmerican Oncology Conference
October 5-6, 2017
Buenos Aires, Argentina

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NEW Postdoctoral Fellowships – Epithelial Cell Biology & Gastrointestinal Neoplasia (Vanderbilt University Medical Center)

NEW Postdoctoral Research Associate – Cancer Research (Southern Research Institute)

Postdoctoral Position – Intestinal Epithelial Cell Biology (University of Gothenburg)

Postdoctoral Fellowships – Epithelial Cell Biology & Gastrointestinal Neoplasia (Vanderbilt University)

Postdoctoral Research Associate – Colorectal Cancer (University of Virginia)

Postdoctoral Position – Cancer Genomics and Precision Medicine (Candiolo Cancer Institute-FPO, IRCCS)

Postdoctoral Fellow – Intestinal Pathogen Research (Boston Children’s Hospital and Harvard Medical School)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

Postdoctoral Research Fellow – Cancer Epidemiology (Fred Hutchinson Cancer Research Center)

Assistant or Associate Member – Stem Cell/Gene Therapy (Fred Hutchinson Cancer Research Center)

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