Intestinal Cell News Volume 5.19 | May 31 2019

TOP STORY

Transcriptional and Metabolic Rewiring of Colorectal Cancer Cells Expressing the Oncogenic KRAS^G13D Mutation

To better understand the cellular reprogramming which occurs in mutant KRAS cells, investigators undertook a systems-level analysis of four colorectal cancer cell lines which expressed either wild type KRAS or the oncogenic KRASG13D allele (mtKRAS). RNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were significantly upregulated in mtKRAS cells. [Br J Cancer] Full Article

(Ranked by impact factor of the journal)

Suppression of Fumarate Hydratase Activity Increases the Efficacy of Cisplatin-Mediated Chemotherapy in Gastric Cancer

Scientists investigated the relationship between fumarate hydratase (FH) and cisplatin (CDDP) sensitivity in gastric cancer cell lines. They found that FH was the most significant gene which induced by CDDP treatment and the suppression of FH could enhance the cytotoxicity of CDDP. [Cell Death Dis] Full Article

The Natural Product Butylcycloheptyl Prodiginine Binds Pre-miR-21, Inhibits Dicer-Mediated Processing of Pre-miR-21, and Blocks Cellular Proliferation

Using a high-throughput differential scanning fluorimetry assay, researchers identified small-molecule natural products with the capacity to bind the discrete stem-looped structure of pre-miR-21. The most potent compound identified was a prodiginine-type compound, butylcycloheptyl prodiginine, with the ability to inhibit Dicer-mediated processing of pre-miR-21 in vitro. [Cell Chem Biol] Abstract

Fluorescence-Based Tracing of Transplanted Intestinal Epithelial Cells Using Confocal Laser Endomicroscopy

Researchers investigated the applicability of a panel of fluorescent dyes and nanoparticles to label intestinal organoids for visualization using the clinically approved imaging modality, confocal laser endomicroscopy (CLE). Staining homogeneity, durability, cell viability, differentiation capacity, and organoid forming efficiency were evaluated, together with visualization of labeled organoids in vitro and ex vivo using CLE. [Stem Cell Res Ther] Full Article

Trp53 Null and R270H Mutant Alleles Have Comparable Effects in Regulating Invasion, Metastasis, and Gene Expression in Mouse Colon Tumorigenesis

The fraction of adenocarcinomas with submucosa or deeper invasion was higher in AKP^270/fl mice than in AKP^fl/fl mice, but the incidence of adenocarcinomas per mouse did not differ significantly between AKP^fl/fl and AKP^270/fl mice. In line with their comparable biological behaviors, mouse primary tumors and tumor-derived organoids with the Trp53^R270H or Trp53^null alleles had highly similar gene expression profiles. [Lab Invest] Abstract

Modulation of Intestinal Epithelial Glycocalyx Development by Human Milk Oligosaccharides and Non-Digestible Carbohydrates

The authors investigated effects of human milk oligosaccharides (hMOs) and non-digestible carbohydrates (NDCs) on human gut epithelial cells by quantifying thickness and area coverage of adsorbed albumin, heparan sulfate and hyaluronic acid in the glycocalyx. Effects of hMOs and NDCs and pectins with degrees of methylation were tested using immunofluorescence staining at one and five days stimulation. [Mol Nutr Food Res] Abstract

Vitamin D and Wnt3A Have Additive and Partially Overlapping Modulatory Effects on Gene Expression and Phenotype in Human Colon Fibroblasts

Investigators showed by global transcriptomic studies that 1,25(OH)₂D₃ and Wnt3A had profound, additive, partially overlapping effects on the gene expression profile of colorectal (CCD)-18Co human colon myofibroblasts. Moreover, 1,25(OH)₂D₃ and Wnt3A inhibited CCD-18Co cell proliferation and migration, while 1,25(OH)₂D₃ reduced, but Wnt3A increased, their capacity to contract collagen gels. [Sci Rep] Full Article

miR-139-5p Reverses Stemness Maintenance and Metastasis of Colon Cancer Stem-Like Cells by Targeting E2-2

Scientists discovered that miR-139-5p targeted the Wnt/β-catenin/TCF7L2 downstream effector E2-2 in colon cancer stem cells (CCSCs). E2-2 is a pivot molecule in the negative feedback loop of miR-139-5p/Wnt/β-catenin/TCF7L2. Its small interfering RNA reversed the stemness maintenance and epithelial-mesenchymal transition of CCSCs. [J Cell Physiol] Abstract

Lathyrus sativus Diamine Oxidase Counteracts Histamine-Induced Cell Proliferation, Migration and Pro-Angiogenic Mediators Release in Human Colon Adenocarcinoma Cell Line Caco-2

The authors investigated the effect of L. sativus-derived diamine oxidase (LSAO) and its mechanism of action on the Caco-2 cell line, considering that LSAO catalizes the oxidative deamination of histamine to the corresponding aldehyde, NH₃ and H₂O₂. Histamine caused a proliferative effect on Caco-2 cells promoting cell migration, invasion and nitric oxide and vascular endothelial growth factor release. [Phytother Res] Abstract

Characterization of Antibiotic Resistance Genes, Plasmids, Biofilm Formation, and In Vitro Invasion Capacity of Salmonella enteritidis Isolates from Children with Gastroenteritis

Twenty-two ARGs and 18 different plasmid incompatibility types were investigated using polymerase chain reaction and DNA sequencing. In vitro invasion capacity of S. enteritidis isolates possessing different antibiotic resistance patterns were assessed using the Caco2 human intestinal epithelial cell line and biofilm formation was performed in a 96-well polystyrene well format using crystal violet detection. [Microb Drug Resist] Abstract

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Metabolic Pathways Regulating Colorectal Cancer Initiation and Progression

The authors review key findings implicating cancer metabolism as a major contributor of tumor initiation, growth and metastatic dissemination in colorectal cancer. They summarize the metabolic pathways governing stem cell fate in the intestine, the metabolic adaptations of proliferating colon cancer cells and their crosstalk with oncogenic signaling, and how they fulfill the energetic demands imposed by the metastatic cascade. [Semin Cell Dev Biol] Abstract

The Potential Therapeutic and Prognostic Impacts of the C-MET/HGF Signaling Pathway in Colorectal Cancer

Recent studies have suggested that the c-MET/HGF signaling pathway is involved in the carcinogenesis of colorectal cancer (CRC). Investigators summarize the main findings of recent studies investigating the role of c-MET/HGF signaling pathway in CRC and the potential of the c-MET/HGF signaling pathways in the diagnosis and treatment of CRC. [IUBMB Life] Abstract

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

Darolutamide Data Presented

Results of a new post-hoc analysis showed that treatment with Orion’s and Bayer’s darolutamide plus androgen deprivation therapy (ADT) delayed worsening of urinary and bowel symptoms maintains quality of life beyond end of study versus placebo plus ADT1. [Press release from Bayer AG (GlobeNewswire, Inc.) discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Treos Bio Announces Positive Interim Results from a Phase I/II Clinical Trial of Precision Cancer Vaccine plus Maintenance Therapy in Patients with Metastatic Colorectal Cancer

Treos Bio Limited, an immuno-oncology company developing next-generation, precision cancer vaccines combined with companion diagnostic devices, reported positive interim results from its first-in-man Phase 1/2 study of its precision cancer vaccine with maintenance therapy in patients with metastatic colorectal cancer. [Press release from Treos Bio Limited discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Dr. Caroline Lindemans explains her work on intestinal repair following injury in graft versus host disease. Listen Now

Array BioPharma Announces BRAFTOVI + MEKTOVI + Cetuximab Meet Primary Endpoints of ORR and OS in Phase III BEACON CRC Trial Interim Analysis for the Treatment of BRAF(V600E)-Mutant Metastatic Colorectal Cancer

Array BioPharma, Inc. announced positive results from the interim analysis of the Phase III BEACON CRC trial evaluating the combination of BRAFTOVI^®, a BRAF inhibitor, MEKTOVI®, a MEK inhibitor, and ERBITUX^®, an anti-EGFR antibody, in patients with BRAF^V600E-mutant metastatic colorectal cancer, following one or two prior lines of therapy. [Array BioPharma, Inc.] Press Release

Progenity Presents Proof-of-Concept Data on Proprietary Ingestible Technologies for Diagnosis, Monitoring, and Treatment of Gastrointestinal Disorders

Progenity, Inc. announced results from three studies that represent potential breakthrough systems for diagnosing, treating, and monitoring digestive diseases through ingestible technologies. Proof-of-concept studies in both human and pre-clinical models showed Progenity’s ingestible diagnostic capsule platform is capable of autonomous location-based sampling, biomolecular analysis, and real-time wireless communications for assessing and monitoring gastrointestinal health. [Progenity, Inc.] Press Release

Ambitious Open-Access Plan S Delayed to Let Research Community Adapt

A major push by some science agencies to make the research they fund open-access on publication — Plan S — has been delayed by a year. Funders now don’t have to start implementing the initiative until 2021, the agencies announced, to give researchers and publishers more time to adapt to the changes the bold plan requires. [Nature News] Editorial

No Paper, No PhD? India Rethinks Graduate Student Policy

PhD students in India will no longer be required to publish articles in academic journals before they are awarded their doctorates, if the country’s higher-education regulator adopts recommendations from a committee of researchers. [Nature News] Editorial

Bipartisan Bill Would Create Forum for Discussing How to Counter US Academic Espionage

Academic leaders say more dialogue is urgently needed on one issue now bedeviling the US research community: how to best protect the country against its economic and military competitors without choking off international scientific collaborations and the free flow of people and ideas. [ScienceInsider] Editorial

MD Anderson Clears Researcher Flagged by NIH for Not Disclosing Foreign Ties

MD Anderson Cancer Center in Houston, Texas, says it has concluded an investigation of the last of five researchers flagged by the US National Institutes of Health (NIH) for potential violations of agency rules. The investigation “confirmed non-compliance with NIH and MD Anderson rules and policies, but such violations were not in our view serious or indicative of willful malfeasance,” the center said in a statement. [ScienceInsider] Editorial

NEW 19^th International Congress of Mucosal Immunology
July 16-20, 2019
Brisbane, Australia

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

NEW Postdoctoral Fellow – Immunometabolism of IBD (Luxembourg Institute of Health)

Postdoctoral Researcher – Genetics in IBD (Kennedy Institute of Rheumatology)

Principle Investigator – Gut Physiology (Nestlé Research Center)

Postdoctoral Researcher – Mucosal Immunology and Inflammation (Gilead Sciences, Inc.)

Postdoctoral Fellow – Intestinal Regenerative Medicine (Zhou Lab)

Postdoctoral Fellow – Intestinal and Pulmonary Stem Cell Biology (Stanford School of Medicine)

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 – Oesophago-Gastric Cancer Research (University of Cambridge)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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