Intestinal Cell News Volume 3.11 | Mar 24 2017

TOP STORY

Reference Component Analysis of Single-Cell Transcriptomes Elucidates Cellular Heterogeneity in Human Colorectal Tumors

Using reference component analysis, scientists identified two distinct subtypes of cancer-associated fibroblasts (CAFs). Additionally, epithelial-mesenchymal transition-related genes were found to be upregulated only in the CAF subpopulation of tumor samples. Notably, colorectal tumors previously assigned to a single subtype on the basis of bulk transcriptomics could be divided into subgroups with divergent survival probability by using single-cell signatures. [Nat Genet] Abstract | Press Release

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Amitosis of Polyploid Cells Regenerates Functional Stem Cells in the Drosophila Intestine

Researchers showed that after severe depletion, intestinal stem cells (ISCs) in the Drosophila midgut are replaced by spindle-independent ploidy reduction of cells in the enterocyte lineage through a process known as amitosis. Amitosis is also induced by the functional loss of ISCs coupled with tissue demand and in aging flies, underscoring the generality of this mechanism. [Cell Stem Cell] Abstract | Graphical Abstract

CAMK2γ in Intestinal Epithelial Cells Modulates Colitis-Associated Colorectal Carcinogenesis via Enhancing STAT3 Activation

Investigators showed that calcium/calmodulin-dependent protein kinase II gamma (CAMK2γ) in intestinal epithelial cells modulates inflammatory signals and promotes colitis-associated cancer in mice. They identified CAMK2γ as a downstream target of colitis-induced WNT5A signaling. [Oncogene] Abstract

Dacomitinib-Induced Diarrhea Is Associated with Altered Gastrointestinal Permeability and Disruption in Ileal Histology in Rats

Scientists developed an in vitro and in vivo model of dacomitinib-induced diarrhea to investigate underlying mechanisms. Rats treated with dacomitinib developed severe diarrhea, and had significantly lower weight gain. Further, dacomitinib treatment led to severe histopathological injury localized to the ileum. [Int J Cancer] Abstract

Elevation of GPRC5A Expression in Colorectal Cancer Promotes Tumor Progression through VNN-1 Induced Oxidative Stress

The authors found that the expression of GPRC5A, a well-characterized tumor suppressor in lung cancer, was elevated in colorectal cancer tissues in patients. In both cancer cell lines and a colitis-associated cancer model in mice, they found that GPRC5A deficiency reduced cell proliferation and increased cell apoptosis as well as inhibited tumorigenesis in vivo. [Int J Cancer] Abstract

The Immunosuppressant Mycophenolic Acid Alters Nucleotide and Lipid Metabolism in an Intestinal Cell Model

Researchers elucidated the molecular mechanisms underlying the negative effects of mycophenolic acid (MPA) on human intestinal cells. Effects of MPA exposure and guanosine supplementation on nucleotide concentrations in LS180 cells were assessed using liquid chromatography-mass spectrometry. [Sci Rep] Full Article

In Vivo Evaluation of Mg–6Zn and Titanium Alloys on Collagen Metabolism in the Healing of Intestinal Anastomosis

Scientists compared the effects of the Mg–6Zn and the titanium alloys on collagen metabolism in the healing of the intestinal tract in vivo. They included Sprague-Dawley rats and their effect was compared on rat’s intestinal tract, using serum magnesium, radiology, and immunohistochemistry in vivo. [Sci Rep] Full Article

Elevated Fecal Peptidase D at Onset of Colitis in Galphai2^-/- Mice, a Mouse Model of IBD

Researchers investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms. As a potential top marker of disease, peptidase D was found at a higher ratio in Galphai2^-/- mouse feces relative to controls. Other proteins found to be enriched in Gαi2^-/- mice were mainly pancreatic proteases, and proteins from plasma and blood cells. [PLoS One] Full Article

INTESTINAL STEM CELL & ORGANOID RESEARCH

Lawsonia intracellularis Exploits β-Catenin/Wnt and Notch Signaling Pathways during Infection of Intestinal Crypt to Alter Cell Homeostasis and Promote Cell Proliferation

The authors used immunofluorescence and quantitative reverse transcriptase PCR to examine β-catenin/Wnt and Notch-1 signaling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge. They found that while the significant increase in Ki67⁺ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and intestinal stem cell proliferation respectively, was down-regulated. [PLoS One] Full Article

A Unified Model of the Hierarchical and Stochastic Theories of Gastric Cancer

Researchers discuss existing evidence supporting a unified model of gastric cancer stem cells, including the regulatory mechanisms of this unified model in addition to the current status of stemness-related targeted therapy in gastric cancer patients. [Br J Cancer] Full Article

Autologous Hematopoietic Stem Cells for Refractory Crohn’s Disease

The authors discuss the use of autologous hematopoietic stem cell therapy (AHSCT) in treating patients with Crohn’s disease (CD). Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. [Expert Opin Biol Ther] Abstract

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

Kineta RLR Agonist Demonstrates Tumor Regression and an Adaptive Immune Response in Colon Carcinoma Model

Kineta, Inc. announced the discovery and characterization of several “hit to lead” small molecule compounds that activate interferon response factor 3 via RIG-I like receptor pathways and demonstrate immune-mediated tumor regression in a murine colon carcinoma mouse model. [Press release from Kineta, Inc. discussing research presented at the Keystone Symposia on Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology Conference, Whistler] Press Release

TransEnterix Announces the Senhance^™ Expansion into Robotic Hernia Repair

TransEnterix, Inc. announced that it has expanded the clinical adoption of the Senhance Robotic Surgical System to include a full range of hernia repair surgeries. [TransEnterix, Inc.] Press Release

WntResearch Announces Positive Results from Clinical Study with Drug Candidate Foxy-5

WntResearch announced that the company has obtained positive results from the analyses of patient tumor tissue samples before and after treatment in a Phase Ib study with Foxy-5 – a drug candidate intended to inhibit tumors from spreading in cancer patients. Based on the obtained results, the company has defined the dose level for the upcoming Phase II study, which was one of the objectives with this clinical study. [WntResearch] Press Release

European Commission Approves AMGEVITA^™ (Biosimilar Adalimumab) for the Treatment of Certain Inflammatory Diseases

Amgen announced that the European Commission has granted marketing authorization for AMGEVITA^™ in all available indications. AMGEVITA is authorized for the treatment of certain inflammatory diseases in adults, including moderate-to-severe chronic plaque psoriasis; moderate-to-severe hidradenitis suppurativa; non-infectious intermediate, posterior and panuveitis; moderate-to-severe Crohn’s disease and moderate-to-severe ulcerative colitis. [Amgen] Press Release

Gates Foundation Announces Open-Access Publishing Venture

The Bill & Melinda Gates Foundation is set to launch its own open-access publishing venture later this year. The initiative, Gates Open Research, will be modeled on a service begun last year by the London-based biomedical charity, the Wellcome Trust. Like that effort, the Gates Foundation’s platform is intended to accelerate the publication of articles and data from research funded by the charity. [Nature News] Editorial

Canada Budget Falls Flat with Scientists

The budget that Canadian Prime Minister Justin Trudeau’s government released lives up to his promises to emphasize innovation, and to encourage links between industry and academia. But it also presents scientists with a depressing, and unexpected, freeze on the main funding streams for basic research. [Nature News] Editorial

Predatory Journals Recruit Fake Editor

Thousands of academic journals do not aspire to quality. They exist primarily to extract fees from authors. These ‘predatory’ journals exhibit questionable marketing schemes, follow lax or non-existent peer-review procedures and fail to provide scientific rigor or transparency. [Nature News] Editorial

NEW Cell Culture World Congress
May 23-24, 2017
San Diego, United States

NEW Gordon Research Conferences: Tissue Repair & Regeneration
June 4-9, 2017
New London, United States

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

NEW PhD/PhD-MD Studentship – Intestinal Immunology/Immunophathobiology (Universität Bern)

NEW Assistant Professor – Innate and Adaptive Immune Responses to Intestinal Pathogens and the Microbiota (University of Alabama)

Postdoctoral Fellow – Epigenetics of Intestinal Stem Cells (AstraZeneca)

Postdoctoral Fellow – Intestinal Pathogens on Host Metabolism (Boston Children’s Hospital and Harvard Medical School)

Senior Scientist – Pathology of Immunology and Gastrointestinal Diseases (Takeda Pharmaceuticals)

Assistant & Associate Investigators – Colorectal, Pancreatic, Gastric and Esophageal Cancers (Baylor Scott & White Health)

Postdoctoral Fellow – Intestinal Pathogens on Host Development and Metabolism (Boston Children’s Hospital/Harvard Medical School)

Faculty Position – Intestinal Stem Cell Research (Duke University Division of Gastroenterology)

Postdoctoral Fellowship – Cellular Mechanisms by Which Fatty Acids Are Absorbed in the Gut (UCSF – Cardiovascular Research Institute)

Gastroenterologist(s) – General and Interventional (Temple University)

Postdoctoral Fellow – Translational Intestinal Models (Johnson & Johnson Group)

Postdoctoral Research Fellow – Intestinal Disease (Children’s Hospital Los Angeles)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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

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