Intestinal Cell News Volume 4.44 | Nov 16 2018

TOP STORY

Colorectal Cancer Liver Metastatic Growth Depends on PAD4-Driven Citrullination of the Extracellular Matrix

Scientists showed that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer. [Nat Commun] Full Article

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Selective Expression of Constitutively Activated STAT6 in Intestinal Epithelial Cells Promotes Differentiation of Secretory Cells and Protection against Helminths

Researchers generated mice with specific expression of a constitutively active version of STAT6 in intestinal epithelial cells (IECs). These VillinCre_STAT6vt mice showed accumulation of secretory IECs, increased proliferation of IECs and lengthening of the small intestine. [Mucosal Immunol] Abstract

Intestinal Stem Cells Exhibit Conditional Circadian Clock Function

Investigators tested clock function in vivo at the single cell resolution in the Drosophila intestine, a tissue that is exquisitely sensitive to environmental cues and has circadian rhythms in regeneration. Their results indicate that circadian clocks function in intestinal stem cells and enterocytes but are downregulated during enteroendocrine cell differentiation. [Stem Cell Reports] Abstract | Graphical Abstract

Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer

Researchers discovered that miR-15b expression positively correlated with therapeutic outcome in colorectal cancer. DCLK1 was identified as the direct target gene for miR-15b and its suppression was associated with self-renewal and tumorigenic properties of DCLK1⁺ tumor-initiating cells . [Stem Cell Reports] Full Article

Hyperglycemia Promotes Microvillus Membrane Expression of DMT1 in Intestinal Epithelial Cells in a PKCα-Dependent Manner

Scientists showed that iron uptake and the mRNA expression of iron importer divalent metal transporter 1 (DMT1) were significantly increased in the duodenum of streptozotocin-induced diabetic mice. High-glucose treatment increased plasma membrane DMT1 expression via the activation of PKCα in cultured intestinal epithelial cells. Inhibition of PKCα potentiated the ubiquitination and degradation of DMT1 protein. [FASEB J] Abstract

Loss of Fas Expression and Function Is Coupled with Colon Cancer Resistance to Immune Checkpoint Inhibitor Immunotherapy

Investigators report that decreased Fas expression was coupled with a subset of CD133⁺CD24^lo colon cancer cells in vitro and in vivo. Consistent of the lower Fas expression level, this subset of CD133⁺CD24^lo colon cancer cells exhibited decreased sensitivity to FasL-induced apoptosis. [Mol Cancer Res] Abstract

Anticancer Activity of Paroxetine in Human Colon Cancer Cells: Involvement of MET and ERBB3

The authors investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. [J Cell Mol Med] Full Article

Urolithin A Gains in Anti-Proliferative Capacity by Reducing the Glycolytic Potential via the p53/TIGAR Axis in Colon Cancer Cells

Enterolacton, S-equol and urolithin A as representatives of metabolites of lignans, isoflavones and ellagitannins, respectively, were examined for their impact on HCT116 colon cancer cell growth, cooperativity with oxaliplatin and p53 dependency in vitro. [Carcinogenesis] Abstract

Verbascoside: Identification, Quantification, and Potential Sensitization of Colorectal Cancer Cells to 5-FU by Targeting PI3K/AKT Pathway

Verbascoside in Plantago seeds was identified using UPLC-MS/MS and quantified using newly developed and validated UPLC-DAD followed by investigating its potential sensitization of colorectal cancer cells to 5-fluorouracil (5-FU) in vitro. [Sci Rep] Full Article

Inhibitory Role of AMP-Activated Protein Kinase in Necroptosis of HCT116 Colon Cancer Cells with p53 Null Mutation under Nutrient Starvation

The authors investigated the role of AMP-activated protein kinase in nutrient/serum starvation-induced necroptosis, which is a programmed form of necrosis, in the presence or absence of p53. They detected higher cell proliferation and lower cell death rates in the HCT116 human colon cancer cell line containing a p53 null mutation compared with in HCT116 cells harboring wild-type p53, as determined using a cell viability assay. [Int J Oncol] Abstract

Isolation, Propagation, and Clonogenicity of Intestinal Stem Cells

Researchers describe a detailed methodology for the isolation and expansion of mouse intestinal crypts from three different locations—the colon, proximal, and distal small intestine. [Methods Mol Biol] Abstract

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Tales from the Crypt: New Insights into Intestinal Stem Cells

Scientists discuss the signals, cell types and mechanisms that control homeostasis and regeneration in the intestinal epithelium. They investigate how the niche protects and instructs intestinal stem cells, which processes drive differentiation of mature cells and how imbalance in key signaling pathways can cause human disease. [Nat Rev Gastroenterol Hepatol] Abstract

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Blueprint Medicines Announces Updated NAVIGATOR Trial Results in Patients with Advanced Gastrointestinal Stromal Tumors Supporting Development of Avapritinib Across All Lines of Therapy

Blueprint Medicines Corporation announced updated data for the registration-enabling NAVIGATOR clinical trial of avapritinib, a potent and highly selective KIT and PDGFRA inhibitor in development for patients with advanced gastrointestinal tumors. [Blueprint Medicines Corporation] Press Release

U.S. FDA Accepts for Filing Shire’s Supplemental New Drug Application for GATTEX^® (Teduglutide [rDNA Origin]) for Children with Short Bowel Syndrome

Shire plc announced that the FDA has accepted for filing the supplemental new drug application to extend the indication of GATTEX^® for injection to pediatric patients with short bowel syndrome who are dependent on parenteral support. [Shire plc] Press Release

UC Researchers Granted $3.4 Million by NIH to Study Gastrointestinal Lymphatic System

A team of researchers at the University of Cincinnati (UC) College of Medicine have been awarded $3.4 million by the National Institutes of Health (NIH) to study the role of the gastrointestinal lymphatic system in dietary nutrient absorption and the transport of signaling molecules. [University of Cincinnati] Press Release

Researchers Awarded 2018 Canon Medical Systems USA/RSNA Research Grants

The Radiological Society of North America Research & Education Foundation awarded its 2018 Canon Medical Systems USA/RSNA Research Seed Grants to Pedram Heidari, M.D., Prashant Nagpal, M.D. and Adam Singer, M.D., and the 2018 Canon Medical Systems USA Research Medical Student Grants to Brandon Kenneth-Kouso Fields, B.A., B.M. and Anthony D. Yao, B.S. Pedram Heidari will investigate a novel PET probe for imaging of disease activity in inflammatory bowel disease in mouse models. [The Radiological Society of North America Research & Education Foundation (Business Wire, Inc.)] Press Release

Dr. Jason Spence shares his insights on the derivation of organoids from hPSCs. Listen Now

STEM Candidates Elected to U.S. House Prepare for Their New Jobs

They’ve won their elections and are headed to Washington, D.C. Their next challenge is using their expertise to make Congress work better. [ScienceInsider] Editorial

Brexit: What the Draft Deal Means for Science

After two years of negotiations, the first real glimmers of what Brexit might involve have emerged. On 14 November, the Cabinet, the UK government’s senior decision-making body, backed a draft agreement on the terms of the country’s withdrawal from the European Union. For science, many of the details that will be most relevant are still to be thrashed out. [Nature News] Editorial

In the Palestinian Territories, Science Struggles Against All Odds

Travel restrictions and paltry funding hamper researchers, who are trying to build a scientific base. After decades of conflict, many embittered Palestinians from the occupied territories boycott any form of economic or cultural activities with Israel — including research. But higher education is an exception. [Nature News] Editorial

How Facebook and Twitter Could Be the Next Disruptive Force in Clinical Trials

Participants in medical research are more empowered than ever to influence the design and outcomes of experiments. Now, researchers are trying to keep up. [Nature News] Editorial

NEW Keystone Symposia: Genome Engineering: From Mechanisms to Therapies
February 19-23, 2019
Victoria, British Columbia, Canada

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NEW PhD Scholarship – 3D Printed Microenvironments for Mini-Organ Culture (Technical University of Denmark)

Postdoctoral Researcher – Pesticide Exposure and Effects on Colorectal Cancer (Luxembourg Institute of Health)

PhD Studentship – Colorectal Cancer (Institute of Cancer Research)

Postdoctoral Fellow – Organoid Modeling of Bacterial Infections (Uppsala University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Fellow – Patient Derived Organoids (Rutgers Cancer Institute of New Jersey)

Postdoctoral Fellow – Intestinal & Colonic Stem Cell Research (Albert Einstein College of Medicine of Yeshiva University)

PhD Studentship – Gastrointestinal Adenocarcinomas (University of Cambridge)

Postdoctoral Position – Dendritic Cell Biology & Antigen Presentation (Weill Cornell Medicine)

Postdoctoral Position – Paneth Cells (Erasmus MC Cancer Institute)

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