Volume 1.27 | Sep 25

Intestinal Cell News 1.27 September 25, 2015
Intestinal Cell News
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Increased TEAD4 Expression and Nuclear Localization in Colorectal Cancer Promote Epithelial–Mesenchymal Transition and Metastasis in a YAP-Independent Manner
Dysregulation of the Hippo pathway occurs in a variety of cancers and often correlates with a poor prognosis. To further explore the potential role of Hippo pathway dysregulation in tumor development and progression, researchers investigated its downstream transcription factor TEAD4 in colorectal cancer. [Oncogene] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Tumor-Promoting Role of SOCS1 in Colorectal Cancer Cells
Researchers investigated SOCS1 relevance for colorectal cancer (CRC) by querying gene expression datasets of human CRC specimens from The Cancer Genome Atlas, and by SOCS1 gain/loss-of-function analyses in murine and human colon carcinoma cells. [Sci Rep] Full Article

REG4 Is a Transcriptional Target of GATA6 and Is Essential for Colorectal Tumorigenesis
Scientists showed that regenerating islet-derived (REG)4, a member of the regenerating islet-derived family, is also a target of GATA6. They further demonstrated that REG4 is downregulated by overexpression of miR-363, which suppresses GATA6 expression. [Sci Rep] Full Article

Interleukin-13 Affects the Epithelial Sodium Channel in the Intestine by Coordinated Modulation of STAT6 and p38 MAPK Activity
Scientists investigated whether interleukin-13 (IL-13) also acts as a potent modulator of epithelial sodium transport via epithelial sodium channel (ENaC), and the signaling components involved. The effect of IL-13 on ENaC was examined in HT-29/B6-GR/MR human colon cells, as well as in mouse distal colon, by measuring amiloride-sensitive short-circuit current in Ussing chambers. [J Physiol] Abstract

GSK3β and Gli3 Play a Role in Activation of Hedgehog-Gli Pathway in Human Colon Cancer – Targeting GSK3β Downregulates the Signaling Pathway and Reduces Cell Proliferation
Investigators showed that inhibition of GSK3β with lithium chloride enhances Gli3 processing into its repressor form, consequently downregulating Hedgehog-Gli signaling, reducing cell proliferation and inducing cell death. [Biochim Biophys Acta] Abstract

Flavaglines Ameliorate Experimental Colitis and Protect Against Intestinal Epithelial Cell Apoptosis and Mitochondrial Dysfunction
Researchers tested the therapeutic potential of flavaglines to promote intestinal epithelial cell homeostasis and to protect against a model of experimental colitis in which inflammation is driven by epithelial ulceration. [Inflamm Bowel Dis] Abstract

PI3K/Akt/mTOR Pathway Dual Inhibitor BEZ235 Suppresses the Stemness of Colon Cancer Stem Cells
Investigators isolated colon cancer stem cells through sphere culture and verified with the cancer stem cell markers CD133, CD44, and CD24. They demonstrated that the PI3K/Akt/mTOR signaling pathway was highly activated in the colon cancer stem cells and that inhibition of the PI3K/Akt/mTOR pathway by the inhibitor BEZ235 suppressed the colon cancer stem cell proliferation with reduced stemness indicated by CD133 and Lgr5 expressions. [Clin Exp Pharmacol Physiol] Abstract

Inhibition of Migration and Induction of Apoptosis in LoVo Human Colon Cancer Cells by Polysaccharides from Ganoderma Lucidum
Scientists evaluated the anticancer effects and investigated the underlying molecular mechanisms of ganoderma lucidum polysaccharides (GLPs) on LoVo human colon cancer cells. They demonstrated that the GLP-mediated anticancer effect in LoVo cells was characterized by cytotoxicity, migration inhibition, enhanced DNA fragmentation, morphological alterations and increased lactate dehydrogenase release. [Mol Med Rep] Abstract


Type 3 Innate Lymphoid Cells Maintain Intestinal Epithelial Stem Cells after Tissue Damage
Using type 3 innate lymphoid cells (ILC3s)-deficient Lgr5 reporter mice, researchers showed that maintenance of intestinal stem cells after damage is severely impaired in the absence of ILC3s or the ILC3 signature cytokine IL-22. [J Exp Med] Abstract

Intestinal Stem Cell Growth and Differentiation on a Tubular Scaffold with Evaluation in Small and Large Animals
The authors investigated the growth and differentiation of intestinal stem cells on a novel tubular scaffold in vitro and in vivo. [Regen Med] Abstract

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Genetically Engineered Mouse Models for Studying Inflammatory Bowel Disease
The authors briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. [J Pathol] Abstract

Visit our reviews page to see a complete list of reviews in the intestinal cell research field.
Data in Nine Difficult-to-Treat Cancers from Merck’s KEYTRUDA® (Pembrolizumab) Development Program to be Presented at European Cancer Congress 2015, Including Data in Four New Cancer Types
Merck announced that new data investigating the anti-tumor activity of KEYTRUDA® (pembrolizumab) across a broad range of advanced cancers will be presented. [Press release from Merck discussing research to be presented at the European Cancer Congress (ECC) 2015, Vienna] Press Release

Celimmune to Present Overview of Non-Dietary Celiac Disease Therapies in Development
Dr. Francisco Leon, CEO and Chief Medical Officer, will discuss the characteristics and mechanism of action of several investigational non-dietary treatments for celiac disease and gluten-related conditions, including AMG 714, a Phase II-stage, anti-IL-15 monoclonal antibody that Celimmune is developing for the treatment of diet non-responsive celiac disease and refractory celiac disease type II. [Press release from Celimmune LLC (PR Newswire Association LLC) discussing research to be presented at the Kansas City Gluten & Allergen-Free Wellness Event, Overland Park] Press Release

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FDA Approves New Oral Medication to Treat Patients with Advanced Colorectal Cancer
The U.S. Food and Drug Administration (FDA) approved Lonsurf (a pill that combines two drugs, trifluridine and tipiracil) for patients with an advanced form of colorectal cancer who are no longer responding to other therapies. [U.S. Food and Drug Administration] Press Release

Lilly Announces CYRAMZA Phase III Second-Line Colorectal Cancer Trial Meets Primary Endpoint of Overall Survival
Eli Lilly and Company announced that the RAISE trial, a Phase III study of ramucirumab (CYRAMZA) in combination with chemotherapy in patients with metastatic colorectal cancer, met its primary endpoint of overall survival. [Eli Lilly and Company] Press Release

Protagonist Therapeutics Receives SBIR Funding for Oral IL-23 Receptor Antagonists for Treatment of Inflammatory Bowel Diseases
Protagonist Therapeutics, Inc., a company developing novel, orally stable peptide therapeutics for gastrointestinal diseases and disorders, announced receipt of a Phase I Small Business Innovation Research (SBIR) Grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. [Protagonist Therapeutics, Inc.] Press Release
Canadian Election Spotlights Scientists’ Frustrations
Canadians will head to the polls on October 19th, in a federal election that many scientists hope will mark a turning point after years of declining research budgets and allegations of government censorship. Although science has not emerged as a top issue during the campaign, researchers are fighting to make their concerns heard. [Nature News] Editorial

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW Innovation and Biomarkers in Cancer Drug Development (IBCD) 2015
December 3-4, 2015
Brussels, Belgium

Visit our events page to see a complete list of events in the intestinal cell research community.
NEW Postdoctoral Fellow – Investigation of Intestinal Epithelial Integrity with Organoid Cultures (AbbVie Inc.)

NEW PhD Positions – Gut Microbiota and Colon Cancer (University of Southern Denmark)

NEW Senior Stem Cell Scientist (Medicines and Healthcare Products Regulatory Agency)

Research Associate – Intestinal Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Immunology (University of Oxford)

Postdoctoral Researcher – Epigenetic Modifiers (Van Andel Research Institute)

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

Postdoctoral Position – Drug Discovery and Action (University of Illinois)

Genetic Counselor – Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Ex Vivo Tumor Organoid Models (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Intestinal Immunology (Shanghai Institute of Immunology)

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