Intestinal Cell News Volume 2.45 | Dec 9 2016

TOP STORY

Induced Quiescence of Lgr5⁺ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells

Scientists induced Lgr5⁺ stem cell quiescence in vitro by blocking epidermal growth factor receptor or mitogen-associated protein kinase signaling pathways in organoids and showed that their quiescent state is readily reverted. Quiescent Lgr5⁺ stem cells acquired a distinct molecular signature biased toward enteroendocrine cells differentiation. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Conversion of Human Gastric Epithelial Cells to Multipotent Endodermal Progenitors Using Defined Small Molecules

Researchers described derivation of human induced endodermal progenitor cells (hiEndoPCs) from gastrointestinal epithelial cells using a cocktail of defined small molecules along with support from tissue-specific mesenchymal feeders. The hiEndoPCs showed clonal expansion in culture and give rise to hepatocytes, pancreatic endocrine cells, and intestinal epithelial cells when treated with defined soluble molecules directing differentiation. [Cell Stem Cell] Abstract | Graphical Abstract

ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer

Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Researchers identified the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer. [Clin Cancer Res] Abstract

The Involvement of M2 Macrophage Polarization Inhibition in Fenretinide-Mediated Chemopreventive Effects on Colon Cancer

Clinical studies have shown that fenretinide (4-HPR) is an attractive chemopreventive agent for cancer treatment. Investigators revealed that 4-HPR could significantly suppress IL-4/IL-13 induced M2-like polarization of macrophages, which was demonstrated by the reduced expression of M2 surface markers, the down-regulation of M2 marker genes, and the inhibition of M2-like macrophages promoted angiogenesis. [Cancer Lett] Abstract

Nuclear Export of Ubiquitinated Proteins Determines the Sensitivity of Colorectal Cancer to Proteasome Inhibitor

The authors found in that proteasome inhibition induced a remarkable nuclear exportation of ubiquitinated proteins. Inhibition of CRM1, the nuclear export carrier protein, hampered protein export and synergistically enhanced the cytotoxic action of bortezomib on colon cancer cells containing wild type p53, which underwent G2/M cell cycle block and apoptosis. [Mol Cancer Ther] Abstract

FOXD3 Is a Tumor Suppressor of Colon Cancer by Inhibiting EGFR-Ras-Raf-MEK-ERK Signal Pathway

Investigators showed that forkhead box D3 (FOXD3) knockdown dramatically increased the proliferation of human colon cancer cells, enhanced cell invasive ability and inhibited cell apoptosis. In vivo xenograft studies confirmed that the FOXD3-knockdown cells were more tumorigenic than the controls. [Oncotarget] Full Article

p38 and JNK Pathways Control E-Selectin-Dependent Extravasation of Colon Cancer Cells by Modulating miR-31 Transcription

The authors showed that E-selectin expression induced by the pro-inflammatory cytokine IL-1β is directly and negatively regulated by miR-31. The transcription of miR-31 is activated by IL-1β. This activation depends on p38 and JNK MAP kinases, and their downstream transcription factors GATA2, c-Fos and c-Jun. [Oncotarget] Full Article

Reelin Expression Is Up-Regulated in Mice Colon in Response to Acute Colitis and Provides Resistance against Colitis

Activation of mucosal reelin is greater in magnitude and is delayed until after the activation of the myofibroblasts marker, α-SMA. This indicates that the dextran sulphate sodium (DSS)-induced reelin up-regulation results from changes in the reelin gene expression rather than from myofibroblasts proliferation. [Biochim Biophys Acta] Abstract

Preparation and Characterization of Polymeric Nanoparticles Surface Modified with Chitosan for Target Treatment of Colorectal Cancer

5-Fluorouracil loaded chitosan coated polylactic-co-glycolic acid nanoparticles and polycaprolactone were employed as the carriers for cancer treatment. [Int J Biol Macromol] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Ketogenesis Contributes to Intestinal Cell Differentiation

The authors showed that the ketone body β-hydroxybutyrate, an endogenous inhibitor of histone deacetylases induces intestinal cell differentiation as noted by the increased expression of differentiation markers. [Cell Death Differ] Abstract

Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. [Lancet] Full Article

From Tumor Heterogeneity to Advances in Precision Treatment of Colorectal Cancer

Advances in molecular biology over the past decade have enabled a better understanding of the development of colorectal cancer (CRC), as well as the more-precise use of innovative targeted therapies for this disease, and include three fundamental achievements. [Nat Rev Clin Oncol] Abstract

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

Takeda Presents Seventeen Abstracts

Takeda Pharmaceuticals, U.S.A., Inc. announced that data highlighting the efficacy and safety of vedolizumab for the treatment of adults with moderately to severely active ulcerative colitis and Crohn’s disease, will be presented. [Press release from Takeda Pharmaceuticals, U.S.A., Inc. discussing research presented at the Crohn’s & Colitis Foundation of America’s 2016 Advances in Inflammatory Bowel Diseases (AIBD) Annual Conference, Orlando] Press Release

Theravance Biopharma Receives FDA Fast Track Designation for Velusetrag (TD-5108) for Idiopathic and Diabetic Gastroparesis

Theravance Biopharma, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to velusetrag for the treatment of symptoms associated with idiopathic and diabetic gastroparesis. Velusetrag is an oral investigational drug in development for the treatment of patients with gastroparesis, and is currently being studied in a large, multinational Phase IIb study in patients with confirmed gastroparesis of either diabetic or idiopathic origin. [Theravance Biopharma, Inc.] Press Release

AbbVie and Northwestern University’s Lurie Cancer Center to Collaborate on Multi-Year Cancer Research Agreement

AbbVie and Northwestern University announced they signed a five-year collaboration agreement with the goal of advancing research and discovery in oncology. Together, AbbVie and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University will work in several areas of oncology research, which in addition to others could include, lung, colorectal, breast, prostate and hematological cancer. [AbbVie] Press Release

NEW Cell Plasticity within the Tumor Microenvironment
January 8-12, 2017
Big Sky, United States

NEW Stem Cells in Drug Discovery
March 6-7, 2017
Cambridge, United Kingdom

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NEW Assistant Professor – Gastrointestinal Health/Physiology Tenure-Track Faculty Position (University of Maryland)

NEW Postdoctoral Research Scientist – tRNA Repertoire Influence Ribosome Function during Intestinal Differentiation and Fibroblast Activation (Medical Research Council)

NEW Scientific Writing Associate – Literature Review/Analysis and Relevant Scientific and Medical Material (Genfit SA)

Tenure-Track Position – Various Projects (University Medical Center Utrecht)

Project Manager I – Clinical Trials (Fred Hutchinson Cancer Research Center)

Molecular and Cellular Biology – Scientist(s) (Immunocore)

Research Officer – Transcriptional and Epigenetic Regulation in Colon Cancer and Intestinal Development (Hudson Institute of Medical Research)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Academic Gastrointestinal Pathologist – Faculty Position (University of Utah)

Research Technician III IV – Gastrointestinal Cancer (Fred Hutchinson Cancer Research Center)

Portfolio Manager – Material and Recipe Manager (Nestle Institute of Health Sciences)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

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