Intestinal Cell News Volume 3.22 | Jun 16 2017

TOP STORY

TGFβ Pathway Limits Dedifferentiation following WNT and MAPK Pathway Activation to Suppress Intestinal Tumorigenesis

Previous work has shown that activating mutations of Kras or the NF-κB pathway could drive dedifferentiation of intestinal cells lacking Apc. Researchers profiled both cells undergoing dedifferentiation in vitro and tumors generated from these cells in vivo by gene expression analysis. No clear differences were observed in the tumors; however, during dedifferentiation in vitro they found a marked upregulation of TGFβ signaling, a pathway commonly mutated in colorectal cancer. [Cell Death Differ] Full Article

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Aldose Reductase Inhibitor Increases Doxorubicin-Sensitivity of Colon Cancer Cells and Decreases Cardiotoxicity

Investigators showed that treatment of colorectal cancer cells with fidarestat increased the efficacy of doxorubicin (DOX)-induced death in HT-29 and SW480 cells and in nude mice xenografts. Aldose reductase inhibition resulted in higher intracellular accumulation of DOX and decreased the expression of drug transporter proteins MDR1, MRP1, and ABCG2. [Sci Rep] Full Article

RUFY3 Interaction with FOXK1 Promotes Invasion and Metastasis in Colorectal Cancer

RUFY3 or FOXK1 have been correlated with the malignance of tumor cells. However, the role of these molecules in colorectal cancer (CRC) progression remained unknown. The authors assessed the migration and invasive abilities of CRC cells using shRNA-mediated inhibition in vitro and in vivo. RUFY3 suppression inhibited anchorage independent cell tumorigenesis. Moreover, RUFY3 physically interacted with FOXK1 in CRC. [Sci Rep] Full Article

Guar Gum Fiber Increases Suppressor of Cytokine Signaling-1 Expression via Toll-Like Receptor 2 and Dectin-1 Pathways, Regulating Inflammatory Response in Small Intestinal Epithelial Cells

Scientists investigated the anti-inflammatory regulation by intact guar gum (GG) using mice and human intestinal Caco-2 cells. Intact GG activated toll-like receptor 2 and dectin-1, and increased suppressor of cytokine signaling-1 expression via JAK and cSrc pathways, resulting in anti-inflammatory regulation in intestinal epithelium. [Mol Nutr Food Res] Abstract

EPEC Effector EspF Promotes Crumbs3 Endocytosis and Disrupts Epithelial Cell Polarity

Investigators demonstrated that enteropathogenic Escherichia coli (EPEC) displaces Crb3 and Pals1 from the apical membrane to the cytoplasm of cultured intestinal epithelial cells and colonocytes of infected mice. In vitro studies showed that EspF, but not Map alters Crb3, while both effectors modulate Pals1. EspF perturbed polarity formation in cyst morphogenesis assays and induced endocytosis and apical redistribution of Na⁺/K⁺ ATPase. [Cell Microbiol] Abstract

NLRC3 Regulates Cellular Proliferation and Apoptosis to Attenuate the Development of Colorectal Cancer

Researchers explored possible mechanisms through which nucleotide-binding domain, leucine-rich-repeat–containing protein (NLR) C3 regulates cellular proliferation and cell death. They showed that NLRC3 suppressed c-Myc expression and activation of PI3K–AKT targets FoxO3a and FoxO1 in the colon of Nlrc3^−/− mice, suggesting that additional signaling pathways contribute to increased cellular proliferation. [Cell Cycle] Abstract

Antiproliferative Activity of Ontario Grown Onions against Colorectal Adenocarcinoma Cells

Scientists assessed the antiproliferative, cytotoxic, apoptosis-inducing, and anti-migratory activities of five onion varieties grown in Ontario against human adenocarcinoma cells (Caco-2). They found that all onion varieties exhibited antiproliferative activity similar to purified flavonoids. The cytotoxic effects of the Stanley and Fortress onion varieties were strongest among the selected cultivars, as determined via lactate dehydrogenase assays, while Safrane extracts showed the weakest activity. [Food Res Int] Abstract | Press Release | Graphical Abstract

Gastrointestinal Cancer Cells Treatment with Bevacizumab Activates a VEGF Autoregulatory Mechanism Involving Telomerase Catalytic Subunit HTERT via PI3K-AKT, HIF-1α and VEGF Receptors

Researchers investigated the interrelationship between vascular endothelial growth factor (VEGF) and hTERT in gastrointestinal cancers and explored the cell response to a combined inhibition of telomerase and VEGF. Their results showed that telomerase regulates VEGF expression and secretion through its catalytic subunit hTERT in AGS, Caco2, and HepG2/C3A, independent of its catalytic activity. [PLoS One] Full Article

Shigella Depends on SepA to Destabilize the Intestinal Epithelial Integrity via Cofilin Activation

Mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To address this question, the authors used both an intestinal polarized model and a human ex-vivo model to further characterize the early events of host-bacteria interactions. Their results showed that secreted Serine Protease A (SepA), which belongs to the serine protease autotransporter of Enterobacteriaceae family, is responsible for critically disrupting the intestinal epithelial barrier. [Gut Microbes] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Intestinal Organoids Model Human Responses to Infection by Commensal and Shiga Toxin Producing Escherichia coli

Scientists showed that induced human intestinal organoids with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses. Commensal E. coli did not cause damage, and were completely contained within the lumen, suggesting defenses, such as mucus production, can constrain non-pathogenic strains. [PLoS One] Full Article

Systematic Review with Meta-Analysis: The Efficacy and Safety of Stem Cell Therapy for Crohn’s Disease

Stem cell therapy (SCT) for the treatment of Crohn’s disease (CD) is still in its infancy, and whether SCT is associated with improved outcomes is unclear. The authors performed a meta-analysis to evaluate the efficacy and safety of patients receiving SCT. They analyzed 21 studies comprising 514 patients with active CD. A random-effects meta-analysis of studies of SCT as systemic infusion showed 56% of patients achieved clinical response. [Stem Cell Res Ther] Full Article

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

OSE Immunotherapeutics Presents Positive Preclinical Results and Human Ex Vivo Data for OSE-127 (Effi-7) to Support Next Clinical Applications in Inflammatory Bowel Diseases

OSE Immunotherapeutics SA presented new data for OSE-127, an antagonist of the interleukin-7 receptor (IL-7R). The communication entitled “IL-7 pathway controls human T cell homing to the gut and culminates in inflammatory bowel disease mucosa” showed efficacy results for OSE-127 in various preclinical acute or chronic colitis models and ex vivo human biopsies. [Press release from OSE Immunotherapeutics SA discussing research presented at the Federation of Clinical Immunology Societies (FOCIS), Chicago] Press Release

TiGenix Partners with U.S. and European Patient Advocacy Groups Focused on Crohn’s Disease and Ulcerative Colitis

TiGenix NV announced partnerships with the largest patient advocacy groups focused on Crohn’s disease and ulcerative colitis. In the United States, TiGenix has joined the Crohn’s and Colitis Foundation’s President’s Corporate Circle, and in Europe, TiGenix has signed a sponsorship agreement with the European Federation of Crohn’s and Ulcerative Colitis Associations. [TiGenix NV] Press Release

TiGenix Launches Global Phase III Trial for Cx601

TiGenix NV announced that it had hosted its first European investigator meeting, which formally launched the global pivotal Phase III clinical trial for Cx601 for the treatment of complex perianal fistulas in patients with Crohn’s disease. [TiGenix NV] Press Release

Corrona Announces First Patient Has Enrolled in Its Inflammatory Bowel Disease Registry

Corrona announced that the first patient has been enrolled in its groundbreaking Inflammatory Bowel Disease Registry. No national registry presently collects data from patients with inflammatory bowel disease, including ulcerative colitis and Crohn’s disease. [Corrona, LLC.] Press Release

Biologists Debate How to License Preprints

Biology’s zeal for preprints — papers posted online before peer review — is opening up a thorny legal debate: should scientists license their manuscripts on open-access terms? Researchers have now shared more than 11,000 papers at the popular bioRxiv preprints site. But where some researchers allow their bioRxiv manuscripts to be freely redistributed and reused, others have chosen to lock them down with restrictive terms. [Nature News] Editorial

Indian Research Labs Face Financial Crisis

India’s 38 premier scientific laboratories are in a budgetary pinch. A jump in expenditures on salaries, pensions, and perks for government employees, recommended by an advisory commission, is leaving little money for new research in the budget of the Council of Scientific & Industrial Research, based in New Delhi, which oversees the labs and their 4600 scientists. [ScienceInsider] Editorial

Texas Has Sanctioned Unapproved Stem Cell Therapies. Will It Change Anything?

Texas Governor Greg Abbott signed a bill allowing clinics and companies in the state to offer people unproven stem cell interventions without the testing and approval required under federal law. Like the “right to try” laws that have sprung up in more than 30 states, the measure is meant to give desperately ill patients access to experimental treatments without oversight from the U.S. Food and Drug Administration. [ScienceInsider] Editorial

Empty Rhetoric over Data Sharing Slows Science

Government agencies lack the funds to build platforms for data sharing and resist taking responsibility for such infrastructure. They may hope that universities will host data, but the development of institutional repositories is patchy, and to rely on them is effectively to discourage common data standards and curation. [Nature News] Editorial

NEW 3^rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 6-9, 2017
Mainz/Frankfurt, Germany

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

NEW Postdoctoral Fellow – Intestinal Pathogen Research (Boston Children’s Hospital and Harvard Medical School)

PhD Positions – Tight Junction Research (Charite, University Medicine Berlin)

Postdoctoral Researcher – Colorectal Cancer (NUI Galway)

Postdoctoral Fellowships – Epithelial Cell Biology & Gastrointestinal Neoplasia (Vanderbilt University Medical Center)

PhD Studentship – Human Intestinal Epithelial Cell Biology (University of Cambridge)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

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

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

PhD Position – Colorectal Cancer (German Cancer Research Center/DKFZ)

Postdoctoral Fellow – Nanomedicine (Johns Hopkins University)

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

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