Intestinal Cell News Volume 3.23 | Jun 23 2017

TOP STORY

Nlrp9b Inflammasome Restricts Rotavirus Infection in Intestinal Epithelial Cells

Rotavirus infects intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signaling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. Investigators uncovered and mechanistically characterized the NOD-like receptor Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Intestinal Cancer Progression by Mutant p53 through the Acquisition of Invasiveness Associated with Complex Glandular Formation

The authors generated Apc^Δ716 Trp53^LSL•R270H villin–CreER compound mice, in which mutant p53^R270H was expressed in the intestinal epithelia upon tamoxifen treatment, and examined the intestinal tumor phenotypes and tumor-derived organoids. Mutant Trp53^R270H, but not Trp53-null mutation accelerated submucosal invasion with generation of desmoplastic microenvironment. [Oncogene] Full Article

AQP9-Induced Cell Cycle Arrest Is Associated with RAS Activation and Improves Chemotherapy Treatment Efficacy in Colorectal Cancer

Researchers demonstrated that aquaporin-9 (AQP9) can serve as an independent predictive marker for adjuvant chemotherapy in colorectal cancer. Patients with high AQP9 expression had higher rate of disease-free survival than those with low AQP9 expression. [Cell Death Dis] Full Article

Tumor-Suppressive miR-26a and miR-26b Inhibit Cell Aggressiveness by Regulating FUT4 in Colorectal Cancer

To identify potential key miRNAs and their target genes for colorectal cancer (CRC), investigators compared miRNA expression profiles between metastatic CRC cell SW620 and primary CRC cell SW480. Microarray analysis revealed that there were 85 differentially expressed miRNAs in SW620 cells with highly metastatic potential compared to SW480 cells with lowly metastatic potential. [Cell Death Dis] Full Article

miR-15b-5p Resensitizes Colon Cancer Cells to 5-Fluorouracil by Promoting Apoptosis via the NF-κB/XIAP Axis

Scientists report that miR-15b-5p is a tumor suppressor whose level is globally decreased in colorectal cancer cells and tissues. Over-expression of miR-15b-5p not only promoted 5-fluorouracil (5-FU)-induced cellular apoptosis but also reversed the chemoresistance of 5-FU in vitro and in vivo. [Sci Rep] Full Article

Dietary Mastic Oil Extracted from Pistacia lentiscus var. chia Suppresses Tumor Growth in Experimental Colon Cancer Models

Researchers analyzed the volatile dietary phytochemicals (terpenes) present in mastic oil extracted from the resin of Pistacia lentiscus var. chia and comparatively investigated their effects on colon carcinoma proliferation, a) in vitro against colon cancer cell lines and b) in vivo on tumor growth in mice following oral administration. Mastic oil inhibited – more effectively than its major constituents- proliferation of colon cancer cells in vitro, attenuated migration and downregulated transcriptional expression of survivin. [Sci Rep] Full Article

Therapeutic Suppression of miR-4261 Attenuates Colorectal Cancer by Targeting MCC

The authors used miRNA target prediction algorithms, and previously reported microarray data in human colorectal cancer, and found that only miR-4261 was predicted by all three databases to directly target mutated colorectal cancer. Based on specimens from a cohort of colorectal cancer patients, they further demonstrated that miR-4261 was overexpressed in colorectal cancer. [Mol Ther Nucleic Acids] Full Article

CRH Promotes Human Colon Cancer Cell Proliferation via IL-6/JAK2/STAT3 Signaling Pathway and VEGF-Induced Tumor Angiogenesis

Cell proliferation and colony formation assays revealed that corticotrophin-releasing hormone (CRH) contributed to cell proliferation. Tube formation assay showed that CRH-treated colon cancer cell supernatant significantly promoted tube formation of human umbilical vein endothelial cells. These effects could be reversed by the CRHR1 specific antagonist antalarmin. [Mol Carcinog] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Colonic Organoids Derived from Human Induced Pluripotent Stem Cells for Modeling Colorectal Cancer and Drug Testing

With the goal of modeling human disease of the large intestine, the authors sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells or induced pluripotent stem cells. Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. [Nat Med] Abstract | Press Release

Differentiation of Human Pluripotent Stem Cells into Colonic Organoids via Transient Activation of BMP Signaling

Scientists report the differentiation of human colonic organoids (HCOs) from human pluripotent stem cells (hPSCs). They found that BMP signaling is required to establish a posterior SATB2⁺ domain in developing and postnatal intestinal epithelium. Brief activation of BMP signaling was sufficient to activate a posterior HOX code and direct hPSC-derived gut tube cultures into HCOs. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract | Video

Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5⁺ Intestinal Stem Cells

Researchers showed that GFP⁺ cells from Bmi1^GFP mice are preterminal enteroendocrine cells and they identified CD69⁺CD274⁺ cells as related goblet cell precursors. Upon loss of native Lgr5⁺ intestinal stem cells, both populations reverted toward an Lgr5⁺ cell identity. [Cell Stem Cell] Abstract | Graphical Abstract

Intestinal Barrier Integrity and Inflammatory Bowel Disease: Stem Cell-Based Approaches to Regenerate the Barrier

The authors review the intestinal barrier’s role in healthy and diseased states, and discuss the clinical application of stem cell-based approaches to accomplish mucosal healing in inflammatory bowel disease. [J Tissue Eng Regen Med] Abstract

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

eFFECTOR Therapeutics to Collaborate with Pfizer and Merck KGaA, Darmstadt, Germany to Evaluate a Novel Immuno-Oncology Combination in Microsatellite Stable Colorectal Cancer

eFFECTOR Therapeutics announced that it has entered into a clinical collaboration and supply agreement with Pfizer and Merck KGaA, Darmstadt, Germany, to evaluate the combination of two immuno-oncology agents in patients with microsatellite stable colorectal cancer. [eFFECTOR Therapeutics] Press Release

Celyad Reports Promising Early Results at First Dose Level of the Solid Arm of the THINK Trial

Celyad announced promising early clinical results at the three-month follow-up of the first dose-level in the solid tumor arm of the therapeutic immunotherapy with CAR-T NKR-2 (THINK) trial. At the first 3 x 10⁸ cell dose-level administered to a total of three patients with metastatic cancer, the two colorectal cancer patients, who were progressing after at least two prior chemotherapy regimens, achieved a confirmed Stable Disease according to RECIST criteria at three months. [Celyad] Press Release

US Court Grants Elsevier Millions in Damages From Sci-Hub

One of the world’s largest science publishers, Elsevier, won a default legal judgement against websites that provide illicit access to tens of millions of research papers and books. A New York district court awarded Elsevier US$15 million in damages for copyright infringement by Sci-Hub, the Library of Genesis project and related sites. [Nature News] Editorial

University of Tokyo Scientist Hit by Anonymous Allegations Fights Back

Last September, anonymous allegations of questionable data and images in 22 papers by six prominent groups at the prestigious University of Tokyo prompted the school to set up an investigating committee. Now, even before the panel completes its investigation, one of the accused researchers has mounted a staunch defense of his work, with a point-by-point rebuttal of the allegations and an apology for mistakes confirmed in several of the questioned papers. [ScienceInsider] Editorial

China Cracks Down on Fake Peer Reviews

The Chinese government is going on the offensive against scientists who dupe journals by creating fraudulent reviews of submitted papers. A coalition of agencies led by the science ministry announced that the government would suspend the grants of researchers involved in such fraud, which surfaced earlier this year when a cancer journal retracted 107 research papers from Chinese authors. [Nature News] Editorial

NEW Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond
September 24-27, 2017
Orlando, Florida, United States

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

NEW Postdoctoral Research Associate – Colorectal Cancer (University of Virginia)

NEW Postdoctoral Position – Cancer Genomics and Precision Medicine (Candiolo Cancer Institute-FPO, IRCCS)

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)

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)

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

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