Intestinal Cell News Volume 3.09 | Mar 10 2017

TOP STORY

Interplay between Metabolic Identities in the Intestinal Crypt Supports Stem Cell Function

Researchers showed that freshly isolated Lgr5⁺ crypt base columnar cells (CBCs) and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5⁺ CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5⁺ CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. [Nature] Abstract

(Ranked by impact factor of the journal)

INTESTINAL CANCERS & DISEASES

Genetic Dissection of Colorectal Cancer Progression by Orthotopic Transplantation of Engineered Cancer Organoids

Researchers demonstrated that sequential accumulation of oncogenic mutations in Wnt, EGFR, P53, and TGF-β signaling pathways facilitates efficient tumor growth, migration, and metastatic colonization. They showed that reconstitution of specific niche signals can restore metastatic growth potential of tumor cells lacking one of the oncogenic mutations. [Proc Natl Acad Sci USA] Full Article

CSF-1 Regulates the Function of Monocytes in Crohn’s Disease Patients in Remission

To decipher inflammatory mechanisms still operating during Crohn’s disease (CD) remission, investigators compared the expression of chemokine receptors on monocytes from CD and healthy donors, and how these differences could modulate monocyte maturation and cytokine production. [Sci Rep] Full Article

Nucleome Analysis Reveals Structure-Function Relationships for Colon Cancer

The nucleome of the colorectal cancer cell line HT-29 was analyzed using chromosome conformation capture (Hi-C) to study genome structure, complemented by RNA sequencing to determine consequent changes in genome function. Translocations and copy number changes were identified at high resolution from Hi-C data and the structure-function relationships present in normal cells were maintained in cancer. [Mol Cancer Res] Abstract

Preparation of Carotenoid Extracts and Nanoemulsions from Lycium barbarum L. and Their Effects on Growth of HT-29 Colon Cancer Cells

The authors determined the carotenoid content in L. barbarum by high-performance liquid chromatography-mass spectrometry, followed by preparation of a carotenoid nanoemulsion to evaluate the mechanism of inhibition on HT-29 colon cancer cells. [Nanotechnology] Abstract

Geniposide Ameliorates TNBS-Induced Experimental Colitis in Rats via Reducing Inflammatory Cytokine Release and Restoring Impaired Intestinal Barrier Function

Researchers investigated the effects of geniposide on experimental rat colitis and to reveal the related mechanisms. Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide or with sulfasalazine as positive control for 14 consecutive days. [Acta Pharmacol Sin] Abstract

Immunomodulatory Effect of Low Molecular-Weight Seleno-Aminopolysaccharides in Intestinal Epithelial Cells

Seleno-polysaccharides possess a variety of biological activities. Scientists investigated the immunomodulatory effects of low molecular-weight seleno-aminopolysaccharides in intestinal porcine epithelial cells, and the molecular mechanisms of these effects. [Int J Biol Macromol] Abstract

Cell Cycle Arrest and Apoptosis Induced by Enteroaggregative Escherichia coli in Cultured Human Intestinal Epithelial Cells

Investigators assessed enteroaggregative E. coli-induced apoptosis and cell cycle modulation in human intestinal epithelial cell lines. [J Med Microbiol] Abstract

INTESTINAL STEM CELL & ORGANOID RESEARCH

Mex3a Marks a Slowly Dividing Subpopulation of Lgr5⁺ Intestinal Stem Cells

Scientists found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5⁺ intestinal stem cells (ISCs) that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5⁺ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

ATF3 Acts as a Rheostat to Control JNK Signaling during Intestinal Regeneration

The authors showed that the stress inducible transcription factor ATF3 restricts JNK activity in the Drosophila midgut. ATF3 regulates JNK-dependent apoptosis and regeneration through the transcriptional regulation of the JNK antagonist, Raw. [Nat Commun] Full Article

Gut Microbiota Modulation of Chemotherapy Efficacy and Toxicity

Investigators outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds. [Nat Rev Gastroenterol Hepatol] Abstract

Stem Cell Therapy for Inflammatory Bowel Disease

There is a clear need for improved treatment practices in order to avoid systemic complications with medical management and surgical intervention. Stem cell therapy is emerging as a promising treatment alternative. The authors review key basic science articles to discuss important mechanistic aspects as to why stem cell therapy may be an effective treatment strategy to bring to the bedside. [Clin Transl Gastroenterol] Full Article

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

Immunicum AB Announces Enrollment of First Patient in Phase I/II GIST Trial following Study Protocol Amendment

Immunicum AB announced that a new patient has been enrolled in the Phase I/II Gastrointestinal Stromal Tumor (GIST) study following the study protocol amendment, which was recently approved by the ethical committee and the Swedish Medical Products Agency. The study is conducted in collaboration with the Karolinska Institute and investigates the safety and efficacy of INTUVAX^® in combination with tyrosine kinase inhibitors in patients with incurable GIST. [Immunicum AB] Press Release

AXIM^® Biotechnologies Starts Phase II Clinical Trial for IBS Treatment

Medical Marijuana, Inc. investment company AXIM^® Biotechnologies has announced it has completed enrollment of the required 40 patients for its Phase II clinical trial for CanChew Plus^® CBD gum for the treatment of irritable bowel syndrome (IBS) and has commenced the start of the research with an anticipated return of the results this spring. [Medical Marijuana, Inc.] Press Release

Patchy Progress on Fixing Global Gender Disparities in Science

Although women are publishing more studies, being cited more often, and securing more coveted first-author positions than they were in the mid-1990s, overall progress towards gender parity in science varies widely by country and field. This is according to a massive report released on 8^th March that is the first to examine such a broad swath of disciplines and regions of the world over time. [Nature News] Editorial

Open-Data Contest Unearths Scientific Gems — and Controversy

When a prestigious medical journal challenged scientists to analyze data from a pivotal blood-pressure study in search of new findings, hundreds of researchers around the world rushed to sign up. The contest, sponsored by the New England Journal of Medicine, offered scientists a rare opportunity to access detailed trial data that otherwise might have remained proprietary for another year — if not indefinitely. But the competition, whose winners were announced on 7^th March, also illustrates the tension between speeding access to data and protecting the interests of those who labored to collect them. [Nature News] Editorial

NEW American Society of Gene & Cell Therapy (ASGCT)
May 10-13, 2017
Washington, D.C., United States

NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
May 11-13, 2017
Heidelberg, Germany

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

NEW Postdoctoral Fellow – Intestinal Pathogens on Host Metabolism (Boston Children’s Hospital and Harvard Medical School)

Senior Scientist – Pathology of Immunology and Gastrointestinal Diseases (Takeda Pharmaceuticals)

Postdoctoral Fellow – Unraveling Oncotherapy Stem Cell Toxicity (AstraZeneca)

Assistant & Associate Investigators – Colorectal, Pancreatic, Gastric and Esophageal Cancers (Baylor Scott & White Health)

Postdoctoral Fellow – Intestinal Pathogens on Host Development and Metabolism (Boston Children’s Hospital/Harvard Medical School)

Faculty Position – Intestinal Stem Cell Research (Duke University Division of Gastroenterology)

Postdoctoral Fellowship – Cellular Mechanisms by Which Fatty Acids Are Absorbed in the Gut (UCSF – Cardiovascular Research Institute)

Research Associate – Colorectal Cancer (University of Virginia)

Gastroenterologist(s) – General and Interventional (Temple University)

Postdoctoral Fellow – Translational Intestinal Models (Johnson & Johnson Group)

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

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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

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