Intestinal Cell News Volume 5.30 | Aug 16 2019

TOP STORY

Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells

Based on unbiased genetic labeling and biophysical modeling, scientists showed that corpus glands were compartmentalized into two independent zones, with slow-cycling stem cells maintaining the base and actively cycling stem cells maintaining the pit-isthmus-neck region through a process of “punctuated” neutral drift dynamics. [Cell Stem Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Molecular Characterization of Colorectal Adenomas Reveals POFUT1 as a Candidate Driver of Tumor Progression

Protein expression was independently validated by immunohistochemistry on tissue microarrays and in patient-derived colorectal adenoma organoids. Stroma percentage was determined by digital image analysis of tissue sections. [Int J Cancer] Abstract

BRAF^V600E-Induced, Tumor Intrinsic PD-L1 Can Regulate Chemotherapy-Induced Apoptosis in Human Colon Cancer Cells and in Tumor Xenografts

Endogenous or exogenous mutant vs. wild-type BRAF were shown to increase programmed death ligand 1 (PD-L1) messenger RNA and protein expression that was attenuated by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibition or c-JUN and YAP knockdown. [Oncogene] Abstract

MYO1D Binds with Kinase Domain of the EGFR Family to Anchor Them to Plasma Membrane before Their Activation and Contributes Carcinogenesis

Overexpressed MYO1D increased colorectal and breast cancer cell motility and viability through upregulating EGFR level, and thereby promoted colorectal tumor progression in a syngeneic mouse model. MYO1D was upregulated in human colorectal cancer tissues from advanced stages. [Oncogene] Abstract

MCT1 Relieves Osimertinib-Induced CRC Suppression by Promoting Autophagy through the LKB1/AMPK Signaling

Researchers found that osimertinib (OSI) exhibited potent anti-colorectal cancer cell (CRC) effects by inducing apoptosis, independent of its selective inhibitory activity targeting the EGFR T790M mutation. Intriguingly, OSI treatment triggers autophagic flux in CRC cells. [Cell Death Dis] Full Article

A Protective Mechanism of Probiotic Lactobacillus against Hepatic Steatosis via Reducing Host Intestinal Fatty Acid Absorption

By using quantitative methods under both in vitro and in vivo conditions, investigators found that bacteria and hosts competed for fatty acid absorption in the intestine, resulting in decreased weight gain, body fat mass, and hepatic lipid accumulation without differences in calorie intake and excretion in mice fed the probiotic bacteria. [Exp Mol Med] Full Article

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

Using a combination of in silico analysis of large datasets, ex vivo analysis of protein expression in patients, and mechanistic studies using in vitro models of colorectal cancer, the authors investigated the oncogenic role of KH-type splicing regulatory protein. They demonstrated KH-type splicing regulatory protein expression in the epithelial and stromal compartments of both primary and metastatic tumors. [Am J Pathol] Abstract

PACSIN2-Dependent Apical Endocytosis Regulates the Morphology of Epithelial Microvilli

To determine if loss of endocytic machinery could explain defects in microvillar morphology, scientists examined the impact of PACSIN2 KD and endocytosis inhibition on live intestinal epithelial cells. These assays revealed that when endocytic vesicle scission failed, tubules were pulled into the cytoplasm and this, in turn, led to a membrane lifting phenomenon reminiscent of that observed in PACSIN2 KO brush borders. [Mol Biol Cell] Abstract

Hyperosmolar Environment and Intestinal Epithelial Cells: Impact on Mitochondrial Oxygen Consumption, Proliferation, and Barrier Function In Vitro

Investigators found that a hyperosmolar environment slowed down cell proliferation compared to normal osmolarity without inducing cell detachment or necrosis. This was associated with a transient reduction of cell mitochondrial oxygen consumption, increase in proton leak, and decrease in intracellular ATP content. [Sci Rep] Full Article

Migration of Bacteriocins across Gastrointestinal Epithelial and Vascular Endothelial Cells, as Determined Using In Vitro Simulations

After three hours, 75% of nisin, 85% of plantaricin 423 and 82% of bacST4SA migrated across the Caco-2 cell monolayer. Over the same time span, 88% nisin, 93% plantaricin 423 and 91% bacST4SA migrated across the human umbilical vein endothelial cells monolayer. [Sci Rep] Full Article

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Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies

The authors provide a systematic review of epidemiological studies investigating epigenetic biomarkers in colorectal cancer (CRC) patients receiving neoadjuvant or adjuvant therapy, and their potential role for the prediction of outcomes and response to treatment. With this aim in mind, they identify several epigenetic markers in CRC patients who received surgery with adjuvant or neoadjuvant therapy. [Int J Mol Sci] Full Article

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

Oncologie, Inc. Announces Clinical Trial Collaboration with Merck to Evaluate Bavituximab in Combination with KEYTRUDA^® (Pembrolizumab) in Advanced Gastric or Gastroesophageal Cancer

Oncologie, Inc. announced that it has entered into a clinical collaboration agreement with Merck to evaluate the combination of Oncologie’s investigational drug Bavituximab, an antibody that blocks the activity of phosphatidylserine , and Merck’s anti-PD-1 therapy, KEYTRUDA^® in patients with advanced gastric or gastroesophageal cancer. [Oncologie, Inc.] Press Release

Innovate Biopharmaceuticals, Inc. Announces First Patient Dosed in the First Phase III Clinical Trial for Patients with Celiac Disease

Innovate Biopharmaceuticals, Inc. announced that it has dosed the first patient in its Phase III clinical trial, CeD LA 3001. This marks the first time any company has dosed a patient in a Phase III trial for celiac disease. [Innovate Biopharmaceuticals, Inc.] Press Release

CytoDyn Files a Phase II Protocol with the FDA for Leronlimab (PRO 140) and Regorafenib as a Combination Therapy for Metastatic Colorectal Cancer

CytoDyn Inc. announced the filing of a Phase II protocol with the FDA for a combination therapy of leronlimab and Regorafenib in patients with metastatic colorectal cancer. [CytoDyn Inc.] Press Release

Deciphera Pharmaceuticals Reports Positive Updated Phase I Data for Ripretinib in Gastrointestinal Stromal Tumors

Deciphera Pharmaceuticals, Inc. reported updated data from its ongoing Phase I clinical study of ripretinib, a broad-spectrum KIT and PDGFRα inhibitor, in patients with second-line through fourth-line plus gastrointestinal stromal tumors. [Deciphera Pharmaceuticals, Inc.] Press Release

Alfasigma USA Announces ZELNORM™ (Tegaserod) Now Available for Treatment of Irritable Bowel Syndrome with Constipation

Alfasigma USA, Inc. announced that ZELNORM™ is now available in the United States as a prescription pharmaceutical treatment for irritable bowel syndrome with constipation in adult women less than 65 years of age. [Alfasigma USA, Inc. (Business Wire, Inc.)] Press Release

Beyond Celiac Awards Nearly $450,000 in Research Grants for Groundbreaking Studies on Celiac Disease

Beyond Celiac has awarded close to $450,000 to two scientists conducting groundbreaking celiac disease studies. One study is aimed at killer cells that cause the actual intestinal tissue damage in celiac disease and the other is researching a more exact way to measure intestinal damage revealed in a biopsy. [Beyond Celiac] Press Release

Crohn’s and Colitis Canada Selects Ten Outstanding Students to Receive the 2019 AbbVie IBD Scholarship

Crohn’s and Colitis Canada has awarded ten scholarships to post-secondary students living with Crohn’s disease or ulcerative colitis through the AbbVie IBD Scholarship Program. These students, who attend universities across the country, are all leaders in their communities, taking the initiative to advocate for diverse causes and create sustainable solutions that will positively impact their peers. [Crohn’s and Colitis Canada] Press Release

Get an overview of intestinal organoids and their applications. Learn More

For a Decade, Francis Collins Has Shielded NIH—While Making Waves of His Own

Collins has helped shield National Institutes of Health (NIH) from threatened budget cuts as well as the upheaval that has shaken many other federal agencies under the Trump administration. [Nature News] Editorial

In Departure for NIH, Cancer Moonshot Requires Grantees to Make Papers Immediately Free

In the United States, federal agencies have stuck to a decade-old policy that allows grantees to publish in journals that keep papers behind a paywall for up to one year. Now, the divide is starting to blur, with one prominent US research program starting to require immediate open access to the peer-reviewed publications it funds. [ScienceMagazine] Editorial

NEW 13 ^th European Colorectal Congress of St. Gallen
December 1-5, 2019
St. Gallen, Switzerland

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

NEW Research Assistant – Pathophysiology of Enteroviruses (University of Cambridge)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Research Technologist – Intestinal Stem Cell Biology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Microbiome in IBD (GIGA-Medical Genomics Unit)

Postdoctoral Fellow – Quantifying Intra-tumour Heteregeneity with Multi-Omics Data (The Institute of Cancer Research)

Postdoctoral Fellow – Designer Probiotics (Massacheusetts General Hospital)

Postdoctoral Fellow – Multi-Omics in Intra-Tumor Heteregenity (The Institute of Cancer Research)

Postdoctoral Researchers – Microbiota in Neonatal Immunity and Imprinting (Institut Pasteur)

Postdoctoral Fellowship – Cancer Biology (Ninewells Hospital and Medical School)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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