Intestinal Cell News Volume 5.43 | Nov 15 2019

TOP STORY

Rapid Evolution and Biogeographic Spread in a Colorectal Cancer

Researchers’ analyses strongly supported an early monoclonal metastatic colonization, followed by a rapid population expansion at both primary and secondary sites. They inferred a hematogenous metastatic spread under positive selection, plus the return of some tumoral cells from the liver back to the colon lymph nodes. [Nat Commun] Full Article

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Irisin Reverses Intestinal Epithelial Barrier Dysfunction During Intestinal Injury via Binding to the Integrin αVβ5 Receptor

Scientists discovered that serum and gut irisin levels were decreased during gut ischemia reperfusion (IR) and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. [J Cell Mol Med] Full Article

Visualization of Epithelial-Mesenchymal Transition in an Inflammatory Microenvironment-Colorectal Cancer Network

Investigators showed the spatiotemporal visualization of colorectal cancer (CRC) cells undergoing epithelial-mesenchymal transition (EMT) using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drove red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-α, IL-1β, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. [Sci Rep] Full Article

Insulin Enhancement of the Antitumor Activity of Chemotherapeutic Agents in Colorectal Cancer Is Linked with Downregulating PIK3CA and GRB2

The authors performed in vivo analysis on mice bearing MC38 colon tumors. To assess the underlying mechanism of the therapy, they examined the mRNA expression of pathways related to the signaling downstream of insulin receptors (INSR). They performed Western blotting to confirm expression patterns derived from the genetic analysis. For the quantification of circulating tumor cells in the peripheral blood, they used the maintrac method. [Sci Rep] Full Article

Tim-3 Suppresses the Killing Effect of Vγ9Vδ2 T Cells on Colon Cancer Cells by Reducing Perforin and Granzyme B Expression

The proportion of Tim-3+ γδ T cells was significantly increased in both the peripheral blood and colon cancer tissue of patients and was significantly associated with TNM staging and tumor volume. Additionally, the activation of Tim-3 signaling significantly inhibited the killing efficiency of Vγ9Vδ2 T cells against colon cancer cells. [Exp Cell Res] Full Article

VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells

Researchers found angiogenesis-independent novel crosstalk between the VEGF and the epidermal growth factor (EGF) pathways in the regulation of colon cancer cell proliferation. Stimulation of colon cancer cells with VEGF-A and placental growth factor activated VEGF receptor-1 (VEGFR-1) and increased proliferation activity in an autocrine EGF/EGF receptor-dependent manner. [Int J Mol Sci] Full Article | Graphical Abstract

Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells

Peripheral blood mononuclear cells were sorted for expression of CD14 and co-cultured with intestinal epithelial cells. Barrier function, as well as tight junctional alterations, were determined. Monocytes were characterized by profiling of cytokines and surface marker expression. [Int J Mol Sci] Full Article

The miR-28-5p-CAMTA2 Axis Regulates Colon Cancer Progression via Wnt/β-Catenin Signaling

Scientists found out that CAMTA2 was high-level expressed in colon cancer, and the upregulated CAMTA2 expression was markedly correlated with poor survival. Functional experiments showed that knockdown of CAMTA2 repressed colon cancer cell proliferation/migration in vitro and attenuated proliferation in vivo. [J Cell Biochem] Full Article

Paclitaxel Loaded EDC-Crosslinked Fibroin Nanoparticles: A Potential Approach for Colon Cancer Treatment

Investigators reported novel paclitaxel loaded EDC-crosslinked fibroin nanoparticles for anticancer purpose. The particles were formulated using a desolvation method and the physicochemical properties were controlled favorably, including the particle size, zeta potential, drug entrapment efficiency, crystallinity, drug solubility, dissolution profiles, and stability. [Drug Deliv Transl Res] Abstract | Graphical Abstract

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Wnt Signaling in 3D: Recent Advances in the Applications of Intestinal Organoids

The authors show alterations in growth factor dependency and organoid morphology can be exploited to identify Wnt signaling mechanisms, characterize mutated pathway components, and predict responses of patient-derived tumors to targeted therapy. They discuss current deficits in the understanding of genotype-phenotype relationships that are to be considered when interpreting mutation-induced changes in organoid morphology. [Trends Cell Biol] Full Article

Molecular Mechanisms of Curcumin and Its Analogs in Colon Cancer Prevention and Treatment

Curcuminoids and their synthetic analogs are now of interest due to their bioactive attributes, especially their action as anticancer activity in various cancer cell line models. Several in vivo and in vitro studies have substantially proved their anticancer activities against colon cancer cell lines. [Life Sci] Abstract | Graphical Abstract

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OSE Immunotherapeutics Announces Licensing Deal for Neoepitope Combination Tedopi^® in Korea with Chong Kun Dang Pharmaceutical Corporation

OSE Immunotherapeutics announced a new licensing deal with Chong Kun Dang Pharmaceutical Corporation for Tedopi^®, a combination of neoepitopes selected and optimized from five tumor antigens shown to generate a specific response of cytotoxic T cells versus cancer cells expressing at least one of these tumor associated antigens and an associated T-helper cell response, for potential registration and commercialization in Korea. [OSE Immunotherapeutics] Press Release

EMD Serono and Pfizer Provide Update on Phase III JAVELIN Gastric 100 Trial

EMD Serono and Pfizer Inc. announced topline results of the Phase III JAVELIN Gastric 100 study evaluating avelumab as first-line maintenance therapy following induction chemotherapy in patients with unresectable, locally advanced or metastatic HER2-negative gastric or gastroesophageal junction cancer versus continuation of chemotherapy or best supportive care. [EMD Serono] Press Release

Zealand Pharma Completes Phase III Clinical Program for HypoPal^® Rescue Pen, Initiates a New Phase II Clinical Proof of Concept Trial with Dasiglucagon, and Secures DKK 560 Million in Additional Investment

Zealand Pharma completes Phase III clinical program for HypoPal^® rescue pen, initiates a new Phase II clinical proof of concept trial with dasiglucagon, and secures DKK 560 million in additional investment. [Zealand Pharma (GlobNewswire, Inc.)] Press Release

EPA’s ‘Secret Science’ Plan Is Back, and Critics Say It’s Worse

Critics are blasting a revised Trump administration plan to give the US Environmental Protection Agency (EPA) broad power to ignore research results when setting public health rules if officials decide the underlying data are not adequately accessible to the public. [ScienceInsider] Editorial

The Mental Health of PhD Researchers Demands Urgent Attention

Two years ago, a student responding to Nature’s biennial PhD survey called on universities to provide a quiet room for “crying time” when the pressures caused by graduate study become overwhelming. At that time, 29% of 5,700 respondents listed their mental health as an area of concern – and just under half of those had sought help for anxiety or depression caused by their PhD study. Things seem to be getting worse. [Nature News] Editorial

NEW Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies
January 9-12, 2020
San Diego, California, United States

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NEW Research Position – Microscopy of Human Tumors (Vienna University of Technology)

Postdoctoral Researcher – Mucosal Immunology (KU Leuven)

Postodoctoral Fellow – Neonatal Microbiota on Immune Imprinting (Pasteur Institute)

PhD Student – Gut Microbiota on Intestinal Inflammation (Flanders Institute for Biotechnology)

Research Fellow – Intestinal In Vivo/In Vitro Correlations (AbbVie)

Postdoctoral Fellow – Gut Microbiome & IBD (Case Western Reserve University)

Postdcotoral Scientist – iPSC Models of Intestinal Fibrosis (Cedars-Sinai Medical Center)

Assistant Professors – Microbiome Research (University of Illinois at Urbana-Champaign)

Senior Scientist – Immunology and Gastroenterology (Johnson & Johnson)

Research Scientist – In Vivo Research on Wnt Signaling in Self-Renewel (Surrozen)

Principal Researcher – Systems Disease Biology (Boehringer Ingelheim)

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