Hepatic Cell News Volume 2.06 | Feb 16 2018

TOP STORY

Study Shows Liver Cells with Whole Genome Duplications Protect against Cancer

Researchers discovered that cells in the liver with whole genome duplications, known as polyploid cells, can protect the liver against cancer. [Press release from the Children’s Research Institute discussing online prepublication in Developmental Cell] Press Release | Full Article | Graphical Abstract

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3D Microfluidic Liver Cultures as a Physiological Preclinical Tool for Hepatitis B Virus Infection

Scientists demonstrated that the co-culture of primary human hepatocyte with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for hepatitis B virus research. [Nat Commun] Full Article | Press Release

Tumor Cell-Intrinsic Tim-3 Promotes Liver Cancer via NF-κB/IL-6/STAT3 Axis

Investigators showed that human liver cancer tissues contained high ratio of T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes. [Oncogene] Abstract

Glycogen Synthase Kinase-3β Inhibition Promotes Lysosome-Dependent Degradation of c-FLIP_L in Hepatocellular Carcinoma

Researchers showed that glycogen synthase kinase-3β (GSK-3β) was aberrantly activated in hepatocellular carcinoma (HCC). Pharmacological inhibition and genetic depletion of GSK-3β suppressed the growth and induced caspase-dependent apoptosis in HCC cells. [Cell Death Dis] Full Article

STK17B Promotes Carcinogenesis and Metastasis via AKT/GSK-3β/Snail Signaling in Hepatocellular Carcinoma

Scientists reported that serine/threonine kinase 17B (STK17B) had a critical role in hepatocellular carcinoma (HCC) progression. STK17B was significantly upregulated in HCC cell lines and specimens, and patients with ectopic STK17B expression characterized with poor clinicopathological features. [Cell Death Dis] Full Article

Directed Differentiation of Adult Liver Derived Mesenchymal Like Stem Cells into Functional Hepatocytes

The authors report the derivation of novel mesenchymal-like stem cells (arHMSCs) from adult rat hepatocytes. These arHMSCs proliferated in vitro for four passages yielding 104 fold increase in cell number in 28 days, and differentiated into hepatocyte-like cells. [Sci Rep] Full Article

Induction of Differentiation of Intrahepatic Cholangiocarcinoma Cells to Functional Hepatocytes Using an Organoid Culture System

To investigate whether intrahepatic cholangiocarcinoma (IHCC) cells can be converted to functional hepatocytes, scientists established organoids derived from human IHCC and cultured them under conditions suitable for hepatocyte differentiation. [Sci Rep] Full Article

Sestrin2 Facilitates Glutamine Dependent Transcription of PGC-1α and Survival of Liver Cancer Cells under Glucose Limitation

Sestrin2 (SESN2), a stress inducible protein has been reported to regulate survival in glutamine depleted cancer cells, based on this, researchers explored if SESN2 could regulate glutamine metabolism during glucose starvation. They demonstrated that downregulation of SESN2 induces decrease in the levels of intracellular glutamine and PGC-1α under glucose deprivation, concomitant with decline in cell survival but no effect was observed on invasive or migration potential of the cells. [FEBS J] Abstract

PRMT5 Promotes Cell Proliferation by Inhibiting BTG2 Expression via the ERK Signaling Pathway in Hepatocellular Carcinoma

Scientists showed that PRMT5 expression was frequently upregulated in hepatocellular carcinoma (HCC) tissues, and its expression was inversely correlated with overall survival in HCC patients. PRMT5 knockdown markedly inhibited in vitro HCC proliferation and in vivo tumorigenesis. [Cancer Med] Full Article

The Metabolism of Flubendazole in Human Liver and Cancer Cell Lines

Investigators identified all metabolites of Phase I and Phase II of flubendazole (FLU) in human liver and in various cancer cells using UHPLC/MS/MS analysis. They showed that FLU with a reduced carbonyl group was the only FLU metabolite formed in the human liver. [Drug Test Anal] Abstract

Mesenchymal Stromal Cell Therapy for Liver Diseases

The authors summarize the safety, efficacy, potential transplantation routes and therapeutic effects of mesenchymal stromal cells in patients with liver fibrosis. [J Hepatol] Abstract

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New Jersey Health Foundation Awards $50,000 Innovation Grant to Princeton University Researcher Advancing Hepatitis Treatments

New Jersey Health Foundation has awarded a $50,000 Innovation Grant to Alexander Ploss, Ph.D, assistant professor of Molecular Biology at Princeton University. Dr. Ploss is addressing the urgent need of finding better treatments to combat hepatitis B and E viruses. He will use the funding to investigate novel compounds that inhibit hepatitis B and E virus infections. [New Jersey Health Foundation (PR Newswire Association LLC.)] Press Release

Intercept Announces Phase III REVERSE Trial Evaluating OCA for the Treatment of NASH Patients with Compensated Cirrhosis

Intercept Pharmaceuticals, Inc. announced the REVERSE trial. REVERSE is a randomized, double-blind, placebo-controlled, multi-center study that will evaluate the efficacy and safety of the investigational therapy obeticholic acid in approximately 540 patients with a biopsy-confirmed diagnosis of cirrhosis due to Nonalcoholic Steatohepatitis (NASH). [Intercept Pharmaceuticals, Inc.] Press Release

Arrowhead Receives Regulatory Clearance to Begin Phase I/II Study of ARO-HBV for Treatment of Hepatitis B

Arrowhead Pharmaceuticals Inc. announced that it has received approval from the New Zealand Medicines and Medical Devices Safety Authority and from the local Ethics Committee to proceed with a first-in-human study of ARO-HBV, which is being developed as a potentially curative therapy for patients with chronic hepatitis B virus infection. [Arrowhead Pharmaceuticals Inc.] Press Release

Can-Fite BioPharma Announces New Pre-Clinical Data Supporting a Novel Anti-NASH Mechanism of Action for Namodenoson

Can-Fite BioPharma Ltd. announced that pre-clinical studies show Namodenoson’s novel mechanism of action which entails de-regulation of three key signaling pathways which mediate the etiology and pathology of NAFLD/NASH and are responsible for the anti-inflammatory and anti-fibrogenic effect in the liver. [Can-Fite BioPharma Ltd.] Press Release

Trump’s Science Advisor, Age 31, Has a Political Science Degree

A job that’s been held by some of the nation’s top scientists is now occupied by a 31-year-old politics major from Princeton University. And it’s unlikely to change soon, observers say, leaving President Trump without a science advisor as the administration wrestles with a severe outbreak of the flu, lead-poisoned drinking water and record-breaking disasters that many scientists say are sharpened by rising temperatures. [Scientific American] Editorial

Few UK Universities Have Adopted Rules Against Impact-Factor Abuse

Institutions have made little progress against the misuse of research metrics when hiring and promoting academics. [Nature News] Editorial

Researchers Debate Whether Journals Should Publish Signed Peer Reviews

Scientific journals should start routinely publishing the text of peer reviews for each paper they accept, said attendees at a meeting last week of scientists, academic publishers, and funding organizations. But there was little consensus on whether reviewers should have to publicly sign their critiques, which traditionally are accessible only to editors and authors. [ScienceInsider] Editorial

NIH Stays Flat, Absorbs Three Institutes in President’s 2019 Budget Proposal

Biomedical research funding was one of the budget lines saved from cuts by last-minute adjustments to President Donald Trump’s administration’s 2019 budget proposal. Still, advocates say they had hoped for more. [ScienceInsider] Editorial

NEW MDI Biological Laboratory: Origins and Frontiers in Hepatobiliary and Gastrointestinal Physiology 2018
September 8-15, 2018
Bar Harbor, Maine, United States

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NEW Postdoctoral Research Scientist – Hepatocellular Carcinoma (Cancer Research UK Beatson Institute)

Postdoctoral Fellowship – Immunology of Chronic Infections (F. Hoffmann-La Roche AG)

Postdoctoral Fellowship – Translational Cancer Research (Lund University)

Postdoctoral Scholar – Stem Cell Biology and Cancer Biology (University of Iowa)

Lectureship – Stem Cell Biology and Regenerative Medicine (University of Edinburgh)

Postdoctoral Fellow – Liver Cancer Research (University of California, San Francisco)

Postdoctoral Position – Liver Diseases (University of Illinois)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer (University Health Network)

Postdoctoral Fellow – Liver Tissue Engineering (Massachusetts General Hospital and Harvard Medical School)

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