Hepatic Cell News Volume 1.30 | Aug 25 2017

TOP STORY

Targeting VCP Enhances Anticancer Activity of Oncolytic Virus M1 in Hepatocellular Carcinoma

Researchers describe an anticancer drug screen for compounds that enhance M1 oncolytic virus activity in hepatocellular carcinoma. An inhibitor of the valosin-containing protein was identified as the top sensitizer, selectively increasing potency of the oncolytic virus up to 3600-fold. [Sci Transl Med] Abstract

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Telomere Length Variation in Tumor Cells and Cancer-Associated Fibroblasts: Potential Biomarker for Hepatocellular Carcinoma

Scientists delineated the variation and prognostic value of telomere length in hepatocellular carcinoma (HCC). Telomere-specific fluorescence in situ hybridization and qPCR were used to evaluate telomere length in HCC cell lines, tumor tissues and isolated non-tumor cells within the tumor. [J Pathol] Abstract

Pseudogene PDIA3P1 Promotes Cell Proliferation, Migration and Invasion, and Suppresses Apoptosis in Hepatocellular Carcinoma by Regulating the p53 Pathway

The authors investigated a novel pseudogene, PDIA3P1, which was upregulated in hepatocellular carcinoma tissues compared with paired normal adjacent tissues. The expression of PDIA3P1 was significantly correlated with tumor size, metastasis, TNM stage, and overall stage. [Cancer Lett] Abstract

Fibroblast Growth Factor 21 (FGF21) Is Robustly Induced by Ethanol and Has a Protective Role in Ethanol Associated Liver Injury

Researchers examined the role of FGF21 on liver pathology in two models of chronic ethanol consumption in both wild type mice and mice lacking FGF21. Acute or binge ethanol consumption significantly increased circulating FGF21 levels in both humans and mice. [Mol Metab] Full Article | Press Release

Activation of PERK-Nrf2 Oncogenic Signaling Promotes Mdm2-Mediated Rb Degradation in Persistently Infected HCV Culture

Scientists reported a novel mechanism for how sustained activation of PERK axis of endoplasmic reticulum-stress during chronic hepatitis C virus infection activates oncogenic Nrf2 signaling that promotes hepatocyte survival and oncogenesis by inducing Mdm2-mediated retinoblastoma protein degradation. [Sci Rep] Full Article

Quercetin Prevents Hepatic Fibrosis by Inhibiting Hepatic Stellate Cell Activation and Reducing Autophagy via the TGF-β1/Smads and PI3K/Akt Pathways

The authors investigated the effect of quercetin on hepatic fibrosis, a characteristic response to acute or chronic liver injury. They showed that quercetin reduced BDL or CCl₄ liver fibrosis, inhibited extracellular matrix formation, and regulated matrix metallopeptidase-9 and tissue inhibitor of metalloproteinase-1. [Sci Rep] Full Article

Augmenter of Liver Regeneration Potentiates Doxorubicin Anticancer Efficacy by Reducing the Expression of ABCB1 and ABCG2 in Hepatocellular Carcinoma

Researchers reported that the transfection of augmenter of liver regeneration (ALR) enhances the antitumor effect of chemotherapy with doxorubicin, a typical anticancer drug, on hepatocellular carcinoma in vitro and in vivo. They demonstrated that ALR inhibits the AKT/Snail signaling pathway, resulting in the downregulation of ABCB1 and ABCG2 expression. [Lab Invest] Abstract

Apelin Protects against Liver X Receptor-Mediated Steatosis through AMPK and PPARα in Human and Mouse Hepatocytes

In order to assess the functional roles of apelin and APJ in hepatocytes, investigators used an in vitro model of liver X receptor-mediated hepatocellular steatosis. Specific inhibitors of cellular signaling components showed inhibition of lipid accumulation by apelin was mediated through G_i/o proteins, AMPK, and SREBP-1c suppression during the early stage and through AMPK, ERKs, and PPARα induction during the late stage. [Cell Signal] Abstract | Graphical Abstract

Enhanced Hepatic Functions of Genetically Modified Mouse Hepatoma Cells by Spheroid Culture for Drug Toxicity Screening

Investigators employed genetically engineered mouse hepatoma cells, Hepa/8F5, wherein expression of liver enriched transcription factors is induced by doxycycline leading to increased functionality. Further enhancement in functionality was achieved by spheroid culture in a previously developed 3D cell culture platform. [Biotechnol J] Abstract

Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells

Induced pluripotent stem cells can differentiate into a wide variety of cell types, including hepatocytes, thereby offering an innovative approach to unravel the mechanisms underlying inborn errors of hepatic metabolism. Moreover, such cell models could potentially provide a platform for the discovery of therapeutics. [Arterioscler Thromb Vasc Biol] Abstract

Progress and Prospects of Circular RNAs in Hepatocellular Carcinoma: Novel Insights into their Function

The authors summarize the functions and mechanisms of those aberrantly expressed circRNAs in hepatocellular carcinoma tissues. The correlation of circRNA abundance in the proliferation of liver regeneration has recently been clarified and different circRNA profiles served as candidates for nonalcoholic steatohepatitis (NASH) diagnosis. [J Cell Physiol] Abstract

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

Blueprint Medicines to Present Updated Data from Ongoing Phase I Clinical Trial of BLU-554 in Patients with Advanced Hepatocellular Carcinoma

Blueprint Medicines Corporation announced that updated data from its ongoing Phase I clinical trial evaluating BLU-554 in patients with advanced hepatocellular carcinoma will be presented in oral presentations. [Press release from Blueprint Medicines Corporation discussing research presented at European Society for Medical Oncology 2017 Congress, Madrid, and 11^th International Liver Cancer Association Annual Conference, Seoul] Press Release

10 Million Reasons that Treatment of Cancers Caused by Viruses May Advance

The National Institute of General Medical Sciences has awarded Louisiana State University Health New Orleans a $10 million grant over five years to support new basic research studies advancing the development new diagnostic and therapeutic approaches for virus-induced cancers. [Louisiana State University Health Sciences Center New Orleans] Press Release

Boehringer Ingelheim Initiates Phase IIa Study of Compound Acquired from Pharmaxis in Debilitating Liver Disease NASH

Boehringer Ingelheim and pharmaceutical company Pharmaxis announce that Boehringer Ingelheim has initiated a European and North American Phase IIa trial in non-alcoholic steatohepatitis with BI 1467335, acquired from Pharmaxis in May 2015. The compound is an oral inhibitor of amine oxidase, copper containing 3, and works by blocking leukocyte adhesion and tissue infiltration in inflammatory processes underlying NASH. [Boehringer Ingelheim GmbH] Press Release

Biomedical Ph.D. Program at Major Research University Drops GRE Requirement for Admission

The University of Michigan’s biomedical sciences graduate program announced that it will no longer require GRE scores for its Ph.D. admissions. Following a review of the available evidence and a public discussion involving the program’s faculty, staff, and trainees, the exam’s ability to predict student performance seems “weak at best” while it significantly disadvantages women, minorities, and students from low socioeconomic backgrounds, writes Scott Barolo, director of the Program in Biomedical Sciences, in the announcement. [Science Careers] Editorial

Leaked Documents Expose Long-Standing Gender Tensions at Salk Institute

Senior female faculty at the Salk Institute for Biological Studies raise more than twice as much in National Institutes of Health funding for scientists working in their labs as their male counterparts, according to a 2016 internal report on “faculty issues” requested by leaders of the San Diego, California institution. Yet Salk leaders favored male scientists by granting them greater access to internal funds and other resources, the report implies, echoing gender discrimination lawsuits filed last month against the research center. [ScienceInsider] Editorial

A Bold Open-Access Push in Germany Could Change the Future of Academic Publishing

Over the past two years, more than 150 German libraries, universities, and research institutes have formed a united front trying to force academic publishers into a new way of doing business. Instead of buying subscriptions to specific journals, consortium members want to pay publishers an annual lump sum that covers publication costs of all papers whose first authors are at German institutions. Those papers would be freely available around the world; meanwhile, German institutions would receive access to all the publishers’ online content. [ScienceInsider] Editorial

NEW 27^th Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL)
March 14-18, 2018
New Delhi, India

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

NEW Postdoctoral Position – Tumor Immunology and Metastasis (Vrije Universiteit Brussel)

Research Associate – Hepatitis B Virus Pathogenesis (Imperial College London)

Research Scientist – Chronic Fibrotic and Metabolic Diseases (Gilead Sciences, Inc.)

Senior Lab Manager – Notch Control of Liver Development (Karolinska Institutet)

Research Fellows – Cancer Research (National University of Singapore)

Multiple Positions – Cancer Research (National University of Singapore)

Assistant Professor – Biomedical Research (National Institutes of Health)

Postdoctoral Scholar – Computational Biology/Cancer Genomics (University of Chicago)

Postdoctoral Fellow – Stem Cell Biology (University of Louisville)

Postdoctoral Research Fellow – Pathogenesis of Metabolic Diseases (Columbia University)

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

Postdoctoral or PhD Position – Cancer Research (University Medical Center Groningen)

Postdoctoral Research Fellow – Translational Liver Cancer Research (Fred Hutchinson Cancer Research Center)

Senior Investigator/Investigator – Molecular Pathology (Novartis Institutes for BioMedical Research)

Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

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