Hepatic Cell News Volume 2.47 | Dec 7 2018

TOP STORY

An Inflammatory-CCRK Circuitry Drives mTORC1-Dependent Metabolic and Immunosuppressive Reprogramming in Obesity-Associated Hepatocellular Carcinoma

Scientists showed that an androgen receptor-driven oncogene, cell cycle-related kinase, collaborates with obesity-induced pro-inflammatory signaling to promote non-alcoholic steatohepatitis-related hepatocarcinogenesis. [Nat Commun] Full Article

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Hepatocyte Nuclear Factor 4 Alpha Activation Is Essential for Termination of Liver Regeneration

Deletion of hepatocyte nuclear factor 4 alpha (HNF4α) resulted in sustained proliferation accompanied by c-Myc and Cyclin D1 over expression and a complete deficiency of hepatocyte function after PH. Overexpression of degradation-resistant HNF4α in hepatocytes delayed but did not prevent initiation of regeneration after PH. [Hepatology] Abstract

A Novel lncRNA, TCONS_00006195, Represses Hepatocellular Carcinoma Progression by Inhibiting Enzymatic Activity of ENO1

LncRNA-6195 acted as a tumor repressor in the development of hepatitis B-related hepatocellular carcinoma (HCC), inhibiting HCC cell proliferation in vitro and in vivo. LncRNA-6195 could combine with α-enolase and repressed its enzymatic activity, thus further inhibiting the energy metabolism in HCC cells. [Cell Death Dis] Full Article

Sestrin 2 Attenuates Rat Hepatic Stellate Cell Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

Researchers found that Sestrin 2 was elevated in both hepatic stellate cells (HSC)-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1), suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the alanine transaminase and aspartate transaminase levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. [Cell Physiol Biochem] Full Article

Sodium Butyrate Reduces High-Fat Diet-Induced Non-Alcoholic Steatohepatitis through Upregulation of Hepatic Glp-1R Expression

Sodium butyrate (NaB) treatment upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. NaB-enhanced GLP-1 receptor expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. [Exp Mol Med] Full Article

Dual Functions of STAT3 in LPS-Induced Angiogenesis of Hepatocellular Carcinoma

Investigators report a novel mechanism by which LPS/STAT3 signaling promoted the angiogenesis of hepatocellular carcinoma (HCC) both in vitro and in vivo. STAT3 activated by LPS increases the production of vascular endothelial growth factor by tumor cells, which not only promoted the proliferation of HCC cells but also stimulated the migration and tubulogenesis of endothelial cells through STAT3 activation and hence promoted angiogenesis in HCC. [Biochim Biophys Acta] Abstract | Graphical Abstract

High Density Huh7.5 Cell Hollow Fiber Bioreactor Culture for High-Yield Production of Hepatitis C Virus and Studies of Antivirals

Scientists established a system based on Huh7.5 cells cultured in a hollow fiber bioreactor in the presence or absence of bovine serum. Using an adapted chimeric genotype 5a virus, they achieved peak HCV infectivity and RNA titers of 7.6 log₁₀ FFU/mL and 10.4 log₁₀ IU/mL, respectively. [Sci Rep] Full Article

LINC00857 Contributes to Hepatocellular Carcinoma Malignancy via Enhancing Epithelial-Mesenchymal Transition

Downregulation of LINC00857 was able to restrain hepatocellular carcinoma (HCC) cell migration and invasion capacity via enhancing epithelial‐mesenchymal transition process. As displayed, E-cadherin protein expression was increased by LINC00857 silence, while N-cadherin protein level was repressed by LV-shLINC00857 in HCC cells. [J Cell Biochem] Abstract

The Long Noncoding RNA Chrome Regulates Cholesterol Homeostasis in Primates

CHROME knockdown in human hepatocytes and macrophages increased the levels of miR-27b, miR-33a, miR-33b and miR-128, thereby reducing the expression of their overlapping target gene networks and associated biological functions. Cells that lack CHROME showed reduced expression of ABCA1, which regulated cholesterol efflux and nascent high-density lipoprotein particle formation. [Nat Metab] Full Article

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Metabolic Aspects in NAFLD, NASH and Hepatocellular Carcinoma: The Role of PGC1 Coactivators

The authors discuss the roles of proliferator-activated receptor-γ coactivators in healthy liver and explore their contribution to the pathogenesis and future therapy of nonalcoholic steatohepatitis and hepatocellular carcinoma. [Nat Rev Gastroenterol Hepatol] Abstract

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Exelixis and Ipsen Initiate Phase III Pivotal Trial of Cabozantinib in Combination with Atezolizumab versus Sorafenib in Previously Untreated Advanced Hepatocellular Carcinoma

Exelixis, Inc. and Ipsen announced the initiation of COSMIC-312, a Phase III pivotal trial of cabozantinib in combination with atezolizumab versus sorafenib in previously untreated advanced hepatocellular carcinoma. [Exelixis, Inc] Press Release

Genfit: Launch of a U.S. Phase II Investigator-Initiated Study with Nitazoxanide in Patients with NASH-Induced Fibrosis

GENFIT announced the initiation of a Phase II proof-of-concept clinical trial evaluating nitazoxanide in patients with non-alcoholic steatohepatitis-induced fibrosis, following submission of the study protocol by Pinnacle Clinical Research to the U.S. FDA. [Genfit] Press Release

Genfit: Positive Phase II Results from Study of Elafibranor in Primary Biliary Cholangitis

GENFIT announced positive results from its Phase II study of elafibranor in patients with primary biliary cholangitis, a chronic liver disease. [Genfit] Press Release

Conatus Announces Results from Encore-Ph Phase IIb Clinical Trial in NASH Cirrhosis

Conatus Pharmaceuticals Inc. announced top-line results from the company’s Phase IIb ENCORE-PH clinical trial showing clinically meaningful treatment effects in compensated NASH cirrhosis patients at high risk of decompensation. [Conatus Pharmaceuticals Inc] Press Release

Tiziana Completes Patient Enrollment in a Phase IIa Trial to Evaluate Tolerability and Anti-Tumor Activity of Milciclib in Hepatocellular Carcinoma

Tiziana Life Sciences plc announced that patient enrollment in the ongoing Phase IIa clinical trial is completed. [Tiziana Life Sciences] Press Release

Integral Molecular’s Therapeutic MAbs against CB1 to Treat NASH Enter New Development Phase following $1.4M NIH Award

Integral Molecular, was awarded $1.4M by the NIH to develop its lead antibodies against cannabinoid receptor 1 for treating the liver disease nonalcoholic steatohepatitis and metabolic disorders, including obesity and metabolic syndrome. [Integral Molecular] Press Release

Research Funders Make Secretive Overseas Investments: Report

An investigation by Science reveals that charities’ investments support activities opposed to their own missions, such as human health and environmental protection. [The Scientist] Editorial

China Backs Bold Plan to Tear Down Journal Paywalls

In a huge boost to the open-access movement, librarians and funders in China have said that they intend to make results of publicly funded research free to read immediately on publication. The move includes a pledge of support for Plan S, a bold initiative launched in September by a group of European funders to ensure that, by 2020, their scientists make papers immediately open. [Nature News] Editorial

NEW AACR Annual Meeting 2019
March 29-April 3, 2019
Atlanta, Unites States

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NEW Research Associate – Cancer Research (University of Cambridge)

Research Associate – Cancer Structural Biology (University of British Columbia)

Postdoctoral Position – Cancer Biology (Fox Chase Cancer Center)

Postdoctoral Scholarships – Medicinal Chemistry, Experimental Biology & Systems Biology (KTH Royal Institute of Technology)

PhD Position – Non-Alcoholic Fatty Liver Disease (Deutsche Diabetes Forschungsgesellschaft e. V)

Postdoctoral Positions – Experimental and Computational Quantitative Single-Cell Biology (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Research Fellow – 3D Organoid Development (University of Oslo)

Postdoctoral Researcher – Alcohol-Induced Liver Injury (Indiana University)

Postdoctoral Researcher – Gene Regulation in Obesity Related Liver Cancer (Umeå University)

Post Doctoral Fellowship – Liver Biology and Pathophysiology (Johns Hopkins University)

Postdoctoral Fellow – Molecular Mechanisms of Alcoholic Liver Disease (Northeast Ohio Medical University)

Postdoctoral Position – Liver Cancer Translational Research (August Pi i Sunyer Biomedical Research Institute)

Postdoctoral Position – Molecular & Integrative Physiology (University of Michigan)

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