Hepatic Cell News Volume 1.02 | Feb 3 2017

TOP STORY

Stearoyl-CoA Desaturase Promotes Liver Fibrosis and Tumor Development in Mice via Wnt Signaling and Stabilization of Low Density Lipoprotein Receptor-Related Proteins 5 and 6

The authors investigated whether and how stearoyl-CoA desaturase (SCD) promotes liver fibrosis and tumor development in mice. In rodent hepatic stellate cells and tumor-initiating stem cell-like cells, they found Scd expression to be regulated by Wnt-beta-catenin signaling and monounsaturated fatty acids produced by SCD to provide a positive-feedback loop that amplifies Wnt signaling via stabilization of low-density lipoprotein receptor-related protein (Lrp) 5 and Lrp6 mRNAs, leading to liver fibrosis and tumor growth. [Gastroenterology] Abstract

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Dosage-Dependent Copy Number Gains in E2f1 and E2f3 Drive Hepatocellular Carcinoma

A mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, researchers showed that copy number gains in E2f1 or E2f3 resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. [J Clin Invest] Full Article

The Anticoagulant Rivaroxaban Lowers Portal Hypertension in Cirrhotic Rats Mainly by Deactivating Hepatic Stellate Cells

Scientists investigated the effects of the oral anticoagulant rivaroxaban, a direct anti-factor Xa, on hepatic stellate cells phenotype, liver fibrosis, liver microthrombosis and portal hypertension in cirrhotic rats. Rivaroxaban decreased portal pressure in two rat models of cirrhosis. [Hepatology] Abstract

The Human Longevity Gene Homolog INDY and Interleukin-6 Interact in Hepatic Lipid Metabolism

The authors aimed to study a possible role of mammalian homolog of I am Not Dead, Yet (mIndy) in human hepatic fat metabolism. In obese, insulin resistant patients with non-alcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. [Hepatology] Abstract

A Single Non-Synonymous NCOA5 Variation in Type 2 Diabetic Patients with Hepatocellular Carcinoma Impairs the Function of NCOA5 in Cell Cycle Regulation

The authors report the identification and characterization of a single nucleotide variation in nuclear receptor coactivator 5 (NCOA5), causing an amino acid Thr to Ala substitution, in adjacent non-tumorous liver tissues derived from patients with concurrent hepatocellular carcinoma (HCC) and type 2 diabetes. Their data showed that the T445A variation impairs the ability of NCOA5 to inhibit growth of HCC. [Cancer Lett] Full Article

The Anti-Tumor Activities of Neferine on Cell Invasion and Oxaliplatin Sensitivity Regulated by EMT via Snail Signaling in Hepatocellular Carcinoma

Investigators reported that Neferine had no obvious effects on hepatocellular carcinoma (HCC) cells proliferation, but significantly enhanced cytotoxicity and apoptosis caused by oxaliplatin in vitro and in vivo. Through an upregulation of E-cadherin and downregulation of Vimentin, Snail and N-cadherin, Neferine suppressed epithelial-mesenchymal transition (EMT)-induced migration and invasion abilities of HCC cells. [Sci Rep] Full Article

Low-Dose Acetaminophen Induces Early Disruption of Cell-Cell Tight Junctions in Human Hepatic Cells and Mouse Liver

Scientists demonstrated that acetaminophen, even at low-dose, disrupts the integrity of tight junction and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. [Sci Rep] Full Article | Press Release

Hepatocyte-Specific Smad7 Deletion Accelerates DEN-Induced HCC via Activation of STAT3 Signaling in Mice

Investigators showed that conditional hepatocyte-specific SMAD7 knockout mice develop more tumors than wild-type and corresponding SMAD7 transgenic mice 9 months after diethylnitrosamine challenge, verifying SMAD7 as a tumor suppressor in hepatocellular carcinoma (HCC). [Oncogenesis] Full Article

Egr-1 Regulates Irradiation-Induced Autophagy through Atg4B to Promote Radioresistance in Hepatocellular Carcinoma Cells

Scientists determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in hepatocellular carcinoma (HCC) cell lines SMMC-7721 and HepG2. They showed that autophagy-related gene 4B is induced by Egr-1 upon ionizing radiation in HCC cells. [Oncogenesis] Full Article

Cancer Stem-Like Cells Can Be Induced through Dedifferentiation under Hypoxic Conditions in Glioma, Hepatoma and Lung Cancer

Studies have shown that OCT-4 and Nanog overexpression induced the formation of cancer stem cell-like cells through dedifferentiation and enhanced malignancy in lung adenocarcinoma, and reprogramming SOX-2 in pancreatic cancer cells also promoted the dedifferentiation process. Researchers investigated this phenomenon in glioma, lung cancer and hepatoma cells and found that the transcription factors mentioned before were highly expressed under hypoxic conditions and induced the formation of spheres, which exhibited asymmetric division and cell cycle arrest. [Cell Death Discov] Full Article

The Evolving Concept of Liver Cancer Stem Cells

In the past few decades, cancer stem cells (CSCs) have been identified and characterized in many tumors including liver cancer. The authors review the recent advances in our understanding of the biology of liver CSCs and the development of strategies for their treatment. [Mol Cancer] Full Article

Effects of Natural Products on Fructose-Induced Nonalcoholic Fatty Liver Disease (NAFLD)

Researchers review the natural products and their mechanisms of ameliorating fructose-induced NAFLD over the past years. Although, as lead compounds, natural products usually have fewer activities compared with synthesized compounds, it will shed light on studies aiming to discover new drugs for NAFLD. [Nutrients] Abstract | Full Article (Download)

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

NeuroVive’s New Generation of Sanglifehrin-Based Compounds Demonstrate Potent Inhibitory Effects on Human Hepatocellular Cancer Cells

NeuroVive Pharmaceutical AB will present preclinical data from a new generation of sanglifehrin-based compounds with potent inhibitory effects on hepatocellular carcinoma (HCC) cells and anti-cancer activity in an experimental model of HCC at a scientific conference. [Press release from NeuroVive Pharmaceutical AB discussing research to be presented at the 2017 European Association for the Study of the Liver (EASL) Hepatocellular Carcinoma (HCC) Summit, Geneva] Press Release

Onxeo Completes Enrollment in Phase III Study of Livatag^® for the Treatment of Hepatocellular Carcinoma

Onxeo S.A. announced the completion of enrollment in ReLive, the international Phase III clinical trial evaluating Livatag^® for the treatment of advanced hepatocellular carcinoma. [Onxeo S.A.] Press Release

Enanta Announces U.S. FDA Grants Priority Review to Abbvie’s Investigational HCV Regimen of Glecaprevir/Pibrentasvir (G/P) for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6)

Enanta Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted AbbVie’s New Drug Application (NDA) for its investigational, pan-genotypic regimen of G/P being evaluated for the treatment of GT1-6 of chronic hepatitis C virus (HCV), and has granted the NDA priority review. [Enanta Pharmaceuticals, Inc.] Press Release

The £6 Billion Man: New Top Job in U.K. Science Goes to Mark Walport

The government announced the selection of Mark Walport, currently the chief science adviser to the U.K. government, as head of UK Research and Innovation. The umbrella organization for the existing research councils will serve as the strategic command center of government research funding. [ScienceInsider] Editorial

Trump Immigration Ban Upends International Work on Disease

Efforts to combat diseases rely on networks of scientists to detect outbreaks early, understand how the diseases operate and then intervene. Researchers say that President Donald Trump’s travel ban challenges that process, putting the United States at risk. [Nature News] Editorial

NEW Cell Culture & Downstream World Congress 2017
February 21-22, 2017
Munich, Germany

NEW Innovations in Cancer Research and Regenerative Medicine
September 10-13, 2017
Ho Chi Minh City, Vietnam

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

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

Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

PhD Studentship – Hepatocytes (KU Leuven, Stem Cell Institute)

PhD Position – Pathogens Infecting Liver (Helmholtz Association)

PhD Studentships – Liver Organ Growing (Downstate Medical Center)

Research Scientist – Liver Diseases (Gilead Sciences)

Postdoctoral Research Fellow – Liver Genetics (National Jewish Health)

Postdoctoral Research Fellow – Liver Cancer and Developmental Biology (Fred Hutchinson Cancer Research Center)

Senior Scientist – Oncology (Genentech Research)

Training Fellowship – Clinical Research (University of Oxford)

Postdoctoral Associate – Cancer Biology (University of Florida)

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