Hepatic Cell News Volume 1.01 | Jan 27 2017

TOP STORY

Fibroblast Growth Factor 15/19 (FGF15/19) Protects from Diet-Induced Hepatic Steatosis: Development of an FGF19-Based Chimeric Molecule to Promote Fatty Liver Regeneration

Investigators studied the role of FGF15/19 in response to a high fat diet and its regulation by saturated fatty acids. They developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration. [Gut] Abstract

(Ranked by impact factor of the journal)

The Linear Ubiquitin Chain Assembly Complex Acts as a Liver Tumor Suppressor and Inhibits Hepatocyte Apoptosis and Hepatitis

To understand the underlying mechanisms of maintenance of liver homeostasis and the role of linear ubiquitination specifically in liver parenchymal cells, researchers investigated the physiological role of HOIP in the liver parenchyma. HOIP deficiency in liver parenchymal cells triggered tumorigenesis at eighteen months of age preceded by spontaneous hepatocyte apoptosis and liver inflammation within the first month of life. [Hepatology] Abstract

An RNA-Based Signature Enables High Specificity Detection of Circulating Tumor Cells in Hepatocellular Carcinoma

The authors examined hepatocellular carcinoma (HCC), a cancer that is derived from liver cells bearing a unique gene expression profile. After identifying a digital signature of 10 liver-specific transcripts, they used a cross-validated logistic regression model to identify the presence of HCC-derived circulating tumor cells in nine of 16 untreated patients with HCC versus one of 31 patients with nonmalignant liver disease at risk for developing HCC. [Proc Natl Acad Sci USA] Full Article | Press Release

The Novel MKL Target Gene Myoferlin Modulates Expansion and Senescence of Hepatocellular Carcinoma

Researchers identified myoferlin as a novel megakaryoblastic leukemia (MKL)/serum response factor (SRF) target gene by gene expression profiling and verification in vivo in hepatocellular carcinoma (HCC) xenografts. Myoferlin was overexpressed in human and murine HCCs triggered by conditional expression of constitutively active SRF-VP16 protein in hepatocytes. [Oncogene] Abstract

Hepatitis B Virus X Protein Promotes the Stem-Like Properties of OV6⁺ Cancer Cells in Hepatocellular Carcinoma

Scientists showed that the concomitant expression of hepatitis B virus X protein (HBx) and OV6 was closely associated with the clinical outcomes and prognosis of patients with HBV-related hepatocellular carcinoma. HBx was required for the stem-like properties of OV6⁺ liver cancer stem-like cells, including self-renewal, stem cell-associated gene expression, tumorigenicity and chemoresistance. [Cell Death Dis] Full Article

Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo

The effects of lidocaine on apoptosis-related and mitogen-activated protein kinase protein expression were evaluated by Western blot analysis. Lidocaine inhibited the growth of HepG2 cells in a dose- and time-dependent manner. The authors also found that lidocaine arrested cells in the G0/G1 phase of the cell cycle and induced apoptosis. [Anesthesiology] Abstract

Patient-Specific Hepatocyte-Like Cells Derived from Induced Pluripotent Stem Cells Model Pazopanib-Mediated Hepatotoxicity

Scientists demonstrated the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. [Sci Rep] Full Article

Decoding the Role of the Nuclear Receptor SHP in Regulating Hepatic Stellate Cells and Liver Fibrogenesis

Previous studies have determined that small heterodimer partner (SHP) activation protects against development of liver fibrosis a process driven by trans-differentiation and activation of hepatic stellate cells (HSCs), a miofibroblast like cell type, involved in extracellular matrix deposition. To dissect signals involved in this activity the authors generated SHP-overexpressing human and rat HSCs. [Sci Rep] Full Article

Plumbagin Restrains Hepatocellular Carcinoma Angiogenesis by Suppressing the Migration and Invasion of Tumor-Derived Vascular Endothelial Cells

Researchers investigated whether plumbagin can abrogate angiogenesis-mediated tumor growth in hepatocellular carcinoma and, if so, through which molecular mechanisms. They observed that in co-cultures of the human endothelial cell line EA.hy926 and the human hepatoma cell line SMMC-7721 and Hep3B, the hepatoma cells induced migration, invasion, tube formation and viability of the EA.hy926 cells in vitro, and these processes were inhibited by plumbagin. [Oncotarget] Full Article

CBX6 Overexpression Contributes to Tumor Progression and Is Predictive of a Poor Prognosis in Hepatocellular Carcinoma

Investigators found that chromobox (CBX) 6 was frequently up-regulated in hepatocellular carcinoma (HCC) clinical samples and HCC cell lines and that CBX6 expression was significantly correlated with larger tumor sizes and multiple tumors. They demonstrated that CBX6 profoundly promoted HCC cell growth both in vitro and in vivo, and mechanistic investigation revealed that the S100A9/NF-κB/MAPK pathway was essential for mediating CBX6 function. [Oncotarget] Full Article

Molecular Bases Underlying the Hepatoprotective Effects of Coffee

In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. The authors critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. [Nutrients] Full Article

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

Positive Topline Results of Large Phase III Trial Show Eisai’s Lenvatinib Meets Primary Endpoint in Unresectable Hepatocellular Carcinoma

Eisai Inc. announced positive topline results from the randomized, multicenter Phase III trial evaluating the company’s multiple receptor tyrosine kinase inhibitor, lenvatinib, for the first-line treatment of patients with unresectable hepatocellular carcinoma. [Eisai Inc.] Press Release

European Medicines Agency Grants Accelerated Assessment, Validates Marketing Authorization Application for AbbVie’s Investigational Regimen of Glecaprevir/Pibrentasvir (G/P) for the Treatment of Chronic Hepatitis C in All Major Genotypes (GT1-6)

AbbVie announced that its marketing authorization application has been validated and is now under accelerated assessment by the European Medicines Agency for the company’s investigational, pan-genotypic regimen of G/P for the treatment of all major chronic hepatitis C virus (HCV) genotypes. If approved, G/P may provide a shorter treatment duration for GT1-6 patients without cirrhosis, who make up the majority of HCV patients, and an additional treatment option to patients with compensated cirrhosis. [AbbVie] Press Release

Proposed U.S. Biotech Rules Raise Industry Hopes and Anxieties

Makers of genetically engineered products have long been on the lookout for changes in U.S. regulations. The system that divvies up the safety review of these products between the Food and Drug Administration, Environmental Protection Agency, and U.S. Department of Agriculture is in the middle of a years-long overhaul, in part to accommodate modern gene-editing technologies such as CRISPR. And a set of new proposals released last week offers hints about what those agencies still hope to change. [ScienceInsider] Editorial

Trump Agenda Threatens US Legacy of Science Diplomacy

A newly minted leader with no experience governing at home or establishing policy abroad now oversees the United States’ vast diplomatic enterprise. US President Donald Trump has a deep bench of scientific and technical expertise to tap across multiple government agencies — but it is not clear that he will use it. [Nature News] Editorial

World’s Foremost Institute on Death and Disease Metrics Gets Massive Cash Boost

The world’s premier centre for health metrics — the science of measuring and analyzing global health problems, and how they relate to healthcare and biomedical research funding — will receive a US$279-million cash injection from the Bill & Melinda Gates Foundation. The cash will go towards expanding the institute’s work over the next decade and consolidating its primacy in the field. It is considered by far the biggest and most influential research centre for health metrics, and its work informs the funding and policy decisions of many national governments and local, regional and global organizations, including the World Bank and the US National Institutes of Health. [Nature News] Editorial

NEW 29^th Lorne Cancer Conference
February 9-11, 2017
Lorne, Australia

NEW Gordon Research Conference: Stem Cells & Cancer
February 12-17, 2017
Barga, Italy

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

NEW 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)

Postdoc/Research Associate – Liver Cancer (Icahn School of Medicine at Mount Sinai)

Research Scientist – Liver Diseases (Gilead Sciences)

Postdoctoral Research Fellow – Liver Genetics (National Jewish Health)

Postdoctoral Research Fellow – Liver Cancer (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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