Hepatic Cell News Volume 1.11 | Apr 7 2017

TOP STORY

A Drug Screen Using Human iPSC-Derived Hepatocyte-Like Cells Reveals Cardiac Glycosides as a Potential Treatment for Hypercholesterolemia

Scientists used hepatocyte-like cells generated from homozygous familial hypercholesterolemia induced pluripotent stem cells (iPSCs) to identify drugs that can potentially be repurposed to lower serum LDL-C. They found that cardiac glycosides reduce the production of apolipoprotein B from human hepatocytes in culture and the serum of avatar mice harboring humanized livers. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Large, Diverse Population Cohorts of hiPSCs and Derived Hepatocyte-Like Cells Reveal Functional Genetic Variation at Blood Lipid-Associated Loci

The authors recruited a multi-ethnic cohort of healthy volunteers and used their tissue to generate induced pluripotent stem cells and hepatocyte-like cells for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression. They identified many eQTL genes not observed in the comparably sized Genotype-Tissue Expression project’s human liver cohort. [Cell Stem Cell] Abstract | Graphical Abstract

A Functional mTORC1 Signaling Is Indispensable for c-Myc Driven Hepatocarcinogenesis

Investigators demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) cascade is activated and necessary for c-Myc dependent hepatocarcinogenesis. They found that ablation of Raptor, the unique member of the mTORC1 complex, strongly inhibits c-Myc liver tumor formation. [Hepatology] Abstract

Hepatic Stellate Cells Limit Hepatocellular Carcinoma Progression through the Orphan Receptor Endosialin

Based on the established role of endosialin in regulating hepatic stellate cell (HSC)/hepatocyte cross talk, the authors hypothesized that HSC‐expressed endosialin might similarly affect cell proliferation during hepatocarcinogenesis. The histological analysis of human hepatocellular carcinoma samples revealed an inverse correlation between tumor cell proliferation and stromal endosialin expression. [EMBO Mol Med] Full Article

Transcription Factor SPZ1 Promotes TWIST-Mediated Epithelial-Mesenchymal Transition and Oncogenesis in Human Liver Cancer

Investigators compared the expression of spermatogenic leucine zipper 1 (SPZ1) and TWIST1 in specimens of hepatocarcinoma cells (HCCs) and non-HCCs. Forced expression and knockdown of SPZ1 in hepatoma cells showed that SPZ1 was able to regulate the cellular proliferation, invasion, and tumorigenic activity in a TWIST1-dependent manner in vitro and in vivo. [Oncogene] Full Article

ATGL Promotes Autophagy/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism

Hepatic lipid droplet (LD) catabolism is thought to occur via cytosolic lipases such as adipose triglyceride lipase (ATGL) or through autophagy of LDs, a process known as lipophagy. Researchers tested the potential interplay between these metabolic processes and its effects on hepatic lipid metabolism. They showed that hepatic ATGL is both necessary and sufficient to induce both autophagy and lipophagy. [Cell Rep] Full Article | Graphical Abstract

Targeting KDM1A Attenuates Wnt/β-Catenin Signaling Pathway to Eliminate Sorafenib-Resistant Stem-Like Cells in Hepatocellular Carcinoma

Scientists report that the activity of lysine-specific histone demethylase 1A (KDM1A) was required for the emergence of cancer stem cells following prolonged sorafenib treatment. As such, KDM1A inhibitors, such as pargyline and GSK2879552, dramatically suppressed stem-like properties of sorafenib-resistant hepatocellular carcinoma cells. [Cancer Lett] Abstract

Deregulated AJAP1/β-Catenin/ZEB1 Signaling Promotes Hepatocellular Carcinoma Carcinogenesis and Metastasis

Investigators examined the role of adherens junctions-associated protein 1 (AJAP1) in hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. They found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis. [Cell Death Dis] Full Article

Human Induced-Pluripotent Stem Cell-Derived Hepatocyte-Like Cells as an In Vitro Model of Human Hepatitis B Virus Infection

The authors examined the potential of human induced-pluripotent stem cell-derived hepatocyte-like cells (iPS-HLCs) as an in vitro hepatitis B virus (HBV) infection model. Following inoculation with HBV, they found significant production of HBV proteins and viral RNAs in iPS-HLCs. [Sci Rep] Full Article

Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy

Scientists aimed to characterize the antitumor efficacy of sesamol and unveil the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner. [Sci Rep] Full Article

Placental Growth Factor Silencing Ameliorates Liver Fibrosis and Angiogenesis and Inhibits Activation of Hepatic Stellate Cells in a Murine Model of Chronic Liver Disease

Researchers aimed to assess the effect of reducing placental growth factor (PlGF) expression using small interfering RNA on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms. They showed that PlGF was highly expressed in cirrhotic human and mice livers; which mainly distributed in activated hepatic stellate cells. [J Cell Mol Med] Abstract | Full Article

Biomarkers in Hepatocellular Carcinoma: An Overview

The authors review the recent evidence based on hepatocellular carcinoma biomarkers which seems to have a regulative role according to tumor cell development leading to a specific biological response. Epigenetic regulation, microRNAs, and genome sequencing analysis propose molecular expression signatures as novel biomarkers, which allowed for the use of biomarkers in clinical practice. [Expert Rev Gastroenterol Hepatol] Abstract

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

H3 Biomedicine Presents Data on Emerging Pipeline Compounds

H3 Biomedicine Inc. announced that it presented data on two programs. The presentation provided an overview of the pre-clinical data for H3B-6527, an orally available, selective and potent FGFR4 inhibitor which may play an important role in FGF19-driven hepatocellular carcinoma. [Press release from H3 Biomedicine Inc. discussing research presented at the 2017 American Association for Cancer Research Annual Meeting (AACR), Washington, D.C.] Press Release

NGM Bio to Present Phase II Data of NGM282 in NASH

NGM Bio announced that new data from the company’s lead product candidate, NGM282, will be presented in oral and poster presentations. [Press release from NGM Biopharmaceuticals discussing research to be presented at the 2017 International Liver Congress™ of the European Association for the Study of the Liver (EASL), Amsterdam] Press Release | Abstract 1 | Abstract 2 | Abstract 3

Eiger Announces Abstracts and Presentations of LOWR HDV Program

Eiger BioPharmaceuticals, Inc. announced that abstracts from its Lonafarnib with Ritonavir in Hepatitis Delta Virus (LOWR HDV) program will be presented. Forty-eight week data from the Phase II LOWR HDV Program will be presented. [Press release from Eiger BioPharmaceuticals, Inc. (PR Newswire Association LLC.) discussing research to be presented at the 2017 European Association for the Study of the Liver (EASL) meeting, Amsterdam] Press Release

Enanta Pharmaceuticals Announces Data Presentations

Enanta Pharmaceuticals, Inc. announced that several abstracts regarding Enanta’s wholly-owned EDP-305 development program for non-alcoholic steatohepatitis and primary biliary cholangitis, as well as abstracts regarding AbbVie’s investigational, pan-genotypic regimen of glecaprevir/pibrentasvir for the treatment of chronic hepatitis C virus infection, have been accepted for presentation. [Press release from Enanta Pharmaceuticals, Inc. discussing research to be presented at the 2017 International Liver Congress™ of the European Association for the Study of the Liver (EASL), Amsterdam] Press Release

Arrowhead Pharmaceuticals Announces Presentations

Arrowhead Pharmaceuticals Inc. announced that it will present clinical data on ARC-520, ARC-521, and ARC-AAT, the company’s prior generation investigational medicines that were being studied for the treatment of chronic hepatitis B infection and liver disease associated with alpha-1 antitrypsin deficiency. [Press release from Arrowhead Pharmaceuticals Inc. discussing research to be presented at the 2017 International Liver Congress™ of the European Association for the Study of the Liver (EASL), Amsterdam] Press Release

Merck to Present New Data on ZEPATIER^® (Elbasvir and Grazoprevir) and Investigational Combination Therapy MK-3682B for the Treatment of Chronic Hepatitis C Infection

Merck announced that new data from the company’s chronic hepatitis C virus clinical development programs as well as real-world studies on ZEPATIER^® will be presented. [Press release from Merck & Co., Inc. discussing research to be presented at the 2017 International Liver Congress™ of the European Association for the Study of the Liver (EASL), Amsterdam] Press Release

NeuroVive’s Lead NASH Project to Be Presented

NeuroVive Pharmaceutical AB announced that an abstract with preclinical data related to the company’s lead project for non-alcoholic steatohepatitis (NASH) has been accepted for presentation. [Press release from NeuroVive Pharmaceutical AB discussing research to be presented at the 2017 International Liver Congress™ of the European Association for the Study of the Liver (EASL), Amsterdam] Press Release

Galmed Pharmaceuticals to Present Data that Shows Aramchol™ Has a Potential Direct Effect on Liver Fibrosis

Galmed Pharmaceuticals Ltd. announced that it will present data. Galmed’s presentations report the efficacy of Aramchol in methionine/choline-deficient nonalcoholic steatohepatitis and thioacetamide fibrosis models. [Press release from Galmed Pharmaceuticals Ltd. discussing research to be presented at the 2017 International Liver Congress™ of the European Association for the Study of the Liver (EASL), Amsterdam] Press Release

New Data on MIV-818 Will Be Presented

Medivir AB informs that preclinical data on MIV-818 will be presented. The poster presentation, abstract SAT-123, is entitled “Liver-targeting with the novel nucleotide prodrug MIV-818 designed for the treatment of liver cancers” and will include data on the anticancer activity and pharmacokinetic profile of MIV-818. [Press release from Medivir AB discussing research to be presented at the 2017 International Liver Congress™ of the European Association for the Study of the Liver (EASL), Amsterdam] Press Release

Maxwell Biotech Venture Fund’s Portfolio Company Hepatera LLC Announces Completion of Recruitment for Phase IIb Clinical Trials of Myrcludex B in Chronic Hepatitis Delta

Hepatera LLC and its development partner MYR GmbH announced the completion of recruitment for MYR 202 and 203 clinical trials, a Phase IIb program investigating Myrcudex B in chronic hepatitis delta infection. 180 subjects have been enrolled in 20 centers in Russia and Germany. [Hepatera LLC (PR Newswire Association LLC.)] Press Release

Sorrento Therapeutics Anti-CEA CAR-T Demonstrates Promising Clinical Activity and Safety in Phase Ib Clinical Trial

Sorrento Therapeutics, Inc. announced the results from the Hepatic ImmunoTherapy for Metastases-Selective Internal Radiation Therapy Study, a Phase Ib single arm trial testing its anti-CEA CAR-T administered regionally by hepatic artery infusion followed by selective internal radiation therapy in heavily pre-treated patients with CEA positive liver metastases. [Sorrento Therapeutics, Inc.] Press Release

U.S. FDA Approves New Indications for Harvoni^® and Sovaldi^® in Pediatric Patients 12 Years and Older with Chronic Hepatitis C Infection

Gilead Sciences, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved supplemental indications for Harvoni^® tablets and Sovaldi^® tablets for the treatment of chronic hepatitis C virus infection in adolescents without cirrhosis or with compensated cirrhosis, 12 years of age and older, or weighing at least 35kg. [Gilead Sciences, Inc.] Press Release

Keystone Nano Announces Start of Clinical Testing of Ceramide NanoLiposome for the Improved Treatment of Cancer

Keystone Nano, Inc. announced that clinical testing has been started for Ceramide NanoLiposome. Ceramide is a biologically active lipid that has shown efficacy in multiple models of liver cancer, as well as in breast cancer, leukemia and pancreatic cancer. [Keystone Nano, Inc. (PR Newswire Association LLC.)] Press Release

Japanese Scientists Call for Boycott of Military Research

The Science Council of Japan, an advisory body to the cabinet, representing some 850,000 Japanese scientists, released a statement calling on scientists to boycott military research and for universities and research organizations to evaluate the threats posed by such work. [Nature News] Editorial

Initiative Aims to Break Science’s Citation Paywall

The Initiative for Open Citations (I4OC) aims to allow anyone to access science papers’ reference lists and to build analytical services on top of that raw data. Started by the Wikimedia Foundation in San Francisco, California and five other partner organizations, I4OC announced at its official launch that 29 organizations, including some of the world’s largest scientific publishers, have now agreed to openly release citation data. [Nature News] Editorial

NEW Rapid Signaling and Genomic Steroid Hormone Actions in Health and Disease
June 11-16, 2017
Snowmass Village, United States

NEW ISSCR Annual Meeting 2017
June 14-17, 2017
Boston, United States

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

NEW Faculty Member – GI/Liver Pathology (Merritt Hawkins)

NEW Postdoctoral Fellow – Liver microRNAs in Non-Alcoholic Steatohepatitis (AstraZeneca)

Postdoctoral Researchers – Hepatology and Liver Transplantation (Instituto Maimónides de Investigación Biomédica de Córdoba/University of Cordoba)

Academic Surgical Pathologist – Liver/Gastrointestinal (Brigham and Women’s Hospital)

Principal Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

Postdoctoral Position – Alcoholic Liver Fibrosis (University of Copenhagen)

Research Fellow – Hepatocytes (National University of Singapore)

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

Associate or Full Professor – Gastroenterology (University of Washington)

Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

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