Hepatic Cell News Volume 1.12 | Apr 21 2017

TOP STORY

Hepatocyte Nuclear Factor 1α Suppresses Steatosis-Associated Liver Cancer by Inhibiting PPARγ Transcription

Researchers combined preclinical mouse models of liver cancer and genetic studies of a human liver biopsy atlas with the aim of identifying putative therapeutic targets in the context of liver steatosis and cancer. They revealed a protumoral interaction of Akt2 signaling with hepatocyte nuclear factor 1α and PPARγ, transcription factors that are master regulators of hepatocyte and adipocyte differentiation, respectively. [J Clin Invest] Full Article

(Ranked by impact factor of the journal)

Efficient Replication of Blood Borne Hepatitis C Virus in Human Fetal Liver Stem Cells

Scientists established a hepatitis C virus (HCV) cell culture model based on human fetal liver stem cells (hFLSCs) that supports the entire blood-borne hepatitis C virus (bbHCV) life cycle. More than 90% of cells remained infected by various genotypes. bbHCV was efficiently propagated, and progeny virus were infectious to hFLSCs. [Hepatology] Abstract

Exosome-Delivered EGFR Regulates Liver Microenvironment to Promote Gastric Cancer Liver Metastasis

The authors showed that EGFR in exosomes secreted from gastric cancer cells could be delivered into the liver and integrated on the plasma membrane of liver stromal cells. The translocated EGFR proved to effectively activate hepatocyte growth factor by suppressing miR-26a/b expression. [Nat Commun] Full Article

Impact of Higher-Order Heme Degradation Products on Hepatic Function and Hemodynamics

Scientists studied the impact of Z-BOX A and B on hepatic functions and explored their alterations in health and cholestatic conditions. Functional implications and mechanisms were investigated in rats, hepatocytic HepG2 and HepaRG cells, human immortalized hepatocytes, and isolated perfused livers. Z–BOX A and B are found in similar amounts in humans and rodents under physiological conditions. [J Hepatol] Abstract | Graphical Abstract

Small Molecule-Mediated Inhibition of Myofibroblast Transdifferentiation for the Treatment of Fibrosis

Investigators report the development of a high throughput image-based screen using primary hepatic stellate cells that identified the antifungal drug itraconazole as an inhibitor of matrix-secreting activated myofibroblasts cell fate in resident fibroblasts derived from multiple murine and human tissues. [Proc Natl Acad Sci USA] Abstract

Deubiquitinase YOD1 Potentiates YAP/TAZ Activities through Enhancing ITCH Stability

Scientists showed that the miR-21-mediated regulation of YOD1 is responsible for the cell-density-dependent changes in YAP/TAZ levels. Using a transgenic mouse model, they demonstrated that the inducible expression of YOD1 enhances the proliferation of hepatocytes and leads to hepatomegaly in a YAP/TAZ-activity-dependent manner. [Proc Natl Acad Sci USA] Abstract

MiR-375 and Doxorubicin Co-Delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma

Investigators report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of hepatocellular carcinoma (HCC) and drug resistance reversion of doxorubicin (DOX). In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX. [Mol Ther] Abstract

Discs Large Homolog 5 Decreases Formation and Function of Invadopodia in Human Hepatocellular Carcinoma via Girdin and Tks5

Researchers investigated the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in hepatocellular carcinoma (HCC). They found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent non-tumor tissues and liver cells. [Int J Cancer] Abstract

Human Neutrophil Peptide-1 Promotes Alcohol-Induced Hepatic Fibrosis and Hepatocyte Apoptosis

Scientists determined if human neutrophil peptide (HNP)-1 affects ethanol-induced liver injury and examined the mechanism of liver injury induced by HNP-1. After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte apoptosis were significantly more severe in transgenic mice than in wild-type C57BL/6N mice. [PLos One] Full Article

Lipid Droplets and Liver Disease: From Basic Biology to Clinical Implications

The authors review the latest insights into the biology of lipid droplets and their role in maintaining lipid homeostasis in the liver. They also offer a perspective of liver diseases that feature lipid accumulation in these lipid storage organelles, which include NAFLD and viral hepatitis. [Nat Rev Gastroenterol Hepatol] Abstract

Unraveling the Regulation of Hepatic Metabolism by Insulin

Researchers summarize recent literature highlighting the importance of both hepatic and extrahepatic mechanisms in insulin regulation of liver glucose and lipid metabolism. They posit that a failure of insulin to inappropriately regulate liver metabolism during type 2 diabetes mellitus is not exclusively from an inherent defect in canonical liver insulin signaling but is instead due to a combination of hyperinsulinemia, altered substrate supply, and the input of several extrahepatic signals. [Trends Endocrinol Metab] Abstract

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

Eiger Announces Additional Phase II Clinical Trial Results for Lonafarnib

Eiger BioPharmaceuticals, Inc. announced additional supportive and encouraging lonafarnib (LNF) data from the Lonafarnib with Ritonavir in Hepatitis Delta Virus (LOWR HDV) program will be presented. After 24 weeks of treatment, all-oral LNF-based regimens suppressed HDV-RNA below the limit of quantitation in 36% of patients, and 60% achieved ALT normalization. [Press release from Eiger BioPharmaceuticals, Inc. (PR Newswire Association LLC.) discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

AbbVie’s Investigational, Pan-Genotypic, Ribavirin-Free Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved 99 Percent SVR(12) Rate in Chronic Hepatitis C Patients with Compensated Cirrhosis

AbbVie announced that 99 percent of chronic hepatitis C virus infected patients with genotype one, two, four, five or six and compensated cirrhosis achieved sustained virologic response at 12 weeks post-treatment (SVR₁₂) with its investigational, pan-genotypic regimen of G/P. These high SVR₁₂ rates were seen following 12 weeks of G/P treatment without ribavirin. [Press release from AbbVie discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

NeuroVive Presents Preclinical Findings of NV556 in NASH Showing Confirmatory Anti-Fibrotic Effects

NeuroVive Pharmaceutical AB announced positive preclinical results demonstrating anti-fibrotic effects with NV556, the company’s preclinical compound for non-alcoholic steatohepatitis (NASH), in an additional well-validated experimental NASH model. [Press release from NeuroVive Pharmaceutical AB discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

DURECT to Present Clinical Data

DURECT Corporation announced that it will present clinical data on DUR-928. The poster presentation will report safety, pharmacokinetics and biomarker data from both cohorts of a Phase Ib study utilizing DUR-928 in patients with nonalcoholic steatohepatitis. [Press release from DURECT Corporation discussing research to be presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

Metacrine to Present Two Abstracts on Its Novel FXR Non-Bile Acid Agonist Program

Metacrine, Inc. announced it will present two abstracts on its novel FXR agonist program. [Press release from Metacrine discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

Prometic’s PBI-4050 Shown to Reduce Liver Damage and Fibrosis in High-Fat Diet Induced Obesity and Metabolic Syndrome Mouse Model

Prometic Life Sciences Inc. presented new results on the positive effects of PBI-4050 on reduction of non-alcoholic steatohepatitis in a mouse model of obesity and metabolic syndrome. [Press release from ProMetic Life Sciences Inc. discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

Gilead Announces Scientific Presentations Demonstrating Efficacy of Harvoni^® (Ledipasvir/Sofosbuvir) in Special Patient Populations with HCV Infection

Gilead Sciences, Inc. announced results from two Phase II studies evaluating Harvoni^® tablets in chronic hepatitis C virus (HCV)-infected patient populations not previously studied in dedicated clinical trials with direct-acting antiviral therapies. [Press release from Gilead Sciences, Inc. discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

Gilead Presents Proof-of-Concept Data for GS-0976 in Nonalcoholic Steatohepatitis (NASH)

Gilead Sciences, Inc. announced results from an open-label, proof-of-concept study evaluating GS-0976, an investigational inhibitor of acetyl-CoA carboxylase, in patients with NASH. [Press release from Gilead Sciences, Inc. discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

Promethera Biosciences Presents Preclinical Data on Novel H2Stem Cell Therapy

Promethera Biosciences SA, a global innovator in cell-based medicines, presented novel in vitro and in vivo data on its preclinical pipeline program H2Stem. [Press release from Promethera Biosciences SA discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

Enanta Announces New Preclinical Data on Its FXR Agonist EDP-305 for Non-Alcoholic Steatohepatitis (NASH) and Primary Biliary Cholangitis (PBC)

Enanta Pharmaceuticals, Inc. announced new data from its lead farnesoid X receptor (FXR) agonist candidate EDP-305 for NASH and PBC. Data from three poster presentations are being presented at the congress that will demonstrate that EDP-305 is a potent FXR agonist that has been shown to reduce expression of fibrogenic genes, reduce fibrosis progression and improve NAFLD activity scores in a variety of preclinical models. [Press release from Enanta Pharmaceuticals, Inc. discussing research to be presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

Inventiva Announces Presentation of Preclinical Results on IVA337 in NASH

Inventiva announced the presentation of a poster on its lead drug candidate IVA337. The results of this preclinical study further confirm the potential of IVA337 as a treatment for NASH. [Press release from Inventiva discussing research presented at The International Liver Congress™ (ILC) 2017, Amsterdam] Press Release

First European Patients Treated with DC Bead LUMI™ Radiopaque Drug-Eluting Beads

BTG plc announced the treatment of the first patients in the EU with DC Bead LUMI™. Two patients were treated for hepatocellular carcinoma and one patient was treated for malignant colorectal cancer metastasized to the liver. [BTG plc] Press Release

Allergan Partners with TARGET PharmaSolutions to Advance NASH Research

Allergan announced that it will collaborate with TARGET PharmaSolutions on its TARGET-nonalcoholic steatohepatitis (NASH) study. TARGET-NASH is a five-year longitudinal observational study that looks at patients with nonalcoholic fatty liver disease or NASH. [Allergan plc] Press Release

Allergan Expands Leading Research & Development NASH Program with Novartis Clinical Collaboration

Allergan announced that it has entered into a clinical trial agreement with Novartis to conduct a Phase IIb study, using Allergan’s cenicriviroc and Novartis’ lead FXR agonist for the treatment of non-alcoholic steatohepatitis (NASH). The Phase IIb study will assess the safety, efficacy and tolerability of this multi-therapy treatment approach for NASH. [Allergan plc] Press Release

FDA Approves Two Hepatitis C Drugs for Pediatric Patients

The U.S. Food and Drug Administration approved supplemental applications for Sovaldi and Harvoni to treat hepatitis C virus in children ages 12 to 17. [U.S. Food and Drug Administration] Press Release

Cerenis Therapeutics Announces the Initiation of the Phase I Clinical Study with CER-209 in NAFLD and NASH

Cerenis Therapeutics announced that their Phase I clinical trial with CER-209, a P2Y13 receptor agonist, has been initiated. The launch follows the FDA Investigational New Drug application approval to initiate the clinical development of CER-209 in healthy volunteers for the clinical investigation of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). [Cerenis Therapeutics Inc.] Press Release

Bristol-Myers Squibb and Nordic Bioscience Announce Collaboration for Fibrosis Biomarker Technology

Bristol-Myers Squibb Company and Nordic Bioscience announced a collaboration agreement to develop biomarker technology to potentially aid in the diagnosis and monitoring of fibrotic diseases including non-alcoholic steatohepatitis. [Bristol-Myers Squibb Company] Press Release

FDA Signs Collaborative Agreement with Emulate, Inc. to Use Organs-on-Chips Technology as a Toxicology Testing Platform for Understanding How Products Affect Human Health and Safety

Emulate, Inc. announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. Food and Drug Administration’s (FDA) Office of Foods and Veterinary Medicine. Under this multi-year CRADA, Emulate and FDA will collaborate to evaluate and qualify the use of Emulate’s Organs-on-Chips technology as a platform for toxicology testing to meet regulatory evaluation criteria for products – including foods, dietary supplements and cosmetics. [Emulate, Inc.] Press Release | Editorial

Power Struggle Erupts at Utah Cancer Institute over Director’s Firing

The abrupt dismissal of the head of a Utah cancer center is causing backlash from its faculty—and its major philanthropic funder—in a struggle over the center’s autonomy from the University of Utah in Salt Lake City. And nearly 2000 researchers have signed a petition calling on the university to reverse its decision. [ScienceInsider] Editorial

For Congress, March for Science is a Democratic Event

Organizers of the March for Science have deliberately avoided reaching out to U.S. elected officials, saying that they want the rallies to be apolitical. As a result, few members of Congress will be participating in the main event in Washington, D.C., and at hundreds of satellite marches across the country. [ScienceInsider] Editorial

NEW Summit for Cancer Immunotherapy 2017
June 25-28, 2017
Gatineau, Canada

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

NEW Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease Research (University of Groningen)

NEW Research Lead – Liver Discovery (Spark Therapeutics)

NEW Research Technician II – Translational Liver Cancer (Fred Hutchinson Cancer Research Center)

Faculty Member – GI/Liver Pathology (Merritt Hawkins)

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)

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)

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