Hepatic Cell News Volume 2.44 | Nov 16 2018

TOP STORY

NUAK2 Is a Critical Yap Target in Liver Cancer

By evaluating several human cancer cell lines scientists determined that NUAK2 is selectively required for YAP-driven growth. They found that NUAK2 participates in a feedback loop to maximize YAP activity via promotion of actin polymerization and myosin activity. [Nat Commun] Full Article

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Endoplasmic Reticulum Stress Mediates Inflammatory Response Triggered by Ultra-Small Superparamagnetic Iron Oxide Nanoparticles in Hepatocytes

Ultra-small superparamagnetic iron oxide nanoparticles (USPIO-NPs) caused higher cytotoxicity and lactate dehydrogenase leakage in hepatic L02 cells than SPIO-NPs. Subsequently, USPIO-NPs affected more genes’ expression than SPIO-NPs analyzed through microarray and bioinformatics analysis. [Nanotoxicology] Abstract

YTHDF2 Suppresses Cell Proliferation and Growth via Destabilizing the EGFR mRNA in Hepatocellular Carcinoma

Researchers report that the down-regulation of YTHDF2 was specifically induced by hypoxia in hepatocellular carcinoma (HCC) cells, and that overexpression of YTHDF2 suppressed cell proliferation, tumor growth and activation of MEK and ERK in HCC cells. [Cancer Lett] Full Article

Long-Term and Mechanistic Evaluation of Drug-Induced Liver Injury in Upcyte Human Hepatocytes

Scientists evaluated the potential of using Upcytes human hepatocytes (UHH) for repeated-dose long-term exposure to drugs. The UHH were incubated with 15 toxic and non-toxic compounds for up to 21 days using a repeated-dose approach, and, in addition to conventional examination of effects on viability, the mechanisms implicated in cell toxicity were also assessed by means of high-content screening. [Arch Toxicol] Full Article

Restoration of FBP1 Suppressed Snail-Induced Epithelial to Mesenchymal Transition in Hepatocellular Carcinoma

Researchers demonstrated that fructose-1,6-bisphosphatase (FBP1) was significantly inhibited during Snail-induced epithelial to mesenchymal transition (EMT) and tissues in hepatocellular carcinoma (HCC). Restoration of FBP1 expression in HCC cancer cells suppressed EMT phenotype, tumor migration and tumor growth induced by Snail overexpression in SMMC-7721 cells. [Cell Death Dis] Full Article

4 in 1: Antibody-Free Protocol for Isolating the Main Hepatic Cells from Healthy and Cirrhotic Single Rat Livers

Isolated cells showed high viability and purity and were characterized as functional: hepatocytes synthetized albumin and urea, liver sinusoidal endothelial cells maintained endocytic capacity and in vivo fenestrae distribution, hepatic macrophages increased expression of inflammatory markers in response to LPS and hepatic stellate cells were activated upon in vitro culture. [J Cell Mol Med] Full Article

Liver-Specific Repin1 Deficiency Impairs Transient Hepatic Steatosis in Liver Regeneration

In vitro steatosis experiments with primary hepatocytes revealed attenuated lipid accumulation and occurrence of smaller lipid droplets in Repin1-deficient cells, while no direct effect on proliferation in HepG2 cells was observed. [Sci Rep] Full Article

Safranal Induces DNA Double-Strand Breakage and Er-Stress-Mediated Cell Death in Hepatocellular Carcinoma Cells

Researchers investigated the anticancer effects of safranal against hepatocellular carcinoma using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 hours, and at S-phase at 24 hours, and a pronounced effect on DNA damage machinery. [Sci Rep] Full Article

Oncogenic Potential of N-Terminal Deletion and S45Y Mutant β-Catenin in Promoting Hepatocellular Carcinoma Development in Mice

Authors found that both β-catenin mutations were able to induce hepatocellular carcinoma (HCC) formation in combination with c-Met at the same latency and efficiency. Tumors showed similar histological features and proliferation rates. Immunohistochemistry showed predominantly nuclear staining of β-catenin in c-Met/∆N90-β-catenin HCC, but membrane immunoreactivity in c-Met/β-cateninS45Y HCC. [BMC Cancer] Full Article

Luteolin Sensitizes Human Liver Cancer Cells to Trail-Induced Apoptosis via Autophagy and Jnk-Mediated Death Receptor 5 Upregulation

Investigators demonstrated that treatment with luteolin and TRAIL exerted a synergistic effect and the mechanisms on TRAIL-resistant Huh7 cells. They demonstrated that luteolin induced an autophagic flux in human liver cancer cells. The attenuation of the autophagic flux by applying the specific inhibitor of autophagy, chloroquine, significantly suppressed DR5 expression. [Int J Oncol] Abstract

Conjugation with Phenylalanine Enhances Autophagy-Inducing Activity of EGCG in Hepatic Cells

Scientists investigated the autophagy-enhancing activity of (-)-epigallocatechin gallate (EGCG) derivatives. Among 14 EGCG derivatives, E10 with a phenylalanine attached to the D-ring of the EGCG exhibited the most promising effects in stimulating autophagy in Huh7 cells. [J Agric Food Chem] Abstract

Preclinical Models for Studying NASH-Driven HCC: How Useful Are They?

The Authors review current literature on the molecular etiology of non-alcoholic steatohepatitis-related hepatocellular carcinoma and critically evaluate existing mouse models and their suitability for studying this malignancy. [Cell Metab] Abstract | Graphical Abstract

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

CymaBay Therapeutics Presents Positive Results from Its Ongoing Phase II Study of Seladelpar in Patients with PBC

CymaBay Therapeutics, Inc. presented data from its ongoing Phase II study of seladelpar in patients with primary biliary cholangitis. Presentations were delivered during two late-breaking presentations as well as multiple additional clinical and pre-clinical presentations. [Press release from CymaBay Therapeutics discussing research presented at The Liver Meeting^® 2018, San Francisco] Press Release

Phase II Results for Madrigal’s Mgl-3196 in Non-Alcoholic Steatohepatitis Presented

Madrigal Pharmaceuticals, Inc. announced the oral presentation of statistically significant results from a double-blind, placebo-controlled 36-week Phase II clinical trial in patients with biopsy-proven non-alcoholic steatohepatitis. [Press release from Madrigal discussing research presented at The Liver Meeting^® 2018, San Francisco] Press Release

Assembly Biosciences Presents Final Results of Phase Ib Study of Abi-H0731

Assembly Biosciences, Inc. presented final data from the Phase Ib study of ABI-H0731 in patients with chronic hepatitis B virus. [Press release from Assembly Biosciences discussing research at The Liver Meeting^® 2018, San Francisco] Press Release

Poxel Presents Promising Data for PXL770 and PXL065 for the Treatment of Non-Alcoholic Steatohepatitis

POXEL SA announced that poster presentations for PXL770 and PXL065 showing promising data for the treatment of NASH. [Press release from Poxel discussing research presented at The Liver Meeting^® 2018, San Francisco] Press Release

Transgene – Positive Results from Phase I Clinical Trial of TG1050 in Chronic Hepatitis B Presented

Transgene announced the complete data from the Phase I trial evaluating the safety and immunogenicity of TG1050 in patients with chronic hepatis B. [Press release from Transgene discussing research presented at The Liver Meeting^® 2018, San Francisco] Press Release

Acquist Presents Positive Results for Its Lead NASH Drug, ACQT1127, at the Liver Meeting^®

Acquist Therapeutics, Inc. presented results for its investigational drugs for patients with nonalcoholic steatohepatitis (NASH). [Press release from Acquist discussing research presented at The Liver Meeting^® 2018 (PR Newswire Association LLC), San Francisco] Press Release

Phase II Data for Galmed Pharmaceutical’s Aramchol^™ in Non-Alcoholic Steatohepatitis Presented

Galmed Pharmaceuticals Ltd. announced the oral abstract presentation of one-year results of the company’s global Phase IIb ARREST study of Aramchol in patients with non-alcoholic steatohepatitis. [Press release from Galmed discussing research presented at The Liver Meeting^® 2018, San Francisco] Press Release

FDA Approves Merck’s KEYTRUDA^® (Pembrolizumab) for the Treatment of Patients with Hepatocellular Carcinoma Who Have Been Previously Treated with Sorafenib

Merck announced that the U.S. FDA has approved KEYTRUDA, Merck’s anti-PD-1 therapy, for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib. [Merck & Co., Inc] Press Release

Valbiotis Announces Expansion of Application for Valedia to Include NASH Prevention

VALBIOTIS announced an expansion of application for VALEDIA to NASH2 prevention. [VALBIOTIS (Business Wire Inc)] Press Release

European Commission Approves Ipsen’s Cabometyx^® (Cabozantinib) for the Treatment of Hepatocellular Carcinoma in Adults Previously Treated with Sorafenib

Ipsen announced that the European Commission has approved Cabometyx® 20, 40, 60 mg as a monotherapy for hepatocellular carcinoma in adults who have previously been treated with sorafenib. [Ipsen Pharma] Press Release

Arix Bioscience Plc: Pharmaxis Releases Positive Results of Phase I Clinical Trial for Second LOXL2 Inhibitor Compound

Arix Bioscience plc has announced positive results from the Phase I clinical trial for the second of its Lysyl Oxidase Like 2 (LOXL2) inhibitor compounds being developed to treat fibrotic diseases such as Non-Alcoholic Steatohepatitis and Idiopathic Pulmonary Fibrosis. [Arix Bioscience] Press Release

The Medicines Patent Pool Signs Licence with AbbVie to Expand Access to Key Hepatitis C Treatment, Glecaprevir/Pibrentasvir

The Medicines Patent Pool announced a new, royalty-free licence agreement with AbbVie for glecaprevir/pibrentasvir (G/P) – a World Health Organization (WHO)-recommended treatment for people living with chronic hepatitis C. [Medicines Patent Pool (PR Newswire Association LLC)] Press Release

STEM Candidates Elected to U.S. House Prepare for Their New Jobs

They’ve won their elections and are headed to Washington, D.C. Their next challenge is using their expertise to make Congress work better. [ScienceInsider] Editorial

Ban on ‘Gene Drives’ Is Back on the UN’s Agenda — Worrying Scientists

Government representatives from nearly 170 countries will this month consider whether to temporarily ban the release of organisms carrying gene drives — a controversial technology that can quickly propagate a chosen gene throughout a population. [Nature News] Editorial

NEW 15^th Annual Stem Cell Symposium: Stem Cells B2B – Bench to Bedside
February 1, 2019
Los Angeles, United States

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

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

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

Postdoctoral Training Fellow – Metabolic Reprograming in Liver Cancer (The Francis Crick Institute)

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

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

Principal Investigator/Group Leader – Non-Alcoholic Fatty Liver Disease (Foundation for Liver Research)

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

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

Principal Scientific Officer – Liver Regeneration & Cancer (Cancer Research UK Beatson Institute)

Postdoctoral Fellow – Inflammation/Innate Immunity/Cell Signaling (University of Colorado Denver)

Faculty Position – Biochemistry and/or Biophysics (University of Kansas Medical Center)

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