Hepatic Cell News Volume 3.17 | May 17 2019

TOP STORY

Ciclopirox Inhibits Hepatitis B Virus Secretion by Blocking Capsid Assembly

Investigators screened 978 FDA-approved compounds for their ability to inhibit hepatitis B virus (HBV) replication in HBV-expressing HepG2.2.15 cells. They found that ciclopirox, a synthetic antifungal agent, strongly inhibited HBV replication in cells and in mice by blocking HBV capsid assembly. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Nucleoporin Nup155 Is Part of the p53 Network in Liver Cancer

Researchers discovered by integrating large scale proteomics, polysome fractionation and a focused RNAi approach that Nup155 controlled mRNA translation of p21, a key mediator of the p53 response. The underlying mechanism involved transcriptional regulation of the putative tRNA and rRNA methyltransferase FTSJ1 by Nup155. [Nat Commun] Full Article

Dysregulated Autophagy and Lysosome Function Are Linked to Exosome Production via miR-155 in Alcoholic Liver Disease

Alcohol reduced autophagy flux in vivo in chloroquine treated mice as well as in vitro in hepatocytes and macrophages treated with bafilomycin A. Scientists revealed that alcohol targeted multiple steps in the autophagy pathway. [Hepatology] Abstract

sGC Stimulator Praliciguat Suppresses Stellate Cell Fibrotic Transformation and Inhibits Fibrosis and Inflammation in Models of NASH

The authors found that soluble guanylate cyclase (sGC) was expressed in hepatic stellate cells and stellate-derived myofibroblasts, but not in hepatocytes. Praliciguat acted directly on isolated hepatic stellate cells to inhibit fibrotic and inflammatory signaling potentially through regulation of AMPK and SMAD7. [Proc Natl Acad Sci USA] Full Article

7-Deoxynarciclasine Shows Promising Antitumor Efficacy by Targeting Akt against Hepatocellular Carcinoma

Scientists found that 7-deoxynarciclasine (7-DONCS) suppressed the growth of hepatocellular carcinoma by inducing the apoptotic and autophagic capacities, as well as by inhibiting epithelial-mesenchymal transition (EMT) in vitro and in vivo. Pre-treatment of cells with specific autophagy inhibitor or knockdown of endogenous LC-3B by siRNA strongly abrogated 7-DONCS-regulated apoptosis and EMT. [Int J Cancer] Abstract

HNRNPAB-Regulated LncRNA-ELF209 Inhibits the Malignancy of Hepatocellular Carcinoma

Researchers indicate that long non-coding RNA (lncRNA)-ELF209 inhibited cell migration, invasion, and epithelial-mesenchymal transition regulated by HNRNPAB. They found that lnc-ELF209 could stabilize triosephosphate isomerase protein expression. They also found that lnc-ELF209 overexpression in HCCLM3 cell resulted in a lower rate of lung metastatic, which suggested a less aggressive hepatocellular carcinoma phenotype. [Int J Cancer] Abstract

miR-455-3p Alleviates Hepatic Stellate Cell Activation and Liver Fibrosis by Suppressing HSF1 Expression

miR-455-3p regulated heat shock factor 1 (HSF1) expression by binding to the 3’UTR of its mRNA directly. Overexpression of HSF1 facilitated hepatic stellate cell activation and proliferation by promoting heat shock protein 47 expression, leading to activation of TGF-β/Smad4 signaling pathway. [Mol Ther Nucleic Acids] Abstract | Full Article

LXRα Limits TGFβ-Dependent Hepatocellular Carcinoma Associated Fibroblast Differentiation

The authors report that agonist-activated liver X receptors (LXR) limited the expression of key components of myofibroblast differentiation, including the α-smooth muscle actin (αSMA) gene in liver cancer cells. Cancer-associated fibroblasts derived from hepatocellular carcinoma expressed high αSMA and low LXRα levels, whereas hepatocarcinoma cells exhibited an inverse expression pattern. [Oncogenesis] Full Article

The Importance of Inter-Individual Kupffer Cell Variability in the Governance of Hepatic Toxicity in a 3D Primary Human Liver Microtissue Model

Scientists utilized a 3D human liver microtissue model to investigate the importance of inter-donor variability of the non-parenchymal cell population in the overall governance of toxicological response following exposure to a panel of nanomaterials. They showed that Kupffer cells were crucial in dictating the overall hepatic toxicity following exposure to the materials. [Sci Rep] Full Article

Triglyceride-Rich Lipoprotein Binding and Uptake by Heparan Sulfate Proteoglycan Receptors in a CRISPR/Cas9 Library of Hep3B Mutants

Investigators used CRISPR/Cas9 gene editing to create a library of mutants in the human hepatoma cell line, Hep3B. Inactivation of EXT1 encoding the heparan sulfate copolymerase, N-deacetylase-N-sulfotransferase 1 and uronyl 2-O-sulfotransferase dramatically reduced binding of triglyceride-rich lipoproteins. [Glycobiology] Abstract

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Roles of Exosomes in Liver Metastases: Novel Diagnosis and Treatment Choices

Based on the mechanism of premetastatic niche formation, the authors summarize the therapeutic and diagnostic potential of exosomes in inhibiting liver metastases in an attempt to provide new avenues for the prevention and treatment of liver metastases. [J Cell Physiol] Abstract

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TriSalus Life Sciences’ Pressure-Enabled Drug Delivery (PEDD) Increases Penetration and Antitumor Activity of Anti-CEA CAR-T in Mouse Model of Liver Metastases

A preclinical trial demonstrated that administering anti-carcinoembryonic antigen (anti-CEA) CAR-T to liver metastases using high delivery pressure in an animal model simulating TriSalus™ Life Sciences’ innovative PEDD™ significantly increased penetration and antitumor activity when compared with standard low-pressure delivery. [Press release from TriSalus™ Life Sciences discussing research to be presented at the 2019 American Association of Immunologists (AAI) Annual Meeting, San Diego] Press Release

Agios Announces the Randomized Phase III ClarIDHy Trial of TIBSOVO^® (Ivosidenib) Achieved Its Primary Endpoint in Previously Treated IDH1 Mutant Cholangiocarcinoma Patients

Agios Pharmaceuticals, Inc. announced that the global Phase III ClarIDHy trial of TIBSOVO^® in previously treated cholangiocarcinoma patients with an isocitrate dehydrogenase 1 (IDH1) mutation met its primary endpoint. [Agios Pharmaceuticals, Inc.] Press Release

Mallinckrodt Completes Enrollment of Phase III Terlipressin CONFIRM Trial

Mallinckrodt plc announced that the company has achieved target enrollment of 300 participants in its Phase III CONFIRM clinical study to evaluate the efficacy and safety of terlipressin, an investigational agent, in adult patients with hepatorenal syndrome type 1. [Mallinckrodt plc] Press Release

GENFIT: Positive 36-Month DSMB Recommendation for Continuation of Phase III RESOLVE-IT Study of Elafibranor in NASH

GENFIT announced that the Data Safety Monitoring Board (DSMB) issued a new positive recommendation for the continuation, without any modifications, of the RESOLVE-IT Phase III trial evaluating elafibranor in NASH. This sixth planned review by the DSMB reiterates previous positive guidance and saw no safety concerns. [GENFIT] Press Release

Abivax and Scripps Research Announce FDA Approval to Initiate a Phase I/II Clinical Trial with ABX196 in Patients with Hepatocellular Carcinoma

Abivax announced, with their collaborator, Scripps Research, that the FDA has accepted an investigational new drug application for ABX196, which showed potent efficacy in hepatocellular carcinoma animal models. [Abivax] Press Release

Dicerna Announces Dosing of First Patient in Phase I Clinical Trial of DCR-HBVS for the Treatment of Chronic Hepatitis B Virus

Dicerna Pharmaceuticals, Inc. announced the dosing of the first patient in its Phase I clinical trial of DCR-HBVS, the company’s investigational GalXCTM-based therapy for the treatment of chronic hepatitis B virus (HBV) infection in adults. [Dicerna Pharmaceuticals, Inc.] Press Release

CytoDyn Initiates Pre-Clinical Study of Leronlimab (PRO 140) to Prevent NASH with the Cleveland Clinic’s Dr. Daniel J. Lindner, M.D., Ph.D.

CytoDyn Inc. announced an agreement with The Cleveland Clinic’s Dr. Daniel Lindner, M.D., Ph.D. to test leronlimab’s ability to prevent non-alcoholic steatohepatitis (NASH) in humanized murine models. The goals of these exploratory pre-clinical studies are to establish the ability of leronlimab to prevent the progression of non-alcoholic fatty Liver disease into NASH. [CytoDyn Inc.] Press Release

Lilly’s CYRAMZA^® (Ramucirumab) Becomes First FDA-Approved Biomarker-Driven Therapy in Patients with Hepatocellular Carcinoma

Eli Lilly and Company announced that the FDA has approved CYRAMZA^®, as a single agent, for the treatment of patients with hepatocellular carcinoma who have an alpha-fetoprotein of ≥400 ng/mL and have been treated with sorafenib. [Eli Lilly and Company] Press Release

Enzo Biochem Inc. Announces Issuance of United States Patent for Treatment of Liver Cancer Using Ozanimod

Enzo Biochem, Inc. announced that it was issued US Patent No. 10,278,960 entitled “Sphingosine Pathway Modulating Compounds for the Treatment of Cancers” that is directed to methods for treating hepatocellular carcinoma, the most common human liver cancer, using the compound Ozanimod. [Enzo Biochem, Inc.] Press Release

Sequana Medical Announces Inclusion of Alfapump^® in German Treatment Guidelines (DGVS) for Complications of Liver Cirrhosis

Sequana Medical NV announced that the alfapump has been included in the DGVS guidelines for complications of liver cirrhosis. [Sequana Medical NV] Press Release

To Meet the ‘Plan S’ Open-Access Mandate, Journals Mull Setting Papers Free at Publication

Plan S, the funder-backed scheme to require free online access to scientific literature, aims to shake up the subscription journals that have long dominated scholarly publishing. Now, some publishers are considering an approach they hope will both comply with the plan and maintain their subscription income: allowing authors to post manuscripts in public archives as soon as their papers are published. [ScienceInsider] Editorial

Indonesia Tops Open-Access Publishing Charts

European funders have been leading a charge under ‘Plan S’ to make more of the scientific literature free to read. Yet the nations that publish the highest proportion of their research papers open access aren’t in Europe, according to a preliminary analysis shared with Nature. [Nature News] Editorial

NEW 6^th Annual European Congress on Clinical and Translational Medicine (EUSTM)
October 18-20, 2019
Vienna, Austria

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

NEW Postdoctoral Research Scientists – Hepatitis Virus Research (Ohio State University)

NEW Faculty Position/Director – Cancer Research (Lewis Katz School of Medicine at Temple University)

Research Assistant – Liver Damage Research (University of Colorado Denver)

Tier I CIHR Canada Research Chair – Mechanisms of Health & Disease (Brock University)

Postdoctoral Fellow – Profiling Single Exosomes & Liver Metastasis Research (McGill University)

Postdoctoral Research Fellow – Organ on a Chip Organoid Development (Universtiy of Oslo)

Research Scientist – Head of the Human Liver Cell Isolation Lab (University of California, San Diego)

Postdoctoral Researcher – Liver Mutagenesis (IRSET)

Postdoctoral Fellow – Fatty Liver Disease Research (Northeast Ohio Medical Universtiy)

Postdoctoral Research Scholarship – Liver Function & Disease (Karolinska Institutet)

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