Hepatic Cell News 3.17 May 17, 2019 | |
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TOP STORYCiclopirox 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 | |
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PUBLICATIONS(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 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 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 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 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 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 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 Subscribe to one of our other 19 science newsletters such as Intestinal Cell News & Pancreatic Cell News. | |
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REVIEWSRoles 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 Visit our reviews page to see a complete list of reviews in the hepatic cell research field. | |
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SCIENCE NEWSA 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 | |
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INDUSTRY NEWSAgios 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 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 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 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 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 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. 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 NV announced that the alfapump has been included in the DGVS guidelines for complications of liver cirrhosis. [Sequana Medical NV] Press Release | |
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POLICY NEWSTo 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
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EVENTSNEW 6th Annual European Congress on Clinical and Translational Medicine (EUSTM) Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW 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) Postdoctoral Researcher – Liver Mutagenesis (IRSET) Postdoctoral Fellow – Fatty Liver Disease Research (Northeast Ohio Medical Universtiy) Postdoctoral Research Scholarship – Liver Function & Disease (Karolinska Institutet) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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