Hepatic Cell News Volume 3.18 | May 24 2019

TOP STORY

Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids

Scientists introduced BAP1 loss-of-function by CRISPR/Cas9 in normal human cholangiocyte organoids. They found that BAP1 controlled the expression of junctional and cytoskeleton components by regulating chromatin accessibility. Consequently, they observed loss of multiple epithelial characteristics while motility increased. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

Investigators revealed both mono- and multiclonal origins in the separate type of combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC), whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. [Cancer Cell] Abstract | Graphical Abstract

Oncofetal HLF Transactivates c-Jun to Promote Hepatocellular Carcinoma Development and Sorafenib Resistance

Hepatic leukemia factor (HLF) was a novel oncofetal protein which was reactivated in hepatocellular carcinoma (HCC) by SOX2 and OCT4. Functional studies revealed that HLF transactivated c-Jun to promote tumor initiating cell (TIC) generation and enhanced TIC-like properties of hepatoma cells, thus driving HCC initiation and progression. [Gut] Abstract

Recapitulation of HDV Infection in a Fully Permissive Hepatoma Cell Line Allows Efficient Drug Evaluation

By stably transducing HepG2 cells with genes encoding the NTCP-receptor and the hepatitis B virus envelope proteins the authors produced a cell line that allowed continuous secretion of infectious progeny hepatitis delta virus (HDV) following primary infection. Evaluation of antiviral drugs showed that the entry inhibitor myrcludex B and interferon-α interfered with primary infection. [Nat Commun] Full Article

Clonorchis sinensis Excretory-Secretory Products Increase Malignant Characteristics of Cholangiocarcinoma Cells in Three-Dimensional Co-Culture with Biliary Ductal Plates

Excretory-secretory product treatment resulted in elevated secretion of interleukin-6 and transforming growth factor-beta1 by H69 cells and a cadherin switch in HuCCT1 cells, indicating an increase in epithelial-mesenchymal transition-like changes by HuCCT1 cells. [PLoS Pathog] Full Article

Central Role of IP₃R2-Mediated Ca²⁺ Oscillation in Self-Renewal of Liver Cancer Stem Cells Elucidated by High-Signal ER Sensor

Researchers found that niche factor-stimulated Ca²⁺ oscillation was a signature feature of cancer stem cell (CSC)-enriched Hep-12 cells and purified α2δ1⁺ CSC fractions from hepatocellular carcinoma cell lines. In Hep-12 cells, the Ca²⁺ oscillation frequency positively correlated with the self-renewal potential. [Cell Death Dis] Full Article

Parvifoline AA Promotes Susceptibility of Hepatocarcinoma to Natural Killer Cell-Mediated Cytolysis by Targeting Peroxiredoxin

Scientists determined that parvifoline AA covalently bound to the conserved cysteine site of peroxiredoxins I/II and inhibited their catalytic activity, subsequently activating the ROS/ERK axis and the immunogenicity of hepatocellular carcinoma toward natural killer cells. [Cell Chem Biol] Abstract | Graphical Abstract

FABP1 Controls Hepatic Transport and Biotransformation of Δ⁹-THC

Investigators demonstrated that fatty acid binding protein 1 (FABP1) accommodated one molecule of Δ⁹-tetrahydrocannabinol (THC) within its ligand binding pocket. Consistent with its role as a THC carrier, biotransformation of THC was reduced in primary hepatocytes obtained from FABP1-knockout mice. [Sci Rep] Full Article

IL-17 and TNFα Cooperation Contributes to the Pro-Inflammatory Response of Hepatic Stellate Cells

IL-17 enhanced TNFα effects on the induction of IL-6, IL-1β, and the chemokine IL-8, CCL20 and MCP-1 expression/secretion in isolated hepatic stellate cell (HSC) cultures. HSC-hepatocyte interactions did not enhance IL-6, IL-8 and CCL20 production compared to hepatocyte alone. However, HSC-hepatocyte interactions increased C-reactive protein expression. [Clin Exp Immunol] Abstract

Subscribe to one of our other 19 science newsletters such as Intestinal Cell News & Pancreatic Cell News.

Fibrosis in Chronic Liver Disease: An Update on Diagnostic and Treatment Modalities

Recent advances have been made in areas of diagnostic and therapeutic modalities, with an increasing number of potential drugs currently in Phase II and III trials, particularly in the field of non-alcoholic steatohepatitis-related liver fibrosis. These new drugs target multiple pathways involved in the pathogenesis of chronic liver disease, and the authors anticipate that some of them may soon be approved for use in patients. [Drugs] Abstract

Epigenetic Mechanisms in Hepatic Stellate Cell Activation during Liver Fibrosis and Carcinogenesis

Investigators focus on the epigenetic alterations participating in the transdifferentiation of hepatic stellate cells from the quiescent to activated state. Recent advances in the field of DNA methylation and post-translational modifications of histones patterns are discussed, together with altered expression and activity of epigenetic remodelers. [Int J Mol Sci] Full Article

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

CymaBay Therapeutics Presents Data in Patients with Primary Biliary Cholangitis

CymaBay Therapeutics, Inc. announced results related to its seladelpar clinical development program for the treatment of primary biliary cholangitis (PBC). Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta agonist currently in development for PBC and nonalcoholic steatohepatitis. [Press release from CymaBay Therapeutics, Inc. discussing research presented at Digestive Disease Week^® (DDW) 2019, San Diego] Press Release

Innovate Biopharmaceuticals Announces Presentation of Three Posters Focusing on the Molecular Biology and Pharmacology of Larazotide

Three posters presented highlighted the protective effect and molecular mechanism of action of larazotide acetate in pre-clinical models via myosin light chain phosphorylation. [Press release from Innovate Biopharmaceuticals, Inc. discussing research presented at Digestive Disease Week^® (DDW) 2019, San Diego] Press Release

The Anti-NASH Effect of Namodenoson Will Be Presented

Can-Fite BioPharma Ltd. announced that it has been selected for a podium presentation in a session of ‘Selected Abstracts of Excellence’ titled, “Namodenoson anti-NAFLD/NASH Activity is Mediated via De-regulation of the Wnt/β-catenin Pathway”. [Press release from Can-Fite BioPharma Ltd. discussing research to be presented at the 2^nd Annual International Conference on Fatty Liver (ICFL), Berlin] Press Release

Albireo Announces Data on Pediatric Cholestatic Liver Diseases to Be Presented

Albireo Pharma, Inc. announced that clinical data and important findings from studies of lead candidate odevixibat in biliary atresia, Alagille syndrome and progressive familial intrahepatic cholestasis have been selected for presentation. [Press release from Albireo Pharma, Inc. discussing research to be presented at the 52^nd European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Annual Meeting, Glasgow] Press Release

Synlogic Announces Clinical Collaboration to Evaluate SYNB1891 in Combination with PD-L1 Checkpoint Inhibitor in Patients with Advanced Solid Tumors

Synlogic, Inc. announced a new clinical collaboration with Roche to explore Synlogic’s Synthetic Biotic™ medicine, SYNB1891, a dual innate immune activator engineered to express a STING agonist, in combination with Roche’s PD-L1-blocking checkpoint inhibitor atezolizumab in patients with advanced solid tumors. [Synlogic, Inc.] Press Release

Cocrystal Pharma Commences Patient Enrollment for Hong Kong Phase IIa Study of CC-31244 for Ultra-Short Treatment of Hepatitis C Virus

The Phase IIa open-label study being conducted at Humanity & Health Research Centre, Humanity and Health Medical Group, in Hong Kong will evaluate the safety, tolerability and preliminary efficacy of Cocrystal’s CC-31244 in combination with sofosbuvir and daclatasvir with or without a protease inhibitor, for the treatment of hepatitis C. [Cocrystal Pharma, Inc.] Press Release

GENFIT Launches a Combination Therapy Clinical Program in NASH

GENFIT announced the launch of a combination program to identify new treatment options for NASH, using elafibranor as backbone therapy. Elafibranor, a PPAR alpha/delta agonist and GENFIT’s lead compound, is currently the only therapy in an advanced Phase III trial targeting “NASH resolution without worsening of fibrosis”. [GENFIT] Press Release

89bio Reports Positive Top-Line Data from Phase I Single-Ascending Dose Clinical Trial of BIO89-100, an Investigational Medicine for NASH

89bio LTD announced positive top-line results from a Phase I single ascending dose study of its investigational medicine, BIO89-100, in healthy volunteers. BIO89-100 is a novel long-acting glycopegylated fibroblast growth factor 21 analogue in clinical development for the treatment of patients with NASH. [89bio LTD] Press Release

Inventiva Announces that FDA Lifts Target Class Clinical Hold Which Allows Long-Term Clinical Studies with Lanifibranor in NASH

Inventiva announced that the FDA has lifted for lanifibranor the clinical hold in place on the peroxisome proliferator-activated receptor target class. This decision enables Inventiva to conduct clinical trials equal to or longer than six months evaluating lanifibranor for the treatment of NASH. [Inventiva] Press Release

Taiwan Considers Double-Blind Peer Review for Grants

Taiwan’s science ministry is thinking of introducing double-blind peer review to assess research-grant proposals, a trend being adopted by some journals to eliminate bias. [Nature News] Editorial

Emory Ousts Two Chinese-American Researchers after Investigation Into Foreign Ties

Emory University has ousted two veteran biomedical researchers and shuttered their laboratory after the National Institutes of Health expressed concern about their foreign ties. The researchers “had failed to fully disclose foreign sources of research funding and the extent of their work for research institutions and universities in China,” the Atlanta-based university said in a statement first reported today by The Atlanta Journal-Constitution. [ScienceInsider] Editorial

NEW The 5^th Canadian Cancer Research Conference (CCRC)
November 3-5, 2019
Ottawa, Ontario, Canada

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

NEW Research Assistant – Liver Immunology (Maynooth University)

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

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Hepatic Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.