Hepatic Cell News Volume 2.26 | Jul 13 2018

TOP STORY

Loss of Tumor Suppressor IGFBP4 Drives Epigenetic Reprogramming in Hepatic Carcinogenesis

Researchers showed that EZH2 acted antagonistically to AKT signaling in maintaining H3K27 methylome through epigenetic silencing of IGFBP4. The in vivo tumorigenicity of IGFBP4-silenced HCC cells was vulnerable to pharmacological inhibition of EZH2, but not AKT. [Nucleic Acids Res] Full Article

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Primary Tumor-Derived Exosomes Facilitate Metastasis by Regulating Adhesion of Circulating Tumor Cells via SMAD3 in Liver Cancer

In vitro and in vivo data showed that hepatocellular carcinoma (HCC) cells promoted cancer cell proliferation and lung metastases formation in a paracrinal/endocrinal way. Investigators found that HCC-derived exosomes mediated this phenomenon and observed enhanced cell adhesion in the presence of these malignant exosomes. Attached HCC cells released exosomes containing both SMAD Family Member 3 (SMAD3) protein and mRNA, which were delivered to detached HCC cells and facilitated their adhesion. [Oncogene] Full Article

Brahma Related Gene 1 (Brg1) Contributes to Liver Regeneration by Epigenetically Activating the Wnt/β-Catenin Pathway in Mice

Researchers investigated the mechanism whereby the chromatin remodeling protein Brg1 regulates liver regeneration in mice. They report that Brg1 deletion in hepatocytes compromised liver regeneration and dampened survival after partial hepatectomy in mice. Brg1 interacted with β-catenin to potentiate Wnt signaling and promote hepatocyte proliferation. [FASEB J] Abstract

ER Stress Regulating Protein Phosphatase 2A-B56γ, Targeted by Hepatitis B Virus X Protein, Induces Cell Cycle Arrest and Apoptosis of Hepatocytes

The expression of B56γ positively correlated with the level of hepatitis B virus X (HBx) in hepatitis B virus (HBV)-infected primary human hepatocytes in human-liver-chimeric mice, HBx-transgenic mice, HBV-infected cells, and HBx-expressing hepatic cells. Mechanistically, B56γ was transactivated by AP-1, which was under the regulation of endoplasmic reticulum stress induced CREBH signaling in HBx-expressing hepatic cells. [Cell Death Dis] Full Article

Somatostatin Octapeptide Inhibits Cell Invasion and Metastasis in Hepatocellular Carcinoma through PEBP1

Somatostatin octapeptide (octreotide) upregulated PEBP1, TIMP-2, and E-cadherin while downregulating MMP-2 and Twist to inhibit cell invasion and metastasis. The in vivo experiments showed no cancer cell metastasis in 4 of the 6 mice in the octreotide-treatment group, while all of the mice in the control group displayed pulmonary metastasis of human hepatocellular carcinoma cells. [Cell Physiol Biochem] Full Article

Three Dimensional Mixed-Cell Spheroids Mimic Stroma-Mediated Chemoresistance and Invasive Migration in Hepatocellular Carcinoma

Researchers developed a mixed-cell spheroid model using Huh-7 hepatocellular carcinoma cells and LX-2 stellate cells to simulate the in vivo tumor environment with respect to tumor-cancer-associated fibroblast interactions. [Neoplasia] Full Article

Up-Regulation of FGF15/19 Signaling Promotes Hepatocellular Carcinoma in the Background of Fatty Liver

A steatohepatitis-hepatocellular carcinoma (HCC) model was established in male C57L/J mice treated with N-nitrosodiethylamine (DEN) and high-fat diet (HFD). A mouse HCC cell line and a mouse hepatocyte line were used to elucidate the mechanism by free fatty acids treatment. Increased levels of FGF15/FGFR4/β-klotho, aberrant epithelial-mesenchymal transition and Wnt/β-catenin signaling were detected in DEN+HFD mice. [J Exp Clin Cancer Res] Full Article

Gut-Liver on a Chip towards an In Vitro Model of Hepatic Steatosis

Investigators introduce a gut-liver chip, which mimicked the gut-absorption and hepatic metabolism in a microfluidic chip. TNF-α, butyrate, and α-lipoic acid were chosen as model molecules that could affect hepatic steatosis via different mechanisms, and their effects were evaluated. [Biotechnol Bioeng] Abstract

High Expression of CD44v9 and xCT in Chemoresistant Hepatocellular Carcinoma: Potential Targets by Sulfasalazine

This study assessed 1) the expression status of CD44v9 and the glutamate-cystine transporter xCT in hepatocellular carcinoma tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization therapy with cisplatin (CDDP) and 2) whether combination of CDDP with sulfasalazine, an inhibitor of xCT, was more effective on the tumor cells than CDDP alone via inducing reactive oxygen species-mediated apoptosis. [Cancer Sci] Abstract

Necroptosis Is a Mechanism of Death in Mouse Induced Hepatocyte-Like Cells Reprogrammed from Mouse Embryonic Fibroblasts

This study investigated the mechanisms underlying the survival, function, and death of hepatocyte-like cells (miHeps). miHeps showed decreased cell viability, increased cytotoxicity, decreased hepatic function, and albumin and urea secretion at passage 14. Addition of necrostatin-1 to miHeps inhibited necrosome formation and reactive oxygen species generation and increased cell survival. [Mol Cells] Abstract

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Animal Models of NAFLD from a Hepatologist’s Point of View

Authors provide a concise overview of the most relevant non-alcoholic fatty liver disease (NAFLD) animal models currently available and discuss the strengths and weaknesses of these models with regard to their comparability to human disease conditions. [Biochim Biophys Acta] Abstract

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

Foundation Aimed at Microbiota Research Awards Grant to Advance Liver Disease Treatment

The Biocodex Microbiota Foundation has announced that Dr. Bernd Schnabl is the 2018 recipient of the Foundation’s international grant to study liver diseases and gut microbiota. Dr. Schnabl, a professor in the Department of Medicine at the University of California San Diego, will use the €200,000 grant to advance his research on the correlation between certain bacteria in the intestines and alcoholic hepatitis. [Biocodex Microbiota Foundation (PR Newswire Association LLC.)] Press Release

Exalenz Bioscience’s Non-Invasive BreathID^® Test to be Evaluated in Two Bristol-Myers Squibb Phase IIb Clinical Trials in Adult Patients with NASH

Exalenz Bioscience Ltd. announced that its BreathID^® 13C-methacetin breath test will be evaluated in two Phase IIb clinical studies sponsored by Bristol-Myers Squibb. The studies are designed to assess the safety and efficacy of its investigational therapy BMS-986036 (PEG-FGF21) in patients with nonalcoholic steatohepatitis (NASH) and either compensated liver cirrhosis, or Stage 3 liver fibrosis. [Exalenz Bioscience Ltd.] Press Release

Assembly Biosciences Initiates Two Phase IIa Trials of ABI-H0731 for the Treatment of Hepatitis B Virus Infection

Assembly Biosciences, Inc. announced the initiation of two multi-center, randomized, placebo controlled Phase IIa trials of ABI-H0731 for the treatment of patients with chronic hepatitis B infection. [Assembly Biosciences, Inc.] Press Release

CohBar Initiates Clinical Study with First-in-Human Dosing of CB4211, a Novel Mitochondria Based Therapeutic for the Treatment of NASH

CohBar, Inc. announced that it has initiated a Phase Ia/Ib safety and biomarker study of CB4211, its lead mitochondria based therapeutic candidate under development as a potential treatment for non-alcoholic steatohepatitis (NASH) and obesity. CB4211 is the first mitochondria based therapeutic to enter clinical testing. [CohBar, Inc.] Press Release

OBI Pharma Granted FDA Orphan Drug Designation for OBI-3424 for the Treatment of Hepatocellular Carcinoma (HCC)

OBI Pharma, Inc. announced that the FDA has granted orphan drug designation for OBI-3424 for the treatment of HCC. OBI-3424 is a first in class DNA alkylating cancer therapeutic agent targeting aldo-keto reductase 1C3 overexpressing cancers. A Phase I/II study of OBI-3424 in patients with solid tumors, including HCC and castrate-resistant prostate cancer, has commenced enrollment at the University of Texas M.D. Anderson Cancer Center. [OBI Pharma, Inc.] Press Release

FDA Grants Priority Review to Merck’s Supplemental Biologics License Application for KEYTRUDA^® (Pembrolizumab) for the Treatment of Patients with Advanced Hepatocellular Carcinoma

Merck announced that the FDA has accepted and granted priority review for a new supplemental biologics license application seeking approval for KEYTRUDA, Merck’s anti-PD-1 therapy, as a treatment for previously treated patients with advanced hepatocellular carcinoma. [Merck & Co., Inc.] Press Release

Dr. Tamara Zietek discusses the use of intestinal organoids as a model system for nutrient transport. Listen Now

Science Journals End Open-Access Trial with Gates Foundation

The publisher of Science last month ended a pilot partnership that allowed open-access publishing for researchers funded by the Bill & Melinda Gates Foundation. [Nature News] Editorial

It’s Time to Burst the Biomedical Bubble in UK Research

A new study calls for a rebalancing of research and innovation funding to better meet the UK’s economic, social and health needs. [The Guardian] Editorial

Petition Asks AAAS to Remove Fellows with Sexual Harassment Records

A petition by members of the scientific community asks the American Association for the Advancement of Science (AAAS) to remove fellows who have been found guilty of sexual harassment or assault. [The Scientist] Editorial

NEW 28^th Annual Conference Asian Pacific Association for the Study of the Liver
February 20-24, 2019
Manila, Philippines

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

NEW Postdoctoral Position – Liver Cancer Translational Research (IDIBAPS)

Postdoctoral Positions – Medicinal Chemistry, Cellular and Experimental Biology and Systems Biology (University of Gothenburg)

Postdoctoral Fellows – Translational Oncology (Baylor College of Medicine)

Postdoctoral Fellow – Liver Cancer (Loyola University Chicago)

Postdoctoral Research Fellow – Gene Regulatory Mechanisms (University of California, Berkeley)

Group Leader – Systems Biology (Center for Systems Biology Dresden)

Postdoctoral/Project Leader – Hepatitis B and D Virus Research (University of Strasbourg)

Postdoctoral Position – Necroptosis in Liver Diseases (Inserm)

EBPOD Fellowship – NAFLD/NASH (European Molecular Biology Laboratory)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

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