Hepatic Cell News Volume 2.31 | Aug 17 2018

TOP STORY

Liver Failure Could Be Eased by Anti-Cancer Drug

People suffering sudden liver failure could one day benefit from a treatment that may reduce the need for transplants. Studies with mice found a class of drugs under development as a cancer treatment can help prompt the liver to regenerate after injury. [Press release from the MRC Centre for Regenerative Medicine discussing online prepublication in Sci Transl Med] Press Release | Abstract

(Ranked by impact factor of the journal)

Neoplastic Transformation of Peribiliary Stem Cell Niche in Cholangiocarcinoma Arisen in Primary Sclerosing Cholangitis

Ducts with neoplastic lesions showed higher inflammation, wall thickness, and peribiliary gland activation compared to non-neoplastic primary sclerosing cholangitis (PSC)-affected ducts. An in vitro study demonstrated that lipopolysaccharide and oxysterols (PSC-related stressors) induced the expression of epithelial-to-mesenchymal transition traits, nuclear factor-κB pathway, autophagy, and the loss of primary cilia in human biliary tree stem/progenitor cells. [Hepatology] Abstract

KIFC1 Regulated by miR-532-3p Promotes Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma via Gankyrin/AKT Signaling

The tumorigenic effect of kinesin family member C1 (KIFC1) depended on gankyrin; inhibiting gankyrin activity reversed epithelial-to-mesenchymal transition via activation of protein kinase B (AKT)/Twist family BHLH transcription factor 1. KIFC1 was directly regulated by the microRNA miR-532-3p, whose downregulation was associated with metastatic progression in hepatocellular carcinoma. [Oncogene] Full Article

HepaRG-Progenitor Cell Derived Hepatocytes Cultured in Bioartificial Livers Are Protected from Healthy- and Acute Liver Failure-Plasma Induced Toxicity

HepaRG cells cultured in bioartificial livers (BALs) were partially protected from plasma-toxicity, which was mainly attributable to medium perfusion and/or 3D configuration applied during BAL culturing. The detrimental human plasma effects were reversible in BAL-cultured cells. [Cell Physiol Biochem] Full Article

CXCL6-EGFR-Induced Kupffer Cells Secrete TGF-β1 Promoting Hepatic Stellate Cell Activation via the SMAD2/BRD4/C-MYC/EZH2 Pathway in Liver Fibrosis

Treatment with CXCL6 stimulated the phosphorylation of EGFR and the expression of TGF-β in cultured Kupffer cells (KCs). Although treatment with CXCL6 directly did not activate the hepatic stellate cell (HSC) line, HSC-T6, HSCs cultured with media taken from KCs treated with CXCL6 or TGF-β showed increased expression of α-SMA, a marker of HSC activation. [J Cell Mol Med] Full Article

HMGB1-Induced Autophagy Facilitates Hepatic Stellate Cells Activation: A New Pathway in Liver Fibrosis

Researchers documented an enrichment of peripheral and intrahepatic high-mobility group box-1 (HMGB1) signal in hepatitis B virus-related liver fibrosis progression. An extracellular regulated protein kinase or c-Jun N-terminal kinase inhibitor not only inhibited recombinant HMGB1-induced autophagy and fibrogenesis in primary hepatic stellate cells, but also restored the suppressed mammalian target of rapamycin and STAT3 pathways. [Clin Sci (Lond)] Abstract

ETS-1 Induces Sorafenib-Resistance in Hepatocellular Carcinoma Cells via Regulating Transcription Factor Activity of PXR

ETS-1 bound to nuclear pregnane X receptor (PXR) directly and enhanced PXR’s transcription factor activity, which further lead to the induction of the PXR’s downstream multi-drug resistance related genes. Overexpression of ETS-1 accelerated the metabolic clearance of sorafenib in hepatocellular carcinoma cells and lead to the better survival and faster migration of those cells. [Pharmacol Res] Abstract | Graphical Abstract

MicroRNA-224 Down-Regulates Glycine N-Methyltransferase Gene Expression in Hepatocellular Carcinoma

Utilizing CCl4-treated hepatoma cells and mice as a cell damage of inflammatory or liver injury model, scientists observed that the decreased expression levels of glycine N-methyltransferase (GNMT) were accompanied with elevated expression levels of miR-224 in hepatoma cells and mouse liver. miR-224 counteracted the effects of GNMT on the reduction of cell proliferation and tumor growth. [Sci Rep] Full Article

Long Non-Coding RNA HOTAIR Promotes Tumorigenesis and Forecasts a Poor Prognosis in Cholangiocarcinoma

Hox transcript antisense intergenic (HOTAIR) was highly expressed both in cholangiocarcinoma (CCA) tissue samples and cell lines compared with corresponding normal bile duct tissues and human intrahepatic biliary epithelial cells. Knockdown of HOTAIR by siRNAs significantly decreased the migration and invasion but increased apoptosis of CCA cells in vitro. [Sci Rep] Full Article

Luteolin Induces Caspase-Dependent Apoptosis via Inhibiting the AKT/Osteopontin Pathway in Human Hepatocellular Carcinoma SK-Hep-1 Cells

Luteolin impaired the AKT pathway by inhibiting the phosphorylation of AKT. SC79, an AKT activator, blocked apoptosis induction, caspases activation, poly (ADP-ribose) polymerase cleavage, downregulation of osteopontin, XIAP, Mcl-1 and Bid in luteolin-treated cells. [Life Sci] Abstract

Somatostatin Analogue, Octreotide, Improves Restraint Stress-Induced Liver Injury by Ameliorating Oxidative Stress, Inflammatory Response, and Activation of Hepatic Stellate Cells

Octreotide treatment provided protection against histopathological changes in the stressed liver in the form of significant reduction in the mean number of degenerated hepatocytes, the area percentage of collagen fibers, and glial fibrillary acid protein immunostaining with a significant increase in the mean number of normal hepatocytes. [Cell Stress Chaperones] Abstract

3D-Spheroid Primary Human Hepatocytes in Mono- and Co-Culture with Non-Parenchymal Cells

Investigators reported successful co-culturing of primary human hepatocytes (PHH) with human liver non-parenchymal cells (NPC). At 3D-spheroid aggregation of PHH/P1c-NPC, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells were successfully integrated and remained present throughout the subsequent 14 culture-period as revealed by the mRNA expression markers and immunostaining. [Tissue Eng Part C Methods] Abstract

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

Alcoholic Liver Disease

Alcoholic liver disease (ALD) can progress from alcoholic fatty liver to alcoholic steatohepatitis (ASH), which is characterized by hepatic inflammation. Chronic ASH can eventually lead to fibrosis and cirrhosis and in some cases hepatocellular cancer. Genetic, epigenetic and non-genetic factors might explain the considerable interindividual variation in ALD phenotype. [Nat Rev Dis Primers] Abstract

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

Eisai and Merck & Co., Inc. Announce FDA Approval of Lenvima^® Capsules for First-Line Treatment of Unresectable Hepatocellular Carcinoma

Eisai Co., Ltd. and Merck & Co., Inc. announced that the FDA approved the kinase inhibitor LENVIMA^® for the first-line treatment of patients with unresectable hepatocellular carcinoma. [Eisai Co., Ltd.] Press Release

Sirnaomics Oncology IND Receives Green Light from US FDA to Initiate Study for Treatment of Cholangiocarcinoma

Sirnaomics, Inc. announced that the FDA has approved the company’s first oncology IND application. The IND approval will allow for the study of the company’s lead product candidate, STP705, in patients with advanced cholangiocarcinoma. [Sirnaomics, Inc.] Press Release

Top Geneticist Loses £3.5-Million Grant in First Test of Landmark Bullying Policy

One of the world’s largest research-funding charities has revoked a £3.5-million (US$4.5-million) grant awarded to a top cancer geneticist, Nazneen Rahman, following allegations that she bullied scientists and other staff when she worked at the Institute of Cancer Research in London. [Nature News] Editorial

What Pakistan’s New Government Means for Science

Pakistan is reeling from a political earthquake — and researchers are both nervous and excited. On 18 August, the former cricket superstar Imran Khan is expected to be sworn in as prime minister. The incoming administration promises to use science to alleviate poverty, but it is facing an imminent economic crisis. [Nature News] Editorial

The NIH Loosens Grip on Gene Therapy Trials

The directors of the National Institutes of Health (NIH) and the US FDA propose limiting the role of the NIH in assessing proposals for gene therapy experiments, the two explain in a commentary in the New England Journal of Medicine. [The Scientist] Editorial

NEW Gordon Research Conference: Vascular Cell Biology
January 20-25, 2019
Ventura, California, United States

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

NEW Postdoctoral Fellowship – Metabolic Research (Umeå University)

NEW Postdoctoral Fellow – Liver and Pancreatic Carcinogenesis (City of Hope)

Senior Research Scientist – Peptide Drug Design & IP (Gubra)

Project Manager – Translational Research and Fundraising (University of Strasbourg)

Postdoctoral Fellow Positions – Metabolic Disorders (Temple University School of Medicine)

Research Faculty Position in Diabetes, Obesity, and Metabolism (University of Pittsburgh)

PhD Positions – Non-Alcoholic Fatty Liver Disease (The Leibniz Institute for Natural Product Research and Infection Biology)

Postdoctoral Position – High-Throughput Functional Screening of iPSC-Derived Models (KU Leuven)

Postdoctoral Position – Liver Cancer Translational Research (IDIBAPS)

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

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.