Hepatic Cell News Volume 1.43 | Nov 24 2017

TOP STORY

The Orphan Nuclear Receptor COUP-TFII Coordinates Hypoxia-Independent Proangiogenic Responses in Hepatic Stellate Cells

The authors explored whether the nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is involved in hepatic stellate cell (HSC) activation and in the multifunctional role of these cells during the response to liver injury. They showed that COUP-TFII is highly expressed in human fibrotic liver and in mouse models of hepatic injury. [J Hepatol] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Cytoplasmic Localization of the Cell Polarity Factor Scribble Supports Liver Tumor Formation and Tumor Cell Invasiveness

Transcriptome data and immunofluorescence stains of tissue samples derived from hepatocellular carcinoma (HCC) patients revealed that overexpression associated with cytoplasmic localization of the baso-lateral cell polarity complex protein Scribble correlated with poor prognosis of HCC patients. [Hepatology] Abstract

Lipopolysaccharide Mediates Hepatic Stellate Cell Activation by Regulating Autophagy and Retinoic Acid Signaling

Scientists studied the role of lipopolysaccharide (LPS) in hepatic stellate cell (HSC) activation and the underlying mechanisms in vitro and in vivo. They demonstrated that LPS treatment led to a dramatic increase in autophagosome formation and autophagic flux in LX-2 cells and HSCs, which was mediated through the AKT-MTOR and AMPK-ULK1 pathway. [Autophagy] Abstract

CISD2 Haploinsufficiency Disrupts Calcium Homeostasis, Causes Nonalcoholic Fatty Liver Disease, and Promotes Hepatocellular Carcinoma

Cisd2 interacted with Serca2b and mediated its Ca²⁺ pump activity via modulation of Serca2b oxidative modification, which regulated ER Ca²⁺ uptake and maintained intracellular Ca²⁺ homeostasis in the hepatocyte. CISD2 haploinsufficiency disrupted calcium homeostasis, causing ER stress and subsequent nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. [Cell Rep] Full Article | Graphical Abstract

Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-Like Cells Produced by Different Strategies from the Same Donor

Employing two strategies, scientists generated induced pluripotent stem cell-hepatocyte-like cells (HLCs) and hiHeps from the same donor cell line. Both types of HLCs clustered distinctly from each other during gene expression profiling. [Stem Cell Reports] Full Article | Graphical Abstract

Long Noncoding RNA HCAL Facilitates the Growth and Metastasis of Hepatocellular Carcinoma by Acting as a ceRNA of LAPTM4B

The authors investigated lncRNA alterations in hepatocellular carcinoma (HCC) by performing lncRNA microarray analysis. They identified a novel lncRNA called HCC-associated lncRNA (HCAL) that was highly expressed in HCC tissues. HCAL silencing significantly inhibited the growth and metastasis of HCC cells both in vitro and in vivo. [Mol Ther Nucleic Acids] Full Article

Eukaryotic Initiation Factor 5A2 Contributes to the Maintenance of CD133(⁺) Hepatocellular Carcinoma Cells via the c-Myc/MicroRNA-29b Axis

Researchers demonstrated that eukaryotic initiation factor 5A2 (EIF5A2) might play a crucial role in cancer stem cells regulation and investigated its potential molecular mechanisms. Hepatocellular carcinoma cells with high expression of EIF5A2 had a strong capacity to form undifferentiated tumor spheres in vitro and showed elevated levels of stem cell-related genes, leading to an increased ability to develop tumors when subcutaneously injected into nude mice. [Stem Cells] Abstract

Inflammatory Cytokine IL-8/CXCL8 Promotes Tumor Escape from Hepatocyte-Induced Dormancy

Scientists hypothesized that inflammatory signals from hepatic stellate cells, the major inflammatory regulators in the sinusoid, could stimulate dormant cancer cells to emerge. Activated, but not quiescent, hepatic stellate cells secreted soluble factors to induce the proliferation of MCF7 and MDA-MB231 cancer cells. [Br J Cancer] Abstract

Piperidylmethyloxychalcone Improves Immune-Mediated Acute Liver Failure via Inhibiting TAK1 Activity

Chalcone derivatives from medicinal plants protect from hepatic damages including acute liver failure (ALF), but their mechanisms remain to be clarified. Post treatment with piperidylmethyloxychalcone sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. [Exp Mol Med] Full Article

The Similarities between smDCs and regDCs in Alleviating the Immune Injury Caused by Transplantation of Hepatocytes Differentiated from ESCs

Researchers investigated the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and confirmed the low immunogenicity of hepatocytes differentiated from ESCs. [Stem Cell Res Ther] Full Article

Hepatitis E Virus: Advances and Challenges

The authors focus on providing an update on the hepatitis E virus life cycle. They discuss existing cell culture and animal models and highlight platforms that have proven to be useful and/or are emerging for studying other hepatotropic pathogens. [Nat Rev Gastroenterol Hepatol] Abstract

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Exelixis Announces Phase III CELESTIAL Trial Results of Cabozantinib in Previously Treated Advanced Hepatocellular Carcinoma to Be Presented

Exelixis, Inc. announced that the Phase III CELESTIAL trial results have been accepted as a late-breaking presentation. Detailed results from CELESTIAL, the randomized, double-blind, placebo-controlled study of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma who have received prior treatment with sorafenib, will be presented. [Press release from Exelixis, Inc. discussing research to be presented at the 2018 American Society of Clinical Oncology (ASCO)-Gastrointestinal Cancers (GI) Symposium, San Francisco] Press Release

Three UNC-Chapel Hill Researchers Named AAAS Fellows

Professors Blossom Damania, Marcey Waters and Mark Zylka of University of North Carolina (UNC)-Chapel Hill have each been named a fellow by the American Association of the Advancement of Science (AAAS), the world’s largest general scientific society. [University of North Carolina at Chapel Hill] Press Release

ArQule Announces Dosing in a Registrational Trial of FGFR Inhibitor, Derazantinib, for Treatment of Intrahepatic Cholangiocarcinoma

ArQule, Inc. announced dosing of the initial patients in a registrational trial with its FGFR inhibitor, derazantinib in fibroblast growth factor receptor (FGFR)2 fusion driven second-line intrahepatic cholangiocarcinoma. [ArQule, Inc.] Press Release

Nobel Laureates Demand Release of Iranian Scholar Facing Death Sentence

Some 75 Nobel prizewinners have called on the Iranian government to release Ahmadreza Djalali, a researcher in disaster medicine who was sentenced to death last month. The letter is the latest and most powerful protest against the ruling by the scientific community so far. [Nature News] Editorial

Still No Science Advisor at the White House

Ten months into his presidency, Donald Trump has yet to name a science advisor. It’s the longest amount of time a modern president has taken to nominate someone to the position since at least 1976, when Congress established the White House’s Office of Science and Technology Policy. [MIT Technology Review] Editorial

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May 27-31, 2018
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NEW Research Scientist – Chronic Fibrotic and Metabolic Diseases (Gilead Sciences Inc.)

NEW Postdoctoral Fellow – Liver-Like Organoids (KU Leuven)

NEW Postdoctoral Position – Bioengineering of Cell Fate in 3D Organoid Mechanobiology (KU Leuven)

Faculty Positions – Liver Health and Disease (University of Pittsburgh)

Postdoctoral Position – Liver Disease (University of Illinois)

Biomedical Scientist – Molecular and Cellular Gastroenterology (Mayo Clinic)

Faculty Position – Cancer Experimental Therapeutics (University of New Mexico)

Postdoctoral Position – 3D Organoid Mechanobiology (KU Leuven)

Postdoctoral Research Fellow – Liver Tissue Engineering (Massachusetts General Hospital)

Faculty Position – Molecular Oncology (Moffitt Cancer Center)

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