Hepatic Cell News Volume 2.02 | Jan 19 2018

TOP STORY

MAIT Cells Are Chronically Activated in Patients with Autoimmune Liver Disease and Promote Pro-Fibrogenic Hepatic Stellate Cell Activation

Scientists addressed the question whether mucosal-associated invariant T (MAIT) cells, innate-like T cells, are functionally altered in patients with autoimmune liver diseases and whether MAIT cells can promote liver fibrosis through activation of hepatic stellate cells. [Hepatology] Abstract

(Ranked by impact factor of the journal)

Kinase-Independent Function of E-Type Cyclins in Liver Cancer

Researchers used conditional cyclin E knockout mice and a liver cancer model to test the requirement for the function of E cyclins in liver tumorigenesis. They showed that a ubiquitous, global shutdown of E cyclins did not visibly affect postnatal development or physiology of adult mice. An acute ablation of E cyclins halted liver cancer progression. [Proc Natl Acad Sci USA] Abstract

Metabolic Reprogramming by PCK1 Promotes TCA Cataplerosis, Oxidative Stress and Apoptosis in Liver Cancer Cells and Suppresses Hepatocellular Carcinoma

Investigators report that the expressions of both phosphoenolpyruvate carboxykinase (PCK)1 and PCK2 genes were downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines resulted in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. [Oncogene] Abstract

Establishment of Practical Recellularized Liver Graft for Blood Perfusion Using Primary Rat Hepatocytes and Liver Sinusoidal Endothelial Cells

Scientists established a seeding method for the optimal distribution of parenchymal and endothelial cells, and evaluated the effect of liver sinusoidal endothelial cells in the decellularized liver. [Am J Transplant] Abstract

MicroRNA-146a-5p Attenuates Irradiation-Induced and LPS-induced Hepatic Stellate Cell Activation and Hepatocyte Apoptosis through Inhibition of TLR4 Pathway

The authors found that irradiation and lipopolysaccharide (LPS) stimulation induced toll-like receptor 4 (TLR4) and miR-146a-5p expression in the human hepatic stellate cell line LX2. [Cell Death Dis] Full Article

Ethanol Sensitizes Hepatocytes for TGF-β-Triggered Apoptosis

Researchers elucidated the crosstalk of transforming growth factor beta1 (TGF-β) and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. [Cell Death Dis] Full Article

A Humanized Mouse Model of Liver Fibrosis following Expansion of Transplanted Hepatic Stellate Cells

To investigate whether hepatic stellate cells (HSCs) could engraft and repopulate the liver, scientists transplanted GFP-transduced immortalized human HSCs into immunodeficient NOD/SCID mice. [Lab Invest] Abstract

Human Liver Organoids Generated with Single Donor-Derived Multiple Cells Rescue Mice from Acute Liver Failure

The authors developed a new strategy for acute liver failure treatment by transplanting functional liver organoids generated from single donor-derived human induced pluripotent stem cell endoderm, endothelial cells, and mesenchymal cells. [Stem Cell Res Ther] Full Article

Proliferation and Survival of Human Amniotic Epithelial Cells during Their Hepatic Differentiation

Researchers studied the proliferation and survival of the human amniotic epithelial cells during their hepatic differentiation. They also analyzed the changes in pluripotency and hepatic markers. [PLoS One] Full Article

Glaucocalyxin A Attenuates the Activation of Hepatic Stellate Cells through the TGF-β1/Smad Signaling Pathway

Scientists investigated the effects of glaucocalyxin A on hepatic stellate cells activation/proliferation and migration in vitro and its possible mechanism in liver fibrosis. [DNA Cell Biol] Abstract

Extrahepatic Cancers and Chronic HCV Infection

The authors report on recent studies analyzing the risk of extrahepatic cancers associated with chronic HCV infection. Although there is no doubt regarding the direct and indirect causality between HCV and non-Hodgkin lymphoma, an increased risk of other cancers is less clear, with the exception of cholangiocarcinoma. [Nat Rev Gastroenterol Hepatol] Abstract

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

Ipsen and Exelixis Announce Phase III Trial Results of Cabozantinib Demonstrating Significant Overall Survival Benefit in Patients with Previously Treated Advanced Hepatocellular Carcinoma

Exelixis, Inc. and Ipsen announced detailed results of the pivotal Phase III CELESTIAL trial in patients with previously treated advanced hepatocellular carcinoma, which will be presented in a late-breaking oral session. [Press release from Exelixis, Inc. discussing research presented at the 2018 American Society of Clinical Oncology (ASCO)-Gastrointestinal (GI) Cancers Symposium, San Francisco] Press Release

Independent Imaging Review Confirmed Positive Data from Primary Analysis of REFLECT Trial Evaluating Lenvatinib Compared to Sorafenib in Unresectable Hepatocellular Carcinoma

Eisai Inc. announced results from the independent imaging review of the REFLECT study, a Phase III trial evaluating lenvatinib, the company’s multiple receptor tyrosine kinase inhibitor, versus sorafenib, for the potential first-line treatment of patients with unresectable hepatocellular carcinoma. [Press release from Eisai Inc. (PR Newswire Association LLC.) discussing research presented at the 2018 American Society of Clinical Oncology (ASCO)-Gastrointestinal (GI) Cancers Symposium, San Francisco] Press Release

First-Time Data for Merck’s KEYTRUDA^® (Pembrolizumab) in Patients with Previously Treated Advanced Hepatocellular Carcinoma (HCC) to be Presented

Merck announced findings from the registrational Phase II KEYNOTE-224 trial investigating the use of KEYTRUDA^®, the company’s anti-PD-1 therapy, in patients with advanced hepatocellular carcinoma, the most common type of liver cancer, who were previously treated with systemic therapy. [Press release from Merck & Co., Inc. discussing research presented at the 2018 American Society of Clinical Oncology (ASCO)-Gastrointestinal (GI) Cancers Symposium, San Francisco] Press Release

AVEO Oncology Announces Presentation of Data from Phase Ib/II Study of Tivozanib in Patients with Advanced Hepatocellular Carcinoma

AVEO Oncology announced the presentation of data from a multicenter, Phase Ib/II study of FOTIVDA^®, a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor receptors, in patients with advanced, unresectable hepatocellular carcinoma. [Press release from AVEO Pharmaceuticals, Inc. discussing research presented at the 2018 American Society of Clinical Oncology (ASCO)-Gastrointestinal (GI) Cancers Symposium, San Francisco] Press Release

TRACON Pharmaceuticals Announces Positive Data from Ongoing Phase Ib/II Trial of TRC105 in Hepatocellular Carcinoma Patients

TRACON Pharmaceuticals announced that positive initial clinical data from its ongoing Phase Ib/II study of TRC105 and Nexavar^® in patients with advanced hepatocellular carcinoma were presented in a poster presentation. [Press release from TRACON Pharmaceuticals discussing research presented at the 2018 American Society of Clinical Oncology (ASCO)-Gastrointestinal (GI) Cancers Symposium, San Francisco] Press Release

Arcturus Therapeutics Announces Expansion of Collaboration with Takeda Pharmaceuticals to Develop RNA-Based Therapeutics for the Treatment of Nonalcoholic Steatohepatitis (NASH) and Other GI Disorders

Arcturus Therapeutics Ltd. announced that it is extending its partnership with Takeda Pharmaceutical Company Limited. Under the collaboration, Takeda and Arcturus will advance their efforts to develop RNA-based therapeutics for the treatment of NASH and other gastrointestinal (GI) related disorders using Arcturus’s wholly-owned LUNAR^™ lipid-mediated delivery systems and UNA Oligomer chemistry. [Arcturus Therapeutics Ltd.] Press Release

GC Pharma Confirms Phase II/III Clinical Trial of New Protein Therapy for Hepatitis B

GC Pharma announced that it will proceed with a Phase II/III clinical trial for GC1102, the company’s investigational recombinant hepatitis B immune globulin for preventing the recurrence of hepatitis B virus infection following liver transplantation. [GC Pharma (PR Newswire Association LLC.)] Press Release

First Chronic Hepatitis B Patient Dosed in China in a Phase I Trial of T101 (Transgene’s TG1050 Technology)

Transgene announced that the first patient has been dosed in a Phase I clinical trial in China, evaluating T101, a therapeutic vaccine based on Transgene’s immunotherapy technology for the treatment of chronic hepatitis B virus infection. [Transgene] Press Release

Broad Institute Takes a Hit in European CRISPR Patent Struggle

A decision from the European Patent Office (EPO) has put the Broad Institute in Cambridge, Massachusetts, on shaky ground with its intellectual property claims to the gene-editing tool CRISPR. EPO revoked a patent granted to the Broad for fundamental aspects of the technology, one of several of its patents facing opposition in Europe. [ScienceInsider] Editorial

Brexit Vote Didn’t Spur Quick Exodus from UK Universities

The number of European Union nationals working as academics at British universities increased slightly in the year that the United Kingdom voted to leave the EU, according to figures published by the Higher Education Statistics Agencyon. [Nature News] Editorial

In Trump’s First Year, Science Advice Sees a Marked Decline

Since U.S. President Donald Trump took office, expert panels that provide key federal agencies with science advice have had fewer members and met less often than at any time since 1997, when the government started tracking such numbers, a new analysis concludes. [ScienceInsider] Editorial

What a US Government Shutdown Would Mean for Science

The clock is ticking for US lawmakers, who have fewer than two days to pass a new budget or face a government shutdown. Nature explains why politicians are struggling to reach a deal, what is at stake for science and whether a crisis can be avoided. [Nature News] Editorial

NEW Aegean Conferences: 2^nd International Conference on Tissue Repair, Regeneration, and Fibrosis
June 13-18, 2018
Crete, Greece

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NEW Locum Chief Editor – Nature Reviews Gastroenterology & Hepatology (Nature Research)

Postdoctoral Position – Feeding Regulated Chromatin Organization and Gene Transcription in the Liver (University of Southern Denmark)

Postdoctoral Position – Liver Diseases (University of Illinois)

Part-Time Postdoctoral Scientist – HCV Vaccine Model Development (University of Oxford)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer (University Health Network)

Postdoctoral Scholar Position – Cancer & Stem Cell Epigenomics (University of California, Davis)

Postdoctoral Fellow – Liver Tissue Engineering (Massachusetts General Hospital and Harvard Medical School)

Assistant, Associate or Full Professor – Hepatology (University of California, San Diego)

Research Fellow – Hepatitis B Virology (National University of Singapore)

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