Hepatic Cell News Volume 2.21 | Jun 8 2018

TOP STORY

Kras and Tp53 Mutations Cause Cholangiocyte- and Hepatocyte-Derived Cholangiocarcinoma

While intrahepatic cholangiocarcinoma (iCCA) is conventionally thought to arise from the biliary tract, studies have suggested that both hepatocytes and biliary cells (cholangiocytes) may give rise to iCCA. Researchers generated mouse models to examine the consequence of targeting mutant Kras and Tp53, common alterations in human iCCA, to different adult liver cell types. [Cancer Res] Abstract

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Genetic and Chemical Screenings Identify HDAC3 as a Key Regulator in Hepatic Differentiation of Human Pluripotent Stem Cells

By taking advantage of CRISPR-Cas9-based genome-wide screening technology and a high-throughput human pluripotent stem cells screening platform with a reporter readout, scientists identified several potential genetic regulators of hepatocyte-like cell differentiation. [Stem Cell Reports] Graphical Abstract | Full Article

Intrahepatic HBV Large Surface Antigen Induces Hepatocyte Hyperploidy via Failure of Cytokinesis

Investigators showed that expression of viral large surface antigen (LHBS) was sufficient to induce cytokinesis failure of immortalized hepatocytes. Pre-mitotic defects with DNA damage and G2/M checkpoint attenuation preceded cytokinesis in LHBS-expressing cells, and ultimately resulted in hyperploidy. [J Pathol] Abstract

Humanized Mice Reveal an Essential Role for Human Hepatocytes in the Development of the Liver Immune System

The mechanisms regulating the development and homeostasis of the specialized immune system, especially in humans, remain largely unknown. Researchers addressed this question in humanized mice that were constructed by transplantation of human fetal thymus and CD34⁺ hematopoietic stem/progenitor cells in immunodeficient mice with or without autologous human hepatocyte engraftment. [Cell Death Dis] Full Article

DDX39 Promotes Hepatocellular Carcinoma Growth and Metastasis through Activating Wnt/Β-Catenin Pathway

Scientists determined the role of DDX39, a DEAD-box RNA helicase in hepatocellular carcinoma (HCC) progression, and found DDX39 was upregulated in HCC tissues and cells. DDX39 expression was positively correlated with advanced clinical stage, survival analysis which showed patients with high-DDX39 levels had poor outcome. [Cell Death Dis] Full Article

Long Non-Coding RNA UBE2CP3 Enhances HCC Cell Secretion of VEGFA and Promotes Angiogenesis by Activating ERK1/2/HIF-1α/VEGFA Signaling in Hepatocellular Carcinoma

In co-culture systems, hepatocellular carcinoma (HCC) cells overexpressing ubiquitin conjugating enzyme E2C pseudogene 3 (UBE2CP3) promoted HUVEC proliferation, migration and tube formation via the activation of ERK/HIF-1α/p70S6K/VEGFA signaling, increasing the level of VEGFA in HCC cell supernatant. [J Exp Clin Cancer Res] Full Article

Extracellular Matrix Components Indicate Remodeling Activity in Different Fibrosis Stages of Human Non-Alcoholic Fatty Liver Disease

Researchers aimed to investigate the proportion of hepatic stellate cells and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in human non-alcoholic fatty liver disease liver tissue with respect to severity of inflammation and fibrosis. [Histopathology] Abstract

A Combination of Astragaloside I, Levistilide A and Calycosin Exerts Anti-Liver Fibrosis Effects In Vitro and In Vivo

Researchers evaluated 14 ingredients from Danggui Buxue Tang in human hepatic stellate cell line LX-2, and found that astragaloside I, levistilide A and calycosin produced synergistic proliferation inhibition on LX-2 cells and TGF-β1-activated LX-2 cells. [Acta Pharmacol Sin] Abstract

ILDR2 Has a Negligible Role in Hepatic Steatosis

Congenital and acute liver-specific and hepatocyte-specific knockout mice did not develop hepatic steatosis. However, administration of Ildr2 shRNA to Ildr2 knock-out mice did cause hepatic steatosis, indicating that the Ildr2 shRNA had apparent “off-target” effects on gene(s) other than Ildr2. [PLoS One] Full Article

Alpha Lipoic Acid Exerts Antioxidant Effect via Nrf2/HO-1 Pathway Activation and Suppresses Hepatic Stellate Cells Activation Induced by Methotrexate in Rats.

Scientists explored the hepatoprotective mechanisms of alpha lipoic acid against methotrexate-induced hepatic injury in rats. [Biomed Pharmacother] Abstract

Clinico-Pathological Importance of TGF-β/Phospho-Smad Signaling during Human Hepatic Fibrocarcinogenesis

The authors address TGF-β/Smad signal transduction in chronic liver injuries and carcinogenic processes. They also discuss the reversibility of Smad signaling after antiviral therapy. [Cancers] Abstract | Full Article

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Exelixis Announces Results from Sub-Group Analyses of the Phase III Pivotal CELESTIAL Trial of Cabozantinib for Advanced Hepatocellular Carcinoma

Exelixis, Inc. announced results from sub-group analyses of the CELESTIAL Phase III pivotal trial of cabozantinib in advanced hepatocellular carcinoma comparing outcomes by duration of sorafenib treatment in patients whose only prior treatment was sorafenib and outcomes based on age. [Press release from Exelixis, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting, Chicago] Press Release

Mayo Clinic Researchers Take a Step Closer to Developing a DNA Test for Liver Cancer

A group of researchers from Mayo Clinic and Exact Sciences Corporation have completed a Phase II study comparing a set of DNA markers to alpha fetoprotein as a method to test for liver cancer. [Press release from Mayo Clinic discussing research presented at the 2018 Digestive Disease Week, Washington] Press Release

MiNA Therapeutics Presents Initial Results from First-in-Human MTL-CEBPA Study in Advanced Liver Cancer Patients

MiNA Therapeutic announced preliminary results from its ongoing Phase I study of small activating RNA candidate MTL-CEBPA in advanced liver cancer. [Press release from MiNA Therapeutics Limited discussing research presented at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting, Chicago] Press Release

Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. Announce Data from Investigational Studies of Lenvima^® and Keytruda^® Combination Therapy in Four Different Tumor Types

Eisai Co., Ltd. and Merck & Co., announced that results from presentations of new data and analyses of LENVIMA^®, an orally available kinase inhibitor discovered by Eisai, in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s anti-PD-1 therapy, KEYTRUDA^®, in four different tumor types: unresectable hepatocellular carcinoma, squamous cell carcinoma of the head and neck, advanced renal cell carcinoma, and advanced endometrial carcinoma. [Press release from Eisai Co., Ltd. discussing research presented at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting, Chicago] Press Release

Viking Therapeutics Completes Enrollment in Phase II Study of VK2809 in Patients With Hypercholesterolemia and Non-Alcoholic Fatty Liver Disease

Viking Therapeutics, Inc. announced that enrollment has been completed in the company’s ongoing Phase II clinical trial of VK2809 in patients with primary hypercholesterolemia and non-alcoholic fatty liver disease. [Viking Therapeutics] Press Release

Hookipa and Gilead Enter Into a Collaboration and License Agreement to Develop Immunotherapies Against HIV and Hepatitis B

Hookipa Biotech AG and Gilead Sciences, Inc. announced that they have entered into a research collaboration and license agreement that grants Gilead exclusive rights to Hookipa’s TheraT^® and Vaxwave^® arenavirus vector-based immunization technologies for two major chronic infectious disease indications, hepatitis B virus and human immunodeficiency virus (HIV). [Gilead Sciences, Inc.] Press Release

EU to World: Join Our €100-Billion Research Program

The European Commission has outlined how it plans to spend the biggest research and innovation budget in its history. In a document that sets out plans for its next major science-funding program, the Commission also confirmed new rules that will, for the first time, allow any country in the world — including a post-Brexit United Kingdom — to take part. [Nature News] Editorial

Go for Launch: A Former Astronaut Becomes Spain’s Science Minister

Spain has a ministry of science again—and none other than the first Spanish astronaut is leading it. The new transition government led by socialist Pedro Sánchez announced that Pedro Duque, who visited space twice, will be at the helm of the newly created Ministry for Science, Innovation, and Universities. The announcement was cheered by the Spanish scientific community, which has long suffered from declining budgets and bureaucratic hurdles. [ScienceInsider] Editorial

Scientists Fare Poorly in Super Tuesday Primary Vote

Science-minded candidates seeking seats in the next U.S. Congress took a drubbing from their Democratic opponents in a raft of primary elections across the country. [ScienceInsider] Editorial

Chile, Keen to Become a Knowledge Society, Creates a Ministry of Science

Scientists in Chile have welcomed a decision by Congress to create a science ministry. Many researchers hope that a dedicated ministry will give science more prominence and better-coordinated policies—provided the ministry’s budget matches the government’s ambitions to “bring Chile towards an information and knowledge society,” as Gonzalo Blumel, the country’s minister secretary-general of the presidency, put it in a statement issued after the 31 May vote. [ScienceInsider] Editorial

NEW Keystone Symposia: Cellular Plasticity: Reprogramming, Regeneration and Metaplasia
January 27-31, 2019
Keystone, Colorado, United States

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

Research Technologist – Liver Biology (STEMCELL Technologies Inc.)

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

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

Postdoctoral Scholar – Cancer Biology (Penn State College of Medicine)

Postdoctoral Fellow – Liver Injury, Hepatocellular Carcinoma and Metabolic Liver Diseases (University of Rhode Island)

Postdoctoral Position – Necroptosis in Liver Diseases (Inserm)

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

Academic Position – Cancer Research (Cedars-Sinai Medical Center)

Postdoctoral Research Associate – Liver Disease and Injury (University of Pittsburgh)

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

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