Hepatic Cell News Volume 1.04 | Feb 17 2017

TOP STORY

Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity

Researchers showed that the hepatic translocation of obesity-induced lipoteichoic acid, a Gram positive gut microbial component, promotes hepatocellular carcinoma development by creating a tumor-promoting microenvironment. [Cancer Discov] Abstract

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Sodium Taurocholate Cotransporting Polypeptide Is the Limiting Host Factor of Hepatitis B Virus Infection in Macaque and Pig Hepatocytes

As an essential premise towards the establishment for an hepatitis B (HBV)-susceptible animal model, the authors investigated the role of human sodium taurocholate cotransporting polypeptide (hNTCP) as a limiting factor of hepatocytes in commonly used laboratory animals. Primary hepatocytes from mouse, rat, dog, pig, rhesus and cynomolgus macaque were transduced with adeno-associated viral vectors encoding hNTCP and subsequently infected with HBV. [Hepatology] Abstract

Stepwise Reprogramming of Liver Cells to a Pancreas Progenitor State by the Transcriptional Regulator Tgif2

Investigators report that the TALE homeoprotein TGIF2 acts as a developmental regulator of the pancreas versus liver fate decision and is sufficient to elicit liver-to-pancreas fate conversion both ex vivo and in vivo. Hepatocytes expressing Tgif2 underwent extensive transcriptional remodeling, which represses the original hepatic identity and, over time, induces a pancreatic progenitor-like phenotype. [Nat Commun] Full Article | Press Release

Loss of KLF4 and Consequential Downregulation of Smad7 Exacerbate Oncogenic TGF-β Signaling in and Promote Progression of Hepatocellular Carcinoma

Scientists explored the mechanisms that loss of Krüppel-like factor 4 (KLF4) exacerbates oncogenic transforming growth factor-β (TGF-β) signaling in human hepatocellular carcinoma (HCC). TGF-β signaling components were expressed in most HCC cells, and activation of TGF-β signaling promoted cell migration and invasion. [Oncogene] Abstract

Evaluation of Transcriptomic Signature as a Valuable Tool to Study Drug-Induced Cholestasis in Primary Human Hepatocytes

Primary human hepatocyte sandwich cultures from five different donors were daily exposed to cyclosporine A, ibuprofen, chlorpromazine, amiodarone and paracetamol at their respective C_max for short-term and long-term treatment. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated. [Arch Toxicol] Abstract

Interleukin-33 Drives Hepatic Fibrosis through Activation of Hepatic Stellate Cells

The authors investigated the role of interleukin-33 (IL-33) in human patients and experimental bile-duct ligation (BDL)-induced fibrosis in mice. They report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis. [Cell Mol Immunol] Abstract

Reliable Rate Measurements for Active and Passive Hepatic Uptake Using Plated Human Hepatocytes

Researchers evaluated the plated human hepatocytes (PHH) and studied the effect of incubation temperature and inhibitor concentration on uptake measurements, in order to reliably estimate hepatic uptake components. Uptake rates measured using PHH, without and with rifamycin SV, were comparable with those obtained from suspension hepatocytes and sandwich-cultured hepatocytes for a set of compounds. [AAPS J] Abstract

Re-Programming Pullulan for Targeting and Controlled Release of Doxorubicin to the Hepatocellular Carcinoma Cells

Cell culture studies were performed by using HepG2/SERPINB3 cells that overexpress the serpine B3 receptor and control HepG2/EMPTY cells that do not overexpress the receptor. A comparative study by cytofluorimetry and confocal microscopy performed using PreS1-Pull-rhodamine (Rhod) and Pull-Rhod showed that PreS1 conveys to the conjugate high cell selectivity. [Eur J Pharm Sci] Abstract | Graphical Abstract

Activation of Insulin-PI3K/Akt-p70S6K Pathway in Hepatic Stellate Cells Contributes to Fibrosis in Nonalcoholic Steatohepatitis

Investigators explored insulin signaling in the regulation of hepatic stellate cell (HSC) activation and the progression of nonalcoholic fatty liver disease and steatohepatitis-fibrosis. Insulin enhanced the expression of smooth muscle actin-α in quiescent but not in activated HSC in culture. [Dig Dis Sci] Abstract

Caffeic Acid Phenethyl Ester Attenuates Liver Fibrosis via Inhibition of TGF-β1/Smad3 Pathway and Induction of Autophagy Pathway

Researchers investigated the mechanism underlying caffeic acid phenethyl ester (CAPE) against liver fibrosis in a liver fibrosis model induced by toxic carbon tetrachloride in male Sprague-Dawley rats and in vitro in CAPE treated hepatic stellate cells. [Biochem Biophys Res Commun] Abstract

Regression of Liver Fibrosis

The authors provide a short overview of the mechanisms regulating the profibrotic and proresolution response, with the aim of highlighting potential new therapeutic targets. [Semin Liver Dis] Abstract

The Role of Akt in Chronic Liver Disease and Liver Regeneration

Researchers describe the benefits of the Akt signaling pathway, emphasizing its importance in coordinating proper cellular growth and differentiation during liver regeneration, hepatic function, and liver disease. [Semin Liver Dis] Abstract

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ContraVir to Highlight Clinical Data from Ongoing Phase IIa Study of Tenofovir Exalidex (TXL^™) for Treating Hepatitis B

ContraVir Pharmaceuticals, Inc. announced that it will present clinical data. John Sullivan-Bolyai, MD, MPH, Chief Medical Officer of ContraVir, will give an oral presentation highlighting Phase IIa data for TXL^™, formerly CMX157, the company’s highly potent lipid prodrug of the successful antiviral drug tenofovir for treating hepatitis B virus. [Press release from ContraVir Pharmaceuticals, Inc. discussing research to be presented at the 26^th Conference of the Asian Pacific Association for the Study of the Liver (APASL), Shanghai] Press Release

Benitec Biopharma to Present Expanded Data Set from Pivotal Data in Hepatitis B Virus (HBV) In Vivo Model

Benitec Biopharma Limited announced that it will present pivotal data from the company’s HBV in vivo model. Dr David Suhy, Benitec’s Chief Scientific Officer will detail the expanded data set during an oral presentation entitled, ‘Combinations of a DNA-directed RNA interference Agent with Standard of Care Drugs Results in Superior Suppression of Hepatitis B Virus (HBV) in a Chimeric Mouse Model.’ [Press release from Benitec Biopharma Limited (PR Newswire Association LLC.) discussing research to be presented at the 26^th Conference of the Asian Pacific Association for the Study of the Liver (APASL), Shanghai] Press Release

Median Technologies to Attend the Annual Meeting of the Asian Pacific Association for the Study of the Liver

Median Technologies announced that it will participate in the Annual Meeting of the Asian Pacific Association for the Study of the Liver. The company will demonstrate its new Imaging Phenomics^™ platform iBiopsy™ applied to the assessment of nonalcoholic steatohepatitis. [Press release from Median Technologies discussing research to be presented at the 26^th Conference of the Asian Pacific Association for the Study of the Liver (APASL), Shanghai] Press Release

Daiichi Sankyo and ArQule Announce the Completion of the METIV-HCC Phase III Study of Tivantinib in Second-Line Treatment of MET-Overexpressing Hepatocellular Carcinoma

ArQule, Inc. and Daiichi Sankyo announced that the METIV-HCC Phase III study of tivantinib in hepatocellular carcinoma (HCC) did not meet its primary endpoint of improving overall survival. [ArQule, Inc.] Press Release

Salk Scientist Awarded Inaugural SjöBerg Prize for Cancer Breakthrough

Salk Professor Tony Hunter, who holds an American Cancer Society Professorship, has been awarded $500,000 as part of the $1 million Royal Swedish Academy of Sciences’ inaugural Sjöberg Prize for Cancer Research for “groundbreaking studies of cellular processes that have led to the development of new and effective cancer drugs.” [Salk Institute for Biological Studies] Press Release

Why the CRISPR Patent Verdict Isn’t the End of the Story

The US Patent and Trademark Office issued a key verdict this week in the battle over the intellectual property rights to the potentially lucrative gene-editing technique CRISPR–Cas9. But the fight for patent rights to CRISPR technology is by no means over. [Nature News] Editorial

Ebola Funding Surge Hides Falling Investment in Other Neglected Diseases

Global funding for research on neglected diseases — which include tuberculosis, HIV/AIDS and malaria — is at its lowest level since 2007, according to the annual G-FINDER investment report by Policy Cures, a health-policy analysis firm in Sydney, Australia. [Nature News] Editorial

Robert F. Kennedy Jr. Says a ‘Vaccine Safety’ Commission Is Still in the Works

The vocal vaccine critic Robert F. Kennedy Jr. is still talking with President Donald Trump’s administration about establishing a commission to look into vaccine safety, Kennedy said at a press conference held at the National Press Club in Washington, D.C. [ScienceInsider] Editorial

NEW Bile Acid Receptors as Signal Integrators in Liver and Metabolism
March 3-7, 2017
Monterey, United States

NEW Stem Cells in Drug Discovery
March 6-7, 2017
Cambridge, United Kingdom

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NEW Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

Postdoctoral Fellow or Research Scientist – Diabetes (Novo Nordisk)

Postdoctoral Research Fellow – Liver Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

PhD Studentship – Hepatocytes (KU Leuven, Stem Cell Institute)

PhD Position – Pathogens Infecting Liver (Helmholtz Association)

PhD Studentships – Liver Organ Growing (Downstate Medical Center)

Senior Scientist – Oncology (Genentech Research)

Training Fellowship – Clinical Research (University of Oxford)

Postdoctoral Associate – Cancer Biology (University of Florida)

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