Hepatic Cell News Volume 1.10 | Mar 31 2017

TOP STORY

BMP-9 Interferes with Liver Regeneration and Promotes Liver Fibrosis

Levels of bone morphogenetic protein (BMP)-9 and its receptors were analyzed in primary liver cells. Direct effects of BMP-9 on hepatic stellate cells (HSCs) and hepatocytes were studied in vitro, and the role of BMP-9 was examined in acute and chronic liver injury models in mice. Quiescent and activated HSCs were identified as major BMP-9 producing liver cell type. [Gut] Abstract

(Ranked by impact factor of the journal)

Liver Carcinogenesis by FOS-Dependent Inflammation and Cholesterol Dysregulation

Human hepatocellular carcinomas (HCCs), which arise on a background of chronic liver damage and inflammation, express c-Fos, a component of the AP-1 transcription factor. Using mouse models, the authors showed that hepatocyte-specific deletion of c-Fos protects against diethylnitrosamine (DEN)-induced HCCs, whereas liver-specific c-Fos expression leads to reversible premalignant hepatocyte transformation and enhanced DEN-carcinogenesis. [J Exp Med] Abstract

O-GlcNAc Transferase Promotes Fatty Liver-Associated Liver Cancer through Inducing Palmitic Acid and Activating Endoplasmic Reticulum Stress

Researchers investigated the functional role of O-GlcNAc transferase (OGT) in non-alcoholic fatty liver disease-associated hepatocellular carcinoma. They revealed that OGT significantly induced palmitic acid production identified by liquid chromatography-tandem mass spectrometry, which enhanced the protein expression of endoplasmic reticulum stress masters of glucose-regulated protein 78 and inositol-requiring enzyme 1α. [J Hepatol] Full Article | Graphical Abstract

Mutational Spectra of Aflatoxin B₁ In Vivo Establish Biomarkers of Exposure for Human Hepatocellular Carcinoma

Aflatoxin B₁ (AFB₁) and/or hepatitis B and C viruses are risk factors for human hepatocellular carcinoma. Responding to a need for early-onset evidence predicting disease development, highly accurate duplex sequencing was used to monitor acquisition of high-resolution mutational spectra (HRMS) during the process of hepatocarcinogenesis. HRMS of cells surrounding the tumors revealed predominantly G:C→T:A mutations characteristic of AFB₁ exposure. [Proc Natl Acad Sci USA] Full Article | Press Release

Hepatic Cyclooxygenase-2 Overexpression Induced Spontaneous Hepatocellular Carcinoma Formation in Mice

The authors investigated the role and molecular pathogenesis of cyclooxygenase (COX)-2 in hepatocellular carcinoma (HCC) by using liver-specific COX-2 transgenic (TG) mice. By reduced representation bisulfite sequencing, DNA promoter hypermethylation was identified in HCC from TG mice. Induction of promoter hypermethylation was associated with reduced tet methylcytosine dioxygenase 1 expression by COX-2. [Oncogene] Full Article

Cell Traversal Activity Is Important for Plasmodium falciparum Liver Infection in Humanized Mice

The molecular basis of how P. falciparum sporozoites migrate through host cells is poorly understood, and direct evidence of its importance in vivo is lacking. Researchers generated traversal-deficient sporozoites by genetic disruption of sporozoite microneme protein essential for cell traversal (SPECT) or perforin-like protein 1 (PLP1). They demonstrated that SPECT and PLP1 are critical for transcellular migration by P. falciparum sporozoites and they demonstrated the importance of cell traversal for liver infection by this human pathogen. [Cell Rep] Full Article | Graphical Abstract

Liver-Specific Activation of AMPK Prevents Steatosis on a High-Fructose Diet

Investigators identified a mutation in the γ1 subunit that lead to activation of AMP-activated protein kinase (AMPK). They generated mice with this mutation to study the effect of chronic liver-specific activation of AMPK in vivo. Primary hepatocytes isolated from these mice have reduced gluconeogenesis and fatty acid synthesis, but there was no effect on fatty acid oxidation compared to cells from wild-type mice. [Cell Rep] Full Article | Press Release | Graphical Abstract

Polymeric Nanoparticles as Cancer-Specific DNA Delivery Vectors to Human Hepatocellular Carcinoma

Scientists described a non-viral strategy for effective and cancer-specific DNA delivery to human hepatocellular carcinoma (HCC) using biodegradable poly(beta-amino ester) (PBAE) nanoparticles (NPs). PBAE NP administration to a subcutaneous HCC mouse model, established with one of the human lines tested in vitro, confirmed effective DNA transfection in vivo. [J Control Release] Abstract | Graphical Abstract

MiRNA199a-3p Suppresses Tumor Growth, Migration, Invasion and Angiogenesis in Hepatocellular Carcinoma by Targeting VEGFA, VEGFR1, VEGFR2, HGF and MMP2

The role of microRNA miR-199a-3p in the regulation of microenvironment and development of hepatocellular carcinoma (HCC) was investigated by several in vitro and in vivo assays. Expression of miR-199a-3p was significantly low in HCC tissues and its overexpression remarkably inhibited in vivo tumor growth and metastasis to lung in NOD-SCID mice. [Cell Death Dis] Full Article

Towards a Humanized Mouse Model of Liver Stage Malaria Using Ectopic Artificial Livers

Scientists previously incorporated primary human hepatocytes into engineered polyethylene glycol (PEG)-based nanoporous human ectopic artificial livers (HEALs), implanted them in mice without liver injury, and rapidly generated human liver chimeric mice in a reproducible and scalable fashion. By re-designing the PEG scaffold to be macroporous, they demonstrated the facile fabrication of implantable porous HEALs that support liver stage human malaria infection in vitro, and also after implantation in mice with normal liver function, 60% of the time. [Sci Rep] Full Article

FAM46C Is Critical for the Anti-Proliferation and Pro-Apoptotic Effects of Norcantharidin in Hepatocellular Carcinoma Cells

Norcantharidin (NCTD), a demethylated analog of cantharidin derived from Chinese traditional medicine blister beetle, has been currently used as an anticancer drug for various cancers including hepatocellular carcinoma (HCC). For a more comprehensive understanding of the targets of NCTD in HCC, next-generation RNA-Seq was utilized. Investigators revealed that the expression of FAM46C, which has been reported as a tumor suppressor for multiple myeloma, was enhanced after NCTD treatment. [Sci Rep] Full Article

New Knowledge of the Mechanisms of Sorafenib Resistance in Liver Cancer

The authors describe the function of sorafenib, its clinical application, and the molecular mechanisms for drug resistance, especially for hepatocellular carcinoma patients. [Acta Pharmacol Sin] Full Article

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

ArQule Announces Top-Line Results of Phase III Clinical Study of Tivantinib in Hepatocellular Carcinoma in Japan

ArQule, Inc. reported that its partner, Kyowa Hakko Kirin, announced top-line results of the JET-HCC Phase III trial of tivantinib in Japan, and that the trial did not meet its primary endpoint of progression free survival. [ArQule, Inc.] Press Release

Technology That Could Detect Cancer More Accurately Wins Innovation Award

A system that automatically classifies cancer biopsies, developed by an Imperial physicist, has won a Royal Society prize to help it get to market. [Imperial College London] Press Release

Bezos Family Gives $35 Million to Fred Hutch

Fred Hutch’s quest for cures was propelled forward with a $35 million gift from the Bezos family. It is the single largest philanthropic commitment to Fred Hutch in the center’s 41-year history. [Fred Hutchinson Cancer Research Center] Press Release

Trump Wants 2018 NIH Cut to Come From Overhead Payments

The Trump administration could slash $5.8 billion from the 2018 budget of the National Institutes of Health (NIH), yet still fund as least as much research by eliminating overhead payments to universities and research institutions, Secretary of Health and Human Services Tom Price told lawmakers. [ScienceInsider] Editorial

European Commission Considering Leap into Open-Access Publishing

One of Europe’s biggest science spenders could soon branch out into publishing. The European Commission, which spends more than €10 billion annually on research, may follow two other big league funders, the Wellcome Trust and the Bill & Melinda Gates Foundation, and set up a “publishing platform” for the scientists it funds, in an attempt to accelerate the transition to open-access publishing in Europe. [ScienceInsider] Editorial

NEW 12^th Biennial Regional Congress of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA)
May 23-26, 2017
Mainz, Germany

NEW Protein Aggregation in Health and Disease
June 11-16, 2017
Steamboat Springs, United States

NEW 19^th International Symposium on Cells of the Hepatic Sinusoid
June 14-17, 2017
Galway, Republic of Ireland

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

NEW Postdoctoral Researchers – Hepatology and Liver Transplantation (Instituto Maimónides de Investigación Biomédica de Córdoba/University of Cordoba)

NEW Academic Surgical Pathologist – Liver/Gastrointestinal (Brigham and Women’s Hospital)

Principal Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

Postdoctoral Position – Alcoholic Liver Fibrosis (University of Copenhagen)

PhD Position – MicrobLiver (KU Leuven)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University)

Research Fellow – Hepatocytes (National University of Singapore)

Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

Associate or Full Professor – Gastroenterology (University of Washington)

Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

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