Hepatic Cell News Volume 4.09 | Mar 13 2020

TOP STORY

Amino Acid Levels Determine Metabolism and CYP450 Function of Hepatocytes and Hepatoma Cell Lines

Researchers demonstrated that hepatic functionality depended more on cellular metabolism and extracellular nutrients than on developmental regulators. They demonstrated that increasing extracellular amino acids beyond the nutritional need of hepatocyte-like cells and HepG2 cells induced glucose independence, mitochondrial function, and the acquisition of a transcriptional profile that was closer to primary human hepatocytes. [Nat Commun] Full Article

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AAV6 Vexosomes Mediate Robust Suicide Gene Delivery in a Murine Model of Hepatocellular Carcinoma

Researchers generated adeno-associated virus (AAV) serotype 6 vexosomes containing an inducible caspase 9 suicide gene, by a differential ultracentrifugation based protocol. They further tested the cytotoxic potential of these vexosomes, in a human hepatocellular carcinoma (HCC) model in vitro and in a xenotransplantation model of HCC in vivo. [Mol Ther Methods Clin Dev] Abstract | Full Article | Graphical Abstract

Fibroblast Growth Factor 9 Is Expressed by Activated Hepatic Stellate Cells and Promotes Progression of Hepatocellular Carcinoma

Analysis of the expression of the fifteen paracrine fibroblast growth factor (FGF)-members revealed that FGF9 was only expressed by hepatic stellate cells (HSC) but not by hepatocellular carcinoma (HCC) cells. Also in human HCC tissues, HSC/stromal myofibroblasts were identified as cellular source of FGF9. [Sci Rep] Full Article

Downregulation of Histone Methyltransferase SET8 Inhibits Progression of Hepatocellular Carcinoma

The authors performed a functional analysis for SET8 to assess its effect on hepatocellular carcinoma (HCC) progression. SET8 knockdown inhibited proliferation, migration and invasion of HCC cells. [Sci Rep] Full Article

LncRNA-LALR1 Upregulates Small Nucleolar RNA SNORD72 to Promote Growth and Invasion of Hepatocellular Carcinoma

Investigators demonstrated that lncRNA-LALR1 was significantly upregulated in hepatocellular carcinoma tissues compared with adjacent tissues and high expression of lncRNA-LALR1 was associated with advanced TNM stage, poor differentiation, and distant metastasis. RNA fluorescence in situ hybridization analysis showed lncRNA-LALR1 was expressed not only in cytoplasm but also in nucleolus. [Aging (Albany NY)] Full Article

Hydrostatic Pressure Regulates CYP1A2 Expression in Human Hepatocytes via a Mechanosensitive AhR-Dependent Pathway

Scientists demonstrated that hepatocytes also respond to a small increase in hydrostatic pressure relative to the atmospheric pressure. They demonstrated that hydrostatic pressure improved albumin production and increased CYP1A2 expression levels in an AhR-dependent manner in human hepatocytes. [Am J Physiol Cell Physiol] Abstract

Sp2 Promotes Invasion and Metastasis of Hepatocellular Carcinoma by Targeting TRIB3 Protein

Tissue microarray immunohistochemistry and western blot were used to study the expression of Sp2 in hepatocellular tissue and adjacent non-neoplastic tissues. In hepatocellular carcinoma cell lines, the role of Sp2 was determined by in vitro experiments such as CCK8, clone formation test, Transwell assay, wound-healing assay, and flow cytometry apoptotic analysis, and its possible mechanism was analyzed. [Cancer Med] Full Article

Targeting the Wnt Signaling Pathway through R-Spondin 3 Identifies an Anti-Fibrosis Treatment Strategy for Multiple Organs

Mechanistically, the authors showed that R-spondin proteins induced multiple pro-fibrotic chemokines and cytokines in Kupffer cells and hepatocytes. They found that the anti-fibrotic activity of OMP-131R10 was associated with its inhibition of β-catenin activation in vivo. [PLoS One] Full Article

CNOT7 Depletion Reverses Natural Killer Cell Resistance by Modulating the Tumor Immune Microenvironment of Hepatocellular Carcinoma

Scientists examined correlation between CNOT7, STAT1, TGF‐β1, and IFN‐γ expression with hepatocellular carcinoma (HCC)BC and HBC. They found that modulation of CNOT7 expression altered TGF-β1 secretion in HCC and IFN-γ secretion in NK cells. [FEBS Open Bio] Abstract

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Biology and Clinical Application of Regulatory RNAs in Hepatocellular Carcinoma

While in the past it was thought that non-coding RNAs would be redundant without relevant functions, it is now well established that ncRNAs identify a class of regulatory molecules that finely tune cell homeostasis and are deregulated in disease states, including hepatocellular carcinoma [Hepatology] Abstract

Immune-Based Therapies for Hepatocellular Carcinoma

Investigators review the evidence supporting a therapeutic role for vaccines, cell-based therapies and immune-checkpoint inhibitors and discuss the potential for patient stratification in an attempt to overcome the series of failures that has characterised drug development in this disease area. [Oncogene] Abstract

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

US Food and Drug Administration Approves Opdivo^® (Nivolumab) + Yervoy^® (Lpilimumab) for Patients with Hepatocellular Carcinoma (HCC) Previously Treated with Sorafenib

Bristol Myers Squibb Company announced that Opdivo (nivolumab) 1 mg/kg plus Yervoy 3 mg/kg (injections for intravenous use) was approved by the FDA to treat HCC in patients who have been previously treated with sorafenib. [Bristol Myers Squibb Company] Press Release

Cancer Council NSW Awards Over $9 Million of Funding to Innovative Cancer Research

Cancer Council NSW has awarded over $9 million of new funding to 14 ground-breaking cancer research projects. The projects span a range of cancers, including four low survival cancers: ovarian, stomach, liver and pancreatic. [Cancer Council NSW] Press Release

UK Government to Boost R&D Spending

The British government has announced a 15 percent increase in public funding for research and development as part of its 2020 budget in a move that was generally welcomed by scientists. [The Scientist] Editorial

Universities Are Forging Ties with the FBI as US Cracks Down on Foreign Influence

US universities are forging closer ties with FBI agents, encouraging scientists to disclose foreign sources of research funding, and tightening restrictions on researchers’ travel. [Nature News] Editorial

NEW Adhesion Across Scales: From Molecules to Morphogenesis
June 28-July 3, 2020
Manchester, New Hampshire, United States

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

NEW Research Scientist – Liver and Gastric Cancer (University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – The Microbiome in Liver Disease (University of Oslo)

Postdoctoral Researcher – Liver Pathogenesis (Washington University in St. Louis)

Senior Postdoctoral Research Assistant – Liver Research (University of Dundee)

Postdoctoral Researchers – Diabetes, Liver, and Renal Disease (University of Oxford)

Network Manager – Non-Alcoholic Liver Disease (Hans-Knöll-Institute)

Postdoctoral Fellow – Fatty Liver Dieases (University of Kansas Medical Center)

Team Leader – Cholangiocytes (Miromatrix Medical)

Postdoctoral Fellow – Diabetes and Fatty Liver Disease (NIH National Heart, Lung, and Blood Institute)

Postdoctoral Position – Culturing ‘Foie Gras’ (KU Leuven)

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