Hepatic Cell News Volume 1.33 | Sep 15 2017

TOP STORY

Hypoxia Inducible Factor HIF-1 Promotes Myeloid-Derived Suppressor Cells Accumulation through ENTPD2/CD39L1 in Hepatocellular Carcinoma

Researchers demonstrated that ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2) converts extracellular ATP to 5′-AMP, which prevents the differentiation of myeloid-derived suppressor cells (MDSCs) and therefore promotes the maintenance of MDSCs. They further found that ENTPD2 inhibition is able to mitigate cancer growth and enhance the efficiency and efficacy of immune checkpoint inhibitors. [Nat Commun] Full Article

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Cell-Cell Adhesion Accounts for the Different Orientation of Columnar and Hepatocytic Cell Divisions

Scientists described a rescue mechanism that drives substrate-parallel spindle alignment of quasi-diagonal metaphase spindles in anaphase. It required a Rho- and E-cadherin adhesion–dependent, substrate-parallel contractile actin belt at the apex that governs anaphase cell flattening. [J Cell Biol] Abstract

Camptothecin Suppresses NRF2–ARE Activity and Sensitizes Hepatocellular Carcinoma Cells to Anticancer Drugs

The expression and transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) in human hepatocellular carcinoma biopsies and camptothecin-treated culture cells were determined using immunostaining, western blot, reverse-transcription quantitative real-time PCR and luciferase reporter assay. The effect of camptothecin on chemosensitivity of cancer cells was assessed in vitro and in xenografts. [Br J Cancer] Full Article

Sorafenib Suppresses Extrahepatic Metastasis De Novo in Hepatocellular Carcinoma through Inhibition of Mesenchymal Cancer Stem Cells Characterized by the Expression of CD90

Investigators examined the influence of sorafenib, a multiple-receptor tyrosine kinase inhibitor used as a first-line treatment for advanced hepatocellular carcinoma on EpCAM⁺ and CD90⁺ cancer stem cells. CD90⁺ cells showed higher c-Kit gene/protein expression than EpCAM⁺ cells. [Sci Rep] Full Article

Inhibition of Fucosylation by 2-Fluorofucose Suppresses Human Liver Cancer HepG2 Cell Proliferation and Migration as Well as Tumor Formation

Cell proliferation and integrin-mediated cell migration were significantly suppressed in cells treated with L-fucose analog, 2-fluoro-L-fucose (2FF). Researchers analyzed cell colony formation in soft agar and tumor xenograft efficacy, and found that both were greatly suppressed in the 2FF-treated cells, compared with the control cells. [Sci Rep] Full Article

Response of Human Fetal Liver Progenitor Cell Types to Temperature and pH Stresses In Vitro

Scientists identified how various stresses affect liver progenitors, and determined whether distinct effects exist on different progenitor cells of the human liver. At 40°C, numbers of adherent hepatic cells decreased, but those of hematopoietic non-adherent cells increased. [Rejuvenation Res] Abstract

Effects of Cyclin D1 Gene Silencing on Cell Proliferation, Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

The authors investigated the effects of Cyclin D1 silencing on cell cycle, cell proliferation and apoptosis of hepatocellular carcinoma cells. Cyclin D1 expression levels were found to be correlated with tumor size and tumor staging. [J Cell Biochem] Abstract

Hepatitis C Virus-Induced Innate Immune Responses in Human iPS Cell-Derived Hepatocyte-Like Cells

Researchers examined the potential of hepatocyte-like cells differentiated from human iPS cells as an in vitro hepatitis C virus (HCV) infection model, especially for evaluation of the relationship between HCV infection levels and HCV-induced innate immunity. [Virus Res] Abstract

HepG2 and Human Healthy Hepatocyte In Vitro Culture and Co-Culture in PCL Electrospun Platforms

Investigators studied electrospun scaffolds made of polycaprolactone (PCL) as an in vitro model that could mimic the morphological organization of native extracellular matrix and the co-culture of hepatic cell lines – i.e., HepG2, Human Healthy Hepatocytes (HHH). A much lower proliferation rate was observed for the HepG2 cells compared to the HHH cells, when cultured on the fibrous scaffolds over a time course of four weeks. [Biomed Mater] Abstract

Simultaneous Silencing of ACSL4 and Induction of GADD45B in Hepatocellular Carcinoma Cells Amplifies the Synergistic Therapeutic Effect of Aspirin and Sorafenib

The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of hepatocellular carcinoma (HCC) and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib acted synergistically on HCC cells with aspirin in vitro. [Cell Death Discov] Full Article

Human Hepatic Organoids for the Analysis of Human Genetic Diseases

Scientists developed an in vitro model system where induced pluripotent stem cells differentiated into three-dimensional human hepatic organoids through stages that resemble human liver during its embryonic development. The organoids provide a potentially new model for liver regenerative processes, and were used to characterize the effect of different JAG1 mutations. [JCI Insight] Full Article

Response to Hepatitis B Vaccination in Patients with Liver Cirrhosis

The authors examine, discuss, and summarize the immunogenicity of hepatitis B vaccination in patients with liver cirrhosis. [Rev Med Virol] Abstract

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Onxeo Announces Top-Line Results from ReLive Phase III Study of Livatag^® in Advanced Hepatocellular Carcinoma

Onxeo S.A. announced top line results from the Phase III ReLive trial of Livatag^® in adult patients with unresectable hepatocellular carcinoma, intolerant to sorafenib or having progressed after a systemic therapy including sorafenib, when compared to best standard of care. [Onxeo S.A.] Press Release

Blueprint Medicines Announces New Data from Ongoing Phase I Clinical Trial of BLU-554 in Patients with Advanced Hepatocellular Carcinoma

Blueprint Medicines Corporation announced updated data from its ongoing Phase I clinical trial of BLU-554, a potent and highly selective inhibitor of fibroblast growth factor receptor 4 for the treatment of patients with advanced hepatocellular carcinoma. [Blueprint Medicines] Press Release

Janssen to Discontinue Hepatitis C Development Program

Janssen Sciences Ireland UC announced a strategic decision to discontinue further development of the investigational hepatitis C treatment regimen JNJ-4178, a combination of three direct acting antivirals – AL-335, odalasvir and simeprevir. The ongoing Phase II studies with JNJ-4178 will be completed as planned, but there will be no additional development thereafter. [Janssen Global Services, LLC.] Press Release

FDA Approves Two Ortho Clinical Diagnostics Specialty Hepatitis B Assays

Ortho Clinical Diagnostics has received approval from the FDA for Ortho’s VITROS^® Immunodiagnostic Products HBeAg Assay and the VITROS^® Immunodiagnostic Products Anti-HBe Assay for use on Ortho’s VITROS^® 3600 Immunodiagnostic System and Ortho’s VITROS^® 5600 Integrated System. Both assays are used as an aid in diagnosis of hepatitis B infection in individuals with acute or chronic hepatitis B or recovery from hepatitis B infection. [Ortho Clinical Diagnostics] Press Release

U.S. House Approves 2018 Spending Bills, but Process Far from Finished

The U.S. House of Representatives took a major step toward setting federal science budgets for the 2018 fiscal year. But Congress is still far from the finish line, and final spending levels aren’t likely to be finalized until late this year at the earliest. [ScienceInsider] Editorial

Congress Rejects Trump Proposals to Cut Health Research Funds

Congress has not only rejected the president’s National Institutes of Health proposal; lawmakers from both parties have joined forces to increase spending on biomedical research — and have bragged about it. [The New York Times] Editorial

UK Gender-Equality Scheme Spreads Across the World

A program that grades UK universities on gender equality in science is going global. Versions of the rating scheme have started up in the past two years in Australia and Ireland, and a small-scale pilot begins next month in the United States. [Nature News] Editorial

After Uproar, U.K. Parliament’s Science Committee Now Has a Female Member

The House of Commons Science and Technology Committee tweeted that it was “pleased to announced our membership has been confirmed.” Parliamentary committees had been dissolved after the recent U.K. election, and now the panel was rolling out its new contingent of lawmakers. The only problem: All eight of the mostly smiling faces belonged to men. [ScienceInsider] Editorial

NEW EMBO-EMBL Symposia: Tissue Self-Organization: Challenging the Systems
March 11-14, 2018
Heidelberg, Germany

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