Hepatic Cell News Volume 2.46 | Nov 30 2018

TOP STORY

Metabolic Network-Based Stratification of Hepatocellular Carcinoma Reveals Three Distinct Tumor Subtypes

Scientists identified three distinct subtypes with substantial differences in metabolic and signaling pathways reflecting at genomic, transcriptomic, and proteomic levels. The subtypes showed large differences in clinical survival associated with altered kynurenine metabolism, WNT/β-catenin-associated lipid metabolism, and PI3K/AKT/mTOR signaling. [Proc Natl Acad Sci USA] Abstract

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Application of Patient-Derived Liver Cancer Cells for Phenotypic Characterization and Therapeutic Target Identification

Morphological and histological characteristics of obtained cell lines and xenograft tumors were analyzed and compared to original tumors. Time course analyses of transcriptomic and genomic changes were performed using next-generation sequencing (NGS). Key oncogenic alterations were identified by targeted NGS and cell lines carrying potentially actionable mutations were treated with corresponding specific inhibitors. [Int J Cancer] Abstract

Sex Hormone-Binding Globulin Expression Correlates with Acetyl-CoA Carboxylase and Triglyceride Content in Human Liver

Sex hormone binding globulin (SHBG) mRNA and protein levels were lower in subjects with metabolic syndrome when compared with subjects without metabolic syndrome; these differences were only significant at mRNA level. SHBG mRNA levels correlated positively with SHBG protein levels and hepatic triglyceride content.SHBG mRNA and protein levels correlated negatively with acetyl-CoA Carboxylase mRNA levels and triglyceride content. [J Clin Endocrinol Metab] Abstract

Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. [Cell Physiol Biochem] Full Article

Gain of UBE2D1 Facilitates Hepatocellular Carcinoma Progression and Is Associated with DNA Damage Caused by Continuous Il-6

Four hepatocellular carcinoma (HCC) cell lines and two immortalized hepatic cell lines were used to evaluate the functional roles and underlying mechanisms of UBE2D1 in HCC initiation and progression in vitro and in vivo. [J Exp Clin Cancer Res] Full Article

Proteomic Profiling of Human Hepatic Stellate Cell Line LX2 Responses to Irradiation and TGF-β1

Researchers treated human hepatic stellate cells line LX2 with X-ray irradiation and/or TGF-β1 and profibrogenic molecules were evaluated. The iTRAQ LC-MS/MS technology was performed to identify global protein expression profiles in LX2 following exposure to different stimuli. [J Proteome Res] Abstract

miR-663a Inhibits Tumor Growth and Invasion by Regulating TGF-β1 in Hepatocellular Carcinoma

miR-663a was significantly downregulated in hepatocellular carcinoma (HCC) cells relative to immortal normal liver cells, as indicated using qRT-PCR, and the lower expression of miR-663a was also confirmed in HCC tissue samples and the data from TCGA. The expression of miR-663a in HCC tissue samples was statistically significantly associated with size and the number of tumors. [BMC Cancer] Full Article

Rhein Reverses Doxorubicin Resistance in SMMC-7721 Liver Cancer Cells by Inhibiting Energy Metabolism and Inducing Mitochondrial Permeability Transition Pore Opening

Treatment with rhein increased accumulation of doxorubicin-resistant cells (DOX) in SMMC-7721/DOX cells, inhibited mitochondrial energy metabolism, decreased cellular ATP, and ADP levels, and altered the ratio of ATP to ADP. [Biofactors] Abstract

A pH-Responsive Glycyrrhetinic Acid-Modified Small Molecular Conjugate for NIR Imaging of Hepatocellular Carcinoma

Researchers demonstrated that NIR-GA was efficiently up-taken by liver cancer cell lines such as HepG2 and Huh7 through GA receptors-mediated endocytic pathway. NIR-GA mainly localized into the lysosome where acidic pH results in activation of fluorescent dye via H+_triggered spirolactam ring opening to give strong fluorescence in NIR region. [Chembiochem] Abstract

Life Cycle and Morphogenesis of the Hepatitis E Virus

The authors summarize the current knowledge regarding the HEV life cycle, viral morphogenesis, established model systems and vaccine development. [Emerg Microbes Infect] Full Article

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Vir Biotechnology and Alnylam Pharmaceuticals Initiate Phase I/II Study of VIR-2218

Vir Biotechnology, Inc. and Alnylam Pharmaceuticals, Inc. announced the initiation of a Phase I/II study of VIR-2218, a novel, investigational RNA interference therapeutic for the treatment of chronic hepatitis B virus infection. [VIR BIOTECHNOLOGY, INC.] Press Release

Poxel Announces Initiation of Part 2 of Phase Ia Study for PXL065, Which Is Being Developed for the Treatment of NASH

POXEL SA announced that part 2 of the Phase Ia study for PXL065, a deuterium-stabilized R-stereoisomer of pioglitazone, has been initiated. This second part of the Phase Ia study will enroll six healthy subjects per group, with a primary objective to assess safety and tolerability and a secondary objective to assess dose proportionality. [Poxel SA] Press Release

HighTide Therapeutics Receives Fast Track Designation from the U.S. FDA for HTD1801 Treating Nonalcoholic Steatohepatitis

HighTide Therapeutics Inc. announced that the U.S. FDA has granted Fast Track Designation to its investigational new drug, HTD1801, for the treatment of patients with nonalcoholic steatohepatitis [HighTide Therapeutics Inc.] Press Release

NIH Director Says There’s Work to Do on Regulating Genome Editing Globally

The apparent birth this month of the first genetically modified babies is “a lesson in the potential for human hubris to overtake us,” Dr. Francis Collins, the director of the National Institutes of Health (NIH), told STAT, but he said there is little U.S. officials can do to influence how China sanctions the rogue scientist who claims to have led the ethically dubious scientific breakthrough. [STAT News] Editorial

Researcher Who Created CRISPR Twins Defends His Work but Leaves Many Questions Unanswered

The researcher who set off a global firestorm when he announced the birth of the world’s first gene-edited babies defended his study at a meeting. He Jiankui of the Southern University of Science and Technology in nearby Shenzhen, China, said he was “proud” of the work, which he said could lead to disease prevention “for millions of children,” and provided some details about the unpublished research that many scientists and bioethicists—as well as a phalanx of journalists—were clamoring to hear. [ScienceInsider] Editorial

NEW Keystone Symposia: Lipidomics and Functional Metabolic Pathways in Disease
March 31-April 4, 2019
Steamboat Springs, United States

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NEW Research Associate – Cancer Structural Biology (University of British Columbia)

Postdoctoral Position – Cancer Biology (Fox Chase Cancer Center)

Postdoctoral Scholarships – Medicinal Chemistry, Experimental Biology & Systems Biology (KTH Royal Institute of Technology)

PhD Position – Non-Alcoholic Fatty Liver Disease (Deutsche Diabetes Forschungsgesellschaft e. V)

Postdoctoral Positions – Experimental and Computational Quantitative Single-Cell Biology (Max Planck Institute of Immunobiology and Epigenetics)

Postdoctoral Research Fellow – 3D Organoid Development (University of Oslo)

Postdoctoral Researcher – Alcohol-Induced Liver Injury (Indiana University)

Postdoctoral Researcher – Gene Regulation in Obesity Related Liver Cancer (Umeå University)

Post Doctoral Fellowship – Liver Biology and Pathophysiology (Johns Hopkins University)

Postdoctoral Fellow – Molecular Mechanisms of Alcoholic Liver Disease (Northeast Ohio Medical University)

Postdoctoral Position – Liver Cancer Translational Research (August Pi i Sunyer Biomedical Research Institute)

Postdoctoral Position – Molecular & Integrative Physiology (University of Michigan)

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