Hepatic Cell News Volume 1.19 | Jun 9 2017

TOP STORY

Interrupted Glucagon Signaling Reveals Hepatic α Cell Axis and Role for L-Glutamine in α Cell Proliferation

To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation, scientists used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of mouse, zebrafish, and human α cells was mTOR and FoxP transcription factor dependent. [Cell Metab] Abstract | Graphical Abstract

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DNA Methyltransferases Modulate Hepatogenic Lineage Plasticity of Mesenchymal Stromal Cells

Researchers found that hepatogenic differentiation of mesenchymal stromal cells is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor β1, which in turn controls hepatogenic differentiation and de-differentiation. [Stem Cell Reports] Full Article | Graphical Abstract

MicroRNA-199b-5p Attenuates TGF-β1-Induced Epithelial–Mesenchymal Transition in Hepatocellular Carcinoma

The authors investigated the expression status of N-cadherin and its molecular mechanisms in hepatocellular carcinoma (HCC). The expression of N-cadherin was markedly overexpressed in HCC tissues and cell lines. [Br J Cancer] Abstract

TGF-β-Induced Hepatocyte lincRNA-p21 Contributes to Liver Fibrosis in Mice

Researchers isolated hepatocytes from CCl₄-induced fibrotic liver and found that hepatocyte lincRNA-p21 significantly increased during liver fibrosis. [Sci Rep] Full Article

Downregulation of UHRF1 Increases Tumor Malignancy by Activating the CXCR4/AKT-JNK/IL-6/Snail Signaling Axis in Hepatocellular Carcinoma Cells

Scientists observed that hypoxia-induced downregulation of ubiquitin-like, with PHD and RING finger domains 1 (UHRF1) contributes to the induction of the epithelial-mesenchymal transition in hepatocellular carcinoma cells. [Sci Rep] Full Article

Mesenchymal Stem Cells Support Growth and Organization of Host-Liver Colorectal-Tumor Organoids and Possibly Resistance to Chemotherapy

Host-liver colorectal-tumor spheroids composed of primary human hepatocytes, mesenchymal stem cells and colon carcinoma HCT116 cells were created in simulated microgravity rotating wall vessel bioreactors. [Biofabrication] Abstract

Lipopolysaccharide Induces the Differentiation of Hepatic Progenitor Cells into Myofibroblasts via Activation of the Hedgehog Signaling Pathway

Hepatic progenitor cells (HPCs) promoted liver fibrosis in rats following carbon tetrachloride treatment. Meanwhile, the lipopolysaccharide (LPS) level in the portal vein was elevated and played a primary role in the fate of HPCs. In vitro, LPS inhibited the hepatobiliary differentiation of HPCs. [Cell Cycle] Abstract

Synthesis and Characterization of Novel BMI1 Inhibitors Targeting Cellular Self-Renewal in Hepatocellular Carcinoma

Investigators synthesized a panel of novel BMI1 inhibitors and examined their ability to alter cellular growth and eliminate cancer progenitor/stem-like cells in hepatocellular carcinoma with different p53 backgrounds. [Target Oncol] Abstract

Microenvironment of a Tumor-Organoid System Enhances Hepatocellular Carcinoma Malignancy-Related Hallmarks

Researchers demonstrated that hepatocellular carcinoma (HCC) cells, fibroblasts, endothelial cells and extracellular matrix can generate organoid-like spheroids that enhanced numerous features of human HCC observed in vivo. [Organogenesis] Abstract

Daucosterol Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Wnt/β-Catenin Signaling

Investigators determined the effects of daucosterol on hepatocellular carcinoma (HCC) by investigating Wnt/β-catenin signaling. HepG2 and SMMC-7721 cells were treated with varying concentrations of daucosterol, and the corresponding inhibitory effects on HCC cells were examined via CCK-8 assays. [Molecules] Full Article

Engineering In Vitro Models of Hepatofibrogenesis

The development of well-defined three-dimensional in vitro models, which mimic extracellular matrix structures as found in vivo, have demonstrated the importance of cell-matrix bio-mechanics, the complex interactions between hepatic stellate cells and hepatocytes and other non-parenchymal cells, and this to improve and promote liver cell-specific functions. [Adv Drug Deliv Rev] Abstract | Graphical Abstract

The Therapeutic Targeting of HGF/c-Met Signaling in Hepatocellular Carcinoma: Alternative Approaches

The poor prognosis of hepatocellular carcinoma (HCC), one of the most devastating cancers worldwide, is due to frequent recurrence and metastasis. Among the metastatic factors in the tumor microenvironment, hepatocyte growth factor (HGF) has been well known to play critical roles in tumor progression, including HCC. [Cancers] Full Article | Graphical Abstract

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Cerenis Therapeutics: Positive Results from the CER-209 Phase I Single Dose Tolerance Study for NAFLD and NASH

Cerenis Therapeutics announced positive results in the SDT Phase I development of CER-209 for the treatment of liver diseases NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steato-hepatitis). [Cerenis Therapeutics] Press Release

Eureka Therapeutics and City of Hope Announce Agreement to Conduct Phase I Clinical Trial of Investigational ET1402L1 CAR-T Therapy in Liver Cancer

Eureka Therapeutics Inc. and City of Hope announced that they have reached agreement to conduct an open-label, dose-escalating Phase I clinical trial of ET1402L1-CAR, a potential CAR-T therapy for the treatment of hepatocellular carcinoma, the predominant type of liver cancer. [Eureka Therapeutics Inc. (Business Wire, Inc.)] Press Release

Viking Therapeutics Announces Promising Top Line Results from In Vivo Study of VK2809 in Non-Alcoholic Steatohepatitis (NASH)

Viking Therapeutics, Inc. announced positive top line results from a study of VK2809 in an in vivo model of NASH. [Viking Therapeutics, Inc.] Press Release

UK Scientists Hope for Softened Brexit after Shock Election Result

The United Kingdom (UK)’s general election produced no clear outcome — but scientists trying to divine meaning from the chaos say they hope the result will ultimately benefit their country’s research ties with the European Union. [Nature News] Editorial

NSF Offers Arm’s-Length Defense of Trump’s 2018 Request

President Donald Trump’s proposal for an 11.3% cut in spending at the National Science Foundation (NSF) may be dead on arrival in Congress. But that doesn’t mean congressional appropriators will be able to avoid any squeeze on NSF’s budget. [ScienceInsider] Editorial

Critics Challenge NIH Finding That Bigger Labs Aren’t Necessarily Better

A strident debate has erupted among biomedical researchers over a proposed National Institutes of Health (NIH) policy that would shift money from richer to poorer labs. The policy—which would limit investigators to the equivalent of three NIH grants—is based largely on an agency-led analysis of lab productivity. It found that once an NIH-funded lab grows to a certain size, each additional grant produces a smaller productivity boost. But NIH’s study, and one graph in particular, has drawn widespread criticism. [ScienceInsider] Editorial

NEW European Society for Medical Oncology (ESMO) 2017 Congress
September 8-12, 2017
Madrid, Spain

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NEW Postdoctoral Associate – Gene Therapy (University of Massachusetts Medical School)

Research Fellow – Cancer Research (National University of Singapore)

Postdoctoral Studies – Liver Functions (Karolinska Instituet)

Postdoctoral Position – Novel Molecular and Cellular Mechanisms of Liver and Pancreatic Carcinogenesis (University of Illinois College of Medicine)

Assistant Professor – Renal and Hepatic Pharmacology (University of Manitoba)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

Postdoctoral Fellow – Obesity-Associated Complications (University of Kentucky College of Medicine)

Postdoctoral Position – Pediatrics/Cell Biology (Washington University School of Medicine)

Scientist – Hepatic Nuclear Receptor Biology (Moderna Therapeutics)

Research Lead – Liver Discovery (Spark Therapeutics)

Research Technician II – Translational Liver Cancer (Fred Hutchinson Cancer Research Center)

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

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