Hepatic Cell News Volume 3.27 | Jul 26 2019

TOP STORY

Modeling Liver Cancer Initiation with Organoids Derived from Directly Reprogrammed Human Hepatocytes

Using directly reprogrammed human hepatocytes (hiHeps) and inactivation of p53 and RB, scientists established organoids possessing liver architecture and function. HiHep organoids were genetically engineered to model the initial alterations in human liver cancers. [Nat Cell Biol] Abstract

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Single Cell Analysis of Human Fetal Liver Captures the Transcriptional Profile of Hepatobiliary Hybrid Progenitors

The authors report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human fetal liver using single-cell RNA sequencing. HHyPs were anatomically restricted to the ductal plate of fetal liver and maintained a transcriptional profile distinct from fetal hepatocytes, mature hepatocytes and mature bile duct epithelial cells. [Nat Commun] Full Article | Press Release

LncRNA HAND2-AS1 Promotes Liver Cancer Stem Cell Self-Renewal via BMP Signaling

Human HAND2-AS1 and its mouse ortholog lncHand2 displayed a high level of conservation. HAND2-AS1 was required for the self-renewal maintenance of liver cancer stem cells to initiate hepatocellular carcinoma development. [EMBO J] Abstract | Graphical Abstract

DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing

DIS3-like 3′-5′ exoribonuclease 2 (DIS3L2) directly interacted with hnRNP U through its cold-shock domains and promoted inclusion of exon 3b during splicing of pre-Rac1 independent of its exonuclease activity, yielding an oncogenic splicing variant, Rac1b, which is known to stimulate cellular transformation and tumorigenesis. [Cancer Res] Abstract

Identification of a CIP4 PKA Phosphorylation Site Involved in the Regulation of Cancer Cell Invasiveness and Metastasis

In vitro and in vivo experiments using hepatocellular carcinoma (HCC) and breast cancer cells showed that expression of a CIP4(T225E) phosphomimetic mutant increased cancer cell metastatic capacity and that, conversely, expression of a CIP4(T225A) non-phosphorylatable mutant reduced invasive properties. [Cancer Lett] Abstract

Tcf7l1 Acts as a Suppressor for the Self-Renewal of Liver Cancer Stem Cells and Is Regulated by IGF/MEK/ERK Signaling Independent of β-Catenin

In liver cancer stem cell (CSC) populations, Tcf7l1 expression was downregulated. Ectopic expression of Tcf7l1 attenuated the self-renewal abilities of liver CSCs. [Stem Cells] Abstract

Liver Cancer Cell Lines Treated with Doxorubicin under Normoxia and Hypoxia: Cell Viability and Oncologic Protein Profile

Liver cancer cells HepG2, Huh7, and SNU449 were exposed to doxorubicin, hypoxia, or doxorubicin + hypoxia for different durations. Treatment response was evaluated with cell viability, apoptosis, oxidative stress, and summarized with IC₅₀. [Cancers] Full Article

Procyanidin B2 Inhibits the Activation of Hepatic Stellate Cells and Angiogenesis via the Hedgehog Pathway during Liver Fibrosis

The CCl₄-induced mouse liver fibrosis model and a human hepatic stellate cell (HSC) line were used to study the activation, extracellular matrix production and angiogenesis of HSCs through Western blotting analysis, immunohistochemistry, immunofluorescence staining, flow cytometry and tubulogenesis assay. [J Cell Mol Med] Full Article

The Preventative Effects of Procyanidin on Binge Ethanol-Induced Lipid Accumulation and ROS Overproduction via the Promotion of Hepatic Autophagy

In vitro, dimer procyanidin (DPC) significantly decreased intracellular lipid deposition, diminished reactive oxygen species (ROS) formation and elevated the level of mitochondrial membrane potential. These beneficial effects could be blocked by 3-methyladenine, a potent autophagy inhibitor, suggesting the autophagy-dependent protective role of DPC. [Mol Nutr Food Res] Abstract

Three-Dimensional HepaRG Spheroids as a Liver Model to Study Human Genotoxicity In Vitro with the Single Cell Gel Electrophoresis Assay

HepaRG spheroids were used at ten days after seeding and exposed for 24 and 48-hours to certain selected chemical compounds. After treatment, the comet assay was performed on single cell suspensions and cytotoxicity was determined by the ATP assay. [Sci Rep] Full Article

A Critical Role of Autophagy in Regulating the Mesenchymal Transition of Ductular Cells in Liver Cirrhosis

Using both human liver specimens and a rat model of liver cirrhosis induced by 2-acetylaminofluorene (AAF) and carbon tetrachloride (CCL₄), investigators explored the involvement of autophagy in regulating mesenchymal transition of ductular cells. Ductular cells from AAF/CCL₄ livers exhibited increased autophagy compared to those of normal livers. [Sci Rep] Full Article

Folic Acid Conjugated Polymeric Drug Delivery Vehicle for Targeted Cancer Detection in Hepatocellular Carcinoma

Scientists evaluated the specificity and toxicity of a folic acid-containing drug delivery vehicle (DDV) in a hepatocellular carcinoma model. The DDV was prepared with two units each of folic acid and fluorescein isothiocyanate molecules and conjugated to a central poly (ethylene glycol) core via a modified chemo-enzymatic synthetic process. [J Biomed Mater Res A] Abstract

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Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

Scientists dissect the genetic landscape of the TGF-β superfamily genes in hepatocellular carcinoma HCC and discuss the essential effects of this pathway on the tumor immune microenvironment. They highlight the TGF-β signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. [Trends Mol Med] Full Article

Roles and Regulation of Long Non-Coding RNAs in Hepatocellular Carcinoma

The authors map the oncogenic roles of deregulated long non-coding (lnc)RNAs by integrating diverse datasets including clinicopathological features, affected cancer phenotypes, associated miRNA and/or protein interacting partners as well as modulated gene/protein expression. Notably, 63 deregulated lncRNAs are significantly associated with clinicopathological features of hepatocellular carcinoma. [Cancer Res] Abstract

Research Progress on the Anti-Hepatic Fibrosis Action and Mechanism of Natural Products

Mechanisms of anti-liver fibrosis include inhibition of liver inflammation, anti-lipid peroxidation injury, inhibition of the activation and proliferation of hepatic stellate cells, modulation of the synthesis and secretion of pro-fibrosis factors, and regulation of the synthesis and degradation of the extracellular matrix (ECM). Investigators provide suggestions for the development of anti-hepatic fibrosis drugs. [Int Immunopharmacol] Abstract

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Genkyotex Announces Positive Post-Hoc Analysis of PBC Phase II Trial

Genkyotex announced positive post-hoc analysis of PBC Phase II trial. As previously reported, setanaxib achieved clinically meaningful reductions in liver stiffness, statistically significant reduction in gamma glutamyl transpeptidase and alkaline phosphatase over the 24-week treatment period, but did not achieve statistical significance in the reduction of GGT at week 24, the predefined primary efficacy endpoint. [Genkyotex] Press Release

Tiziana Reports Phase IIa Clinical Data with Milciclib Monotherapy in Sorafenib-Refractory or -Intolerant Patients with Unresectable or Metastatic Hepatocellular Carcinoma

Tiziana Life Sciences plc announced preliminary topline clinical data from a Phase IIa trial of Milciclib as a monotherapy in patients with advanced hepatocellular carcinoma, the most common form of liver cancer. [Tiziana Life Sciences plc] Press Release

The WHO Recognizes NOX Inhibitors as New Therapeutic Class and Approves Setanaxib for GKT831

Genkyotex announced that the World Health Organization (WHO) has recommended setanaxib as the international nonproprietary name (INN) for GKT831. The new stem “naxib” approved by WHO refers to NADPH oxidase inhibitors, and formally establishes a new therapeutic class under the WHO INN system. [Genkyotex] Press Release

Former UK Science Minister Returns as Brexit Government Assembles

The prime minister shake-up sees a return to the Conservative government for Jo Johnson, the prime minister’s brother and a former minister for universities and science. Johnson, who was generally popular with scientists, is back as a minister straddling the Department for Business, Energy and Industrial Strategy — which oversees research — and the Department for Education. [Nature News] Editorial

Scientists Doing Basic Studies of Human Brain Win Longer Reprieve from Clinical Trials Reporting Rule

US scientists who challenged a new rule that would require them to register their basic studies of the human brain and behavior in a federal database of clinical trials have won another reprieve. The National Institutes of Health in Bethesda, Maryland, says it now understands why some of that kind of research won’t easily fit the format of ClinicalTrials.gov, and the agency has delayed the reporting requirements for another two years. [Science Magazine] Editorial

NEW Cardiovascular and Interventional Radiological Society of Europe (CRISE) 2019
September 7-11, 2019
Barcelona, Spain

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NEW Scientific Communications Coordinator (STEMCELL Technologies Inc.)

NEW Research Assistant – Cell and Tissue Investigation (University of Texas MD Anderson Cancer Center)

NEW Associate Scientist – In Vitro ADME Research (Gilead Sciences)

NEW Researcher – Cell Biologist and Bioengineer (3D BioLabs, LLC)

Postdoctoral Fellow – Hepatitis C Virus (The Research Institute at Nationwide Children’s Hospital)

Postdoctoral Fellow – Inflammatory Liver Disease (The University of Kansas Medical Center)

Project Leader – Chronic Liver Disease Drug Discovery (Inserm Institute for Viral and Liver Disease)

Research Associate – System Level Analysis of Human Organogenesis (The University of Manchester)

Postdoctoral Position – Human Liver Microphysiology Systems (University of Pittsburgh Drug Discover Institute)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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