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https://www.readbyqxmd.com/read/28931802/hepatitis-c-virus-infection-increases-c-jun-n-terminal-kinase-jnk-phosphorylation-and-accentuates-hepatocyte-lipoapoptosis
#1
Hiroko Takaki, Yuko Akazawa, Youko Kido, Mami Morishita, Takuya Honda, Hidetaka Shibata, Satoshi Miuma, Hisamitsu Miyaaki, Naota Taura, Hisayoshi Kondo, Kazuhiko Nakao
BACKGROUND Hepatitis C virus (HCV) infection and metabolic diseases including nonalcoholic steatohepatitis (NASH) exhibit a complex interplay. Although free fatty acid-mediated apoptosis is a prominent feature of NASH, the impact of HCV infection on hepatocyte lipotoxicity has remained largely unexplored. The study aimed at identifying whether infection by HCV affected the apoptotic pathway in hepatocytes during fatty acid assault. MATERIAL AND METHODS OR6 cells, which are derived from human hepatocellular carcinoma Huh-7 cells and harbor a full-length HCV RNA genome replication system, were treated with palmitate...
September 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28930164/liver-cancer-molecular-characterization-clonal-evolution-and-cancer-stem-cells
#2
REVIEW
Germana Castelli, Elvira Pelosi, Ugo Testa
Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV) infection (frequent in Asia and Africa), hepatitis C virus (HCV), chronic alcohol abuse, or metabolic syndrome (frequent in Western countries)...
September 20, 2017: Cancers
https://www.readbyqxmd.com/read/28923827/mutant-ctnnb1-and-histological-heterogeneity-define-metabolic-subtypes-of-hepatoblastoma
#3
Stefania Crippa, Pierre-Benoit Ancey, Jessica Vazquez, Paolo Angelino, Anne-Laure Rougemont, Catherine Guettier, Vincent Zoete, Mauro Delorenzi, Olivier Michielin, Etienne Meylan
Hepatoblastoma is the most common malignant pediatric liver cancer. Histological evaluation of tumor biopsies is used to distinguish among the different subtypes of hepatoblastoma, with fetal and embryonal representing the two main epithelial components. With frequent CTNNB1 mutations, hepatoblastoma is a Wnt/β-catenin-driven malignancy. Considering that Wnt activation has been associated with tumor metabolic reprogramming, we characterized the metabolic profile of cells from hepatoblastoma and compared it to cells from hepatocellular carcinoma...
September 18, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28919607/impact-of-adrenocortical-insufficiency-on-clinical-parameters-in-haemodynamically-stable-cirrhotic-patients-with-ascites
#4
H Ahmed, M R Karim, R K Paul, M Chowdhury, M S Alam, A Saha, F Rahman, M A Rouf
Cirrhosis has many complications regardless of the aetiology. Complications include splenomegaly, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome and hepatocellular carcinoma and also linked to abnormalities in the endocrine system, including abnormal sex hormone metabolism, thyroid disease, osteoporosis, and, most recently identified, adrenal insufficiency. This prospective cohort study was done to evaluate the impact of adrenocortical insufficiency on clinical parameters in haemodynamically stable cirrhotic patients with ascites and had been performed at the inpatient of GHPD Department, BIRDEM, Dhaka, Bangladesh from April 2011 to March 2012...
July 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28918389/glucagon-like-peptide-1-receptor-agonists-for-the-management-of-obesity-and-non-alcoholic-fatty-liver-disease-a-novel-therapeutic-option
#5
REVIEW
Gauri Dhir, Kenneth Cusi
Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM), and is associated with a cluster of metabolic factors that lead to poor cardiovascular outcomes. In non-alcoholic fatty liver disease (NAFLD), liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. It is now recognized as the most common chronic liver disease in Westernized societies, often progressing to more severe forms of the disease such as nonalcoholic steatohepatitis (NASH), or cirrhosis and hepatocellular carcinoma...
September 15, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28915658/oxidative-stress-mediates-an-increased-formation-of-vascular-endothelial-growth-factor-in-human-hepatocarcinoma-cells-exposed-to-erlotinib
#6
Nataliya Rohr-Udilova, Florian Klinglmüller, Martha Seif, Hubert Hayden, Martin Bilban, Matthias Pinter, Klaus Stolze, Wolfgang Sieghart, Markus Peck-Radosavljevic, Michael Trauner
The tyrosine kinase inhibitor erlotinib targets the receptor of epidermal growth factor (EGFR) involved in development of hepatocellular carcinoma (HCC). Although inefficient in established HCC, erlotinib has been recently proposed for HCC chemoprevention. Since Cyp3A4 and Cyp1A2 enzymes metabolize erlotinib in the liver, the insights into the mechanisms of erlotinib effects on liver cells with maintained drug metabolizing activity are needed. We applied erlotinib to both commercially available (SNU398, Huh7) and established in Austria HCC cell lines (HCC-1...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#7
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28910694/an-epidemiologic-perspective-on-the-stem-cell-hypothesis-in-human-carcinogenesis
#8
REVIEW
David Schottenfeld
BACKGROUND: Tomasetti and Vogelstein have hypothesized that the patterns of cancer incidence in various cells and tissues are highly correlated with the estimated lifetime number of stem cell divisions. The authors reviewed the risks in tissues of 17 types of cancer from the United States and 69 additional countries. Positive correlations were observed consistently between the tissue - specific cancer incidence and the estimated lifetime number of stem cell divisions. The authors concluded that approximately two-thirds of global cancer incidence may be attributed to random DNA replication errors...
September 11, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28903501/sex-differential-responses-of-tumor-promotion-associated-genes-and-dysregulation-of-novel-long-noncoding-rnas-in-constitutive-androstane-receptor-activated-mouse-liver
#9
Nicholas J Lodato, Tisha Melia, Andy Rampersaud, David J Waxman
Xenobiotic agonists of constitutive androstane receptor (CAR) induce many hepatic drug metabolizing enzymes, but following prolonged exposure, promote hepatocellular carcinoma, most notably in male mouse liver. Here, we used nuclear RNA-seq to characterize global changes in the mouse liver transcriptome following exposure to the CAR-specific agonist ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), including changes in novel long noncoding RNAs that may contribute to xenobiotic-induced pathophysiology...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903330/inhibition-of-hsf1-suppresses-the-growth-of-hepatocarcinoma-cell-lines-in-vitro-and-akt-driven-hepatocarcinogenesis-in-mice
#10
Antonio Cigliano, Chunmei Wang, Maria G Pilo, Marta Szydlowska, Stefania Brozzetti, Gavinella Latte, Giovanni M Pes, Rosa M Pascale, Maria A Seddaiu, Gianpaolo Vidili, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Upregulation of the heat shock transcription factor 1 (HSF1) has been described as a frequent event in many cancer types, but its oncogenic role in hepatocellular carcinoma (HCC) remains poorly delineated. In the present study, we assessed the function(s) of HSF1 in hepatocarcinogenesis via in vitro and in vivo approaches. In particular, we determined the importance of HSF1 on v-Akt murine thymoma viral oncogene homolog (AKT)-induced liver cancer development in mice. We found that knockdown of HSF1 activity via specific siRNA triggered growth restraint by suppressing cell proliferation and inducing massive cell apoptosis in human HCC cell lines...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902419/reassessing-the-safety-concerns-of-utilizing-blood-donations-from-patients-with-hemochromatosis
#11
REVIEW
Adam C Winters, Douglas Tremblay, Suzanne Arinsburg, John Mascarenhas, Thomas D Schiano
Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism which may lead to iron overload. Clinical penetrance is low, however those afflicted may develop cirrhosis, hepatocellular carcinoma, diabetes mellitus and cardiomyopathy. Treatment involves regular phlebotomy to reduce the systemic iron burden. In many countries-including the United States-numerous blood centers do not accept donated blood obtained from HH patients during therapeutic phlebotomy and there are inconsistent positions regarding this globally...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#12
Eunüs S Ali, Grigori Y Rychkov, Greg J Barritt
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca(2+) in the lumen of the ER. In steatotic hepatocytes, store-operated Ca(2+) entry (SOCE) is substantially inhibited...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28894223/long-term-administration-of-nuclear-bile-acid-receptor-fxr-agonist-prevents-spontaneous-hepatocarcinogenesis-in-abcb4-mice
#13
Marica Cariello, Claudia Peres, Roberta Zerlotin, Emanuele Porru, Carlo Sabbà, Aldo Roda, Antonio Moschetta
Altered bile acid (BA) signaling is associated with hepatotoxicity. The farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates BA homeostasis. Mice with FXR ablation present hepatocarcinoma (HCC) due to high toxic BA levels. Mice with Abcb4 ablation accumulate toxic BA within the bile ducts and present HCC. We have previously shown that intestinal specific activation of FXR by transgenic VP16-FXR chimera is able to reduce BA pool size and prevent HCC. Here we tested chemical FXR activation by administering for 15 months the dual FXR/ membrane G protein-coupled receptor (TGR5) agonist INT-767 (6α-ethyl-3α,7α,23-trihydroxy-24-nor-5β-cholan-23-sulphate) to Fxr(-/-) and Abcb4(-/-) mice...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892791/in-vitro-in-silico-and-in-vivo-antitumor-activity-of-crude-methanolic-extract-of-tetilla-dactyloidea-carter-1869-on-den-induced-hcc-in-a-rat-model
#14
Gowri Shankar Krishnan, Vidhya Rajagopal, Sophy Renilda Antony Joseph, Divya Sebastian, Ignacimuthu Savarimuthu, Karthick Raja Namasivayam Selvaraj, Albin Fleming Thobias
Tetilla dactyloidea (Carter, 1869) is a marine sponge classified under Demospongia and recent studies have demonstrated that active constituents of Demospongia class have exhibited several potential medical applications. However, no preliminary pharmacological studies have been reported so far. The present investigation was carried out to evaluate the zoo-chemical status, antioxidant potential and anticancer activity of Crude Methanolic Extract of Tetilla dactyloidea (CMETD). Hepatocellular Carcinoma (HCC) was induced in the liver of male Sprague Dawley (SD) rats by treating with diethylnitrosamine (DEN)...
September 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28892047/a-system-for-detecting-high-impact-low-frequency-mutations-in-primary-tumors-and-metastases
#15
M Anjanappa, Y Hao, E R Simpson, P Bhat-Nakshatri, J B Nelson, S A Tersey, R G Mirmira, A A Cohen-Gadol, M R Saadatzadeh, L Li, F Fang, K P Nephew, K D Miller, Y Liu, H Nakshatri
Tumor complexity and intratumor heterogeneity contribute to subclonal diversity. Despite advances in next-generation sequencing (NGS) and bioinformatics, detecting rare mutations in primary tumors and metastases contributing to subclonal diversity is a challenge for precision genomics. Here, in order to identify rare mutations, we adapted a recently described epithelial reprograming assay for short-term propagation of epithelial cells from primary and metastatic tumors. Using this approach, we expanded minor clones and obtained epithelial cell-specific DNA/RNA for quantitative NGS analysis...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28886081/orexin-a-affects-hepg2-human-hepatocellular-carcinoma-cells-glucose-metabolism-via-hif-1%C3%AE-dependent-and-independent-mechanism
#16
Xing Wan, Yuanyuan Liu, Yuyan Zhao, Xiaoqi Sun, Dongxiao Fan, Lei Guo
Orexins are hypothalamic neuropeptides that regulate feeding, reward, wakefulness and energy homeostasis. The present study sought to characterize the involvement of orexin A in glucose metabolism in HepG2 human hepatocellular carcinoma cells, and investigated the role of hypoxia-inducible factor-1α (HIF-1α) in the response. HepG2 cells were exposed to different concentrations of orexin A (10-9 to 10-7 M) in vitro, without or with the orexin receptor 1 (OX1R) inhibitor (SB334867), HIF-1α inhibitor (YC-1) or a combination of both inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28884605/nanomedicines-a-theranostic-approach-for-hepatocellular-carcinoma
#17
Afreen Usmani, Anuradha Mishra, Mohd Ahmad
The liver is an imperative organ of tremendous importance concerned with maintenance of metabolic functions and detoxification of exogenous and endogenous challenges like xenobiotics, viral infections and chronic alcoholism. Liver diseases particularly hepatitis B virus infections, liver cirrhosis and hepatocellular carcinoma continue to pose a significant health challenge worldwide due to the lack of therapeutic management options besides liver resection and transplantation. Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer mortality worldwide...
September 8, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28884001/6-7-dimethoxy-1-2-3-4-tetrahydro-isoquinoline-3-carboxylic-acid-attenuates-heptatocellular-carcinoma-in-rats-with-nmr-based-metabolic-perturbations
#18
Pranesh Kumar, Ashok K Singh, Vinit Raj, Amit Rai, Siddhartha Maity, Atul Rawat, Umesh Kumar, Dinesh Kumar, Anand Prakash, Anupam Guleria, Sudipta Saha
AIM: 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) was synthesized and evaluated for in-vivo antiproliferative action in diethylnitrosamine-induced hepatocarcinogenic rats. MATERIALS & METHODS: The antiproliferative effect of M1 was assessed by various biochemical parameters, histopathology of liver and HPLC analysis. Proton nuclear magnetic resonance-based serum metabolic study was implemented on rat sera to explore the effects of M1 on hepatocellular carcinoma-induced metabolic alterations...
August 2017: Future Science OA
https://www.readbyqxmd.com/read/28881813/differential-metabonomic-profiles-of-primary-hepatocellular-carcinoma-tumors-from-alcoholic-liver-disease-hbv-infected-and-hcv-infected-cirrhotic-patients
#19
Ding Cao, Can Cai, Mingxin Ye, Junhua Gong, Menghao Wang, Jinzheng Li, Jianping Gong
Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC tumors from the three groups...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28876464/novel-mutations-in-transthyretin-gene-associated-with-hepatocellular-carcinoma
#20
Deepshikha Pande Katare, Shabnam Malik, Ruchi Jakhmola Mani, Maryam Ranjpour, S K Jain
Hepatocellular carcinoma (HCC) is one of the major health problems with increasing incidence worldwide. We report the elevation in transthyretin (TTR) expression following HCC induction using diethylnitrosamine (DEN) and 2-aminoacetylfluorine (2-AAF) in male Wistar rats. The increase in its expression took place at very early stage and remained elevated throughout HCC progression. The analysis of TTR gene in HCC bearing rats revealed four novel mutations that alter three amino acids at positions 61, 100 and 115...
September 6, 2017: Molecular Carcinogenesis
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