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Lipoproteine, HCC

Xiao-Lu Ma, Xing-Hui Gao, Zi-Jun Gong, Jiong Wu, Lu Tian, Chun-Yan Zhang, Yan Zhou, Yun-Fan Sun, Bo Hu, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Wei Guo, Xin-Rong Yang
As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage...
September 23, 2016: Oncotarget
Y Luo, W J Yang, J Y Chen, J Zhang, X D Zeng, Z J Zhuang, S F Zang, G Zhou, C H Di, J P Shi
OBJECTIVE: To establish an apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) double-knockout (ApoE(-/-)/LDLR(-/-)) mouse model of nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) induced by high-fat and high-cholesterol (HFHC) diet. METHODS: ApoE(-/-) knockout mice were crossed with LDLR(-/-) knockout mice to obtain ApoE(-/-)/LDLR(-/-) mice. The ApoE(-/-)/LDLR(-/-) mice mated with each other, and the offspring were injected with low-dose streptozotocin (STZ) at 2-3 days after birth...
April 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Dan Cao, Xinhua Song, Li Che, Xiaolei Li, Maria G Pilo, Gianpaolo Vidili, Alberto Porcu, Antonio Solinas, Antonio Cigliano, Giovanni M Pes, Silvia Ribback, Frank Dombrowski, Xin Chen, Lei Li, Diego F Calvisi
BACKGROUND & AIMS: Although it is well established that fatty acids (FA) are indispensable for the proliferation and survival of cancer cells in hepatocellular carcinoma (HCC), inhibition of Fatty Acid Synthase (FASN) cannot completely repress HCC cell growth in culture. Thus, we hypothesized that uptake of exogenous FA by cancer cells might play an important role in the development and progression of HCC. Lipoprotein lipase (LPL) is the enzyme that catalyses the hydrolysis of triglycerides into free fatty acids (FFA) and increases the cellular uptake of FA...
June 6, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Yuanyuan Wang, Junli Hao, Xiaohong Liu, Hongxin Wang, Xin Zeng, Jing Yang, Lei Li, Xi Kuang, Tao Zhang
BACKGROUND: Hepatitis B virus (HBV) infection correlated with the development of cirrhosis, liver failure and hepatocellular carcinoma (HCC), poses a huge health burden on the global community. However, the pathogenesis of chronic hepatitis B (CHB) remains unclear. Apolipoprotein A1 (ApoA1) mainly secreted by hepatocytes, represents the major protein component of high-density lipoprotein. ApoA1 secretion may be disrupted by HBV infection. In this study, we mainly investigated the molecular mechanism of ApoA1 down regulated by HBV for revealing the pathogenesis of CHB...
2016: Lipids in Health and Disease
Mohamed I F Shariff, Joshua M Tognarelli, Matthew R Lewis, Elizabeth J Want, Fatma El Zahra Mohamed, Nimzing G Ladep, Mary M E Crossey, Shahid A Khan, Rajiv Jalan, Elaine Holmes, Simon D Taylor-Robinson
BACKGROUND/AIMS: The primary aim of this study was to characterise the blood metabolic profile of hepatocellular carcinoma (HCC) in a rat model, and the secondary aim was to evaluate the effect of the quinolone, norfloxacin on metabolic profiles and exploring the role that gut sterilisation may have on HCC development. METHODS: HCC was induced in 10 Fischer rats by administration of intra-peritoneal diethylnitrosamine (DEN) and oral N-nitrosomorpholine. Plasma was collected upon sacrifice...
December 2015: Journal of Clinical and Experimental Hepatology
Batur Mamtimin, Guo Xia, Mahmut Mijit, Mawlanjan Hizbulla, Nazuk Kurbantay, Li You, Halmurat Upur
BACKGROUND: Abnormal Savda Munziq (ASMq) is a traditional Uyghur herbal preparation used as a therapy for abnormal Savda-related diseases. In this study, we investigate ASMq's dynamic effects on abnormal Savda rat models under different disease conditions. MATERIALS AND METHODS: Abnormal Savda rat models with hepatocellular carcinoma (HCC), type 2 diabetes mellitus (T2DM), and asthma dosed of ASMq. Serum samples of each animal tested by nuclear magnetic resonance spectroscopy and analyzed by orthogonal projection to latent structure with discriminant analysis...
October 2015: Pharmacognosy Magazine
Jaleh Varshosaz, Maryam Farzan
Hepatocellular carcinoma (HCC) is the 5(th) most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorable systemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs (siRNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and siRNA to cells...
November 14, 2015: World Journal of Gastroenterology: WJG
Petr Protiva, Jingjing Gong, Bharath Sreekumar, Richard Torres, Xuchen Zhang, Glenn S Belinsky, Mona Cornwell, Susan E Crawford, Yasuko Iwakiri, Chuhan Chung
BACKGROUND & AIMS: Pigment epithelium-derived factor (PEDF) is a secretory protein that inhibits multiple tumor types. PEDF inhibits the Wnt coreceptor, low-density lipoprotein receptor-related protein 6 (LRP6), in the eye, but whether the tumor-suppressive properties of PEDF occur in organs such as the liver is unknown. METHODS: Wnt-dependent regulation of PEDF was assessed in the absence and presence of the Wnt coreceptor LRP6. Whole genome expression analysis was performed on PEDF knockout (KO) and control livers (7 months)...
September 1, 2015: Cellular and Molecular Gastroenterology and Hepatology
Javier Ampuero, Manuel Romero-Gómez
Chronic hepatitis C virus (HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk factor for cardiovascular diseases (CVD) due to its association with insulin resistance, diabetes and steatosis. HCV infection represents an initial step in the chronic inflammatory cascade, showing a direct role in altering glucose metabolism. After achieving sustained virological response, the incidence of insulin resistance and diabetes dramatically decrease...
September 8, 2015: World Journal of Hepatology
Michele Vacca, Michael Allison, Julian L Griffin, Antonio Vidal-Puig
The term nonalcoholic fatty liver disease (NAFLD) covers a pathologic spectrum from lipid accumulation alone (simple steatosis) to steatosis with associated inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Nonalcoholic steatohepatitis can progress to cirrhosis and potentially to hepatocellular carcinoma. Although a genetic predisposition has been highlighted, NAFLD is strongly associated with an unhealthy lifestyle and hypercaloric diet in the context of obesity and metabolic disease. The dysregulation of specific pathways (insulin signaling, mitochondrial function, fatty acid, and lipoprotein metabolism) have been linked to steatosis, but elucidating the molecular events determining evolution of the disease still requires further research before it can be translated into specific personalized interventional strategies...
August 2015: Seminars in Liver Disease
Paola Dongiovanni, Stefano Romeo, Luca Valenti
Liver fat accumulation generally related to systemic insulin resistance characterizes nonalcoholic fatty liver disease (NAFLD), which in the presence of nonalcoholic steatohepatitis (NASH) can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease in Western countries. Epidemiological, familial, and twin studies provide evidence for a strong genetic component of NAFLD susceptibility. Recently, genome-wide association studies led to the identification of the major inherited determinants of hepatic fat accumulation: patatin-like phospholipase domain-containing 3 (PNPLA3) I148M gene and transmembrane 6 superfamily member 2 (TM6SF2) E167K gene variants, involved in lipid droplets remodelling and very low-density lipoproteins secretion, are the major determinants of interindividual differences in liver steatosis, and susceptibility to progressive NASH...
2015: BioMed Research International
Sandra Pisonero-Vaquero, Javier González-Gallego, Sonia Sánchez-Campos, María Victoria García-Mediavilla
Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is one of the most common chronic liver diseases, which may progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD is characterized by the accumulation of lipids in the liver arising from multiple factors: increased fatty acid uptake, increased de novo lipogenesis, reduced fatty acid oxidation and very low density lipoproteins (VLDL) secretion. Most therapeutic approaches for this disease are often directed at reducing body mass index and improving insulin resistance through lifestyle modifications, bariatric surgery and pharmacological treatments...
2015: Current Medicinal Chemistry
Stefan Traussnigg, Christian Kienbacher, Emina Halilbasic, Christian Rechling, Lili Kazemi-Shirazi, Harald Hofer, Petra Munda, Michael Trauner
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC...
2015: Digestive Diseases
Jian Tao, Kyung-Don Kang, Stacy D Hall, Audra H Laube, Jia Liu, Matthew B Renfrow, Jan Novak, Guangxiang Luo
UNLABELLED: Recent studies demonstrated that transgenic mice expressing key human hepatitis C virus (HCV) receptors are susceptible to HCV infection, albeit at very low efficiency. Robust mouse models of HCV infection and replication are needed to determine the importance of host factors in HCV replication, pathogenesis, and carcinogenesis as well as to facilitate the development of antiviral agents and vaccines. The low efficiency of HCV replication in the humanized mouse models is likely due to either the lack of essential host factors or the presence of restriction factors for HCV infection and/or replication in mouse hepatocytes...
July 2015: Journal of Virology
Jürgen Borlak, Prashant Singh, Giuseppe Gazzana
BACKGROUND: Hepatocellular carcinoma (HCC) is on the rise and the sixth most common cancer worldwide. To combat HCC effectively research is directed towards its early detection and the development of targeted therapies. Given the fact that epidermal growth factor (EGF) is an important mitogen for hepatocytes we searched for disease regulated proteins to improve an understanding of the molecular pathogenesis of EGF induced HCC. Disease regulated proteins were studied by 2DE MALDI-TOF/TOF and a transcriptomic approach, by immunohistochemistry and advanced bioinformatics...
2015: BMC Genomics
Jürgen Borlak, Prashant Singh, Giuseppe Gazzana
BACKGROUND: Hepatocellular carcinoma (HCC) is on the rise and the sixth most common cancer worldwide. To combat HCC effectively research is directed towards its early detection and the development of targeted therapies. Given the fact that epidermal growth factor (EGF) is an important mitogen for hepatocytes we searched for disease regulated proteins to improve an understanding of the molecular pathogenesis of EGF induced HCC. Disease regulated proteins were studied by 2DE MALDI-TOF/TOF and a transcriptomic approach, by immunohistochemistry and advanced bioinformatics...
2015: BMC Genomics
Yan Xu, Pierre Martinez, Karin Séron, Guangxiang Luo, Fabrice Allain, Jean Dubuisson, Sandrine Belouzard
UNLABELLED: Hepatitis C virus (HCV) entry involves binding to cell surface heparan sulfate (HS) structures. However, due to the lipoprotein-like structure of HCV, the exact contribution of virion components to this interaction remains controversial. Here, we investigated the relative contribution of HCV envelope proteins and apolipoprotein E in the HS-binding step. Deletion of hypervariable region 1, a region previously proposed to be involved in HS binding, did not alter HCV virion binding to HS, indicating that this region is not involved in this interaction in the context of a viral infection...
April 2015: Journal of Virology
Chiao-Fang Teng, Wen-Chuan Hsieh, Ching-Wen Yang, Hui-Min Su, Ting-Fen Tsai, Wang-Chou Sung, Wenya Huang, Ih-Jen Su
Metabolic syndrome has closely linked to the development of human hepatocellular carcinoma (HCC). By using the hepatitis B virus (HBV) X (HBx) transgenic mouse model, we studied the dynamic evolution of serum and liver profiles of lipids and global cDNA expression at different stages of HBx tumorigenesis. We observed that the lipid (triglycerides, cholesterol, and fatty acids) profiles revealed a biphasic response pattern during the progression of HBx tumorigenesis: a small peak at early phase and a large peak or terminal switch at the tumor phase...
January 2016: Molecular Carcinogenesis
Ahmed M Kabel, Maaly A Abd Elmaaboud, Ahmed A Albarraq
Non-alcoholic steatohepatitis (NASH) has a relation to obesity. It may lead to hepatocellular carcinoma. To date, the therapeutic options are limited due to complex pathogenesis. This study aimed to investigate the effect of atorvastatin and omega 3 fatty acids on experimentally-induced NASH. Sixty male albino rats were divided into 6 equal groups; control group, high fat emulsion/sucrose (HFE/S) diet, HFE/S+carboxymethyl cellulose, HFE/S +Atorvastatin, HFE/S+Fish oil and HFE/S+Atorvastatin+Fish oil. Serum alanine aminotransferase, total cholesterol (TC), triglycerides (TG), high density lipoproteins, insulin, glucose, C-reactive protein and quantitative insulin sensitivity check index were measured...
May 2015: Prostaglandins, Leukotrienes, and Essential Fatty Acids
Charlène Brault, Pierre Lévy, Sarah Duponchel, Maud Michelet, Aurèlie Sallé, Eve-Isabelle Pécheur, Marie-Laure Plissonnier, Romain Parent, Evelyne Véricel, Alexander V Ivanov, Münevver Demir, Hans-Michael Steffen, Margarete Odenthal, Fabien Zoulim, Birke Bartosch
OBJECTIVE: Inflammation and oxidative stress drive disease progression in chronic hepatitis C (CHC) towards hepatocellular carcinoma. HCV is known to increase intracellular levels of reactive oxygen species (ROS), but how it eliminates ROS is less well known. The role of the ROS scavenger glutathione peroxidase 4 (GPx4), induced by HCV, in the viral life cycle was analysed. DESIGN: The study was performed using a replicative in vitro HCV infection model and liver biopsies derived from two different CHC patient cohorts...
January 2016: Gut
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