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metabolic hcc

Jinhua Wang, Wan Li, Xiangjin Zheng, Xiaocong Pang, Guanhua Du
FOXC1 is a vital member of FOX families which play important roles in biological processes including proliferation, differentiation, apoptosis, migration, invasion, metabolism, and longevity. Here we are focusing on roles of FOXC1 and their mechanisms in cancers. FOXC1 promoted progress of many cancers, such as breast cancer (especially basal-like breast cancer), hepatocellular carcinoma, gastric cancer and so on. FOXC1 was also found to be associated with drug resistance of cancers. FOXC1 promoted metastasis of cancers by increasing expression of MMP7, NEDD9 and Snail...
February 23, 2018: Oncotarget
Weihua Li, Huimin Bai, Shiping Liu, Dongyan Cao, Hongying Wu, Keng Shen, Yanhong Tai, Jiaxin Yang
Stearoyl-CoA desaturase 1 (SCD1) is an established molecular target in many primary tumors including breast, lung, pancreatic, colon and hepatocellular carcinomas. However, its potential role in supporting endometrial cancer growth and progression has not yet been determined. In this study, we evaluated the value of SCD1 as a candidate therapeutic target in human endometrial cancer. Compared with secretory and post-menopausal endometrium, SCD1 was highly expressed in normal endometrium of proliferative phase, endometrial hyperplasia and endometrial carcinoma, while was absent or low expression in non-malignant control stromal cells and adjacent normal endometrium...
February 23, 2018: Oncotarget
Jun-Ho Cho, Goo-Young Kim, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis...
March 12, 2018: Biochemical and Biophysical Research Communications
Safi Dokmak, Béatrice Aussilhou, Tiziana Marchese, Nizar Kardoun, François Cauchy, Anne Sophie Schneck, Olivier Soubrane
BACKGROUND: Hepatocellular carcinoma (HCC) can be complicated by major vascular invasion, and resection can be beneficial in some patients.1 Some of these patients are traditionally operated under total vascular exclusion (TVE), refrigeration, extracorporeal circulatory bypass, and cardiac surgery, with high morbidity and mortality.2 However, HCC thrombi are not adherent to the venous wall, and with advances in surgical techniques, resection can be simplified and performed during short-duration TVE alone...
March 13, 2018: Annals of Surgical Oncology
Xiaoying Wang, Jiefu Peng, Jing Wang, Miao Li, Di Wu, Songyan Wu, Jipei Liao, Jun Dou
Background: Despite the breadth of understanding the noncoding RNAs' function in molecular biology, their functional roles in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated the effect of hepatitis C virus (HCV) core upon the expression of noncoding RNAs. Methods: The lncRNAs, mRNAs, and circRNAs were employed for identification of HCV core protein gene expression in human Huh7 hepatoma (Huh7) cell line. In data analysis, we applied a threshold that eliminated all genes that were not increased or decreased by at least a 2-fold change in a comparison between transfected and control cells...
2018: OncoTargets and Therapy
Julian A Gingold, Dandan Zhu, Dung-Fang Lee, Ahmed Kaseb, Jian Chen
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), the two most common primary liver cancers, represent the second most common cancer-related cause of death worldwide, with most cases being diagnosed at an advanced stage. Recent genome-wide studies have helped to elucidate the molecular pathogenesis and genetic heterogeneity of liver cancers. This review of the genetic landscape of HCC and iCCA discusses the most recent findings from genomic profiling and the current understanding of the pathways involved in the initiation and progression of liver cancer...
March 9, 2018: Trends in Molecular Medicine
Vladimir Alexei Morozov, Sylvie Lagaye
Hepatitis C virus (HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a public healthy challenge. It is worth mentioning, that the HCV prevalence is dependent on the countries with infection rates around 20% in high endemic countries. The review summarizes recent data on HCV molecular biology, the physiopathology of infection (immune-mediated liver damage, liver fibrosis and lipid metabolism), virus diagnostic and treatment...
February 27, 2018: World Journal of Hepatology
Hao Zhuang, Qiang Li, Xinran Zhang, Xuda Ma, Zun Wang, Yun Liu, Xianfu Yi, Ruibing Chen, Feng Han, Ning Zhang, Yongmei Li
Metabolic reprogramming is a hallmark of cancer. Glycine decarboxylase (GLDC), an oxidoreductase, plays an important role in amino acid metabolism. While GLDC promotes tumor initiation and proliferation in non-small cell lung cancer and glioma and it was reported as a putative tumor suppressor gene in gastric cancer, the role of GLDC in hepatocellular carcinoma (HCC) is unknown. In the current study, microarray-based analysis suggested that GLDC expression was low in highly malignant HCC cell lines, and clinicopathological analysis revealed a decrease in GLDC in HCC tumor samples...
March 7, 2018: Free Radical Biology & Medicine
Silvano Fasolato, Elisabetta Trevellin, Mariagrazia Ruvoletto, Marnie Granzotto, Giacomo Zanus, Elisa Boscaro, Enrico Babetto, Liliana Terrin, Maria Alberta Battocchio, Francesco Ciscato, Cristian Turato, Santina Quarta, Umberto Cillo, Patrizia Pontisso, Roberto Vettor
AIMS: In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models. MATERIALS AND METHODS: DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC...
March 7, 2018: Life Sciences
Ivy N Haskins, Julietta Chang, Zubaidah Nor Hanipah, Tavankit Singh, Neal Mehta, Arthur J McCullough, Stacy A Brethauer, Philip R Schauer, Ali Aminian
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized. OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity. SETTING: A tertiary, academic, referral hospital...
March 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
M Tieleman, A P van den Berg, B van Hoek, W G Polak, J Dubbeld, R J Porte, C Konijn, R A de Man, B E Hanssen, H J Metselaar
OBJECTIVE: To calculate the chance of receiving a liver transplant for patients on the liver transplant waiting list in the Netherlands. DESIGN: Retrospective cohort research. METHOD: Data of all patients in the Netherlands on the waiting list for liver transplantation, from the introduction of the model of end-stage liver disease score on 16th December 2006 through to 31st December 2013 were collected. Survival analysis was computed with competing risk analyses...
2018: Nederlands Tijdschrift Voor Geneeskunde
Hong-Qiang Chen, Ji Zhao, Yan Li, Li-Xiong He, Yu-Jing Huang, Wei-Qun Shu, Jia Cao, Wen-Bin Liu, Jin-Yi Liu
Microcystin (MC) is a cyclic heptapeptide compound which could lead to the development of hepatocellular carcinoma. However, the underlying epigenetic regulation mechanism is largely unknown. In this study, microcystin-LR (L: lysine, R: arginine, MC-LR) was used to induce the malignant transformation of human hepatocyte L02 cell line. The profile of gene expression, microRNA (miRNA) and DNA methylation were detected through high-throughput sequencing. Compared with control group, the expression of 826 genes and 187 miRNAs changed significantly in MC-LR treated group...
March 5, 2018: Toxicology Letters
Shoji Yamada, Yoko Takashina, Mitsuhiro Watanabe, Ryogo Nagamine, Yoshimasa Saito, Nobuhiko Kamada, Hidetsugu Saito
Gut microbiota plays a significant role in the development of hepatocellular carcinoma (HCC) in non-alcoholic steatohepatitis (NASH). However, understanding of the precise mechanism of this process remains incomplete. A new class steatohepatitis-inducing high-fat diet (HFD), namely STHD-01, can promote the development of HCC without the administration of chemical carcinogens. Using this diet, we comprehensively analyzed changes in the gut microbiota and its metabolic functions during the development of HCC in NASH...
February 9, 2018: Oncotarget
Xiaoping Zhao, Li Zhao, Hao Yang, Jiajin Li, Xuejie Min, Fajun Yang, Jianjun Liu, Gang Huang
Dysregulation of lipid metabolism is common in cancer cells, but the underlying mechanisms are poorly understood. Sterol regulatory element-binding proteins (SREBPs) stimulate lipid biosynthesis through transcriptional activation of lipogenic enzymes. However, SREBPs' roles and potential interacting partners in cancer cells are not fully defined. Using a biochemical approach, we found here that pyruvate kinase M2 (PKM2) physically interacts with the nuclear form of SREBP-1a (nBP1a), by binding to amino acids 43-56 in nBP1a...
March 7, 2018: Journal of Biological Chemistry
Sha Li, Hor Yue Tan, Ning Wang, Fan Cheung, Ming Hong, Yibin Feng
Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases...
2018: Oxidative Medicine and Cellular Longevity
Yanjiao Shao, Liren Wang, Nana Guo, Shengfei Wang, Lei Yang, Yajing Li, Mingsong Wang, Shuming Yin, Honghiu Han, Li Zeng, Ludi Zhang, Lijian Hui, Qiurong Ding, Jiqin Zhang, Hongquan Geng, Mingyao Liu, Dali Li
Hereditary tyrosinemia type I (HTI) is a metabolic genetic disorder caused by mutation of fumarylacetoacetate hydrolase (FAH). Because of the accumulation of toxic metabolites, HTI causes severe liver cirrhosis, liver failure andeven hepatocellular carcinoma. HTI is an ideal model for gene therapy, and several strategies have been shown to ameliorate HTI symptoms in animal models. Although CRISPR/Cas9 mediated genome editing is able to correct the Fahmutation in mouse models, wild-type Cas9 induces numerous undesired mutations that have raised safety concerns for clinical applications...
March 5, 2018: Journal of Biological Chemistry
Ying Wu, Bo Shan, Jianli Dai, Zhixiong Xia, Jie Cai, Tianwei Chen, Songya Lv, Yuxiong Feng, Ling Zheng, Yan Wang, Jianfeng Liu, Jing Fang, Dong Xie, Liangyou Rui, Jianmiao Liu, Yong Liu
Obesity is associated with both endoplasmic reticulum (ER) stress and chronic metabolic inflammation. ER stress activates the unfolded protein response (UPR) and has been implicated in a variety of cancers, including hepatocellular carcinoma (HCC). It is unclear whether individual UPR pathways are mechanistically linked to HCC development, however. Here we report a dual role for inositol-requiring enzyme 1α (IRE1α), the ER-localized UPR signal transducer, in obesity-promoted HCC development. We found that genetic ablation of IRE1α in hepatocytes not only markedly reduced the occurrence of diethylnitrosamine (DEN)-induced HCC in LKO mice when fed a normal chow (NC) diet, but also protected against the acceleration of HCC progression during high-fat diet (HFD) feeding...
March 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jacey J Liu, Yanjie Li, Wendy S Chen, Yan Liang, Gaowei Wang, Min Zong, Kota Kaneko, Ruiyun Xu, Michael Karin, Gen-Sheng Feng
BACKGROUND AND AIMS: Shp2 is an SH2-tyrosine phosphatase acting downstream of receptor tyrosine kinases (RTKs). Most recent data demonstrated a liver tumor-suppressing role for Shp2, as ablating Shp2 in hepatocytes aggravated hepatocellular carcinoma (HCC) induced by chemical carcinogen or Pten loss. We further investigated the effect of Shp2 deficiency on liver tumorigenesis driven by classical oncoproteins c-Met (receptor for HGF), β-catenin and PIK3CA. METHODS: We performed hydrodynamic tail vein injection of two pairs of plasmids expressing c-Met and ΔN90-β-catenin (MET/CAT), or c-Met and PIK3CAH1047R (MET/PIK), into WT and Shp2hep-/- mice...
March 2, 2018: Journal of Hepatology
Sun Ha Jee, Minjoo Kim, Minkyung Kim, Hye Jin Yoo, Hyungyoon Kim, Keum Ji Jung, Seri Hong, Jong Ho Lee
In the prospective Korean Cancer Prevention Study-II (KCPS-II), we investigated the application of metabolomics to differentiate subjects with incident hepatocellular carcinoma (HCC group) from subjects who remained free of cancer (control group) during a mean follow-up period of 7 years with the aim of identifying valuable metabolic biomarkers for HCC. We used baseline serum samples from 75 subjects with incident HCC and 134 age- and gender-matched cancer-free subjects. Serum metabolic profiles associated with HCC incidence were investigated via metabolomics analysis...
March 2, 2018: Cancer Prevention Research
Saravana Kumar Kailasam Mani, Ourania Andrisani
Chronic Hepatitis B Virus (HBV) infection is linked to hepatocellular carcinoma (HCC) pathogenesis. Despite the availability of a HBV vaccine, current treatments for HCC are inadequate. Globally, 257 million people are chronic HBV carriers, and children born from HBV-infected mothers become chronic carriers, destined to develop liver cancer. Thus, new therapeutic approaches are needed to target essential pathways involved in HCC pathogenesis. Accumulating evidence supports existence of hepatic cancer stem cells (hCSCs), which contribute to chemotherapy resistance and cancer recurrence after treatment or surgery...
March 2, 2018: Genes
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