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https://www.readbyqxmd.com/read/28454235/metabolic-profiling-of-hepatitis-b-virus-related-hepatocellular-carcinoma-with-diverse-differentiation-grades
#1
Lei Zhang, Ya Huang, Mingjian Lian, Zhijuan Fan, Yaqiong Tian, Yufan Wang, Hua Kang, Shuang Liu, Shuye Liu, Tong Li, Zhongqiang Shan
The most effective diagnostic tool for the majority of hepatocellular carcinoma (HCC) patients is determining the differentiation grade of their tumors. However liver biopsies, which are currently the most effective way of determining tumor differentiation grade, have several limitations. The present study was designed to select serum characteristic metabolites that correlate with the differentiation grades of hepatitis B virus (HBV)-related HCC, and so could be used in the clinic as a non-invasive method of differentiating patients with different grades of HCC...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28446728/inhibition-of-hsf1-suppresses-the-growth-of-hepatocarcinoma-cell-lines-in-vitro-and-akt-driven-hepatocarcinogenesis-in-mice
#2
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...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445971/stat3-regulates-glycolysis-via-targeting-hexokinase-2-in-hepatocellular-carcinoma-cells
#3
Man Li, Rui Jin, Weihua Wang, Tieying Zhang, Jiao Sang, Na Li, Qunying Han, Wenxuan Zhao, Chunyan Li, Zhengwen Liu
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2) are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics involving an increase in glycolysis is a characteristic of HCC. This study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28436948/mitochondrial-elongation-mediated-glucose-metabolism-reprogramming-is-essential-for-tumour-cell-survival-during-energy-stress
#4
J Li, Q Huang, X Long, X Guo, X Sun, X Jin, Z Li, T Ren, P Yuan, X Huang, H Zhang, J Xing
To date, mechanisms of tumour cell survival under energy stress are not well understood. Cumulative evidence is beginning to reveal that specific mitochondrial morphologies are often associated with energetic states and survival of cells. However, the functional roles of mitochondria in the metabolic adaptation of tumour cells to energy stress remain to be elucidated. In this study, we first investigated the changes in mitochondrial morphology induced by nutrition deprivation in tumour cells, and the underlying molecular mechanism...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436449/metabolism-dysregulation-induces-a-specific-lipid-signature-of-nonalcoholic-steatohepatitis-in-patients
#5
Franck Chiappini, Audrey Coilly, Hanane Kadar, Philippe Gual, Albert Tran, Christophe Desterke, Didier Samuel, Jean-Charles Duclos-Vallée, David Touboul, Justine Bertrand-Michel, Alain Brunelle, Catherine Guettier, François Le Naour
Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#6
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28430663/co-expression-network-analysis-identified-six-hub-genes-in-association-with-metastasis-risk-and-prognosis-in-hepatocellular-carcinoma
#7
Pengfei Chen, Fan Wang, Juerong Feng, Rui Zhou, Ying Chang, Jing Liu, Qiu Zhao
Hepatocellular carcinoma (HCC) has a high incidence and mortality worldwide, and its carcinogenesis and progression are influenced by a complex network of gene interactions. A weighted gene co-expression network was constructed to identify gene modules associated with the clinical traits in HCC (n = 214). Among the 13 modules, high correlation was only found between the red module and metastasis risk (classified by the HCC metastasis gene signature) (R2 = -0.74). Moreover, in the red module, 34 network hub genes for metastasis risk were identified, six of which (ABAT, AGXT, ALDH6A1, CYP4A11, DAO and EHHADH) were also hub nodes in the protein-protein interaction network of the module genes...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430653/preventive-effects-of-the-sodium-glucose-cotransporter-2-inhibitor-tofogliflozin-on-diethylnitrosamine-induced-liver-tumorigenesis-in-obese-and-diabetic-mice
#8
Koki Obara, Yohei Shirakami, Akinori Maruta, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Mitsuru Seishima, Masahito Shimizu
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease. In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb obese and diabetic mice. The direct effects of tofogliflozin on human liver cancer cell proliferation were also evaluated. Mice were administered diethylnitrosamine-containing water for 2 weeks and were treated with tofogliflozin throughout the experiment...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426878/microbiota-nash-hcc-and-the-potential-role-of-probiotics
#9
Giovanni Brandi, Stefania De Lorenzo, Marco Candela, Maria Abbondanza Pantaleo, Stefano Bellentani, Francesco Tovoli, Gioconda Saccoccio, Guido Biasco
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Clearly identifiable risk factors are lacking in up to 30% of HCC patients and most of these cases are attributed to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Beyond the known risk factors for NAFLD, the intestinal microbiota, in particular dysbiosis (defined as any change in the composition of the microbiota commonly found in healthy conditions) is emerging as a new factor promoting the development of chronic liver diseases and HCC...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28425467/hyperpolarized-13-c-spectroscopic-evaluation-of-oxidative-stress-in-a-rodent-model-of-steatohepatitis
#10
David M Wilson, Valentina Di Gialleonardo, Zhen J Wang, Valerie Carroll, Cornelius Von Morze, Andrew Taylor, Victor Sai, Mark VanCriekinge, Robert Bok, Michael A Ohliger, Kayvan R Keshari
Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, now considered the most common liver disease in the western world. Approximately one-third of patients with NASH develop non-alchoholic steatohepatitis (NASH), histologically defined by lobular and portal inflammation, and accompanied by marked oxidative stress. Patients with NASH are at increased risk for cirrhosis and hepatocellular carcinoma, and diagnosis currently requires invasive biopsy. In animal models of NASH, particularly the methionine-choline deficient (MCD) model, profound changes are seen in redox enzymes and key intracellular antioxidants...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424556/nonalcoholic-steatohepatitis-related-hepatocellular-carcinoma-is-there-a-role-for-the-androgen-receptor-pathway
#11
REVIEW
Mahmoud A Ali, Sahin Lacin, Reham Abdel-Wahab, Mark Uemura, Manal Hassan, Asif Rashid, Dan G Duda, Ahmed O Kaseb
The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28422962/docosahexaenoic-acid-blocks-progression-of-western-diet-induced-nonalcoholic-steatohepatitis-in-obese-ldlr-mice
#12
Kelli A Lytle, Carmen P Wong, Donald B Jump
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma. NASH is predicted to be the leading cause of liver transplants by 2020. Despite this growing public health concern, there remain no Food and Drug Administration (FDA) approved NASH treatments...
2017: PloS One
https://www.readbyqxmd.com/read/28421422/hepatitis-c-virus-genotype-3-update-on-current-and-emergent-therapeutic-interventions
#13
REVIEW
Steven W Johnson, Dorothea K Thompson, Brianne Raccor
PURPOSE OF REVIEW: Direct-acting antiviral agents (DAAs) have markedly improved the prognosis of hepatitis C virus (HCV)-genotype 3 (GT3), a highly prevalent infection worldwide. However, in patients with hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC), GT3 infection presents a treatment challenge compared with other genotypes. The dependence of the HCV life cycle on host lipid metabolism suggests the possible utility of targeting host cellular factors for combination anti-HCV therapy...
June 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28420094/nonalcoholic-fatty-liver-disease-and-insulin-resistance-new-insights-and-potential-new-treatments
#14
REVIEW
Hironori Kitade, Guanliang Chen, Yinhua Ni, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood...
April 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28416267/molecular-mechanisms-and-targets-of-therapy-for-hepatocellular-carcinoma
#15
REVIEW
Vivian Klungboonkrong, Dola Das, Gordon McLennan
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC develops through a multistep process that involves the local tumor microenvironment, intracellular signaling pathways, and altered metabolic system that allows the cancer proliferation. Understanding the mechanisms of tumor development and progression is critical to developing improved therapies aimed at better survival. This article reviews the molecular mechanisms of HCC development and highlights the potential therapeutic targets for treatments...
April 14, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28415887/amelioration-of-late-onset-hepatic-steatosis-in-idh2-deficient-mice
#16
Su Jeong Lee, Hanvit Cha, Hyunjin Kim, Jin Hyup Lee, Jeen-Woo Park
Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the general population and can evolve into nonalcoholic steatohepatosis (NASH), cirrosis, and complications such as liver failure and hepatocellular carcinoma. Recently, we reported that mitochondrial NADP(+)-dependent isocitrate dehydrogenase, encoded by the IDH2, plays an important role in the regulation of redox balance and oxidative stress levels which are tightly associated with intermediary metabolism and energy production. In the present study, we showed that in mice targeted disruption of IDH2 attenuates age-associated hepatic steatosis by the activation of p38/cJun NH2-terminal kinase (JNK) and p53, presumably induced by the elevation of mitochondrial reactive oxygen species (ROS), which in turn resulted in the suppression of hepatic lipogenesis and inflammation via the upregulation of fibroblast growth factor 21 (FGF21) and the inhibition of NFκB signaling pathways...
April 18, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28415783/mass-spectral-analysis-of-the-multikinase-inhibitor-bzg-and-its-metabolites-and-analysis-of-their-binding-to-vascular-endothelial-growth-factor-receptor-2
#17
Yan Lou, Wenqi Qiu, Zhe Wu, Qian Wang, Yunqing Qiu, Su Zeng
We previously showed that BZG is a novel multitarget kinase inhibitor, which inhibited hepatocellular carcinoma in vivo and in vitro. In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) to characterize BZG and its metabolites generated in vivo. The probable metabolic mechanism was further confirmed by analysis of Phase I and Phase II metabolism in liver microsomes and with recombinant enzymes. In addition, the binding affinities of BZG metabolites to vascular endothelial growth factor receptor 2 (VEGFR2) were predicted using electronic high throughput screening (eHiTS)...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415592/identification-and-functional-analysis-of-differentially-expressed-genes-in-poorly-differentiated-hepatocellular-carcinoma-using-rna-seq
#18
Yi Huang, Jianbo Pan, Dunyan Chen, Jiaying Zheng, Funan Qiu, Feng Li, Yanan Wu, Wenbing Wu, Xiaoli Huang, Jiang Qian
Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis compared to moderately differentiated (MD) and well differentiated (WD) HCC. We aimed to identify differentially expressed genes (DEGs) to explore the mechanism of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non-tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus identified and functionally analyzed. Further RT-PCR was performed to validate DEGs specific for PD HCC in 47 pairs of samples (15 for PD, 18 for MD, 14 for WD)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404072/distinctive-features-of-hepatocellular-carcinoma-in-non-alcoholic-fatty-liver-disease
#19
REVIEW
Elisabetta Degasperi, Massimo Colombo
Hepatocellular carcinoma is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis have been identified as emergent risk factors for this primary liver cancer. Incidence of NAFLD is increasing as a consequence of the epidemic spread of metabolic syndrome, which can result in progressive liver disease, leading to cirrhosis and its complications. Most data about the prevalence and incidence of hepatocellular carcinoma in patients with NAFLD are from a few population and cohort studies; its incidence is increasing and it is likely to become a leading indication for liver transplantation, especially in industrialised countries...
October 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28401010/downregulation-of-acsm3-promotes-metastasis-and-predicts-poor-prognosis-in-hepatocellular-carcinoma
#20
Hao-Yu Ruan, Chen Yang, Xue-Mei Tao, Jia He, Ting Wang, Hui Wang, Cun Wang, Guang-Zhi Jin, Hao-Jie Jin, Wen-Xin Qin
Understanding mechanisms of cancer metastasis is crucial for reduction of cancer mortality. Acyl-CoA medium-chain synthetase 3 (ACSM3) is an acyl-CoA synthetase which takes part in the first step of fatty acid metabolism. However, the expression, clinical significance and biological function of ACSM3 remain unknown in hepatocellular carcinoma (HCC). In this study, the expression and prognostic relevance of ACSM3 were investigated by tissue microarray and HCC clinical samples. Migration and invasion assays were carried out for functional analysis in vitro and a xenograft model was used to analyze the effects of ACSM3 on cancer metastasis in vivo...
2017: American Journal of Cancer Research
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