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https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#1
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908546/effects-of-branched-chain-amino-acid-supplementation-after-radiofrequency-ablation-for-hepatocellular-carcinoma-a-randomized-trial
#2
Shunsuke Nojiri, Kei Fujiwara, Noboru Shinkai, Etsuko Iio, Takashi Joh
OBJECTIVE: Maintenance of liver function is important for better outcomes after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study was to examine the effects of oral branched-chain amino acid (BCAA) supplementation on liver function, intrahepatic recurrence rate, and incidence of complications after RFA for HCC. METHODS: Patients with cirrhosis who underwent RFA were enrolled between August 2009 and April 2012, randomized to oral supplementation with Aminoleban EN (BCAA group) or diet alone (control group), and followed to determine changes in serum parameters and health status...
January 2017: Nutrition
https://www.readbyqxmd.com/read/27895723/cisplatin-induced-regulation-of-signal-transduction-pathways-and-transcription-factors-in-p53-mutated-subclone-variants-of-hepatoma-cells-potential-application-for-therapeutic-targeting
#3
Jinn-Rung Kuo, Hung-Sheng Shang, Chun-Te Ho, Kun-Goung Lai, Tsan-Zon Liu, Yin-Ju Chen, Jeng-Fong Chiou
Cisplatin is commonly recognized as a DNA-damaging drug; however, its versatile antitumor effects have been demonstrated to extend beyond this narrow functional attribute. The present study determined how cisplatin regulates alternative pathways and transcription factors to exert its additional antitumor actions. Cisplatin was observed to be able to trigger an endoplasmic reticulum stress response through aggravated nitrosative stress coupled to perturbed mitochondrial calcium (Ca(2+)) homeostasis, which substantially downregulated glucose-regulated protein (GRP) 78 expression by suppressing the cleavage of activating transcription factor (ATF) 6α (90 kDa) to its active 50 kDa subunit...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894955/blocking-preferential-glucose-uptake-sensitizes-liver-tumor-initiating-cells-to-glucose-restriction-and-sorafenib-treatment
#4
Hui-Lu Zhang, Ming-Da Wang, Xu Zhou, Chen-Jie Qin, Gong-Bo Fu, Liang Tang, Han Wu, Shuai Huang, Ling-Hao Zhao, Min Zeng, Jiao Liu, Dan Cao, Lin-Na Guo, Hong-Yang Wang, He-Xin Yan, Jie Liu
Cancer cells display altered metabolic phenotypes characterized by a high level of glycolysis, even under normoxic conditions. Because of a high rate of glycolytic flux and inadequate vascularization, tumor cells often suffer from nutrient deficiency and require metabolic adaptations to address such stresses. Although tumor-initiating cells (T-ICs) have been identified in various malignancies, the cells' metabolic phenotypes remain elusive. In this study, we observed that liver T-ICs preferentially survived under restricted glucose treatment...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894242/indazolo-3-2-b-quinazolinones-attack-hepatocellular-carcinoma-hep3b-cells-by-inducing-mitochondrial-dependent-apoptosis-and-inhibition-of-nrf2-are-signaling-pathway
#5
Y Zhang, R Qiao, D He, Z Zhao, S Yang, H Zou, X Zhang, M Wu, J Chen, P Chen
Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Genotoxic stress resistance in patients often contributes to poor clinical outcomes, and is intensively associated to the upregulation of Nrf2/ARE signaling pathway. In this study, we examined the connection between the anti-cancer activity of two novel indazolo[3,2-b]quinazolinone (IQ) derivatives, IQ-7 and IQ-12, and their effect on the Nrf2/ARE signaling pathway. The two compounds were shown to induce apoptosis and inhibit the Nrf2/ARE signaling pathway in Hep3B cells (human hepatoma cell line)...
November 28, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27889327/epigenetics-in-non-alcoholic-fatty-liver-disease
#6
REVIEW
Jooho Lee, Yuri Kim, Simonetta Friso, Sang-Woon Choi
Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an emerging health concern. NAFLD is a pathologic condition characterized by the buildup of extra fat in liver cells that is not caused by alcohol consumption. Excess hepatic fat accumulation results from increased delivery of triglycerides (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a subgroup of NAFLD results in hepatocellular injury and inflammation, which is referred to as non-alcoholic steatohepatitis (NASH), and may progress to irreversible cirrhosis and hepatocellular carcinoma (HCC)...
November 23, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27885796/hepatocellular-carcinomas-with-intracellular-hyaline-bodies-have-a-poor-prognosis
#7
Ariane Aigelsreiter, Jens Neumann, Martin Pichler, Judith Halasz, Kurt Zatloukal, Andrea Berghold, Philipp Douschan, Florian Rainer, Rudolf Stauber, Johannes Haybaeck, Helmut Denk, Carolin Lackner
BACKGROUND & AIMS: Mallory-Denk-bodies (MDB) and intracellular hyaline bodies (IHB) are cytoplasmic inclusions found in a subset of hepatocellular carcinoma (HCC). MDB are mainly composed of the intermediate filament proteins keratin (K) 8 and K18, the cellular stress- and adapter-protein sequestosome 1/p62 (p62) and ubiquitin, whereas IHB consist of p62 and/or ubiquitin. Of note, cytoplasmic inclusions containing p62 can serve as markers of suppressed autophagy which in turn has been associated with poor prognosis...
November 25, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27881436/knockdown-of-histidine-rich-calcium-binding-protein-hrc-suppresses-liver-fibrosis-by-inhibiting-the-activation-of-hepatic-stellate-cells
#8
Jingmei Liu, Mengke Li, Jin Gong, Ping Han, Yunwu Wang, Dean Tian, Jiazhi Liao
The histidine-rich calcium binding protein (HRC) is a regulator of Ca(2+)- homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrated that HRC was upregulated in fibrotic liver and activated HSCs. TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagens expression, and inhibited HSCs proliferation and migration...
November 23, 2016: Biology Open
https://www.readbyqxmd.com/read/27878253/development-of-a-therapeutic-model-of-precancerous-liver-using-crocin-coated-magnetite-nanoparticles
#9
Rkia El-Kharrag, Amr Amin, Soleiman Hisaindee, Yaser Greish, Sherif M Karam
Despite considerable advances in understanding hepatocellular carcinoma, it is one of the common and deadliest cancers worldwide. Hence, increasing efforts are needed for early diagnosis and effective treatments. Saffron has been recently found to inhibit growth of liver cancer in rats. The aim of this study was to develop an effective method for treatment of liver cancer using magnetite nanoparticles (MNPs) coated with crocin, the main active component of saffron. MNPs were prepared and initially coated with dextran and a cross-linker to enhance conjugation of crocin using a modified coprecipitation method...
November 15, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27868197/expression-of-a-hepatitis-b-virus-pre-s2-deletion-mutant-in-the-liver-results-in-hepatomegaly-and-hepatocellular-carcinoma-in-mice
#10
Yuan-Chi Teng, Jenq Chyuan Neo, Jaw-Ching Wu, Yi-Fan Chen, Cheng-Heng Kao, Ting-Fen Tsai
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and has a poor prognosis and a low survival rate; its incidence is on the rise. Hepatitis B virus (HBV) infection is one of the main causes of HCC. A high prevalence of pre-S deletions of HBV surface antigen, which encompass T-cell and/or B-cell epitopes, is found in HBV carriers; antiviral therapy and viral immune escape may cause and select for these HBV mutants. In particular, the presence of pre-S2 deletion mutants is an important risk factor associated with cirrhosis and HCC...
November 21, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27867096/ptgr1-expression-is-regulated-by-nrf2-in-rat-hepatocarcinogenesis-and-promotes-cell-proliferation-and-resistance-to-oxidative-stress
#11
Ricardo Sánchez-Rodríguez, Julia Esperanza Torres-Mena, Valeria Quintanar-Jurado, Victoria Chagoya-Hazas, Emilio Rojas Del Castillo, Luis Del Pozo Yauner, Saul Villa-Treviño, Julio Isael Pérez-Carreón
Prostaglandin reductase-1 (Ptgr1) is an alkenal/one oxidoreductase that is involved in the catabolism of eicosanoids and lipid peroxidation such as 4-hydroxynonenal (4-HNE). Recently, we reported that Ptgr1 is overexpressed in human clinical and experimentally induced samples of hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated and its role in carcinogenesis are not yet known. Here, we studied parameters associated with antioxidant responses and the mechanisms underlying the induction of Ptgr1 expression by the activation of Nuclear Factor (erythroid-derived-2)-like-2 (NRF2)...
November 18, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27863447/hepatitis-c-virus-infection-triggers-a-tumor-like-glutamine-metabolism
#12
Pierre L Lévy, Sarah Duponchel, Hannah Eischeid, Jennifer Molle, Maud Michelet, Gaëlle Diserens, Martina Vermathen, Peter Vermathen, Jean-Francois Dufour, Hans-Peter Dienes, Hans-Michael Steffen, Margarete Odenthal, Fabien Zoulim, Birke Bartosch
Chronic infection with hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma. However, the molecular mechanisms linking the infection to cancer development remain poorly understood. Here we used HCV-infected cells and liver biopsies to study how HCV modulates the glutaminolysis pathway, which is known to play an important role in cellular energetics, stress defense and neoplastic transformation. Transcript levels of glutaminolytic factors were quantified in Huh7.5 cells or primary human hepatocytes infected with the JFH1 HCV strain as well as in biopsies of chronic HCV patients...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27862769/ns5abp37-inhibits-liver-cancer-by-impeding-lipogenesis-and-cholesterogenesis
#13
Shenghu Feng, Ming Han, Li Zhou, Qi Wang, Zhongshu Li, Yaru Li, Hongping Lu, Ting Liu, Yanhua Ma, Shunai Liu, Jun Cheng
The molecular mechanism underlying nonalcoholic fatty liver disease (NAFLD) progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining result showed that NS5ABP37 protein, which is in a state of lower expression in tumor tissues, decreased as with increasing degree of HCC malignancy. Two cell models, HepG2 and L02, are used to analyze the mechanism between NS5ABP37 and HCC. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1/S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels...
November 11, 2016: Cancer Science
https://www.readbyqxmd.com/read/27851986/blocking-wnt-secretion-reduces-growth-of-hepatocellular-carcinoma-cell-lines-mostly-independent-of-%C3%AE-catenin-signaling
#14
Wenhui Wang, Lei Xu, Pengyu Liu, Kiran Jairam, Yuebang Yin, Kan Chen, Dave Sprengers, Maikel P Peppelenbosch, Qiuwei Pan, Ron Smits
Aberrant activation of Wnt/β-catenin signaling plays a key role in the onset and development of hepatocellular carcinomas (HCC), with about half of them acquiring mutations in either CTNNB1 or AXIN1. However, it remains unclear whether these mutations impose sufficient β-catenin signaling or require upstream Wnt ligand activation for sustaining optimal growth, as previously suggested for colorectal cancers. Using a panel of nine HCC cell lines, we show that siRNA-mediated knockdown of β-catenin impairs growth of all these lines...
November 13, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27847552/schisandrin-b-a-double-edged-sword-in-nonalcoholic-fatty-liver-disease
#15
REVIEW
Pou Kuan Leong, Kam Ming Ko
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit of Schisandra chinensis (a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes in vitro and in rodent livers in vivo...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27834813/the-potential-of-non-provitamin-a-carotenoids-for-the-prevention-and-treatment-of-non-alcoholic-fatty-liver-disease
#16
REVIEW
Ana Gabriela Murillo, Diana M DiMarco, Maria Luz Fernandez
Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated spectrum of comorbidities defined by the presence of metabolic dysfunction, oxidative stress, inflammation, and fibrosis in the liver. If left untreated, NAFLD can progress to cirrhosis, liver failure, or hepatocellular carcinoma. NAFLD is recognized as the most common liver disease in the United States, affecting around 30% of the population. Identification of dietary components capable of reducing or preventing NAFLD is therefore essential to battle this condition...
November 8, 2016: Biology
https://www.readbyqxmd.com/read/27833850/baicalin-promoted-site-2-protease-and-not-site-1-protease-in-endoplasmic-reticulum-stress-induced-apoptosis-of-human-hepatocellular-carcinoma-cells
#17
Zhe Yu, Xin Luo, Chen Wang, Jianhong Ye, Shourong Liu, Lei Xie, Fei Wang, Jianfeng Bao
Baicalin (5,6-dihydroxy-7-o-glucuronide flavone) is an extract from the roots of Chinese herb Huang Qin (Scutellaria baicalensis Georgi) and is reported to have antioxidative, antiproliferative, anti-inflammatory, and anticancer activities. This study aimed to investigate the inhibitory effect of baicalin on human hepatocellular carcinoma (HCC) cells and the involvement of endoplasmic reticulum stress-induced cell apoptosis. Two human HCC cell lines, HepG2 and SMMC7221, were used in this study. The cells were incubated with baicalin solutions at various concentrations...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27827850/interferon-%C3%AE-induces-the-apoptosis-of-cervical-cancer-hela-cells-by-activating-both-the-intrinsic-mitochondrial-pathway-and-endoplasmic-reticulum-stress-induced-pathway
#18
Wei-Ye Shi, Cheng Cao, Li Liu
The interferon α (IFN-α) has been often used as a sensitizing agent for the treatment of various malignancies such as hepatocellular carcinoma, malignant melanoma, and renal cell cancer by promoting the apoptosis of thesetumor cell types. However, the effect of IFN-α on cervical cancer remains unknown. In this study, HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer. The results indicate that IFN-α markedly inhibits the proliferation and induces the apoptosis of HeLa cells...
November 2, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27822418/inhibition-of-mtorc1-signaling-sensitizes-hepatocellular-carcinoma-cells-to-glycolytic-stress
#19
Xin Zhao, Peng Jiang, Xiang Deng, Zhonghu Li, Feng Tian, Fei Guo, Xiaowu Li, Shuguang Wang
Reprogrammed glucose metabolism, especially glycolysis, is profoundly implicated in tumor development or metastasis. As the interconnectedness and flexibility of metabolic signaling, targeting a metabolic signaling molecule may have limited anti-tumor effects. Here, Gene set enrichment analysis (GSEA) was used to explore the accompanied effectors of glycolysis in hepatocellular carcinoma (HCC). Based on the expression of lactate dehydrogenase A (LDHA), a key enzyme in catalyzing pyruvate into lactate, the glycolytic ability of HCC was defined as low group and high group...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27801949/maternal-prenatal-stress-and-child-atopic-dermatitis-up-to-age-2-years-the-ulm-spatz-health-study
#20
Stefanie Braig, Johannes M Weiss, Tobias Stalder, Clemens Kirschbaum, Dietrich Rothenbacher, Jon Genuneit
BACKGROUND: Evidence linking maternal psychosocial stress during pregnancy to subsequent child atopic dermatitis (AD) is growing but the definition of AD is diverse and results are inconsistent. We aimed to analyze the relationship between stress and AD using alternative methods of measurement of stress and AD. METHODS: In the Ulm SPATZ Health Study, chronic stress and symptoms of anxiety and depression were assessed by standardized self-reported questionnaires in 934 mothers of singletons following delivery in Ulm, Germany, from 04/2012-05/2013...
November 1, 2016: Pediatric Allergy and Immunology
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