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https://www.readbyqxmd.com/read/28073184/functional-lipidomics-palmitic-acid-impairs-hepatocellular-carcinoma-development-by-modulating-membrane-fluidity-and-glucose-metabolism
#1
Ling Lin, Ying Ding, Yi Wang, Zhenxin Wang, Xuefei Yin, Guoquan Yan, Lei Zhang, Pengyuan Yang, Huali Shen
: Lipids are essential cellular components and energy sources of living organisms, altered lipid composition is increasingly recognized as a signature of cancer. We performed the lipidomic analysis in a series of hepatocellular carcinoma (HCC) cells and identified over 1700 intact lipids originating from 3 major lipid categories. Comparative lipidomic screening revealed 93 significantly changed lipids and decreased palmitic acyl (C16:0)-containing glycerophospholipids (GPs) were positively associated with metastatic abilities of HCC cells...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28069382/antibiotic-tigecycline-enhances-cisplatin-activity-against-human-hepatocellular-carcinoma-through-inducing-mitochondrial-dysfunction-and-oxidative-damage
#2
Jun Tan, Meijun Song, Mi Zhou, Yaoren Hu
Targeting mitochondrial metabolism has been recently demonstrated to be a promising therapeutic strategy for the treatment of various cancer. In this work, we demonstrate that antibiotic tigecycline is selectively against hepatocellular carcinoma (HCC) through inducing mitochondrial dysfunction and oxidative damage. Tigecycline is more effective in inhibiting proliferation and inducing apoptosis of HCC than normal liver cells. Importantly, tigecycline significantly enhances the inhibitory effects of chemotherapeutic drug cisplatin in HCC in vitro and in vivo...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28057471/partial-least-squares-regression-and-fourier-transform-infrared-ftir-microspectroscopy-for-prediction-of-resistance-in-hepatocellular-carcinoma-hepg2-cells
#3
Cholpajsorn Junhom, Natthida Weerapreeyakul, Waraporn Tanthanuch, Kanjana Thumanu
We evaluated the feasibility of FTIR microspectroscopy combined with partial least squares regression (PLS-R) for determination of resistance in HepG2 cells. Cell viability testing was performed using neutral red assay for the concentration of cisplatin resulting in 50% antiproliferation (IC50). The resistance index (RI) is the ratio of the IC50 in resistant HepG2 cells vs. parental HepG2 cells. Principal component and unsupervised hierarchical cluster analyses were applied and a differentiation of samples of cells (parental, 1...
January 3, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28051253/antioxidant-diet-and-genotyping-as-tools-for-the-prevention-of-liver-disease
#4
R Di Francia, L Rinaldi, M Cillo, E Varriale, G Facchini, C D'Aniello, G Marotta, M Berretta
It is well-known that 75% of risk factors of chronic liver disease (CLD) are related to nutrition. These circumstances potentially progress towards liver steatosis, fibrosis and hepatocellular carcinoma (HCC). It still represents an enormous problem for the economy of public health worldwide. Furthermore, validated prevention programs could be the solution. Recent knowledge in understanding molecular determinants of energy liver metabolism and new genetic markers offers new insights into the pathogenesis of CLD and HCC...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28049764/the-scf%C3%AE-trcp-e3-ubiquitin-ligase-complex-targets-lipin1-for-ubiquitination-and-degradation-to-promote-hepatic-lipogenesis
#5
Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seira Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M Asara, Satoshi Fukumoto, Keiichi I Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, Wenyi Wei
The SCF(β-TRCP) E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF(β-TRCP) biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28036299/v-atpase-inhibition-increases-cancer-cell-stiffness-and-blocks-membrane-related-ras-signaling-a-new-option-for-hcc-therapy
#6
Karin Bartel, Maria Winzi, Melanie Ulrich, Andreas Koeberle, Dirk Menche, Oliver Werz, Rolf Müller, Jochen Guck, Angelika M Vollmar, Karin von Schwarzenberg
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide and the third leading cause of cancer-related death. However, therapy options are limited leaving an urgent need to develop new strategies. Currently, targeting cancer cell lipid and cholesterol metabolism is gaining interest especially regarding HCC. High cholesterol levels support proliferation, membrane-related mitogenic signaling and increase cell softness, leading to tumor progression, malignancy and invasive potential. However, effective ways to target cholesterol metabolism for cancer therapy are still missing...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030819/hyperhomocysteinemia-results-from-and-promotes-hepatocellular-carcinoma-via-cyp450-metabolism-by-cyp2j2-dna-methylation
#7
Donghong Zhang, Jinli Lou, Xu Zhang, Lin Zhang, Fei Wang, Danfei Xu, Na Niu, Yidong Wang, Yue Wu, Wei Cui
Hyperhomocysteinemia (HHcy) can result from liver disease or dysfunction and further alters intracellular lipid metabolism. Cytochrome P450 (CYP) arachidonic acid epoxygenases are expressed in human cancers and promote cancer metastasis. This study explored the interaction of Hcy and CYP450 metabolism in hepatocellular carcinoma (HCC). The levels of 4-epoxyeicosatrienoic acid (EET) isomers and their generative enzyme CYP2J2 level as well as intracellular Hcy level were higher in 42 cases of HCC than in paired non-tumor tissue...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027934/histone-modifications-in-fasn-modulated-by-sterol-regulatory-element-binding-protein-1c-and-carbohydrate-responsive-element-binding-protein-under-insulin-stimulation-are-related-to-nafld
#8
Wei Shen, Xuan Du, Can Cai, Jialing Yao, Youping Zhou, Huihong Yu
Non-alcoholic fatty liver disease (NAFLD) and its causal factors of hepatic insulin resistance (IR) and type 2 diabetes are rapidly growing worldwide. Developing new therapeutic methods for these conditions requires a comprehensive understanding between hepatic lipid metabolism and IR. Sterol regulatory element-binding transcription factor 1c (SREBP-1c) and carbohydrate responsive-element binding protein (ChREBP) are the major regulators of fatty acid synthase (FASN), a key enzyme of de novo fatty acid synthesis...
December 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28027595/inhibition-of-the-srebp-pathway-suppresses-hepatocellular-carcinoma-through-repressing-inflammation
#9
Na Li, Zhang-Sen Zhou, Yang Shen, Jie Xu, Hong-Hua Miao, Ying Xiong, Feng Xu, Bo-Liang Li, Jie Luo, Bao-Liang Song
: Obesity is a critical risk factor for hepatocellular carcinoma (HCC). However, it remains unknown whether inhibition of de novo lipid biosynthesis can suppress HCC. In this study, we blocked the sterol regulatory element binding protein (SREBP) pathway, one of the key determinants of lipid homeostasis, by ablating gp78 or SCAP in hepatocytes as well as by administering a chemical compound called betulin. We found that either genetically or pharmacologically inhibiting the SREBP pathway dramatically reduced diethylnitrosamine (DEN)-induced HCC progression through down-regulating tumor promoting cytokines including IL-6, TNF-α and IL-1β...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28012856/increased-fndc5-irisin-expression-in-human-hepatocellular-carcinoma
#10
Melania Gaggini, Manuela Cabiati, Serena Del Turco, Teresa Navarra, Paolo De Simone, Franco Filipponi, Silvia Del Ry, Amalia Gastaldelli, Giuseppina Basta
The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors...
December 21, 2016: Peptides
https://www.readbyqxmd.com/read/27981621/targeting-%C3%AE-catenin-in-hepatocellular-cancers-induced-by-co-expression-of-mutant-%C3%AE-catenin-and-k-ras-in-mice
#11
Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P Monga
Recently we have shown that co-expression of hMet and mutant-β-catenin using sleeping beauty transposon/transposase leads to HCC in mice that represents around 10% of human HCC. In the current study, we investigate if Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-β-catenin. We also tested therapeutic efficacy of targeting β-catenin in HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with β-catenin mutants (S33Y, S45Y) to yield HCC in mice...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27981605/hepatocyte-autotaxin-expression-promotes-liver-fibrosis-and-cancer
#12
Eleanna Kaffe, Aggeliki Katsifa, Nikos Xylourgidis, Ioanna Ninou, Markella Zannikou, Vaggelis Harokopos, Pelagia Foka, Alexios Dimitriadis, Kostas Evangelou, Anargyros N Moulas, Urania Georgopoulou, Vassilis G Gorgoulis, George N Dalekos, Vassilis Aidinis
: Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the production of lysophosphatidic acid (LPA), a pleiotropic growth factor-like lysophospholipid. Increased ATX expression has been detected in various chronic inflammatory disorders and different types of cancer; however little is known about its role and mode of action in liver fibrosis and cancer. Here, increased ATX expression was detected in chronic liver diseases (CLDs) patients of different etiologies, associated with shorter overall survival...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27936481/patients-with-ultrasound-diagnosis-of-hepatic-steatosis-are-at-high-metabolic-risk
#13
J Kälsch, H Keskin, A Schütte, T Baars, H A Baba, L P Bechmann, A Canbay, J P Sowa
Background and aims: Hepatic steatosis is the basis of non-alcoholic fatty liver disease (NALFD). Mere fat accumulation within hepatocytes is considered the mild form of NAFLD, but can progress in some patients to advanced steatohepatitis (NASH), which may lead to fibrosis, cirrhosis or hepatocellular carcinoma. However, even hepatic steatosis alone may be a risk factor for cardiovascular disease (CVD). Patients and methods: In the present real life study 106 patients from the outpatient clinic of the Department for Gastroenterology and Hepatology with either NAFLD (n = 60) or other typical diagnoses (n = 46) were included...
December 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27916647/ppars-and-nonalcoholic-fatty-liver-disease
#14
REVIEW
Kim H H Liss, Brian N Finck
Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver pathology ranging from simple steatosis to varying degrees of inflammation, hepatocyte injury and fibrosis. Without intervention it can progress to end-stage liver disease and hepatocellular carcinoma. Given its close association with obesity, the prevalence of NAFLD has increased dramatically worldwide. Currently, there are no FDA-approved medications for the treatment of NAFLD and although lifestyle modifications with appropriate diet and exercise have been shown to be beneficial, this has been difficult to achieve and sustain for the majority of patients...
December 2, 2016: Biochimie
https://www.readbyqxmd.com/read/27867096/ptgr1-expression-is-regulated-by-nrf2-in-rat-hepatocarcinogenesis-and-promotes-cell-proliferation-and-resistance-to-oxidative-stress
#15
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)...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27863537/high-resolution-proteomic-and-lipidomic-analysis-of-exosomes-and-microvesicles-from-different-cell-sources
#16
Reka A Haraszti, Marie-Cecile Didiot, Ellen Sapp, John Leszyk, Scott A Shaffer, Hannah E Rockwell, Fei Gao, Niven R Narain, Marian DiFiglia, Michael A Kiebish, Neil Aronin, Anastasia Khvorova
Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are explored for use in diagnostics, therapeutics and drug delivery. However, little is known about the relationship of protein and lipid composition of EVs and their source cells. Here, we report high-resolution lipidomic and proteomic analyses of exosomes and MVs derived by differential ultracentrifugation from 3 different cell types: U87 glioblastoma cells, Huh7 hepatocellular carcinoma cells and human bone marrow-derived mesenchymal stem cells (MSCs)...
2016: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/27860262/ferroptosis-a-new-form-of-cell-death-and-its-relationships-with-tumourous-diseases
#17
REVIEW
Haitao Yu, Pengyi Guo, Xiaozai Xie, Yi Wang, Gang Chen
Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis and results from iron-dependent lipid peroxide accumulation. Ferroptotic cell death is characterized by cytological changes, including cell volume shrinkage and increased mitochondrial membrane density. Ferroptosis can be induced by two classes of small-molecule substances known as class 1 (system Xc(-) inhibitors) and class 2 ferroptosis inducers [glutathione peroxidase 4 (GPx4) inhibitors]. In addition to these small-molecule substances, a number of drugs (e...
November 10, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27847552/schisandrin-b-a-double-edged-sword-in-nonalcoholic-fatty-liver-disease
#18
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/27826559/immune-surveillance-of-liver-cancer-in-non-alcoholic-fatty-liver-disease-excess-lipids-cause-cd4-t-cells-loss-and-promote-hepatocellular-carcinoma-development
#19
EDITORIAL
Ralf Weiskirchen, Frank Tacke
No abstract text is available yet for this article.
October 2016: Hepatobiliary Surgery and Nutrition
https://www.readbyqxmd.com/read/27825803/protective-effects-of-dieckol-on-n-nitrosodiethylamine-induced-hepatocarcinogenesis-in-rats
#20
Velayutham Sadeeshkumar, Arul Duraikannu, Samuthrapandian Ravichandran, Wilson Sylvester Fredrick, Ramar Sivaperumal, Paulrasu Kodisundaram
Dieckol (DEK) is a naturally occuring phlorotannins found in marine brown algae Ecklonia cava which is attributed with various pharmacological properties. This study was aimed to investigate the protective role of DEK on N-Nitrosdiethylamine (NDEA) induced rat hepatocarcinogenesis. In this investigation 0.01% NDEA in drinking water for 15 weeks to induce hepatocellular carcinoma (HCC). DEK was administered orally (10, 20 and 40mg/kg body weight) for 15 weeks with 0.01% NDEA through drinking water. Hepatocarcinogesis was measured by the increased activities of serum liver marker enzymes namely aspartate trasaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), α-fetoprotein (AFP) and total bilirubin along with increased elevation of cytochrome p450, lipid peroxidation markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP), protein carbonyl content (PCC) and conjugated dienes (CD)...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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