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https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#1
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212554/afb1-hepatocarcinogenesis-is-via-lipid-peroxidation-that-inhibits-dna-repair-sensitizes-mutation-susceptibility-and-induces-aldehyde-dna-adducts-at-p53-mutational-hotspot-codon-249
#2
Mao-Wen Weng, Hyun-Wook Lee, Bongkun Choi, Hsiang-Tsui Wang, Yu Hu, Manju Mehta, Dhimant Desai, Shantu Amin, Yi Zheng, Moon-Shong Tang
Aflatoxin B1 (AFB1) contamination in the food chain is a major cause of hepatocellular carcinoma (HCC). More than 60% of AFB1 related HCC carry p53 codon 249 mutations but the causal mechanism remains unclear. We found that 1) AFB1 induces two types of DNA adducts in human hepatocytes, AFB1-8,9-epoxide-deoxyguanosine (AFB1-E-dG) induced by AFB1-E and cyclic α-methyl-γ-hydroxy-1,N2-propano-dG (meth-OH-PdG) induced by lipid peroxidation generated acetaldehyde (Acet) and crotonaldehyde (Cro); 2) the level of meth-OH-PdG is >30 fold higher than the level of AFB1-E-dG; 3) AFB1, Acet, and Cro, but not AFB1-E, preferentially induce DNA damage at codon 249; 4) methylation at -CpG- sites enhances meth-OH-PdG formation at codon 249; and 5) repair of meth-OH-PdG at codon 249 is poor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198443/serum-lipid-alterations-identified-in-chronic-hepatitis-b-hepatitis-b-virus-associated-cirrhosis-and-carcinoma-patients
#3
Tao Wu, Xiaojiao Zheng, Ming Yang, Aihua Zhao, Meng Li, Tianlu Chen, Jun Panee, Wei Jia, Guang Ji
The incidences of chronic hepatitis B (CHB), Hepatitis B virus (HBV)-associated cirrhosis and HBV-associated carcinoma are high and increasing. This study was designed to evaluate serum lipid metabolite changes that are associated with the progression from CHB to HBV-associated cirrhosis and ultimately to HBV-associated HCC. A targeted metabolomic assay was performed in fasting sera from 136 CHB patients, 104 HBV-associated cirrhosis, and 95 HBV-associated HCC using ultra-performance liquid chromatography triple quadrupole mass spectrometry...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192155/modality-of-tumor-endothelial-vegfr2-silencing-mediated-improvement-in-intratumoral-distribution-of-lipid-nanoparticles
#4
Shoshiro Yamamoto, Akari Kato, Yu Sakurai, Tomoya Hada, Hideyoshi Harashima
The vascular endothelial growth factor (VEGF)-mediated enhancement in vascular permeability is considered to be a major factor in tumor-targeting delivery via the enhanced permeability and retention (EPR) effect. We previously reported that the silencing of the endothelial VEGF receptor (VEGFR2) by a liposomal siRNA system (RGD-MEND) resulted in an enhanced intratumoral distribution of polyethylene glycol (PEG)-modified liposomes (LPs) in a renal cell carcinoma, a type of hypervascularized cancer, although the inhibition of VEGF signaling would be expected to decrease the permeability of the tumor vasculature...
February 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28178326/quantitative-liver-proteomics-identifies-fgf19-targets-that-couple-metabolism-and-proliferation
#5
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Boudewijn M T Burgering, Saskia W C van Mil
Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28167506/lipid-nanoparticle-mediated-delivery-of-anti-mir-17-family-oligonucleotide-suppresses-hepatocellular-carcinoma-growth
#6
Xinqiang Huang, Jill Magnus, Vivek Kaimal, Priya Karmali, Jian Li, Marlena Walls, Rene Prudente, Eric Sung, Mehran Sorourian, Robin Lee, Scott Davis, Xia Yang, Heather Estrella, Edmund C Lee, B Nelson Chau, Adam Pavlicek, Sonya Zabludoff
Hepatocellular carcinoma (HCC) is one of the most common human malignancies with poor prognosis and urgent unmet medical need. Aberrant expression of multiple members of the microRNA-17 (miR-17) family are frequently observed in HCC and their overexpression promotes tumorigenic properties of HCC cells. However, whether pharmacological inhibition of the miR-17 family inhibits HCC growth remains unknown. In the present study, we validated that the miR-17 family was up-regulated in a subset of HCC tumors and cell lines and its inhibition by a tough decoy inhibitor suppressed growth of Hep3B and HepG2 cells, which overexpress the miR-17 family...
February 6, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28139721/therapeutic-properties-of-scutellaria-baicalensis-in-db-db-mice-evaluated-using-connectivity-map-and-network-pharmacology
#7
Bu-Yeo Kim, Kwang Hoon Song, Chi-Yeon Lim, Su-In Cho
We have reported that an extract of Scutellaria baicalensis (ESB) has effects against obesity and hypertriglyceridemia in type 2 diabetic animal model (db/db mouse). In the present study, we tried to explain the pharmacological effects of ESB by integrating gene expression information from db/db mouse liver with that of ESB-treated HepG2 hepatocellular carcinoma cells. Using Connectivity Map (cmap) analysis, we found an inverse relationship in the pharmaceutical profiles based on gene expression between db/db mouse liver and ESB-treated HepG2 cells...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28126468/autotaxin-lysophosphatidic-acid-receptor-signalling-regulates-hepatitis-c-virus-replication
#8
Michelle J Farquhar, Isla S Humphreys, Simon A Rudge, Garrick K Wilson, Bishnupriya Bhattacharya, Maria Ciaccia, Ke Hu, Qifeng Zhang, Laurent Mailly, Gary M Reynolds, Margaret Aschcroft, Peter Balfe, Thomas F Baumert, Stephanie Roessler, Michael J O Wakelam, Jane A McKeating
BACKGROUND AND AIMS: Chronic hepatitis C is a global health problem with an estimated 170 million HCV infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX) is a phospholipase with diverse roles in physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood...
January 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28125040/silymarin-silybin-and-chronic-liver-disease-a-marriage-of-many-years
#9
REVIEW
Alessandro Federico, Marcello Dallio, Carmelina Loguercio
Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation...
January 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28119815/synthesis-of-hydroxycinnamic-acid-derivatives-as-mitochondria-targeted-antioxidants-and-cytotoxic-agents
#10
Jiyu Li, Dian He, Baitao Wang, Ling Zhang, Kun Li, Qinjian Xie, Lifang Zheng
In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids (MitoHCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OH(∙-) and ROO(∙-) induced lipid peroxidation. H2O2 production was decreased significantly by increasing glutathione peroxidase and catalase activities...
January 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28118080/oncogene-dependent-requirement-of-fatty-acid-synthase-in-hepatocellular-carcinoma
#11
Li Che, Maria G Pilo, Antonio Cigliano, Gavinella Latte, Maria M Simile, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Hepatocellular carcinoma (HCC), the most frequent primary tumor of the liver, is an aggressive cancer type with limited treatment options. Cumulating evidence underlines a crucial role of aberrant lipid biosynthesis (a process known as de novo lipogenesis) along carcinogenesis. Previous studies showed that suppression of fatty acid synthase (FASN), the major enzyme responsible for de novo lipogenesis, is highly detrimental for the in vitro growth of HCC cell lines. To assess whether de novo lipogenesis is required for liver carcinogenesis, we have generated various mouse models of liver cancer by stably overexpressing candidate oncogenes in the mouse liver via hydrodynamic gene delivery...
January 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28109303/uptake-of-dna-by-cancer-cells-without-a-transfection-reagent
#12
Yanping Kong, Xianbo Zhang, Yongliang Zhao, Yanfang Xue, Ye Zhang
BACKGROUND: Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis...
January 21, 2017: Biological Research
https://www.readbyqxmd.com/read/28105255/pi3k-ship2-pten-pathway-in-cell-polarity-and-hepatitis-c-virus-pathogenesis
#13
REVIEW
Aline Awad, Ama Gassama-Diagne
Hepatitis C virus (HCV) infects hepatocytes, polarized cells in the liver. Chronic HCV infection often leads to steatosis, fibrosis, cirrhosis and hepatocellular carcinoma, and it has been identified as the leading cause of liver transplantation worldwide. The HCV replication cycle is dependent on lipid metabolism and particularly an accumulation of lipid droplets in host cells. Phosphoinositides (PIs) are minor phospholipids enriched in different membranes and their levels are tightly regulated by specific PI kinases and phosphatases...
January 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28073184/functional-lipidomics-palmitic-acid-impairs-hepatocellular-carcinoma-development-by-modulating-membrane-fluidity-and-glucose-metabolism
#14
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
#15
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 29, 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
#16
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
#17
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
#18
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
#19
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...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28030819/hyperhomocysteinemia-results-from-and-promotes-hepatocellular-carcinoma-via-cyp450-metabolism-by-cyp2j2-dna-methylation
#20
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
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