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https://www.readbyqxmd.com/read/29050312/non-alcoholic-steatohepatitis-related-liver-tumorigenesis-is-suppressed-in-mice-lacking-hepatic-retinoid-storage
#1
Takayasu Ideta, Yohei Shirakami, Masaya Ohnishi, Akinori Maruta, Koki Obara, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Hiroyuki Tomita, Takuji Tanaka, William S Blaner, Masahito Shimizu
Non-alcoholic fatty liver disease has become one of the most common causes of chronic liver disease that can develop into a more serious form, non-alcoholic steatohepatitis, leading to liver cirrhosis and hepatocellular carcinoma. Although hepatic retinoid stores are progressively lost during the development of liver disease, how this affects steatohepatitis and its related hepatocarcinogenesis is unknown. In order to investigate these, we used subcutaneous injection of streptozotocin (0.2 mg/body) and high-fat diet to induce steatohepatitis and hepatic tumorigenesis in lecithin:retinol acyltransferase -deficient mice (n = 10), which lack stored retinoid in the liver, and control mice (n = 12)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29043595/stress-hormone-cortisol-enhances-bcl2-like-12-expression-to-inhibit-p53-in-hepatocellular-carcinoma-cells
#2
Weizhong Wu, Sanguang Liu, Yunfei Liang, Zegao Zhou, Wei Bian, Xueqing Liu
BACKGROUND AND AIMS: The pathogenesis of hepatocellular carcinoma (HC) is unclear. It is suggested that psychological stress associates with the pathogenesis of liver cancer. Bcl2-like protein 12 (Bcl2L12) suppresses p53 protein. This study tests a hypothesis that the major stress hormone, cortisol, inhibits the expression of p53 in HC cells (HCC) via up regulating the expression of Bcl2L12. METHODS: Peripheral blood samples were collected from patients with HC to be analyzed for the levels of cortisol...
October 17, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29038587/cell-surface-major-vault-protein-promotes-cancer-progression-through-harboring-mesenchymal-and-intermediate-circulating-tumor-cells-in-hepatocellular-carcinomas
#3
Hyun Min Lee, Jae Won Joh, Se-Ri Seo, Won-Tae Kim, Min Kyu Kim, Hong Seo Choi, So Young Kim, Young-Joo Jang, Dong Hyun Sinn, Gyu Seong Choi, Jong Man Kim, Choon Hyuck David Kwon, Hee Jin Chang, Dae Shick Kim, Chun Jeih Ryu
Circulating tumor cells (CTCs) play a major role in the metastasis and recurrence of hepatocellular carcinoma (HCC). Here, we found that major vault protein (MVP) is expressed on the surface of HCC cells and further induced under stressful environments. MVP knockdown reduces cell proliferation and induces apoptosis in HCC cells. Treatment of HCC cells with anti-MVP antibody (α-MVP) recognizing cell-surface MVP (csMVP) inhibits cell proliferation, migration, and invasion. csMVP-positive HCC cells have a higher clonogenic survival than csMVP-negative HCC cells, and treatment of HCC cells with α-MVP inhibits clonogenic survival, suggesting that csMVP contributes to HCC cell survival, migration, and invasion...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29032312/advanced-oxidation-protein-products-induce-s-phase-arrest-of-hepatocytes-via-the-ros-dependent-%C3%AE-catenin-cdk2-mediated-pathway
#4
Shibo Sun, Fang Xie, Xiaoping Xu, Qing Cai, Qifan Zhang, Zhonglin Cui, Yujian Zheng, Jie Zhou
Liver regeneration has important clinical importance in the setting of partial hepatectomy (PH). Following PH, quiescent hepatocytes can reenter cell cycle to restore liver mass. Hepatocyte cell cycle progression, as the basic motivations of liver regeneration, can be disrupted by multiple pathological factors such as oxidative stress. This study aimed to evaluate the role of advanced oxidation protein products (AOPP) in S-phase arrest in hepatocytes. Serum AOPP level were measured during the perioperative period of PH in 33 patients with hepatocellular carcinoma (HCC)...
October 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29024780/toxicogenomics-of-the-flame-retardant-tris-2-butoxyethyl-phosphate-in-hepg2-cells-using-rna-seq
#5
Boris V Krivoshiev, Gerrit T S Beemster, Katrien Sprangers, Bart Cuypers, Kris Laukens, Ronny Blust, Steven J Husson
Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29023783/melatonin-application-in-targeting-oxidative-induced-liver-injuries-a-review
#6
REVIEW
Keywan Mortezaee, Neda Khanlarkhani
It is believed that oxidative stress is a key causing factor of liver damage induced by a variety of agents, and it is a major contributing factor in almost all conditions compromising liver function, including ischemia-reperfusion injury (IRI), nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, liver cirrhosis and hepatocellular carcinoma (HCC). Liver is the organ that high concentration of melatonin (N-acetyl-5-methoxytryptamine) accumulates, and it is the sole organ where circulating melatonin is metabolized...
October 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29022011/placental-extract-ameliorates-non-alcoholic-steatohepatitis-nash-by-exerting-protective-effects-on-endothelial-cells
#7
Akihiro Yamauchi, Akiko Kamiyoshi, Teruhide Koyama, Nobuyoshi Iinuma, Shumpei Yamaguchi, Hiroyuki Miyazaki, Eiichi Hirano, Taiichi Kaku, Takayuki Shindo
Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE) reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD) diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water) to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE...
September 2017: Heliyon
https://www.readbyqxmd.com/read/29018945/-nuclear-her2-expression-in-hepatocytes-in-liver-disease
#8
REVIEW
P Döring, G M Pilo, D F Calvisi, F Dombrowski
BACKGROUND: Her2 is a well-known member of the epidermal growth factor receptor (EGFR) superfamily, a group of transmembrane receptors that mediate effects of proliferation and survival and thus play an important role in tumorigenesis. EGFRs can translocate to the nucleus and may mediate DNA repair and cell cycle arrest. OBJECTIVES: The aim of this study was to characterize hepatocellular Her2 expression in different liver diseases. MATERIALS AND METHODS: Her2 expression was analyzed by immunohistochemistry in 674 liver biopsies...
October 10, 2017: Der Pathologe
https://www.readbyqxmd.com/read/29018509/circrna_0046367-prevents-hepatoxicity-of-lipid-peroxidation-an-inhibitory-role-against-hepatic-steatosis
#9
Xing-Ya Guo, Jian-Neng Chen, Fang Sun, Yu-Qin Wang, Qin Pan, Jian-Gao Fan
Hepatic steatosis reflects the miRNA-related pathological disorder with triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma. Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a that underlies hepatic steatosis. In contrast to its expression loss during the hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization abolished miR-34a's inhibitory effect on peroxisome proliferator-activated receptor α (PPARα) via blocking the miRNA/mRNA interaction with miRNA response elements (MREs)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28991167/achiral-mannich-base-curcumin-analogs-induce-unfolded-protein-response-and-mitochondrial-membrane-depolarization-in-panc-1-cells
#10
Gábor J Szebeni, Árpád Balázs, Ildikó Madarász, Gábor Pócz, Ferhan Ayaydin, Iván Kanizsai, Roberta Fajka-Boja, Róbert Alföldi, László Hackler, László G Puskás
Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549), hepatocellular carcinoma (HepG2) and pancreatic cancer cell line (PANC-1). Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells...
October 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28984147/celastrol-ameliorates-acetaminophen-induced-oxidative-stress-and-cytotoxicity-in-hepg2-cells
#11
A T Jannuzzi, M Kara, B Alpertunga
Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. However, hepatotoxicity caused by APAP overdose is the most frequent cause of acute liver failure worldwide and oxidative stress involved in the pathogenesis of APAP hepatotoxicity. Celastrol is a natural triterpenoid derived from Tripterygium wilfordii Hook F. that exhibits antioxidant, anti-inflammatory, and antitumor activities. In this study, we aimed to investigate the potential ameliorative effects of celastrol against APAP-induced cytotoxicity and oxidative stress...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28975986/csr1-suppresses-tumor-growth-and-metastasis-of-human-hepatocellular-carcinoma-via-inhibition-of-hpip
#12
L Jiang, G Hu, F-F Chen, X-Y Du, B Liu, C Liu
OBJECTIVE: Cellular stress response 1 (CSR1) is a tumor suppressor gene that was frequently down-regulated in prostate cancer. CSR1 has critical roles in the regulation of cell apoptosis via inactivation of CPSF3 or preventing the interaction of XIAP with caspases. However, whether CSR1 plays a role in human hepatocellular carcinoma (HCC) is completely unknown. PATIENTS AND METHODS: The expression of CSR1 in HCC clinic samples and cell lines was detected by Real-time PCR and Western blot...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28954551/heat-stress-induced-ligand-independent-met-and-egfr-signaling-in-hepatocellular-carcinoma
#13
Scott M Thompson, Danielle E Jondal, Kim A Butters, Bruce E Knudsen, Jill L Anderson, Matthew P Stokes, Xiaoying Jia, Joseph P Grande, Lewis R Roberts, Matthew R Callstrom, David A Woodrum
PURPOSE: The aims of the present study were two-fold: first, to test the hypothesis that heat stress induces MET and EGFR signaling in hepatocellular carcinoma (HCC) cells and inhibition of this signaling decreases HCC clonogenic survival; and second, to identify signaling pathways associated with heat-stress induced MET signaling. MATERIALS AND METHODS: MET(+) and EGFR(+) HCC cells were pre-treated with inhibitors to MET, EGFR, PI3K/mTOR or vehicle and subjected to heat stress or control ± HGF or EGF growth factors and assessed by colony formation assay, Western blotting and/or quantitative mass spectrometry...
September 27, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28951455/fgf19-protects-hepatocellular-carcinoma-cells-against-endoplasmic-reticulum-stress-via-activation-of-fgfr4-gsk3%C3%AE-nrf2-signaling
#14
Yong Teng, Huakan Zhao, Lixia Gao, Wenfa Zhang, Austin Y Shull, Chloe Shay
The tumor microenvironment induces endoplasmic reticulum (ER) stress in tumor cells, an event that can promote progression, but it is unknown how tumor cells adapt to this stress. In this study, we show that the fibroblast growth factor FGF19, a gene frequently amplified in hepatocellular carcinoma (HCC), facilitates a survival response to ER stress. Levels of FGF19 expression were increased in stressed HCC cells in culture and in a mouse xenograft model. Induction of ER stress required the transcription factor ATF4, which directly bound the FGF19 promoter...
September 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28943956/hbv-suppresses-thapsigargin-induced-apoptosis-via-inhibiting-chop-expression-in-hepatocellular-carcinoma-cells
#15
Danqi Zhao, Yan Liu, Xing Liu, Tao Li, Zhenhui Xin, Xilin Zhu, Xiaopan Wu, Ying Liu
Hepatocellular carcinoma (HCC) accounts for a proportion of cancer-associated mortalities worldwide. Hepatitis B virus (HBV) infection is a major cause of HCC in China. Thapsigargin (TG) is a potential antitumor prodrug, eliciting endoplasmic reticulum (ER) stress via the inhibition of the ER calcium pump, effectively inducing apoptosis. The present study therefore examined the role of HBV in TG-induced apoptosis using two HCC cell lines, HBV positive HepG2.2.15 and HBV negative HepG2. When these two cell lines were treated with TG, HepG2...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28938597/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#16
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932315/experimental-hepatic-carcinogenesis-oxidative-stress-and-natural-antioxidants
#17
REVIEW
Velid Unsal, Ergül Belge-Kurutaş
Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C). Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN) mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons...
August 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28931802/hepatitis-c-virus-infection-increases-c-jun-n-terminal-kinase-jnk-phosphorylation-and-accentuates-hepatocyte-lipoapoptosis
#18
Hiroko Takaki, Yuko Akazawa, Youko Kido, Mami Morishita, Takuya Honda, Hidetaka Shibata, Satoshi Miuma, Hisamitsu Miyaaki, Naota Taura, Hisayoshi Kondo, Kazuhiko Nakao
BACKGROUND Hepatitis C virus (HCV) infection and metabolic diseases including nonalcoholic steatohepatitis (NASH) exhibit a complex interplay. Although free fatty acid-mediated apoptosis is a prominent feature of NASH, the impact of HCV infection on hepatocyte lipotoxicity has remained largely unexplored. The study aimed at identifying whether infection by HCV affected the apoptotic pathway in hepatocytes during fatty acid assault. MATERIAL AND METHODS OR6 cells, which are derived from human hepatocellular carcinoma Huh-7 cells and harbor a full-length HCV RNA genome replication system, were treated with palmitate...
September 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28928813/heat-shock-protein-70-downregulation-inhibits-proliferation-migration-and-tumorigenicity-in-hepatocellular-carcinoma-cells
#19
Ju Xiong, Xue-Mei Jiang, Shan-Shan Mao, Xiang-Nan Yu, Xiao-Xi Huang
The overexpression of heat shock protein 70 (HSP70), a major stress-inducible heat shock protein, has been identified to enhance the proliferation, survival, invasion and metastasis of diverse types of human cancer. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. The present study demonstrated that HSP70 expression was higher in tested HCC cell lines, compared with the normal hepatocyte LO2, and the suppression of HSP70 significantly inhibited the proliferation of SMMC-7721 and Hep3B cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28924544/analysis-of-the-mitochondrial-4977-bp-deletion-in-patients-with-hepatocellular-carcinoma
#20
Z S Guo, C L Jin, Z J Yao, Y M Wang, B T Xu
Mutations in the mitochondrial (mt) genome that result in mt dysfunction, have long been proposed to play important roles in the pathogenesis of hepatocellular carcinoma (HCC). Among these, the common mtDNA 4977 bp deletion is one of the most frequent mutations observed in various cancers. To understand the relationship between the mtDNA 4977 bp deletion and HCC, we performed mutational screening for the presence of this deletion in 105 HCC patients and 69 unrelated healthy subjects. After nested-polymerase chain reaction (nested-PCR) amplification, we found that there were 10 patients carrying the mtDNA 4977 bp deletion, and this deletion was absent in control subjects...
June 30, 2017: Balkan Journal of Medical Genetics: BJMG
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