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chronic stress hcc

Deborah Repullo, Marie Diaz, Stéphane Holbrechts, Maria Gomez-Galdón, Dirk Van Gestel, Ali Bohlok, Gabriel Liberale, Vincent Donckier
BACKGROUND: The development of a second primary tumor is a potential late side effect of radiotherapy. Particularly, an increased risk of secondary cancers, mostly of digestive or breast origin, has been observed in patients treated with high-dose radiotherapy for Wilms tumor (WT) in childhood. However, hepatocellular carcinoma (HCC) has been very rarely described as a potentially radiotherapy-induced tumor. We describe the case of a patient with an aggressive HCC 50 years after the treatment of a WT...
March 7, 2018: World Journal of Surgical Oncology
Ying Wu, Bo Shan, Jianli Dai, Zhixiong Xia, Jie Cai, Tianwei Chen, Songya Lv, Yuxiong Feng, Ling Zheng, Yan Wang, Jianfeng Liu, Jing Fang, Dong Xie, Liangyou Rui, Jianmiao Liu, Yong Liu
Obesity is associated with both endoplasmic reticulum (ER) stress and chronic metabolic inflammation. ER stress activates the unfolded protein response (UPR) and has been implicated in a variety of cancers, including hepatocellular carcinoma (HCC). It is unclear whether individual UPR pathways are mechanistically linked to HCC development, however. Here we report a dual role for inositol-requiring enzyme 1α (IRE1α), the ER-localized UPR signal transducer, in obesity-promoted HCC development. We found that genetic ablation of IRE1α in hepatocytes not only markedly reduced the occurrence of diethylnitrosamine (DEN)-induced HCC in LKO mice when fed a normal chow (NC) diet, but also protected against the acceleration of HCC progression during high-fat diet (HFD) feeding...
March 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xiaoling Li, Liansheng Liu, Ran Li, Ailing Wu, Jinqiu Lu, Qingzhe Wu, Junling Jia, Mujun Zhao, Hai Song
The liver is a major organ in lipid metabolism and its malfunction leads to various diseases. Nonalcoholic fatty liver disease, the most common chronic liver disorder in developed countries is characterized by the abnormal retention of excess lipid within hepatocytes and predisposes individuals to liver cancer. We previously reported that the levels of Lissencephaly 1 (LIS1, also known as Pafah1b1) are down-regulated in human hepatocellular carcinoma. Following up on this observation, we found that genetic deletion of Lis1 in the mouse liver increases lipid accumulation and inflammation in this organ...
February 23, 2018: Journal of Biological Chemistry
Patrizia Burra, Alberto Zanetto, Giacomo Germani
Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized...
February 9, 2018: Cancers
Antonella Borrelli, Patrizia Bonelli, Franca Maria Tuccillo, Ira D Goldfine, Joseph L Evans, Franco Maria Buonaguro, Aldo Mancini
Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory"...
January 27, 2018: Redox Biology
Yucel Aydin, Animesh Chatterjee, Partha K Chandra, Srinivas Chava, Weina Chen, Anamika Tandon, Asha Dash, Milad Chedid, Martin W Moehlen, Frederic Regenstein, Luis A Balart, Ari Cohen, Hua Lu, Tong Wu, Srikanta Dash
The mechanism why hepatitis C virus (HCV) clearance by direct-acting antivirals (DAAs) does not eliminate the risk of hepatocellular carcinoma (HCC) among patients with advanced cirrhosis is unclear. Many viral and bacterial infections degrade p53 in favor of cell survival to adapt an endoplasmic reticulum (ER)-stress response. In this study, we examined whether HCV clearance by interferon-alpha or DAAs normalizes the ER stress and restores the expression of p53 tumor suppressor in cell culture. We found that HCV infection induces chronic ER stress and unfolded protein response in untransformed primary human hepatocytes...
May 2017: Hepatology Communications
Antonietta Stellavato, Anna Virginia Adriana Pirozzi, Francesca de Novellis, Ilaria Scognamiglio, Valentina Vassallo, Andrea Maria Giori, Mario De Rosa, Chiara Schiraldi
BACKGROUND: Steatosis is a chronic liver disease that depends on the accumulation of intracellular fatty acids. Currently, no drug treatment has been licensed for steatosis; thus, only nutritional guidelines are indicated to reduce its progression. The aim of this study is to combine different nutraceutical compounds in order to evaluate their synergistic effects on a steatosis in vitro model compared to their separate use. In particular, three different formulations based on silymarin, curcumin, vitamin E, docosahexaenoic acid (DHA), choline, and phosphatidylcholine were assayed...
February 5, 2018: Lipids in Health and Disease
Sidrah Naseem, Tabinda Hussain, Sobia Manzoor
Liver pathologies (fibrosis, cirrhosis, alcoholic, non-alcoholic diseases and hepatocellular carcinoma) represent one of the most common causes of death worldwide. A number of genetic and environmental factors contribute to the development of liver diseases. Interleukin-6 (IL-6) is a pleiotropic cytokine, exerting variety of effects on inflammation, liver regeneration, and defence against infections by regulating adaptive immunity. Due to its high abundance in inflammatory settings, IL-6 is often viewed as a detrimental cytokine...
January 12, 2018: Cytokine & Growth Factor Reviews
Mohammad Irshad, Priyanka Gupta, Khushboo Irshad
Present study outlines a comprehensive view of published information about the underlying mechanisms operational for progression of chronic hepatitis C virus (HCV) infection to development of hepatocellular carcinoma (HCC). These reports are based on the results of animal experiments and human based studies. Although, the exact delineated mechanism is not yet established, there are evidences available to emphasize the involvement of HCV induced chronic inflammation, oxidative stress, insulin resistance, endoplasmic reticulum stress, hepato steatosis and liver fibrosis in the progression of HCV chronic disease to HCC...
December 28, 2017: World Journal of Hepatology
Haristi Gaitantzi, Christoph Meyer, Pia Rakoczy, Maria Thomas, Kristin Wahl, Franziska Wandrer, Heike Bantel, Hamed Alborzinia, Stefan Wölfl, Sabrina Ehnert, Andreas Nüssler, Ina Bergheim, Loredana Ciuclan, Matthias Ebert, Katja Breitkopf-Heinlein, Steven Dooley
Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels...
January 19, 2018: Cell Death & Disease
Yuki Mizuno, Shu Shimada, Yoshimitsu Akiyama, Shuichi Watanabe, Tomomi Aida, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Daisuke Ban, Atsushi Kudo, Shigeki Arii, Shoji Yamaoka, Minoru Tanabe, Shinji Tanaka
Decrease in blood concentration of branched-chain amino acids, especially leucine, is known to promote liver carcinogenesis in patients with chronic liver disease, but the mechanism is unclear. We herein established hepatocellular carcinoma (HCC) cells knocked out for DEPDC5 by using the CRISPR/Cas9 system, and elucidated that cell viability of the DEPDC5 knockout (DEPDC5-KO) cells was higher than that of the DEPDC5 wild-type (DEPDC5-WT) under leucine starvation. Considering that autophagy deficiency might be involved in acquired resistance to leucine deprivation, we observed reduction of LC3-II followed by accumulation of p62 in the DEPDC5-KO, which induced reactive oxygen species (ROS) tolerance...
January 8, 2018: Scientific Reports
Mohamed El Kassas, Anna L Funk, Mohamed Salaheldin, Yusuke Shimakawa, Mohammed Eltabbakh, Kévin Jean, Adel El Tahan, Ahmad T Sweedy, Shimaa Afify, Naglaa Fa Youssef, Gamal Esmat, Arnaud Fontanet
In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV infected population from one Egyptian specialized HCC management center starting from the time of successful HCC intervention...
December 23, 2017: Journal of Viral Hepatitis
J J Hu, X N Duan, J Fang, N Xu, Y H Wan, P Y Su, F B Tao, Y Sun
Objective: To determine the possible relations between hair cortisol concentration (HCC) as a biomarker of chronic stress and childhood overweight and obesity. Methods: Children from grade 1 to 3 from 2 primary schools in Bengbu were invited to participate in the study; and those who suffer from mental disorders, endocrine diseases and those who took hormone drugs were excluded. Parental questionnaire was implemented to collect information on physical activity, screen time, sleep duration, sugar-beverage consumption, as well as socio-economic status...
December 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Somenath Datta, Debanjali Dasgupta, Alip Ghosh, Suchandrima Ghosh, Alak Manna, Simanti Datta, Mitali Chatterjee, Abhijit Chowdhury, Soma Banerjee
Despite widespread distribution of hepatitis B virus (HBV)-genotype D, the clinical implications of its ten subgenotypes (D1-D10) have not been well documented. Here, we have investigated the impact of two major circulating HBV/D subgenotypes, D1 and D3 in Eastern India towards pathogenesis of liver disease progression to hepatocellular carcinoma (HCC). HBV subgenotypes were determined using full-length genome sequences of HBV isolates from patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC...
February 9, 2018: Carcinogenesis
B Uma Reddy, Ranajoy Mullick, Anuj Kumar, Geetika Sharma, Paromita Bag, Chaitrali Laha Roy, Govindarajan Sudha, Himani Tandon, Pratik Dave, Ashutosh Shukla, Priyanka Srinivasan, Madhusudhan Nandhitha, Narayanaswamy Srinivasan, Saumitra Das
Hepatitis C virus (HCV) infection causes chronic liver disease, which often leads to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against viral hepatitis. Here, we report identification of a principal bioactive component 'corilagin', which showed significant inhibition of the HCV key enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound could effectively inhibit viral replication in the infectious cell culture system, displayed strong antioxidant activity by blocking HCV induced generation of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-β mRNA levels...
February 2018: Antiviral Research
Jia Li, Jiang He, Yongming Fu, Xingwang Hu, Lun-Quan Sun, Yan Huang, Xuegong Fan
Chronic Hepatitis B virus (HBV) infection is a major risk of hepatocellular carcinoma (HCC) worldwide. Hepatitis B virus X protein (HBx) is encoded by one of the four open reading frames of HBV, and is well known as an important coactivator for HBV replication and HBV-associated hepatocellular carcinogenesis. However, its role in keeping cells from apoptosis to promote HCC proliferation remains controversial. Here, we used HBx expressing HCC cells as a model, to investigate the mechanism of HBx-mediated cellular response to endoplasmic reticulum (ER) stress...
November 10, 2017: Oncotarget
Jiang Nan, Yan-Fang Xing, Bo Hu, Jian-Xin Tang, Hui-Min Dong, Yu-Mei He, Dan-Yun Ruan, Qing-Jian Ye, Jia-Rong Cai, Xiao-Kun Ma, Jie Chen, Xiu-Rong Cai, Ze-Xiao Lin, Xiang-Yuan Wu, Xing Li
A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphisms myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX-1+  CD15+ PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases...
December 6, 2017: Immunology
So Young Kim, Yi Yi Kyaw, Jaehun Cheong
Hepatitis B virus (HBV) is a non-cytopathic virus that causes acute and chronic inflammatory liver diseases, often leading to the pathogenesis of hepatocellular carcinoma (HCC). Although many studies for the roles of HBV on pathogenesis of the liver diseases, such as non-alcoholic fatty liver disease (NAFLD), hepatic inflammation, cirrhosis, and HCC, have been reported, the mechanisms are not fully understood. Endoplasmic reticulum (ER) and mitochondria have the protective mechanisms to restore their damaged function by intrinsic or extrinsic stresses, but their chronic dysfunctions are associated with the pathogenesis of the various diseases...
November 21, 2017: World Journal of Gastroenterology: WJG
Liang Wu, Qingchun Pan, Guangyu Wu, Lingling Qian, Jing Zhang, Lei Zhang, Qichen Fang, Guoqing Zang, Yudong Wang, George Lau, Huating Li, Weiping Jia
Fibroblast growth factor 21 (FGF21), a stress-induced hormone in the liver, has been shown the protective functions in pathological conditions. The study investigated the association of circulating FGF21 with hepatitis B virus (HBV) infection and its related diseases. Serum FGF21 levels were measured in 33 acute hepatitis B (AHB), 75 chronic hepatitis B (CHB) and 66 CHB patients with advanced liver diseases including liver cirrhosis, acute-on-chronic liver failure (ALCF) and hepatocellular carcinoma (HCC) together with 200 age- and BMI-matched healthy controls...
November 28, 2017: Scientific Reports
Marcus Hollenbach
Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC)...
November 20, 2017: International Journal of Molecular Sciences
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