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hepatocellular carcinoma, metformin

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https://www.readbyqxmd.com/read/29117515/metformin-and-epothilone-a-treatment-up-regulate-pro-apoptotic-parp-1-casp-3-and-h2ax-genes-and-decrease-of-akt-kinase-level-to-control-cell-death-of-human-hepatocellular-carcinoma-and-ovary-adenocarcinoma-cells
#1
Aneta Rogalska, Barbara Bukowska, Agnieszka Marczak
High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy. Here, we investigated genotoxic and pro-oxidant effects of metformin (MET) and epothilone A (A) in combination with respect to apoptosis in HepG2 and SKOV-3 cancer cells. Reactive oxygen species (ROS) was studied using 2',7'-dichlorodihydrofluoresein diacetate, and samples were analyzed for the presence and absence of the N-acetylcysteine (NAC). Expression of genes involved in programmed cell death, oxidative and alkylating DNA damage was measured...
November 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29094287/targeting-ampk-mtor-and-%C3%AE-catenin-by-combined-metformin-and-aspirin-therapy-in-hcc-an-appraisal-in-egyptian-hcc-patients
#2
Doaa Ali Abdelmonsif, Ahmed S Sultan, Wessam F El-Hadidy, Dina Mohamed Abdallah
BACKGROUND: Hepatocellular carcinoma (HCC) is an expanding health problem with a great impact on morbidity and mortality, both in Egypt and worldwide. Recently, metformin and aspirin showed a potential anticancer effect on HCC, although the mechanism of this effect is not fully elucidated. OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and β-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients...
November 1, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28985579/metformin-and-insulin-impact-on-clinical-outcome-in-patients-with-advanced-hepatocellular-carcinoma-receiving-sorafenib-validation-study-and-biological-rationale
#3
Andrea Casadei Gardini, Luca Faloppi, Serena De Matteis, Francesco Giuseppe Foschi, Nicola Silvestris, Francesco Tovoli, Vincenzo Palmieri, Giorgia Marisi, Oronzo Brunetti, Umberto Vespasiani-Gentilucci, Giuseppe Perrone, Martina Valgiusti, Anna Maria Granato, Giorgio Ercolani, Giulia Negrini, Emiliano Tamburini, Giuseppe Aprile, Alessandro Passardi, Daniele Santini, Stefano Cascinu, Giovanni Luca Frassineti, Mario Scartozzi
PURPOSE: In 2015, we published a study on a small series of patients with hepatocellular carcinoma (HCC) treated chronically with metformin for type II diabetes mellitus (DM2) who showed a poorer response to sorafenib. The aim of the present study was to validate the prognostic significance of metformin in HCC patients treated with sorafenib, providing a biological rationale for the mechanism of resistance to sorafenib in patients on chronic metformin therapy, and to clarify the role of sirtuin-3 (SIRT-3), a protein involved in metabolic diseases and acknowledged as a tumour suppressor in HCC, in this resistance...
October 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28964787/negative-regulation-of-sirtuin-1-by-amp-activated-protein-kinase-promotes-metformin-induced-senescence-in-hepatocellular-carcinoma-xenografts
#4
Xinke Zhou, Jitao Chen, Liangcai Chen, Xiao Feng, Zhaoyu Liu, La Hu, Zicheng Zeng, Xiaoting Jia, Min Liang, Boyun Shi, Gao Yi, Jifang Liu
Increasing evidence suggests that therapy-induced senescence (TIS), a novel therapeutic approach in which low doses of therapeutic drugs or radiation are used to induce senescence, suppresses tumor development. Our previous in vitro studies have demonstrated that a low dose of metformin promoted hepatoma cell senescence instead of apoptosis via activation of AMP-activated protein kinase (AMPK) and inactivation of Sirtuin 1 (SIRT1) deacetylase activity. However, the intricate relationship between AMPK and SIRT1, and how they cooperate to induce senescence remains elusive...
September 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28881582/metformin-requires-4e-bps-to-induce-apoptosis-and-repress-translation-of-mcl-1-in-hepatocellular-carcinoma-cells
#5
Mamatha Bhat, Akiko Yanagiya, Tyson Graber, Nataliya Razumilava, Steve Bronk, Domenick Zammit, Yunhao Zhao, Chadi Zakaria, Peter Metrakos, Michael Pollak, Nahum Sonenberg, Gregory Gores, Maritza Jaramillo, Masahiro Morita, Tommy Alain
Metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which is frequently upregulated in hepatocellular carcinoma (HCC). Metformin has also been shown to induce apoptosis in this cancer. Here, we investigate whether metformin-induced apoptosis in HCC is mediated by the downstream mTORC1 effectors eukaryotic initiation factor 4E and (eIF4E)-binding proteins (4E-BPs). Further, we ask whether changes in 4E-BPs activity during metformin treatment negatively regulate translation of the anti-apoptotic myeloid cell leukemia 1 (Mcl-1) mRNA...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28833603/metformin-incombination-with-curcumin-inhibits-the-growth-metastasis-and-angiogenesis-of-hepatocellular-carcinoma-in-vitro-and-in-vivo
#6
Hui-Hui Zhang, Ying Zhang, Yan-Na Cheng, Fu-Lian Gong, Zhan-Qi Cao, Lu-Gang Yu, Xiu-Li Guo
Hepatocellular carcinoma (HCC) has poor prognosis due to the advanced disease stages by the time it is diagnosed, high recurrence rates and metastasis. In the present study, we investigated the effects of metformin (a safe anti-diabetic drug) and curcumin (a turmeric polyphenol extracted from rhizome of Curcuma longa Linn.) on proliferation, apoptosis, invasion, metastasis and angiogenesis of HCC in vitro and in vivo. It was found that co-treatment of metformin and curcumin could not only induce tumor cells into apoptosis through activating the mitochondria pathways, but also suppress the invasion, metastasis of HCC cells and angiogenesis of HUVECs...
August 19, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28766170/aegle-marmelos-differentially-affects-hepatic-markers-of-glycolysis-insulin-signalling-pathway-hypoxia-and-inflammation-in-hepg2-cells-grown-in-fructose-versus-glucose-rich-environment
#7
H Aggarwal, J Nair, P Sharma, R Sehgal, U Naeem, P Rajora, R Mathur
Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated...
August 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28758096/type-2-diabetes-mellitus-and-risk-of-hepatocellular-carcinoma-spotlight-on-nonalcoholic-fatty-liver-disease
#8
REVIEW
Alessandro Mantovani, Giovanni Targher
The incidence of both type 2 diabetes mellitus (T2DM) and multiple cancer types are rapidly increasing worldwide. Several studies documented that T2DM is closely associated with an increased incidence of cancer. However, while some methodological considerations preclude a definitive association between T2DM and the risk of certain cancers, the relationship between T2DM and increased risk of incident hepatocellular carcinoma (HCC) remains significant even after adjustment for detection bias and reverse causation, indicating that such association is clinically reliable and robust...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28719078/luseogliflozin-improves-liver-fat-deposition-compared-to-metformin-in-type-2-diabetes-patients-with-non-alcoholic-fatty-liver-disease-a-prospective-randomized-controlled-pilot-study
#9
Takashi Shibuya, Nobutoshi Fushimi, Miyuka Kawai, Yohei Yoshida, Hiroki Hachiya, Shun Ito, Hiromi Kawai, Noritsugu Ohashi, Akihiro Mori
This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD). Thirty-two T2D patients with NAFLD diagnosed by computed tomography or abdominal sonography were recruited. Participants were randomly assigned to receive either luseogliflozin (2.5 mg, newly administered) or metformin (1500 mg, newly or additionally administrated). Data on the liver-to-spleen attenuation ratio (L/S), visceral fat area, body mass index, glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), fasting plasma glucose, C-peptide immunoreactivity (CPR), and CPR index were collected at baseline and after 6 months...
July 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28676020/current-and-potential-future-pharmacological-approaches-for-non-alcoholic-fatty-liver-disease
#10
Konstantinos Imprialos, Konstantinos Stavropoulos, Sofia Bouloukou, Georgios Kerpiniotis, Asterios Karagiannis, Michael Doumas
BACKGOUND: Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the general population. The disease ranges from simple steatosis, to non-alcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. Several drugs are used in daily clinical practice to manage the disease. However, data on their efficacy in liver histology are not consistent. AIM: We discuss current treatment options for NAFLD and NASH and preliminary results from novel drugs under investigation...
June 20, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28526827/activated-hepatic-stellate-cells-secrete-periostin-to-induce-stem-cell-like-phenotype-of-residual-hepatocellular-carcinoma-cells-after-heat-treatment
#11
Rui Zhang, Rong-Rong Yao, Jing-Huan Li, Gang Dong, Min Ma, Qiong-Dan Zheng, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28509327/the-occurrence-of-hepatocellular-carcinoma-in-different-risk-stratifications-of-clinically-noncirrhotic-nonalcoholic-fatty-liver-disease
#12
Teng-Yu Lee, Jaw-Ching Wu, Shi-Hang Yu, Jaw-Town Lin, Ming-Shiang Wu, Chun-Ying Wu
Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis...
October 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28459036/consensus-statement-on-dose-modifications-of-antidiabetic-agents-in-patients-with-hepatic-impairment
#13
REVIEW
Kalyan Kumar Gangopadhyay, Parminder Singh
Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia...
March 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28450808/metformin-exhibits-the-anti-proliferation-and-anti-invasion-effects-in-hepatocellular-carcinoma-cells-after-insufficient-radiofrequency-ablation
#14
Qingyun Zhang, Jian Kong, Shuying Dong, Wenlei Xu, Wenbing Sun
BACKGROUND: The mechanisms and prevention of progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily investigated, therefore, new strategy needs to be investigated to prevent the process. Whether metformin could be used to inhibit the growth of HCC after insufficient RFA and further prevent the progression of residual HCC remains unclearly. METHODS: MTT assay, colony formation assay and transwell assay were used to observe the cell viability, migration and invasion...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28290049/type-2-diabetes-and-hepatocellular-carcinoma-risk-factors-and-pathogenesis
#15
REVIEW
P Wainwright, E Scorletti, C D Byrne
PURPOSE OF REVIEW: This review aims to assess the epidemiological evidence for a link between type 2 diabetes and hepatocellular carcinoma and to investigate possible pathophysiological mechanisms. RECENT FINDINGS: The presence of type 2 diabetes significantly increases the risk of developing hepatocellular carcinoma, and treatment with metformin may be associated with a lower risk. Treatment with insulin and sulphonylureas may be associated with increased risk...
April 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28109969/independent-of-cirrhosis-hepatocellular-carcinoma-risk-is-increased-with-diabetes-and-metabolic-syndrome
#16
Allison J Kasmari, Amy Welch, Guodong Liu, Doug Leslie, Thomas McGarrity, Thomas Riley
BACKGROUND: Hepatocellular carcinoma is the most common primary liver malignancy, commonly a sequelae of hepatitis C infection, but can complicate cirrhosis of any cause. Whether metabolic syndrome and its components, type II diabetes, hypertension, and hyperlipidemia increase the risk of hepatocellular carcinoma independent of cirrhosis is unknown. METHODS: A retrospective cohort study was conducted using the MarketScan insurance claims database from 2008-2012...
June 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28099155/metformin-promotes-apoptosis-in-hepatocellular-carcinoma-through-the-cebpd-induced-autophagy-pathway
#17
Hsin-Hwa Tsai, Hong-Yue Lai, Yueh-Chiu Chen, Chien-Feng Li, Huei-Sheng Huang, Hsiao-Sheng Liu, Yau-Sheng Tsai, Ju-Ming Wang
Metformin, as an AMP-activated protein kinase (AMPK) activator, can activate autophagy. A study showed that metformin decreased the risk of hepatocellular carcinoma (HCC) in diabetic patients. However, the detailed mechanism in the metformin-mediated anticancer effect remains an open question. Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) has been suggested to serve as a tumor suppressor and is responsive to multiple anticancer drugs in HCC. In this study, we found that CEBPD and autophagy are involved in metformin-induced cell apoptosis in Huh7 cells...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-non-alcoholic-fatty-liver-disease-with-type-2-diabetes-mellitus
#18
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM...
March 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27959383/combination-of-metformin-and-sorafenib-suppresses-proliferation-and-induces-autophagy-of-hepatocellular-carcinoma-via-targeting-the-mtor-pathway
#19
Sunbin Ling, Lei Song, Ning Fan, Tingting Feng, Lu Liu, Xu Yang, Mingjie Wang, Yanling Li, Yu Tian, Feng Zhao, Ying Liu, Qihong Huang, Zhaoyuan Hou, Fei Xu, Lei Shi, Yan Li
The multi‑kinase inhibitor sorafenib is the only drug for which randomized control trials have shown improved patient survival in advanced hepatocellular carcinoma (HCC). However, life expectancy is extended in these cases by only a few months. The anti‑type II diabetes agent metformin was used in this study in an effort to find a more efficient approach to HCC treatment. Sorafenib effectively reversed the activation status of mTORC2 induced by metformin and enhanced the suppression of the mTORC1 and MAPK pathway by metformin in HCC cells, which may be responsible for reduced proliferation upon combined treatment...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27861855/effect-of-statin-on-hepatocellular-carcinoma-in-patients-with-type-2-diabetes-a-nationwide-nested-case-control-study
#20
Gyuri Kim, Suk-Yong Jang, Eugene Han, Yong-Ho Lee, Se-Young Park, Chung Mo Nam, Eun Seok Kang
Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population-based nested case-control study was conducted within the National Health Insurance Service National Sample Cohort 2002-2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow-up time, and the date of diabetes diagnosis at a five-to-one ratio...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
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