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hepatocellular carcinoma, metformin

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https://www.readbyqxmd.com/read/29449537/predictive-and-preventive-significance-of-ampk-activation-on-hepatocarcinogenesis-in-patients-with-liver-cirrhosis
#1
Xiaoli Yang, Yan Liu, Menghui Li, Hao Wu, Yunbing Wang, Yu You, Peizhi Li, Xiong Ding, Chang'an Liu, Jianping Gong
Metformin has been demonstrated to prevent hepatocellular carcinoma (HCC). Metformin acts mainly by phosphorylation of AMPK. However, the phosphorylation status of AMPK and its role in the prediction and prevention of HCC in cirrhotic patients remains unclear. The phosphorylation status of AMPK (Thr172) was determined by immunostaining in tissue microarrays of 426 cirrhotic liver tissues. Low expression of p-AMPK was observed in 94 (22.1%) cases. The median follow-up time was 87 months. HCC occurrence probability at 1/3/5/10 years after Hassab procedure was 3...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29386513/hexokinase-2-depletion-inhibits-glycolysis-and-induces-oxidative-phosphorylation-in-hepatocellular-carcinoma-and-sensitizes-to-metformin
#2
Dannielle DeWaal, Veronique Nogueira, Alexander R Terry, Krushna C Patra, Sang-Min Jeon, Grace Guzman, Jennifer Au, Christopher P Long, Maciek R Antoniewicz, Nissim Hay
Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human HCC cells inhibits tumorigenesis and increases cell death, which cannot be restored by GCK or mitochondrial binding deficient HK2. Upon HK2 silencing, glucose flux to pyruvate and lactate is inhibited, but TCA fluxes are maintained...
January 31, 2018: Nature Communications
https://www.readbyqxmd.com/read/29385181/simvastatin-and-metformin-inhibit-cell-growth-in-hepatitis-c-virus-infected-cells-via-mtor-increasing-pten-and-autophagy
#3
José A Del Campo, Marta García-Valdecasas, Antonio Gil-Gómez, Ángela Rojas, Paloma Gallego, Javier Ampuero, Rocío Gallego-Durán, Helena Pastor, Lourdes Grande, Francisco J Padillo, Jordi Muntané, Manuel Romero-Gómez
Hepatitis C virus (HCV) infection has been related to increased risk of development of hepatocellular carcinoma (HCC) while metformin (M) and statins treatment seemed to protect against HCC development. In this work, we aim to identify the mechanisms by which metformin and simvastatin (S) could protect from liver cancer. Huh7.5 cells were infected with HCV particles and treated with M+S. Human primary hepatocytes were treated with M+S. Treatment with both drugs inhibited Huh7.5 cell growth and HCV infection...
2018: PloS One
https://www.readbyqxmd.com/read/29344225/metformin-enhances-the-chemosensitivity-of-hepatocarcinoma-cells-to-cisplatin-through-ampk-pathway
#4
Hao Dong, Jungang Huang, Kang Zheng, Dong Tan, Qi Chang, Genqiang Gong, Qing Zhang, Hanqiu Tang, Jianguo Sun, Shaoyu Zhang
This study investigated the effect of metformin on chemosensitivity of hepatocarcinoma cells to cisplatin and the possible mechanism. HepG2 and Huh-7 hepatoma cells were treated with cisplatin at concentrations of 0, 2, 4, 6, 8 and 10 µM for 48 h. Proliferation of HepG2 and Huh-7 hepatoma cells were detected by MTT assay. Apoptosis of hepatocellular carcinoma cells was detected by flow cytometry. Western blot analysis was used to detect the expression of 5-monophosphate-activated protein kinase (AMPK) and p-AMPK protein...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29231919/-non-alcoholic-liver-disease-diagnosis-and-treatment
#5
REVIEW
Anna Sarosiekjeznach-Steinhagen, Joanna Ostrowska, Aneta Czerwonogrodzka-Senczyna, Iwona Boniecka
Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in the developed world (15% to 40% of the adult population). Introduction of lifestyle changes including dietary intervention and increased physical activity is most often the first-line treatment and is intended to support not only the treatment of liver disease, but also for diseases associated with obesity, insulin resistance, diabetes and dyslipidemia. In addition to well-known metformin, there are new classes of antidiabetic drugs, including GLP-1analog, SGLT-2 antagonist, pioglitazon...
November 23, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29231260/metformin-inhibits-tumorigenesis-in-hbv-induced-hepatocellular-carcinoma-by-suppressing-hulc-overexpression-caused-by-hbx
#6
Zhen Jiang, Haichao Liu
BACKGROUND: We aimed to understand whether metformin imposes the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway. METHOD: Luciferase assay, RT-PCR and western-blot, MTT and flow cytometry analysis were performed to understand and the mechanism, by which metformin enhance the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway. RESULT: HBX promoted viability of three types of cell lines, while metformin inhibited apoptosis of above two cells...
December 12, 2017: Journal of Cellular Biochemistry
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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