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hepatocellular carcinoma, metformin

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https://www.readbyqxmd.com/read/28290049/type-2-diabetes-and-hepatocellular-carcinoma-risk-factors-and-pathogenesis
#1
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
#2
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...
January 19, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28099155/metformin-promotes-apoptosis-in-hepatocellular-carcinoma-through-the-cebpd-induced-autophagy-pathway
#3
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...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#4
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: 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
#5
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
#6
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
https://www.readbyqxmd.com/read/27803295/strong-antineoplastic-effects-of-metformin-in-preclinical-models-of-liver-carcinogenesis
#7
François Cauchy, Mouniya Mebarki, Benjamin Leporq, Samira Laouirem, Miguel Albuquerque, Simon Lambert, Pierre Bourgoin, Olivier Soubrane, Bernard E Van Beers, Sandrine Faivre, Pierre Bedossa, Valérie Paradis
Studies suggest that metformin, widely used for treating Type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma (HCC), metformin may provide antitumoral effects. We evaluated the impact of metformin on tumour growth and visceral fat composition using relevant preclinical models of metabolic syndrome. Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow (SC) diet, 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured HCC slices...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27802188/metformin-enhances-the-radiosensitivity-of-human-liver-cancer-cells-to-%C3%AE-rays-and-carbon-ion-beams
#8
Eun Ho Kim, Mi-Sook Kim, Yoshiya Furusawa, Akiko Uzawa, Soorim Han, Won-Gyun Jung, Sei Sai
The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ-rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ-rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27775209/metformin-confers-risk-reduction-for-developing-hepatocellular-carcinoma-recurrence-after-liver-resection
#9
Kun-Ming Chan, Chang-Fu Kuo, Jun-Te Hsu, Meng-Jiun Chiou, Yu-Chao Wang, Tsung-Han Wu, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou, Wei-Chen Lee
BACKGROUND: Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study. METHODS: All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed...
March 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27642100/systematic-review-with-network-meta-analysis-antidiabetic-medication-and-risk-of-hepatocellular-carcinoma
#10
Yao-Yao Zhou, Gui-Qi Zhu, Tian Liu, Ji-Na Zheng, Zhang Cheng, Tian-Tian Zou, Martin Braddock, Shen-Wen Fu, Ming-Hua Zheng
Antidiabetic medication may modify the incidence of hepatocellular carcinoma (HCC). We aimed to compare the use of different antidiabetic strategies and the incidence of HCC. PubMed, Embase.com and Cochrane Library databases were searched up to 31 October 2015 and randomized controlled trials (RCTs), cohort studies or case-control studies were included for our analyses. A total of thirteen studies enrolling 481358 participants with 240678 HCC cases who received at least two different strategies were retrieved in this analysis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27621764/reversal-of-multidrug-resistance-of-hepatocellular-carcinoma-cells-by-metformin-through-inhibiting-nf-%C3%AE%C2%BAb-gene-transcription
#11
Wei Wu, Jun-Ling Yang, Yi-Lang Wang, Han Wang, Min Yao, Li Wang, Juan-Juan Gu, Yin Cai, Yun Shi, Deng-Fu Yao
AIM: To interfere with the activation of nuclear factor-κB (NF-κB) with metformin and explore its effect in reversing multidrug resistance (MDR) of hepatocellular carcinoma (HCC) cells. METHODS: Expression of P-glycoprotein (P-gp) and NF-κB in human HepG2 or HepG2/adriamycin (ADM) cells treated with pCMV-NF-κB-small interference RNA (siRNA) with or without metformin, was analyzed by Western blot or fluorescence quantitative PCR. Cell viability was tested by CCK-8 assay...
August 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27577068/sirolimus-and-metformin-synergistically-inhibit-hepatocellular-carcinoma-cell-proliferation-and-improve-long-term-survival-in-patients-with-hcc-related-to-hepatitis-b-virus-induced-cirrhosis-after-liver-transplantation
#12
Chuan Shen, Chenghong Peng, Baiyong Shen, Zhecheng Zhu, Ning Xu, Tao Li, Junjie Xie
Immunosuppressive agents used postoperatively after liver transplantation (LT) for hepatocellular carcinoma (HCC) favor recurrence and metastasis. Therefore, new effective immunosuppressants are needed. This retrospective study assessed combined sirolimus and metformin on survival of HCC patients after LT. In 2001-2013, 133 HCC patients with LT were divided into four groups: sirolimus and metformin combination (Sir+Met), sirolimus monotherapy (Sir), other immunosuppressants in diabetes mellitus (DM) patients without metformin (No Sir with DM), and other immunosuppressants in patients without DM (No Sir without DM)...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27468203/diabetes-mellitus-and-metformin-in-hepatocellular-carcinoma
#13
REVIEW
Koji Fujita, Hisakazu Iwama, Hisaaki Miyoshi, Joji Tani, Kyoko Oura, Tomoko Tadokoro, Teppei Sakamoto, Takako Nomura, Asahiro Morishita, Hirohito Yoneyama, Tsutomu Masaki
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects...
July 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27447552/metformin-requires-4e-bps-to-induce-apoptosis-and-repress-translation-of-mcl-1-in-hepatocellular-carcinoma-cells
#14
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...
July 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27439433/improving-treatment-and-liver-fibrosis-outcomes-with-metformin-in-hcv-hiv-co-infected-and-hcv-mono-infected-patients-with-insulin-resistance-study-protocol-for-a-randomized-controlled-trial
#15
Mary-Anne Doyle, Joel Singer, Terry Lee, Miriam Muir, Curtis Cooper
BACKGROUND: Approximately 180 million people worldwide, (3 % of the world's population) are infected with hepatitis C (HCV). Insulin resistance (IR) and type 2 diabetes (T2DM) are common extrahepatic manifestations of chronic HCV infection and associated with poor treatment and liver-related outcomes. The presence of these metabolic complications have been associated with poor response to interferon-based HCV antiviral therapy and increased risk of liver-related outcomes. Metformin, an insulin sensitizer is known to improve HCV treatment response and has been associated with a reduced risk of developing hepatocellular carcinoma (HCC)...
July 20, 2016: Trials
https://www.readbyqxmd.com/read/27405060/hepatic-b-cell-leukemia-3-promotes-hepatic-steatosis-and-inflammation-through-insulin-sensitive-metabolic-transcription-factors
#16
Nadine Gehrke, Marcus A Wörns, Yvonne Huber, Moritz Hess, Beate K Straub, Nadine Hövelmeyer, Ari Waisman, Yong Ook Kim, Detlef Schuppan, Peter R Galle, Jörn M Schattenberg
BACKGROUND & AIMS: The pathomechanisms underlying non-alcoholic fatty liver disease (NAFLD) and the involved molecular regulators are incompletely explored. The nuclear factor-kappa B (NF-κB)-cofactor gene B cell leukemia-3 (Bcl-3) plays a critical role in altering the transcriptional capacity of NF-κB - a key inducer of inflammation - but also of genes involved in cellular energy metabolism. METHODS: To define the role of Bcl-3 in non-alcoholic steatohepatitis (NASH), we developed a novel transgenic mouse model with hepatocyte-specific overexpression of Bcl-3 (Bcl-3(Hep)) and employed a high-fat, high-carbohydrate dietary feeding model...
December 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27326258/liver-label-retaining-cancer-cells-are-relatively-resistant-to-the-reported-anti-cancer-stem-cell-drug-metformin
#17
Hong-Wu Xin, Chenwi M Ambe, Tyler C Miller, Jin-Qiu Chen, Gordon W Wiegand, Andrew J Anderson, Satyajit Ray, John E Mullinax, Danielle M Hari, Tomotake Koizumi, Jessica D Godbout, Paul K Goldsmith, Alexander Stojadinovic, Udo Rudloff, Snorri S Thorgeirsson, Itzhak Avital
BACKGROUND & AIMS: Recently, we reported that liver Label Retaining Cancer Cells (LRCC) can initiate tumors with only 10 cells and are relatively resistant to the targeted drug Sorafenib, a standard of practice in advanced hepatocellular carcinoma (HCC). LRCC are the only cancer stem cells (CSC) isolated alive according to a stem cell fundamental function, asymmetric cell division. Metformin has been reported to preferentially target many other types of CSC of different organs, including liver...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27323827/metformin-mediates-resensitivity-to-5-fluorouracil-in-hepatocellular-carcinoma-via-the-suppression-of-yap
#18
Yu Tian, Bo Tang, Chengye Wang, Deguang Sun, Rixin Zhang, Nan Luo, Zhao Han, Rui Liang, Zhenming Gao, Liming Wang
Metformin plays an anti-proliferative role in tumor cells in many types of cancer. However, the correlation between metformin and sensitivity to chemotherapeutic agents in hepatocellular carcinoma (HCC) and the relevant mechanism are unclear. The present study showed that HCC patients with type 2 diabetes mellitus benefited from metformin administration, with a longer overall survival. Metformin resensitized Bel-7402/5-fluorouracil (Bel/Fu) cells to 5-fluorouracil (5-Fu) in vitro and in vivo, and the combination of metformin and 5-Fu inhibited cell proliferation, promoted cell apoptosis and induced G0/G1 cell cycle arrest in the Bel/Fu cells...
July 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27274280/metformin-induces-apoptosis-of-human-hepatocellular-carcinoma-hepg2-cells-by-activating-an-ampk-p53-mir-23a-foxa1-pathway
#19
Yunpeng Sun, Chonglin Tao, Xiaming Huang, Han He, Hongqi Shi, Qiyu Zhang, Huanhuan Wu
The antidiabetic drug metformin has been shown to possess antitumor functions in many types of cancers. Although studies have revealed its beneficial effects on the prognosis of hepatocellular carcinoma (HCC), the detailed molecular mechanism underlying this event remains largely unknown. In this work, we showed that miR-23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells. We next established forkhead box protein A1 (FOXA1) as the functional target of miR-23a, and silencing FOXA1 mimicked the effect of metformin...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27124061/association-of-metformin-use-with-cancer-specific-mortality-in-hepatocellular-carcinoma-after-curative-resection-a-nationwide-population-based-study
#20
Young-Seok Seo, Yun-Jung Kim, Mi-Sook Kim, Kyung-Suk Suh, Sang Bum Kim, Chul Ju Han, Youn Joo Kim, Won Il Jang, Shin Hee Kang, Ha Jin Tchoe, Chan Mi Park, Ae Jung Jo, Hyo Jeong Kim, Jin A Choi, Hyung Jin Choi, Michael N Polak, Min Jung Ko
Many preclinical reports and retrospective population studies have shown an anticancer effect of metformin in patients with several types of cancer and comorbid type 2 diabetes mellitus (T2DM). In this work, the anticancer effect of metformin was assessed in hepatocellular carcinoma (HCC) patients with T2DM who underwent curative resection.A population-based retrospective cohort design was used. Data were obtained from the National Health Insurance Service and Korea Center Cancer Registry in the Republic of Korea, identifying 5494 patients with newly diagnosed HCC who underwent curative resection between 2005 and 2011...
April 2016: Medicine (Baltimore)
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