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Metformin pancreatic cancer

Wanxing Duan, Ke Chen, Zhengdong Jiang, Xin Chen, Liankang Sun, Jiahui Li, Jianjun Lei, Qinhong Xu, Jiguang Ma, Xuqi Li, Liang Han, Zheng Wang, Zheng Wu, Fengfei Wang, Erxi Wu, Qingyong Ma, Zhenhua Ma
Emerging evidence suggests that metformin, as an activator of AMP-activated protein kinase (AMPK), may be useful in preventing and treating PDAC. However, whether metformin has an effect on the stromal reaction of PDAC remains unknown. In this study, we first evaluated the expression of AMPK and phosphorylated-AMPK (P-AMPK) in normal and PDAC tissues, our data indicate that reduced P-AMPK expression is a frequent event in PDAC and correlated with poor prognosis and the dense stromal reaction. We then determined the efficacy of metformin on PDAC growth in vitro and in vivo...
October 20, 2016: Cancer Letters
A Kautzky-Willer, S Thurner, P Klimek
AIM: There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population. METHODS: Medical claims data of 1 847 051 patients with hospital stays during 2006-2007 were used to estimate age- and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins...
October 21, 2016: Journal of Internal Medicine
Stepana Boukalova, Jan Stursa, Lukas Werner, Zuzana Ezrova, Jiri Cerny, Ayenachew Bezawork-Geleta, Alena Pecinova, Lanfeng Dong, Zdenek Drahota, Jiri Neuzil
Pancreatic cancer is one of the hardest-to-treat types of neoplastic diseases. Metformin, a widely prescribed drug against type 2 diabetes mellitus, is being trialed as an agent against pancreatic cancer, although its efficacy is low. With the idea of delivering metformin to its molecular target, the mitochondrial complex I (CI), we tagged the agent with the mitochondrial vector, triphenylphosphonium group. Mitochondrially targeted metformin (MitoMet) was found to kill a panel of pancreatic cancer cells 3-4 orders of magnitude more efficiently than found for the parental compound...
October 7, 2016: Molecular Cancer Therapeutics
M B Rehman, B V Tudrej, J Soustre, M Buisson, P Archambault, D Pouchain, H Vaillant-Roussel, F Gueyffier, J-L Faillie, M-C Perault-Pochat, C Cornu, R Boussageon
BACKGROUND: Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial...
October 10, 2016: Diabetes & Metabolism
Mengmeng Zhu, Qiong Zhang, Xiaoling Wang, Licheng Kang, Yinan Yang, Yuansheng Liu, Lei Yang, Jing Li, Liang Yang, Jie Liu, Yin Li, Lingling Zu, Yanna Shen, Zhi Qi
Our previous study showed that resveratrol (RSV) exhibited not only anti-tumor effect, but also had potential tumor promotion effect on pancreatic cancer (Paca) cells through up-regulation of VEGF-B. We determined whether metformin (MET) could potentiate the anti-tumor effect of RSV on PaCa in this study. Combination of RSV (100 μmol/l) and MET (20 mmol/l) significantly inhibited tumor growth and increased apoptosis of human PaCa in comparison with RSV or MET alone treatment in PaCa cell lines (Miapaca-2, Panc-1 and Capan-2)...
October 1, 2016: Oncotarget
Ming-Jie Jiang, Juan-Juan Dai, Dian-Na Gu, Qian Huang, Ling Tian
Pancreatic cancer is one of the most aggressive malignancies with dismal prognosis. Recently, aspirin has been found to be an effective chemopreventive agent for many solid tumors. However, the function of aspirin use in pancreatic cancer largely remains unknown. We herein argued that aspirin could also lower the risk of pancreatic cancer. Importantly, aspirin assumes pleiotropic effects by targeting multiple molecules. It could further target the unique tumor biology of pancreatic cancer and modify the cancer microenvironment, thus showing remarkable therapeutic potentials...
August 24, 2016: Biochimica et Biophysica Acta
Sunil Amin, Paolo Boffetta, Aimee L Lucas
Survival from pancreatic cancer remains poor. Conventional treatment has resulted in only marginal improvements in survival compared with survival in the previous several decades. Thus, considerable interest has emerged regarding the potential use of common pharmaceutical agents as chemopreventative and chemotherapeutic options. Aspirin, metformin, statins, β-blockers, and bisphosphonates have biologically plausible mechanisms to inhibit pancreatic neoplasia, whereas dipeptidyl-peptidase 4 inhibitors may promote it...
September 15, 2016: Gut and Liver
Amira Elgogary, Qingguo Xu, Brad Poore, Jesse Alt, Sarah C Zimmermann, Liang Zhao, Jie Fu, Baiwei Chen, Shiyu Xia, Yanfei Liu, Marc Neisser, Christopher Nguyen, Ramon Lee, Joshua K Park, Juvenal Reyes, Thomas Hartung, Camilo Rojas, Rana Rais, Takashi Tsukamoto, Gregg L Semenza, Justin Hanes, Barbara S Slusher, Anne Le
Targeting glutamine metabolism via pharmacological inhibition of glutaminase has been translated into clinical trials as a novel cancer therapy, but available drugs lack optimal safety and efficacy. In this study, we used a proprietary emulsification process to encapsulate bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a selective but relatively insoluble glutaminase inhibitor, in nanoparticles. BPTES nanoparticles demonstrated improved pharmacokinetics and efficacy compared with unencapsulated BPTES...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yuqi Shi, Zhilong He, Zhenyu Jia, Chunfang Xu
Pancreatic cancer is a malignant digestive system tumor with a particularly poor prognosis, and is the fourth leading cause of cancer‑associated mortality in the USA. The anti‑diabetic therapeutic agent, metformin (MET) has been demonstrated to exert anti‑tumor effects. The present study assessed the ability of MET, alone or in combination with gemcitabine (GEM), to inhibit the growth of the human CFPAC‑1 pancreatic cancer cell line in vitro and in vivo. Cell counting kit‑8 assays were performed to measure CFPAC‑1 cell viability and apoptosis was detected with annexin V/propidium iodide...
October 2016: Molecular Medicine Reports
Dietmar Zechner, Florian Bürtin, Ann-Christin Albert, Xianbin Zhang, Simone Kumstel, Maria Schönrogge, Josefine Graffunder, Hao-Yu Shih, Sarah Müller, Tobias Radecke, Robert Jaster, Brigitte Vollmar
Cancer heterogeneity and microenvironmental aspects within a tumor are considered key factors influencing resistance of carcinoma cells to distinct chemotherapeutical agents. We evaluated a high concentration of metformin in combination with gemcitabine on a syngeneic orthotopic mouse model using 6606PDA cells. We observed reduced tumor size and reduced cancer cell proliferation after three weeks of chemotherapy with either compound and noticed an additive effect between gemcitabine and metformin on tumor weight...
July 28, 2016: Oncotarget
S Amin, G Mhango, J Lin, A Aronson, J Wisnivesky, P Boffetta, Aimee L Lucas
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity. METHODS: We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011...
September 2016: American Journal of Gastroenterology
İlhan Elmaci, Meric A Altinoz
Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L)...
October 2016: Biochemical Genetics
Marcelo Cerullo, Faiz Gani, Sophia Y Chen, Joe Canner, Timothy M Pawlik
Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected...
September 2016: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
Adriana Albini, Andrea DeCensi, Franco Cavalli, Alberto Costa
At several recent, internationally attended scientific meetings, including the American Association for Cancer Research (AACR)'s "Shaping the Future of Cancer Prevention: A Roadmap for Integrative Cancer Science and Public Health" summit in Leesburg (VA) and the AACR Annual Meeting in New Orleans, the focus on cancer prevention to reduce cancer-related deaths was extensively discussed with renewed attention and emphasis. Cancer prevention should be actively proposed even to healthy individuals, and not just to individuals with high cancer risk...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Gang Cheng, Jacek Zielonka, Olivier Ouari, Marcos Lopez, Donna McAllister, Kathleen Boyle, Christy S Barrios, James J Weber, Bryon D Johnson, Micael Hardy, Michael B Dwinell, Balaraman Kalyanaraman
Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its mitochondria-targeting potential by attaching a positively charged lipophilic substituent would enhance the antitumor activity of Met. In pursuit of this question, we synthesized a set of mitochondria-targeted Met analogues (Mito-Mets) with varying alkyl chain lengths containing a triphenylphosphonium cation (TPP(+))...
July 1, 2016: Cancer Research
Archana Bhaw-Luximon, Dhanjay Jhurry
PURPOSE: Three major chemotherapy strategies have emerged in the treatment of PDAC in the recent past: multiple drug combination, stroma depletion, and use of nanodrug therapy. Anti-diabetic metformin was shown to improve the outcome of a number of cancer types the first seminal report on an observational study published in 2005 and the first hospital-based case-control study on pancreatic cancer in 2009. METHODS: In this review paper, we confront the findings of a selected number of epidemiological studies and clinical trials on the use of metformin in pancreatic cancer treatment with basic knowledge and research...
October 2016: Journal of Cancer Research and Clinical Oncology
Hui-Hui Zhang, Xiu-Li Guo
Chemotherapeutic regimens are the most common treatment to inhibit tumor growth, but there is great variability in clinical responses of cancer patients; cancer cells often develop resistance to chemotherapeutics which results in tumor recurrence and further progression. Metformin, an extensively prescribed and well-tolerated first-line therapeutic drug for type 2 diabetes mellitus, has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutic drugs to improve treatment efficacy and lower doses...
July 2016: Cancer Chemotherapy and Pharmacology
Roongruedee Chaiteerakij, Gloria M Petersen, William R Bamlet, Kari G Chaffee, David B Zhen, Patrick A Burch, Emma R Leof, Lewis R Roberts, Ann L Oberg
PURPOSE: The inclusion of metformin in the treatment arms of cancer clinical trials is based on improved survival that has been demonstrated in retrospective epidemiologic studies; however, unintended biases may exist when analysis is performed by using a conventional Cox proportional hazards regression model with dichotomous ever/never categorization. We examined the impact of metformin exposure definitions, analytical methods, and patient selection on the estimated effect size of metformin exposure on survival in a large cohort of patients with pancreatic ductal adenocarcinoma (PDAC)...
June 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Chenwi M Ambe, Amit Mahipal, Jimmy Fulp, Lu Chen, Mokenge P Malafa
Observational studies have demonstrated that metformin use in diabetic patients is associated with reduced cancer incidence and mortality. Here, we aimed to determine whether metformin use was associated with improved survival in patients with resected pancreatic cancer. All patients with diabetes who underwent resection for pancreatic adenocarcinoma between 12/1/1986 and 4/30/2013 at our institution were categorized by metformin use. Survival analysis was done using the Kaplan-Meier method, with log-rank test and Cox proportional hazards multivariable regression models...
2016: PloS One
Chen Shen, Sun-O Ka, Su Jin Kim, Ji Hye Kim, Byung-Hyun Park, Ji Hyun Park
NANOG, a marker of stemness, impacts tumor progression and therapeutic resistance in cancer cells. In human hepatocellular carcinoma (HCC), upregulation of NANOG is associated with metastasis and a low survival rate, while its downregulation results in a lower colony formation rate and enhanced chemosensitivity. Metformin, an agent widely used for diabetes treatment, and AICAR, another AMP-activated protein kinase (AMPK) activator, have been reported to inhibit the growth of several types of cancer. Although inhibitory effects of metformin on NANOG in pancreatic cancer cells and of AICAR in mouse embryonic stem cells have been described, the underlying molecular mechanisms remain uncertain in HCC...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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