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Metformin breast cancer

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https://www.readbyqxmd.com/read/28193239/buformin-inhibits-the-stemness-of-erbb-2-overexpressing-breast-cancer-cells-and-premalignant-mammary-tissues-of-mmtv-erbb-2-transgenic-mice
#1
Amanda B Parris, Qingxia Zhao, Erin W Howard, Ming Zhao, Zhikun Ma, Xiaohe Yang
BACKGROUND: Metformin, an FDA-approved drug for the treatment of Type II diabetes, has emerged as a promising anti-cancer agent. Other biguanide analogs, including buformin and phenformin, are suggested to have similar properties. Although buformin was shown to reduce mammary tumor burden in carcinogen models, the anti-cancer effects of buformin on different breast cancer subtypes and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the effects of buformin on erbB-2-overexpressing breast cancer with in vitro and in vivo models...
February 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28169131/association-of-dipeptidyl-peptidase-4-inhibitors-with-risk-of-metastases-in-patients-with-type-2-diabetes-and-breast-prostate-or-digestive-system-cancer
#2
Wolfgang Rathmann, Karel Kostev
AIMS: Experimental and animal studies have supported the hypothesis that dipeptidyl peptidase-4 inhibitors (DPP-4i) may accelerate tumor metastasis. The aim was to analyze the relationships between DPP-4i therapy with risk of metastases in type 2 diabetes patients with breast, prostate and digestive organ cancers. METHODS: Type 2 diabetes patients with first diagnoses of breast, prostate or digestive organ cancer were selected in general and internal medicine practices (Disease Analyzer Germany: 01/2008-12/2014)...
January 26, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28166101/comparative-effect-of-initiating-metformin-versus-sulfonylureas-on-breast-cancer-risk-in-older-women
#3
Jin-Liern Hong, Michele Jonsson Funk, John Buse, Louise M Henderson, Jennifer L Lund, Virginia Pate, Til Stürmer
BACKGROUND: Several observational studies have reported that metformin may be associated with reduced risk of breast cancer; however, many of these studies were affected by time-related biases such as immortal time bias and time-window bias. This study aimed to examine the relative risk of breast cancer for older women initiating metformin versus sulfonylureas while avoiding such biases. METHODS: The study cohort consisted of women aged 65+ who initiated monotherapy with metformin (n=45,900) or sulfonylureas (n=13,904) and were free of cancer and renal disease within 6 months before treatment initiation using 2007-2012 US Medicare claims data...
February 3, 2017: Epidemiology
https://www.readbyqxmd.com/read/28154203/metformin-accumulation-correlates-with-organic-cation-transporter-2-protein-expression-and-predicts-mammary-tumor-regression-in-vivo
#4
L Allyson Checkley, Michael C Rudolph, Elizabeth A Wellberg, Erin D Giles, Reema S Wahdan-Alaswad, Julie A Houck, Susan M Edgerton, Ann D Thor, Pepper Schedin, Steven M Anderson, Paul S MacLean
Several epidemiologic studies have associated metformin treatment with a reduction in breast cancer incidence in prediabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiologic reports consistently link western-style high fat diets (HFD), which drive overweight and obesity, with increased risk of breast cancer...
February 2, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28128472/effects-on-energy-metabolism-of-two-guanidine-molecules-boc-2-creatine-and-metformin
#5
Patrizia Garbati, Silvia Ravera, Sonia Scarfì, Annalisa Salis, Camillo Rosano, Alessandro Poggi, Gianluca Damonte, Enrico Millo, Maurizio Balestrino
Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc)2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc)2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism...
January 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28078601/inhibition-of-epithelial-mesenchymal-transition-and-metastasis-by-combined-tgfbeta-knockdown-and-metformin-treatment-in-a-canine-mammary-cancer-xenograft-model
#6
Camila Leonel, Thaiz Ferraz Borin, Lívia de Carvalho Ferreira, Marina Gobbe Moschetta, Marcio Chaim Bajgelman, Alicia M Viloria-Petit, Debora Aparecida Pires de Campos Zuccari
Epithelial mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce EMT. Metformin, has been shown to inhibit EMT in breast cancer cells. Based on this evidence we hypothesize that treatment with metformin and the silencing of TGF-β, inhibits the EMT in cancer cells. Canine metastatic mammary tumor cell line CF41 was stably transduced with a shRNA-lentivirus, reducing expression level of TGF-β1...
January 11, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28052008/targeting-p-glycoprotein-function-p53-and-energy-metabolism-combination-of-metformin-and-2-deoxyglucose-reverses-the-multidrug-resistance-of-mcf-7-dox-cells-to-doxorubicin
#7
Chaojun Xue, Changyuan Wang, Yaoting Sun, Qiang Meng, Zhihao Liu, Xiaokui Huo, Pengyuan Sun, Huijun Sun, Xiaodong Ma, Xiaochi Ma, Jinyong Peng, Kexin Liu
Multidrug resistance(MDR) is a major obstacle to efficiency of breast cancer chemotherapy. We investigated whether combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced cytotoxicity of doxorubicin against MCF-7/Dox cells. Combination of the two drugs resumed p53 function via inhibiting overexpression of murine doubleminute 2(MDM2) and murine doubleminute 4(MDM4) leading to G2/M arrest and apoptosis in MCF-7/Dox cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28042775/inhibition-of-epithelial-mesenchymal-transition-in-response-to-treatment-with-metformin-and-y27632-in-breast-cancer-cell-lines
#8
Camila Leonel, Lívia Carvalho Ferreira, Thaiz Ferraz Borin, Marina Gobbe Moschetta, Gabriela Scavacini Freitas, Michel Raineri Haddad, João Antonio de Camargos Pinto Robles, Debora Aparecida Pires de Campos Zuccari
BACKGROUND: ROCK-1 expression is associated with the malignant character of tumors, while inhibiting this molecule results in a significant suppression of tumor metastasis. Likewise, transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce epithelial-mesenchymal transition (EMT). Metformin, a drug used in the treatment of diabetes, has previously been shown to inhibit EMT in breast cancer cells. OBJECTIVE: The aim of this study is to evaluate the TGF-β1 action model for induction of EMT and the action of metformin and ROCK-1 inhibitor (Y27632) in EMT process in breast cancer cell lines...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28035400/ampk-activators-suppress-breast-cancer-cell-growth-by-inhibiting-dvl3-facilitated-wnt-%C3%AE-catenin-signaling-pathway-activity
#9
Yu-Feng Zou, Chun-Wei Xie, Shi-Xin Yang, Jian-Ping Xiong
Adenosine monophosphate-activated protein kinase (AMPK) is a principal regulator of metabolism and the conservation of energy in cells, and protects them from exposure to various stressors. AMPK activators may exhibit therapeutic potential as suppressors of cell growth; however, the molecular mechanism underlying this phenomenon in various cancer cells remains to be fully elucidated. The present study investigated the effects of AMPK activators on breast cancer cell growth and specified the underlying molecular mechanism...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27990091/novel-applications-of-cox-2-inhibitors-metformin-and-statins-for-the-primary-chemoprevention-of-breast-cancer
#10
REVIEW
Darren Micallef, Sarah Micallef, Pierre Schembri-Wismayer, Jean Calleja-Agius
Recent evidence shows that commonly prescribed drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), metformin, and statins, may have beneficial roles in the primary chemoprevention of breast cancer. Therefore, these drugs could potentially be used in addition to the hormonal drugs currently used for this purpose (namely, selective estrogen receptor modulators and aromatase inhibitors) due to their alternative mechanisms of action.
2016: Journal of the Turkish German Gynecological Association
https://www.readbyqxmd.com/read/27984108/the-effect-of-metformin-use-during-docetaxel-chemotherapy-on-prostate-cancer-specific-and-overall-survival-of-diabetic-castration-resistant-prostate-cancer-patients
#11
Michelle J Mayer, Laurence H Klotz, Vasundara Venkateswaran
PURPOSE: Docetaxel is the first-line chemotherapy currently used to treat symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients. Although it provides survival benefits it is associated with significant side effects. Novel therapeutic options are needed for mCRPC patients and one approach is combining docetaxel with chemosensitizing agents. Metformin has been shown to improve the survival of patients receiving chemotherapy in breast, lung, and endometrial cancer and enhance chemotherapeutic efficacy in breast cancer and colon cancer cells...
October 27, 2016: Journal of Urology
https://www.readbyqxmd.com/read/27936468/rosiglitazone-reduces-breast-cancer-risk-in-taiwanese-female-patients-with-type-2-diabetes-mellitus
#12
Chin-Hsiao Tseng
This study investigated whether rosiglitazone may affect breast cancer risk in female patients with type 2 diabetes mellitus in Taiwan. The reimbursement database of all female patients with type 2 diabetes mellitus under oral antidiabetic agents or insulin from 1996 to 2009 was retrieved from the National Health Insurance. An entry date was set on 1 January 2006 and a total of 431447 patients were followed up for breast cancer incidence till the end of 2009. Incidences for ever users, never users and subgroups of rosiglitazone dose-response parameters (tertile cutoffs of cumulative duration and cumulative dose) were calculated and hazard ratios estimated by Cox regression...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27926515/metformin-and-propranolol-combination-prevents-cancer-progression-and-metastasis-in-different-breast-cancer-models
#13
María Rico, María Baglioni, Maryna Bondarenko, Nahuel Cesatti Laluce, Viviana Rozados, Nicolas André, Manon Carré, O Graciela Scharovsky, Mauricio Menacho Márquez
Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite low.Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy.In this work, we evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models.By in vitro studies with five different breast cancer derived cells, we observed that combined treatment decreased proliferation (P < 0...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27908558/time-varying-risk-for-breast-cancer-following-initiation-of-glucose-lowering-therapy-in-women-with-type-2-diabetes-exploring-detection-bias
#14
Samantha L Bowker, Mu Lin, Dean T Eurich, Jeffrey A Johnson
OBJECTIVES: To explore detection bias in the association between glucose-lowering therapies and breast cancer in a cohort of women with type 2 diabetes. METHODS: This was a retrospective, population-based cohort study. We identified new users of metformin, sulfonylureas, thiazolidinediones and insulin during the index period of January 1, 2003, to December 31, 2010. The main outcome was incident breast cancer, and patients were followed up from drug exposure index date until death, diagnosis of another type of cancer, termination of medical insurance or December 31, 2010...
November 29, 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/27903149/obesity-and-breast-cancer-prognosis-evidence-challenges-and-opportunities
#15
Sao Jiralerspong, Pamela J Goodwin
Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27779715/mir-27a-mediated-antiproliferative-effects-of-metformin-on-the-breast-cancer-cell-line-mcf-7
#16
Wei Zhao, Xiaohui Zhang, Jia Liu, Bei Sun, Hua Tang, Hong Zhang
Metformin was demonstrated to have effects on breast cancer, and microRNA-27a (miR-27a) is a prognostic marker for breast cancer progression and patient survival. AMPKα2 was found to be a suppressor in breast cancer MCF-7 cells. Therefore, the present study aimed to explain this phenomenon in regards to the relationship between microRNAs (miRNAs) and their target genes and to predict how AMPKα2 may be a downstream target gene of miR-27a, thus exploring the new mechanism of metformin in the treatment of breast cancer regarding miRNAs...
December 2016: Oncology Reports
https://www.readbyqxmd.com/read/27753529/cyclin-g2-promotes-cell-cycle-arrest-in-breast-cancer-cells-responding-to-fulvestrant-and-metformin-and-correlates-with-patient-survival
#17
Maike Zimmermann, Aruni P S Arachchige-Don, Michaela S Donaldson, Tommaso Patriarchi, Mary C Horne
Definition of cell cycle control proteins that modify tumor cell resistance to estrogen (E2) signaling antagonists could inform clinical choice for estrogen receptor positive (ER+) breast cancer (BC) therapy. Cyclin G2 (CycG2) is upregulated during cell cycle arrest responses to cellular stresses and growth inhibitory signals and its gene, CCNG2, is directly repressed by E2-bound ER complexes. Our previous studies showed that blockade of HER2, PI3K and mTOR signaling upregulates CycG2 expression in HER2+ BC cells, and that CycG2 overexpression induces cell cycle arrest...
December 2016: Cell Cycle
https://www.readbyqxmd.com/read/27748082/metformin-induces-degradation-of-mtor-protein-in-breast-cancer-cells
#18
Mohamed Alalem, Alpana Ray, Bimal K Ray
Activation of mTOR is implicated in the development and progression of breast cancer. mTOR inhibition exhibited promising antitumor effects in breast cancer; however, its effect is compromised by several feedback mechanisms. One of such mechanisms is the upregulation of mTOR pathway in breast cancer cells. Despite the established role of mTOR activation in breast cancer, the status of total mTOR protein and its impact on the tumor behavior and response to treatment are poorly understood. Besides, the mechanisms underlying mTOR protein degradation in normal and cancer breast cells are still largely unknown...
November 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27724912/risk-factors-for-cancer-development-in-type-2-diabetes-a-retrospective-case-control-study
#19
Mariusz Dąbrowski, Elektra Szymańska-Garbacz, Zofia Miszczyszyn, Tadeusz Dereziński, Leszek Czupryniak
BACKGROUND: The risk of several types of cancer is increased in type 2 diabetes mellitus. The earliest possible diagnosis of cancer - difficult within regular outpatient diabetes care - is of utmost importance for patients' survival. The aim of this multicenter, retrospective (years 1998-2015), case-control study was to identify risk factors associated with malignancy in subjects with diabetes treated in a typical outpatient setting. METHODS: In the databases of 3 diabetic and 1 primary care clinics 203 patients (115 women) with type 2 diabetes mellitus who developed malignancy while treated for diabetes were identified...
October 10, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27708283/obesity-associated-nlrc4-inflammasome-activation-drives-breast-cancer-progression
#20
Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M Janowski, Qing Xie, Kathleen R Markan, Wei Li, Matthew J Potthoff, Enrique Fuentes-Mattei, Lesley G Ellies, C Michael Knudson, Mong-Hong Lee, Sai-Ching J Yeung, Suzanne L Cassel, Fayyaz S Sutterwala, Weizhou Zhang
Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis...
October 6, 2016: Nature Communications
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