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Metformin and breast cancer

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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
#1
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
#2
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...
December 30, 2016: 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
#3
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
#4
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
#5
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
#6
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
#7
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...
December 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926515/metformin-and-propranolol-combination-prevents-cancer-progression-and-metastasis-in-different-breast-cancer-models
#8
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...
December 1, 2016: 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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27681864/metformin-as-an-adjuvant-treatment-for-cancer-a-systematic-review-and-meta-analysis
#16
REVIEW
C Coyle, F H Cafferty, C Vale, R E Langley
BACKGROUND: Metformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented. PATIENTS AND METHODS: We systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer...
December 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27648070/the-association-between-treatment-for-metabolic-disorders-and-breast-cancer-characteristics
#17
Hadar Goldvaser, Shulamith Rizel, Daniel Hendler, Victoria Neiman, Daniel Shepshelovich, Tzippy Shochat, Aaron Sulkes, Baruch Brenner, Rinat Yerushalmi
Purpose. To evaluate the associations between metformin, insulin, statins, and levothyroxine and breast cancer characteristics and outcome. Methods. Retrospective chart review of patients treated in our institute for early estrogen receptor (ER) positive, human epidermal growth factor receptor 2 negative breast cancer, whose tumors were sent to Oncotype DX (ODX) analysis. Patients were grouped according to medications usage during the time of breast cancer diagnosis. Each group was compared to the rest of the study population...
2016: International Journal of Endocrinology
https://www.readbyqxmd.com/read/27616566/metformin-pharmacogenomics-a-genome-wide-association-study-to-identify-genetic-and-epigenetic-biomarkers-involved-in-metformin-anticancer-response-using-human-lymphoblastoid-cell-lines
#18
Nifang Niu, Tongzheng Liu, Junmei Cairns, Reynold C Ly, Xianglin Tan, Min Deng, Brooke L Fridley, Krishna R Kalari, Ryan P Abo, Gregory Jenkins, Anthony Batzler, Erin E Carlson, Poulami Barman, Sebastian Moran, Holger Heyn, Manel Esteller, Liewei Wang
Metformin is currently considered as a promising anticancer agent in addition to its anti-diabetic effect. To better individualize metformin therapy and explore novel molecular mechanisms in cancer treatment, we conducted a pharmacogenomic study using 266 lymphoblastoid cell lines (LCLs). Metformin cytotoxicity assay was performed using the MTS assay. Genome-wide association (GWA) analyses were performed in LCLs using 1.3 million SNPs, 485k DNA methylation probes, 54k mRNA expression probe sets, and metformin cytotoxicity (IC50s)...
September 11, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27569287/trail-restores-dca-metformin-mediated-cell-death-in-hypoxia
#19
Sung-Eun Hong, Chang Soon Kim, Sungkwan An, Hyun-Ah Kim, Sang-Gu Hwang, Jie-Young Song, Jin Kyung Lee, Jungil Hong, Jong-Il Kim, Woo Chul Noh, Hyeon-Ok Jin, In-Chul Park
Previous studies have shown that hypoxia can reverse DCA/metformin-induced cell death in breast cancer cells. Therefore, targeting hypoxia is necessary for therapies targeting cancer metabolism. In the present study, we found that TRAIL can overcome the effect of hypoxia on the cell death induced by treatment of DCA and metformin in breast cancer cells. Unexpectedly, DR5 is upregulated in the cells treated with DCA/metformin, and sustained under hypoxia. Blocking DR5 by siRNA inhibited DCA/metformin/TRAIL-induced cell death, indicating that DR5 upregulation plays an important role in sensitizing cancer cells to TRAIL-induced cell death...
September 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27517917/the-antitumor-effect-of-metformin-is-mediated-by-mir-26a-in-breast-cancer
#20
Paula Cabello, Begoña Pineda, Eduardo Tormo, Ana Lluch, Pilar Eroles
Metformin, a drug approved for diabetes type II treatment, has been associated with a reduction in the incidence of breast cancer and metastasis and increased survival in diabetic breast cancer patients. High levels of miR-26a expression have been proposed as one of the possible mechanisms for this effect; likewise, this miRNA has also been associated with survival/apoptosis processes in breast cancer. Our aim was to evaluate if miR-26a and some of its targets could mediate the effect of metformin in breast cancer...
August 10, 2016: International Journal of Molecular Sciences
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