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Metformin anti-cancer

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https://www.readbyqxmd.com/read/29665787/valproic-acid-sensitizes-metformin-resistant-human-renal-cell-carcinoma-cells-by-upregulating-h3-acetylation-and-emt-reversal
#1
Muyun Wei, Shaowei Mao, Guoliang Lu, Liang Li, Xiaopeng Lan, Zhongxian Huang, Yougen Chen, Miaoqing Zhao, Yueran Zhao, Qinghua Xia
BACKGROUND: Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear...
April 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29663879/anti-cancer-effects-of-metformin-recent-evidences-for-its-role-in-prevention-and-treatment-of-cancer
#2
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Warda Kamal, Mohammad A Kamal
Metformin is widely used for the management of type 2 diabetes mellitus (T2DM). Recently growing evidence has shown its anti-cancer effects. The results are mainly obtained from observational studies and thus, little information is available concerning the mechanisms of action. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays an important role in the mechanism of action of metformin. The anti-cancer mechanisms of metformin include direct and indirect effects. The direct effects of metformin include AMPK-independent and AMPK-dependent effects, whereas the decrease in glucose level, hyperinsulinemia, and Insulin-like growth factor 1 (IGF-1) level was considered its indirect effects...
April 16, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29662316/metformin-inhibits-proliferation-and-cytotoxicity-and-induces-apoptosis-via-ampk-pathway-in-cd19-chimeric-antigen-receptor-modified-t-cells
#3
Qian Mu, Miao Jiang, Yuzhu Zhang, Fei Wu, Hui Li, Wen Zhang, Fang Wang, Jiang Liu, Liang Li, Dongshan Wang, Wenjuan Wang, Shiwu Li, Haibo Song, Dongqi Tang
Background: CD19-chimericantigen receptor (CAR) modified T cells (CD19-CAR T cells) have been well documented to possess potent anti-tumor properties against CD19-expressingleukemia cells. As a traditional medicine, metformin has been widely used to treat type II diabetes mellitus and more recently has become a candidate for the treatment of cancer. However, no report has revealed the direct effect of metformin on CD19-CAR T cell biological function and its underling mechanisms. Purpose: The purpose of this research was to explore the effect of metformin on CD19-CAR T cell biological function and the mechanisms involved...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29655834/metformin-use-associates-with-longer-progression-free-survival-of-patients-with-diabetes-and-pancreatic-neuroendocrine-tumors-receiving-everolimus-and-or-somatostatin-analogues
#4
Sara Pusceddu, Claudio Vernieri, Massimo Di Maio, Riccardo Marconcini, Francesca Spada, Sara Massironi, Toni Ibrahim, Maria Pia Brizzi, Davide Campana, Antongiulio Faggiano, Dario Giuffrida, Maria Rinzivillo, Sara Cingarlini, Francesca Aroldi, Lorenzo Antonuzzo, Rossana Berardi, Laura Catena, Chiara De Divitiis, Paola Ermacora, Vittorio Perfetti, Annalisa Fontana, Paola Razzore, Carlo Carnaghi, Maria Vittoria Davì, Carolina Cauchi, Marilina Duro, Sergio Ricci, Nicola Fazio, Federica Cavalcoli, Alberto Bongiovanni, Anna La Salvia, Nicole Brighi, Annamaria Colao, Ivana Puliafito, Francesco Panzuto, Silvia Ortolani, Alberto Zaniboni, Francesco Di Costanzo, Mariangela Torniai, Emilio Bajetta, Salvatore Tafuto, Silvio Ken Garattini, Daniela Femia, Natalie Prinzi, Laura Concas, Giuseppe Lo Russo, Massimo Milione, Luca Giacomelli, Roberto Buzzoni, Gianfranco Delle Fave, Vincenzo Mazzaferro, Filippo de Braud
BACKGROUND & AIMS: Metformin seems to have anti-cancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with NETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy, from 1999 through 2015...
April 12, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29627688/chemosensitizing-effects-of-metformin-on-cisplatin-and-paclitaxel-resistant-ovarian-cancer-cell-lines
#5
Isabella Dos Santos Guimarães, Taciane Ladislau-Magescky, Nayara Gusmão Tessarollo, Diandra Zipinotti Dos Santos, Etel Rodrigues Pereira Gimba, Cinthya Sternberg, Ian Victor Silva, Leticia Batista Azevedo Rangel
BACKGROUND: Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy. Primary cytoreductive surgery with adjuvant taxane-platinum chemotherapy is the standard treatment to fight ovarian cancer, however, their side effects are severe, and chemoresistance emerges at high rates. Therefore, EOC clinic urges for novel treatment strategies to reverse chemoresistance and to improve the survival rates. Metformin has been shown to act in synergy with certain anti-cancer agents, overcoming chemoresistance in various types of tumors...
November 21, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29617321/exosome-mediated-transfer-of-cancer-cell-resistance-to-antiestrogen-drugs
#6
Svetlana E Semina, Alexander M Scherbakov, Anna A Vnukova, Dmitry V Bagrov, Evgeniy G Evtushenko, Vera M Safronova, Daria A Golovina, Ludmila N Lyubchenko, Margarita V Gudkova, Mikhail A Krasil'nikov
Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery...
April 4, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29610032/personalized-prevention-in-high-risk-individuals-managing-hormones-and-beyond
#7
D Gareth Evans, Sacha J Howell, Anthony Howell
Increasing numbers of women are being identified at 'high-risk' of breast cancer, defined by The National Institute of Health and Care Excellence (NICE) as a 10-year risk of ≥8%. Classically women have been so identified through family history based risk algorithms or genetic testing of high-risk genes. Recent research has shown that assessment of mammographic density and single nucleotide polymorphisms (SNPs), when combined with established risk factors, trebles the number of women reaching the high risk threshold...
March 30, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29609037/%C3%AE-cyano-4-hydroxycinnamate-impairs-pancreatic-cancer-cells-by-stimulating-the-p38-signaling-pathway
#8
Maria Schönrogge, Hagen Kerndl, Xianbin Zhang, Simone Kumstel, Brigitte Vollmar, Dietmar Zechner
Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death...
March 30, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29573032/visualizing-the-effects-of-metformin-on-tumor-growth-vascularity-and-metabolism-in-head-and-neck-cancer
#9
Aparajita Verma, Laurie J Rich, Vincent Chong Vui King, Mukund Seshadri
BACKGROUND: The anti-diabetic drug Metformin (Met) is believed to inhibit tumor proliferation by altering the metabolism of cancer cells. In this study, we examined the effects of on tumor oxygenation, metabolism and growth in head and neck squamous cell carcinoma (HNSCC) using non-invasive multimodal imaging MATERIALS AND METHODS: Severe combined immunodeficient (SCID) mice bearing orthotopic FaDu HNSCC xenografts were treated with Met (200 mg/kg, i.p.) once daily for 5 days. Tumor oxygen saturation (%sO2 ) and hemoglobin concentration (HbT) were measured using photoacoustic imaging (PAI)...
March 23, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29558957/prognostic-value-of-metformin-for-non-small-cell-lung-cancer-patients-with-diabetes
#10
Tongbai Xu, Dongsheng Li, Yuan He, Fuliang Zhang, Man Qiao, Yanhua Chen
BACKGROUND: The anti-cancer role of metformin has been reported in many different kinds of solid tumors, but how it affects non-small cell lung cancer (NSCLC) is currently elusive. The aim of this study was to investigate the influence of metformin treatment on diabetic NSCLC. METHODS: Two hundred fifty-five patients of diabetic NSCLC receiving therapy in our hospital from 2014 to 2016 were enrolled in our study. The information on clinical diagnosis, pathology, and prognosis as well as the influence of metformin in diabetic NSCLC were collected and assessed...
March 20, 2018: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29554968/metformin-induces-autophagy-and-g0-g1-phase-cell-cycle-arrest-in-myeloma-by-targeting-the-ampk-mtorc1-and-mtorc2-pathways
#11
Yan Wang, Wenbin Xu, Zixun Yan, Weili Zhao, Jianqing Mi, Junmin Li, Hua Yan
BACKGROUND: Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the underlying molecular mechanisms have not been clearly elucidated. METHODS: The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29549214/does-a-prostate-cancer-diagnosis-affect-management-of-pre-existing-diabetes-results-from-pcbase-sweden-a-nationwide-cohort-study
#12
Danielle Crawley, Hans Garmo, Sarah Rudman, Pär Stattin, Björn Zethelius, Jo Armes, Lars Holmberg, Jan Adolfsson, Mieke Van Hemelrijck
OBJECTIVES: Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment. SETTING: This study uses observational data from Prostate Cancer database Sweden Traject. PARTICIPANTS: The study was undertaken in a cohort of 16 778 men with T2DM, of whom 962 were diagnosed with PCa during mean follow-up of 2...
March 16, 2018: BMJ Open
https://www.readbyqxmd.com/read/29540614/obesity-promotes-resistance-to-anti-vegf-therapy-in-breast-cancer-by-up-regulating-il-6-and-potentially-fgf-2
#13
Joao Incio, Jennifer A Ligibel, Daniel T McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M Chin, Trupti D Vardam, Yuhui Huang, Nuh N Rahbari, Sylvie Roberge, Dannie Wang, Igor L Gomes-Santos, Stefan B Puchner, Christopher L Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M Tolaney, Ian E Krop, Dan G Duda, Yves Boucher, Dai Fukumura, Rakesh K Jain
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment...
March 14, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29524400/ampk-activation-by-pterostilbene-contributes-to-suppression-of-hepatic-gluconeogenic-gene-expression-and-glucose-production-in-h4iie-cells
#14
Guang Ren, Agnes M Rimando, Suresh T Mathews
Pterostilbene, a bioactive component of blueberries and grapes, shows structural similarity to resveratrol, and exhibits antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, and cholesterol lowering effects. Recent evidence indicates that pterostilbene is an agonist of the nuclear receptor, peroxisome proliferator-activated receptor-alpha (PPAR-α). Since PPAR-α agonists induce peroxisomal proliferation and fatty acid oxidation, we examined gene expression of acyl CoA oxidase (ACO) and carnitine palmitoyl transferase-1 (CPT-1)...
April 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29512924/down-regulation-of-pkm2-enhances-anticancer-efficiency-of-thp-on-bladder-cancer
#15
Qiongli Su, Ting Tao, Lei Tang, Jun Deng, Kwame Oteng Darko, Sichun Zhou, Mei Peng, Shanping He, Qing Zeng, Alex F Chen, Xiaoping Yang
Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non-muscle-invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down-regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches...
March 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29496445/deficiency-of-atg6-impairs-beneficial-effect-of-metformin-on-intestinal-stem-cell-aging-in-drosophila
#16
Hyun-Jin Na, Jung-Hoon Pyo, Ho-Jun Jeon, Joung-Sun Park, Hae-Young Chung, Mi-Ae Yoo
Age-related changes of adult stem cell are crucial for tissue aging and age-related diseases. Thus, clarifying mechanisms to prevent adult stem cell aging is indispensable for healthy aging. Metformin, a drug for type 2 diabetes, has been highlighted for its anti-aging and anti-cancer effect. In Drosophila intestinal stem cell (ISC), we previously reported the inhibitory effect of metformin on age-related phenotypes of ISC. Here, we showed that knockdown of Atg6, a crucial autophagy-related factor, in ISC induces age-related phenotypes of ISC such as hyperproliferation, centrosome amplification, and DNA damage accumulation...
February 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29482945/metformin-influences-drug-sensitivity-in-pancreatic-cancer-cells
#17
Saverio Candido, Stephen L Abrams, Linda Steelman, Kvin Lertpiriyapong, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Matilde Y Follo, Ramiro M Murata, Pedro L Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Pann-Gill Suh, Massimo Libra, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5-10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes...
February 12, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29461625/beyond-symptomatic-relief-for-chemotherapy-induced-peripheral-neuropathy-targeting-the-source
#18
REVIEW
Jiacheng Ma, Annemieke Kavelaars, Patrick M Dougherty, Cobi J Heijnen
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy-induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious...
February 20, 2018: Cancer
https://www.readbyqxmd.com/read/29423103/metformin-induces-distinct-bioenergetic-and-metabolic-profiles-in-sensitive-versus-resistant-high-grade-serous-ovarian-cancer-and-normal-fallopian-tube-secretory-epithelial-cells
#19
Melissa Hodeib, Martin P Ogrodzinski, Laurent Vergnes, Karen Reue, Beth Y Karlan, Sophia Y Lunt, Paul-Joseph P Aspuria
Metformin is a widely used agent for the treatment of diabetes and infertility, however, it has been found to have anti-cancer effects in a variety of malignancies including high grade serous ovarian cancer (HGSC). Studies describing the mechanisms by which metformin affects HGSC are ongoing, but detailed analysis of its effect on the cellular metabolism of both HGSC cells and their precursor, normal fallopian tube secretory epithelial cells (FTSECs), is lacking. We addressed the effects of metformin and the more potent biguanide, phenformin, on HGSC cell lines and normal immortalized FTSECs...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416677/identification-of-human-age-associated-gene-co-expressions-in-functional-modules-using-liquid-association
#20
Jialiang Yang, Yufang Qin, Tiantian Zhang, Fayou Wang, Lihong Peng, Lijuan Zhu, Dawei Yuan, Pan Gao, Jujuan Zhuang, Zhongyang Zhang, Jun Wang, Yun Fang
Aging is a major risk factor for age-related diseases such as certain cancers. In this study, we developed Age Associated Gene Co-expression Identifier (AAGCI), a liquid association based method to infer age-associated gene co-expressions at thousands of biological processes and pathways across 9 human tissues. Several hundred to thousands of gene pairs were inferred to be age co-expressed across different tissues, the genes involved in which are significantly enriched in functions like immunity, ATP binding, DNA damage, and many cancer pathways...
January 2, 2018: Oncotarget
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