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metformin cancer sarcoma

J Pierro, C Saba, K McLean, R Williams, E Karpuzoglu, R Prater, K Hoover, R Gogal
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8...
October 2017: Research in Veterinary Science
Fan Cheng, Meilan He, Jae U Jung, Chun Lu, Shou-Jiang Gao
UNLABELLED: The host intracellular antiviral restriction factors inhibit viral infection and replication. The 5'-AMP-activated protein kinase (AMPK) is a cellular energy sensor regulating metabolic homeostasis. Activated AMPK inhibits the replication of numerous RNA viruses but enhances the entry of vaccinia virus. However, the role of AMPK in herpesvirus infection is unclear. In this study, we showed that the constitutive AMPK activity restricted Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication in primary human umbilical vein endothelial cells while KSHV infection did not markedly affect the endogenous AMPK activity...
July 15, 2016: Journal of Virology
Muhammad R Khawaja, Alpa M Nick, Vinu Madhusudanannair, Siqing Fu, David Hong, Lacey M McQuinn, Chaan S Ng, Sarina A Piha-Paul, Filip Janku, Vivek Subbiah, Apostolia Tsimberidou, Daniel Karp, Funda Meric-Bernstam, Karen H Lu, Aung Naing
PURPOSE: Mammalian target of rapamycin (mTOR) inhibitors like temsirolimus may result in undesirable AKT upregulation. Metformin inhibits mTOR through different mechanisms and may enhance temsirolimus's antitumor activity. We conducted an open-label phase I dose escalation trial of this drug combination in patients with advanced/refractory cancers. METHODS: Temsirolimus, 25 mg weekly, was combined with an escalating daily dose of metformin (level 1: 500; level 2: 1000; level 3: 1500; level 4: 2000 mg) by utilizing a standard 3 + 3 trial design...
May 2016: Cancer Chemotherapy and Pharmacology
Timothy C Tan, Tomas G Neilan, Sanjeev Francis, Juan Carlos Plana, Marielle Scherrer-Crosbie
Anthracyclines are one of the most commonly used antineoplastic agent classes, and a core part of the treatment in breast cancers, hematological malignancies, and sarcomas. Their benefit is decreased by their well-recognized cardiotoxicity. The purpose of this review is to outline the presentation, mechanisms, diagnosis, and treatment of anthracyclines-induced cardiotoxicity. Symptomatic heart failure occurs in 2% to 5% of patients treated with anthrayclines and may be higher in older patients or patients with cardiovascular risk factors...
July 1, 2015: Comprehensive Physiology
I V Anikin, N V Goncharov, M L Tyndyk, N G Voĭshenko, G B Pliss, M A Zabezhinskiĭ, I G Popovich, V N Anisimov
Previously it was found that sodium fluoroacetate (SF) inhibited the growth of the Ehrlich cancer by means of monotherapy and enhanced the antitumor effect of cyclophosphamide (CP) in experiments with autochthonous subcutaneous tumors induced by benzo (a) pyrene. In this study a comparison of the antitumor activity of SF and metformin showed that both substances did not have significant effect in monotherapy but enhanced the effect of CP, increasing the percentage of tumors with the same or reduced volume. Besides, SF, unlike metformin increased the average duration of effect...
2014: Voprosy Onkologii
Igor Vujic, Martina Sanlorenzo, Christian Posch, Rosaura Esteve-Puig, Adam J Yen, Andrew Kwong, Aaron Tsumura, Ryan Murphy, Klemens Rappersberger, Susana Ortiz-Urda
Attempts to directly block the mutant neuroblastoma rat sarcoma oncogene (NRAS) protein, a driving mutation in many cancer types, have been unsuccessful. Current treatments focus on inhibition of different components of NRAS' two main downstream cascades: PI3K/AKT/mTOR and MAPK. Here we test a novel dual therapy combination of metformin and trametinib on a panel of 16 NRAS mutant cell lines, including melanoma cells, melanoma cells with acquired trametinib resistance, lung cancer and neuroblastoma cells. We show that both of the main downstream cascades of NRAS can be blocked by this combination: metformin indirectly inhibits the PI3K/AKT/mTOR pathway and trametinib directly impedes the MAPK pathway...
January 20, 2015: Oncotarget
Qiang Yang, Ting Zhang, Chunling Wang, Jiao Jiao, Jing Li, Yihui Deng
Cancer stem cells (CSCs), also known as tumor-initiating cells, which constitute a subpopulation of tumor cells, are key drivers of tumorigenesis and potential recurrence of cancer. The CSC theory has brought new opportunities as well as challenges to the development of sophisticated drug delivery systems for treating cancer. In the present study, CD133+ cells were sorted from S180 cell lines by magnetic activated cell sorting and a fraction (approximately 1.01%) of CD133+ cells with higher proliferative potential and stronger tumorigenicity in vivo compared with CD133- cells was identified...
November 2014: European Journal of Pharmaceutics and Biopharmaceutics
Sameer H Issaq, Beverly A Teicher, Anne Monks
Sarcomas represent a diverse group of malignancies with distinct molecular and pathological features. A better understanding of the alterations associated with specific sarcoma subtypes is critically important to improve sarcoma treatment. Renewed interest in the metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a therapeutic strategy. In this study, we have characterized key bioenergetic properties of human sarcoma cells in order to identify metabolic vulnerabilities between sarcoma subtypes...
2014: Cell Cycle
Cecilia Garofalo, Mariantonietta Capristo, Maria Cristina Manara, Caterina Mancarella, Lorena Landuzzi, Antonino Belfiore, Pier-Luigi Lollini, Piero Picci, Katia Scotlandi
Metformin, a well-known insulin-sensitizer commonly used for type 2 diabetes therapy, has recently emerged as potentially very attractive drug also in oncology. It is cheap, it is relatively safe and many reports have indicated effects in cancer prevention and therapy. These desirable features are particularly interesting for pediatric sarcomas, a group of rare tumors that have been shown to be dependent on IGF and insulin system for pathogenesis and progression. Metformin exerts anti-mitogenic activity in several cancer histotypes through several molecular mechanisms...
2013: PloS One
Maria Cristina Manara, Cecilia Garofalo, Stefano Ferrari, Antonino Belfiore, Katia Scotlandi
Drug "repurposing" is the process of finding new therapeutic indications for existing drugs, and can be considered as a more efficient and realistic strategy for the design of therapies against rare diseases than the current efforts to develop targeted-drugs. In this review, we explore the difficulties related to the identification and development of tailored therapies for individual patients with sarcomas, which are relatively rare diseases characterized by an extreme genetic and histologic variability. Overall, sarcomas comprise about 1% of all adult tumors and 10% of pediatric cancers...
2013: Current Pharmaceutical Design
Francesco Atzori, Josep Tabernero, Andrés Cervantes, Ludmila Prudkin, Jordi Andreu, Edith Rodríguez-Braun, Amparo Domingo, Jorge Guijarro, Cristina Gamez, Jordi Rodon, Serena Di Cosimo, Holly Brown, Jason Clark, James S Hardwick, Robert A Beckman, William D Hanley, Karl Hsu, Emiliano Calvo, Susana Roselló, Ronald B Langdon, José Baselga
PURPOSE: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose. EXPERIMENTAL DESIGN: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks...
October 1, 2011: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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