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Barbara Salani, Alberto Del Rio, Cecilia Marini, Gianmario Sambuceti, Renzo Cordera and Davide Maggi

Introduction Metformin is a biguanide, whose chemical scaffold was discovered by the extraction of the galegine, a guanidine analogue, from French lilac ( Galega officinalis ) plants. Metformin is the first-line therapy for type 2 diabetes

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Athanasios Bikas, Kirk Jensen, Aneeta Patel, John Costello Jr, Dennis McDaniel, Joanna Klubo-Gwiezdzinska, Olexander Larin, Victoria Hoperia, Kenneth D Burman, Lisa Boyle, Leonard Wartofsky and Vasyl Vasko

Introduction Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat cancers ( Pollak 2012 ). Recent epidemiological and laboratory studies have demonstrated that the anti-diabetic drug metformin has anti-cancer activity

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Sunmi Park, Mark C Willingham, Jun Qi and Sheue-Yann Cheng

preclinical studies provided supporting evidence that Thrb PV/PV Pten +/ − mice could be used to test other potential therapeutics to prevent obesity-activated thyroid cancer. Accordingly, we tested metformin (1,1-dimethylbiguanide

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Joanna Klubo-Gwiezdzinska, Kirk Jensen, John Costello, Aneeta Patel, Victoria Hoperia, Andrew Bauer, Kenneth D Burman, Leonard Wartofsky and Vasyl Vasko

suggested that under metabolic stress, binding of AMPK to KSR2 prevents RAF/MEK to be targeted to the plasma membrane for their activation ( Luo et al . 2010 ). The antidiabetic drug metformin has been shown to be a potent AMPK activator. On the

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Carolyn Algire, Mahvash Zakikhani, Marie-Jose Blouin, Jian Hua Shuai and Michael Pollak

Introduction Population studies provide early circumstantial evidence that patients with type II diabetes treated with metformin have reduced cancer incidence ( Evans et al . 2005 ) and mortality ( Bowker et al . 2006 ), when compared with type II

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K M Biernacka, R A Persad, A Bahl, D Gillatt, J M P Holly and C M Perks

. 2004 , Kasper & Giovannucci 2006 ). Therefore, new ways are needed to improve response to current treatment and to decrease mortality associated with diabetes and PCa. There is currently a lot of interest in metformin, a drug commonly used to treat

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Hyun-Seuk Moon and Christos S Mantzoros

risk for several obesity-associated malignancies including endometrial, breast, prostate, and especially colon cancer ( Wei et al . 2005 , Moon et al . 2011 , 2013 , Dalamaga et al . 2012 ). Metformin (Met), an insulin sensitizer, acts mainly by

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Carolyn Algire, Lilian Amrein, Mahvash Zakikhani, Lawrence Panasci and Michael Pollak

( Frasca et al . 1999 , Becker et al . 2009 ), reviewed in Pollak (2008) . Metformin, an antidiabetic drug, lowers the elevated insulin levels found in type II diabetes by inhibiting gluconeogenesis and hepatic glucose output, which in turn reduces

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Carly Jade Dool, Haider Mashhedi, Mahvash Zakikhani, Stéphanie David, Yunhua Zhao, Elena Birman, Joan M Carboni, Marco Gottardis, Marie-José Blouin and Michael Pollak

activation would be predicted to lead to severe metabolic toxicity such as that seen when IRs are ablated in all organs ( Kitamura et al . 2003 ). However, biguanides such as metformin, which are commonly used for treatment of type II diabetes, are known to

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Dara Hope Cohen and Derek LeRoith

an increased risk of colorectal and pancreatic cancers compared with patients treated with metformin. Insulin analogs, developed as an alternative to human insulin, are commonly used in the treatment of T2D. In order to create the insulin analogs