European Journal of Translational Myology/Basic Applied Myology 2013; 23: 7-50 Proceedings of the 2013 Spring Padua Muscle Days Terme Euganee, Padova (Italy), March 15 - 17, 2013 Abstracts - 17 - studies showed that physical activity after cancer diagnosis ameliorates the prognosis, although the underling mechanisms are still poorly understood. With the aim to delineate the pathways involved in exercise-mediated rescue of cachexia, we investigated the effects of spontaneous physical activity (wheel running) in colon carcinoma (C26)- bearing mice. All major diagnostic criteria for cachexia were reversed by exercise, including rescue of body weight, muscle atrophy and fatigue, ultimately leading to increased survival. These data suggested a potential use of exercise mimetics (that is, pharmacological treatments activating pathways physiologically triggered by exercise) to counteract cachexia. To test this approach, we treated C26-bearing mice with AICAR, an analog of AMP that is capable of activating AMPK-mediated pathways, thus mimicking endurance exercise adaptations in skeletal muscle [2]. Strikingly, AICAR treated mice looked healthier, lost significantly less body and muscle weight and show reduced expression of atrogenes in respect to vehicle treated mice. The molecular mechanisms by which AICAR can rescue muscle cachexia are under investigation. We first hypothesized that AICAR could increase PGC1a expression and mitochondriogenesis, therefore promoting a shift towards a more oxidative status that may render skeletal muscle more resistant to wasting. This was not the case. We are now evaluating if AICAR rescue cancer cachexia by increasing autophagy in skeletal muscle. We propose that physical activity counteracts cachexia and reveal a potential use of exercise mimetics to ameliorate patient muscle wasting. [1] Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12: 489-495 [2] Narkar VA, Downes M, Yu RT, Embler E, Wang Y-X, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw R, Evans1 RM. AMPK and PPAR agonists are exercise mimetics. Cell 2008; 134: 405–415. ***** Exercise-based rehabilitation in complicated patients with anemia Leonida Compostella, Nicola Russo, Tiziana Setzu, Caterina Compostella, Sabino Iliceto, Fabio Bellotto Istituto Codivilla Putti, Cortina d'Ampezzo (Bl), Italy; Department of Medicine, University of Padua, Italy E-mail: leonida.compostella@gmail.com After completion of cancer treatment, a relatively high percentage of patients (17-56%) present fatigue. It is associated with considerable impairments in cardio- respiratory fitness and is likely due to complex inter- relationships between direct effects of cancer on the affected organs, direct toxic effects of anticancer therapy on multiple systems (especially on heart, blood components, muscles, neuroendocrine system), as well as indirect consequences of therapy (physical deconditioning, depression). Anemia is one of the most common manifestations, reaching a prevalence as high as 68-77% of patients in advanced stages of cancer. Likewise in heart failure patients, fatigue, impaired cardiovascular fitness and anemia are associated with an increased risk of cardiovascular morbidity and mortality. The effects of exercise training on these parameters and the adaptation mechanisms that could prevent or mitigate dysfunction in oncologic patients are still poorly known; so, some data are derived from the larger experience of exercise- based rehabilitation in cardiac patients. Exercise training modifies muscle fibers composition and muscle blood distribution, contrasts treatment-induced sarcopenia, and increases muscle mass and functional performance (independently of heart function); physical exercise reduces the risk of morbidity and mortality from other chronic diseases (such as diabetes and coronary artery disease), that could be induced or worsened by cancer therapy and whose effects could outweigh the initial cancer diagnosis. Observational studies and meta-analises reports confirm that exercise-based interventions during or after cancer treatment are effective in reducing cancer related fatigue and anxiety, and - similarly to general population and chronic heart failure patients - improve quality of life and possibly increase survivorship. Likewise in coronary artery diseases, in oncology patients blood transfusions seem to be linked to increased or accelerated mortality, and erythrocyte stimulating agents - though effective in improving quality of life - could have an unfavourable effect on life expectancy. Individually tailored exercise training is well tolerated in complicated patients with anemia and allows similar physical improvements as in non-anemic populations; it can increase total Hb and red cell mass and thus enhance oxygen-carrying capacity to the working muscles and all other organs. It is reasonable to presume that a wider application of comprehensive exercise-based rehabilitation in oncologic patients could be worthwhile. [1] Lakoski SG, Eves ND, Douglas PS, Jones LW. Exercise rehabilitation in patients with cancer. Nat Rev Clin Oncol 2012; 9: 288-296. [2] Bellotto F, Compostella L, Agostoni P, Torregrossa G, Setzu T, Gambino A, Russo N, Feltrin G, Tarzia V, Gerosa G. Peripheral adaptation mechanisms in physical training and cardiac rehabilitation: the case of a patient supported by a CardioWest total artificial heart. J Cardiac Fail 2011; 17: 670-675. [3] Mishra SI, Scherer RW, Snyder C, Geigle PM, Berlanstein DR, Topaloglu O. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev 2012 Aug 15; 8: CD008465. [4] Preston NJ, Hurlow A, Brine J, Bennett MI. Blood transfusions for anaemia in patients with advanced cancer. Cochrane Database Syst Rev 2012 Feb 15; 2: CD009007. [5] Bellotto F, Palmisano P, Compostella L, Russo N, Zaccaria M, Guida P, Setzu T, Cati A, Maddalozzo A, Favale S, Iliceto S. Anemia does not preclude increments in cardiac performance during a short period of intensive, exercise-based cardiac rehabilitation. Eur J Cardiovasc Prev Rehabil 2011; 18: 150-157.