40 Tumor weight (mg) Tumor volume (ml) Metastases number Metastases volume % Lung metastases Table 3 Effects of sActRIIB treatment on tumor mass and metastases in mice bearing the Lewis lung carcinoma T 4,354±213 5.0±0.33 6.2±1.1 29.9±13.3 15.7±6.7 T+A 3,790±153 4.2 ±0.2 3.6 ±0.8 28.7±11 19.9±7.5 ANOVA 0.0497 0.0492 ns ns ns Results are mean±S.E.M. for eight animals. Statistically significant difference by post hoc Duncan test. Statistical significance of the results by one-way analysis of variance (ANOVA), treatment effect T tumor-bearing mice, T + A tumor-bearing mice treated with sActRIIB, ns nonsignificant differences cachexia. This tumor has been described as an anaplastic epidermoid with a marked haemorrhagic tendency, which produces multiple lung metastasis and is extremely refractory to most chemotherapeutic agents [32]. It is a well-known neoplasia that because of its fast growth rate and lung metastatic potential quickly causes death [27]. The growth of the Lewis lung carcinoma causes a rapid and progressive loss of body weight and tissue wasting, particularly in skeletal muscle [33]. Different therapeutic approaches have lead to positive results in neutralizing muscle wasting in this experimental model [34, 35], and recently a new strategy has been developed: to specifically block myostatin pathway [22]. J Cachexia Sarcopenia Muscle (2012) 3:37–43 As can be seen in Table 1, administration of sActRIIB resulted in an improvement in final body weight, the body weight increase being around 9%, while in untreated animals, the loss of weight was around 8%. This increase in body weight resulted also in an increase in carcass weight (mainly muscle and bone). Interestingly, sActRIIB treatment also resulted in an increase in food intake. Moreover, the increase in body weight affected individual muscle weights. Thus, as can be seen in Table 2, sActRIIB treatment resulted in a significant increase in gastrocnemius and tibialis muscles (31% and 36%, respectively). In fact, similar results has recently been published using the sActRIIB administration strategy in another mouse tumor model [22]. The authors concluded that in addition of an amelioration of muscle weight, treatment with the myostatin antagonist leads to prolonged survival [22]. In the rest of muscles analyzed (EDL and soleus), a clear tendency for bigger muscles as a result of treatment was observed; however, the differences did not reach statistical significance. Treatment slightly decreases the tumor weight and its volume, although it did not influence the metastatic lung area or the volume of the metastasis (Table 3). Bearing in mind, the effects of the treatment on body weight and particularly in individual muscle weights, a set of experiments to measure physical performance were carried out using a physical actimeter [36]. As can be seen in Table 4, the implantation of the tumor resulted in a decrease of total physical activity (75%), mean velocity Table 4 Last 24 h of physical activity in mice bearing the Lewis lung carcinoma treated with sActRIIB Physical activity Total physical activity Stereotyped movements Locomotor movements Mean velocity Total traveled distance Time Resting time (%) Slow-movements time (%) Fast-movements time (%) C T T+A 56,401±531 4,005±876 52,396±1,373 0.32±0.04 27,455±3,316 86.9±0.5 9.4±0.7 3.6±0.66 14,118±2,633 1,245±387 12,874 ±2,615 0.06±0.01 5,603±599 95.7±0.5 4.0 ±0.6 0.3 ±0.03 12,395±1,199 1,517±330 10,878±1,240 0.09±0.02 7,979±1,234 91±1.8 8.6±1.7 0.4±0.12 ANOVA A 0.0000 0.0087 0.0000 0.0000 0.0000 0.0009 0.0074 0.0002 B ns ns ns ns ns 0.0292 0.0173 ns Physical activity is expressed in activity units. Stereotyped movements include movements without displacement (eating and cleaning movements); conversely, locomotor movements include movements with displacement. Mean velocity is expressed in centimeters per second. Traveled distance is expressed in centimeters. Time is expressed as percentage of total time (24 h). The thresholds of time are the following: time involving resting (sleeping, cleaning, and eating time): [0–2] cm/s, time involving slow movements: [2–5] cm/s and time involving fast movements: [>5] cm/s. Results are mean±S.E.M. for four animals. Statistical significance of the results by two-way analysis of variance (ANOVA) C control mice, T tumor-bearing mice, T+A tumor-bearing mice treated with sActRIIB, ns nonsignificant differences, A (tumor effect), B (treatment effect)