The timing of APT discontinuation after stent implantation was also taken into consideration

tric analysis using the ImageJ software. Statistical analysis Statistical analysis of the data was performed by means of one-way analysis of variance. Statistically significant differences was analysed by post hoc Duncan test. All statistical tests were performed using SPSS version 21. Results and Discussion In order to ascertain the effects of sorafenib on tumour-bearing animals we used three distinct experimental models: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma. All of them are associated with a clear cachectic response. From this point of view, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19682730 as can be seen in animals) in both the B16 and LLC models, proportionally to the reduction of tumour mass, thus linking directly the onset of anaemia with tumour burden. The decreased body weight was associated with a concomitant loss of muscle mass. As can be seen in 6 / 16 Cancer Cachexia in Sorafenib-Treated Tumour-Bearing Mice were significantly reduced. No effects of tumour growth were observed in the heart neither in the B16 nor in the LLC tumour models. Sorafenib treatment had significant effects in the rescue of both gastrocnemius and tibialis mass in the C26 animal model, despite the ineffectiveness against tumour growth. Similarly, the treatment caused a recovery of the gastrocnemius muscle in the LLC model; however it did not have any statistical effects on the tibialis muscle. Concerning the muscle, in contrast with the prevention of body weight loss, no statistically significant effects were observed in the B16 animals after sorafenib administration.Different letters in superscript indicate significant differences between groups. doi:10.1371/journal.pone.0113931.t001 cachexia is linked with muscle wasting and adipose tissue loss. A recent report suggests that muscle wasting is linked to the loss of adipose tissue; if fat mobilization is prevented, muscle wasting does not take place, at least in experimental animals. The largest reduction is observed in the LLC-bearing animals, with losses over 90% of total tissue. Sorafenib treatment induced a rescue of adipose tissues in all the cachexia models ONO4059 site tested, the amelioration being especially marked in the case of B16 where almost total recovery is accomplished, explaining partially the above reported discrepancy between body PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19682619 and muscle wasting. Values significantly different of the results by one-way analysis of variance, statistically significant differences by post hoc Duncan test. Different letters in superscript indicate significant differences between groups. doi:10.1371/journal.pone.0113931.t002 8 / 16 Cancer Cachexia in Sorafenib-Treated Tumour-Bearing Mice Taking into consideration the fact that the rescue of muscle mass does not necessarily mean a concomitant recovery of muscle function, we decided to measure total physical activity as a surrogate for muscle function and behavioural adaptation. 9 / 16 Cancer Cachexia in Sorafenib-Treated Tumour-Bearing Mice 10 / 16 Cancer Cachexia in Sorafenib-Treated Tumour-Bearing Mice the B16 model, precisely where sorafenib treatment was not able to fully revert muscle wasting. Therefore, some other factors must be taken into consideration for explaining the improvement in total activity, including the reduction of the tumour mass. It is possible to speculate that animal activity does not rely on the muscle mass alone, rather depending also on the energy availability and the presence of anaemia, a clear limiting factor for physical activity. Sorafenib treatment also impro