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Pharmacological and non-pharmacological management of muscle wasting

Grant number: 19/01244-7
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): April 08, 2019
Effective date (End): March 25, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:José Cesar Rosa Neto
Grantee:Edson Alves de Lima Junior
Supervisor abroad: Silvia Busquets Rius
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Universitat de Barcelona (UB), Spain  
Associated to the scholarship:15/17068-2 - Effect of aerobic exercise training associated with doxorubicin chemotherapy ín mice with Lewis Lung Carcinoma (LLC). role of adiponectin ín skeletal muscle ánd tumor, BP.DR

Abstract

The pathogenesis of muscle wasting plays a central role in cancercachexia. In addition to this, muscular dysregulation may also be the result ofchemotherapy. Based on the evidence that a large number of types of cancer areassociated to cachexia and cancer patients are often treated withchemotherapeutic agents, it is important to understand the combined effect ofstrategies for counteract muscle wasting.In order to better characterize this aspect, the objective of present projectis to evaluate the effects of the association of pharmacological andnonpharmacological approaches on muscle disorders induced by cancercachexia and chemotherapy. Thus, we will evaluate the effectiveness offormoterol (b² adrenergic agonist) and moderate aerobic exercise in a mousemodel of cancer cachexia during chemotherapy treatment. The relevance of thisproject comes from its multifactorial approach to muscle management. Ourhypothesis is that the combination of ²-2-agonist drug (formoterol) and moderateaerobic exercise could attenuate the muscle mass loss without causing cardiacimpairment in cachectic mice on chemotherapy.For this, we will use an experimental model of cancer cachexia (LewisLung Carcinoma). Tumor bearing-mice (TB group) will receive saline (CT group)or doxorubicin chemotherapy (DOX group). TB group will be subdivided intogroups that will be treated with formoterol (DOX + FOR), endurance exercise(DOX + EXER) or combination (DOX + FOR + EXER). The treatments willextended until the end of protocol. Protein synthesis, proteolysis, cardiacfunction, and muscle performance will be performed using standard methods(gene expression, immunobloting, total protein degradation, SUnSETMethod,proteasome activity, morphometric analysis and echocardiographic study).