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Role of exercise training on prevention of cardiotoxicity provoked by doxorubicin

Grant number: 14/13690-8
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): October 01, 2014
Effective date (End): March 05, 2017
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Carlos Eduardo Negrão
Grantee:Igor Lucas Gomes dos Santos
Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases , AP.TEM
Associated scholarship(s):16/21320-1 - Influence of aerobic exercise on drug delivery and doxorubicin-based chemotherapy response in obesity-associated breast cancer, BE.EP.PD


Doxorubicin (DOX) is a potent antibiotic, used in the cancer treatment. However, this therapeutic strategy provokes side effects, such as cardiotoxicity. Macroscopic disarray and cardiomyocyte death are among the most common cardiac alterations, which have been attributed to reactive oxygen species generation and suppression of important mechanisms of stress-mediated cellular survival response, like the transcription factor GATA4. These alterations may result in heart failure (HF), a complex syndrome of poor prognosis. Previous data show that one out four patients treated with DOX can develop cardiac dysfunction or severe HF. Therefore, the prevention and treatment of HF caused by DOX is a great challenge in current medical practice. Exercise training is an important non-pharmacological tool in the treatment of HF. Moreover, recent studies show that exercise training can be useful in the adjuvant treatment of cancer Exercise training has been shown to preserve cardiac function before DOX treatment. However, in clinical practice, chemotherapy is usually begun shortly after cancer diagnosis. Thus, it seems reasonable that exercise training has to be conducted simultaneously to chemotherapy. Some studies suggest that exercise training improves cardiac function during treatment with DOX, but the molecular mechanisms involved in the preservation and even recovery of cardiac structure and function are virtually unknown. Therefore, the aim of the present study is to investigate whether exercise training preserves cardiac structure and function during DOX treatment. In addition, the study will investigate the molecular mechanisms involved in these phenotype changes, especially those associated with transcription factor GATA4. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GOMES-SANTOS, IGOR L.; JORDAO, CAMILA P.; PASSOS, CLEVIA S.; BRUM, PATRICIA C.; OLIVEIRA, EDILAMAR M.; CHAMMAS, ROGER; CAMARGO, ANAMARIA A.; NEGRAO, CARLOS E.. Exercise Training Preserves Myocardial Strain and Improves Exercise Tolerance in Doxorubicin-Induced Cardiotoxicity. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 8, . (16/21320-1, 15/19076-2, 15/22814-5, 14/13690-8)
NEGRAO, CARLOS E.; MIDDLEKAUFF, HOLLY R.; GOMES-SANTOS, IGOR L.; ANTUNES-CORREA, LIGIA M.. Effects of exercise training on neurovascular control and skeletal myopathy in systolic heart failure. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 308, n. 8, p. H792-H802, . (10/50048-1, 13/15651-7, 14/13690-8)
GOMES-SANTOS, IGOR L.; AMOOZGAR, ZOHREH; KUMAR, ASHWIN S.; HO, WILLIAM W.; ROH, KANGSAN; TALELE, NILESH P.; CURTIS, HANNAH; KAWAGUCHI, KOSUKE; JAIN, RAKESH K.; FUKUMURA, DAI. Exercise Training Improves Tumor Control by Increasing CD8(+) T-cell Infiltration via CXCR3 Signaling and Sensitizes Breast Cancer to Immune Checkpoint Blockade. CANCER IMMUNOLOGY RESEARCH, v. 9, n. 7, p. 765-778, . (14/13690-8, 16/21320-1)
DA COSTA, TASSIA S. R.; URIAS, URSULA; NEGRAO, V, MARCELO; JORDAO, CAMILA P.; PASSOS, CLEVIA S.; GOMES-SANTOS, IGOR L.; SALEMI, VERA MARIA C.; CAMARGO, ANAMARIA A.; BRUM, PATRICIA C.; OLIVEIRA, EDILAMAR M.; et al. Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca2+-Handling Protein Expression That is Not Reversed by Exercise Training. JOURNAL OF THE AMERICAN HEART ASSOCIATION, v. 10, n. 5, . (15/22814-5, 15/19076-2, 14/13690-8)

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