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Action of melatonin on the tumor microenvironment verified by anaerobic markers of energy metabolism in an experimental model of breast cancer

Grant number: 14/25022-0
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2015
Effective date (End): May 31, 2017
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Debora Aparecida Pires de Campos Zuccari
Grantee:André de Lima Mota
Home Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Breast cancer is the most common among women and has a high mortality rate. The tumor growth can hinder perfusion O2, particularly in the central region of the tumor. These adverse conditions in the tumor microenvironment may exert selective pressure on the tumor selecting subpopulations with beneficial traits for survival in anaerobic environments. In this context is characterized intratumoral heterogeneity, consisting of subpopulations of tumor cells with different characteristics, which differ in the degree of aggressiveness and sensitivity to treatment. Melatonin, a hormone naturally produced by the pineal gland, has physiological effects and han been shown significant action in cancer. Studies suggest that changes in melatonin levels may be related to the development of breast tumors and indicate their therapeutic use in different types of cancer. However, it is necessary a better understanding of their mechanisms of action and oncostatic effects. Thus, this proposal aims to assess the action of melatonin in the anaerobic microenvironment tumor verified by images obtained by Positron Emission Tomography (PET) and different markers of energy metabolism (pimonidazole, HIF-1 alpha, GLUT1, GLUT3 and carbonic anhydrase IX and XII) in an experimental model of breast cancer. (AU)