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Melatonin effect on intratumor heterogeneity by hypoxia immunohistochemistry markers in animal model of breast cancer

Grant number: 14/16201-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2015
Effective date (End): March 31, 2016
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal Investigator:Debora Aparecida Pires de Campos Zuccari
Grantee:Victor Keniti Gomes Nishiyama
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


Breast cancer is considered the most common neoplasm among women and the tumor growth is the major cause of evolution and mortality of patients. The large tumor extension hinders the perfusion of O2, mainly in the central region of the tumor. This results in hipoxic regions, which cause a selective pressure on the tumor, selecting subpopulations with advantageous characteristics to survive on deprived oxygen environments. These subpopulations have distinct characteristics and are organized at different locations within the tumor, featuring intratumoral heterogeneity. In addition, they differ in aggressiveness and sensitivity to treatment. The treatments that have a tumor cells population with certain characteristics as therapeutic target, as some chemotherapeutic agents, may not show efficacy against other populations with different characteristics, failing in tumor eradication. In this context, as melatonin has been highlighted for its many oncostatic effects, the aim of this study is to evaluate the effect of melatonin on the intratumoral heterogeneity, detecting intratumoral hypoxic regions by immunohistochemistry with pimonidazole and hypoxia-inducible factor 1 (HIF-1 alpha) markers and, after, comparing the immunohistochemistry analysis with images obtained by positron emission tomography (PET) in animal model of breast cancer treated or not with melatonin.