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| Author(s): |
Janio da Silva Mororó
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2019-02-01 |
| Examining board members: |
Carlos Alberto Buchpiguel;
Paula Fontes Asprino;
Fabio Luiz Navarro Marques;
Ana Maria Moro
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| Advisor: | Roger Chammas; Carlos Alberto Buchpiguel |
| Abstract | |
The tumor vasculature is structurally and functionally abnormal in relation to the vasculature of normal organs, resulting in regions of intratumoral heterogeneity for oxygen parcial pressure, nutrients and inflammatory cells. Thus dysfunctional vascularization often leads to inefficient drug delivery, thereby compromising the efficacy of treatment. Recently, it has been demonstrated that anti-angiogenic therapies and physical exercises could \"normalize\" tumor vasculature, improving survival in patients with cancer. However, it would be important to analyze in BRAFV600E melanoma tumors, which are highly resistant to therapy, whether exercise would promote vascular normalization. Based on this, this work aimed to analyze the impact of voluntary physical exercise on the vascular function of human melanomas with BRAFV600E mutation in immunodeficient mice (BALB / c Nude). In relation to the tumor growth, we did not observe significant differences between the groups of the exercised and sedentary animals, neither difference in the expression levels of genes characteristic of M1 and M2 macrophages in the tumor microenvironment of these animals. On the other hand, analysis of gene expression in tumor cells showed that 8 genes were differentially expressed in the exercised group ( < 4 km) in comparision to the Sedentary Group, among them: FLOT2, STK4, STAT3, LATS1, PTEN, MCL1, PCNA and ACTA2. In addition, we did not observe any significant differences in the percentage of necrotic, hypoxic area and CD31 positive vessels. Thus, we concluded that physical exercise induces an increase in the expression levels of genes involved in epigenetic modifications, apoptosis, proliferation and survival, cell cycle and cell motility (AU) | |
| FAPESP's process: | 14/27188-2 - Analysis of subpopulation of CD20 positive melanoma cells in response to chemotherapy agents, using radionuclide imaging |
| Grantee: | Janio da Silva Mororó |
| Support Opportunities: | Scholarships in Brazil - Doctorate |