Efeitos da privação de sono paradoxal sobre a implantação e a progressão de metástases experimentais em modelo de melanoma murino
Ano de defesa: | 2015 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de São Paulo (UNIFESP)
|
Programa de Pós-Graduação: |
Não Informado pela instituição
|
Departamento: |
Não Informado pela instituição
|
País: |
Não Informado pela instituição
|
Palavras-chave em Português: | |
Link de acesso: | https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=2688391 http://repositorio.unifesp.br/handle/11600/46392 |
Resumo: | Deprivation of REM sleep (PSP) is a stress induction model because it results in a increased concentrations of glucocorticoids (GCs) in humans (cortisol) and rodents (corticosterone) and others neurotransmitters stress-response-related via activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is able to produce many disorders resulting from prolonged and/or increased secretion of these hormones. Stress is associated with functional reduction of cytotoxic T cells and natural killer cells (NK), processes such as immune surveillance against tumors, the mainly role performed by these populations, genomic stability mechanisms and somatic mutations are affected. Thus, persistent activation of the HPA axis by sleep deprivation (PS) may contribute to the development and progression of some cancers. Melanoma is considered one of the hightest type of angiogenic and aggressive cancers in the world and remains in the lead of deaths from skin cancer in industrialized countries. It has a high capacity to escape from mechanisms that protect the body against it and has a high affinity for vital organs like lungs, liver and brain. Therefore, this study aimed to evaluate the effects of PSP in the development of melanoma lung metastases and the immunological mechanisms involved in the development of this cancer. Therefore, C57BL/6 male mice were inoculated with B16F10 melanoma murine strain cells and subjected to PSP protocol for 72 h after inoculation. Starting at day 8 until day 15 postinoculation, established through pilot experiments the will be show in sequence, the monitoring of metastasis and pulmonary immune populations and the analysis of pulmonary production of interferon gamma (IFN- ?), the main pro-inflammatory cytokine involved in inflammatory processes, and the functional activity of T cells began. Mice from the PSP group had decreased of lung metastases in all the days of evaluation when compared to the control group (CTL), a higher percentage of NK cells and higher concentrations of IFN-?. NK cells are an essential population of killer cells against mutagenic processes and it was the mainly responsible for the restraining metastases in the PSP group showed here. In addition, mice of the CTL group showed a higher percentage of CD8 + CD25 + Foxp3 + lymphocytes (T8reg), which indicated a process of "immune brake" in those animals that had released of metastases. Together, the results point to an important role of NK cells, stimulated by a stressor, presented in greater quantities in the tumor microenvironment of PSP animals. |