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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2016.tde-16082016-105656
Document
Author
Full name
Isabella Katz Migliori Leão de Moura
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Albuquerque, José Antonio Tavares de
Ferreira, Zulma Felisbina da Silva
Laginha, Fábio Martins
Negro, Sonia Jancar
Title in Portuguese
Avaliação funcional de NF-κB em células dendríticas de pacientes com câncer de mama.
Keywords in Portuguese
  Fatores  de  transcrição
 Células  dendríticas
 Neoplasias  mamárias
 Quimiocinas
 Radioimunoensaio
 Tolerância  imunológica
Abstract in Portuguese
Considerando que processos cruciais de diferenciação e maturação das células dendríticas (DCs) são regulados pelo fator de transcrição nuclear kappa B (NF-κB), nos propusemos a estudar esta via em DCs derivadas de monócitos de pacientes com câncer de mama, partindo da hipótese de que alterações desta via contribuam, nesses indivíduos, para a geração de DCs com fenótipo e função alterados, levando ao escape tumoral. A análise da presença de NF-κB no núcleo de monócitos, DCs imaturas (iDCs) e maduras indicou que as pacientes falham em modular tal fator de transcrição, de modo que a quantidade de NF-κB no núcleo de iDCs de pacientes supera os níveis encontrados em controles, fenômeno possivelmente decorrente de alterações nas proteínas inibidoras do NF-κB em pacientes. Observou-se menor frequência de células CD86+, CD83+ e HLA-DR+ (p < 0,05) ao final das culturas das pacientes, e aumento na concentração de IL-8 no sobrenadante das culturas. Coletivamente, estes dados corroboram a hipótese formulada.
Title in English
Functional evaluation of NF-­κB in dendritic cells of breast cancer patients.  
Keywords in English
Breast  neoplasms
  Dendritic  cells
  Immunological  tolerance
  Transcription  factors
 Chemokines
 Radioimmunoassay
Abstract in English
Considering that crucial processes of differentiation and maturation of dendritic cells (DCs) are regulated by nuclear factor kappa B (NF-κB), we proposed to study this pathway in monocyte-derived DCs from breast cancer patients, based on the hypothesis that alterations in such pathway may contribute in these individuals to the generation of DCs having phenotypic and functional changes, leading to tumor escape. The analysis of the presence of NF-κB in the nucleus of monocytes, immature and mature DCs indicated that patients fail to modulate this transcription factor, so that the amount of NF-κB in the nucleus of iDCs from patients exceeds levels found in controls, a phenomenon possibly due to alterations in inhibitory proteins of NF-κB in patients. It was also observed diminished frequency of CD86+, CD83+ and HLA-DR+ cells (p <0.05) at the end of the patients cultures, as well as increased IL-8 concentration in the culture supernatants. Collectively, these data support the hypothesis previously formulated.
 
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Publishing Date
2016-08-16
 
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