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Doctoral Thesis
DOI
10.11606/T.87.2019.tde-22022010-115327
Document
Author
Full name
Juliana Colozzo Gregorio
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Strauss, Eugenia Costanzi (President)
Barbuto, Jose Alexandre Marzagao
Moreira Filho, Carlos Alberto
Pinto Júnior, Décio dos Santos
Silva, Celio Lopes
Title in Portuguese
Estudo do efeito da remediação simultânea dos genes p16INK4a  e p53 mediada pelo adenovírus bicistrônico Adp16IRESp53 em um modelo de carcinoma de pulmão humano.
Keywords in Portuguese
Carcinoma pulmonar humano
Morte celular
p16INK4a e p53
Vetor adenoviral bicistrônico
Abstract in Portuguese
Considerando que várias mutações gênicas estão envolvidas no estabelecimento dos tumores, surge a idéia de que o alcance da melhor eficiência no tratamento do câncer é dado pela entrega de múltiplos genes. Este trabalho apresenta a construção, produção e caracterização funcional in vitro e in vivo do vetor adenoviral bicistrônico Adp16IRESp53 e dos monocistrônicos Adp16 e Adp53 em modelo de câncer de pulmão. Nossos resultados indicam uma forte indução de morte celular nas células H358 transduzidas com Adp16IRESp53 em comparação com vetores monocistrônicos Adp16, Adp53 ou o reporter AdeGFP e/ou AdLacZ. Nos ensaios in vivo, utilizando modelo xenografico onde as células H358 foram implantadas no subcutâneo de camundongos atímicos Balb/C nude, pudemos confirmar também in vivo a significativa inibição do crescimentos dos tumores tratados com Adp16IRESp53. Em conclusão, a remediação simultânea de p16INK4a e p53, mediada pelo arranjo bicistrônico, pode ser considerada como uma estratégia promissora para terapia gênica do câncer de pulmão.
Title in English
Effect of the simultaneous replacement of p16INK4a and p53 genes mediated by a bicistronic adenovirus Adp16IRESp53 in a human lung carcinoma model.
Keywords in English
Bicistronic adenoviral vector
Cell death
Human lung carcinoma
p16INK4a e p53
Abstract in English
This work presents the construction, production and functional evaluation in vitro and in vivo of the bicistronic adenoviral vector Ap16IRESp53 as well as the monocistronic vectors Adp16 and Adp53 in a lung cancer model. Considering that several mutation events are involved in tumorigenesis, comes the idea that a greater efficiency in cancer treatment would be reached with delivery of multiples genes. Our data demonstrate a strong cell death effect in H358 cells transduced with Adp16IRESp53 when compared with Adp16, Adp53 or the reporter AdeGFP and/or AdLacZ. For the in vivo studies, we have used H358 cells implanted subcutaneously in athymic Balb/c nude mice. Our data show significant suppression of tumors treated with the therapeutic adenoviral vector, Adp16IRESp53. In conclusion, the simultaneous replacement of p16INK4a and p53, mediated by the bicistronic vector, may prove to be a promising strategy for gene therapy of lung cancer.
 
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Publishing Date
2019-01-28
 
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