Full text
| |
| Author(s): |
Juliana Colozzo Gregorio
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2008-08-29 |
| Examining board members: |
Eugenia Costanzi Strauss;
Jose Alexandre Marzagao Barbuto;
Carlos Alberto Moreira Filho;
Décio dos Santos Pinto Júnior;
Celio Lopes Silva
|
| Advisor: | Eugenia Costanzi Strauss |
| Abstract | |
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. (AU) | |