| Texto completo | |
| Autor(es): Mostrar menos - |
de Goes Rocha, Flavia Gomes
[1, 2]
;
Calvo, Fernanda B.
[2]
;
Chaves, Karen C.
[1, 2]
;
Peron, Jean P. S.
[3]
;
Marques, Rodolfo F.
[2]
;
de Borba, Tania R.
[4]
;
Braga, Marina S.
[2]
;
Pereira, Cleide B.
[5]
;
Vicente, Elisabete J.
[5]
;
Chammas, Roger
[6]
;
Schor, Nestor
[1]
;
Bellini, Maria H.
[1, 2]
Número total de Autores: 12
|
| Afiliação do(s) autor(es): | [1] Univ Fed Sao Paulo, Dept Med, Div Nephrol, Sao Paulo - Brazil
[2] IPEN CNEN, Dept Biotechnol, Sao Paulo - Brazil
[3] Univ Sao Paulo, Dept Immunol, ICB 4, Sao Paulo - Brazil
[4] IPEN CNEN, Radioact Waste Management Dept, Sao Paulo - Brazil
[5] Univ Sao Paulo, Dept Microbiol, ICB 2, Sao Paulo - Brazil
[6] Univ Sao Paulo, Dept Radiol, Sao Paulo - Brazil
Número total de Afiliações: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF GENE MEDICINE; v. 13, n. 3, p. 148-157, MAR 2011. |
| Citações Web of Science: | 12 |
| Resumo | |
Background Metastatic renal cell carcinoma (mRCC) is one of the most treatment-resistant malignancies. Despite all new therapeutic advances, almost all patients develop resistance to treatment and cure is rarely seen. In the present study, we evaluated the antitumor effect of a bicistronic retrovirus vector encoding both endostatin (ES) and interleukin (IL)-2 using an orthotopic metastatic RCC mouse model. Methods Balb/C-bearing Renca cells were treated with NIH/3T3-LendIRES-IL-2-SN cells. In the survival studies, mice were monitored daily until they died. At the end of the in vivo experiment, serum levels of IL-2 and ES were measured, the lung was weighed, and the number of metastatic nodules, nodule area, tumor vessels and proliferation of tumor-infiltrating Renca cells were determined. Results Inoculation of NIH/3T3-LendIRES-IL-2-SN cells resulted in an increase in ES and IL-2 levels in the treated group (p < 0.05). There was a significant decrease in lung wet weight, lung nodule area and tumor vessels in the treated group compared to the control group (p < 0.001). The proliferation of Renca cells in the bicistronic-treated group was significantly reduced compared to the control group (p < 0.05). Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice submitted to bicistronic therapy (log-rank test, p = 0.0016). Bicistronic therapy caused an increase in the infiltration of CD4, CD4 interferon (IFN)gamma-producing, CD8, CD8 IFN gamma-producing and natural killer (CD49b) cells. Conclusions Retroviral bicistronic gene transfer led to the secretion of functional ES and IL-2 that was sufficiently active to: (i) inhibit tumor angiogenesis and tumor cell proliferation and (ii) increase the infiltration of immune cells (C) Copyright. 2011 John Wiley \& Sons, Ltd. (AU) | |
| Processo FAPESP: | 07/54253-6 - Construção e caracterização de vetor retroviral bicistrônico pL(end-IL2)SN e avaliação de sua eficácia na terapia gênica anti-tumoral |
| Beneficiário: | Maria Helena Bellini Marumo |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |