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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Combined p19Arf and interferon-beta gene transfer enhances cell death of B16 melanoma in vitro and in vivo

Texto completo
Autor(es):
Merkel, C. A. [1, 2, 3] ; Medrano, R. F. V. [1] ; Barauna, V. G. [2] ; Strauss, B. E. [1, 2, 3]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Inst Heart, Viral Vector Lab, BR-05403900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Inst Heart, Lab Genet & Mol Cardiol LIM13, BR-05403900 Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Med, Anim Care Facil, BR-05403900 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Cancer Gene Therapy; v. 20, n. 5, p. 317-325, MAY 2013.
Citações Web of Science: 12
Resumo

Approximately 90% of melanomas retain wild-type p53, a characteristic that may help shape the development of novel treatment strategies. Here, we employed an adenoviral vector where transgene expression is,controlled by p53 to deliver the p19 alternate reading frame (An) and interferon-beta (IFN beta) complementary DNAs in the B16 mouse model of melanoma. In vitro, cell death was enhanced by combined gene transfer (63.82 +/- 15.30% sub-GO cells); yet introduction of a single gene resulted in significantly fewer hypoploid cells (37.73 +/- 7.3% or 36.96 +/- 11.58%, p19Arf or IFN beta, respectively, P < 0.05). Annexin V staining and caspase-3 cleavage indicate a cell death mechanism consistent with apoptosis. Using reverse transcriptase quantitative PCR, we show that key transcriptional targets of p53 were upregulated in the presence of p19Arf, although treatment with IFN beta did not alter expression of the genes studied. In situ gene therapy revealed significant inhibition of subcutaneous tumors by IFN beta (571 +/- 25 mm(3)) or the combination of p19Arf and IFN beta (489 +/- 124 mm(3)) as compared with the LacZ control (1875 +/- 33 mm(3), P < 0.001); whereas p19Arf yielded an intermediate result (1053 +/- 169 mm(3), P < 0.01 vs control). However, only the combination was associated with increased cell death and prolonged survival (P < 0.01). As shown here, the combined transfer of p19Arf and IFN beta using p53-responsive vectors enhanced cell death both in vitro and in vivo. (AU)

Processo FAPESP: 06/57823-5 - Terapia gênica combinando interferon-beta e p-53 em um modelo murino de melanoma maligno
Beneficiário:Christian Albert Merkel
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 10/03958-2 - Utilização do IFN-beta e da via p53/Arf na elaboração de uma nova imunoterapia para melanoma
Beneficiário:Ruan Felipe Vieira Medrano
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 07/50210-0 - Combinações estratégicas entre os promotores virais e transgenes destinadas a terapia gênica do câncer
Beneficiário:Bryan Eric Strauss
Linha de fomento: Auxílio à Pesquisa - Regular