Bystander-Mediated Regression of Murine Neuroblastoma via Retroviral Transfer of the HSV-TK Gene
Journal of Korean Medical Science
;
: 107-112, 2004.
Artigo
em Inglês
| WPRIM
| ID: wpr-20643
ABSTRACT
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirusmediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Retroviridae
/
Timidina Quinase
/
Fatores de Tempo
/
Imuno-Histoquímica
/
Terapia Genética
/
Linfócitos T CD4-Positivos
/
Apoptose
/
Simplexvirus
/
Técnicas de Transferência de Genes
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Journal of Korean Medical Science
Ano de publicação:
2004
Tipo de documento:
Artigo
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