Transcriptional targeted gene therapy for hepatocellular carcinoma by adenovirus vector.
Mol Biotechnol
; 18(3): 243-50, 2001 Jul.
Article
en En
| MEDLINE
| ID: mdl-11503518
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis and is highly amenable to the development of novel therapeutic strategy. The human alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but overexpressed in HCC. In order to destroy AFP-producing HCC specifically, replication defective adenoviral vectors containing the transcriptional control elements of the AFP gene were designed. Expression of suicide genes by the AFP promoter/enhancer induced prodrug sensitivity in AFP (+) cells but not AFP (-) cells. The expression of suicide genes by ubiquitous promoter, however, showed no selectivity after prodrug treatment. Adenoviral vector transduced genes efficiently not only in vitro but also in vivo, and AFP-producing HCC xenografts regressed by transduction with transcriptionally targeted vectors and subsequent systemic administration of prodrug in animal model. Utilization of the transcriptional regulatory element to drive drug sensitive genes can be a promising strategy for cancer specific therapy.
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Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Terapia Genética
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Alfa-Fetoproteínas
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Adenovirus Humanos
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Carcinoma Hepatocelular
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Vectores Genéticos
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Neoplasias Hepáticas
Límite:
Animals
/
Humans
Idioma:
En
Año:
2001
Tipo del documento:
Article