Intracranial therapy of glioblastoma with the fusion protein DTAT in immunodeficient mice.
Int J Cancer
; 120(2): 411-9, 2007 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-17075792
ABSTRACT
A gene splicing technique was used to create a hybrid fusion protein DTAT encoding the 390 amino acid portion of diphtheria toxin (DT(390)), a linker, and the downstream 135-amino terminal fragment portion of human urokinase plasminogen activator. DTAT was assembled to target human glioblastoma cell lines in a murine intracranial model. Previously published in vitro studies demonstrated that DTAT was highly selective and toxic to human glioblastoma cell lines in a flank tumor model. The purpose of this study was to determine the toxicity, specificity and possible therapeutic efficacy of DTAT in an intracranial model. Convection enhanced delivery of DTAT resulted in about a 16-fold increase in maximum tolerated dose. Intracranial administration of DTAT on an every-other-day basis in nude mice with established U87 MG brain tumors resulted in significant reductions in tumor volume and significantly prolonged survival (p < 0.0001). Magnetic resonance imaging proved to be a powerful tool in mice and rats for demonstrating tumor growth in a xenograft intracranial model, assessing the efficacy of DTAT in tumor volume reduction and detecting DTAT-associated intracranial toxicity and vascular damage. These results suggest that the DTAT recombinant fusion protein is highly effective in an intracranial model and DTAT might be an effective treatment for glioblastoma.
Buscar no Google
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes de Fusão
/
Neoplasias Encefálicas
/
Glioblastoma
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos