Curative potential of herpes simplex virus thymidine kinase gene transfer in rats with 9L gliosarcoma.

Détails

ID Serval
serval:BIB_A8792B40446B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Curative potential of herpes simplex virus thymidine kinase gene transfer in rats with 9L gliosarcoma.
Périodique
Human Gene Therapy
Auteur(s)
Cool V., Pirotte B., Gérard C., Dargent J.L., Baudson N., Levivier M., Goldman S., Hildebrand J., Brotchi J., Velu T.
ISSN
1043-0342 (Print)
ISSN-L
1043-0342
Statut éditorial
Publié
Date de publication
1996
Peer-reviewed
Oui
Volume
7
Numéro
5
Pages
627-635
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The transfer of the gene coding for the thymidine kinase of the herpes simplex virus (HSV-tk), followed by ganciclovir (GCV) administration, has been described for the treatment of several types of cancer, especially brain tumors. We further studied the efficacy of this approach by using the 9L rat gliosarcoma model, and cells producing 5 x 10(3), 9 x 10(4), 3 x 10(5) HSV-tk retroviral particles per milliliter. Their stereotactic injection in 9L brain tumors and GCV treatment did not result in any increase of survival. To study a model of optimal in vivo transduction, we examined the survival of rats with tumors growing from 9L cells that had been previously transduced in vitro with the HSV-tk vectors (9LTk cells). We observed that GCV administration cured 26% (n = 42) of the animals with 9LTk brain tumors, with most of the relapsing tumors remaining HSV-tk positive. The increase of either the dose or the duration of GCV treatment did not improve the survival rate. But the cerebral localization of the tumor played an important role, because this survival rate reached 67% (n = 12) when similar tumors were growing subcutaneously. No or only marginal antitumoral responses were induced by the presence of a selectable marker gene in the HSV-tk vectors. These results demonstrate that in vitro HSV-tk gene transfer in 9L tumor cells, but not in vivo gene transfer, followed by GCV treatment, is able to cure rats at a rate that is higher for subcutaneous than for intracerebral tumors.
Mots-clé
Animals, Brain Neoplasms/therapy, DNA Primers, Ganciclovir/therapeutic use, Gene Transfer Techniques, Genetic Markers, Genetic Vectors, Gliosarcoma/therapy, Male, Rats, Rats, Inbred F344, Retroviridae/genetics, Retroviridae/metabolism, Simplexvirus/enzymology, Simplexvirus/genetics, Skin Neoplasms/therapy, Thymidine Kinase/metabolism, Thymidine Kinase/therapeutic use, Transduction, Genetic
Pubmed
Web of science
Création de la notice
20/01/2008 18:35
Dernière modification de la notice
20/08/2019 16:12
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