RRC ID 39285
Author Hayashi N, Ido E, Ohtsuki Y, Ueno H.
Title An experimental application of gene therapy for human retinoblastoma.
Journal Invest Ophthalmol Vis Sci
Abstract PURPOSE:The purpose was to determine the potential of gene therapy for retinoblastoma using transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene into retinoblastoma cells (Y79 cell line).
METHODS:A retrovirus-packaging cell line PA317 was electroporated with a retroviral vector plasmid bearing HSV-TK and neomycin-resistance genes to produce a PA317-TK cell line releasing a replication-defective vector bearing both genes. Y79 was transduced by exposure to transmissible virus-containing medium from PA317-TK, and new clones of Y79 containing the HSV-TK gene (Y79-TK) were established. Sensitivity to ganciclovir (GCV) and acyclovir (ACV) was investigated in Y79 and Y79-TK and the effect of HSV-TK-positive cells on negative cells ("bystander effect") was determined in vitro. The effect of antitumorigenesis in a nude mouse system was also investigated.
RESULTS:There were no differences in the growth pattern or the morphology between Y79 and Y79-TK. Y79-TK was more sensitive to GCV and ACV than was Y79. The cytotoxicity of Y79-TK was dose dependent. An obvious "bystander effect" was present with the addition of GCV. In vivo studies confirmed the ability of GCV to kill Y79-TK.
CONCLUSIONS:In this study a model is proposed for the introduction of a drug-sensitivity gene into Y79 and the possibility is raised of treating retinoblastoma with gene therapy. The results suggest that the transfer of the HSV-TK gene into Y79 followed by the administration of GCV could serve as a model for gene therapy for retinoblastoma.
Volume 40(2)
Pages 265-72
Published 1999-2-1
PMID 9950583
MeSH Acyclovir / pharmacology Animals Defective Viruses Dose-Response Relationship, Drug Electroporation Ganciclovir / pharmacology Gene Transfer Techniques Genetic Therapy* Genetic Vectors Herpesvirus 1, Human / drug effects Herpesvirus 1, Human / enzymology Herpesvirus 1, Human / genetics Humans Male Mice Mice, Inbred BALB C Mice, Nude Retinal Neoplasms / pathology Retinal Neoplasms / therapy* Retinal Neoplasms / virology Retinoblastoma / pathology Retinoblastoma / therapy* Retinoblastoma / virology Retroviridae / genetics Thymidine Kinase / genetics Tumor Cells, Cultured
IF 3.47
Times Cited 8
Human and Animal Cells Y79(RCB0427)