Enhanced efficacy of transcriptionally targeted suicide gene/prodrug therapy for thyroid carcinoma with the Cre-loxP system.
Our recent study demonstrates the feasibility of the thyroglobulin (TG) promoter in transcriptionally targeted gene therapy for thyroid carcinomas expressing TG, albeit less effectively than the constitutive viral promoter. The present study was, therefore, designed to enhance the activity of the TG promoter with the Cre-loxP system. Our data demonstrate that the in vitro cytotoxic effect of herpes simplex virus thymidine kinase/ganciclovir obtained with the TG promoter and the Cre-loxP system is approximately 5-10-fold higher than that with the TG promoter alone. Enhanced tumor growth inhibition was also observed in in vivo tumor models. These data indicate the usefulness of the Cre-loxP system to enhance the activity of a tissue (or tumor)-specific promoter in transcriptionally targeted cancer gene therapy.
Department of Pharmacology 1, Nagasaki University School of Medicine, Japan. nagayama@net.nagasaki-u.ac.jp
Y
Y
Nagayama
E
E
Nishihara
M
M
Iitaka
H
H
Namba
S
S
Yamashita
M
M
Niwa
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D015774:Ganciclovir / Q000627:therapeutic use; D018390:Gene Targeting; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011355:Prodrugs / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland; D013964:Thyroid Neoplasms / Q000628:therapy*; D014158:Transcription, Genetic; D014162:Transfection
D011355:Prodrugs; D011994:Recombinant Proteins; D013954:Thyroglobulin; D013937:Thymidine Kinase; D015774:Ganciclovir