Treatment of thyroid carcinoma cells with four different suicide gene/prodrug combinations in vitro.
To develop a suitable suicide gene/prodrug therapy for the treatment of thyroid carcinomas, the relative therapeutic efficacy of four different suicide gene/prodrug combinations was compared in thyroid carcinomas in vitro. Herpes simplex virus thymidine kinase and ganciclovir (HSV-TK/GCV), Escherichia coli cytosine deaminase and 5-fluorocytosine (CD/5FC), E coli nitroreductase and CB1954 (NTR/CB1954), and human deoxycytidine kinase and cytosine arabinoside (dCK/AraC) were employed. The suicide genes were transduced into two thyroid carcinoma cell lines with retroviral vectors in which all the suicide genes were under the control of the same promoter. When the relative efficacy of four suicide gene/prodrugs was compared with therapeutic index and degree of bystander effect, we found a clear dissociation between these two parameters. Thus, HSV-TKIGCV demonstrated the widest therapeutic index, while CD/5FC and NTR/CB1954 showed the stronger bystander effect than HSV-TK/GCV. dCK/AraC had little efficacy. Advantages and limitations of each suicide gene/prodrug combinations are discussed.
Department of Nature Medicine, Nagasaki University School of Medicine, Japan.
E
E
Nishihara
Y
Y
Nagayama
M
M
Narimatsu
H
H
Namba
M
M
Watanabe
M
M
Niwa
S
S
Yamashita
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001388:Aziridines / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000633:toxicity*; D043525:Cytosine Deaminase; D003842:Deoxycytidine Kinase / Q000096:biosynthesis; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005437:Flucytosine / Q000633:toxicity*; D015774:Ganciclovir / Q000633:toxicity*; D005822:Genetic Vectors; D006801:Humans; D009601:Nitroreductases / Q000096:biosynthesis; D009700:Nucleoside Deaminases / Q000096:biosynthesis; D011355:Prodrugs / Q000633:toxicity*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001388:Aziridines; D011355:Prodrugs; D011994:Recombinant Proteins; D003561:Cytarabine; C100099:tretazicar; D005437:Flucytosine; D009601:Nitroreductases; D013937:Thymidine Kinase; D003842:Deoxycytidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D015774:Ganciclovir