Retrovirally transmitted gene therapy for gastric carcinoma using herpes simplex virus thymidine kinase gene.
BACKGROUND
Herpes simplex thymidine kinase (HTK) is known to phosphorylate ganciclovir (GCV). Phosphorylated GCV is incorporated into genomic DNA, which leads to inhibition of cell growth and cell death in the replicating cells. Recently, much attention has been drawn to the use of retrovirally mediated gene therapy using HTK as a new therapeutic approach for brain tumors. However, little is known about this phenomenon in gastrointestinal carcinomas.


METHODS
The authors transfected the HTK gene packaged in retroviral vector into TMK-1 gastric carcinoma cells (TMK-HTK cells). Sensitivity of TMK-HTK cells to GCV was examined in vitro. Moreover, TMK-HTK cells were transduced into nude mice subcutaneously, and the effects of GCV therapy was examined at the concentration of 20 mg/kg daily for 14 days.


RESULTS
TMK-HTK cells were sensitive to GCV at the concentration of 0.1 to 100 micrograms/ml in a dose- and time-dependent manner in vitro. Moreover, 12 of 13 TMK-HTK tumors, which were transduced into nude mice subcutaneously, shrunk from the average diameter of 6.5 mm.


CONCLUSIONS
The results indicate that retrovirally transmitted gene therapy with GCV may provide a new therapeutic approach for treatment of gastric carcinomas.
Yoshida
K
K
Department of Surgery, Hiroshima University, Japan.
Kawami
H
H
Yamaguchi
Y
Y
Kuniyasu
H
H
Nishiyama
M
M
Hirai
T
T
Yanagihara
K
K
Tahara
E
E
Toge
T
T
D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D015774:Ganciclovir / Q000494:pharmacology; D005814:Genes, Viral; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D018139:Simplexvirus / Q000235:genetics*; D013274:Stomach Neoplasms / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir