| RRC ID |
64619
|
| Author |
Kunishige I, Samejima Y, Shiki Y, Moriyama A, Meruelo D, Saji F, Murata Y.
|
| Title |
Suicide gene therapy for human uterine adenocarcinoma cells using herpes simplex virus thymidine kinase.
|
| Journal |
Gynecol Oncol
|
| Abstract |
In gene therapy, the herpes simplex virus thymidine kinase (HSV-tk) gene is widely used as a suicide agent. Tumor cells expressing HSV-tk are sensitive to nucleoside analogs such as ganciclovir (GCV). An advantage of this system is the bystander killing effect whereby HSV-tk-positive cells exposed to GCV are lethal to surrounding HSV-tk-negative cells. We transfected the HSV-tk gene into a human cervical adenocarcinoma cell line, BU25TK-, and a human endometrial adenocarcinoma cell line, HHUA, by the Lipofectine method. The sensitivity of HSV-tk-positive cells to GCV and bystander killing effect on HSV-tk-negative cells were examined in vitro. HSV-tk-positive cells were sensitive to GCV at concentrations of 1 to 100 microg/ml in a dose- and time-dependent manner. The growth of HSV-tk-negative cells was inhibited when the population of cultured cells contained more than about 3% HSV-tk-positive cells. Moreover, for BU25TK- cells, HSV-tk-positive cells were injected into SCID mice subcutaneously and the effects of GCV therapy and bystander killing at a daily concentration of 25 mg/kg for 14 days were examined. HSV-tk-positive tumors transduced into SCID mice almost disappeared upon GCV treatment. Furthermore, tumor reduction was observed when mixtures of HSV-tk-negative cells containing more than 20% HSV-tk-positive cells were injected into SCID mice. In conclusion, the HSV-tk/GCV system might be applied to both cervical and endometrial adenocarcinoma.
|
| Volume |
72(1)
|
| Pages |
16-25
|
| Published |
1999-1-1
|
| DOI |
10.1006/gyno.1998.5224
|
| PII |
S0090-8258(98)95224-6
|
| PMID |
9889024
|
| MeSH |
Adenocarcinoma / genetics
Adenocarcinoma / therapy*
Animals
Female
Ganciclovir / therapeutic use
Genetic Therapy / methods*
Humans
Mice
Mice, SCID
Simplexvirus* / genetics
Thymidine Kinase* / genetics
Tumor Cells, Cultured
Uterine Neoplasms / genetics
Uterine Neoplasms / therapy*
|
| IF |
4.623
|
| Resource |
| Human and Animal Cells |
HHUA(RCB0658)
BU25 TK-(RCB0205) |
