Bystander Effect of HSV-TK/GCV Gene
Therapy in Murine Neuroblastoma |
Eun Jung Shim, Se Ryoung Kim, Eun Hae Park, Hyun Sang Cho, Jae Kook Cha, Hae Ran Lee |
Department of Pediatrics, College of Medicine, Hallym University, Seoul, Korea |
HSV-TK 유전자가 발현된 신경모세포종에서 Bystander 효과 |
심은정, 김세령, 박은혜, 조현상, 차재국, 이혜란 |
한림대학교 의과대학 소아과학교실 |
Correspondence:
Hyun Sang Cho, Email: hscho@hallym.or.kr |
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Abstract |
Purpose : To demonstrate the bystander effect in murine neuroblastoma model which transduced with HSV-TK gene in vitro and in vivo.
Methods : The LNC/TK vector was transfered in vitro into the neuro-2a cells, murine neuroblastoma cell line. Variable mixed populations of neuro-2a cells consisting of HSV-TK+ or HSV-TK- were plated into culture plates and treated with GCV for another 4 days. Surviving cells were counted and cell viability was determinated. For investigating the in vivo bystander effect, variable mixed populations of neuro-2a cells consisting of HSV-TK+ and HSV-TK- were inoculated into A/J mice. The tumor size was measured following injection of GCV for 7 days.
Results : The survival rate of the 100% neuro-2a/TK group was 90%, 25%, 5% and 0%, of 50% neuro-2a/TK group was 92%, 30%, 10% and 0%, and of the 10% neuro-2a/TK group was 95%, 40%, 15% and 5%. But, the survival rate of 0% neuro-2a/TK group was 120%, 150%, 180% and 220% on days 1, 2, 3, and 4 respectively. In the 100% and 50% neuro-2a/TK groups, tumor had disappeared following administration of GCV and in 10% neuro-2a/TK group, tumor size was not increased during GCV treatment. In 0% neuro-2a/TK group, tumor size increased during administration of GCV and all mice died after 6 weeks.
Conclusion : We demonstrated the bystander effect in a murine neuroblastoma model which transduced with HSV-TK gene in vitro and in vivo. These results suggest that HSV-TK/GCV gene therapy may be useful for treatment of neuroblastoma. |
Key Words:
Bystander effect, HSV-TK, Neuroblastoma |
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