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Bystander Effect of HSV-TK/GCV Gene Therapy in Murine Neuroblastoma

Journal of the Korean Pediatric Society 2001;44(11):1249-1253.
Published online November 15, 2001.
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
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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