Suicide Gene therapy for Malignant Gilomas using Neural Stem Cells

INTRODUCTION: Despite advanced neurosurgical techniques and various multimodal therapeutic approach have been developed for malignant gliomas, these can not save the patients from the tumors due to infiltrating behavior of these glioma cells. Here, author investigated the possibility of treatment for the malignant gliomas with neural stem cell (HB1.F3) transduced with suicidal gene using the tropism of stem cells. MATERIALS AND METHODS: E.coli cytosine deaminase(CD) of suicide gene is enzyme that catalyzes the conversion of noncytotoxic 5-FC to the cytotoxic and radiosensitizing drug 5-FU. Cytotoxic 5-FU and its toxic metabolites can readily diffuse unto surrounding tumor cells giving CD. HB1.F3 were transduced with retroviral vectors expressing the E.coli CD. Rats were implanted with U373MG, U251MG human glioblastoma(hGM) line and F3/CD were injected directly into the tumor mass 6 days later. The rats with tumors were injected IP 5-FC or saline daily for 7 days since 6 days after implantation of tumors. RESULTS: HB1.F3 which were injected into the contralateral hemisphere to the tumor implantation site migrated through the corpus callosum to the tumor cells 3days after hGM transplantation. The growth inhibition of treated cells 5-FU in comparison to untreated controls was remarkable in vitro. The tumor mass in the rats with transplantation of F3/CD were reduced markedly in size comparing to that with F3 after injection of 5-FC. CONCLUSIONS: 1. The human neural stem cells can trace to the glioma cells in the rat brain. Systemic treatment with 5-FC reduced the size of tumor with direct transplantation of F3/CD. 2. Our data indicate that suicide gene therapy using neural stem cells would be promising as a new therapeutic approach for malignant glioma.

Author dc:creator

• 안, 영민

Contributors dc:contributor

• 조, 경기
• 대학원 의학과
• 200224481

• cytosine deaminase
• 5-Fluorocytosine
• Neural stem cell
• 악성 신경교종
• 신경줄기세포

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001755
000000001755

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1613