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KMID : 0942820060050020085
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Journal of Korean Brain Tumor Society
2006 Volume.5 No. 2 p.85 ~ p.91
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Suicide Gene Therapy for Malignant Gilomas Using Neural Stem Cells
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Ahn Young-Min
Cho Kyung-Gi
Lee Chang-Mi
Bang Joung-Hee
Ryu Myung-Yi
Kim Se-Joong
Suh Hae-Young
Kim Seung-Up
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Abstract
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Introduction: Despite the 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 glioma cells. Here the authors investigated the possibility of treatment for the malignant gliomas with neural stem cel (HB1.F3) transduced with suicidal gene using the tropism of stem cells.
Materials and Methods: Methods：E.coli cytosine deaminase(CD) is an 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 into surroundingtumor cells giving CD. HB1.F3 were transduced with retroviral vectors expressing the E.coli CD. Rats were implanted with U373MG, U251MG human glioblastoma(hGM) cell 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: Results：HB1.F3 which were injected into the contralateral hemisphere to the tumor implantation site migrated through the corpus callosum to the tumor cells 3 days after hGM transplantation . The growth inhibition of 5-FU treated cells 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: The human neural stem cells can trace to the glioma cells in the rat brain. 5-FC systemic treatment with direct transplantation of F3/CD reduces tumor size. Our data indicates that suicide gene therapy using neural stem cells would be promising as a new therapeutic approach for malignant glioma.
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KEYWORD
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Suicide gene therapy, Malignant glioma, Neural stem cell, Cytosine deaminase, 5-FU
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