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Neural stem cell-based dual suicide gene delivery for metastatic brain tumors

Cancer Gene Therapy volume 19, pages 796–801 (2012)Cite this article

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Abstract

In our previous works, we demonstrated that human neural stem cells (NSCs) transduced with the cytosine deaminase (CD) gene showed remarkable ‘bystander killer effect’ on glioma and medulloblastoma cells after administration of the prodrug 5-fluorocytosine (5-FC). In addition, herpes simplex virus thymidine kinase (TK) is a widely studied enzyme used for suicide gene strategies, for which the prodrug is ganciclovir (GCV). To apply this strategy to brain metastasis treatment, we established here a human NSC line (F3.CD-TK) expressing the dual suicide genes CD and TK. We examined whether F3.CD-TK cells intensified the antitumor effect on lung cancer brain metastases. In vitro studies showed that F3.CD-TK cells exerted a marked bystander effect on human lung cancer cells after treatment with 5-FC and GCV. In a novel experimental brain metastases model, intravenously administered F3 cells migrated near lung cancer metastatic lesions, which were induced by the injection of lung cancer cells via the intracarotid artery. More importantly, F3.CD-TK cells in the presence of prodrugs 5-FC and GCV decreased tumor size and considerably prolonged animal survival. The results of the present study indicate that the dual suicide gene–engineered, NSC-based treatment strategy might offer a new promising therapeutic modality for brain metastases.

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Authors and Affiliations

  1. Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan

    C Wang, A Natsume, K Motomura, Y Nishimira, M Ohno, M Ito, S Kinjo, H Momota, K Iwami, F Ohka & T Wakabayashi

  2. China Scholarship Council, Beijing, China

    C Wang

  3. Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada and Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea

    H J Lee & S U Kim

Authors
  1. C Wang
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  2. A Natsume
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  3. H J Lee
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  4. K Motomura
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  5. Y Nishimira
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  6. M Ohno
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  7. M Ito
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  8. S Kinjo
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  9. H Momota
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  10. K Iwami
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  11. F Ohka
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  12. T Wakabayashi
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  13. S U Kim
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Correspondence to A Natsume or S U Kim.

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Wang, C., Natsume, A., Lee, H. et al. Neural stem cell-based dual suicide gene delivery for metastatic brain tumors. Cancer Gene Ther 19, 796–801 (2012). https://doi.org/10.1038/cgt.2012.63

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