Document Detail

Neural stem cell-based dual suicide gene delivery for metastatic brain tumors.
MedLine Citation:
PMID:  23018623     Owner:  NLM     Status:  Publisher    
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.Cancer Gene Therapy advance online publication, 28 September 2012; doi:10.1038/cgt.2012.63.
C Wang; A Natsume; H J Lee; K Motomura; Y Nishimira; M Ohno; M Ito; S Kinjo; H Momota; K Iwami; F Ohka; T Wakabayashi; S U Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-28
Journal Detail:
Title:  Cancer gene therapy     Volume:  -     ISSN:  1476-5500     ISO Abbreviation:  Cancer Gene Ther.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9432230     Medline TA:  Cancer Gene Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1] Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan [2] China Scholarship Council, Beijing, China.
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