Cited 25 times in
Combined antitumor effects of an adenoviral cytosine deaminase/thymidine kinase fusion gene in rat C6 glioma
DC Field | Value | Language |
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dc.contributor.author | 김주항 | - |
dc.date.accessioned | 2019-11-11T05:22:38Z | - |
dc.date.available | 2019-11-11T05:22:38Z | - |
dc.date.issued | 2000 | - |
dc.identifier.issn | 0148-396X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/171822 | - |
dc.description.abstract | OBJECTIVE: In this study, we investigated the feasibility of a double-suicide gene/prodrug therapy, involving direct introduction of the herpes simplex virus Type 1 thymidine kinase (TK) gene and the Escherichia coli cytosine deaminase (CD) gene, via a recombinant adenoviral vector, and ganciclovir (GCV) and/or 5-fluorocytosine (5-FC) treatment, in a rat C6 glioma model. METHODS: Efficient gene transfer and transduction of C6 glioma cells via a recombinant adenovirus were evaluated by infecting cells with adenovirus bearing the beta-galactosidase gene and then staining cells with X-5-bromo-4-chloro-3-indolyl-13-D-galactoside. CD/TK expression in cells infected with adenovirus bearing the CD/TK gene (ad-CD/TK) was examined by immunoblotting analysis. For in vitro cytotoxicity experiments, the cells were infected with ad-CD/TK or ad-deltaE1 (as a control). After the addition of a variety of concentrations of GCV and 5-FC, either separately or in combination, cell viability was determined by staining the cells with crystal violet solution 6 days after infection. For in vivo antitumor experiments, 1x10(5) cells were stereotactically injected into the right caudate-putamen of female Wistar rat brains. At 3 days after implantation, 1x10(8) plaque-forming units of ad-CD/TK or ad-deltaE1 (as a control) were stereotactically injected into the tumors and GCV (25 mg/kg) and 5-FC (250 mg/kg), alone or in combination, were intraperitoneally administered. Animals were then killed, and tumor volumes were measured by determining the tumor area in every fifth section, using a light microscope. RESULTS: C6 glioma cells were efficiently transduced with recombinant adenoviral vector at multiplicities of infection of 200 or more. In vitro cytotoxicity of GCV and/or 5-FC, either alone or in combination, was exclusively observed in the cells transduced with ad-CD/TK. Obvious cytotoxicity (>50% inhibition) was observed in the presence of 5-FC at concentrations greater than 30 microg/ml or GCV at concentrations greater than 0.3 microg/ml at a multiplicity of infection of 100. Additionally, cytotoxicity in the presence of both GCV and 5-FC was greater than that after single-prodrug treatments, indicating additive effects of the prodrug treatments. In in vivo experiments, the tumor volumes of the rats treated with GCV or 5-FC alone after ad-CD/TK injection (59.1+/-4.6 and 57.4+/-7.1 mm3, respectively) were significantly smaller than that of the control rats (157+/-8.9 mm3, P<0.05). Furthermore, the tumor volume of the rats treated with GCV and 5-FC in combination was 14.7+/-1.8 mm3. CONCLUSION: These results demonstrated the efficient transduction of C6 glioma cells with a recombinant adenovirus and the additive effects of CD/TK fusion gene/GCV/5-FC treatment, compared with single-gene therapy with the TK or CD gene. Therefore, our data suggest that the direct administration of a double-suicide gene/prodrug therapy has great potential in the treatment of brain tumors. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Lippincott Williams & Wilkins | - |
dc.relation.isPartOf | Neurosurgery | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adenoviridae/genetics* | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antimetabolites/therapeutic use | - |
dc.subject.MESH | Antiviral Agents/therapeutic use | - |
dc.subject.MESH | Artificial Gene Fusion* | - |
dc.subject.MESH | Brain Neoplasms/metabolism | - |
dc.subject.MESH | Brain Neoplasms/therapy* | - |
dc.subject.MESH | Combined Modality Therapy | - |
dc.subject.MESH | Cytosine Deaminase | - |
dc.subject.MESH | Feasibility Studies | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Flucytosine/therapeutic use | - |
dc.subject.MESH | Ganciclovir/therapeutic use | - |
dc.subject.MESH | Glioma/metabolism | - |
dc.subject.MESH | Glioma/therapy* | - |
dc.subject.MESH | Neoplasm Transplantation | - |
dc.subject.MESH | Nucleoside Deaminases/genetics* | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Rats, Wistar | - |
dc.subject.MESH | Recombinant Fusion Proteins/metabolism | - |
dc.subject.MESH | Thymidine Kinase/genetics* | - |
dc.subject.MESH | Transduction, Genetic | - |
dc.subject.MESH | Tumor Cells, Cultured | - |
dc.title | Combined antitumor effects of an adenoviral cytosine deaminase/thymidine kinase fusion gene in rat C6 glioma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Jin Woo Chang | - |
dc.contributor.googleauthor | Heuiran Lee | - |
dc.contributor.googleauthor | Eunhee Kim | - |
dc.contributor.googleauthor | Yong Lee | - |
dc.contributor.googleauthor | Sang Sup Chung | - |
dc.contributor.googleauthor | Joo-Hang Kim | - |
dc.identifier.doi | 10.1097/00006123-200010000-00026 | - |
dc.contributor.localId | A00945 | - |
dc.relation.journalcode | J02366 | - |
dc.identifier.eissn | 1524-4040 | - |
dc.identifier.pmid | 11014433 | - |
dc.identifier.url | https://academic.oup.com/neurosurgery/article/47/4/931/2748520 | - |
dc.subject.keyword | Adenoviridae | - |
dc.subject.keyword | genetics | - |
dc.subject.keyword | Animals | - |
dc.subject.keyword | Antimetabolites | - |
dc.subject.keyword | therapeutic use | - |
dc.subject.keyword | Antiviral Agents | - |
dc.subject.keyword | Artificial Gene Fusion | - |
dc.subject.keyword | Brain Neoplasms | - |
dc.subject.keyword | metabolism | - |
dc.subject.keyword | therapy | - |
dc.subject.keyword | Combined Modality Therapy | - |
dc.subject.keyword | Cytosine Deaminase | - |
dc.subject.keyword | Feasibility Studies | - |
dc.subject.keyword | Female | - |
dc.subject.keyword | Flucytosine | - |
dc.subject.keyword | Ganciclovir | - |
dc.subject.keyword | Glioma | - |
dc.subject.keyword | Neoplasm Transplantation | - |
dc.subject.keyword | Nucleoside Deaminases | - |
dc.subject.keyword | Rats | - |
dc.subject.keyword | Rats | - |
dc.subject.keyword | Wistar | - |
dc.subject.keyword | Recombinant Fusion Proteins | - |
dc.subject.keyword | Thymidine Kinase | - |
dc.subject.keyword | Transduction | - |
dc.subject.keyword | Genetic | - |
dc.subject.keyword | Tumor Cells | - |
dc.subject.keyword | Cultured | - |
dc.contributor.alternativeName | Kim, Joo Hang | - |
dc.contributor.affiliatedAuthor | 김주항 | - |
dc.citation.volume | 47 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 931 | - |
dc.citation.endPage | 939 | - |
dc.identifier.bibliographicCitation | Neurosurgery, Vol.47(4) : 931-939, 2000 | - |
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