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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2008.1
- 수록면
- 811 - 818 (8page)
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초록· 키워드
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Purpose: We have used a genetically attenuated adenoviral vector which expresses HSVtk to assess the possible additive role of suicidal gene therapy for enhanced oncolytic effect of the virus. Expression of TK was measured using a radiotracer- based molecular counting and imaging system. Materials and Methods: Replication-competent recombinant adenoviral vector (Ad-ΔE1B19/55) was used in this study, whereas replication- incompetent adenovirus (Ad-ΔE1A) was generated as a control. Both Ad-ΔE1B19/55-TK and Ad-ΔE1A-TK comprise the HSVtk gene inserted into the E3 region of the viruses. YCC-2 cells were infected with the viruses and incubated with 2'-deoxy- 2'-fluoro-β-D-arabinofuranosyl-5-iodouracil (I-131 FIAU) to measure amount of radioactivity. The cytotoxicity of the viruses was determined, and gamma ray imaging of HSVtk gene was performed. MTT assay was also performed after GCV treatment. Results: On gamma counter-analyses, counts/ minute (cpm)/μg of protein showed MOIs dependency with ΔE1B19/55-TK infection. On MTT assay, Ad-ΔE1B19/55-TK led to more efficient cell killing than Ad-ΔE1A-TK. On plate imaging by gamma camera, both Ad-ΔE1B19/55-TK and Ad-ΔE1A-TK infected cells showed increased I-131 FIAU uptake in a MOI dependent pattern, and with GCV treatment, cell viability of ΔE1B19/55-TK infection was remarkably reduced compared to that of Ad-ΔE1A-TK infection. Conclusion: Replicating Ad-ΔE1B19/55-TK showed more efficient TK expression even in the presence of higher-cancer cell killing effects compared to non-replicating Ad-ΔE1A-TK. Therefore, GCV treatment still possessed an additive role to oncolytic effect of Ad-ΔE1B19/55-TK. The expression of TK by oncolytic viruses could rapidly be screened using a radiotracer-based counting and imaging technique.
목차
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참고문헌 (20)
참고문헌 신청
Barnett BG / 2002 / Targeted adenoviral vectors / Biochim Biophys Acta 1575 : 1 ~ 14
Bischoff JR / 1996 / An adenovirus mutant that replicates selectively in p53-deficient human tumor cells / Science 274 : 373 ~ 376
Braithwaite AW / 2001 / Induction of cell death by adenoviruses / Apoptosis 6 : 359 ~ 370
Cascante A / 2007 / GCV modulates the antitumoural efficacy of a replicative adenovirus expressing the Tat8-TK as a late gene in a pancreatic tumour model / Gene Ther 14 : 1
Dix BR / 2000 / Efficient induction of cell death by adenoviruses requires binding of E1B55k and p53 / Cancer Res 60 : 2666 ~ 2672
Bischoff JR / 1996 / An adenovirus mutant that replicates selectively in p53-deficient human tumor cells / Science 274 : 373 ~ 376
Braithwaite AW / 2001 / Induction of cell death by adenoviruses / Apoptosis 6 : 359 ~ 370
Cascante A / 2007 / GCV modulates the antitumoural efficacy of a replicative adenovirus expressing the Tat8-TK as a late gene in a pancreatic tumour model / Gene Ther 14 : 1
Dix BR / 2000 / Efficient induction of cell death by adenoviruses requires binding of E1B55k and p53 / Cancer Res 60 : 2666 ~ 2672
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