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Recombinant Adenoviral Vector Containing Tumor-Specific L-Plastin Promoter Fused to Cytosine Deaminase Gene as a Transcription Unit: Generation and Functional Test  

Chung, In-Jae (College of Pharmacy, Duksung Women＇s University)
Deisseroth, Albert-B. (Sidney Kimmel Cancer Center)
Publication Information
Archives of Pharmacal Research / v.27, no.6, 2004 , pp. 633-639 More about this Journal
Abstract
The expression of therapeutic transgenes in recombinant adenoviral vectors is a major cause of toxicity in dividing cancer cells as well as non dividing normal cells. To solve the problem of toxicity to normal cells, we have reported on a recombinant adenoviral vector system （AdLP-） in which the expression of the transgene is directed by the tumor-specific L-plastin promoter （LP） （Chung et al., 1999）. The object of this study was to generate a recombinant adenoviral vector system which would generate tumor cell specific expression of cytosine deaminase （CD） gene. We report the construction of a replication-incompetent adenoviral vector in which CD is driven by the L-plastin promoter （AdLPCD）. Infection of 293 cells by AdLPCD generated the functional CD protein as measured by HPLC analysis for the conversion of 5-Fluorocy-tosine （5-FC） to 5-Fluorouracil （5-FU）. HPLC analysis in conjunction with counting radioactivity for ［6-$^3$H］-5FC and ［6-$^3$H］-5FU demonstrated vector dose-dependent conversion of 5-FC to 5-FU in AdLPCD infected ovarian cancer cells. The results from present and previous studies（Peng et al., 2001； Akbulut et al., 2003） suggest that the use of the AdLPCD／5-FC system may be of value in the treatment of cancer including microscopic ovarian cancer in the peritoneal cavity.
Keywords
L-Plastin promoter; Tumor-specific promoter; Cytosine deaminase; AdLPCD; Adenoviral Vector;
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Times Cited By Web Of Science : 3  (Related Records In Web of Science)
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