Abstract | OBJECTIVES: METHODS: Human testicular embryonal carcinoma cell line, NEC 8, a human prostate cancer cell line, PC-3, and a human bladder cancer cell line, WH, were used in this study. A transient expression experiment was used to analyze the activity of a 729-bp hCG-beta promoter in all three cell lines. A recombinant adenovirus carrying thymidine kinase (Ad- hCG-beta-TK) under control of the hCG-beta promoter was generated. The tissue-specific activity of Ad- hCG-beta-TK was tested in vitro and in vivo. RESULTS: The hCG-beta promoter had significantly greater activity in the hCG-beta-producing cell line (NEC 8) than in the non- hCG-beta-producing cell lines (PC-3 and WH). In vitro, Ad- hCG-beta-TK with acyclovir significantly inhibited NEC 8 growth but not PC-3 or WH cell growth. In vivo, Ad- hCG-beta-TK with acyclovir significantly inhibited NEC 8 subcutaneous tumor growth in nude mice. CONCLUSIONS: In this study, we explored the possibility of developing a new therapeutic agent to target and induce the killing of testicular germ cell tumor selectively by using tissue-specific hCG-beta promoters.
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Authors | Toshiro Shirakawa, Akinobu Gotoh, Zhujun Zhang, Chinghai Kao, Leland W K Chung, Thomas A Gardner |
Journal | Urology
(Urology)
Vol. 63
Issue 3
Pg. 613-8
(Mar 2004)
ISSN: 1527-9995 [Electronic] United States |
PMID | 15028478
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers, Tumor
- Chorionic Gonadotropin, beta Subunit, Human
- Enzyme Inhibitors
- Neoplasm Proteins
- Prodrugs
- Recombinant Fusion Proteins
- Thymidine Kinase
- Acyclovir
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Topics |
- Acyclovir
(therapeutic use)
- Adenoviridae
(genetics)
- Animals
- Biomarkers, Tumor
(blood)
- Carcinoma
(pathology)
- Carcinoma, Embryonal
(metabolism, pathology, therapy)
- Cell Line, Tumor
- Chorionic Gonadotropin, beta Subunit, Human
(biosynthesis, genetics)
- Enzyme Inhibitors
(therapeutic use)
- Genes, Transgenic, Suicide
- Genetic Therapy
- Genetic Vectors
(genetics)
- Humans
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Proteins
(biosynthesis, genetics)
- Prodrugs
(therapeutic use)
- Promoter Regions, Genetic
- Prostatic Neoplasms
(pathology)
- Recombinant Fusion Proteins
(biosynthesis, genetics)
- Salvage Therapy
- Testicular Neoplasms
(metabolism, pathology, therapy)
- Thymidine Kinase
(biosynthesis, genetics)
- Urinary Bladder Neoplasms
(pathology)
- Xenograft Model Antitumor Assays
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