RRC ID 42113
Author Shirakawa T, Gotoh A, Zhang Z, Kao C, Chung LW, Gardner TA.
Title Development of human chorionic gonadotropin subunit-beta promoter-based toxic gene therapy for testicular cancer.
Journal Urology
Abstract OBJECTIVES:To develop a new toxic gene therapy using the tissue-specific human chorionic gonadotropin-beta (hCG-beta) promoter for testicular cancer. Although most patients presenting with disseminated testicular tumor are cured through the use of chemotherapy with or without surgery, those patients with relapse after initial therapy present a difficult clinical problem. The serum tumor marker hCG-beta is frequently elevated in patients with testicular cancer, and the pretreatment and post-treatment levels of serum hCG-beta are highly predictive of treatment outcome.
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.
Volume 63(3)
Pages 613-8
Published 2004-3-1
DOI 10.1016/j.urology.2003.09.054
PII S0090429503010574
PMID 15028478
MeSH Acyclovir / therapeutic use Adenoviridae / genetics Animals Biomarkers, Tumor / blood Carcinoma / pathology Carcinoma, Embryonal / metabolism Carcinoma, Embryonal / pathology Carcinoma, Embryonal / therapy* Cell Line, Tumor Chorionic Gonadotropin, beta Subunit, Human / biosynthesis Chorionic Gonadotropin, beta Subunit, Human / 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 Neoplasm Proteins / genetics Prodrugs / therapeutic use Promoter Regions, Genetic* Prostatic Neoplasms / pathology Recombinant Fusion Proteins / biosynthesis Recombinant Fusion Proteins / genetics Salvage Therapy Testicular Neoplasms / metabolism Testicular Neoplasms / pathology Testicular Neoplasms / therapy* Thymidine Kinase / biosynthesis Thymidine Kinase / genetics Urinary Bladder Neoplasms / pathology Xenograft Model Antitumor Assays
IF 1.924
Times Cited 4
Human and Animal Cells