ENHANCED TRANSGENE EXPRESSION IN ANDROGEN INDEPENDENT PROSTATE CANCER GENE THERAPY BY TAXANE CHEMOTHERAPEUTIC AGENTS
2002; Lippincott Williams & Wilkins; Volume: 167; Issue: 1 Linguagem: Inglês
10.1016/s0022-5347(05)65465-1
ISSN1527-3792
AutoresYingming Li, Takatsugu Okegawa, Donald P. Lombardi, Eugene P. Frenkel, Jer‐Tsong Hsieh,
Tópico(s)Ubiquitin and proteasome pathways
ResumoNo AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Jan 2002ENHANCED TRANSGENE EXPRESSION IN ANDROGEN INDEPENDENT PROSTATE CANCER GENE THERAPY BY TAXANE CHEMOTHERAPEUTIC AGENTS YINGMING LI, TAKATSUGU OKEGAWA, DONALD P. LOMBARDI, EUGENE P. FRENKEL, and JER-TSONG HSIEH YINGMING LIYINGMING LI More articles by this author , TAKATSUGU OKEGAWATAKATSUGU OKEGAWA More articles by this author , DONALD P. LOMBARDIDONALD P. LOMBARDI More articles by this author , EUGENE P. FRENKELEUGENE P. FRENKEL More articles by this author , and JER-TSONG HSIEHJER-TSONG HSIEH More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)65465-1AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Chemotherapy is often used as a primary therapy for metastatic cancer because it kills cells en masse. However, high doses of chemotherapeutic drugs can cause toxicity in nontarget organs. Gene therapy may provide a better alternative to chemotherapy because its targeting of specific genes may reduce the undesirable toxicity associated with chemotherapy. We evaluated whether the chemotherapeutic agent docetaxel or paclitaxel may be combined with gene therapy to create a new therapeutic regimen for metastatic androgen independent prostate cancer. Materials and Methods: The 2 androgen independent prostate cancer cell lines PC-3 and DU 145 were treated with docetaxel or paclitaxel. Three recombinant adenoviruses containing p21WAF-1/CIP1, p53 protein or β-galactosidase complementary DNA under the control of cytomegalovirus promoter were used to determine transgene expression. They were evaluated by Western blot analysis, β-galactosidase activity or in vitro growth assays. The [3H] labeled E1 deleted adenovirus dl312 was used to determine adenovirus uptake into cells. Results: Docetaxel and paclitaxel enhanced adenovirus mediated transgene expression. Docetaxel appears to be a more potent growth inhibitor in vitro. Elevated transgene expression in virus infected cells induced by these 2 drugs was produced by increased cytomegalovirus promoter activity rather than increased virus uptake. Conclusions: The potential synergy of gene therapy with docetaxel and paclitaxel may be an important direction for future therapy for metastatic androgen independent prostate cancer. References 1 : Cancer Statistics, 1999. Ca Cancer J Clin2000; 50: 7. Google Scholar 2 : Recent advances in the treatment of prostate cancer. Ann Oncol1999; 10: 891. Google Scholar 3 : Phase II trial of docetaxel in-patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol1997; 15: 1853. Google Scholar 4 : Phase II trials of docetaxel in advanced ovarian cancer: an update drug review. Eur J Cancer1997; 33: 2167. Google Scholar 5 : Docetaxel: an active drug for squamous cell carcinoma of head and neck. J Clin Oncol1996; 14: 1672. 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Google Scholar From the Departments of Urology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 167Issue 1January 2002Page: 339-346 Advertisement Copyright & Permissions© 2002 by American Urological Association, Inc.Keywordsprostateprostatic neoplasmsneoplasm metastasispaclitaxelgene expressionMetrics Author Information YINGMING LI More articles by this author TAKATSUGU OKEGAWA More articles by this author DONALD P. LOMBARDI More articles by this author EUGENE P. FRENKEL More articles by this author JER-TSONG HSIEH More articles by this author Expand All Advertisement PDF downloadLoading ...
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