5-aza-2'-deoxycytidine delays androgen-independent disease and improves survival in the transgenic adenocarcinoma of the mouse prostate mouse model of prostate cancer.

Zorn, CS; Wojno, KJ; McCabe, MT; Kuefer, R; Gschwend, JE; Day, ML

doi:10.1158/1078-0432.CCR-06-2381

journal article

Titel:: 5-aza-2'-deoxycytidine delays androgen-independent disease and improves survival in the transgenic adenocarcinoma of the mouse prostate mouse model of prostate cancer.
Dokumenttyp:: Journal Article; Research Support, N.I.H., Extramural; Article
Autor(en):: Zorn, CS; Wojno, KJ; McCabe, MT; Kuefer, R; Gschwend, JE; Day, ML
Abstract:: PURPOSE: We have previously shown that 5-aza-2'-deoxycytidine (5-aza) is an effective chemopreventive agent capable of preventing early disease progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. The purpose of this study was to determine the effect of 5-aza on preexisting TRAMP prostate cancers and prevention of androgen-independent prostate cancer. EXPERIMENTAL DESIGN: TRAMP mice with established prostate cancers were treated with 5-aza, castration, castration + 5-aza, or vehicle control (PBS). One cohort of 22 mice per treatment was euthanized after 10 weeks of treatment, whereas a second cohort of 14 mice per group was followed until death to determine survival. Histologic sections of prostate, pelvic lymph nodes, lung, and liver were blinded and analyzed by a certified genitourinary pathologist (K.J.W.). RESULTS: Combined treatment (castration + 5-aza) provided significant survival benefits over either single treatment (combined versus castration P = 0.029, combined versus 5-aza P = 0.036). At 24 weeks of age, 86% of mice within the PBS cohort exhibited histologic evidence of prostate cancer, whereas only 47% of the combined cohort exhibited malignant disease (P < 0.0001). Additionally, whereas 43% of the PBS treatment group exhibited lymph node metastases, these were only observed in 21% of the combined treatment mice. CONCLUSIONS: This is the first study to examine the effect of 5-aza and combined castration + 5-aza on preexisting prostate cancer in an animal model. Based on these preclinical findings, we suggest that 5-aza treatment may prolong the time to an androgen-independent status and thus survival in a hormone-deprived setting in prostate cancer.
Zeitschriftentitel:: Clin Cancer Res
Jahr:: 2007
Band / Volume:: 13
Heft / Issue:: 7
Seitenangaben Beitrag:: 2136-43
Sprache:: eng
Volltext / DOI:: doi:10.1158/1078-0432.CCR-06-2381
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/17404097
Print-ISSN:: 1078-0432
TUM Einrichtung:: Urologische Klinik und Poliklinik
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Urologie (Prof. Gschwend)2007