Background: Cancer chemoprevention trials require enormous resources due to the large numbers of patients and the years of follow-up needed to achieve sufficient statistical power. Examination of candidate prevention agents using biomarkers as surrogate end points has been proposed as a method to rapidly identify promising agents for prevention trials. Treatment of patients with candidate agents prior to scheduled biopsy or surgical resection of malignancy allows for direct examination of the treatment effects on tumor tissue. In this study, we selected this approach to test several hypotheses about the effect of calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, on early-stage human prostate cancer. Methods: After selection of surgical treatment for histologically confirmed adenocarcinoma of the prostate, patients were randomized to either calcitriol 0.5 μ/kg or placebo weekly for 4 weeks. The expression levels of the vitamin D receptor (VDR), proliferating cell nuclear antigen, PTEN (MMAC1/TEP1), c-Myc, transforming growth factor (TGF) β receptor type II (TGFβ RII), and Bcl-2 were quantified using immunohistochemistry in the patients' prostate specimens post surgery. Results: Thirty-seven of 39 prostate tumors were evaluable for molecular end points. VDR expression was reduced in patients treated with calcitriol (mean, 75.3% of cells) compared with those that received placebo (mean, 98.6%; P = 0.005). Calcitriol treatment did not result in a statistically significant change in the fraction of cells expressing TGFβ RII, PTEN, or proliferating cell nuclear antigen. Bcl-2 and c-Myc expression was at the lower limits of detection in both the calcitriol group and the placebo group; therefore, we were unable to determine whether drug treatment induced a significant change in these biomarkers. Conclusions: High-dose calcitriol down-regulates VDR expression in human prostate cancer. Further study is needed to determine the biological consequences of VDR down-regulation in prostate cancer. This study shows that the use of the preprostatectomy model is feasible and can be used to test the effect of candidate chemopreventive agents on prostate cancer.
|Original language||English (US)|
|Number of pages||8|
|Journal||Cancer Epidemiology Biomarkers and Prevention|
|State||Published - Dec 2004|
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