) Effective therapies for androgen-independent prostate cancer are urgently needed. The principal investigator has pioneered the hypothesis that the hormonal form of vitamin D, 1,25-Dihydroxyvitamin D (1,25(OH)2-D), modulates the growth and normal differentiation of prostatic cells. This evidence includes the ubiquitous presence of receptors for 1,25(OH)2D (VDRs), and the antiproliferative and prodifferentiating effects of 1,25(OH)2D in prostatic cells in vitro and in vivo. These findings strongly support the use of 1,25(OH)2D in prostate cancer therapy. However, the use of 1,25(OH)2D in men with prostate cancer is limited by the risk of hypercalcemia. The principal investigator recently demonstrated that prostate cancer cells synthesize 1,25(OH)2.D from its precursor, 25-Hydroxyvitamin D (25-OH-D, also known as calcidiol). Moreover, we showed that in vitro, prostate cells respond to 25-OH-D by a significant inhibition of proliferation. These findings have important implications for prostate cancer therapy because 25- OH-D carries a much lower risk of hypercalcemia than 1,25(OH)2D. We hypothesize that 25-OH-D will inhibit the in vivo proliferation of human prostate cancer cells xenografted into nude mice. Furthermore, we hypothesize that 25-OH-D will not cause elevations in serum 1,25(OH)2D and serum calcium.
The Specific Aims of this research are to: 1. Compare the growth of xenografted human prostatic tumors in mice treated with 25-OH-D vs. placebo control. 2. Determine the possible toxicity of 25-OH-D by measuring serum 1,25(OH)2D, calcium, and body weight. 3. Correlate 25-OH-D treatment with tumor markers in the xenografts and with histological differentiation of the normal mouse prostates.
| Schwartz, Gary G (2005) Vitamin D and the epidemiology of prostate cancer. Semin Dial 18:276-89 |
| Young, Michael V; Schwartz, Gary G; Wang, Lilin et al. (2004) The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. Carcinogenesis 25:967-71 |
