||5R03CA085750-02 Interpret this number
||Wake Forest University Health Sciences
||Calcidiol Therapy for Prostate Cancer
DESCRIPTION (Applicant's Description)
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.
Vitamin D and the epidemiology of prostate cancer.
Seminars in dialysis, 2005 Jul-Aug; 18(4), p. 276-89.
The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D.
, Schwartz G.G.
, Wang L.
, Jamieson D.P.
, Whitlatch L.W.
, Flanagan J.N.
, Lokeshwar B.L.
, Holick M.F.
, Chen T.C.
Carcinogenesis, 2004 Jun; 25(6), p. 967-71.