CALCIDIOL THERAPY FOR PROSTATE CANCER

描述(申请人的描述) 雄激素非依赖性前列腺癌的有效治疗迫在眉睫 需要的。首席研究员率先提出了一种假设，即 维生素D的激素形式，1，25-二羟基维生素D(1，25(OH)2-D)，调节 前列腺细胞的生长和正常分化。这一证据 包括普遍存在的1，25(OH)2D(VDR)受体，以及 1，25(OH)2D在前列腺中的抗增殖和分化作用 细胞在体外和体内。这些发现有力地支持了使用 1，25(OH)2D在前列腺癌治疗中的应用然而，1，25(OH)2D在男性中的使用 患有前列腺癌的人受到高钙血症风险的限制。 首席研究人员最近证明，前列腺癌细胞 由其前体25-羟基维生素D(25-OH-D)合成1，25(OH)2.D 称为钙化二醇)。此外，我们还表明，在体外，前列腺细胞 对25-羟基-D有明显的抑制增殖作用。这些 研究结果对前列腺癌治疗具有重要意义，因为25- OH-D与1，25(OH)2D相比，患高钙血症的风险要低得多。我们 25-羟基-D对人卵巢癌细胞体内增殖的抑制作用 将前列腺癌细胞移植到裸鼠体内。此外，我们假设 25-羟基-D不会引起血清1，25(OH)2D和血钙升高。 这项研究的具体目的是： 1.比较治疗后小鼠移植人前列腺癌的生长情况 25-羟基-D与安慰剂对照。 2.通过测定血清1，25(OH)2D来确定25-OH-D的可能毒性。 钙和体重。 3.25-OH-D治疗与移植瘤中肿瘤标志物的相关性 正常小鼠前列腺的组织学分化。

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.