SELENIUM BASED CHEMOPREVENTION

我们建议评估男性前列腺癌的化学预防 由于被诊断患有高级别前列腺增生症， 上皮内瘤变（HGPIN），在前列腺癌中显著升高 风险在HGPIN的活检诊断后，每例受试者将被重新检查。 活检以最大限度地减少首次活检时遗漏PC的可能性。 然后，受试者将被随机分配至200 mcg/天的硒组， 形式的L-硒代甲硫氨酸或匹配的安慰剂。随机分组后， 每个受试者将被跟踪三年。 本研究的主要终点是PC。次要终点将包括 两种已确立的替代终点生物标志物（SEB）：Ki-67评价 细胞增殖和凋亡的TUNEL评价。这一切成功都 将评价终点的重现性、预测关联性 与随后的PC，并为响应硒补充。在 此外，我们还建议对两个潜在的SEB进行发展研究 基于机器视觉的组织测量： 前列腺导管和染色质模式的组织计量学特征。 将研究这些开发SEB的重现性。

We propose to evaluate the chemoprevention of prostate cancer among men who are, by virtue of having been diagnosed with High Grade Prostatic Intraepithelial Neoplasia (HGPIN), at a greatly elevated prostate cancer risk. After a biopsy-based diagnosis of HGPIN, each subject will be re- biopsied to minimize the probability he has PC missed by the first biopsy. Subjects will then be randomized to either 200 mcg/day of selenium in the form of L-selenomethionine or to a matching placebo. After randomization, each subjective will be followed for three years. The primary endpoint of this study is PC. Secondary endpoints will include two established Surrogate Endpoint Biomarkers (SEBs): Ki-67 evaluation of cell proliferation and TUNEL evaluation of apoptosis. Each of these endpoints will be evaluated for reproducibility, predictive association with subsequent PC, and for response to selenium supplementation. In addition, we propose a developmental investigation of two potential SEBs that are based on machine vision histometry: erosion of the basal cells of prostatic ducts and histometric characteristics of chromatin patterns. These developmental SEBs will be investigated for reproducibility.