Effects of Lycopene on High-Risk Prostatic Tissue

描述：(申请人提供)番茄红素是一种很有前途的 前列腺癌化学保护剂(CAP)。然而，这一政策的实际效果是 这种饮食中的抗氧化剂对前列腺组织的作用还知之甚少。这个 CAP的临床前阶段的特点是从正常到逐渐进展 高级别前列腺上皮内瘤变(HGPIN)， 这很可能是CAP的前驱病变。我们建议进行一项 安慰剂对照随机试验，6个月后， 番茄红素补充剂(每天30毫克)对小鼠分子和细胞形态标志的影响 核心针活检样本取自有记录的HGPIN患者。参与者将是 从西北纪念医院的泌尿外科和 湖畔退伍军人管理医院。我们建议调查 以下是具体目标： 具体目标1：组织中的分子标记。我们将使用传统的 免疫组织化学和计算机图像分析来验证这一假说 番茄红素补充剂改变了标志着 细胞增殖、分化、细胞调控和细胞凋亡的研究现状 高危组织。我们已经选择了一组标记，并对其进行了优先排序 在癌前病变过程中差异表达。 具体目标2：核形态计量学。我们将使用计算机图像分析 为化学预防设置而设计的系统，用于测试假设 抗氧化剂引起核形态指数的有利变化，基于 核的大小、形状和染色质质地。 具体目标3：血清雄激素水平。我们假设，基于事后的结果 一项Ill期抗氧化剂试验，干预将降低 睾酮(总的和非SHBG结合的)和Cx-雄烷二醇葡萄糖醛酸苷。 具体目标4：前列腺液中的生长因子(EPF)。在以前的工作中，我们 建立了EPF中EGF、转化生长因子-α和转化生长因子-β1的检测方法，并报道了Low EGF和高水平的转化生长因子-β1与CAP有关。我们假设这种治疗 增加这些前列腺液中的EGF和降低转化生长因子-β1。 具体目标5：血液中的DNA氧化标记物。我们假设这种治疗 减少淋巴细胞中氧化碱基HMdU和8-OHdG，增加HMdU 一种新的ELISA方法检测血清中的自身抗体。评选结果 拟议的研究将有助于澄清 前列腺中的番茄红素，用于设计III期试验，更广泛地说， 为了确定这种相对无毒的化学预防潜力 饮食化合物。

DESCRIPTION: (provided by applicant) Lycopene is a promising chemopreventiveagent for prostatecancer (CaP). However, the actual effects of this dietary antioxidant on prostatic tissue are poorly understood. The preclinical phase of CaP is characterized by a gradual progression from normal epithelium through high-grade prostatic intraepithelial neoplasia (HGPIN), which is very likely the precursor lesion for CaP. We propose to conduct a placebo-controlled randomized trial to investigate the effects, after 6 months, of lycopene supplements (30 mg/day) on molecular and cell morphology markers in core needle biopsy samples from men with documented HGPIN. Participants will be recruited from the Urology services at Northwestern Memorial Hospital and the Lakeside Veterans Administration Hospital. We propose to investigate the following specific aims: Specific Aim 1:Molecular markers in tissue. We will use conventional immunohistochemistry and computer-based image analysis to test the hypothesis that the lycopene supplements alter the expression of proteins marking the status of proliferation, differentiation, cell regulation and apoptosis in high-risk tissue. We have chosen and prioritized a panel of markers that are differentially expressed during precancerous progression. Specific Aim 2: Nuclear morphometry. We will use a computerized image analysis system designed for the chemoprevention setting to test the hypothesis that the antioxidants cause a favorable change in a nuclear morphometry index based on nuclear size, shape and chromatin texture. Specific Aim 3:Serum androgen levels. We hypothesize, based on post hoc results of a phase Ill antioxidant trial, that the intervention will reduce levels of testosterone (total and non-SHBG bound) and cx-androstanediol glucuronide. Specific Aim 4: Growth factors in prostatic fluid (EPF). In previous work, we developed assays for EGF, TGF-a and TGF-Beta 1 in EPF, and reported that low EGF and high TGF-f3 1 were associated with CaP. We hypothesize that treatment increases EGF and decreases TGF-Beta 1 in these-prostatic secretions. Specific Aim 5: DNA oxidation markers in blood. We hypothesize that treatment decreases the oxidized bases HMdU and 8-OHdG in lymphocytes, and increases HMdU auto-antibodies in serum detected by a novel ELISA method. Results of the proposed research will be useful for clarifying the mechanisms of action of lycopene in the prostate, for designing phase III trials, and, more generally, for determining the chemopreventive potential of this relatively non-toxic dietary compound.