Effects of Lycopene on High-Risk Prostatic Tissue

描述：（由申请人提供）番茄红素是一种有前途的 癌症化学预防剂（CaP）。然而，实际效果 这种饮食抗氧化剂对前列腺组织的影响知之甚少。的 CaP的临床前阶段的特征在于从正常的 上皮通过高级别前列腺上皮内瘤变（HGPIN）， 这很可能是前列腺癌的先兆病变我们建议进行一项 安慰剂对照的随机试验，以调查效果，6个月后， 番茄红素补充剂（30毫克/天）的分子和细胞形态标志物， 来自有HGPIN记录的男性的空芯针活检样本。参与者将被 从西北纪念医院的泌尿科服务和 湖滨退伍军人管理医院我们建议调查 具体目标如下： 具体目标1：组织中的分子标记物。我们将使用传统的 免疫组织化学和基于计算机的图像分析来验证假设 番茄红素补充剂改变了标志着 肿瘤细胞增殖、分化、细胞调节和凋亡的研究进展 高危组织我们已经选择了一组标记并进行了优先排序， 在癌前进展过程中差异表达。 具体目标2：核形态测定。我们会用电脑图像分析 系统设计的化学预防设置，以测试的假设， 抗氧化剂引起核形态指数的有利变化， 核大小、形状和染色质纹理。 具体目标3：血清雄激素水平。我们假设，基于事后结果 第三阶段的抗氧化剂试验，干预将降低水平， 睾酮（总睾酮和非SHBG结合睾酮）和环雄甾烷葡糖苷酸。 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 开发了EPF中EGF、TGF-α和TGF-β 1的测定方法，并报告低 EGF和高TGF-β 1与CaP相关。我们假设治疗 在这些前列腺分泌物中增加EGF和减少TGF-β 1。 具体目标5：血液中的DNA氧化标记物。我们假设治疗 降低淋巴细胞中的氧化碱基HMdU和8-OHdG，并增加HMdU 通过新的ELISA方法检测血清中的自身抗体。结果 拟议的研究将有助于澄清的行动机制， 番茄红素在前列腺中的作用，用于设计III期试验，更一般地说， 为了确定这种相对无毒的化学预防潜力， 膳食化合物

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.