Tomato-Soy Juice for Prostate Cancer

描述（由申请人提供）：依据。富含番茄制品和大豆的饮食被假设可以降低前列腺癌的风险，或者可能提高前列腺癌治疗的效果。支持性数据来自流行病学调查、啮齿动物模型和体外细胞培养研究。我们的研究团队已经开发出一种将富含番茄红素的番茄汁与大豆胚芽相结合的加工食品/营养品，其目标是开发一种标准化且易于食用的营养品，可用于未来的大规模，随机，长期干预试验，重点是预防或治疗前列腺癌。假说.我们提出，每天服用一种新型的番茄-大豆营养品（OSU-TSJ-001）将导致前列腺中生物活性成分（异黄酮、多酚、类胡萝卜素）的剂量依赖性增加，并改变生物标志物模式，表明前列腺癌的化学预防或治疗特性。 实验方法。我们将在60名患有临床局限性前列腺癌并选择前列腺切除术进行治疗的男性中进行剂量递增的I期前列腺切除术前临床试验。剂量递增研究将开始，15名男性食用常规饮食作为对照组，随后的15名男性队列每天食用5盎司、10盎司和15盎司的番茄-大豆汁（OSU-TSJ-001）。男性将在接受乳房切除术前28天内食用番茄大豆营养品。 目标1。我们假设男性将遵守番茄-大豆营养品（OSU-TSJ- 001）的消费，没有剂量限制毒性。历史表明，确定毒性和安全性特征的努力至关重要。 目标二。我们假设食用番茄-大豆营养品（OSU-TSJ-001）将导致血液和前列腺组织中番茄-大豆植物化学物质生物分布的剂量依赖性增加。 目标3：我们假设食用番茄-大豆营养品（OSU-TSJ-001）改变了血液激素模式和氧化应激生物标志物，有利于前列腺癌的预防。 目标4。我们将研究与前列腺癌发生相关的组织病理学和分子生物标志物，这些生物标志物可作为替代终点生物标志物，并提供有关番茄-大豆营养品（OSU-TSJ-001）调节其能力的信息。意义这项拟议的研究代表了在针对前列腺癌的临床试验中首次尝试评估一种含有番茄和大豆成分的新型“功能性食品”/中性药物。我们的目标是为未来的大规模随机试验开发番茄-大豆汁，以评估前列腺癌预防或改善癌症治疗（预防复发或改善激素，生物或化学治疗的结果）。I / II期研究提供了基本的安全性和有效性数据，沿着有价值的信息，关于番茄-大豆植物化学物质的吸收和生物分布，以及与作用机制相关的替代终点生物标志物的表征，这些生物标志物可能在未来的随机临床试验中有用。

DESCRIPTION (provided by applicant): Rationale. Diets rich in tomato products and soy are hypothesized to reduce the risk of prostate cancer or perhaps, enhance the efficacy of prostate cancer therapy. Supporting data is derived from epidemiologic investigations, rodent models, and in vitro cell culture studies. Our research team has developed a processed food/nutriceutical combining lycopene-rich tomato juice with soy germ, with the goal of developing a standardized and easily consumed nutriceutical that can be employed in future large-scale, randomized, long-term intervention trials focusing upon prevention or treatment of prostate cancer. Hypothesis. We propose that a daily serving of a novel tomato-soy nutriceutical (OSU-TSJ-001) will cause a dose dependent increase in bioactive components (isoflavones, polyphenols, carotenoids) in the prostate, and alter biomarker patterns suggesting chemopreventive or therapeutic properties for prostate cancer. Experimental Approach. We will conduct a dose escalating phase I pre-prostatectomy clinical trial in 60 men that have clinically localized prostate cancer and have chosen prostatectomy for therapy. The dose escalating study will begin with 15 men consuming usual diets as the control group, with subsequent cohorts of 15 men consuming 5 oz per day, 10 oz per day, and 15 oz per day of the tomato-soy juice (OSU-TSJ-001). Men will consume the tomato-soy nutriceutical for a target of 28 days prior to undergoing prostatectomy. Aim 1. We hypothesize men will be compliant with consumption of the tomato-soy nutriceutical (OSU-TSJ- 001 ) with no dose limiting toxicity. History indicates that efforts to define toxicity and safety profiles are essential. Aim 2. We hypothesize that consumption of the tomato-soy nutriceutical (OSU-TSJ-001) will result in a dose dependent increase in the biodistribution of tomato-soy phytochemicals in blood and prostate tissue. Aim 3. We hypothesize that consumption of the tomato-soy nutriceutical (OSU-TSJ-001) alters blood hormonal patterns and biomarkers of oxidative stress that favor prostate cancer prevention. Aim 4. We will investigate histopathologic and molecular biomarkers associated with prostate carcinogenesis that may serve as surrogate endpoint biomarkers and provide information regarding their ability to be modulated by the tomato-soy nutriceutical (OSU-TSJ-001). Significance. The proposed study represents the first attempt to evaluate a novel "functional food" / neutriceutical containing tomato and soy components in a clinical trial targeting prostate cancer. Our objective is to develop the tomato-soy juice for future large scale randomized trials evaluating prostate cancer prevention or improved cancer therapy (prevent recurrence or improve outcomes of hormonal, biological, or chemical therapy). The phase I / II study provides essential safety and efficacy data along with valuable information regarding absorption and biodistribution of tomato-soy phytochemicals and the characterization of surrogate endpoint biomarkers relevant to mechanisms of action that may be useful in future randomized clinical trails.