Tomato-Soy Juice for Prostate Cancer

描述(由申请人提供)：基本原理。富含番茄产品和大豆的饮食被认为可以降低前列腺癌的风险，或者可能提高前列腺癌治疗的疗效。支持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。我们的研究团队开发了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/营养食品，目标是开发一种标准化且易于食用的营养食品，可用于未来专注于预防或治疗前列腺癌的大规模、随机、长期干预试验。假设。我们认为，每天食用一种新型的番茄-大豆营养食品(OSU-TSJ-001)将导致前列腺癌中生物活性成分(异黄酮类、多酚类、类胡萝卜素)的剂量依赖性增加，并改变表明前列腺癌具有化学预防或治疗特性的生物标志物模式。 实验方法。我们将在60名临床上有局限性前列腺癌并选择前列腺癌手术治疗的男性患者中进行剂量递增的第一阶段前列腺癌手术前临床试验。剂量递增研究将以15名男性日常饮食作为对照组，随后15名男性每天分别饮用5盎司、10盎司和15盎司的番茄酱油(OSU-TSJ-001)。男性将在接受前列腺切除术前28天内食用西红柿-大豆营养品。 目的1.我们假设男性将遵从番茄-大豆营养食品(OSU-TSJ-001)的消费，并且没有剂量限制毒性。历史表明，努力确定毒性和安全概况是至关重要的。 目的2.我们假设番茄-大豆营养品(OSU-TSJ-001)的摄入将导致番茄-大豆植物化学物质在血液和前列腺组织中的生物分布增加，这是一种剂量依赖关系。 目的3.我们假设食用番茄-大豆营养食品(OSU-TSJ-001)可以改变血液激素模式和有利于前列腺癌预防的氧化应激生物标记物。 目的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记物，作为替代终点生物标记物，并提供有关它们被番茄-大豆营养物质(OSU-TSJ-001)调节的能力的信息。意义重大。这项拟议的研究是首次尝试在针对前列腺癌的临床试验中评估一种含有西红柿和大豆成分的新型“功能食品”/中性食品。我们的目标是开发番茄酱油，用于未来评估前列腺癌预防或改进癌症治疗(防止复发或改善激素、生物或化学治疗结果)的大规模随机试验。I/II阶段研究提供了基本的安全性和有效性数据，以及关于番茄-大豆植物化学物质的吸收和生物分布的有价值的信息，以及与作用机制相关的替代终点生物标记物的特征，这些生物标记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.