Tomato-Soy Juice for Prostate Cancer

描述（由申请人提供）：基本原理。富含番茄制品和大豆的饮食被认为可以降低患前列腺癌的风险或者提高前列腺癌治疗的效果。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芽结合在一起的加工食品/营养品，目的是开发一种标准化、易于食用的营养品，可用于未来大规模、随机、长期的干预试验，重点是预防或治疗前列腺癌。假设。我们建议，每天食用一种新型番茄大豆营养品（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，提示前列腺癌的化学预防或治疗特性。

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.