Effects of Dietary Soy on Biomarkers in Prostate Cancer

描述(由申请人提供)： 食用大豆被广泛推向市场，作为预防和治疗慢性病的补充和替代疗法。膳食来源的大豆异黄酮类化合物在体外和动物模型中具有抗癌活性，这些异黄酮类化合物在摄入富含大豆的膳食后在血清中以高浓度存在。此外，这些异黄酮集中在前列腺组织中，并可能在前列腺中具有选择性活性，因为它们与前列腺上皮中丰富的雌激素受体β有亲和力。我们实验室和我们的合作者的最新发现表明，在正常和肿瘤的前列腺中有潜在的治疗益处。这一翻译应用的目标是确定由全大豆蛋白组成的膳食补充剂是否可以抑制人类患者的前列腺癌细胞的增殖。这个问题将在前列腺癌男性的临床治疗干预中进行测试。我们假设食用大豆会减少肿瘤和邻近正常前列腺组织的增殖，这反映在细胞周期抑制蛋白(p27和p21)的表达增加，细胞凋亡增加，增殖标记物(Ki67-MIB和细胞周期蛋白B1)的表达降低。为了获得支持或反驳这一假设的初步数据，为将来的R01提交做准备，我们打算在前列腺癌前的设计中使用25克饮食大豆提供大约100毫克异黄酮来评估大豆是否对增殖和信号转导的组织生物标记物有短期影响。我们还将测试这种短期干预是否会改变活检和前列腺切除术之间的血清PSA浓度。我们相信，通过本文建议的工作获得的数据将为进一步的前列腺术前模型的机构发展提供有价值的初步数据，以测试未来的补充和替代干预措施。

DESCRIPTION (provided by applicant): Dietary soy is widely marketed and used as both complementary and alternative therapy for the prevention and treatment of chronic diseases. Dietary derived soy isoflavonoids have anticancer activities in vitro and in animal models, and these isoflavones or are found in serum in high concentrations after ingestion of a soy-rich meal. Furthermore, these isoflavones concentrate in prostatic tissue, and may have selective activity in the prostate because of their affinity for estrogen receptor beta, which is abundant in prostatic epithelium. Recent findings in our laboratories and by our collaborators indicate potential for therapeutic benefit in normal and neoplastic prostate. The goal of this translational application is to determine whether a dietary supplement consisting of whole soy protein can inhibit the proliferation of prostate cancer cells in human patients. This question will be tested in a clinical therapeutic intervention in men with prostate cancer. We hypothesize that dietary soy consumption will decrease proliferation in neoplastic and adjacent normal prostatic tissues, as reflected in elevated expression of cell cycle inhibitory proteins (p27 and p21), increased apoptosis, and decreased expression of proliferation markers (KI67-MIB and cyclin B1). In order to obtain preliminary data to support or refute this hypothesis in preparation for a future R01 submission, we intend to use an intervention with 25 grams of dietary soy providing approximately 100 mg of isoflavones in a pre-prostatectomy design to assess whether or not there is a short-term effect of soy on tissue biomarkers of proliferation and signaling. We will also test whether this short-term intervention alters serum PSA concentrations between the time of biopsy and prostatectomy. We believe that the data obtained via the work proposed herein will provide valuable preliminary data for further institutional development of the preprostatectomy model for testing of future complementary and alternative interventions.