Effects of Dietary Soy on Biomarkers in Prostate Cancer

膳食大豆对前列腺癌生物标志物的影响

• 批准号: 6798205
• 负责人: J. MARK CLINE
• 金额: $ 7.18万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-08 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6798205
• 关键词: adult human (21+); alternative medicine; apoptosis; biological signal transduction; biomarker; biopsy; cell cycle proteins; cell differentiation; cell growth regulation; cell proliferation; clinical research; dietary supplements; flavonoids; human subject; human therapy evaluation; immunocytochemistry; male; neoplastic cell; nutrition aspect of cancer; nutrition related tag; patient oriented research; prostate; prostate neoplasms; prostate specific antigen; prostate surgery; soybeans

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.

描述（由申请人提供）： 饮食大豆被广泛销售，并用作预防和治疗慢性疾病的补充和替代疗法。饮食中衍生的大豆异黄酮在体外和动物模型中具有抗癌活性，这些异黄酮或在摄入大豆丰富餐后高浓度的血清中发现。此外，这些异黄酮集中在前列腺组织中，并且可能在前列腺中具有选择性活性，因为它们对雌激素受体β的亲和力（在前列腺上皮中很丰富）。我们的实验室和合作者的最新发现表明，在正常和肿瘤前列腺中具有治疗益处的潜力。这种翻译应用的目的是确定由整个大豆蛋白组成的饮食补充剂是否可以抑制人类患者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。我们假设饮食中的大豆消耗将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的表达升高（p27和p21），凋亡增加，增殖标志物的表达降低（KI67-MIB和环蛋白B1）。为了获得初步数据以支持或反驳这一假设以准备未来的R01提交，我们打算使用25克饮食大豆的干预措施，在术前切除术中提供大约100毫克的异黄酮，以评估大豆对组织生物标志的短期影响和信号的短期影响。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时之间的血清PSA浓度。我们认为，通过本文提出的工作获得的数据将提供有价值的初步数据，以进一步开发前骨前切除术模型，以测试未来的补充和替代干预措施。