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）： 膳食大豆广泛销售并用作预防和治疗慢性疾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，并且在摄入富含大豆的膳食后，这些异黄酮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，并且由于它们对前列腺上皮中丰富的雌激素受体β的亲和力，可能在前列腺中具有选择性活性。我们实验室和合作者的最新研究结果表明，对正常和肿瘤性前列腺具有潜在的治疗益处。该转化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得到检验。我们假设食用大豆会减少肿瘤组织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）表达升高、细胞凋亡增加以及增殖标志物（KI67-MIB 和细胞周期蛋白 B1）表达降低。为了获得初步数据来支持或反驳这一假设，为未来提交 R01 做准备，我们打算在前列腺切除术前设计中使用 25 克膳食大豆进行干预，提供约 100 毫克异黄酮，以评估是否存在是大豆对增殖和信号传导的组织生物标志物的短期影响。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之间的血清 PSA 浓度。我们相信，通过本文提出的工作获得的数据将为前列腺切除术前模型的进一步机构开发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。