EFFECTS OF SOY ISOFLAVONES ON THE PROSTATE, BREAST, AND BONE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。背景：大豆食品中含有大量的异黄酮类“植物雌激素”，虽然不是类固醇，但也有一些雌激素样的特性。关于大豆潜在好处的广泛报道最近导致其在美国的消费量增加。据称的好处包括对前列腺癌、乳腺癌和骨质疏松症的保护作用。受益的证据主要来自流行病学关联和动物或细胞模型的实验室研究。很少有人体临床试验。目的：研究大豆异黄酮摄入对男性和女性体外替代肿瘤标志物、骨密度标志物和生活质量参数的影响。宽泛的假设：摄入异黄酮会有利地影响癌症和骨密度标记物。设计：随机、双盲、交叉试验设计将用于三个人群：i)接受雄激素消融治疗的前列腺癌男性；ii)接受激素替代治疗(HRT)的绝经后女性；以及iii)未接受HRT治疗的绝经后女性。参与者将分别接受为期2个月的异黄酮补充剂和安慰剂。结果将是癌症和骨密度的标志。方法：该项目的重点将是异黄酮类作用的基础科学。参与者的血清和血清提取物将与培养的人类细胞系(前列腺癌、乳腺癌和成骨细胞)孵育，并研究雌激素和非雌激素的作用机制。人类血清数据将得到直接添加结晶异黄酮(染料木素、大豆苷元和木酚)到相同培养的人类细胞系的平行研究的补充。参与者的血清和尿液也将被测试骨吸收和形成的标志。生活质量问题将通过问卷调查进行评估。影响：尽管许多人声称食用大豆制品及其异黄酮具有保健作用，但大多数都没有经过充分的人体测试。在某些情况下，可能会有不利的影响。这项为期5年的研究计划旨在建立异黄酮类作用的基本机制和途径，这些作用是基于它们对前列腺、乳房和骨骼的影响。结果将与患有前列腺癌、乳腺癌和骨质疏松症的大部分美国人有关，并可能为大豆和/或其一种或多种异黄酮组分的更明确的临床试验提供基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Soy foods are high in Isoflavones, one group of "phytoestrogens", which, although non-steroidal, have some estrogen-like properties. Widespread reports of soy's potential benefits have recently led to its increased consumption in the U.S. Purported benefits include protective effects for prostate cancer, breast cancer, and osteoporosis. Evidence for benefit is derived largely from epidemiological associations and laboratory studies with animal or cell models. There are very few human clinical trials. Objective: To study the effects of soy Isoflavone intake on in vitro surrogate cancer markers as well as bone density markers and quality of life parameters in men and women. Broad hypothesis: Isoflavone intake will favorably effect cancer and bone density markers. Design: A randomized, double-blind, cross-over trial design will be used with three populations: i) men with prostate cancer on androgen ablation therapy; ii) postmenopausal women on hormone replacement therapy (HRT); and iii) postmenopausal women not on HRT. Participants will receive an Isoflavone supplement and placebo each for 2-months. Outcomes will be markers of cancers and bone density. Methods: The project's focus will be on the basic science of Isoflavone action. Participants' serum and serum extracts will be incubated with cultured human cell lines (prostate cancer, breast cancer, and osteoblasts) and estrogenic and non-estrogenic mechanisms of action investigated. The human sera data will be complemented by parallel studies of direct addition of crystalline isoflavones (genistein, daidzein, and equol) to the same cultured human cell lines. Participant's serum and urine also will be tested for markers of bone resorption and formation. Quality of life issues will be assessed with questionnaires. Implications: Although many health claims have been made for dietary soy products and their isoflavones, most have not undergone adequate human testing. Under certain conditions, there may be adverse effects. This 5-yr research program seeks to establish the basic mechanisms and pathways of isoflavone actions that underlie their effects on the prostate, the breast and on bone. Results will be relevant to the large segment of the US population suffering from, or at risk of developing, prostate cancer, breast cancer, and osteoporosis and may provide the basis for more definitive clinical trials of soy and/or one or more of its Isoflavone components.