Botanical Estrogen Actions in Bone, Uterus, Mammary,and Breast/William Helferich

植物雌激素对骨骼、子宫、乳腺和乳房的作用/William Helferich

• 批准号: 8007125
• 负责人: William G Helferich
• 金额: $ 27.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8007125
• 关键词: Affect; Affinity; Aging; Agonist; Angelica sinensis preparation; Animal Model; Animals; Architecture; Aromatase Inhibition; Binding; Biological; Biological Assay; Biological Availability; Bioluminescence; Blood; Bone Matrix; Bone Tissue; Botanicals; Breast; Cancer Survivor; Cells; Collaborations; Conflict (Psychology); Disease; Dose; Drug Kinetics; Effectiveness; Equilibrium; Estradiol; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptors; Estrogens; Evaluation; Exposure to; Gene Expression; Gene Expression Profiling; Goals; Growth; Health; Hormone replacement therapy; Human; Image; Implant; Individual; Instruction; Letrozole; Licorice; Life; Ligands; Long-Term Effects; Lung; Maintenance; Malignant Neoplasms; Mammary Neoplasms; Mammary gland; Menopausal Symptom; Metastatic Neoplasm to the Bone; Metastatic Neoplasm to the Lung; Methods; Modeling; Molecular Profiling; Morbidity - disease rate; Mus; Neoplasm Metastasis; Nuclear Protein; Nuclear Proteins; Osteoblasts; Osteoclasts; Pathway interactions; Pattern; Pharmacologic Substance; Plant Roots; Positioning Attribute; Postmenopausal Osteoporosis; Postmenopause; Pre-Clinical Model; Preparation; Primary Neoplasm; Process; Rattus; Resolution; Rodent; Rodent Model; Route; Safety; Sampling Studies; Selective Estrogen Receptor Modulators; Signal Transduction; Site; Structure; Structure of parenchyma of lung; Systems Biology; Tamoxifen; Time; Tissues; Tumor Tissue; Uterus; Visceral; Woman; Work; Yam - dietary; aged; base; bone; bone health; bone mass; dietary supplements; dosage; estrogenic activity; experience; feeding; healthy aging; hormone therapy; implantation; improved; in vivo; malignant breast neoplasm; minimally invasive; mortality; mouse model; older women; pre-clinical; reproductive; soy; tibia; tumor growth; tumor progression

PROJECT SUMMARY (See instructions): As alternatives to the standard estrogen pharmaceuticals used for hormone replacement therapy, many older women are using botanical estrogens to treat menopausal symptoms, believing that these dietary supplements are inherently safe because they are natural. Also, because of improved therapies, many breast cancer survivors are living for many years after their breast cancer arises, and a significant number of these women are using these botanicals in the hope that they will help in managing their disease. The overall goal ofthis project is to evaluate the activity of botanical estrogens on important estrogen target tissues and on breast cancer metastasis. In Aim 1, we will investigate the effects of botanical estrogens (from soy, wild yam, licorice root, and dong quai) on three important target tissues, bone, uterus, and mammary gland, in mice and rats, comparing their effects with that of known estrogens, estrogen receptor subtype-selective ligands, and selective estrogen receptor modulators. In Aim 2, we will evaluate the effects of botanical estrogens on the growth and progression of breast cancer in bone and subsequent metastasis to lung and other visceral sites, in a pre-clinical animal model using in vivo bioluminescence imaging, pathological and histological examination, and analysis of gene expression profiles that correlate with metastatic activity. These findings could be relevant to human health, because metastases to bone and lung are major routes of breast cancer expansion in women and contribute greatly to morbidity and mortality. Botanicals, extracts, fractions and pure isolates will be obtained from Core A, with doses determined by Core B. The work in this project will benefit from the results of the mechanistic studies on the botanical estrogens in Project 1 and will interface with the studies on bone health in older animals obtained from Project 3. Collectively, results from these studies will enable determination ofthe effects of botanical estrogens on estrogen target tissues in pre-clinical rodent models and on cancer progression and metastasis in a mouse model. These findings will be important in understanding the actions and safety of botanical estrogens used by women.

项目总结（见说明）： 作为用于激素替代疗法的标准雌激素药物的替代品，许多 老年妇女正在使用植物雌激素来治疗更年期症状，认为这些饮食 补充剂本质上是安全的，因为它们是天然的。此外，由于治疗方法的改进，许多人 乳腺癌幸存者在乳腺癌发生后生活了很多年， 这些妇女正在使用这些植物药，希望它们能帮助控制她们的疾病。的 本项目的总体目标是评价植物雌激素对重要雌激素靶点的活性 组织和乳腺癌转移。在目标1中，我们将研究植物雌激素的作用 (from大豆、野山药、甘草和当归）对三种重要靶组织骨、子宫和 乳腺，在小鼠和大鼠，比较其效果与已知的雌激素，雌激素受体 亚型选择性配体和选择性雌激素受体调节剂。在目标2中，我们将评估 植物雌激素对乳腺癌骨内生长和进展以及随后转移到 肺和其它内脏部位，在使用体内生物发光成像的临床前动物模型中， 病理学和组织学检查，以及与 转移活性这些发现可能与人类健康有关，因为转移到骨和肺 是女性乳腺癌扩散的主要途径，并极大地增加了发病率和死亡率。 植物药、提取物、馏分和纯分离物将从核心A获得，剂量由核心A确定。 B。本课题的研究将借鉴植物雌激素作用机制的研究成果 在项目1中，并将与项目3中获得的老年动物骨骼健康研究相结合。 总的来说，这些研究的结果将能够确定植物雌激素对 在临床前啮齿动物模型中雌激素靶向组织以及在小鼠中对癌症进展和转移的影响 模型这些发现将是重要的了解行动和安全的植物雌激素使用 被女人。