Identification of Natural Product Inhibitors of Breast Cancer Bone Metastasis

乳腺癌骨转移天然产物抑制剂的鉴定

基本信息

  • 批准号:
    7990371
  • 负责人:
  • 金额:
    $ 23.78万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-08-01 至 2012-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): India has one of the lowest rates of breast cancer - and one of the highest levels of turmeric consumption - in the world. While clearly not proving cause and effect, this inverse relationship between breast cancer and turmeric consumption is of interest given existing scientific evidence that one particular chemical found in turmeric, curcumin, can prevent cancer cell growth. Completely unexplored, however, is the question of whether the natural mixture of interacting compounds present in the turmeric consumed by women in India can work together in a complex way to prevent the progression of breast cancer. Our research team is in a unique position to examine this question, having recently finished a major NIH-funded, seven-year study to isolate and carefully identify the different chemicals present in complex turmeric extracts and fractions, and then to test the ability of these complex mixtures to prevent bone erosion in arthritis. Unique observations made in these studies led to the formulation of our novel postulate that complex turmeric products (rather than purified curcumin) may be particularly effective in preventing the progression of bone metastases in breast cancer. We posit that this protective effect is due to the specific ability of complex turmeric extracts to inhibit tumor cell secretion of parathyroid hormone-related protein (PTHrP), a hormone central to bone metastasis development in breast cancer. In vitro experiments conducted within the last year in our laboratory have now proven this hypothesis and support the design of this application which will use a reductionist approach to test turmeric extracts and fractions in vivo to examine their efficacy and safety in preventing the progression of bone metastases in estrogen receptor positive (ER+) and negative (ER-) breast cancers using an animal model. PUBLIC HEALTH RELEVANCE: Scientific research evaluating the efficacy and safety of herbal products in women diagnosed with breast cancer has not kept pace with prevailing patterns of botanical use in this population. In addition, breast cancer treatments specifically targeting key signaling pathways in tumor cells (eg. PTHrP) within the bone microenvironment to limit the progression of bone metastases do not exist. Should specific extracts of turmeric be found in these pre-clinical studies and subsequent clinical trials to be safe and effective in preventing the development and spread of breast cancer bone metastases by blockade of tumor cell PTHrP expression, their use as dietary supplements could prove to be useful additions to adjuvant treatment options in women diagnosed with early breast cancer. Additionally, standardized turmeric products could also be developed for the treatment of established breast cancer bone metastases. Given the high levels of CAM use currently in breast cancer survivors, the appropriate use of a medicinal botanical in this setting could have a significant impact on breast cancer treatment.
描述(由申请人提供):印度是世界上乳腺癌发病率最低的国家之一,也是姜黄消费水平最高的国家之一。虽然显然没有证明因果关系,但鉴于现有的科学证据表明姜黄中发现的一种特殊化学物质姜黄素可以防止癌细胞生长,乳腺癌和姜黄消费之间的这种反向关系是有趣的。然而,完全未探索的问题是,印度妇女食用的姜黄中存在的相互作用化合物的天然混合物是否可以以复杂的方式共同作用,以防止乳腺癌的进展。我们的研究团队在研究这个问题方面处于独特的地位,最近完成了一项由NIH资助的为期七年的主要研究,以分离和仔细识别复杂姜黄提取物和馏分中存在的不同化学物质,然后测试这些复杂混合物预防关节炎骨质侵蚀的能力。在这些研究中进行的独特观察导致了我们的新假设的形成,即复杂的姜黄产品(而不是纯化的姜黄素)可能特别有效地预防乳腺癌骨转移的进展。我们认为,这种保护作用是由于复杂的姜黄提取物抑制肿瘤细胞分泌甲状旁腺相关蛋白(PTHrP)的特异性能力,PTHrP是乳腺癌骨转移发展的核心激素。去年在我们实验室进行的体外实验现在已经证明了这一假设,并支持本申请的设计,该申请将使用还原方法在体内测试姜黄提取物和级分,以使用动物模型检查其在预防雌激素受体阳性(ER+)和阴性(ER-)乳腺癌骨转移进展中的有效性和安全性。 公共卫生相关性:评估草药产品在诊断为乳腺癌的妇女中的疗效和安全性的科学研究没有跟上这一人群中植物使用的流行模式。此外,专门针对肿瘤细胞中关键信号通路的乳腺癌治疗(例如,PTHrP)限制骨转移进展的骨微环境内不存在。如果在这些临床前研究和随后的临床试验中发现姜黄的特定提取物通过阻断肿瘤细胞PTHrP表达在预防乳腺癌骨转移的发展和扩散方面是安全有效的,那么它们作为膳食补充剂的用途可能被证明是诊断为早期乳腺癌的女性辅助治疗选择的有用补充。 此外,标准化的姜黄产品也可以开发用于治疗乳腺癌骨转移。鉴于目前乳腺癌幸存者中CAM的使用水平很高,在这种情况下适当使用药用植物可能会对乳腺癌治疗产生重大影响。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

JANET L FUNK其他文献

JANET L FUNK的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('JANET L FUNK', 18)}}的其他基金

Mechanistic Determinants of Dietary Polyphenol Bioactivity in Bone
膳食多酚在骨中生物活性的机制决定因素
  • 批准号:
    10303242
  • 财政年份:
    2021
  • 资助金额:
    $ 23.78万
  • 项目类别:
Mechanistic Determinants of Dietary Polyphenol Bioactivity in Bone
膳食多酚在骨中生物活性的机制决定因素
  • 批准号:
    10435568
  • 财政年份:
    2021
  • 资助金额:
    $ 23.78万
  • 项目类别:
Exploiting the Tumor Microenvironment to Block Breast Cancer Bone Metastasis
利用肿瘤微环境阻止乳腺癌骨转移
  • 批准号:
    8902058
  • 财政年份:
    2014
  • 资助金额:
    $ 23.78万
  • 项目类别:
Isolation and Characterization of ER+ Breast Cancer Cells with High Bone Metastat
具有高骨转移的 ER 乳腺癌细胞的分离和表征
  • 批准号:
    8883438
  • 财政年份:
    2014
  • 资助金额:
    $ 23.78万
  • 项目类别:
Exploiting the Tumor Microenvironment to Block Breast Cancer Bone Metastasis
利用肿瘤微环境阻止乳腺癌骨转移
  • 批准号:
    8759032
  • 财政年份:
    2014
  • 资助金额:
    $ 23.78万
  • 项目类别:
Isolation and Characterization of ER+ Breast Cancer Cells with High Bone Metastat
具有高骨转移的 ER 乳腺癌细胞的分离和表征
  • 批准号:
    8771595
  • 财政年份:
    2014
  • 资助金额:
    $ 23.78万
  • 项目类别:
Exploiting the Tumor Microenvironment to Block Breast Cancer Bone Metastasis
利用肿瘤微环境阻止乳腺癌骨转移
  • 批准号:
    9117436
  • 财政年份:
    2014
  • 资助金额:
    $ 23.78万
  • 项目类别:
Curcuma longa L. in Rheumatoid Arthritis (CLaRA): Clinical Planning Study
姜黄在类风湿性关节炎 (CLaRA) 中的应用:临床规划研究
  • 批准号:
    8859531
  • 财政年份:
    2013
  • 资助金额:
    $ 23.78万
  • 项目类别:
Curcuma longa L. in Rheumatoid Arthritis (CLaRA): Clinical Planning Study
姜黄在类风湿性关节炎 (CLaRA) 中的应用:临床规划研究
  • 批准号:
    8490129
  • 财政年份:
    2013
  • 资助金额:
    $ 23.78万
  • 项目类别:
Curcuma longa L. in Rheumatoid Arthritis (CLaRA): Clinical Planning Study
姜黄在类风湿性关节炎 (CLaRA) 中的应用:临床规划研究
  • 批准号:
    8723741
  • 财政年份:
    2013
  • 资助金额:
    $ 23.78万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 23.78万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了