Omega-3 Fatty Acid Modulation of Obesity-Induced Aromatase Expression

Omega-3 脂肪酸对肥胖诱导的芳香酶表达的调节

基本信息

  • 批准号:
    9035932
  • 负责人:
  • 金额:
    $ 17.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-12-24 至 2017-11-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Over the last decade, a large body of evidence has established that obesity is associated with a worse breast cancer prognosis for both pre- and postmenopausal women. There are several mechanism(s) which have been proposed for promoting this effect, with recent evidence suggesting that the obese state is associated with changes in the biology of the disease, promoting a more aggressive phenotype. Clinically, obesity correlates with worse outcome on hormone therapy agents, most notably aromatase inhibitors (AI). Our group, as well as others, has demonstrated that obesity promotes increased local aromatase expression in the mammary gland. Our preliminary studies suggest that this induction is mediated primarily through cyclooxygenase (Cox)-derived prostaglandin E2 (PGE2), that this induction is associated with increased estrogen receptor α (ERα) activity in mammary epithelial cancer cells, and most importantly, that regular use of NSAIDs may reduce the rate of recurrence on AIs by half. These data suggest that interventions that suppress COX-2 PGE2 production may provide significant benefit for the obese ER+ patient. Omega-3 fatty acids have demonstrated anti-cancer benefit through multiple mechanisms, including suppression of inflammation-related signaling. The omega-3 PUFAs serve as competitive substrates for COX- 2 activity, resulting in suppressed PGE2 production. Importantly, our preliminary data suggest that at physiological relevant levels DHA is able to inhibit obesity-induced PGE2 production in vitro. Our exceptional collaborative team of investigators will use highly integrated pre-clinical and clinical studies to test the novel hypothesis that omega-3 fatty acid supplementation can be used to improve response to AIs in the obese postmenopausal breast cancer patient population and prevent many of the tumor-promoting effects of obesity. The results of this study could have an immediate impact on patient outcomes by transitioning directly into a larger intervention trial evaluating both the proposed mechanism of resistance and the use of omega-3 fatty acid supplements to improve response.


项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Andrew Jacob Brenner其他文献

Andrew Jacob Brenner的其他文献

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{{ truncateString('Andrew Jacob Brenner', 18)}}的其他基金

Development of Potent Estrogen Receptor Beta Agonists for Treating Glioblastoma
开发用于治疗胶质母细胞瘤的有效雌激素受体β激动剂
  • 批准号:
    10594832
  • 财政年份:
    2023
  • 资助金额:
    $ 17.68万
  • 项目类别:
Clinical Development of Rhenium Nanoliposomes (RNL186) for Glioblastoma
铼纳米脂质体 (RNL186) 治疗胶质母细胞瘤的临床开发
  • 批准号:
    10242665
  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
  • 项目类别:
Clinical Development of Rhenium Nanoliposomes (RNL186) for Glioblastoma
铼纳米脂质体 (RNL186) 治疗胶质母细胞瘤的临床开发
  • 批准号:
    10013171
  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
  • 项目类别:
Clinical Development of Rhenium Nanoliposomes (RNL186) for Glioblastoma
铼纳米脂质体 (RNL186) 治疗胶质母细胞瘤的临床开发
  • 批准号:
    10687851
  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
  • 项目类别:
Omega-3 Fatty Acid Modulation of Obesity-Induced Aromatase Expression
Omega-3 脂肪酸对肥胖诱导的芳香酶表达的调节
  • 批准号:
    9198761
  • 财政年份:
    2015
  • 资助金额:
    $ 17.68万
  • 项目类别:
Novel ERbeta agonists for the treatment of gliomas
用于治疗神经胶质瘤的新型 ERbeta 激动剂
  • 批准号:
    9326814
  • 财政年份:
    2014
  • 资助金额:
    $ 17.68万
  • 项目类别:
Novel ERbeta agonists for the treatment of gliomas
用于治疗神经胶质瘤的新型 ERbeta 激动剂
  • 批准号:
    8762188
  • 财政年份:
    2014
  • 资助金额:
    $ 17.68万
  • 项目类别:
Phase 2 Study of TH-302 for the Treatment of Glioblastoma
TH-302 治疗胶质母细胞瘤的 2 期研究
  • 批准号:
    8748318
  • 财政年份:
    2014
  • 资助金额:
    $ 17.68万
  • 项目类别:
Phase 2 Study of TH-302 for the Treatment of Glioblastoma
TH-302 治疗胶质母细胞瘤的 2 期研究
  • 批准号:
    9108161
  • 财政年份:
    2014
  • 资助金额:
    $ 17.68万
  • 项目类别:
Phase 2 Study of TH-302 for the Treatment of Glioblastoma
TH-302 治疗胶质母细胞瘤的 2 期研究
  • 批准号:
    9316339
  • 财政年份:
    2014
  • 资助金额:
    $ 17.68万
  • 项目类别:

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靶向 1-磷酸鞘氨醇 (S1P1) 受体治疗芳香酶抑制剂引起的肌肉骨骼症状
  • 批准号:
    10668781
  • 财政年份:
    2023
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    $ 17.68万
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对服用芳香酶抑制剂的乳腺癌患者的身体症状和药物依从性进行价值肯定干预
  • 批准号:
    10063849
  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
  • 项目类别:
A value affirmation intervention for physical symptoms and medication adherence in breast cancer patients taking aromatase inhibitors
对服用芳香酶抑制剂的乳腺癌患者的身体症状和药物依从性进行价值肯定干预
  • 批准号:
    9884954
  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
  • 项目类别:
A value affirmation intervention for physical symptoms and medication adherence in breast cancer patients taking aromatase inhibitors
对服用芳香酶抑制剂的乳腺癌患者的身体症状和药物依从性进行价值肯定干预
  • 批准号:
    10311024
  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
  • 项目类别:
A value affirmation intervention for physical symptoms and medication adherence in breast cancer patients taking aromatase inhibitors
对服用芳香酶抑制剂的乳腺癌患者的身体症状和药物依从性进行价值肯定干预
  • 批准号:
    10535476
  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
  • 项目类别:
Basic research for the development of novel aromatase inhibitors against breast cancer
新型乳腺癌芳香酶抑制剂开发的基础研究
  • 批准号:
    18K07018
  • 财政年份:
    2018
  • 资助金额:
    $ 17.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Aromatase Inhibitors and Weight Loss in Severely Obese Men with Hypogonadism
芳香酶抑制剂与患有性腺功能减退症的严重肥胖男性的减肥
  • 批准号:
    9942488
  • 财政年份:
    2017
  • 资助金额:
    $ 17.68万
  • 项目类别:
Aromatase Inhibitors and Weight Loss in Severely Obese Men with Hypogonadism
芳香酶抑制剂与患有性腺功能减退症的严重肥胖男性的减肥
  • 批准号:
    10412900
  • 财政年份:
    2017
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    $ 17.68万
  • 项目类别:
A motivational intervention to improve adherence to aromatase inhibitors in breast cancer survivors
提高乳腺癌幸存者对芳香酶抑制剂依从性的动机干预
  • 批准号:
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  • 财政年份:
    2016
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    $ 17.68万
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Impact of epigenetic markers of breast adipose tissue on the efficacy of aromatase inhibitors treatments.
乳房脂肪组织的表观遗传标记对芳香酶抑制剂治疗功效的影响。
  • 批准号:
    362464
  • 财政年份:
    2016
  • 资助金额:
    $ 17.68万
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