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.
 描述(由申请人提供):在过去的十年里,大量证据表明,肥胖与绝经前和绝经后女性乳腺癌预后较差有关。有几种机制(S)提出了促进这种效应的机制,最近的证据表明,肥胖状态与疾病生物学的变化有关,促进了更具侵略性的表型。在临床上,肥胖与激素治疗药物的不良结果相关,最明显的是芳香酶抑制剂(AI)。我们的团队以及其他人已经证明,肥胖会促进乳腺局部芳香酶表达的增加。我们的初步研究表明,这种诱导主要是通过环氧合酶(COX)衍生的前列腺素E2(PGE_2)介导的,这种诱导与乳腺上皮癌细胞中雌激素受体α(ER-α)活性的增加有关,最重要的是,定期使用非甾体抗炎药可能会将AIS的复发率降低一半。这些数据表明,抑制COX-2 PGE2产生的干预措施可能会为肥胖的ER+患者提供显著的好处。Omega-3脂肪酸通过多种机制显示出抗癌的益处,包括抑制与炎症有关的信号。Omega-3多不饱和脂肪酸作为COX-2活性的竞争性底物,导致PGE2的产生受到抑制。重要的是,我们的初步数据表明,在生理相关水平上,DHA在体外能够抑制肥胖诱导的PGE2的产生。我们出色的合作研究团队将使用高度整合的临床前和临床研究来测试这一新假设,即补充omega-3脂肪酸可以用来改善肥胖绝经后乳腺癌患者群体对AIS的反应,并防止肥胖的许多促癌作用。这项研究的结果可以直接过渡到一项更大的干预试验,评估拟议的耐药机制和使用omega-3脂肪酸补充剂来改善反应,从而对患者的预后产生直接影响。

项目成果

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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:
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  • 批准号:
    10063849
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    2019
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    $ 17.68万
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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
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    $ 17.68万
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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
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    $ 17.68万
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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:
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  • 财政年份:
    2019
  • 资助金额:
    $ 17.68万
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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:
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  • 财政年份:
    2018
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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
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    9942488
  • 财政年份:
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    $ 17.68万
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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
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    $ 17.68万
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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。
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