Stromal contributions to breast carcinogenesis

基质对乳腺癌发生的贡献

基本信息

  • 批准号:
    10748124
  • 负责人:
  • 金额:
    $ 75.85万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-07-03 至 2028-06-30
  • 项目状态:
    未结题

项目摘要

ABSTRACT The human breast is a highly organized, complex organ that consists of an epithelial tissue surrounded by stroma that regulates its proliferation, differentiation, and survival. Stroma is responsible for sustaining normal breast tissue structure and function via a variety of signaling mechanisms that control and regulate normal processes and suppress malignant transformation. The role of stroma in breast tumor initiation, progression, and responsiveness to treatment as well as potential utility for targeted therapies has been widely discussed in recent reviews. While cancer tissue stroma has been widely explored, the evidence of stromal contributions to early stages of carcinogenesis is extremely limited. To fill these gaps, we propose a conceptually and methodologically novel investigation that will focus on benign breast disease (BBD) and high mammographic breast density (MBD), strong risk factors both independently associated with increased breast cancer (BCa) risk, which presents a unique opportunity for studying early changes in the breast and elucidating underlying molecular mechanisms. The study will be conducted by an interdisciplinary team of experts in BCa epidemiology, breast pathology/image analysis, BCa biology, and biostatistics, with a history of long and productive collaboration. We will use data and breast biopsy samples from three established prospective cohorts (Nurses’ Health Study, Nurses’ Health Study II, and Women’s Health Repository) to address the following aims: (1) prospectively examine associations of reproductive risk factors (e.g., parity, age at first birth) with expression of stromal markers (αSMA, FAP, MMP14, TNC, and S100A6) in benign biopsy samples from cancer-free women (n~1,350); (2) examine associations of stromal markers with MBD (n~1,350); and (3) examine associations of stromal markers in women with a previous benign biopsy and the risk of subsequent BCa in a nested case-control design (~400 cases/~975 controls). This proposal leverages established tissue resources, use of validated multiplex immunoflourence for stromal markers, and automated image analysis for MBD assessment. Understanding the associations of BCa risk factors with stromal markers will advance our knowledge on its role in breast carcinogenesis in epidemiologic studies. We will generate the first comprehensive data on the stromal markers’ expression in non-cancer breast and will identify markers that could significantly advance future risk prediction. Stromal activity is potentially modifiable via a variety of targeted therapies; if our project successfully demonstrates an association between stromal markers in benign breast tissue and increased BCa risk and/or high MBD, these findings could eventually translate into pharmaceutical interventions aimed at primary BCa prevention in high-risk women with high MBD and/or BBD. Importantly, these findings would apply to a large segment of women undergoing routine biopsies and those with high MBD in whom novel prevention strategies, improved risk prediction, and tailored clinical management are urgently needed.
摘要

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 }}

Rulla M Tamimi其他文献

Gene × Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study
  • DOI:
    10.1186/1471-2407-6-217
  • 发表时间:
    2006-08-31
  • 期刊:
  • 影响因子:
    3.400
  • 作者:
    David G Cox;Rulla M Tamimi;David J Hunter
  • 通讯作者:
    David J Hunter

Rulla M Tamimi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('Rulla M Tamimi', 18)}}的其他基金

Administrative Core
行政核心
  • 批准号:
    10661345
  • 财政年份:
    2023
  • 资助金额:
    $ 75.85万
  • 项目类别:
Prediagnostic exposures, germline genetics, and triple negative breast cancer mutational and immune profiles
诊断前暴露、种系遗传学以及三阴性乳腺癌突变和免疫特征
  • 批准号:
    10596120
  • 财政年份:
    2021
  • 资助金额:
    $ 75.85万
  • 项目类别:
Computational pathology to predict breast cancer risk in benign breast disease
计算病理学预测良性乳腺疾病的乳腺癌风险
  • 批准号:
    9047258
  • 财政年份:
    2015
  • 资助金额:
    $ 75.85万
  • 项目类别:
Mammographic density and texture features in relation to breast cancer risk
乳房X线照相密度和纹理特征与乳腺癌风险相关
  • 批准号:
    8896563
  • 财政年份:
    2013
  • 资助金额:
    $ 75.85万
  • 项目类别:
Mammographic density and texture features in relation to breast cancer risk
乳腺X线密度和纹理特征与乳腺癌风险的关系
  • 批准号:
    8741957
  • 财政年份:
    2013
  • 资助金额:
    $ 75.85万
  • 项目类别:
Mammographic density and texture features in relation to breast cancer risk
乳腺X线密度和纹理特征与乳腺癌风险的关系
  • 批准号:
    8629862
  • 财政年份:
    2013
  • 资助金额:
    $ 75.85万
  • 项目类别:
Whole Genome Association Study of Mammographic Density
乳腺X线密度的全基因组关联研究
  • 批准号:
    8018197
  • 财政年份:
    2009
  • 资助金额:
    $ 75.85万
  • 项目类别:
Whole Genome Association Study of Mammographic Density
乳腺X线密度的全基因组关联研究
  • 批准号:
    7656493
  • 财政年份:
    2009
  • 资助金额:
    $ 75.85万
  • 项目类别:
Whole Genome Association Study of Mammographic Density
乳腺X线密度的全基因组关联研究
  • 批准号:
    7777342
  • 财政年份:
    2009
  • 资助金额:
    $ 75.85万
  • 项目类别:
Whole Genome Association Study of Mammographic Density
乳腺X线密度的全基因组关联研究
  • 批准号:
    8239989
  • 财政年份:
    2009
  • 资助金额:
    $ 75.85万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
    n/a
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341426
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341424
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Continuing Grant
PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政​​策的情绪动态
  • 批准号:
    10108433
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
  • 批准号:
    MR/X032809/1
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
  • 批准号:
    MR/X034690/1
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Fellowship
Walkability and health-related quality of life in Age-Friendly Cities (AFCs) across Japan and the Asia-Pacific
日本和亚太地区老年友好城市 (AFC) 的步行适宜性和与健康相关的生活质量
  • 批准号:
    24K13490
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Discovering the (R)Evolution of EurAsian Steppe Metallurgy: Social and environmental impact of the Bronze Age steppes metal-driven economy
发现欧亚草原冶金的(R)演变:青铜时代草原金属驱动型经济的社会和环境影响
  • 批准号:
    EP/Z00022X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Research Grant
ICF: Neutrophils and cellular senescence: A vicious circle promoting age-related disease.
ICF:中性粒细胞和细胞衰老:促进与年龄相关疾病的恶性循环。
  • 批准号:
    MR/Y003365/1
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Research Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
  • 批准号:
    2335955
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Standard Grant
Shaping Competition in the Digital Age (SCiDA) - Principles, tools and institutions of digital regulation in the UK, Germany and the EU
塑造数字时代的竞争 (SCiDA) - 英国、德国和欧盟的数字监管原则、工具和机构
  • 批准号:
    AH/Y007549/1
  • 财政年份:
    2024
  • 资助金额:
    $ 75.85万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了