Cause and Effect Relationships Between Glycation and the Ancestry Specific Tumor Stroma

糖化与祖先特异性肿瘤基质之间的因果关系

基本信息

  • 批准号:
    10586185
  • 负责人:
  • 金额:
    $ 48.11万
  • 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:
    2023-01-01 至 2027-12-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Whole genome analyses support the tumor stroma as the main site of molecular change that promotes deadly prostate cancer in African American men. However, complimentary basic research studies showing a direct cause-and-effect relationship are lacking. As our bodies use the sugars, we consume for energy they generate waste chemicals known as metabolites. One such group of metabolites is known as advanced glycation end products or AGEs for short. AGE accumulation in our tissues and organs causes their functional decline and accelerates the aging process. AGEs represent intrinsic biological elements within health disparity risk factors that align with the stromal profiles that influence prostate cancer in African American men. This group has previously shown that AGEs are elevated in the circulation and tumors of prostate cancer patients with highest levels being observed in men with African ancestry and in more aggressive tumors. Using diet as a surrogate for health inequity, a key and novel finding from this research is that dietary consumption of AGEs can directly accelerate prostate tumor growth. Dietary-AGE mediated effects on tumor growth were shown to be dependent upon stromal signaling by the transmembrane receptor for AGE (RAGE). AGE-RAGE signaling was associated with an activated stroma similar to that observed in African American men with prostate cancer. This was defined by the increased presence of cancer associated fibroblasts (CAFs) and the downregulation of matrix associated genes. The long-term, objective is to integrate ancestral tumor biology into the multilevel framework of health inequity constructs to inform on cancer disparity outcomes. The study hypothesis is that “increased AGE bioavailability contributes to rapid tumor progression in AA men with PCa cancer”. The study will use a combination of prostate cancer cell lines and unique mouse tumor models to define a direct cause-and-effect relationship between AGEs and ancestry specific crosstalk in the tumor associated stroma. It will also assess if the consumption of AGEs has a positive correlation with prostate cancer risk using data from large human cohort studies. By establishing the mechanistic consequences AGEs found in the food chain on ancestry specific tumor biology, defined strategies to limit their accumulation in at risk populations, such as African American men with prostate cancer, may be viewed as cancer preventive or therapeutic strategies when combined with existing treatment regimens.
项目总结/摘要 全基因组分析支持肿瘤间质是分子变化的主要位点, 导致非裔美国人患上致命的前列腺癌。然而,免费的基本 缺乏显示直接因果关系的研究。 当我们的身体使用糖时,我们消耗它们产生的能量, 作为代谢物。一组这样的代谢物被称为晚期糖基化终产物或糖基化终产物。 简称AGEs。AGE在我们组织和器官中的积累导致它们的功能下降, 加速衰老过程AGEs代表健康差异中的内在生物学因素 与影响非裔美国人前列腺癌的基质特征一致的风险因素 男人该小组先前已经表明,AGEs在循环和肿瘤中升高, 前列腺癌患者中,非洲血统的男性和 更有攻击性的肿瘤使用饮食作为健康不平等的替代品,这是一个关键和新颖的发现, 这项研究表明,饮食中AGEs的摄入可以直接加速前列腺肿瘤的生长。 饮食-AGE介导的肿瘤生长效应依赖于基质细胞的增殖。 通过AGE(AGE)的跨膜受体进行信号传导。AGE-beta信号通路与 具有与患有前列腺癌的非洲裔美国人中观察到的类似的活化的基质。 这是由癌症相关成纤维细胞(CAF)的存在增加和癌症相关成纤维细胞(CAF)的存在增加来定义的。 基质相关基因的下调。 长期的目标是将祖先肿瘤生物学整合到多层次的框架中, 健康不公平结构,以告知癌症差异的结果。研究假设是, “增加AGE生物利用度有助于患有PCa的AA男性的快速肿瘤进展 癌症”。该研究将使用前列腺癌细胞系和独特的小鼠肿瘤的组合 模型来定义AGEs和特定祖先之间的直接因果关系 肿瘤相关基质中的串扰。它还将评估AGEs的消费是否具有 与前列腺癌风险正相关,使用来自大型人类队列研究的数据。 通过建立在食物链中发现的AGEs对祖先的机械后果, 特定的肿瘤生物学,定义的策略,以限制其在风险人群中的积累,如 患有前列腺癌的非洲裔美国男性,可被视为癌症预防或治疗 与现有的治疗方案相结合。

项目成果

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David Paul Turner其他文献

David Paul Turner的其他文献

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{{ truncateString('David Paul Turner', 18)}}的其他基金

Project: Survivorship Care Physical Activity Initiative to Improve Disparities in HRQoL for Prostate Cancer Survivors (RELate Study)
项目:旨在改善前列腺癌幸存者 HRQoL 差异的生存护理体力活动计划(RELate 研究)
  • 批准号:
    10911646
  • 财政年份:
    2023
  • 资助金额:
    $ 48.11万
  • 项目类别:
Core: AGE Shared Resource
核心:AGE共享资源
  • 批准号:
    10911642
  • 财政年份:
    2023
  • 资助金额:
    $ 48.11万
  • 项目类别:
Core: AGE Shared Resource
核心:AGE共享资源
  • 批准号:
    10246908
  • 财政年份:
    2017
  • 资助金额:
    $ 48.11万
  • 项目类别:
Project: Survivorship Care Physical Activity Initiative to Improve Disparities in HRQoL for Prostate Cancer Survivors (RELate Study)
项目:旨在改善前列腺癌幸存者 HRQoL 差异的生存护理体力活动计划(RELate 研究)
  • 批准号:
    10246912
  • 财政年份:
    2017
  • 资助金额:
    $ 48.11万
  • 项目类别:
(PQ3) AGEs and Race Specific Tumor Immune Response in Prostate Cancer
(PQ3) 前列腺癌中的 AGE 和种族特异性肿瘤免疫反应
  • 批准号:
    8876216
  • 财政年份:
    2015
  • 资助金额:
    $ 48.11万
  • 项目类别:
Glycation as a Mechanism Promoting Cancer Disparity
糖化是促进癌症差异的机制
  • 批准号:
    8640901
  • 财政年份:
    2013
  • 资助金额:
    $ 48.11万
  • 项目类别:
Glycation as a Mechanism Promoting Cancer Disparity
糖化是促进癌症差异的机制
  • 批准号:
    8494770
  • 财政年份:
    2013
  • 资助金额:
    $ 48.11万
  • 项目类别:
Core: AGE Shared Resource
核心:AGE共享资源
  • 批准号:
    9419080
  • 财政年份:
  • 资助金额:
    $ 48.11万
  • 项目类别:

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