Project 2: Characterization of microenvironmental drivers of neoplasia in BE

项目 2:BE 肿瘤形成微环境驱动因素的表征

基本信息

  • 批准号:
    9277751
  • 负责人:
  • 金额:
    $ 24.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-05-12 至 2022-04-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Barrett’s esophagus (BE) is the replacement of the normal squamous esophageal epithelium with an incompletely intestinalized columnar epithelium. It occurs in response to chronic acid and bile reflux injury to the esophagus and is the most substantial risk factor for esophageal adenocarcinoma (EAC), a disease whose incidence has risen at an alarming rate. Therefore, improving our understanding of the pathogenesis of BE and its progression to EAC is a critical research imperative. A key lesson of recent genomic studies led in part by this team has demonstrated that many potentially pathogenic somatic mutations are present in the BE epithelium of those who do not progress to dysplasia or cancer, highlighting the important role of processes other than genomic mutations for promoting disease onset and progression. Here, we focus on the pivotal role of the tumor microenvironment in the pathogenesis of BE and EAC pathogenesis through aims that are integrated and complementary. We provide new and compelling data implicating a subset of infiltrating activated fibroblasts and immune cells in an interconnected web of mutually reinforcing signaling pathways with BE epithelial cells that enhances carcinogenesis. We hypothesize that these tumor-promoting cell populations in the BE microenvironment are key to understanding how and why BE progresses to EAC and that characterization of these cells and regulatory pathways will serve as a foundation for developing new approaches for screening and therapeutics. This hypothesis will be pursued through the following inter-related Specific Aims: 1) To determine the nature and function of the immune cells and fibroblasts present in human BE and EAC patients. 2) To demonstrate how IL-6 secreted by cancer associated fibroblasts and TP53 mutant epithelium promotes BE pathogenesis and progression to EAC. 3) To examine the effect of Myeloid-Derived Suppressor Cells (MDSC) and regulatory T-cells (TReg) on the progression of BE to EAC. Summary and
项目摘要 Barrett食管(BE)是正常鳞状食管上皮被一种 柱状上皮不完全钙化。它是对慢性酸和胆汁反流损伤的反应, 是食管腺癌(EAC)的最主要危险因素,EAC是一种 发病率以惊人的速度上升。因此,提高我们对BE发病机制的认识, 并且其向EAC的进展是至关重要的研究必要性。最近基因组研究的一个关键教训部分导致了 这个团队已经证明,许多潜在的致病性体细胞突变存在于BE中, 上皮的那些谁不进展到异型增生或癌症,强调过程的重要作用 而不是基因突变来促进疾病的发生和发展。在这里,我们关注的是 肿瘤微环境在BE和EAC发病机制中的作用, 整合和互补。我们提供了新的和令人信服的数据,涉及一个子集的渗透 活化的成纤维细胞和免疫细胞在相互加强的信号通路的互联网中 与BE上皮细胞,增强致癌作用。我们假设这些促癌细胞 BE微环境中的人群是理解BE如何以及为什么发展为EAC的关键, 这些细胞和调节途径的特征将作为开发 筛选和治疗的新方法。这一假设将通过以下几个方面加以探讨: 具体目的:1)确定免疫细胞和成纤维细胞的性质和功能 存在于人类BE和EAC患者中。2)为了证明癌症分泌的IL-6如何与 成纤维细胞和TP 53突变上皮促进BE发病机制和进展为EAC。3)审查 骨髓源性抑制细胞(MDSC)和调节性T细胞(TReg)对BE进展的影响 到EAC。总结和

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)

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Anil K Rustgi其他文献

EGFR inhibitors eliminate esophageal cancer stem cells by suppressing epithelial-mesenchymal transition.
EGFR 抑制剂通过抑制上皮间质转化来消除食道癌干细胞。
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mitsuteru Natsuizaka;Bongani Kaimila;Yoshimasa Kubota;Yutaka Hatanaka;Katsuji Marukawa;Katsumi Terashita;Fumiyuki Sato;Shunsuke Ohnishi;Goki Suda;Shinya Ohashi;Shingo Kagawa;Kelly Whelan;Anil K Rustgi;Hiroshi Nakagawa;Naoya Sakamoto
  • 通讯作者:
    Naoya Sakamoto

Anil K Rustgi的其他文献

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{{ truncateString('Anil K Rustgi', 18)}}的其他基金

ORION: Oncology Research Integration using OHDSI-based NLP (NCI Cancer Informatics Scholar)
ORION:使用基于 OHDSI 的 NLP 进行肿瘤学研究整合(NCI 癌症信息学学者)
  • 批准号:
    10891217
  • 财政年份:
    2023
  • 资助金额:
    $ 24.49万
  • 项目类别:
Core A - Administrative and Biostatistics Core
核心 A - 行政和生物统计核心
  • 批准号:
    10493658
  • 财政年份:
    2021
  • 资助金额:
    $ 24.49万
  • 项目类别:
Mechanisms of Esophageal Carcinogenesis
食管癌发生机制
  • 批准号:
    10305930
  • 财政年份:
    2021
  • 资助金额:
    $ 24.49万
  • 项目类别:
Networks for functional regulation of pancreatic acinar-ductal metaplasia and epithelial plasticity
胰腺腺泡导管化生和上皮可塑性的功能调节网络
  • 批准号:
    9977159
  • 财政年份:
    2019
  • 资助金额:
    $ 24.49万
  • 项目类别:
Weight loss-induced Microbiome and Adipokine Changes in Barrett's Esophagus
减肥引起的巴雷特食管微生物组和脂肪因子变化
  • 批准号:
    8844119
  • 财政年份:
    2011
  • 资助金额:
    $ 24.49万
  • 项目类别:
Stem Cells And The Origins of Barrett's Esophagus
干细胞和巴雷特食管的起源
  • 批准号:
    8208253
  • 财政年份:
    2011
  • 资助金额:
    $ 24.49万
  • 项目类别:
Project 2: Characterization of microenvironmental drivers of neoplasia in BE
项目 2:BE 肿瘤形成微环境驱动因素的表征
  • 批准号:
    10183179
  • 财政年份:
    2011
  • 资助金额:
    $ 24.49万
  • 项目类别:
Stem Cells And The Origins of Barrett's Esophagus
干细胞和巴雷特食管的起源
  • 批准号:
    9325648
  • 财政年份:
    2011
  • 资助金额:
    $ 24.49万
  • 项目类别:
Stem Cells And The Origins of Barrett's Esophagus
干细胞和巴雷特食管的起源
  • 批准号:
    8535691
  • 财政年份:
    2011
  • 资助金额:
    $ 24.49万
  • 项目类别:
SARS-CoV-2, ACE2 and Esophageal Neoplasia
SARS-CoV-2、ACE2 和食管肿瘤
  • 批准号:
    10180483
  • 财政年份:
    2011
  • 资助金额:
    $ 24.49万
  • 项目类别:

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