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
项目总结 Barrett‘s食道(BE)是用来代替正常的鳞状上皮的一种 未完全肠化的柱状上皮。它发生在对慢性胃酸和胆汁反流损伤的反应中 食道,是食管腺癌(EAC)的最重要的危险因素,这种疾病的 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 而它向EAC的发展是一项关键的研究迫切需要。最近基因组研究的一个关键教训在一定程度上导致了 这个团队已经证明了在BE中存在许多潜在的致病体细胞突变 那些没有进展到异型增生或癌症的上皮,突出了过程的重要作用 除了基因组突变之外,还有促进疾病发生和发展的基因突变。在这里,我们关注的是关键角色 肿瘤微环境在BE和EAC发病机制中的作用 综合相辅相成。我们提供了新的令人信服的数据,说明了渗透的一个子集 激活的成纤维细胞和免疫细胞在相互增强的信号通路的相互连接的网络中 与促进癌变的BE上皮细胞有关。我们假设这些促进肿瘤的细胞 BE微环境中的种群是了解BE如何以及为什么进展到EAC和 这些细胞和调控通路的特征将成为发展的基础 筛查和治疗的新方法。这一假设将通过以下几个方面进行探讨 相互关联的特定目标: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)展示癌症患者体内IL-6的分泌情况 成纤维细胞和TP53突变的上皮细胞促进了BE的发生和发展为EAC。3)审查 髓源性抑制细胞(MDSC)和调节性T细胞(Treg)对BE进展的影响 致EAC。摘要和

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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