The Role of PPARgamma in Lung Cancer Progression and Metastasis

PPARγ 在肺癌进展和转移中的作用

基本信息

  • 批准号:
    8970678
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-04-01 至 2017-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in lung cancer research. The applicant completed a structured Pulmonary and Critical Care fellowship at the University of Colorado Denver in 2010, and will now expand his scientific skills to develop into an independent investigator. This program will extend our knowledge of lung cancer progression and metastasis. Dr. Robert Keith will mentor the applicant's scientific development. Dr. Keith is an established researcher in the field of lung cancer, especially with regards to lung cancer chemoprevention. He is the Associate Chief of Staff for Research and Development at the Denver VA Medical Center. To enhance the training, the program will enlist the expertises of Dr. Raphael Nemenoff, Professor of Medicine and a recognized leader in the field of lung cancer research, especially with regards to the tumor microenvironment; and Dr. Mary Weiser-Evans, an Associate Professor of Medicine with extensive experience in developing in vivo animal models. In addition, an advisory committee of highly-regarded medical scientists will provide scientific and career advice. Research will focus on the role of PPARy, which is a member of the nuclear receptor superfamily of ligand-activated transcription factors, in lung cancer progression and metastasis. Recent work in the laboratory of Dr. Nemenoff has shown that treating mice with pioglitazone, which is a pharmacological PPARy activator, accelerates lung cancer metastasis. Previous work from the Nemenoff laboratory and others has shown that activation of PPARy in cancer cells promotes differentiation and inhibits transformed growth. Thus, we hypothesize that treatment with pioglitazone leads to activation of PPARy in cells in the tumor microenvironment, such as tumor-associated macrophages, which accelerates lung cancer metastasis. The specific aims include: 1) determine the effect of systemic PPARy activation on lung cancer progression and metastasis, 2) assess the effect of selective deletion of PPARy in macrophages on metastasis, and 3) establish the role of macrophage-specific PPARy in mediating interactions between cancer cells and macrophages. If pioglitazone, which is a member of the thiazolidinedione class of antidiabetic agents, indeed accelerates metastasis, then there may be far-reaching implications for diabetics currently being prescribed thiazolidinediones. The Denver VA Medical Center and the Division of Pulmonary Sciences and Critical Care Medicine at the University of Colorado Denver provide an ideal setting for training physician-scientists by incorporating expertise from diverse resources into customized programs. Such an environment maximizes the potential for the applicant to establish a scientific niche from which an academic career can be constructed.
描述(由申请人提供): 该建议描述了一项为期5年的培训计划,以开发肺癌研究的学术生涯。申请人于2010年在科罗拉多大学丹佛大学完成了结构化的肺和重症监护奖学金,现在将扩大他的科学技能,以发展为独立的研究者。 该计划将扩展我们对肺癌进展和转移的了解。罗伯特·基思(Robert Keith)博士将指导申请人的科学发展。基思博士是肺癌领域的知名研究员,尤其是在肺癌化学预防方面。他是丹佛VA医疗中心研究与开发的参谋长。为了增强培训,该计划将招募医学教授拉斐尔·尼梅诺夫(Raphael Nemenoff)博士,肺癌研究领域的公认领导者,尤其是在肿瘤微环境方面;以及在发展体内动物模型方面拥有丰富经验的医学副教授Mary Weiser-Evans博士。此外,由备受瞩目的医学科学家组成的咨询委员会将提供科学和职业建议。 研究将集中在PPARY的作用上,PPARY是配体激活转录因子的核受体超家族,在肺癌进展和转移中的成员。 Nemenoff博士实验室的最新工作表明,用吡格列酮治疗小鼠,这是一种药理学促进剂,可以加速肺癌转移。 Nemenoff实验室和其他人的先前工作表明,癌细胞中PPARY的激活促进了分化并抑制了转化的生长。因此,我们假设用吡格列酮治疗会导致肿瘤微环境中细胞中PPARY的激活,例如肿瘤相关的巨噬细胞,从而加速了肺癌转移。具体目的包括:1)确定全身性PPARY激活对肺癌进展和转移的影响,2)评估巨噬细胞中PPARY选择性缺失对转移的影响的影响,3)建立巨噬细胞特异性PPARY在介导癌细胞与癌细胞之间的相互作用中的作用。如果吡格列酮(是硫代二酮类抗糖尿病剂的成员,确实会加速转移,那么对当前处方的噻唑烷二酮的糖尿病患者可能会有深远的影响。 丹佛VA医学中心以及科罗拉多大学丹佛分校的肺科学和重症监护医学部,通过将各种资源的专业知识纳入定制计划中,为培训医师科学家提供了理想的环境。这种环境最大程度地提高了申请人建立科学利基市场的潜力,可以从中建立学术职业。

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)

暂无数据

数据更新时间:2024-06-01

Howard Li的其他基金

The Role of PPARgamma in Lung Cancer Progression and Metastasis
PPARγ 在肺癌进展和转移中的作用
  • 批准号:
    8698276
    8698276
  • 财政年份:
    2012
  • 资助金额:
    --
    --
  • 项目类别:
The Role of PPARgamma in Lung Cancer Progression and Metastasis
PPARγ 在肺癌进展和转移中的作用
  • 批准号:
    8444259
    8444259
  • 财政年份:
    2012
  • 资助金额:
    --
    --
  • 项目类别:
The Role of PPARgamma in Lung Cancer Progression and Metastasis
PPARγ 在肺癌进展和转移中的作用
  • 批准号:
    8803265
    8803265
  • 财政年份:
    2012
  • 资助金额:
    --
    --
  • 项目类别:
The Role of PPARgamma in Lung Cancer Progression and Metastasis
PPARγ 在肺癌进展和转移中的作用
  • 批准号:
    8246209
    8246209
  • 财政年份:
    2012
  • 资助金额:
    --
    --
  • 项目类别:

相似国自然基金

新型IL2Rβγ激动剂逐级控释联合放疗对抗三阴性乳腺癌的作用及机制研究
  • 批准号:
    82303819
  • 批准年份:
    2023
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
负载自组装型非核苷类STING激动剂的亚精胺水凝胶用于抗肿瘤免疫治疗及机制研究
  • 批准号:
    82303561
  • 批准年份:
    2023
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
靶向SIRT3小分子激动剂调控三阴性乳腺癌细胞自噬和免疫微环境的机制研究
  • 批准号:
    82373193
  • 批准年份:
    2023
  • 资助金额:
    49 万元
  • 项目类别:
    面上项目
基于OSMAC-GNPS分析策略的蚂蚱内生真菌Aspergillus sp.中新颖泛PPAR激动剂的发现及治疗NASH研究
  • 批准号:
    82304340
  • 批准年份:
    2023
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目
探究FSP1激动剂在治疗肾缺血再灌注损伤中的分子机理与应用
  • 批准号:
    82304600
  • 批准年份:
    2023
  • 资助金额:
    30 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Elucidating anti-angiogenic tyrosine kinase inhibitor-induced vascular dysfunction
阐明抗血管生成酪氨酸激酶抑制剂诱导的血管功能障碍
  • 批准号:
    10570393
    10570393
  • 财政年份:
    2023
  • 资助金额:
    --
    --
  • 项目类别:
New Therapies for Essential Tremor from Cannabidiols Mechanisms
大麻二酚机制治疗特发性震颤的新疗法
  • 批准号:
    10478737
    10478737
  • 财政年份:
    2022
  • 资助金额:
    --
    --
  • 项目类别:
A Pathogenic Role for Natriuretic Peptide Receptor-C in Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction
钠尿肽受体-C 在肺动脉高压和射血分数保留的心力衰竭中的致病作用
  • 批准号:
    10463813
    10463813
  • 财政年份:
    2021
  • 资助金额:
    --
    --
  • 项目类别:
A Pathogenic Role for Natriuretic Peptide Receptor-C in Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction
钠尿肽受体-C 在肺动脉高压和射血分数保留的心力衰竭中的致病作用
  • 批准号:
    10301687
    10301687
  • 财政年份:
    2021
  • 资助金额:
    --
    --
  • 项目类别:
S1P as regulator of neonatal mucosal immune development and injury
S1P作为新生儿粘膜免疫发育和损伤的调节剂
  • 批准号:
    10039799
    10039799
  • 财政年份:
    2020
  • 资助金额:
    --
    --
  • 项目类别: