Endogenous photosensitizers in skin carcinogenesis

内源性光敏剂在皮肤癌发生中的作用

基本信息

  • 批准号:
    7545687
  • 负责人:
  • 金额:
    $ 5.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-01-01 至 2009-12-31
  • 项目状态:
    已结题

项目摘要

This application aims to establish a causative role of skin structural proteins (keratin, collagen, and elastin) as I endogenous UV-sensitizers in skin photodamage and evaluates modulation of these novel targets for I chemoprevention of photocarcinogenesis and photoaging. Photooxidative stress initiated by solar irradiation Iof endogenous sensitizers is a key mechanism of skin photodamage, but the molecular nature of the photodynamic non-DNA chromophores responsible for light-driven production of reactive oxygen species (ROS) is unknown. Pilot data summarized in the application support the hypothesis that UV chromophores contained exclusively in extracellular matrix proteins of skin are potent endogenous photosensitizers. To test Ithis hypothesis reconstructed epidermis, dermis, and full thickness human skin tissue equivalents will be Iused to allow quantitative control of protein UV-chromophores of both enzymatic and non-enzymatic origin "(aim 1). Sensitizer-dependent and independent ROS production in response to total and fractionated solar UV light will be determined and results will be validated by direct chemical analyses (aim 2). Established molecular and cellular biomarkers of photooxidative stress will be assessed as a function of sensitizer content and radiation dose. Photosensitized enhancement of known biomarkers of photocarcinogenesis and photoaging will be studied (aim 3). The therapeutic potential of physical quenchers of photoexcited states as a novel class of topical chemopreventive agents for suppression of sensitized photodamage in reconstructed human skin will be evaluated. Reconstructed human skin with controlled sensitizer content will be irradiated and the chemopreventive potential of prototype quenchers as direct molecular antagonists of photoexcited states will be evaluated. A novel secondary amine pharmacophore, which protects human skin cells against photosensitization by physical deactivation of excited state molecules and singlet oxygen without chemical Idepletion, will be tested as a prototype chemopreventive agent and derivatized for optimal topical delivery I(aim 4). The efficacy of the lead quencher of photoexcited states will be tested in an animal model of Iphotocarcinogenesis. This study will validate endogenous structural skin components as novel molecular Itargets for chemoprevention in skin photocarcinogenesis and photoaging and lead to a new class of Iphotoprotective agents.
本应用程序旨在建立皮肤结构蛋白(角蛋白,胶原蛋白和弹性蛋白)的致病作用

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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ELAINE L JACOBSON其他文献

ELAINE L JACOBSON的其他文献

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{{ truncateString('ELAINE L JACOBSON', 18)}}的其他基金

Endogenous photosensitizers in skin carcinogenesis
内源性光敏剂在皮肤癌发生中的作用
  • 批准号:
    6869984
  • 财政年份:
    2005
  • 资助金额:
    $ 5.11万
  • 项目类别:
Endogenous photosensitizers in skin carcinogenesis
内源性光敏剂在皮肤癌发生中的作用
  • 批准号:
    6989089
  • 财政年份:
    2005
  • 资助金额:
    $ 5.11万
  • 项目类别:
Endogenous photosensitizers in skin carcinogenesis
内源性光敏剂在皮肤癌发生中的作用
  • 批准号:
    7332241
  • 财政年份:
    2005
  • 资助金额:
    $ 5.11万
  • 项目类别:
Endogenous photosensitizers in skin carcinogenesis
内源性光敏剂在皮肤癌发生中的作用
  • 批准号:
    7537180
  • 财政年份:
    2005
  • 资助金额:
    $ 5.11万
  • 项目类别:
Endogenous photosensitizers in skin carcinogenesis
内源性光敏剂在皮肤癌发生中的作用
  • 批准号:
    7162509
  • 财政年份:
    2005
  • 资助金额:
    $ 5.11万
  • 项目类别:
Endogenous photosensitizers in skin carcinogenesis
内源性光敏剂在皮肤癌发生中的作用
  • 批准号:
    7494192
  • 财政年份:
    2005
  • 资助金额:
    $ 5.11万
  • 项目类别:
Endogenous photosensitizers in skin carcinogenesis
内源性光敏剂在皮肤癌发生中的作用
  • 批准号:
    7753521
  • 财政年份:
    2005
  • 资助金额:
    $ 5.11万
  • 项目类别:
Carbonyl scavengers for skin protection from glycation
用于保护皮肤免受糖化作用的羰基清除剂
  • 批准号:
    6691130
  • 财政年份:
    2003
  • 资助金额:
    $ 5.11万
  • 项目类别:
NAD AND PREVENTION OF MAMMARY CARCINOGENESIS
NAD 与预防乳腺癌
  • 批准号:
    2733114
  • 财政年份:
    1996
  • 资助金额:
    $ 5.11万
  • 项目类别:
NAD AND PREVENTION OF MAMMARY CARCINOGENESIS
NAD 与预防乳腺癌
  • 批准号:
    2443120
  • 财政年份:
    1996
  • 资助金额:
    $ 5.11万
  • 项目类别:

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  • 财政年份:
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