Prevention of photocarcinogenesis by dietary immunomodulation

通过饮食免疫调节预防光致癌

基本信息

  • 批准号:
    8698300
  • 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 2016-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Abstract Overexposure of the human skin to solar ultraviolet (UV) radiation is the major etiologic agent for the development of melanoma and non-melanoma skin cancers in the United States, with non-melanoma skin cancer being the most common cutaneous malignancy. We have demonstrated that dietary grape seed proanthocyanidins (GSPs) provide significant protection against UV-induced skin carcinogenesis in an in vivo mouse model and have further demonstrated that dietary GSPs provide significant protection against UV- induced immunosuppression, a well-established risk factor for skin cancer. The goal of the proposed studies is to establish the mechanisms by which dietary GSPs act to correct UV-induced immunosuppression associated with photocarcinogenesis by: (i) Identifying the mechanisms by which dietary GSPs ameliorate UV radiation- induced immunosuppression and DNA damage; and (ii) Determining the contribution of these mechanisms to GSPs-mediated prevention of skin cancer. Currently, it is known that UV-induced DNA damage in the form of generation of cyclobutane pyrimidine dimers (CPDs) is a risk factor for cancer and is an important molecular trigger for UV-mediated immunosuppression and that UV-mediated immunosuppression is associated with the induction of suppressor cells and impaired function of dendritic cells and effector T cells. The critical question is therefore whether the GSPs act on multiple fronts to prevent or correct UV-induced immunosuppression or act by blocking the early events that initiate immunosuppression. Our pilot studies suggest that GSPs have the ability to enhance the removal or repair of CPD+ cells in UV-exposed skin and our preliminary data further indicate that GSPs can act to enhance the removal of CPDs in UV-exposed dendritic cells and restore dendritic cell-mediated activities, including stimulation of T cells. Notably, dietary GSPs do not inhibit UV-induced immunosuppression in those mice which have a defect in DNA repair. Together, these data suggest the hypothesis that the repair of UVB-induced DNA damage by GSPs in dendritic cells is critical for their chemopreventive effects on UV-induced immunosuppression and photocarcinogenesis. We propose four inter-related Specific Aims in which we will use genetically modified mouse model, including nucleotide excision repair-deficient mice: (1) Determine whether dietary GSPs inhibit the development of UV-induced tolerogenic dendritic cells through restoration of dendritic cell activity; (2) Determine whether dietary GSPs inhibit UV-induced immunosuppression through enhancement of T-cell activation, (3) Determine whether dietary GSPs inhibit the development of UV-induced regulatory T cells; and (4) Determine whether inhibition of photocarcinogenesis by dietary GSPs is mediated through DNA repair. SIGNIFICANCE: These studies address a major public health and VA healthcare concern, i.e., the growing incidence of skin cancers. The development of more effective preventive approaches, such as dietary GSPs that exhibit no toxicity in mice, requires an improved understanding of the mechanisms by which they prevent UVB-induced carcinogenesis.
描述(由申请人提供):

项目成果

期刊论文数量(0)
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SANTOSH KUMAR KATIYAR其他文献

SANTOSH KUMAR KATIYAR的其他文献

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{{ truncateString('SANTOSH KUMAR KATIYAR', 18)}}的其他基金

Prevention of UV-carcinogenesis through DNA methylation-dependent immunomodulation
通过 DNA 甲基化依赖性免疫调节预防紫外线致癌
  • 批准号:
    8883008
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
Prevention of UV-carcinogenesis through DNA methylation-dependent immunomodulation
通过 DNA 甲基化依赖性免疫调节预防紫外线致癌
  • 批准号:
    9070629
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
Proanthocyanidins,Novel bioactive components for prevention of melanoma invasion
原花青素,预防黑色素瘤侵袭的新型生物活性成分
  • 批准号:
    8442533
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Proanthocyanidins,Novel bioactive components for prevention of melanoma invasion
原花青素,预防黑色素瘤侵袭的新型生物活性成分
  • 批准号:
    8601917
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Prevention of photocarcinogenesis by dietary immunomodulation
通过饮食免疫调节预防光致癌
  • 批准号:
    8431273
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Prevention of photocarcinogenesis by dietary immunomodulation
通过饮食免疫调节预防光致癌
  • 批准号:
    8240922
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Prevention of photocarcinogenesis by dietary immunomodulation
通过饮食免疫调节预防光致癌
  • 批准号:
    8803280
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
Epigenetic modulation by green tea in prevention of photocarcinogenesis
绿茶的表观遗传调节预防光致癌
  • 批准号:
    7895438
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Epigenetic modulation by green tea in prevention of photocarcinogenesis
绿茶的表观遗传调节预防光致癌
  • 批准号:
    8033727
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
Prevention of UV-carcinogenesis through DNA repair-dependent immunomodulation
通过 DNA 修复依赖性免疫调节预防紫外线致癌
  • 批准号:
    8210888
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:

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