Effect of UVA Irradiation on Melanocyte Stem Cells and Relationship to Developmen
UVA照射对黑素细胞干细胞的影响及其与发育的关系
基本信息
- 批准号:8301038
- 负责人:
- 金额:$ 5.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAdultAmericanBRAF geneCell AgingCellsDNA RepairDermalDevelopmentDevicesDiseaseEarly DiagnosisEnvironmental CarcinogensEtiologyEventExposure toFishesGoalsHealthHourHumanIncidenceLesionMaintenanceMalignant NeoplasmsMelanocytic NeoplasmMelanophoresMethodsModelingMole the mammalMolecularMutateMutationNatural regenerationNevusNormal tissue morphologyOncogenicPathway interactionsPersonsPharmaceutical PreparationsPlayPreventionPrevention strategyProcessResearchResearch Project GrantsRoleSkinSkin CancerSkin tanningSourceStagingStem cellsSunlightTestingTransgenic OrganismsUVA inducedUltraviolet A radiationUltraviolet RaysUnited StatesWorkZebrafishbasebeta-Galactosidasecell transformationdesignfounder mutationin vivoirradiationmelanocytemelanomapreventprogramssenescencetreatment strategytumor
项目摘要
DESCRIPTION (provided by applicant): Melanoma is the most deadly form of human skin cancer. It is estimated that one American dies from melanoma every hour. However, melanoma is a highly curable disease when detected at early stages. Determining the etiology of melanoma and the early mechanisms involved in its development will permit earlier detection and design of more effective drugs to treat it and prevent its reoccurrence. The long-range goal of this research is to identify the early molecular events responsible for the development of malignant melanoma. Sunlight ultraviolet radiation (UV) is the prominent environmental carcinogen known to be involved in melanoma. The UVA wavelengths (320-400 nm) of the solar spectrum now seem to play a much more important role in melanoma than previous thought. The primary objective of this proposal is to determine if UVA irradiation of melanocyte stem cells increases the incidence of melanocyte tumors in the adult. The central hypothesis is that the more penetrating UVA radiation reaches the dermal layer of the skin and causes mutations in the melanocyte stem cell or in its transit amplifying cells thereby contributing to the early stages of melanoma. This project will use a recently discovered method in zebra fish for eliminating adult melanophores and synchronizing melanocyte regeneration from melanocyte stem cells to determine if UVA irradiation of melanocyte stem cells will increase the incidence of melanocytic tumors. The transgenic zebra fish model for human melanoma which has the human BRAF founder mutation for melanoma will be used to accomplish the following specific aims: (1) determine if UVA irradiation of melanocyte stem cells will increase the incidence of melanocyte proliferations in nevi (moles) and the development of melanoma, and whether additional UVA irradiation of the regenerated adult melanocytes derived from these irradiated stem cells will increase the incidence melanoma, and (2) determine if cellular senescence, known to be a powerful tumor-suppressive process that prevents excessive proliferation, is suppressed in nevi or tumors by UVA irradiation of either melanocyte stem cells or adult melanocytes. The results of this research will help to unravel the early mechanisms that contribute to the development of melanoma, and determine if UVA radiation of melanocyte stem cells plays an important role in this process.
PUBLIC HEALTH RELEVANCE: This research project will help determine how exposure to sunlight and artificial sources of sunlight such as tanning and phototherapeutic devices contribute to the early events in the development of melanoma. It will determine if exposure to the UVA wavelengths will mutate melanocyte stem cells and contribute to the development of melanoma. Understanding the early events in melanoma will permit earlier detection and development of more effective drugs to treat it and prevent it reoccurrence.
描述(由申请人提供):黑色素瘤是最致命的人类皮肤癌。据估计,每小时就有一名美国人死于黑色素瘤。然而,如果在早期发现,黑色素瘤是一种高度可治愈的疾病。确定黑色素瘤的病因及其发展的早期机制将允许更早地发现和设计更有效的药物来治疗它并防止其再次发生。这项研究的长期目标是确定负责恶性黑色素瘤发展的早期分子事件。阳光紫外线辐射(UV)是已知与黑色素瘤有关的主要环境致癌物。太阳光谱的UVA波长(320-400纳米)在黑色素瘤中扮演的角色似乎比之前认为的要重要得多。本提案的主要目的是确定UVA照射黑素细胞干细胞是否会增加成人黑素细胞肿瘤的发生率。核心假设是,穿透性更强的UVA辐射到达皮肤真皮层,导致黑素细胞干细胞或其转运放大细胞发生突变,从而导致黑色素瘤的早期阶段。该项目将使用最近在斑马鱼中发现的一种方法,消除成年黑色素细胞并同步从黑色素细胞干细胞中再生黑色素细胞,以确定UVA照射黑色素细胞干细胞是否会增加黑色素细胞肿瘤的发生率。具有人类黑色素瘤BRAF始祖突变的人类黑色素瘤转基因斑马鱼模型将用于实现以下具体目标:(1)确定UVA照射黑素细胞干细胞是否会增加痣(痣)中黑素细胞增殖的发生率和黑色素瘤的发展,以及来自这些辐照干细胞的再生成人黑素细胞的额外UVA照射是否会增加黑色素瘤的发生率,(2)确定细胞衰老,已知是一个强大的肿瘤抑制过程,可以防止过度增殖,在黑色素细胞干细胞或成人黑色素细胞的UVA照射下,在痣或肿瘤中被抑制。这项研究的结果将有助于揭示黑色素瘤发展的早期机制,并确定UVA辐射黑素细胞干细胞是否在这一过程中起重要作用。
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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James Douglas Hoerter其他文献
James Douglas Hoerter的其他文献
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{{ truncateString('James Douglas Hoerter', 18)}}的其他基金
Effect of UVA Irradiation on Melanocyte Stem Cells and Relationship to Developmen
UVA照射对黑素细胞干细胞的影响及其与发育的关系
- 批准号:
8537732 - 财政年份:2012
- 资助金额:
$ 5.8万 - 项目类别:
Effect of UVA Irradiation on Melanocyte Stem Cells and Relationship to Developmen
UVA照射对黑素细胞干细胞的影响及其与发育的关系
- 批准号:
7937158 - 财政年份:2010
- 资助金额:
$ 5.8万 - 项目类别:
Protein Oxidation in Skin Cells by Tan Bed Irradiation
晒黑床辐射对皮肤细胞中蛋白质的氧化
- 批准号:
7004349 - 财政年份:2004
- 资助金额:
$ 5.8万 - 项目类别:
Protein Oxidation in Skin Cells by Tan Bed Irradiation
晒黑床辐射对皮肤细胞中蛋白质的氧化
- 批准号:
7013531 - 财政年份:2004
- 资助金额:
$ 5.8万 - 项目类别:
Protein Oxidation in Skin Cells by Tan Bed Irradiation
晒黑床辐射对皮肤细胞中蛋白质的氧化
- 批准号:
7269563 - 财政年份:2004
- 资助金额:
$ 5.8万 - 项目类别:
Protein Oxidation in Skin Cells by Tan Bed Irradiation
晒黑床辐射对皮肤细胞中蛋白质的氧化
- 批准号:
6806359 - 财政年份:2004
- 资助金额:
$ 5.8万 - 项目类别:
NUV RESISTANCE-- FUR-DEPENDENT REGULATION OF RPOS.
NUV 抵抗力——RPOS 的毛皮依赖性调节。
- 批准号:
6353721 - 财政年份:2000
- 资助金额:
$ 5.8万 - 项目类别:
NUV RESISTANCE-- FUR-DEPENDENT REGULATION OF RPOS.
NUV 抵抗力——RPOS 的毛皮依赖性调节。
- 批准号:
6084674 - 财政年份:2000
- 资助金额:
$ 5.8万 - 项目类别:
NUV RESISTANCE-- FUR-DEPENDENT REGULATION OF RPOS.
NUV 抵抗力——RPOS 的毛皮依赖性调节。
- 批准号:
6353722 - 财政年份:2000
- 资助金额:
$ 5.8万 - 项目类别:
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