CELLULAR & SUBCELLULAR MECHANISMS: PHOTODYNAMIC THERAPY: CANCER MANAGEMENT

该项目的长期目标是开发 光动力疗法（PDT）在临床管理中的应用 of patients患者with cancer癌症. 这一目标将通过获得 更全面地了解PDT的基本机制， 进行仔细的临床研究，以证明安全性， 功效 基础科学研究的具体目标是 探讨PDT对肿瘤作用的基本机制 微观结构 进一步阐明PDT的作用机制 在细胞水平上，将研究不同的光敏剂， 关于细胞摄取/保留动力学，亚细胞 定位/结合，亚细胞光毒性，光敏剂 光漂白和荧光对光毒性的预测价值， 和细胞摄取的机制。 这些光敏剂显示 PDT活性显著高于Photofrin“标准”， 微血管内皮细胞培养以及其它培养 将对系统研究进行评估。 这些研究的目的将 通过检查每一个细胞，阐明PDT的作用机制。 光敏剂与光和药物剂量学参数的关系 对于最佳的肿瘤微血管破坏，光和电子 肿瘤微血管时间进程的显微镜研究 破坏和光敏剂定位的测定 微血管结构，使用电子显微镜放射自显影。

The long term objective of this project is the development of Photodynamic Therapy (PDT) for application in the clinical management of patients with cancer. This goal will be accomplished by gaining a more completed understanding of the basic mechanisms of PDT and conducting careful clinical studies in order to demonstrate safety and efficacy. The specific aims of the basic science studies are to investigate the fundamental mechanism(s) of PDT action on tumor microstructure. To elucidate further the mechanism(s) of PDT action at the cellular level, different photosensitizers will be studied with respect to cellular uptake/retention kinetics, subcellular localization/binding, subcellular phototoxicity, photosensitizer photobleaching and predictive value of fluorescence for phototoxicity, and mechanism(s) of cellular uptake. Those photosensitizers that show significantly more PDT activity than Photofrin "standard" in the human microvascular endothelial cell cult ure, as well as other culture systems studies will be evaluated. The purpose of these studies will be to elucidate the mechanisms of PDT action by examining each of the photosensitizers with respect to light and drug dosimetry parameters for optimal tumor microvasculature destruction, light and electron microscopic study of the time course of tumor microvasculature destruction and determination of photosensitizer localization in microvasculature structures using electron microscope autoradiography.