CELLULAR & SUBCELLULAR MECHANISMS: PHOTODYNAMIC THERAPY: CANCER MANAGEMENT

这项计划的长远目标是发展 光动力疗法(PDT)在临床管理中的应用 癌症患者的比例。这一目标将通过获得一个 对光动力疗法的基本机制有更全面的了解 进行仔细的临床研究，以证明安全性和 功效。基础科学研究的具体目标是 光动力疗法抗肿瘤的基本机制研究(S) 微观结构。进一步阐明光动力疗法的作用机制(S) 在细胞水平上，不同的光敏剂将用 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(S)。那些光敏剂显示出 人体PDT活性明显高于Photofrin“标准” 微血管内皮细胞培养及其他培养 将对系统研究进行评估。这些研究的目的将是 为了阐明光动力作用的机制，通过研究每一种 光敏剂对光和药物剂量学参数的影响 为了最佳的肿瘤微血管破坏，光和电子 肿瘤微血管形成时程的显微研究 光敏剂局部化的破坏与检测 用电子显微镜放射自显影技术观察微血管结构。

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.