PDT--MECHANISMS AND STRATEGIES FOR OPTIMIZATION

该计划项目的总体目标是获得更多 对光动力疗法(PDT)和TO的机理的了解 优化处理参数。这将通过以下方式实现 个人研究项目： 1.将制备新的同种系列光敏剂，并 特征，以便阐明那些重要的参数 对于最佳活动和那些不相关的活动。量化数据 将获得允许使用多维QSAR模型的产品，以及 我们将检验这些模型的预测价值。两国关系 有效的增敏剂和它们结合特定基因的能力 细胞内的位置将被检查。 2.某些细胞因子的动力学和组织分布 在体内由PDT通过氧化应激机制诱导 探索过了。假设这些细胞因子可以，至少部分， 解释了它的免疫增强和免疫抑制作用 将对PDT进行检查。 3.细胞内结合部位是否有效的问题 光敏剂主要是线粒体，如果外周 该细胞器中的苯并二氮卓类受体在增敏剂中起重要作用。 我们将探索绑定。假设线粒体和PBR- 相关的感光剂在诱导光损伤方面很重要，而 本课程将探讨导致细胞死亡的生理反应。 4.将提供实时和短期的替代变量 关于潜在的机械过程和可能的结果的信息 在临床上进行PDT，并允许为个别患者量身定做治疗 并且会出现病变。作为一个普遍的范例，光剂量和剂量 在不同ALA应用的ALA-PDT中，将探索速率效应 基底细胞癌和皮肤淋巴瘤的次数，并进行检查 造成差异的光化学和生物过程 在效力、效率和选择性方面。该计划将由以下机构支持 三个重要的技术核心组件和一个管理核心。

The overall goals of the Program Project are to gain an increased understanding of the mechanisms of photodynamic therapy (PDT) and to optimize treatment parameters. This will be achieved through the following individual research projects: 1. New, congeneric series of photosensitizers will be prepared and characterized, in order to elucidate those parameters which are important for optimal activity and those which are irrelevant. Quantitative data will be obtained which allow use of multi-dimensional QSAR models, and the predictive value of these models will be examined. The relationship between effective sensitizers and their ability to bind to specific intracellular sites will be examined. 2. The kinetics and tissue distributions of certain cytokines which are induced in vivo by PDT via oxidative stress mechanisms will be explored. The hypotheses that these cytokines can, at least in part, account for the immunopotentiating as well as immunosuppressive effects of PDT will be examined. 3. The questions of whether intracellular binding sites of effective photosensitizers are primarily mitochondrial and if the peripheral benzopdiazepine receptor in this organelle is important in sensitizer binding will be explored. The hypothesis that mitochondrial and PBR- associated sensitizers are important in inducing photodamage and the physiological responses which lead to cell death will be explored. 4. Surrogate variables which will provide real-time and short-term information on the underlying mechanistic processes and probably outcomes in clinical PDT and permit tailoring of the therapy to individual patients and lesions will be developed. As a general paradigm, light dose and dose rate effects will be explored in ALA-PDT with different ALA application times in basal cell carcinomas and cutaneous lymphomas, with examination of the photochemical and biological processes contributing to differences in efficacy, efficiency and selectivity. The Program will be supported by three important technical Core components and an Administrative Core.