MECHANISM OF PHOTODYNAMIC THERAPY IN PATIENTS

光动力疗法的临床应用涉及较大的参数空间。 具有多个变量。直接检查这些是不可行的 患者的变数，特别是在高风险的皮肤损害中 应答率和复发时间较长提供了延迟的信息。我们 假设三个代理变量将允许我们获得实数- 时间和短期信息，并将允许定制治疗 个别患者和病变。 目的1：在细胞、动物模型和 患者，一组替代变量，使我们能够跟踪过程 以预测最终结果，并理性地 优化处理参数。变量是光漂白动力学， 表皮毒性反应，以及最小光毒性光剂量。 我们假设ALA应用和ALA之间的间隔 放射治疗对临床转归有显著影响 在效力、效率和选择性方面。为了评估这些问题， 第二个目标是： 目的2.检验ALA应用之间的间隔时间的影响 和辐射，利用替代变量和常规 选择治疗参数和跟踪反应的治疗终点 在两种目标是角质形成细胞或免疫的皮肤病中 细胞。 对临床结果的机械性理解需要组织水平 有关光敏剂分布、PDT损伤部位和宿主的信息 回应。我们将在AIM 3中收集这些信息。 目标3.支持目标1-2并与项目1-3合作； 为了检查光敏剂的定位和分布 肿瘤和CL中可能的光敏剂受体及其作用 增敏剂和光动力疗法对皮肤相关免疫细胞和细胞因子的影响 综合。

The clinical application of PDT encompasses a large parameter space with multiple variable. It is not feasible to directly examine these variables in patients, particularly in cutaneous lesions where high response rates and long times to recurrence give delayed information. We hypothesize that three surrogate variables will allow us to obtain real- time and short-term information and will permit tailoring the therapy to individual patients and lesions. Aim 1: To investigate and validate in cells, animal models and patients, a set of surrogate variables that enable us to follow the course of PDT treatment, to predict the ultimate outcome, and to rationally optimize treatment parameters. The variables are photobleaching kinetics, epidermal toxic reaction, and minimal phototoxic light dose. We hypothesize that the interval between ALA application and irradiation has significant effects on clinical outcomes with alterations in efficacy, efficiency and selectivity. To evaluate these issues the second aim is: Aim 2. To examine the effects of the interval between ALA application and irradiation, utilizing both surrogate variables and conventional therapeutic endpoints to select treatment parameters and follow responses in two cutaneous diseases where the targets are keratinocytes or immune cells. Mechanistic understanding of clinical outcomes requires tissue-level information on photosensitizer distribution, PDT damage sites, and host responses. We will collect this information in Aim 3. Aim 3. In support of Aims 1-2 and in collaboration with Projects 1-3; to examine the distribution of photosensitizer localization and of putative photosensitizer receptors in carcinomas and CL; and the effects of sensitizers and PDT on skin-associated immune cells and cytokine synthesis.