MECHANISM OF PHOTODYNAMIC THERAPY IN PATIENTS

PDT的临床应用包括一个大的参数空间 多个变量。直接检查这些不可行 患者的变量，特别是在皮肤病变中， 答复率和复发时间长导致信息延迟。我们 假设三个替代变量将允许我们获得真实的- 时间和短期信息，并允许定制治疗， 个别患者和病变。 目的1：在细胞、动物模型和 病人，一组替代变量，使我们能够遵循的过程， PDT治疗，以预测最终结果，并合理地 优化治疗参数。变量是光漂白动力学， 表皮毒性反应和最小光毒性光剂量。 我们假设ALA应用和 放射治疗对临床结果有显著影响， 在功效、效率和选择性方面。为了评估这些问题， 第二个目标是： 目标二。检查ALA应用间隔的影响 和辐照，利用替代变量和常规 治疗终点，以选择治疗参数并随访缓解 在两种皮肤疾病中，目标是角质形成细胞或免疫细胞， 细胞 对临床结局的机制性理解需要组织水平 光敏剂分布、PDT损伤部位和宿主信息 应答我们将在目标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; 以检查光敏剂定位的分布和 癌和CL中假定的光敏剂受体;以及 致敏剂和PDT对皮肤相关免疫细胞和细胞因子的影响 合成.

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.