Project 4

项目4

• 批准号: 6748001
• 负责人: ALLAN R OSEROFF
• 金额: $ 29.96万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6748001
• 关键词: antineoplastics; athymic mouse; basal cell carcinoma; benzopyrans; clinical research; combination cancer therapy; human subject; human therapy evaluation; immunocytochemistry; laboratory mouse; light intensity; mycosis fungoides lymphoma; neoplasm /cancer immunology; neoplasm /cancer pharmacology; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; patient oriented research; pharmacokinetics; photochemistry; photosensitizing agents; photostimulus; respiratory oxygenation; skin neoplasms; topical drug application; tumor necrosis factor alpha

The clinical application of PDT encompasses a large parameter space with multiple variables. In understanding and optimizing efficacy and selectivity, we hypothesize that these factors often are limited by irradiance-dependent photodynamic oxygen depletion. We also hypothesize that non-invasive measurements ofphotobleaching kinetics and hemoglobin absorbance can yield important, real-time information about PDT; that host inflammatory/immune responses will be affected both by irradiance and fluence, and that DMXAA, an inducer of TNF-alpha, will potentiate ALA-PDT. We have the following specific aims: Aim 1 -Examine the effect of irradiance on PpIX photobleaching rates and normal tissue selectivity. This will occur in preclinical models and in patients. Aim 2 - Determine in patients the fluence-response relationships as a function of irradiance. Examine the effect on the host innate and adaptive immune responses. Aim 3 - Examine a rational combination therapy utilizing topical ALA-PDT and DMXAA in preclinical models and in patients.

PDT的临床应用包括具有多个变量的大参数空间。在 为了理解和优化功效和选择性，我们假设这些因素通常受到辐照依赖性光动力氧消耗的限制。我们还假设，非侵入性测量光漂白动力学和血红蛋白吸光度可以产生重要的，实时的信息PDT，主机炎症/免疫反应将受到辐照度和通量，和DMXAA，TNF-α的诱导剂，将增强ALA-PDT。 我们有以下具体目标： 目的1 -检查辐照度对PpIX光漂白速率和正常组织选择性的影响。这将发生在临床前模型和患者中。 目的2 -确定患者的能量密度-响应关系作为辐照度的函数。检查对宿主先天性和适应性免疫反应的影响。 目的3 -在临床前模型和患者中检查利用局部ALA-PDT和DMXAA的合理组合疗法。