OPTIMIZATION OF PHOTODYNAMIC THERAPY USING MESO-TETRA(HYDROXYPHENYL) CLORIN

喉乳头状瘤是一种常见的恶性肿瘤。常规和实验 治疗最多只能控制疾病，但许多患者 频繁复发我们目前正在测试光动力疗法（PDT）， 使用二血卟啉醚（DHE）（Photofrin）。复发率为 现在，有些病人已经痊愈了。然而，大多数患者 仍然有复发性疾病，并不是所有人都有反应。这个项目是一个 继续研究PDT的疗效，但与一种新药，中- 四（羟基苯基）二氢卟酚（mTHPC），具有改善 功效和较低的光敏性。中重度 在PDT前6个月内，将以固定间隔对疾病进行评估， PDT后12个月，以便每名患者将被用作自己的 控制PDT组还将与同期对照组进行比较 疾病严重程度相当的患者接受标准治疗。此外 为了评估疗效，我们会问为什么有些患者有反应，而另一些患者则有反应。 不要。我们将确定组织中的mTHPC水平是否与 反应我们还将确定PDT与mTHPC是否诱导了 临床正常组织中的病毒持续存在或表达。这些研究 应该增加我们对PDT有效性的理解。 具体目标涉及以下问题： L. mTHPC是否降低反映乳头状瘤复发性生长的评分 显著？ 2. 发病或开始治疗时的年龄、性别或疾病 严重程度与治疗前后评分变化相关？ 3.治疗时的组织和血浆mTHPC水平是否相关 临床结果？ 4. PDT联合mTHPC是否能消除HPV DNA的持久性？ 5.如果HPV感染仍然存在，PDT是否可以减少或消除病毒 转录，这是否与临床结果相关？

There is no cure for laryngeal papillomas. Conventional and experimental treatments can, at best, control the disease but many patients suffer frequent recurrences. We are currently testing photodynamic therapy (PDT), using dihematoporphyrin ether (DHE) (photofrin). The recurrence rate was reduced, and some patients are now free of disease. However, most patients still have recurrent disease, and not all responded. This project is a continued study of PDT efficacy, but with a new drug, meso- Tetra(hydroxyphenyl) Chlorin (mTHPC), which has potential for improved efficacy and lower photosensitivity. Patients with moderate to severe disease will be evaluated at fixed intervals for 6 months prior to PDT and 12 months post PDT, such that each patient will be used as his own control. The PDT group will also be compared to a concurrent control group with comparable disease severity receiving standard treatment. In addition to evaluating efficacy, we will ask why some patients respond while others do not. We will determine whether mTHPC levels in tissues correlate with response. We also will determine whether PDT with mTHPC induces changes in viral persistence or expression in clinically normal tissue. These studies should increase our understanding of PDT effectiveness. The specific aims address the following questions: l. Does mTHPC reduce the score reflecting recurrent growth of papilloma significantly? 2. Do age at disease onset or initiation of treatment, gender or disease severity correlate with change in score from pre- to post-treatment? 3. Do tissue and plasma levels of mTHPC at the time of treatment correlate with clinical outcome? 4. Does PDT with mTHPC eliminate persistence of HPV DNA? 5. If HPV infection remains, does PDT reduce or eliminate viral transcription and does this correlate with clinical outcome?