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

喉乳头状瘤是无法治愈的。传统型和试验型 治疗充其量只能控制这种疾病，但许多患者会受到影响。 频繁复发。我们目前正在测试光动力疗法(PDT)， 使用双血卟啉醚(DHE)(PHOTOFRIN)。复发率为 减少，一些患者现在已经没有疾病了。然而，大多数患者 仍然有反复发作的疾病，并不是所有人都有反应。这个项目是一个 继续研究光动力疗法的疗效，但使用一种新药--Meso- 四(羟基苯基)氯(MTHPC)，有改进潜力 功效和较低的光敏性。中度至重度患者 疾病将在PDT之前的6个月内定期进行评估 PDT后12个月，这样每个患者都将被用作他自己的 控制力。还将将PDT组与并发控制组进行比较 接受标准治疗的疾病严重程度相当的患者。此外 在评估疗效时，我们会问为什么一些患者有反应，而另一些患者有反应 不要这样做。我们将确定组织中mTHPC水平是否与 回应。我们还将确定mTHPC的PDT是否会导致 病毒在临床正常组织中的持续或表达。这些研究 应该增加我们对光动力疗法有效性的理解。 具体目标涉及以下问题： L：mTHPC是否降低了反映乳头状瘤复发生长的评分 重要的是？ 2.发病或开始治疗时的年龄、性别或疾病 严重程度与治疗前和治疗后评分的变化相关吗？ 3.DO组织和治疗时血浆mTHPC水平相关 有没有临床结果？ 4.光动力疗法联合mTHPC能消除HPV DNA的持久性吗？ 5.如果HPV感染仍然存在，光动力疗法是否会减少或消除病毒 转录和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?