Laser Assisted Celecoxib Treatment of Oral Leukoplakia

描述：口腔白斑是一种常见的临床表现，恶性转化率高。它的累积特征有力地支持了在侵袭性病变生长之前预防的基本原理。口腔癌的化学预防是非常有前途的策略。然而，目前的方法是非常令人满意的，因为它们的显着毒性。抗血管生成已被认为是癌症预防的基石之一。我们以前的研究表明，585脉冲染料激光（PDL）的激光选择性微血管靶向（MVT）对肿瘤抑制的有效性。PDL与某些化学预防剂之间也有明显的协同作用。在本研究中，我们将通过使用仓鼠模型的检查袋来确定1）是否可以进一步优化用于口腔粘膜的高选择性MVT治疗的激光参数; 2）是否塞来昔布，一种新开发的毒性较小的环氧化酶（考克斯）-2抑制剂，将是治疗口腔白斑的安全和有效的;以及3）如果塞来昔布与PDL组合时存在协同作用，则允许进一步减少塞来昔布的潜在副作用，而不牺牲其治疗功效。这是首次使用MVT技术治疗口腔白斑，并将MVT与塞来昔布联合用于口腔癌化学预防的研究。塞来昔布与PDL联合治疗口腔白斑的实验研究如果成功，将为口腔白斑的光化学预防提供一种新的、理想的方法。这种新疗法将更有效，毒性更小，并且安全方便，足以允许门诊治疗。相同的概念和方法也可用于位于组织表面上的皮肤或其他癌前病变。

DESCRIPTION: Oral leukoplakia is a common clinical finding with a high rate of malignant transformation. Its accumulative features strongly support the rationale for its prevention before invasive lesions can grow. Oral cancer chemoprevention is very promising strategy. Nevertheless, current approaches are very far from being satisfactory because of their significant toxicity. Anti-angiogenesis has been known as one of cornerstones for cancer prevention. Our previous studies have indicated the effectiveness for tumor inhibition of laser selective microvascular targeting (MVT) with a 585 pulsed dye laser (PDL). There was also a significantly synergic effect found between the PDL and some chemopreventive agents. In this proposed study by using check pouch of a hamster model, we will determine 1) if we can further optimize laser parameters for highly-selective MVT treatment for oral mucosa; 2) if Celecoxib, a newly developed less toxic inhibitor of cyclooxygenase (COX)-2, will is safe and effective in treatment of oral leukoplakia; and 3) if there is a synergic effect when combined Celecoxib with PDL, to allow further reduction of potential side-effect with Celecoxib, without sacrificing its treatment efficacy. This is the first study in using a MVT technique for treatment of oral leukoplakia and in combining MVT with Celecoxib for oral cancer chemoprevention. This combined strategy of Celecoxib and PDL, if success in this proposed study, will provide a new and ideal way, called "photo-chemoprevention", for treatment of oral leukoplakia. This new therapy will be more efficacious and less toxic, and is safe and convenient enough to permit an out-patient treatment. The same concept and approach also is available for skin or other pre-malignant lesion located on tissue surface.