Laser Assisted Celecoxib Treatment of Oral Leukoplakia

口腔白斑是一种常见的临床表现，其恶性转化率很高。它的累积特征有力地支持了在侵入性病变生长之前进行预防的理论依据。口腔癌的化学预防是一个非常有前途的策略。然而，目前的方法远不能令人满意，因为它们具有显著的毒性。抗血管生成被认为是预防癌症的基础之一。我们之前的研究表明585脉冲染料激光（PDL）激光选择性微血管靶向（MVT）对肿瘤的抑制作用是有效的。PDL与一些化学预防剂之间也存在显著的协同效应。在本研究中，我们将通过使用仓鼠检查袋模型来确定1)是否可以进一步优化激光参数以进行高选择性口腔黏膜MVT治疗；2)新开发的毒性较低的环氧化酶(COX)-2抑制剂塞来昔布治疗口腔白斑是否安全有效；3)如果塞来昔布与PDL联用存在协同效应，在不牺牲其治疗效果的前提下，进一步减少塞来昔布的潜在副作用。这是首次使用MVT技术治疗口腔白斑，以及MVT与塞来昔布联合用于口腔癌化学预防的研究。如果本研究成功，塞来昔布和PDL的联合治疗将为口腔白斑的治疗提供一种新的、理想的“光化学预防”方法。这种新疗法将更有效，毒性更小，而且安全方便，可以进行门诊治疗。同样的概念和方法也可用于皮肤或其他位于组织表面的恶性病变。

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.