Topical 'photo-chemoprevention' of oral leukoplakia

口腔白斑是一种常见的临床表现，有很高的恶变风险。 局部应用化学预防剂是一种有效控制病变的策略，其毒性小于全身给药。 然而，由于其固有的局限性，其有效性存在争议。 在这项拟议的研究中，假设局部应用585 nm脉冲染料激光和粘膜粘附膜（MAF）将产生显着改善目前的局部方法。 该提案的长期目标是开发一种新的化学预防口腔白斑的联合策略。 具体目的是（1）优化激光参数;（2）制备含有13-顺式-维甲酸（13 c-RA）的外用膜;（3）确定这种组合是否产生协同效应，以便临床应用将具有显著益处。 在仓鼠模型上，通过荧光成像和免疫染色技术定量微血管密度，确定最佳的激光参数。 将在仓鼠模型中评价MAF中使用的药剂在局部粘膜中的潜在副作用和理想剂量。 将通过在具有癌前病变的仓鼠模型的颊囊中将其与常规全身给药和局部溶液涂抹进行比较来确定新策略的疗效。 据我们所知，这是首次尝试将联合收割机激光微血管靶向、聚合物薄膜和化学预防技术结合起来用于癌症预防。 如果成功的话，这种策略很可能提供一种比现有方法更有效、毒性更低的替代方法。 它还广泛应用于预防皮肤癌或其他可触及和浅表区域的癌症。

Oral leukoplakia is a common clinical finding with a high risk of malignant transformation. Topical application of chemopreventive agents provide an attractive strategy in an attempt to effectively control the lesions with less toxicity than that in systemic administration. Its efficacy, however, is controversial due to some inherent limitations. In this proposed study, it is assumed that topical application of 585 nm pulsed dye laser and mucosal-adherent film (MAF) will produce a significant improvement of current topical approach. The long-term objectives of the proposal are to develop a novel combination strategy for chemoprevention of oral leukoplakia. The specific aims are (1) optimizing laser parameters; (2) fabricating the topical film containing 13-cis-retinoid acid (13c-RA); and (3) determine if such a combination produce synergic effects so that clinical application would be of significant benefit. The optimal laser parameters will be determined through quantity of microvascular density with fluorescent imagining and immunostaining techniques, in hamster model. The potential side-effect in local mucosa and ideal dosage of the agent used in MAF will be evaluated in the hamster model. The efficacy of new strategy will be determined by compared it with routine systemic administration and topical solution painting, in cheek pouch of hamster model bearing pre-malignant lesions. To our knowledge this is the first attempt to combine laser microvascular targeting, polymer film, and chemopreventive techniques for cancer prevention. This proposed strategy, if successful, is very likely to provide an alternative with higher efficacy and less toxicity than current methods. It also has extensive applications in prevention of skin cancer or cancers in other accessible and superficial areas.