Topical 'photo-chemoprevention' of oral leukoplakia

口腔白斑是一种常见的临床表现，具有很高的恶性转化风险。化学预防药物的局部应用提供了一个有吸引力的策略，试图有效地控制病变，毒性比全身给药小。然而，由于一些固有的局限性，其有效性是有争议的。在本研究中，我们假设局部应用585 nm脉冲染料激光和粘膜粘附膜（MAF）将对目前的局部方法产生重大改进。该建议的长期目标是开发一种新的联合策略，以化学预防口腔白斑。具体目标是：(1)优化激光参数；(2)制备含有13-顺式类维甲酸（13c-RA）的外用膜；(3)确定这种组合是否产生协同效应，从而使临床应用具有显著的益处。通过荧光成像和免疫染色技术测定仓鼠模型微血管密度，确定最佳激光参数。将在仓鼠模型中评估MAF对局部粘膜的潜在副作用和理想剂量。将新策略与常规全身给药和局部溶液涂敷在患癌前病变的仓鼠颊袋模型上的效果进行比较。据我们所知，这是第一次尝试结合激光微血管靶向，聚合物薄膜和化学预防技术来预防癌症。这一提议的策略如果成功，很可能提供一种比现有方法更有效、毒性更小的替代方法。它还广泛应用于预防皮肤癌或其他可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.