Pulsed Dye Laser Assisted Cancer Chemoprevention

口腔癌是最常见的肿瘤之一，是长期接触烟草等致癌物质后，慢性疾病过程的高潮，即癌变。它的多步骤和累积性特征有力地支持了在侵袭性病变生长之前进行预防的基本原理。化学预防是一种非常有前景的新策略，但目前的策略由于其显著的毒性而远远不能令人满意。抗血管生成已被认为是化学预防的基石之一。我们以前的研究表明，使用585nN脉冲染料激光(PDL)进行选择性微血管靶向治疗肿瘤是有效的，而不会对周围组织造成任何损害。这项拟议的研究的目的是确定PDL是否可以催化维甲酸(RA)在口腔异型增生的癌症化学预防中的有效性。这项建议的长期目标是开发一种新的治疗模式：激光辅助癌症化学预防。利用仓鼠颊囊模型，我们的具体目的是确定1)这种选择性靶向的最佳激光参数，以及2)PDL与RA联合使用是否能够单独提高RA的疗效和降低其毒性。据我们所知，这是第一次将激光微血管靶向技术与化学预防药物相结合的研究。这一拟议的策略如果成功，很可能导致一种比目前的治疗方法更有效、毒性更小的替代方案。

Oral cancer is one of the most common neoplasms, and is the culmination of the chronic disease process, carcinogenesis, after long- term exposure to some carcinogenic insults such as tobacco. Its multistep and accumulative features strongly support the rationale for prevention before invasive lesions can grow. Chemoprevention is a very promising new strategy but current strategies are very far from be satisfactory because of their significant toxicity. Anti-angiogenesis has been known as one of cornerstones for the chemoprevention. Our previous studies have indicated the effectiveness for tumor therapy of selective microvascular targeting with a 585 nn pulsed dye laser (PDL), with no damage to any neighboring tissue. The goal of this proposed study is to determine whether a PDL can catalyze the effectiveness of Retinoic Acid (RA) in cancer chemoprevention of oral dysplasia. The long-term objective of this proposal is to develop a novel treatment paradigm: laser assisted cancer chemoprevention. Using cheek pouch of a hamster model, our specific aims are to determine 1) optimal laser parameters for such selective targeting, and 2) whether PDL, when used in combination with RA, can improve the efficacy and reduce toxicity of RA by itself. To our knowledge this is the first study combining laser microvascular targeting technique with a chemopreventive agent. This proposed strategy, if successful, is very likely to lead to an alternative with higher efficacy and less toxicity than current treatment methods.