黑色素淡化法结合ALA-heptylester光动力学疗法治疗黑色素瘤的实验研究

皮肤黑色素瘤是一种恶性程度高、易转移、对传统治疗方法预后差的恶性皮肤肿瘤。ALA-光动力学疗法的问世在治疗皮肤黑色素瘤方面显示出了一定的优势。但由于受限于光敏剂的肿瘤选择性摄取及照射光的穿透性能力，ALA-光动力学疗法仍有待改进。在我们前期工作中观察到ALA-heptylester对肿瘤具有比ALA更好的选择性，又有文献提出淡化黑色素能增强光对瘤的穿透能力，在此基础上，本项目拟于在体小鼠黑色素瘤模型上，淡化黑色素瘤内的色素含量并比较三种不同给药方式下，ALA-heptylester产生的原卟并啉IX（PpIX）分布情况，以瘤内原卟啉IX（PpIX）浓度、瘤内及邻近正常组织中原卟啉IX产生比值为主要指标，确定ALAheptylester 光动力学治疗中最佳的给药方式、给药时间和光照波段；观察黑色素淡化法结合ALA-heptylester 光动力学疗法对黑素瘤生长的抑制作用。

Mutation,competition and natural selection operation within a population of sometic cells are the basic ingredients of cancer. A tumor is a cancer only if it is malignant,i.e. if its cells have the ability to invade surrounding tissue. Cutaneous melanoma is one of malignant malenoma with high malignancy, easier metastasis and poor prognansis to traditional treatment methods. ALA-photodynamic therapy (ALA-PDT) shows preferable forecasting effect to pigmented melanoma after its coming out. However,ALA-PDT need futher improvement due to its poor selectivity and poor penetrability. Our former results showed that ALA-heptylester has better selective uptake in tumour cells than ALA dose. Also some studies have showed that poor penetration of light in the pigmented melanoma by depigmentation. Based on these results, this work will be divided in several parts: First, we will depigment the pimented melanoma Second, a number of kinetics experiments will be conducted in order to find the appropriate application method of ALA-heptylester and optimal time for light exposure after application. Third, PDT will be performed on pigmented melanomas in order to determine the growth inhibition role of combination of depigmentation and ALA-heptylester-PDT on pigmented melanoma