瘤内缓释治疗对B16黑色素瘤小鼠影响的实验研究.docVIP

瘤内缓释治疗对B16黑色素瘤小鼠影响的实验研究 　　作者：卜洁琼 作者单位：山东大学医学院免疫研究所, 济南 250012 　　【摘要】 探讨肿瘤内缓释治疗对B16黑色素瘤的影响及其机制。方法 将皮下接种B16肿瘤细胞后的成瘤小鼠随机分成4组进行治疗：①生理盐水(NS)对照组，瘤内注射NS;②阿糖胞苷(AraC)对照组，瘤内注射AraC;③单纯缓释治疗组，瘤内注射AraC+缓释液;④免疫缓释液治疗组，瘤内注射AraC+缓释液+二硝基苯 (DNP)。4?d后重复治疗，观察各组小鼠肿瘤的生长情况。两次治疗后1周分离瘤体，HE及网状纤维、弹力纤维、胶原纤维染色，观察瘤体病理改变，用流式细胞术检测脾内CD4+T细胞、CD8+T细胞浸润情况。结果 缓释治疗能够控制肿瘤的生长;HE染色显示，两缓释治疗组瘤内出现大片坏死区域，纤维特殊染色显示，两缓释治疗组三种纤维含量均明显增加(P0.01);流式细胞术检测表明，缓释治疗组的CD4+T细胞数量明显增多(P0.05)，但CD4+/CD8+T比值无明显变化。结论 瘤内缓释治疗通过直接破坏肿瘤细胞及增加肿瘤抗原性，从而发挥明显的抗肿瘤作用，为肿瘤治疗提供了新的思路。 　　【关键词】 黑色素瘤 缓释治疗 肿瘤内化疗 二硝基苯酚 抗原修饰 　　BU Jieqiong1, YU Baofa2 　　(1. Institute of Immunology, School of Medicine, Shandong University, 　　Jinan 250012， China; 　　2. Jinan Baofa Cancer Hospital, Jinan 250012， China) 　　Abstract: Objective To explore the effects and mechanism of slow intratumor release of drugs on B16 melonoma in mice. Methods Tumorbearing mice were randomly divided into four groups: the normal saline group, the AraC group, the AraC plus releasing drugs group and the AraC plus releasing drugs and DNP group. Four days later, mice were treated again and the gross tumor volume was determined. Then 1 week later, the contents of three fibers were detected in the interstitial substances of the tumor and the infiltrations of T cells were determined in the splenic organs. Results HE staining results showed that there was a large part of stenosis in the tumor, the fibers in the matrix of tumor were significantly increased and the CD4+T cells were also significantly increased in the two slowrelease groups. Conclusion Slowrelease of drugs into the tumor is one of the effective managements for directly inhibiting tumor growth and preventing micrometastasis. 　　Key words: Melanoma; Slowrelease drug therapy; Intratumoral chemotherapy; Dinitrophenyl; Modified antigen 化疗为肿瘤治疗的常规方法之一，影响化疗效果的关键因素是药物在肿瘤内的浓度和作用时间。常规的静脉给药难以解决此问题，为此众多学者对肿瘤内化疗方法作了大量的基础和临床研究，但至今未能形成统一的瘤内化疗方案[1,2]。1994年于保法曾提出利用肿瘤组织作为药物载体形成药物缓释库的新概念并进行了有效的动物实验[3,4]。本研究进一步探讨