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山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (5): 67-70.

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无细胞短棒状杆菌制剂联合瘤内缓释化疗对鼠黑色素瘤的抑制效应

郭春 吴南 洪海洁 武文亮 何婧 于保法 高尚先 胡宝芳   

  1. 1. 山东大学医学院免疫学研究所, 济南 250012; 2. 济南保法肿瘤医院, 济南 250012;3. 中国药品生物制品检定所培养基室, 北京 100050; 4. 中华女子学院山东分院计算机系, 济南 250000
  • 收稿日期:2008-11-20 出版日期:2009-06-16 发布日期:2009-05-16
  • 通讯作者: 张利宁(1960- ),女,博士生导师,教授,主要从事肿瘤免疫、心血管免疫、移植免疫等研究。
  • 作者简介:郭春(1979- ),男,硕士研究生,实验师,主要从事肿瘤免疫方面研究。

Non-cell corynebacterium parvum product combined with slow intra-tumorr  elease of drugs inhibits B16 melanoma in mice

 GUO Chun, WUN Na, HONG Hai-Jie, WU Wen-Liang, HE Jing, YU Bao-Fa, GAO Shangxian, HU Bao-Fang   

  1. 1. Institute of Immunology, School of Medicine, Shandong University,Jinan 250012, China; 2. Jinan Baofa Cancer Hospital, Jinan 250012, China;
    3. Department of Medium, National Institute for the Control of Pharmaceutical &Biological Products, Beijing 100050, China;4. Department of Computer, Shandong Branch of Zhonghua Women′s Academy, Jinan 2 50000, China
  • Received:2008-11-20 Online:2009-06-16 Published:2009-05-16

摘要:

 目的  探讨无细胞短棒状杆菌制剂(NCPP)联合瘤内缓释化疗对小鼠黑色素瘤的影响。    方法 给小鼠皮下接种B16肿瘤细胞后建立荷瘤小鼠,随机分成4组,①生理盐水(NS)对照组:瘤内和腹腔注射NS;② 缓释治疗组:瘤内注射含Ara-C缓释液;③ NCPP治疗组:腹腔注射NCPP;④ 联合治疗组:腹腔注射NCPP+瘤内注射含Ara-C缓释液。7d后重复治疗1次,期间观察各组小鼠肿瘤的生长情况;治疗2周处死小鼠,称瘤重量,光镜下观察瘤组织病理变化,采用流式细胞术检测脾内CD4+ T细胞、CD8+ T细胞数量变化。  结果  联合治疗能够明显抑制肿瘤的生长,疗效明显优于其他3组(P<0.05);联合治疗组瘤内出现大片坏死区域(P<0.05),联合治疗组的CD8+ T细胞数量明显增多(P<0.01)。  结论 将NCPP和瘤内缓释化疗技术联合应用能有效地抑制肿瘤的生长。

关键词: 黑色素瘤, 瘤内化疗, 无细胞短棒状杆菌制剂, 联合治疗, 小鼠,近交C57BL

Abstract:

Objective  To explore the effects of non-cell corynebacterium parvum product(NCPP) combined with slow intra-tumor release of drugs on B16 melanoma in mice.  Methods  Tumor-bearing mice were randomly divided intofour groups: the normal saline group, the slow intra-tumor release drug group, the NCPP group and the drug combination group. Seven days later, mice were treated again and the gross tumor volume was determined. Then 2 weeks later, all the tumor-bearing mice were sacrificed to measure tumor weight. Pathologic changes of tumors were observed under light microscopy. Infiltrations of T cells were determined in the splenic organs.  Results   Drug combination can effectively contain the tumor growth (P<0.05). HE staining results showed that there was a large area necrotic tissue in the tumor(P<0.05), and CD8+ T cells were significantly increased in the drug combination group(P<0.01).  Conclusion NCPP combined with slow intra-tumor release drugs is one of the effective management method for directly inhibiting tumor growth.

Key words: Melanoma; Intratumoral chemotherapy; Non-cell corynebacterium parvum product; Drug combination; Mice, inbred C57BL

中图分类号: 

  • R730.58
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