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白细胞介素13介导铜绿假单胞菌外毒素靶向性治疗胶质瘤的体外观察 被引量：3

Targeted therapy of malignant glioma by a chimeric fusion toxin composed of IL-13 Pseudomonas exotoxin in vitro
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摘要 目的观察以白细胞介素（IL）13与铜绿假单胞菌外毒素为基础构建的融合毒素（IL-13PE38）对实体恶性胶质瘤细胞的杀伤作用，分析其效能与恶性胶质瘤细胞表面IL-13α2受体（IL-13Rα2）表达强度的关系。方法对2009年6月至2010年12月温州医学院附属第一医院手术治疗的10例间变型胶质瘤和11例胶质母细胞瘤手术切除新鲜标本，在进行肿瘤细胞的原代培养时加入IL-13PE38并进行细胞MTS代谢率测定同时计算细胞存活率（SR）；采用免疫组织化学ABC法并利用图像分析系统检测IL-13Rα2在恶性胶质瘤表达的积分光密度（IOD），以IOD值代表其表达强度，对恶性胶质瘤的细胞存活率与IL-13Rα2的表达强度做相关性分析。结果（1）21例标本有19例（90％）存在IL-13Rα2的强阳性表达，胶质母细胞瘤中的表达强度高于问变型胶质瘤（P〈0．05）。（2）恶性胶质瘤细胞原代培养时加入IL-13PE38后细胞存活数有不同程度的减少，其中有14例细胞存活率低于70％，9例低于50％；在加入同浓度的IL-13PE38后问变型胶质瘤细胞存活率高于胶质母细胞瘤（P〈0．05）。（3）恶性胶质瘤IL-13Rα2的表达强度和细胞存活率呈高度负相关（r=-0．093，P〈0．01）。结论低浓度的IL-13PE38对实体恶性胶质瘤细胞的有明显的杀伤作用；其杀伤效能的大小取决于恶性胶质瘤细胞表面IL-13Rα2的表达强度。 Objective To examine the antitumor activity of IL-13PE38 on solid malignant glioma cells in vitro and to investigate its relationship between the antitumor activity of IL-13PE38 and the expression level of IL-13Rα2 in malignant glioma. Methods Ten fresh tissues of anaplastic glioma and 11 fresh tissues of glioblastoma multiforme were obtained during craniotomy at First Affiliated Hospital, Wenzhou Medical College between June 2009 and December 2010. All fresh glioma ceils were cultured in vitro with IL-13PE38. Then the cytotoxicity of IL-13PE38 was determined by colorimetric MTS proliferation assay and the SR （survival rate ） calculated. The expression level of IL-13Rα2 was studied by immunohistochemical SABC method in 21 cases of malignant glioma. And the value of integrated optical density （IOD） was examined by computer assisted pathological image analysis system. The correlation between the IOD of IL-13Rα2 and the SR of malignant glioma cells was also studied. Results （ 1 ） There were strongly positive expression of IL-13Rα2 in most cases （ 19/21, 90% ）. And the expression level of IL-13Rα2 in glioblastoma multiforme was higher than the expression level of IL-13Rα2 in anaplastic glioma （P 〈 0. 05）. （2） As the fresh malignant glioma cells were cuhured with IL-13PE38 of same concentration, the number of surviving cells decreased in different degrees. The survival rate of 14 cases were 〈 70% and 9 cases 〈 50%. And the survival rate of anaplastic glioma cells was higher than that of glioblastoma multiforme ceils （P 〈0.05）. （3） The IOD of IL-13Rα2 and the SR of malignant glioma cells were strongly negativelycorrelated （r =-0. 093, P 〈 0. 01 ）. Conclusion A low concentration of IL-13PE38 shows a high level of cytotoxicity for solid malignant glioma cells. And its cytotoxic efficiency depends on the expression level of IL- 13Rα2.
作者 章剑剑 翁睿光 刘俊 陈汉平 刘军 叶晖 郑伟明
机构地区 江汉大学附属第二医院神经外科 武汉大学医学院组织胚胎室 温州医学院附属第一医院神经外科
出处 《中华医学杂志》 CAS CSCD 北大核心 2012年第11期731-734,共4页 National Medical Journal of China
基金 武汉市卫生局科研项目（WXlOC27）
关键词 神经胶质瘤 白细胞介素13 假单胞菌科 外毒素类 Glioma Interleukin-13 Pseudomonas daceae Exotoxins
分类号 R739.4 [医药卫生—肿瘤]
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参考文献11

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二级参考文献8

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共引文献1

同被引文献79

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中华医学杂志
2012年 第11期

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