[1]杜乐辉,郝丽莉,廖遇平,等.磁感应热疗联合免疫佐剂对Wistar大鼠Walker256肿瘤的异位效应的研究[J].中国微创外科杂志,2009,09(3):240-245.
　Du Lehui,Hao Lili,Liao Yuping,et al.Magnetic Fluid Hyperthermia Combined with Immunoadjuvant on the Abscopal Effect of Walker256 Tumor in Wistar Rats[J].Chinese Journal of Minimally Invasive Surgery,2009,09(3):240-245.
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磁感应热疗联合免疫佐剂对Wistar大鼠Walker256肿瘤的异位效应的研究()
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《中国微创外科杂志》[ISSN:1009-6604/CN:11-4526/R]

卷:
09
期数:
2009年3期
页码:
240-245
栏目:
实验研究
出版日期:
2009-08-01

文章信息/Info

Title:
Magnetic Fluid Hyperthermia Combined with Immunoadjuvant on the Abscopal Effect of Walker256 Tumor in Wistar Rats
作者:
杜乐辉; 郝丽莉; 廖遇平; 王晓文; 周菊梅; 王桂华; 张莹莹; 唐劲天**
Author(s):
Du Lehui;  Hao Lili;  Liao Yuping;  et al.
Department of Engineering Physics,Institute of Physics and Engineering in Medicine，Tsinghua University,Beijing 100084,China
关键词:
Walker256肿瘤; 热疗; 免疫佐剂; 细胞免疫; 异位效应; Wistar大鼠
Keywords:
Walker256 tumor; Hyperthermia; Immunoadjuvant; Cell immunity; Abscopal effect; Wistar rats
分类号:
R-332
文献标志码:
A
摘要:
目的观察不同加热温度及联合免疫佐剂对大鼠Walker256肿瘤生长及CD4+T细胞和 CD8+T细胞表达的影响。方法建立大鼠双侧腋下皮下移植Walker256肿瘤模型，接种后7 d随机分成6组：Ⅰ组（单纯植入热籽对照）；Ⅱ组（42～46 ℃单纯热疗）；Ⅲ组（42～46 ℃热疗＋免疫佐剂）；Ⅳ组（50～55 ℃单纯热疗）；Ⅴ组（50～55 ℃热疗＋免疫佐剂）；Ⅵ组（单纯免疫佐剂对照）。每3 d测双侧肿瘤大小的变化，治疗后14 d取肿瘤组织行HE染色，免疫组织化学方法检测肿瘤组织CD8+T细胞的表达，免疫荧光法检测CD4+T细胞的表达。结果热疗后14 d，Ⅱ、Ⅲ、Ⅳ、Ⅴ组两侧肿瘤体积均有不同程度缩小，Ⅴ组治疗侧及对侧肿瘤体积分别缩小346%、601%，并有3只大鼠对侧肿瘤完全消退，与Ⅰ组、Ⅵ组2个对照组比较，有显著性差异（q=4552， P＜005；q=4400， P＜005）。组织学检查肿瘤细胞呈凋亡、坏死性改变，伴大量淋巴细胞浸润，V组还可见大量吞噬细胞，对侧未见明显坏死肿瘤细胞，淋巴细胞浸润较明显。免疫学检查加热后CD4+T细胞和CD8+T细胞较对照组（Ⅰ、Ⅵ组）明显增多，差异具有显著性（P＜005），其中均以V组表达最多（P＜005）。结论50～55 ℃瘤内局部加热不仅能抑制乳腺癌生长，还可增强机体的细胞免疫功能并具有异位效应，免疫佐剂能增强其抑瘤作用及异位效应。
Abstract:
ObjectiveTo observe the effect of hyperthermia at different temperatures combined with immunoadjuvant on the growth of Walker256 tumor and the expressions of CD4+ and CD8+ T cells in rats.MethodsWalker256 tumor models were established by implanting the tumor cells into the bilateral axillary skin in rats. Seven days after the inoculation, the animals were randomly divided into six groups: Group Ⅰ, simple thermoseeds implanted control group; Group Ⅱ, 42-46 ℃ simple hyperthermia group; Group Ⅲ , 42- 46 ℃ hyperthermia + immunoadjuvant group; Group Ⅳ, 50-55 ℃ simply hyperthermia group; Group Ⅴ, 50-55 ℃ hyperthermia + immunoadjuvant group; and Group Ⅵ, simple immunoadjuvant control group. We measured the size of the bilateral tumors every three days, and then at day 14, the rats were killed to obtain the tumor tissues for pathological examinations. The expression of CD8+ T cells were detected by immunohistochemistry and that of CD4+ T cells were tested by immunofluorescence.ResultsThe size of the tumors decreased significantly in the Ⅱ, Ⅲ, Ⅳ, and Ⅴ groups. In the group Ⅴ , the tumor was reduced by 34.6% at the treatment side and by 601% at the control side; 3 of the rats in this group achieved tumor disappearance in the contralateral side; which was significantly different from that in the groups Ⅰ and Ⅵ (q=4552, P＜005; q=4400, P＜005). Pathological examination showed apoptosis, necrosis, and lymphocytes infiltration in the tumor tissues. Moreover, in the group Ⅴ, a large number of phagocytes were observed, but no obvious necrosis occurred in contralateral tumors, while lymphocytes infiltration was apparent. Immunological tests showed that, comparing to the control groups, the number of CD4+ and CD8+ T cells increased significantly (P＜005) in the heated groups, especially the difference was significant in the group Ⅴ(P＜005).Conclusions50-55 ℃ local hyperthermia can not only inhibit the growth of Walker256 tumor, but also enhance cellmediated immunological function and show abscopal effect. Immunoadjuvant may enhance the antitumor and abscopal effects of the treatment.

参考文献/References:

[1]Ronald I, Sham MD. The abscopal effect and chronic lymphocytic leukemia. Am J Med, 1995, 98:307-308.
[2]张俊平. 肿瘤热疗及其免疫效应..国外医学·免疫学学册,2004,27(3):167-170.
[3]Suzuki M, Shinkai M, Honda H,et al. Anticancer effect and immune induction using magnetitc cationic liposomes. Melanoma Res,2003,13(2):129-135.
[4]朱学强, 伍峰.高强度聚焦超声治疗乳癌后的异位效应.四川医学,2006,26(9):933-934.
[5]Kaminski JM, Shinohara E, Summers JB, et al. The controversial abscopal effect. Cancer Treatment Reviews,2005, 31:159-172.
[6]Dickson JA, Shah SA. Immunological aspects of hyperthermia in storm FK ed. Hyperthermia in cancer therapy. Boston Hall Med,1983, 4:487-543.
[7]李渊, 孙红祥. 不同类型免疫佐剂的作用比较. 浙江畜牧兽医,2003,28:16-17.
[8]Morita M, Kuwano H ,Araki K,et al . Prognostic significance of lymphocyte infiltration following preoperative chemoradiotherapy and hyperthermia for esophageal cancer. Int J Radiat Oncol Biol Phys,2001,49 (5):1259-1266.
[9]Ito A, Tannka K, Kondo K， et al. Tumor regression by combined immunotherapy and hyperthermia usingmagnetic nanoparticles in an experimental subcutaneous murine melanoma. Cancer Sci, 2003,94(3):308-313.
[10]叶欣, 费心波, 赫崇军, 等. 高强度聚焦超声治疗肝癌后免疫功能的变化.中国肿瘤临床与康复, 2005,12: 23-25.

备注/Memo

备注/Memo:
基金项目：国家自然科学基金（10775085 ）；国家自然科学基金（30571799）； 北京市科委（Z07000200540704）；清华大学裕元基金**通迅作者作者单位： 410008中南大学湘雅医院肿瘤科（杜乐辉、廖遇平、周菊梅、张莹莹）；154002黑龙江省佳木斯医学院病理科（郝丽莉）；100084清华大学工程物理系医学物理与工程研究所（王晓文、唐劲天）；430060武汉大学人民医院肿瘤科（王桂华）
更新日期/Last Update: 2013-08-19