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人小肠原发性恶性淋巴瘤裸小鼠高转移模型的建立 被引量:2

Reblication of high metastasis model of malignant lymphoma of human small intestine in nude mice
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摘要 目的 为探讨小肠恶性淋巴瘤的发病机制和实验治疗提供理想的动物模型。方法 将人小肠恶性淋巴瘤术中原发灶新鲜组织块和肝转移灶瘤组织分别移植于裸小鼠的小肠黏膜层内和肩胛间皮下 ,观察原位移植和皮下移植的成瘤率、移植瘤的侵袭和转移率。进行形态学 (光镜、电镜和免疫组织化学 )、染色体核型、流式细胞分析。结果  5例人小肠恶性淋巴瘤标本中 3例移植成功。依据WHO新的分类标准 ,从中筛选出 1株同一人体瘤源人小肠原发性 (非霍奇金B细胞性 )恶性淋巴瘤裸鼠原位移植高转移模型 (HSIL 0 10 1)和皮下移植高转移模型(HSIL 0 10 2 )。移植瘤病理组织学为非霍奇金 (大B细胞性 )高度恶性淋巴瘤 ;免疫组化显示CD19、CD2 0、CD2 2、CD4 5阳性 ,CD3、CD7阴性。染色体众数 5 5~5 9条 ;流式细胞示DI值 1 4 7~1 4 9,均为异倍体。HSIL 0 10 1和HSIL 0 10 2分别传至32和 38代 ;共移植裸鼠 35 7只 ;肿瘤的移植生长率和液氮冻存复苏成活率均为 10 0 %。HSIL 0 10 1肝和淋巴结转移率为 10 0 % ;HSIL 0 10 2肝转移率为 6 3 5 % ,淋巴结转移率为 6 2 7%。移植瘤在裸鼠的小肠内和皮下侵袭性生长 ,发生血行(肝、脾 )转移、淋巴转移和腹腔内种植性转移。结论 HSIL 0 10 1和HSIL 0 10 2是首次成功建立的人小肠恶性淋? Objective To replicate an ideal animal model for exploring pathogenesis and experimental treatment of malignant lymphoma of small intestine. Methods Fresh lymphoma tissues derived from primary lesion and liver metastasis of malignant lymphoma of human small intestine obtained during operation were respectively transplanted into mucosa of small intestine and subcutaneous space in the interscapular region in nude mice. Tumorigenicity, invasion and metastasis of transplanted tumors were observed. Morphology (light microscopy, electron microscopy and immunohistochemistry), karyotype analysis, DNA quantitative assay (FCM) were also studied. Results From five patients of malignant lymphoma of small intestine, tumor tissue from 3 patients was successfully transplanted. According to the new classification of the World Health Organization, a strain of high metastatic model of orthotopically transplanted malignant lymphoma in nude mice (HSIL-0101) and another of subcutaneously transplanted highly metastatic model were reproduced from the same human neoplasm (non-Hodgkin B cell type); orthotopically Pathological study showed that the tumor was high-grade large B-cell lymphoma. Histochemitry showed that it was CD19, CD20, CD22 and CD45 positive, and CD3 and CD7 negative. The number of chromosome is ranged from 55 to 59; DI (DNA Index) was 1.47~1.61 (ie, heteroploid). HSIL-0101 and HSIL-0102 had been passaged for 32 and 38 generations in nude mice separately. 357 nude mice were transplanted. Rate of growth of neoplasm transplantation and resuscitation rate of liquid nitrogen cryopreservation were both 100%. In HSIL-0101, metastasis rate of liver and lymph node was 100%. In HSIL-0102, metastasis rate of liver was 63.5% and metastasis rate of lymph node was 62.7%. Transplanted tumors invasively grew in small intestine and subcutaneous region of nude mice. Blood metastasis was found (liver and spleen metastases). There were also lymph metastasis and seeding metastasis in the peritoneal cavity. Conclusions The study first successfully established spontaneous high metastasis models of malignant lymphoma of human small intestine in nude mice by orthotopic and subcutaneous transplantation. HSIL-0101 and HSIL-0102 could be used to carry out the research on pathogenesis, invasion, metastasis, and experimental therapy of malignant lymphoma of small intestine.
出处 《解放军医学杂志》 CAS CSCD 北大核心 2004年第5期409-412,共4页 Medical Journal of Chinese People's Liberation Army
基金 国家"九五"重点医学科技攻关计划资助课题 (编号 96A2 30 60 3)
关键词 肠肿瘤 淋巴瘤 肿瘤移植 肿瘤转移 疾病模型 动物 intestinal neoplasms lymphoma neoplasm transplantation neoplasm metastasis disease model, animal
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