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人小肠原发性恶性淋巴瘤裸小鼠原位和皮下移植高转移模型的建立 被引量:5

High metastasis models of malignant lymphoma of human small intestine established in nude mice by orthotopic and subcutaneous transplantation
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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、染色体核型和流式细胞分析。结果5例人小肠恶性淋巴瘤标本3例移植成功。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-0101)和皮下移植高转移模型(HSIL-0102)。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;免疫组织化学示CD19、CD20、CD22、CD45阳性,CD3、CD7阴性。染色体众数范围55~59条;流式细胞分析示DI值1.47~1.61,均为异倍体。HSIL-0101和HSIL-0102分别传至32和38代;共移植裸鼠357只;肿瘤的移植生长率和液氮冻存复苏成活率均为100%。HSIL-0101肝和淋巴结转移率为100%;HSIL-0102肝转移率为63.5%,淋巴结转移率为62.7%。移植瘤在裸鼠的小肠内和皮下侵袭性生长,发生血液(肝、脾)转移、淋巴转移和腹腔内种植性转移。结论HSIL-0101和HSIL-0102是首次建立成功的人小肠恶性淋巴瘤裸鼠原位移植和皮下移植均出现自发性高转移模型,可用于小肠恶性淋巴瘤的发病机制、侵袭和转移及实验治疗的研究。 Objective To provide an ideal animal model for exploring the pathogenesis and experimental treatment of malignant lymphoma of small intestine. Methods Fresh lymphoma tissues of primary lesions and liver metastatic lesions from the patients with small intestinal malignant lymphoma were respectively transplanted into mucosa of the small intestine and subcutaneous part of the interscapular region in nude mice. Tumorgenecity,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 In five cases of small intestinal malignant lymphoma,transplantation was successfully performed in three cases. A strain of high metastasis was screened from the models of Non-Hodgkin’s lymphoma (B cell) derived from the identical human small intestinal identical lymphoma. Orthotopically transplanted and subcutaneously transplanted models were named HSIL-0101 and HSIL-0102 respectively. Histopathology of transplanted tumor showed high-grade large B-cell lymphoma, CD19,CD20,CD22 and CD45 positivity, and CD3 and CD7 negativity. The number of chromosome was between 55 and 59. DNA Index (DI) was 1.47~1.61(ie,heteroploid). HSIL-0101 and HSIL-0102 were passaged for 32 and 38 generations in nude mice separately. 357 nude mice were used for transplantation. The growth rate of the transplanted neoplasm and resuscitation rate of liquid nitrogen cryopreservation were both 100%. In HSIL-0101, liver and lymph node metastasis rates were both 100%. In HSIL-0102, liver metastasis rate was 63.5%and lymph node metastasis rate was 62.7%. The transplanted tumors invasively grew in small intestine and subcutaneous part of the nude mice, and led to blood metastasis(liver and spleen metastases),lymph metastasis and seeding metastasis in abdominal cavity. Conclusions This study is the first time to successfully establish spontaneous high metastasis models of malignant lymphoma of human small intestine in nude mice by orthotopic and subcutaneous transplantation. HSIL-0101 and HSIL-0102 can be used to perform research on pathogenesis,invasion,metastasis,and experimental therapy of malignant lymphoma of small intestine.
出处 《中华胃肠外科杂志》 CAS 2004年第4期308-311,共4页 Chinese Journal of Gastrointestinal Surgery
基金 "九五"国家重点医学科技攻关计划资助(96A230603)
关键词 小肠原发性恶性淋巴瘤 裸小鼠 肿瘤皮下移植 肿瘤转移 动物模型 发病机制 肿瘤原位移植 Small intestinal neoplasms Lymphoma Neoplasm transplantation Neoplasm metastasis Disease model,animal
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