机构地区:[1]第二军医大学长海医院病理科,上海200433 [2]南方医科大学实验动物学教研室,广州510515
出 处:《中国肿瘤生物治疗杂志》2007年第2期163-168,共6页Chinese Journal of Cancer Biotherapy
摘 要:目的:探讨裸鼠人肝癌20年连续传代的病理变化特征。方法:裸鼠人肝癌组织模型(SMMU-LTNM)连续观察20年(1987-2007年),皮下移植瘤传至228代,建立腹腔移植瘤、肝原位移植瘤及NOD-SCID小鼠肝原位移植瘤的病理资料,经光镜、电镜、图像分析、染色体分析、周围血液AFP检测等方法分析病理变化特征。结果:(1)上述4种肿瘤模型的局部侵袭和转移均长期存在:皮下移植瘤的局部侵袭率为59.70%(40/67),肺内转移率为37.10%(23/62);腹腔移植瘤的肺内转移率为59.02%(36/61);肝原位移植瘤的肝内转移率为18.18%(4/22),肺内转移率为31.82%(7/22);NOD-SCID小鼠肝原位移植瘤的肺内转移率为53.85%。(2)皮下移植瘤的组织学变化:第10代前的瘤细胞分化和组织结构与原人肝癌近似,以Ⅱ级分化、粗梁型为主;第11代至225代瘤细胞以分化Ⅲ级、团块型为主,电镜下亦证实瘤细胞分化更差。(3)AFP检测第32代前为92500μg/L,第33代至130代AFP下降为6729μg/L,220代AFP检测为1000~5000μg/L。(4)腹腔移植瘤的瘤细胞群体与肺转移瘤的瘤细胞群体DNA含量分布范围明显增宽,2C~6C不等,峰值明显右移,前者的分布范围比后者更宽;DNA含量分别为2.60±0.20和2.10±0.26。(5)染色体检测,第55~206代(相隔12年)部分瘤细胞染色体变为裸鼠染色体。结论:裸鼠皮下移植瘤可连续传代20年,局部侵袭及转移的恶性生物学行为不变;瘤细胞分化更差,AFP下降,部分瘤细胞染色体变为裸鼠染色体。这些病理变化可能与裸鼠内环境影响和瘤细胞的多潜能分化有关。Objective: To investigate the pathological changes of human hepatocellular carcinoma (HCC) after continuous passaging in nude mice. Methods: The mice model of HCC SMMU-LTMN were continuously observed for 20 years ( 1987 - 2007) . The subcutaneously transplanted carcinoma had been passaged for 228 generations. The pathological data of abdominally transplanted HCC, orthotopically transplanted HCC in nude mice, and orthotopically transplanted HCC in NOD-SCID mice were recorded. The pathological studies were conducted by light microscope, electron microscope, image analysis, chromosomal analysis, and measurement of alpha-fetoprotein (AFP) in peripheral blood, Results: ( 1 ) The local invasion and metastasis of of tumors were present in all the above 4 models for a long time. The local invasion rate and the pulmonary metastasis rate of subcutaneously transplanted tumors were 59.70% (40/67) and 37.10% (23/62) , respectively. The pulmonary metastasis rate of abdominally transplanted tumors was 59.02% (36/61). The intra-hepatic and pulmonary metastasis rate of the othotopically transplanted tumors were 18.18% (4/22) and 31.82% (7/22) , respectively. The pulmonary metastasis rate of HCC in NOD-SCID mice was 53.85%. (2) The tissue structure and the differentiation of the 10th generation tumor cells was similar to those of primary HCC, with grade 2 differentiation and coarse trabecular pattern as the main characteristics. From the 11 th generation to the 228th generation, the main characteristics of tumor cells were grade 3 differentiation and lump pattern. Electron microscope also showed worse differentiation. ( 3 ) The AFP level was 92 500 μg/L in cells before the 32th generation; it decreased to 6 7291μg/L from the 33th-130th gener-ation cells; and the level of the 220th generation was 1 000-5 000 μg/L. (4)The DNA contents had a wide distribution ( from 2c to 6c) in abdominally transplanted tumors and the pulmonary metastatic tumors ; the mean DNA index in the
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