人胃癌裸鼠原位移植高转移模型的建立

目的 为探讨胃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 采用显微外科原位移植技术,将人胃癌新鲜组织移植裸鼠胃（黏膜层）壁内,观察原位移植成瘤率,侵袭和转移,及形态学特征（光镜,免疫组化电镜）。结果 从47例胃癌标本中筛选出一株人胃腺癌。裸鼠原位移植高转移模型已传至27代,一株人胃鳞腺癌裸鼠原位移植转移模型,已传至25代和一株人胃鳞癌裸鼠原位移植模型,已传至21代。共移植裸鼠426只。肿瘤的移植生长率为96.5％。自发转移率和液氮冻存复苏成活率均为100％。人胃癌在裸鼠胃壁内自主侵袭性生长,侵袭破坏胃壁各层组织结构,并直接侵袭到邻器官和组织。经血行转移到肝、肺、脾、肾等。淋巴道转移到胃的黏膜和黏膜下淋巴丛。局部及远处淋巴结。多伴发幽门梗阻癌性腹水,卵巢和腹腔内广泛种植转移。具有分泌癌胚抗原CEA的功能。移植瘤对p53、C-erbB-2、rasp21癌基因呈阳性表达,并与肿瘤的生长方式侵袭的深度和淋巴结转移有关。移植瘤细胞病理学,超微结构观察,流式细胞仪DNA含量测定,染色体核型分析,结果表明与人胃癌细胞相似。结论 三株人胃癌裸鼠原位移植高转移模型,完整的模拟了人胃癌患者的临床过程,且转移模式与临床患者相似。为研究人胃癌转移机制及实验治疗提供了理想的动物模型。

The high metastasis models of human gastric carcinoma established in nude mice by orthotopic transplantation

Objective To provide an ideal animal model for the research in the field of pathogenesis and experimental treatment of gastric carcinoma. Methods By the microsurgery technique, human specimens of gastric carcinoma were orthotopicly transplanted into the gastrie mucosa layer in nude mice. The tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, immunohistochemistry and electron microscopy. Results The metastasis models of human gastric adenocarcinoma, squamous adenocarcinoma and squamous cell carcinoma were established after screening from 47 specimens of gastric carcinoma by orthotopic transplantation. The mice had been passaged in vivo for 27, 25 and 21 generation respectively. 426 mice were transplanted totally. The growth rate of tumor transplantation was 96.5% . The spontaneous metastasis rate and revival rate after freezing by liguid nitrogon were both 100% . Human gastric carcinoma grew in the gastric mucosa layer of the nude mice spontaneously. It destroyed every gastric mucosa layer and invaded the adjacent organ and tissue directly. The liver, lung, spleen and kidney could be invaded by hematogenous metastasis. Lymphatic: tissue could be invaded by lymphatic metastasis including the gastric mucosa and submucous lymphatic tissue, local and distant lymph node. It could also invade ovary and abdominal cavity by implantation metastasis, which usually occurred pyloric obstruction and carcinomatous ascites. CEA secretion was maintained after transplantation. The oncogenes of p53, C - erbB - 2, rasp21 were expressed positively and relative to the growth style, invasion depth and lymph node metastasis. The transplantation tumors were similar to the original human gastric carcinoma in histopathological, ultrastructural features, DNA content and chromosomal karyotype. Conclusions Three metastasis models of human gastric carcinoma in nude mice simulate the clinic process of patients. The way of metastasis is similar to that of patients. It provides an ideal model for the study for mechanism of metastasis and treatment of human gastric carcinoma.