CAJ | 학술논문

目的建立人原发性胃恶性淋巴瘤裸小鼠原位移植高转移模型.方法采用人原发性胃恶性淋巴瘤术中新鲜瘤组织块植入裸小鼠胃壁黏膜下层,观察原位移植的成瘤率和移植瘤的侵袭、转移,并进行形态学(光镜、电镜、免疫组织化学)、染色体核型和流式细胞分析.结果在裸小鼠体内建成了一株人原发性胃恶性淋巴瘤原位移植高转移模型(HGBL-0305).移植瘤的组织病理学为原发性胃弥漫性大B细胞淋巴瘤.免疫组织化学显示,CD19、CD20、CD22、CD79α阳性,CD3、CD7阴性.染色体众数范围56～69条;移植瘤细胞DNA指数为1.47±0.12,均为异倍体.目前该瘤株在裸鼠体内生长4年,已经传至45代,共移植裸鼠156只;肿瘤移植生长率和液氮冻存复苏成活率均为100%.人胃恶性淋巴瘤在裸鼠胃内自主侵袭性生长,浸润破坏胃壁各层组织结构.HGBL-0305模型的肝转移率为69.5%,脾转移率为55.6%,淋巴结转移率为45.7%,腹腔种植转移率为30.5%.结论 HGBL-0305模型是成功的人原发性胃恶性淋巴瘤裸鼠原位移植自发性高转移模型,完整地模拟了人原发性胃恶性淋巴瘤患者的自然临床病理过程,为研究原发性胃恶性淋巴瘤发病机制、转移生物学和抗转移治疗提供了理想的动物模型.
목적 건립인원발성위악성림파류라소서원위이식고전이모형.방법 채용인원발성위악성림파류술중신선류조직괴식입라소서위벽점막하층,관찰원위이식적성류솔화이식류적침습、전이,병진행형태학(광경、전경、면역조직화학)、염색체핵형화류식세포분석.결과재라소서체내건성료일주인원발성위악성림파류원위이식고전이모형(HGBL-0305).이식류적조직병이학위원발성위미만성대B세포림파류.면역조직화학현시,CD19、CD20、CD22、CD79α양성,CD3、CD7음성.염색체음수범위56～69조;이식류세포DNA지수위1.47±0.12,균위이배체.목전해류주재라서체내생장4년,이경전지45대,공이식라서156지;종류이식생장솔화액담동존복소성활솔균위100%.인위악성림파류재라서위내자주침습성생장,침윤파배위벽각층조직결구.HGBL-0305모형적간전이솔위69.5%,비전이솔위55.6%,림파결전이솔위45.7%,복강충식전이솔위30.5%.결론 HGBL-0305모형시성공적인원발성위악성림파류라서원위이식자발성고전이모형,완정지모의료인원발성위악성림파류환자적자연림상병리과정,위연구원발성위악성림파류발병궤제、전이생물학화항전이치료제공료이상적동물모형.
Objective To construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen. Methods A fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied. Results An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice (HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79α were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47±0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively. Conclusions An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma.