CAJ | 학술논문

目的探讨应用人肿瘤组织块外科原位移植术及体内连续传代法建立人肝原发性淋巴瘤裸鼠模型.方法将人原发性肝淋巴瘤术中新鲜瘤组织块采用外科原位移植术植入裸鼠肝实质内,通过鼠间连续原位传代法建立生物学特性能够完整模拟肝淋巴瘤患者的裸鼠原位移植模型.观察该模型的移植成瘤率及其侵袭、转移情况,并采用组织病理学(光镜、免疫组化)、血清学、染色体核型和流式细胞术进行分析.结果在裸鼠体内建成人原发性肝淋巴瘤原位移植模型,命名为HLBL-0102.移植瘤组织病理学为原发性肝淋巴瘤(弥漫大B细胞性),免疫组化示CD20、CD79a和MUM1阳性.HLBL-0102模型呈甲胎蛋白阴性,HBsAg阳性,乳酸脱氢酶升高[(1223±258)比(124±54) U/L,P＜0.01].移植瘤染色体众数范围56 ～ 59条,DNA指数为1.7±0.2,为异倍体.该模型已传至42代,共移植裸鼠320只,肿瘤移植生长率和液氮冻存复苏成活率均为100％.人原发性肝淋巴瘤在裸鼠肝内自主侵袭性生长,瘤细胞侵入并破坏邻近肝组织和门脉区内胆管、静脉及动脉,无其他组织、器官侵犯及远处淋巴结累及.结论 HLBL-0102模型是成功的人肝原发性淋巴瘤裸鼠原位移植模型.
목적 탐토응용인종류조직괴외과원위이식술급체내련속전대법건립인간원발성림파류라서모형.방법 장인원발성간림파류술중신선류조직괴채용외과원위이식술식입라서간실질내,통과서간련속원위전대법건립생물학특성능구완정모의간림파류환자적라서원위이식모형.관찰해모형적이식성류솔급기침습、전이정황,병채용조직병이학(광경、면역조화)、혈청학、염색체핵형화류식세포술진행분석.결과 재라서체내건성인원발성간림파류원위이식모형,명명위HLBL-0102.이식류조직병이학위원발성간림파류(미만대B세포성),면역조화시CD20、CD79a화MUM1양성.HLBL-0102모형정갑태단백음성,HBsAg양성,유산탈경매승고[(1223±258)비(124±54) U/L,P＜0.01].이식류염색체음수범위56 ～ 59조,DNA지수위1.7±0.2,위이배체.해모형이전지42대,공이식라서320지,종류이식생장솔화액담동존복소성활솔균위100％.인원발성간림파류재라서간내자주침습성생장,류세포침입병파배린근간조직화문맥구내담관、정맥급동맥,무기타조직、기관침범급원처림파결루급.결론 HLBL-0102모형시성공적인간원발성림파류라서원위이식모형.
Objective To establish a nude murine model of human primary hepatic lymphoma (PHL) with surgical orthoiopic implantation of histologically intact human tumor tissue and in vivo continuous orthotopic passage.Methods Histologically intact lymphoma tissues harvested intraoperatively from a PHL patient were othotopically transplanted into liver parenchyma of nude mice and in vivo continuous orthotopic passage in nude mice was used to develop a nude murine model mimicking the biological characteristics of PHL patients.Histopathology (light microscopy and immunohistochemistry),serological test,karyotypic analysis and flow cytometry were used to explore the tumorgenecity, invasion and metastasis.Results An orthotopic nude murine model of PHL,named HLBL-0102,was successfully developed.Histopathology of transplanted tumors showed primary hepatic lymphoma ( diffuse large B cell )stained positive for CD20,CD79a and MUM1.Serological test in tumor-bearing mice indicated that alphafetal protein (AFP) was negative and hepatitis B surface antigen (HBsAg) positive.The serum level of lactate dehydrogenase ( LDH ) was elevated to an average of ( ( 1223 ± 258 ) vs ( 124 ± 54) U/L,P ＜ 0.01 ).The chromosomal number of transplanted tumors was between 55 and 59.The DNA index (DI) of 1.7 ±0.2indicated heteroploid.So far HLBL-0102 model has been passed for 42 generations in nude mice.A total of 320 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100％.The transplanted tumors grew invasively in the liver of nude mice and destroyed adjacent liver tissues and bile ducts,veins and arteries of portal area.There was no involvement of other tissues,organs and distal lymph nodes.Conclusion An orthotopically transplanted model has been successfully established for human primary hepatic lymphoma in nude mice.