机构地区:[1]中国人民解放军第100医院神经外科,江苏苏州215001 [2]苏州大学附属第一人民医院神经外科,江苏苏州215001
出 处:《中华肿瘤防治杂志》2019年第13期924-931,共8页Chinese Journal of Cancer Prevention and Treatment
基 金:江苏省卫计委青年研究课题(Q201606);江苏省卫计委面上科研课题(H201621;H2017064);江苏省六大高峰人才(2014-wsw-021);苏州市民生科技关键技术应用研究(SS201864)
摘 要:目的随着肿瘤基因检测及靶向治疗的应用,开启了肿瘤精准医疗的时代,迫切需要一种有效工具来模拟个体患者的肿瘤特性和基因表达,进行抗肿瘤药物筛选,评价肿瘤药物敏感性,探索耐药机制,达到个性化和精准化的目的.本研究旨在建立患者来源的原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)异种移植瘤(patient-derived xenografts,PDX)颅内模型,为精准治疗PCNSL提供良好的临床前模型.方法取PCNSL手术患者新鲜肿瘤组织标本,在SCID鼠大脑内原位接种肿瘤细胞建立PDX模型,淋巴瘤成瘤以后在体内传代,制作各代免疫缺陷小鼠脑内肿瘤组织石蜡切片并进行HE染色、免疫组化和基因检测分析,全癌基因测序与患者肿瘤组织进行对比分析.结果 HE染色、免疫组化及基因测序提示,SCID小鼠原位移植瘤与PCNSL患者肿瘤基本相同,该模型建立的PCNSL与人PCNSL接近,较好保持了原发肿瘤的生物学和基因突变特征,且颅内生长稳定,未见颅外转移病灶,并可体内传代,扩大模型规模,可用于进一步的研究.结论 PCNSL PDX模型与临床病例有较好的相似性,不仅能忠实地保留患者肿瘤的分子表型和基因型变化,而且能够再现原发肿瘤的异质性,保留了患者肿瘤基因表达模式、突变情况、药物反应和肿瘤结构等生物学特性,可在PCNSL临床评价靶向药物选择、肿瘤药物敏感性、研究耐药机制和抗肿瘤药物筛选的研究中发挥作用.OBJECTIVE With the application of tumor gene detection and targeted therapy in recent years,the era of tumor precise medical treatment has been opened. We urgently need an effective tool to simulate tumor characteristics and gene expression for individual patients and for screen anti-tumor drugs, evaluation of tumor drug sensitivity and drug resistance mechanism to achieve the goal of personalized precision. A patient-derived intracranial model of primary central nervous system lymphoma(PCNSL) xenografts(PDX) was established to provide pre-clinical model for accurate treatment of PCNSL. METHODS The tumor cells of PCNSL were obtained from fresh PCNSL specimens and were inoculated in SCID mouse brains to set up the symbol model. After tumor extended in the mice,the paraffin section of different generation of tumor tissues of immuno deficiency mouse were obtained and HE stained. Immunohistochemical and genetic testing analysis were performed and all cancer gene sequencing and tumor tissues histology were analyzed. RESULTS HE staining ,immunohistochemical and gene sequencing suggested that SCID mice transplantation tumor from surgery were almost identical with PCNSL tumor. The biology and gene mutation characteristics in translanted tumor of SCID mice were close to the primary tumor. Intracranial growth was stable, and no extracranial metastatic lesions were found. CONCLUSIONS PCNSL symbol model has good comparability with clinical cases, not only can keep patients with tumor molecular phenotype and genotype of change,but also can represent the primary tumor heterogeneity, the patterns of mutations in tumor gene expression, drug reactions and tumor biological characteristics such as the structure. It can be used in PCNSL clinical evaluation of targeted drug selection,tumor drug sensitivity,study of resistance mechanisms and antitumor drug screening research work.
关 键 词:原发性中枢神经系统淋巴瘤 人源肿瘤异种移植模型 精准医学 脑
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