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目的:探讨如何建立适合长期研究与治疗的人类神经母细胞瘤(NB)骨侵袭/转移的动物模型。方法:将SMS-KCNR和SMS-SAN细胞采用骨髓腔内注射和静脉注射的方法分别种植到雌性无胸腺裸鼠及Cb-17/IcrHsd-重度联合免疫缺陷(SCID)变异小鼠体内。通过观测放射影像学表现、HE染色病理组织切片,观察肿瘤细胞对骨的侵袭情况,应用Kaplan-Meier曲线分析及Log-rank检验,对实验动物进行生存状况分析。结果:SMS-SAN和SMS-KCNR细胞系细胞在骨髓内直接种植后在全部试验动物中均可以侵袭骨质形成溶骨性病变;同样,在静脉注射后2种细胞系细胞均可以在部分实验动物体内(SMS-SAN:5只;SMS-KCNR:6只)经血行转移到骨或骨髓,并进一步侵袭骨皮质。在骨侵袭模型和骨转移模型之间,2种细胞在无进展生存时间上差异有统计学意义,P<0.000 1;总生存时间的比较上差异也有统计学意义,P<0.000 1。结论:模型的建立极好地模拟了人类NB侵袭和转移的特性,加深了NB骨转移、侵袭机制的理解。
Objective: To explore how to establish an animal model of human neuroblastoma (NB) bone invasion / metastasis for long-term research and treatment. METHODS: SMS-KCNR and SMS-SAN cells were implanted into female athymic nude mice and Cb-17 / IcrHsd-severe combined immunodeficient (SCID) mutant mice respectively by intracavitary and intravenous injection. Observed by radiological imaging, histological sections were stained with hematoxylin and eosin (HE) to observe the invasion of tumor cells to bone. Kaplan-Meier curve analysis and Log-rank test were used to analyze the survival of experimental animals. RESULTS: The cells of SMS-SAN and SMS-KCNR cell lines were able to invade osteolytic lesions in all experimental animals after they were directly planted in the bone marrow. Likewise, both of the cell lines were able to partially inoculate after intravenous injection Animals (SMS-SAN: 5; SMS-KCNR: 6) were transplanted into bone or bone marrow via bloodstream and further penetrated the cortical bone. There was significant difference in the progression-free survival time between the bone invasion model and the bone metastasis model (P <0.0001). There was also a statistically significant difference in the overall survival time (P <0.0001). CONCLUSION: The establishment of the model perfectly mimics the characteristics of human NB invasion and metastasis, deepening the understanding of the mechanism of NB bone metastasis and invasion.