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循环血肿瘤DNA含量变化对评价兔VX2肿瘤放疗早期反应的动物实验研究 被引量:1

An Evaluation of Early Radiotherapy Response of Rabbit VX2 Tumor by Changes of Circulating Tumor Specific DNA Level
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摘要 目的观察外周血循环Shope病毒DNA含量变化比较VX2移植瘤放疗早期治疗效果,探讨液态活检技术在临床的潜在应用价值。方法采用组织块大腿外侧皮下接种法建立兔VX2肿瘤模型,随机分为实验组和对照组,实验组给予单剂量20Gy放射治疗。根据已知的Shope病毒基因库设计Shope病毒特征性探针,应用实时定量PCR法检测放疗前1天、放疗后第3天及放疗后第7天血浆中Shope病毒特征性DNA片段含量。于放疗后第7天留取肿瘤组织块行病理组织学分析肿瘤细胞坏死率,分组标准以肿瘤细胞坏死率达80%为界,≥80%者为放疗有效组,小于80%为放疗抵抗组。采用SAS 9. 1统计软件分析,循环血shope病毒DNA含量组间差别采用方差分析,以P <0. 05为差异有统计学意义。结果根据病理肿瘤坏死率分组,对照组n=4,有效组n=6,抵抗组n=6。病理分析发现放疗有效组肿瘤组织存在大量坏死灶,放疗有效组坏死率明显高于放疗抵抗组(P <0. 05);放疗后3天,有效组的循环血shope病毒DNA含量明显高于抵抗组(P <0. 05),放疗后7天,放疗有效组循环血shope病毒DNA含量明显低于抵抗组(P <0. 01)。外周血中shope病毒的动态变化与VX2肿瘤放疗早期病理改变相关。结论循环血Shope病毒DNA可以作为兔VX2肿瘤特征性肿瘤标志物,循环血肿瘤DNA变化在早期监测肿瘤放疗疗效时具应用价值。 Objective To evaluate the potential clinical value of circulating tumor DNA (ctDNA)by observing the changing of DNA levels of Shope virus in peripheral blood of VX2 tumor bearing rabbits undergoing radiotherapy. Methods VX2 tumor bearing animal models were established by tissue transplantation in left thigh of rabbits.The animals were randomly divided into the experimental group and the control group.The experimental group was given single dose of 20Gy radiotherapy.The Shope virus specific DNA probe was designed according to the known Shope virus gene pool.The DNA fragment of Shope virus was detected by real- time quantitative PCR 1 day before,3 days after the radiotherapy and 7 days after the radiotherapy.Statistical analysis was processed by SAS 9.1 statistical software.The differences of circulating shope virus DNA levels among three groups were calculated by analysis of variance,with P 〈0.05 as statistically significant cutoff. Results Histopathological analysis of tumor cell necrosis were performed on 7days after the radiation treatment,with tumor necrosis ratio ≥80% as the radio- sensitive group(n=6),while tumor necrosis ratio less than 80% as the radio- resistance group(n=6),tumor bearing animal without radiation as the control group(n=4).Pathological analysis showed that there was a large number of necrotic lesions in radiotherapy group,and the necrosis rate of radio- sensitive group was significantly higher than that of radio- resistance group ( P 〈0.05).3 days after the radiotherapy,the circulating shope virus DNA level of sensitive group was significantly higher than that of resistance group( P 〈0.05).At 7 days after the radiotherapy,the circulating shope virus DNA level of radiotherapy sensitive group was significantly lower than that in resistant group ( P 〈0.01).The dynamic changes of shope virus DNA in peripheral blood were related to the early pathological changes of VX2 tumor after the radiotherapy. Conclusion Circulating Shope virus DNA can be used as a spec
作者 车莉萍 夏士安 孙高峰 王涛 李潇 张桉瑜 程超 左长京 CHE Li-ping;XIA Shi-an;SUN Gao-feng;WANG Tao;LI Xiao;ZHANG An-yu;CHENG Chao;ZUO Chang-jing(Department of oncology,Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medcine,Shanghai 200092,China;Department of nuclear medicine,Changhai Hospital,Shanghai 200433,China)
出处 《标记免疫分析与临床》 CAS 2018年第10期1512-1516,1524,共6页 Labeled Immunoassays and Clinical Medicine
基金 国家自然科学基金课题(编号:81471714)
关键词 循环血肿瘤DNA VX2肿瘤 放射治疗 聚合酶链反应 Circulating tumor DNA VX2 tumor Radiotherapy PCR
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