裸鼠肺癌移植瘤模型瘤血管异质性的影像学动态监测

发布时间：2018-03-26 02:47

本文选题：肺癌　切入点：VEGF　出处：《第二军医大学》2017年硕士论文

【摘要】：目的:比较不同对比剂在离体肿瘤血管成像中的作用。比较不同VEGF表达水平两种细胞间的血管定量参数的差异。贝伐单抗抗血管生成治疗后肿瘤血管变化趋势。方法:构建A549细胞移植瘤模型,并使用碘海醇、硫酸钡悬混液、Micro-fil制备不同对比剂的瘤血管灌注模型;构建A549细胞和Calu-6细胞移植瘤模型,采用western-blot法检测两种细胞VEGF表达量,采用显微CT监测两细胞移植瘤模型不同时间点瘤血管定量参数;构建A549细胞移植瘤模型,并采用贝伐单抗干预和生理盐水对照,采用显微CT评价两组移植瘤模型血管参数的变化情况。结果:Micro-fil在离体肿瘤样本中其对比效果要优于硫酸钡悬混液和碘海醇。高VEGF表达的Calu-6细胞模型其肿瘤体积、血管体积、血管节点总数、血管节点密度均高于低VEGF表达的A549细胞模型,但是在反映血管三维复杂程度的分形维度和血管表面积与体积比两参数方面,两者没有统计学差异;Calu-6细胞模型的体积、血管体积、血管节点总数等方面随时间推移而增多,但是在血管体积分数、血管节点密度等方面随时间推移而减少;A549细胞模型的血管体积分数、血管节点密度在前期随时间推移而增多,在第19天出现明显减少。贝伐单抗拮抗的A549细胞模型,在肿瘤体积、血管体积、血管节点总数、血管节点密度等方面与对照组有明显差异,但与对照组表现的血管体积相对不足不同,抗VEGF治疗组其血管体积分数、血管节点密度在缓慢上升,虽然结果没有统计学意义。结论:Micro-fil适合作为离体血管标本的对比剂。同时不同VEGF的肿瘤在肿瘤血管定量参数方面的差异具有显著统计学意义,VEGF在肿瘤血管生成中具有重要意义。抗VEGF治疗后,肿瘤血管相关定量参数明显减少,但是其血管定量参数的改变,提示在肿瘤内部仍有其他血管生成因子的作用,可能与单纯应用抗血管生成治疗出现耐药相关。
[Abstract]:Aim: to compare the effects of different contrast agents on tumor angiography in vitro, and to compare the difference of vascular quantitative parameters between two kinds of cells at different VEGF expression levels. Methods: A549 cell transplantation tumor model was established. The tumor vascular perfusion models with different contrast agents were prepared with iodohexol and barium sulfate suspension solution micro-fil, and the tumor models of A549 cell and Calu-6 cell were constructed, and the expression of VEGF in two kinds of cells was detected by western-blot method. MicroCT was used to monitor the quantitative parameters of tumor at different time points in two-cell transplanted tumor model, and the A549 cell transplantation tumor model was constructed, and bevacizumab intervention and physiological saline control were used to construct A549 cell transplantation tumor model. MicroCT was used to evaluate the changes of vascular parameters in two groups of transplanted tumor models. Results the contrast effect of the two groups was better than that of barium sulfate suspension and iodiol. The tumor volume and vascular volume of the Calu-6 cell model with high VEGF expression were better than those of the isolated tumor samples. The total number of vascular nodes and the density of vascular nodes were higher than those of A549 cell model with low VEGF expression. There was no statistical difference between the two groups in the volume, vascular volume, and the total number of vascular nodes in the Calu-6 cell model over time, but the volume fraction of the blood vessel. The density of vascular node decreased with time, the density of vascular node increased in the early stage and decreased obviously on the 19th day. The A549 cell model was antagonized by bevacizumab. There were significant differences in tumor volume, vascular volume, total number of vascular nodes and density of vascular nodes between the control group and the control group, but the vascular volume fraction of the anti VEGF treatment group was different from that of the control group. The density of vascular nodes is slowly rising. Although the results are not statistically significant. Conclusion: Micro-fil is suitable for comparison of vascular specimens in vitro. Meanwhile, there are significant differences in tumor vascular quantitative parameters between different VEGF and VEGF in tumor angiogenesis. After anti VEGF treatment, The quantitative parameters of tumor angiogenesis were decreased obviously, but the changes of vascular quantitative parameters indicated that there were still other angiogenic factors in the tumor, which might be related to the drug resistance of antiangiogenic therapy alone.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2;R-332;R730.44

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