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纳秒脉冲消融乳腺癌及免疫激活效应的实验研究

发布时间:2019-02-14 17:07
【摘要】:近20年的动物实验及临床前期研究表明,纳秒脉冲具有能量高、微创治疗、不需联合化疗药物等优点。因此本研究将纳秒脉冲作用于MDA MB 231乳腺癌荷瘤小鼠,观察局部原发肿瘤的消融效果,随访局部消融对免疫细胞亚群的影响情况,探索其非热消融的免疫机制。本实验在小鼠皮下接种小鼠乳腺癌MDA MB 231细胞,2周肿瘤直径达到10 mm时进行纳秒脉冲局部消融治疗,治疗参数选择脉冲宽度为300 ns,电场强度为40 k V/cm,脉冲个数为100,治疗频率为隔日重复共3次。研究结果表明原位接种的MDA MB 231乳腺癌细胞成瘤率达到100%。纳秒脉冲治疗后随访肿瘤大小、形态及体积至1个月,肿瘤直径达到20 mm时结束动物实验,B超监测数据显示,纳秒脉冲局部消融对原位肿瘤的消融率为83%,显著降低了原发肿瘤的体积,与对照组相比具有显著性降低;用流式细胞术检测脾脏中各淋巴细胞亚群的变化。射频消融后,小鼠脾脏CD4+T细胞、CD8+T细胞数量和比例升高,提示局部使用的纳秒脉冲刺激脾脏T细胞增殖能力。纳秒脉冲消融不但能够抑制原发肿瘤,还能增强小鼠免疫功能,使得肿瘤生长和转移侵袭力下降,有助于抑制肿瘤的生成及发展。
[Abstract]:Recent 20 years of animal experiments and preliminary clinical studies have shown that nanosecond pulse has the advantages of high energy, minimally invasive therapy and no combination of chemotherapeutic drugs. In this study, nanosecond pulses were applied to MDA MB tumor bearing mice to observe the effect of local primary tumor ablation, to investigate the effect of local ablation on immune cell subsets, and to explore the immune mechanism of non-thermal ablation. In this experiment, mice were inoculated subcutaneously with mouse breast cancer MDA MB 231 cells. Nanosecond pulse ablation was performed at the tumor diameter of 10 mm at 2 weeks. The pulse width of 300 ns, was 40 kV / cm and the number of pulses was 100. The treatment frequency was repeated every other day for 3 times. The results showed that the tumorigenic rate of breast cancer cells inoculated in situ with MDA MB was 100. After nanosecond pulse therapy, the tumor size, shape and volume were followed up to 1 month, and the tumor diameter reached 20 mm. The ultrasound monitoring data showed that the ablation rate of nanosecond pulse local ablation for in situ tumor was 83%. The volume of primary tumor was significantly decreased compared with the control group. The changes of lymphocyte subsets in spleen were detected by flow cytometry. After radiofrequency ablation, the number and proportion of CD4 T cells and CD8 T cells in the spleen of mice were increased, suggesting that the proliferation of spleen T cells was stimulated by nanosecond pulse. Nanosecond pulse ablation can not only inhibit the primary tumor, but also enhance the immune function of mice.
【作者单位】: 浙江大学医学院附属第一医院乳腺疾病诊治中心;浙江大学医学院附属第一医院肝胆胰外科卫生部多器官移植重点实验室;天津医科大学解剖系;浙江大学医学院附属第二医院骨科;
【基金】:国家自然科学基金(81372425) 浙江省自然科学基金(LY17H160018) 新疆重点实验室合作项目(2014KL002)~~
【分类号】:R737.9


本文编号:2422421

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