射频消融和免疫兴奋剂OK-432:联合疗法增强系统性抗肿瘤免疫力以治疗兔VX2肺肿瘤

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目的评估射频消融(RFA)联合局部注射免疫兴奋剂OK-432能否系统性地提高抗肿瘤免疫力。材料与方法本实验经机构动物保护委员会批准。将在肺及外耳接种VX2肿瘤的实验日本兔随机分为4组,每组8只,分别为对照组(支持疗法)、RFA组(肺肿瘤RFA)、OK-432组(直接将OK-432注入肺肿瘤)和联合疗法组(肺RFA和直接将OK-432注入肺肿瘤)。所有操作均于VX2肿瘤种植后1周进行(1周)。此外,RFA组和联合疗法组再次行VX2肿瘤实验。通过Kaplan-Meier方法评估存活时间,并应用时序检验进行组间对比。每周计算外耳肿瘤平均体积。应用秩和检验计算并比较生长速率(SGR)。结果对照组、RFA组、OK-432组及联合疗法组的平均生存时间分别为23、36.5、46.5和105d。与其他3组相比,联合疗法组的存活时间明显延长(P<0.05)。只有联合疗法组的平均外耳肿瘤体积减小。联合疗法组第1~7周平均外耳肿瘤体积分别为205、339、264、227、143、127及115mm3。联合疗法组的SGR明显小于其他3组(P<0.05)。再次进行的实验中,所有再种植肿瘤的体积明显缩小。结论 RFA联合局部注射免疫兴奋剂OK-432可间接地激活系统性抗肿瘤免疫力。 Objective To assess whether radioimmunoassay (RFA) combined with a local injection of immunostimulant OK-432 can systematically improve antitumor immunity. Materials and Methods The experiment was approved by the Animal Protection Committee. The Japanese rabbits vaccinated with VX2 tumors in the lungs and external ears were randomly divided into 4 groups (n = 8 each): control group (RFA group), OK-432 group Injection of lung tumor) and combination therapy group (lung RFA and OK-432 infusion directly into lung tumor). All procedures were performed 1 week after VX2 tumor implantation (1 week). In addition, the VX2 tumor experiment was repeated in the RFA group and the combination therapy group. Survival time was assessed by the Kaplan-Meier method and the comparison between groups was performed using a time series test. The average volume of the outer ear tumors is calculated weekly. The rank-sum test was used to calculate and compare the growth rate (SGR). Results The average survival time of control group, RFA group, OK-432 group and combination therapy group were 23, 36.5, 46.5 and 105 days, respectively. Compared with the other three groups, the survival time of the combination therapy group was significantly longer (P <0.05). Only the combination therapy group had an average reduction in the size of the outer ear tumor. In the combination therapy group, the mean external ear tumor volumes in the first week to the seventh week were 205, 339, 264, 227, 143, 127 and 115 mm3, respectively. SGR was significantly lower in the combination therapy group than in the other three groups (P <0.05). In the experiments conducted again, the volume of all replanted tumors was significantly reduced. Conclusion RFA combined with local injection of immune stimulant OK-432 can indirectly activate systemic anti-tumor immunity.
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