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射频消融联合免疫刺激剂 OK-432:联合治疗增强全身抗肿瘤免疫,治疗兔 VX2 肺肿瘤。

Radiofrequency ablation and immunostimulant OK-432: combination therapy enhances systemic antitumor immunity for treatment of VX2 lung tumors in rabbits.

机构信息

Department of Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

出版信息

Radiology. 2013 May;267(2):405-13. doi: 10.1148/radiol.13120249. Epub 2013 Feb 25.

DOI:10.1148/radiol.13120249
PMID:23440322
Abstract

PURPOSE

To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432.

MATERIALS AND METHODS

Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test.

RESULTS

The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased.

CONCLUSION

Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.

摘要

目的

评估射频消融(RFA)联合局部注射免疫刺激剂 OK-432 是否能全身性增强抗肿瘤免疫。

材料与方法

实验得到机构动物护理委员会的批准。实验用接种 VX2 肺肿瘤和耳肿瘤的日本兔随机分为四组,每组 8 只:对照组(支持治疗)、RFA 组(肺肿瘤的 RFA)、OK-432 组(直接向肺肿瘤注射 OK-432)和联合治疗组(肺 RFA 联合直接向肺肿瘤注射 OK-432)。所有程序均在 VX2 肿瘤植入后 1 周(第 1 周)进行。另外,对 RFA 和联合治疗组进行了 VX2 肿瘤再挑战测试。采用 Kaplan-Meier 法和对数秩检验进行组间比较来评估生存时间。每周计算平均耳肿瘤体积。采用 Mann-Whitney 检验计算和比较特定生长率(SGR)。

结果

对照组、RFA 组、OK-432 组和联合治疗组的中位生存时间分别为 23、36.5、46.5 和 105 天。与其他三组相比,联合治疗组的生存时间显著延长(P <.05)。仅在联合治疗组中,平均耳肿瘤体积减小。联合治疗组从第 1 周到第 7 周的平均耳肿瘤体积分别为 205、339、264、227、143、127 和 115mm3。联合治疗组的 SGR 明显小于其他三组(P <.05)。在再挑战测试中,所有再植入肿瘤的体积均减小。

结论

RFA 联合局部注射免疫刺激剂 OK-432 可能会导致全身性抗肿瘤免疫的间接激活。

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