Combination of sensitizing pretreatment and radiofrequency tumor ablation: evaluation in rat model.
Combination of sensitizing pretreatment and radiofrequency tumor ablation: evaluation in rat model.
复制标题
敏化预处理和射频肿瘤消融的组合：大鼠模型的评估。
DOI：
10.1148/radiol.2463070228
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发表时间：
2008
期刊：
影响因子：
19.7
通讯作者：
Exner,AgataA
中科院分区：
文献类型：
--
作者：
Weinberg,BrentD;Krupka,TianyiM;Haaga,JohnR;Exner,AgataA
目的：在动物肿瘤模型中，前瞻性地确定嵌段共聚物Pluronic P85(巴斯夫，什里夫波特，La)是否使肿瘤细胞对高温敏感，以及瘤内或静脉注射共聚物是否改善射频消融肿瘤的治疗效果。材料和方法：体外检测Pluronic P85和亚高温对DHD/K12/TRB大鼠结直肠癌细胞的影响。细胞在37℃或43℃下与0%、7%或10%wt/wt的Pluronic P85孵育15-60分钟，用线粒体酶分析法检测细胞活力。活体实验是根据凯斯西储大学机构动物护理和使用委员会的批准并根据所有适用的动物使用指南进行的。用Pluronic P85瘤内治疗(13个肿瘤)或静脉注射(15个肿瘤)治疗大鼠双侧皮下肿瘤，然后消融或单独消融(14个肿瘤)，并用卡尺测量肿瘤直径估计的体积监测14天。24小时后，测量Pluronic P85对消融诱导的凝血大小的急性影响，在另外的肿瘤中(6个肿瘤分别按照消融、瘤内和静脉注射组的方案进行治疗)。结果：在43℃条件下，7%和10%的Pluronic P85分别使细胞活力降低22%±5(平均值的标准误差)(P<；.001)和28%±5(P<；.001)。在第14天，局部和全身Pluronic P85处理后的肿瘤体积分别减少了−55%±14(P=0.03)和−59%±14(P=0.02)，而单独消融的肿瘤体积增加了16%±28。瘤内注射Pluronic P85后，24小时凝血面积较对照组减少44%(P=0.03)，而全身注射Pluronic P85后无明显变化。结论：在实验性肿瘤模型中，Pluronic P85可通过减少肿瘤体积和残留肿瘤而改善射频消融的疗效。
Purpose:To prospectively determine, in an animal tumor model, if the block copolymer Pluronic P85 (BASF, Shreveport, La) sensitizes cancer cells to hyperthermia and if intratumorally or intravenously administered copolymer improves the therapeutic outcome of radiofrequency (RF) ablation tumor treatment.Materials and Methods:The effects of Pluronic P85 and mild hyperthermia in vitro were tested in DHD/K12/TRb rat colorectal carcinoma cells. Cells were incubated at 37°C or 43°C for 15–60 minutes with 0%, 7%, or 10% wt/wt Pluronic P85, and cell viability was assessed by using a mitochondrial enzyme assay. In vivo experiments were performed as approved by the Institutional Animal Care and Use Committee at Case Western Reserve University and according to all applicable guidelines on animal use. Bilateral subcutaneous tumors in rats were treated with either intratumoral (13 tumors) or intravenous (15 tumors) Pluronic P85 followed by ablation or with ablation alone (14 tumors) and were monitored for 14 days by using volumes estimated from caliper measurements of tumor diameter. Acute effects of Pluronic P85 on the size of ablation-induced coagulation were measured after 24 hours in additional tumors (six tumors each treated according to the protocol for the ablation-only, intratumoral injection, and intravenous injection groups). Statistical testing was performed by using linear regression analysis and two-sidedttests with a significance level of .05.Results:At 43°C, 7% and 10% Pluronic P85 reduced in vitro cell viability by 22% ± 5 (standard error of the mean) (P< .001) and 28% ± 5 (P< .001), respectively, compared with the viability of control cells. At day 14, the volume of tumors ablated after local and systemic Pluronic P85 pretreatment changed by −55% ± 14 (P= .03) and −59% ± 14 (P= .02), respectively, compared with an increase of 16% ± 28 for tumors treated with ablation alone. Coagulation area at 24 hours was reduced by 44% relative to that in control tumors (P= .03) after intratumoral Pluronic P85 but was unchanged after systemic Pluronic P85.Conclusion:Tumor pretreatment with Pluronic P85 improved the outcome of RF ablation by decreasing the tumor volume and residual tumor in an experimental carcinoma model.© RSNA, 2008