Do Liposomal Apoptotic Enhancers IncreaseTumor Coagulation and End-Point Survival in Percutaneous Radiofrequency Ablation of Tumors in a Rat Tumor Model?
Do Liposomal Apoptotic Enhancers IncreaseTumor Coagulation and End-Point Survival in Percutaneous Radiofrequency Ablation of Tumors in a Rat Tumor Model?
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DOI：
10.1148/radiol.10100500
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发表时间：
2010-12-01
期刊：
影响因子：
19.7
通讯作者：
Goldberg, S. Nahum
中科院分区：
文献类型：
--
作者：
Yang, Wei;Ahmed, Muneeb;Goldberg, S. Nahum
Purpose: To characterize effects of combining radiofrequency (RF) ablation with proapoptotic intravenous liposome-encapsulated paclitaxel and doxorubicin on tumor destruction, apoptosis and heat-shock protein (HSP) production, intratumoral drug accumulation, and end-point survival.Materials and Methods: R3230 mammary adenocarcinomas (n = 177) were implanted in 174 rats in this animal care committee-approved study. Tumors received (a) no treatment, (b) RF ablation, (c) paclitaxel, (d) RF ablation followed by paclitaxel (RF ablation-paclitaxel), (e) paclitaxel before RF ablation (paclitaxel-RF ablation), (f) RF ablation followed by doxorubicin (RF ablation-doxorubicin), (g) paclitaxel followed by doxorubicin without RF ablation (paclitaxel-doxorubicin), or (h) paclitaxel before RF ablation, followed by doxorubicin (paclitaxel-RF ablation-doxorubicin). Tumor coagulation area and diameter were compared at 24-96 hours after treatment. Intratumoral paclitaxel uptake with and without RF ablation were compared. Immunohistochemical staining revealed cleaved caspase-3 and 70-kDa HSP (HSP70) expression. Tumors were randomized into eight treatment arms for Kaplan-Meier analysis of defined survival end-point (3.0-cm diameter).Results: Paclitaxel-RF ablation increased tumor coagulation over RF ablation or paclitaxel (mean, 14.0 mm 6 0.9 [standard deviation], 6.7 mm +/- 0.6, 2.5 mm +/- 0.6, respectively; P < .001). Paclitaxel-RF ablation-doxorubicin had similar tumor coagulation (P < .05), compared with paclitaxel-RF ablation, at 24 and 96 hours. Mean intratumoral paclitaxel accumulation for paclitaxel-RF ablation (6.76 mu g/g +/- 0.35) and RF ablation-paclitaxel (9.28 mu g/g +/- 0.87) increased over that for paclitaxel (0.63 mu g/g +/- 0.25, P < .001). Paclitaxel substantially increased apoptosis and decreased HSP70 expression at coagulation margin. Mean end-point survival for paclitaxel-RF ablation-doxorubicin (56.8 days +/- 25.3) was greater, compared with that for paclitaxel-RF ablation or RF ablation-paclitaxel (17.6 days +/- 2.5), RF ablation-doxorubicin (30.3 days +/- 4.9, P < .002), or paclitaxel-doxorubicin (27.9 days +/- 4.1, P < .001).Conclusion: Selecting adjuvant liposomal chemotherapies (paclitaxel, doxorubicin) to target cellular apoptosis and HSP production effectively increases RF ablation-induced tumor coagulation and end-point survival, and combined multidrug approach results in even better outcomes. (C)RSNA, 2010
