Adjuvant liposomal doxorubicin markedly affects radiofrequency ablation-induced effects on periablational microvasculature.
Adjuvant liposomal doxorubicin markedly affects radiofrequency ablation-induced effects on periablational microvasculature.
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DOI：
10.1016/j.jvir.2013.03.006
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发表时间：
2013-07
影响因子：
2.9
通讯作者：
Ahmed, Muneeb
中科院分区：
文献类型：
--
作者：
Moussa, Marwan;Goldberg, S. Nahum;Tasawwar, Beenish;Sawant, Rupa R.;Levchenko, Tatyana;Kumar, Gaurav;Torchilin, Vladimir P.;Ahmed, Muneeb
评价射频（RF）消融术（无和有辅助IV多柔比星脂质体（Doxil®））对微血管形态和通畅性以及肿瘤内药物输送和滞留的影响。共使用133个肿瘤/动物。首先，将单个皮下肿瘤（Fischer大鼠中的R3230和裸鼠中的786-0）随机接受单独的RF或不接受RF处理，并在处理后0- 72小时处死。接下来，在治疗后0- 72小时在R3230肿瘤中研究了组合RF/脂质体多柔比星（RF后15分钟给予1 mg）。进行组织学评估，包括ced caspase-3、热休克蛋白70和CD 34的免疫组织化学染色，以评估形态学血管外观、血管直径和微血管密度。随后，将动物随机接受单独RF、RF/脂质体阿霉素或对照肿瘤，随后在RF后0- 24小时给予静脉内荧光标记的脂质体（替代标记物）以进行定性评估。单独的射频消融导致0- 4小时的血管扩大和畸形，在射频后12- 24小时达到峰值，优先发生在更靠近电极的地方。加入阿霉素导致血管收缩提前（15分钟时平均血管面积为47539±9544μm²，单独RF为1854±458μm²，p<0.05）。联合RF/脂质体阿霉素在治疗后1小时产生类似的荧光（40.88±33.53 Au/μm² vs. 22.1±13.19 Au/μm²，p=0.14），但与单独RF相比，4小时时的荧光显著更少（24.3±3.65 Au/μm² vs. 2.8 ±3.14 Au/μm²，p<0.002），表明微血管通畅性较早降低。射频消融诱导消融区内血管的形态变化，持续至治疗后12- 24小时。脂质体阿霉素的添加导致早期血管收缩和消融周围微血管通畅性降低。在确定最佳给药和成像模式时，可能需要考虑这些变化。
To evaluate the effects of radiofrequency (RF) ablation without and with adjuvant IV liposomal doxorubicin (Doxil®) on microvessel morphology and patency and intratumoral drug delivery and retention. A total of 133 tumors/animals were used. First, single subcutaneous tumors (R3230 in Fischer rats, and 786-0 in nude mice) were randomized to receive RF alone or no treatment, and sacrificed 0-72hr post-treatment. Next, combined RF/liposomal doxorubicin (1mg given 15min post-RF) was studied in R3230 tumors at 0-72hr post-treatment. Histopathologic assessment including immunohistochemical staining for ced caspase-3), heat shock protein 70 and CD34 were performed to assess morphologic vessel appearance, vessel diameter, and microvascular density. Subsequently, animals were randomized to receive RF alone, RF/liposomal doxorubicin, or control tumors, followed by intravenous fluorescent-labeled liposomes (a surrogate marker) given 0-24hr post-RF to permit qualitative assessment. RF ablation alone results in enlarged and dysmorphic vessels from 0-4hr, peaking at 12-24hr post-RF, occurring preferentially closer to the electrode. The addition of doxorubicin resulted in earlier vessel contraction (mean vessel area 47539±9544μm² vs. 1854±458μm² for RF alone at 15min, p<0.05). Combined RF/liposomal doxorubicin produced similar fluorescence 1hr post-treatment (40.88±33.53 AU/μm² vs. 22.1±13.19 AU/μm², p=0.14), but significantly less fluorescence at 4hr (24.3±3.65 AU/μm² vs. 2.8 ±3.14 AU/μm², p<0.002) compared to RF alone denoting earlier reduction in microvascular patency. RF ablation induces morphologic changes to vessels within the ablation zone lasting up to 12-24hr post-treatment. The addition liposomal doxorubicin causes early vessel contraction and a reduction in periablational microvascular patency. Such changes will likely need to be considered when determining optimal drug administration and imaging paradigms.
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在肝脏恶性肿瘤射频消融过程中，热门部署的脂质体阿霉素的第一阶段研究。
影响因子：
2.9
作者：
Wood, Bradford J.;Poon, Ronnie T.;Locklin, Julia K.;Dreher, Matthew R.;Ng, K. K.;Eugeni, Michelle;Seidel, Geoffrey;Dromi, Sergio;Neennan, Ziv;Kolf, Michael;Black, Christopher D. V.;Prabhakar, Raj;Libutti, Steven K.
通讯作者：
Libutti, Steven K.
影响因子：
4
作者：
Basile, Antonio;Biziato, Daniela;Cajone, Francesco
通讯作者：
Cajone, Francesco
影响因子：
19.7
作者：
Soundararajan, Anuradha;Dodd, Gerald D., III;Goins, Beth A.
通讯作者：
Goins, Beth A.
影响因子：
19.7
作者：
Yang, Wei;Ahmed, Muneeb;Goldberg, S. Nahum
通讯作者：
Goldberg, S. Nahum
DOI：
10.1016/j.jconrel.2011.12.031
发表时间：
2012-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Yang W;Ahmed M;Tasawwar B;Levchenko T;Sawant RR;Torchilin V;Goldberg SN
通讯作者：
Goldberg SN