Improved local and systemic anti-tumor efficacy for irreversible electroporation in immunocompetent versus immunodeficient mice.
Improved local and systemic anti-tumor efficacy for irreversible electroporation in immunocompetent versus immunodeficient mice.
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DOI：
10.1371/journal.pone.0064559
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Davalos RV
中科院分区：
文献类型：
--
作者：
Neal RE 2nd;Rossmeisl JH Jr;Robertson JL;Arena CB;Davis EM;Singh RN;Stallings J;Davalos RV
不可逆电穿孔 (IRE) 是一种非热焦点消融技术，它使用一系列短暂但强烈的电脉冲传递到组织的目标区域，通过不可恢复地破坏细胞膜完整性来杀死细胞。本研究调查了免疫活性 (IC) BALB/c 与免疫缺陷 (ID) 裸鼠相比，局部抗肿瘤反应是否有所改善，包括针对再次攻击的全身保护作用的潜力。采用 IRE 脉冲方案治疗皮下小鼠肾癌肿瘤，该方案使用在 ID 小鼠中引发完全回归所需的预测电压的 60%。每个品系的 11 只治疗小鼠和每个品系的 7 只对照小鼠在治疗后对肿瘤进行了 34 天的随访。相对于治疗的 ID 小鼠和两个品系的假对照小鼠，经治疗的 IC 小鼠的基于肿瘤负荷和无进展疾病期的小鼠存活率显着更长。治疗后 18 天，用相同的细胞系重新攻击接受治疗的 IC 小鼠，第二个肿瘤的生长明显减少或完全被阻止。在一些接受治疗的 BALB/C 小鼠中存在强烈的 CD3+ 细胞浸润，免疫细胞集中在活肿瘤和死亡肿瘤之间的转变。两种菌株中未经治疗的肿瘤、裸鼠和仅注射基质胶的低免疫细胞存在没有差异。这些发现表明，IRE 疗法对免疫功能正常的患者可能具有比免疫缺陷模型所建议的更大的治疗效果，并且 IRE 可能会引起目标消融区域之外的全身反应。
Irreversible electroporation (IRE) is a non-thermal focal ablation technique that uses a series of brief but intense electric pulses delivered into a targeted region of tissue, killing the cells by irrecoverably disrupting cellular membrane integrity. This study investigates if there is an improved local anti-tumor response in immunocompetent (IC) BALB/c versus immunodeficient (ID) nude mice, including the potential for a systemic protective effect against rechallenge. Subcutaneous murine renal carcinoma tumors were treated with an IRE pulsing protocol that used 60% of the predicted voltage required to invoke complete regressions in the ID mice. Tumors were followed for 34 days following treatment for 11 treated mice from each strain, and 7 controls from each strain. Mouse survival based on tumor burden and the progression-free disease period was substantially longer in the treated IC mice relative to the treated ID mice and sham controls for both strains. Treated IC mice were rechallenged with the same cell line 18 days after treatment, where growth of the second tumors was shown to be significantly reduced or prevented entirely. There was robust CD3+ cell infiltration in some treated BALB/C mice, with immunocytes focused at the transition between viable and dead tumor. There was no difference in the low immunocyte presence for untreated tumors, nude mice, and matrigel-only injections in both strains. These findings suggest IRE therapy may have greater therapeutic efficacy in immunocompetent patients than what has been suggested by immunodeficient models, and that IRE may invoke a systemic response beyond the targeted ablation region.
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DOI：
10.1084/jem.20021910
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Curtsinger JM;Lins DC;Mescher MF
通讯作者：
Mescher MF
影响因子：
4.3
作者：
Nuccitelli R;Tran K;Lui K;Huynh J;Athos B;Kreis M;Nuccitelli P;De Fabo EC
通讯作者：
De Fabo EC
影响因子：
2.8
作者：
Garcia, P. A.;Pancotto, T.;Davalos, R. V.
通讯作者：
Davalos, R. V.
影响因子：
14.5
作者：
Andersen, MH;Gehl, J;Straten, PT
通讯作者：
Straten, PT
影响因子：
2.5
作者：
Miyazaki, S;Gunji, Y;Ochiai, T
通讯作者：
Ochiai, T