Controllable Moderate Heating Enhances the Therapeutic Efficacy of Irreversible Electroporation for Pancreatic Cancer.

Controllable Moderate Heating Enhances the Therapeutic Efficacy of Irreversible Electroporation for Pancreatic Cancer.
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DOI:
10.1038/s41598-017-12227-4
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发表时间:
2017-09-18
期刊:
影响因子:
4.6
通讯作者:
Guo S
Guo S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Edelblute CM;Hornef J;Burcus NI;Norman T;Beebe SJ;Schoenbach K;Heller R;Jiang C;Guo S

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不可逆电穿孔(IRE)作为一种非热肿瘤消融技术已被研究用于治疗胰腺癌,并显示出显着的生存益处。我们发现,在43 ° C下适度加热(MH)1 - 2分钟显著增强Pan02细胞的离体IRE肿瘤消融,在750 V/cm下增强5.67倍,在1500 V/cm下增强1.67倍。这种热量本身并不会导致细胞死亡。开发了具有可控激光加热和肿瘤阻抗监测的集成IRE系统来治疗小鼠异位胰腺癌。利用这种新型IRE系统,我们能够在IRE治疗期间加热并将靶向肿瘤区域的温度保持在42 ° C。肿瘤的预加热大大降低了肿瘤的阻抗及其波动。最重要的是,MHIRE已被证明可以显着延长中位生存期,并实现较高的肿瘤完全消退率。对照组、100 μ s、1 Hz、90次脉冲、2000 - 2500 V/cm电场的IRE组和MHIRE组的中位生存期分别为43、46和84天。用MHIRE治疗的55.6%的荷瘤小鼠是无肿瘤的,而在对照组和IRE治疗组中没有观察到完全的肿瘤消退。
Irreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43 °C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.67-fold at 1500 V/cm. This amount of heating alone did not cause cell death. An integrated IRE system with controllable laser heating and tumor impedance monitoring was developed to treat mouse ectopic pancreatic cancer. With this novel IRE system, we were able to heat and maintain the temperature of a targeted tumor area at 42 °C during IRE treatment. Pre-heating the tumor greatly reduced the impedance of tumor and its fluctuation. Most importantly, MHIRE has been demonstrated to significantly extend median survival and achieve a high rate of complete tumor regression. Median survival was 43, 46 and 84 days, for control, IRE with 100 μs, 1 Hz, 90 pulses and electric fields 2000–2500 V/cm and MHIRE treatment respectively. 55.6% of tumor-bearing mice treated with MHIRE were tumor-free, whereas complete tumor regression was not observed in the control and IRE treatment groups.
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