Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma.

Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma.
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肼苯哒嗪联合超声热疗治疗肝癌。

DOI:
10.1038/s41598-021-94323-0
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发表时间:
2021-07-30
期刊:
影响因子:
4.6
通讯作者:
Sehgal CM
Sehgal CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Karmacharya MB;Sultan LR;Hunt SJ;Sehgal CM

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本研究探讨了肼苯哒嗪的使用,以提高超声热疗治疗肝细胞癌(HCC),通过最大限度地减少流量介导的热损失的肿瘤。用连续模式超声处理鼠HCC肿瘤,同时或不同时静脉内施用肼苯哒嗪(5 mg/kg)。分别通过超声造影(CEUS)成像和组织学检查评价肿瘤血流和血管。肼苯哒嗪通过阻断HCC中的肿瘤血流而显著增强超声热疗。肼苯哒嗪超声治疗显著降低CEUS时间-强度曲线的峰值增强(PE)、灌注指数(PI)和曲线下面积(AUC),分别为91.9 ± 0.9%、95.7 ± 0.7%和96.6 ± 0.5%,而不使用肼苯哒嗪时分别为71.4 ± 1.9%、84.7 ± 1.1%和85.6 ± 0.7%。肿瘤温度测量结果显示,肼苯哒嗪超声治疗的累积热剂量(170.8 ± 11.8 min)显著高于无肼苯哒嗪治疗的累积热剂量(137.7 ± 10.7 min)。超声处理肿瘤的组织学评估显示,肼苯哒嗪注射形成更大的出血池并增加肿瘤血管扩张,这与CEUS观察结果一致,表明肼苯哒嗪增强了过热效应。总之,我们证明肼苯哒嗪可以通过调节肿瘤血流来显著增强超声热疗在小鼠HCC肿瘤中的作用。未来的研究证明了超声和肼苯哒嗪联合使用的安全性,将使拟议技术的临床转化成为可能。
This study investigates the use of hydralazine to enhance ultrasound hyperthermia for the treatment of hepatocellular carcinoma (HCC) by minimizing flow-mediated heat loss from the tumor. Murine HCC tumors were treated with a continuous mode ultrasound with or without an intravenous administration of hydralazine (5 mg/kg). Tumor blood flow and blood vessels were evaluated by contrast-enhanced ultrasound (CEUS) imaging and histology, respectively. Hydralazine markedly enhanced ultrasound hyperthermia through the disruption of tumor blood flow in HCC. Ultrasound treatment with hydralazine significantly reduced peak enhancement (PE), perfusion index (PI), and area under the curve (AUC) of the CEUS time-intensity curves by 91.9 ± 0.9%, 95.7 ± 0.7%, and 96.6 ± 0.5%, compared to 71.4 ± 1.9%, 84.7 ± 1.1%, and 85.6 ± 0.7% respectively without hydralazine. Tumor temperature measurements showed that the cumulative thermal dose delivered by ultrasound treatment with hydralazine (170.8 ± 11.8 min) was significantly higher than that without hydralazine (137.7 ± 10.7 min). Histological assessment of the ultrasound-treated tumors showed that hydralazine injection formed larger hemorrhagic pools and increased tumor vessel dilation consistent with CEUS observations illustrating the augmentation of hyperthermic effects by hydralazine. In conclusion, we demonstrated that ultrasound hyperthermia can be enhanced significantly by hydralazine in murine HCC tumors by modulating tumor blood flow. Future studies demonstrating the safety of the combined use of ultrasound and hydralazine would enable the clinical translation of the proposed technique.
DOI: 10.3109/02656739009140980
发表时间: 1990-11-01
影响因子: 3.1
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DOI: 10.1177/1947601910365081
发表时间: 2010-03-01
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