Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model.
Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model.
复制标题
在临床前模型中选择胰腺癌超声穿孔的最佳参数。
DOI：
10.1080/15384047.2021.1881026
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发表时间：
2021
影响因子：
3.6
通讯作者：
Torkzaban
中科院分区：
文献类型：
--
作者：
Schultz,ChristopherW;RuizdeGaribay,Gorka;Langer,Anika;Liu,Ji-Bin;Dhir,Teena;Leitch,Calum;Wessner,CorinneE;Mayoral,Mireia;Zhang,Bo;Popa,Mihaela;Huang,Chunwang;Kotopoulis,Spiros;Luo,Xianghong;Zhen,Yanhua;Niu,Sihua;Torkzaban
胰腺导管腺癌（PDAC）是现代世界中最致命的癌症之一，部分原因是化疗药物的输送不良。声孔作用可用于增强PDAC标准治疗的功效。使用PDAC的异种移植模型，我们使用四种不同的超声造影剂（UCA）和两种超声方案来研究声孔效应，以确定提高治疗效果的理想参数。用吉西他滨和紫杉醇治疗超过175只免疫缺陷小鼠的MIA-PaCa 2异种移植物，并将其与四种不同UCA中的一种联合进行低或高功率超声（分别为60和200 mW/cm 2）。所研究的UCA为Deploy ®、SonoVue®、Optison™或Sonazoid™。测量肿瘤体积、血管分布、血红蛋白和氧合，并与对照组进行比较。高功率治疗联合Sonazoid声致孔在早期开始时导致肿瘤显著更小（肿瘤~ 50 mm 3;p= 0.0105），而在低功率队列中无UCA显著增加疗效。在较大肿瘤（~ 250 mm 3）中也发现了这一趋势，其中所有四种UCA药物均显著增加了高功率组的治疗效果（p< .01），而在低功率组中仅Depletion和SonoVue增加了疗效（p< .03）。总的来说，高功率超声治疗方式在减少肿瘤体积和增加血管特征方面更有效。总之，Sonazoid是在减少肿瘤体积和增加血管分布方面最有效的UCA。因此，我们正在进行一项更大规模的II期临床试验，以验证声致孔联合化疗在PDAC患者中的疗效增加。
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm2respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm3;p= .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm3) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p< .01), while only Definity and SonoVue increased efficacy in the low power cohort (p< .03). Overall, the higher power ultrasound treatment modality was more consistently effective at decreasing tumor volume and increasing vascularity characteristics. In conclusion, Sonazoid was the most consistently effective UCA at decreasing tumor volume and increasing vascularity. Thus, we are pursuing a larger phase II clinical trial to validate the increased efficacy of sonoporation in conjunction with chemotherapy in PDAC patients.