Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy.
Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy.
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DOI：
10.1016/j.ultrasmedbio.2023.07.013
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发表时间：
2023-11
影响因子：
2.9
通讯作者：
Allen, Irving C.
中科院分区：
文献类型：
--
作者：
Imran, Khan Mohammad;Gannon, Jessica;Morrison, Holly A.;Tupik, Juselyn D.;Tintera, Benjamin;Nagai-Singer, Margaret A.;Ivester, Hannah;Madanick, Justin Markov;Hendricks-Wenger, Alissa;Uh, Kyungjun;Luyimbazi, David T.;Edwards, Michael;Coutermarsh-Ott, Sheryl;Eden, Kristin;Byron, Christopher;Clark-Deener, Sherrie;Lee, Kiho;Vlaisavljevich, Eli;Allen, Irving C.
关键词：
迫切需要新的治疗策略和范例来治疗胰腺癌。缺乏合适的胰腺癌临床前动物模型是生物医学设备和治疗开发的主要限制。传统上，猪已被证明是理想的模型，特别是在设计人体大小的器械，完善手术技术和优化临床程序用于人类的背景下。然而，猪研究通常集中在健康组织评估上，由于无法有效地模拟人类肿瘤，因此仅限于一般安全性评价。在这里，我们使用RAG 2/IL 2 RG双敲除免疫功能低下的猪建立了人胰腺癌的原位猪模型，并用组织破坏术在体外和体内治疗肿瘤。使用这些动物，我们描述了Panc-1人胰腺癌细胞系肿瘤的成功植入，并表征其发展。为了说明这些动物在治疗开发中的效用，我们首次确定了使用组织破坏术成功靶向原位胰腺肿瘤。用组织摧毁术治疗导致体内部分消融，并且在猪胰腺中的体内肿瘤和离体患者肿瘤中的胶原蛋白含量减少。这项研究提出了建立组织破坏作为胰腺癌的非侵入性治疗方法的第一步，并暴露了超声引导胰腺组织破坏消融的一些挑战。同时，我们在大型哺乳动物模型中引入了一种高度稳健的胰腺癌模型，该模型可用于评估各种生物医学设备和治疗策略。
New therapeutic strategies and paradigms are direly needed to treat pancreatic cancer. The absence of a suitable pre-clinical animal model of pancreatic cancer is a major limitation to biomedical device and therapeutic development. Traditionally, pigs have proven to be ideal models, especially in the context of designing human-sized instruments, perfecting surgical techniques and optimizing clinical procedures for use in humans. However, pig studies have typically focused on healthy tissue assessments and are limited to general safety evaluations because of the inability to effectively model human tumors. Here, we establish an orthotopic porcine model of human pancreatic cancer using RAG2/IL2RG double-knockout immunocompromised pigs and treat the tumors ex vivo and in vivo with histotripsy. Using these animals, we describe the successful engraftment of Panc-1 human pancreatic cancer cell line tumors and characterize their development. To illustrate the utility of these animals for therapeutic development, we determine for the first time, the successful targeting of in situ pancreatic tumors using histotripsy. Treatment with histotripsy resulted in partial ablation in vivo and reduction in collagen content in both in vivo tumor in pig pancreas and ex vivo patient tumor. This study presents a first step toward establishing histotripsy as a non-invasive treatment method for pancreatic cancer and exposes some of the challenges of ultrasound guidance for histotripsy ablation in the pancreas. Simultaneously, we introduce a highly robust model of pancreatic cancer in a large mammal model that could be used to evaluate a variety biomedical devices and therapeutic strategies.
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影响因子：
4.6
作者：
Hendricks-Wenger A;Aycock KN;Nagai-Singer MA;Coutermarsh-Ott S;Lorenzo MF;Gannon J;Uh K;Farrell K;Beitel-White N;Brock RM;Simon A;Morrison HA;Tuohy J;Clark-Deener S;Vlaisavljevich E;Davalos RV;Lee K;Allen IC
通讯作者：
Allen IC
影响因子：
2.9
作者：
Arnold L;Hendricks-Wenger A;Coutermarsh-Ott S;Gannon J;Hay AN;Dervisis N;Klahn S;Allen IC;Tuohy J;Vlaisavljevich E
通讯作者：
Vlaisavljevich E
兽医患者的临床前动物模型和自发性肿瘤的组织疗法消融：综述。
DOI：
10.1109/tuffc.2021.3110083
发表时间：
2022-01
期刊：
IEEE transactions on ultrasonics, ferroelectrics, and frequency control
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Manresa, Mario C.;Miki, Haruka;Croft, Michae
通讯作者：
Croft, Michae
影响因子：
4.6
作者：
Bailey KL;Cartwright SB;Patel NS;Remmers N;Lazenby AJ;Hollingsworth MA;Carlson MA
通讯作者：
Carlson MA