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一种用于研究不可逆电穿孔效果的同基因胰腺癌小鼠模型。

A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation.

作者信息

Shankara Narayanan Jayanth S, Ray Partha, Naqvi Ibtehaj, White Rebekah

机构信息

Moores Cancer Center, University California San Diego.

Duke University School of Medicine.

出版信息

J Vis Exp. 2018 Jun 8(136):57265. doi: 10.3791/57265.

Abstract

Pancreatic cancer (PC), a disease which kills approximately 40,000 patients each year in the US, has successfully evaded several therapeutic approaches including the promising immunotherapeutic strategies. Irreversible electroporation (IRE) is a non-thermal ablation technique that induces tumor cell death without destruction of adjacent collagenous structures, thus enabling the procedure to be performed in tumors very close to blood vessels. Unlike thermal ablation techniques, IRE results in gradual apoptotic cell death, along with immediate ablation induced necrosis, and is currently in clinical use for selected patients with locally advanced PC. An ablative, non-target specific procedure like IRE can induce a myriad of responses in the tumor microenvironment. A few studies have addressed the effects of IRE on tumor growth in other tumor types, but none have focused on PC. We have developed a syngeneic mouse model of PC in which subcutaneous (SQ) and orthotopic tumors can be successfully treated with IRE in a highly controlled setting, facilitating various longitudinal studies post procedure. This animal model serves as a robust system to study the effects of IRE and ways to improve the clinical efficacy of IRE.

摘要

胰腺癌(PC)是一种在美国每年导致约40000人死亡的疾病,它成功避开了包括前景广阔的免疫治疗策略在内的多种治疗方法。不可逆电穿孔(IRE)是一种非热消融技术,可诱导肿瘤细胞死亡而不破坏相邻的胶原结构,从而能够在非常靠近血管的肿瘤中进行该手术。与热消融技术不同,IRE会导致细胞逐渐凋亡死亡,同时伴有即刻消融诱导的坏死,目前已用于特定的局部晚期胰腺癌患者的临床治疗。像IRE这样的非靶向特异性消融手术可在肿瘤微环境中引发多种反应。一些研究探讨了IRE对其他肿瘤类型肿瘤生长的影响,但均未聚焦于胰腺癌。我们建立了一种胰腺癌同基因小鼠模型,在高度可控的环境中,皮下(SQ)和原位肿瘤均可成功接受IRE治疗,便于术后进行各种纵向研究。这种动物模型是研究IRE的作用以及提高IRE临床疗效方法的强大系统。

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