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结直肠癌腹腔内灌注治疗的小鼠模型。

Murine Models of Intraperitoneal Perfusion for Disseminated Colorectal Cancer.

机构信息

Department of Plastic and Reconstructive Surgery, Wake Forest University Health Sciences, Winston-Salem, North Carolina.

Department of Plastic and Reconstructive Surgery, Wake Forest University Health Sciences, Winston-Salem, North Carolina.

出版信息

J Surg Res. 2019 Jan;233:310-322. doi: 10.1016/j.jss.2018.07.063. Epub 2018 Sep 5.

Abstract

BACKGROUND

Reproduction of the perfusion used in therapy (hyperthermic intraperitoneal chemotherapy) procedures preclinically represents a valuable asset for investigating new therapeutic agents that may improve patient outcomes. This article provides technical descriptions of our execution of closed and open "coliseum" abdominal perfusion techniques in a mouse model of peritoneal carcinomatosis of colorectal cancer.

MATERIALS AND METHODS

BALB/c mice presenting with disseminated colorectal cancer (CT26-luciferin cells) underwent 30-min perfusions mimicking either the closed perfusion or the coliseum perfusion technique. Disease burden was monitored by bioluminescence signaling using an in vivo imaging system. Perfusion circuits consisted of single inflow lines with either a single or dual outflow line.

RESULTS

Twelve mice presenting with disseminated disease underwent the closed perfusion technique. Surgical complications included perfusate leakage and organ constriction/suction into the outflow line(s). Nine mice underwent the coliseum perfusion technique with surgical debulking, using bipolar cauterization to remove tumors attached to the peritoneum. All mice survived the coliseum perfusion with limited intraoperative complications.

CONCLUSIONS

Fewer intraoperative complications were experienced with our coliseum perfusion technique than the closed perfusion. The methods described here can be used as a guideline for developing future perfusion murine models for investigating perfusion models useful for delivery of chemotherapy or other tumor-sensitization agents, including selective targeted agents, nanoparticles, and heat.

摘要

背景

在临床前重现治疗中使用的灌注(高热腹腔内化疗)程序是研究可能改善患者预后的新治疗药物的宝贵资产。本文提供了我们在结直肠癌腹膜转移的小鼠模型中执行封闭和开放“圆形剧场”腹腔灌注技术的技术描述。

材料和方法

出现结直肠转移(CT26-荧光素细胞)的 BALB/c 小鼠接受了 30 分钟的模拟封闭灌注或圆形剧场灌注技术的灌注。通过使用体内成像系统进行生物发光信号监测疾病负担。灌注回路由带有单个或双个流出线的单个流入线组成。

结果

12 只出现弥散性疾病的小鼠接受了封闭灌注技术。手术并发症包括灌注液泄漏和器官收缩/吸入流出线。9 只小鼠接受了圆形剧场灌注技术,并使用双极电灼术切除附着在腹膜上的肿瘤进行手术去瘤。所有小鼠在圆形剧场灌注中均存活,术中并发症有限。

结论

与封闭灌注相比,我们的圆形剧场灌注技术术中并发症较少。这里描述的方法可以作为开发未来用于研究有助于化疗或其他肿瘤增敏剂(包括选择性靶向药物、纳米颗粒和热量)输送的灌注小鼠模型的指南。

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