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腹腔内胶原酶作为一种新型治疗方法在结直肠腹膜转移瘤的实验模型中的应用。

Intraperitoneal collagenase as a novel therapeutic approach in an experimental model of colorectal peritoneal carcinomatosis.

机构信息

New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain.

Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040, Madrid, Spain.

出版信息

Sci Rep. 2021 Jan 12;11(1):503. doi: 10.1038/s41598-020-79721-0.

Abstract

The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.

摘要

最近已经测试了局部胶原酶在实体瘤治疗方法中的作用。在这项研究中,我们评估了腹腔内胶原酶联合或不联合丝裂霉素治疗实验性大鼠结直肠腹膜转移的安全性和疗效。采用固定剂量程序,我们发现,在 37.5°C 的热疗泵下,以 37IU/mL 的胶原酶剂量治疗 15 分钟,无论是单独使用还是与腹腔内丝裂霉素序贯治疗联合使用,均能通过改良腹膜癌指数(mPCI)评估使肿瘤体积宏观减少。关于该程序的安全性,在 8 周的随访期间,动物没有出现生理或行为障碍。在实验性小鼠模型中,经腹腔内胶原酶治疗结直肠来源的腹膜转移已被证明是安全有效的。因此,通过酶促破坏肿瘤细胞外基质中的胶原来治疗间质细胞,为结直肠腹膜转移提供了新的治疗靶点。

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