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裸鼠9L胶质肉瘤的手术切除与光动力疗法联合应用

Combination of surgical resection and photodynamic therapy of 9L gliosarcoma in the nude rat.

作者信息

Zhang Xuepeng, Jiang Feng, Kalkanis Steven N, Yang Hongyan, Zhang Zhenggang, Katakowski Mark, Hong Xin, Zheng Xuguang, Chopp Michael

机构信息

Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI, USA.

出版信息

Photochem Photobiol. 2006 Nov-Dec;82(6):1704-11. doi: 10.1562/2006-06-16-RA-934.

Abstract

The objective of the present study was to investigate the treatment of 9L gliosarcoma brain tumor in the rat with the combination of surgical resection and photodynamic therapy (PDT). Nude rats with intracranial 7-day-old 9L gliomas were randomly subjected to no treatment, PDT alone (Photofrin: 2 mg kg(-1), optical: 80 J cm(-2)), surgical resection alone or resection combined with 2 mg kg(-1) Photofrin-mediated PDT at an optical dose of 80 J cm(-2). All animals were sacrificed 14 days after tumor implantation. Hematoxylin-and-eosin and immunohistochemical stainings were performed to assess the tumor volume and the expression of vascular endothelial growth factor (VEGF) in the brain adjacent to the tumor (BAT) as well as the tumor cell apoptosis and proliferation. Our data show that both surgical resection alone and PDT alone significantly decreased tumor volume, but furthermore, surgical resection combined with PDT significantly reduced the tumor volume and reduced local tumor infiltration compared to either surgical resection or PDT treatment alone. PDT treatment with or without resection increased tumor apoptosis, but resection alone did not alter the tumor cell apoptosis compared with a nontreatment control group. Both surgical resection alone and PDT alone induced a significant increase in VEGF expression in the BAT; however intraoperative PDT did not further increase VEGF expression, compared with surgery alone or PDT alone. No significant differences were found in tumor cell proliferation as indicated by Ki67 immunoreactivity among the four groups. Our results suggest that PDT enhances the efficacy of surgical resection in the management of malignant gliomas without increasing VEGF expression in the BAT.

摘要

本研究的目的是探讨手术切除与光动力疗法(PDT)联合治疗大鼠9L胶质肉瘤脑肿瘤的效果。将颅内接种7日龄9L胶质瘤的裸鼠随机分为未治疗组、单纯PDT组(光敏剂:2 mg kg(-1),光照剂量:80 J cm(-2))、单纯手术切除组或手术切除联合2 mg kg(-1)光敏剂介导的PDT组(光照剂量80 J cm(-2))。肿瘤植入后14天处死所有动物。进行苏木精-伊红染色和免疫组化染色,以评估肿瘤体积、肿瘤周围脑组织(BAT)中血管内皮生长因子(VEGF)的表达以及肿瘤细胞凋亡和增殖情况。我们的数据表明,单纯手术切除和单纯PDT均能显著降低肿瘤体积,但此外,与单纯手术切除或单纯PDT治疗相比,手术切除联合PDT能显著减小肿瘤体积并减少局部肿瘤浸润。无论是否切除,PDT治疗均增加了肿瘤凋亡,但与未治疗对照组相比,单纯切除并未改变肿瘤细胞凋亡情况。单纯手术切除和单纯PDT均诱导BAT中VEGF表达显著增加;然而,与单纯手术或单纯PDT相比,术中PDT并未进一步增加VEGF表达。四组中Ki67免疫反应性所示的肿瘤细胞增殖情况无显著差异。我们的结果表明,PDT可增强手术切除治疗恶性胶质瘤的疗效,且不会增加BAT中VEGF的表达。

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