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布美他尼对光动力疗法诱导的C6胶质瘤异种移植瘤瘤周水肿的影响。

The effect of bumetanide on photodynamic therapy-induced peri-tumor edema of C6 glioma xenografts.

作者信息

Zhang Xufeng, Cong Damin, Shen Dawei, Gao Xin, Chen Lei, Hu Shaoshan

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

出版信息

Lasers Surg Med. 2014 Jul;46(5):422-30. doi: 10.1002/lsm.22248. Epub 2014 Apr 2.

Abstract

OBJECTIVE

The aim of this study was to investigate the effect of bumetanide on peri-tumor edema caused by photodynamic therapy (PDT) of intraparenchymal C6 glioma xenografts.

METHODS

Seven days after inoculation with C6 cells, rats with MRI-confirmed glioma received hematoporphyrin monomethyl ether (HMME)-mediated PDT, injection of bumetanide or a combination of the two treatments. After treatment, tumor volume, tumor weight, brain water content, microvessel density, expression of NKCC-1, Zonula occludens-1 (ZO-1), and animal survival time were examined.

RESULTS

In the PDT group, tumor growth was significantly inhibited and survival prolonged. Bumetanide enhanced the efficacy of PDT and reduced PDT-induced peri-tumor edema in the combined PDT + bumetanide treatment group where NKCC-1 expression in response to PDT was significantly suppressed. ZO-1 expression was significantly suppressed in the PDT-only group. This suppression was not observed in the combined PDT + bumetanide treatment group.

CONCLUSION

PDT, in combination with bumetanide was seen to significantly inhibit the growth of C6 glioma, relieve peri-tumor edema caused by PDT alone and prolong survival. These results suggest that PDT, in combination with bumetanide, may be a useful and promising strategy in the treatment of human glioma.

摘要

目的

本研究旨在探讨布美他尼对脑实质内C6胶质瘤异种移植瘤光动力疗法(PDT)所致肿瘤周围水肿的影响。

方法

接种C6细胞7天后,经磁共振成像(MRI)确诊为胶质瘤的大鼠接受血卟啉单甲醚(HMME)介导的PDT、布美他尼注射或两种治疗方法联合使用。治疗后,检测肿瘤体积、肿瘤重量、脑含水量、微血管密度、NKCC-1、紧密连接蛋白1(ZO-1)的表达及动物存活时间。

结果

在PDT组中,肿瘤生长受到显著抑制,存活时间延长。在联合PDT + 布美他尼治疗组中,布美他尼增强了PDT的疗效并减轻了PDT诱导的肿瘤周围水肿,该组中PDT诱导的NKCC-1表达被显著抑制。仅PDT组中ZO-1表达被显著抑制。在联合PDT + 布美他尼治疗组中未观察到这种抑制现象。

结论

PDT联合布美他尼可显著抑制C6胶质瘤生长,减轻单纯PDT所致的肿瘤周围水肿并延长存活时间。这些结果表明,PDT联合布美他尼可能是治疗人类胶质瘤的一种有效且有前景的策略。

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