Antiangiogenic effect of oral 2-methoxyestradiol on choroidal neovascularization in mice

Antiangiogenic effect of oral 2-methoxyestradiol on choroidal neovascularization in mice
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DOI:
10.1016/j.exer.2006.05.016
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发表时间:
2006-11-01
影响因子:
3.4
通讯作者:
D'Amato, Robert J.
D'Amato, Robert J.
中科院分区:
医学3区
文献类型:
--
作者:
Funakoshi, Taisaku;Birsner, Amy E.;D'Amato, Robert J.

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我们评价了系统性2-甲氧基雌二醇(2ME2)在激光诱导的小鼠脉络膜新生血管(CNV)模型中的疗效。本研究选用8周龄雄性C57BL/6J小鼠,随机分为4组。激光治疗后,开始每日口服30、50、75 mg/kg的2-甲基-2-甲基-3-甲基-2-酮。激光治疗2周后,行荧光素-异硫氰酸酯-葡聚糖(FITC-葡聚糖)血管造影术及FITC-葡聚糖灌注后脉络膜平片成像。用NIH图像软件对图像进行量化处理。对FITC-葡聚糖血管造影术和脉络膜平片FITC-葡聚糖灌注图像的分析表明,2ME2治疗组的CNV下降具有统计学意义,呈剂量依赖性。治疗过程中未见毒性反应或体重减轻。口服2ME2对激光诱导的CNV有明显的抗血管生成作用。由于2ME2(Panzem(R))在I/II期癌症试验中表现出良好的安全性,它有可能被用作治疗老年性黄斑变性的一种新的口服疗法。(C)2006爱思唯尔有限公司。保留所有权利。
We evaluated the efficacy of systemic 2-methoxyestradiol (2ME2) in a laser-induced murime model of choroidal neovascularization (CNV). C57BL/6J mice (8 week old males) were used in this study and divided into four groups. After laser treatment, daily oral treatment with vehicle control, and 30, 50, and 75 mg/kg of 2ME2 was started. Two weeks after laser treatment, digital images of CNV were obtained from fluorescein isothiocyanate-dextran (FITC-dextran) angiography and choroidal flat mount after FITC-dextran perfusion. These images were quantified by NIH image software. Analysis of images from both FITC-dextran angiography and choroidal flat mount with FITC-dextran perfusion demonstrated that the 2ME2 treated groups showed a statistically significant, dose-dependent decrease in CNV. No toxicity or weight loss was observed during the treatment. Significant antiangiogenic effects of oral 2ME2 on laser induced CNV were observed. Since 2ME2 (Panzem (R)) has demonstrated good safety in phase I/II trials for cancer, it has the potential to be used as a novel oral treatment for age-related macular degeneration. (c) 2006 Elsevier Ltd. All rights reserved.