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转基因小鼠视网膜母细胞瘤的局部卡铂治疗

Local carboplatin therapy in transgenic murine retinoblastoma.

作者信息

Harbour J W, Murray T G, Hamasaki D, Cicciarelli N, Hernández E, Smith B, Windle J, O'Brien J M

机构信息

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Florida 33101, USA.

出版信息

Invest Ophthalmol Vis Sci. 1996 Aug;37(9):1892-8.

PMID:8759359
Abstract

PURPOSE

To determine the efficacy and toxicity associated with intraocular delivery of carboplatin in the treatment of murine transgenic hereditary retinoblastoma.

METHODS

Forty-eight transgenic BLH-SV40 Tag retinoblastoma mice were administered five intravitreal injections of carboplatin in one eye. After 12 weeks, the eyes were examined histopathologically to evaluate tumor burden. Twelve rabbits were administered intravitreal injections of carboplatin in one eye, after which they underwent serial electroretinography. All experimental and control eyes were obtained for histopathology and electron microscopy.

RESULTS

A dose-dependent inhibition of intraocular tumor growth by carboplatin was observed in transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the mouse eyes at doses of 1.4 micrograms. In rabbits, retinal toxicity resulted when intravitreal injections of carboplatin were administered at doses of 10 micrograms or higher.

CONCLUSIONS

Local delivery of carboplatin in serial doses effectively inhibits intraocular tumor growth in a dose-dependent manner in transgenic murine retinoblastoma.

摘要

目的

确定玻璃体内注射卡铂治疗小鼠转基因遗传性视网膜母细胞瘤的疗效和毒性。

方法

对48只转基因BLH-SV40 Tag视网膜母细胞瘤小鼠的一只眼睛进行5次玻璃体内注射卡铂。12周后,对眼睛进行组织病理学检查以评估肿瘤负荷。对12只兔子的一只眼睛进行玻璃体内注射卡铂,之后进行系列视网膜电图检查。获取所有实验眼和对照眼用于组织病理学和电子显微镜检查。

结果

在转基因视网膜母细胞瘤小鼠中观察到卡铂对眼内肿瘤生长的剂量依赖性抑制。在剂量为1.4微克时,50%的小鼠眼睛的肿瘤发展受到抑制。在兔子中,当玻璃体内注射卡铂的剂量为10微克或更高时会导致视网膜毒性。

结论

在转基因小鼠视网膜母细胞瘤中,连续剂量的卡铂局部给药以剂量依赖性方式有效抑制眼内肿瘤生长。

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