Intravitreal and subconjunctival melphalan for retinoblastoma in transgenic mice.

Intravitreal and subconjunctival melphalan for retinoblastoma in transgenic mice.
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DOI:
10.1155/2014/829879
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发表时间:
2014
影响因子:
1.9
通讯作者:
Houston SK
Houston SK
中科院分区:
医学4区
文献类型:
--
作者:
Shah NV;Pham DG;Murray TG;Decatur C;Hernandez E;Shah NN;Cavalcante M;Houston SK

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目的。目的 测量局灶性美法仑(玻璃体内和结膜下)对 LHBETATAG 鼠视网膜母细胞瘤模型中肿瘤负荷、缺氧和脉管系统的化疗效果。方法。 LHBETATAG 转基因小鼠接受单次 1 mcg 玻璃体内注射马法兰、100 mcg 结膜下注射或每半周 10 mcg 结膜下注射,持续 3 周。 1 或 3 周时,眼睛被摘除,连续切片,并用苏木精和伊红 (H&E) 处理以测量肿瘤负荷,并用免疫荧光探测以分析肿瘤缺氧和脉管系统。结果。当玻璃体内或结膜下给药时,局灶性马法兰可显着减小视网膜肿瘤大小(P < 0.02)。一次性玻璃体内注射 1μg 美法仑治疗的眼睛在注射后 1 周 (P = 0.017) 和 3 周 (P = 0.005) 时肿瘤明显较小。瘤内缺氧显示玻璃体内注射后1周和最大剂量的结膜下美法仑后缺氧显着下降。玻璃体内给药后总脉管系统没有受到显着影响。结论。在小鼠视网膜母细胞瘤的治疗中,通过玻璃体内或结膜下注射局部递送马法兰对于减轻肿瘤负荷、缺氧和脉管系统具有显着效果。
Purpose. To measure the chemotherapeutic effects of focal melphalan (intravitreal and subconjunctival) on tumor burden, hypoxia, and vasculature in LHBETATAG murine retinoblastoma model. Methods. LHBETATAG transgenic mice were treated with a single 1 mcg intravitreal injection of melphalan, 100 mcg subconjunctival injection, or semiweekly 10 mcg subconjunctival injections for 3 weeks. At 1 or 3 weeks, eyes were enucleated, serially sectioned, and processed with haematoxylin and eosin (H&E) for tumor burden measurements and probed with immunofluorescence to analyze tumor hypoxia and vasculature. Results. Focal melphalan significantly reduced retinal tumor size (P < 0.02) when given intravitreally or subconjunctivally. Eyes treated with a one-time intravitreal injection of 1 mcg melphalan had significantly smaller tumors at both 1 week (P = 0.017) and at 3 weeks after injection (P = 0.005). Intratumoral hypoxia showed a significant decline in hypoxia at 1 week following intravitreal injection and after maximum dosage of subconjunctival melphalan. Total vasculature was not significantly affected following intravitreal administration. Conclusion. Focal delivery of melphalan via intravitreal or subconjunctival injection has a significant effect on reducing tumor burden, hypoxia, and vasculature, in the treatment of murine retinoblastoma tumors.
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