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L-丁硫氨酸-亚砜亚胺介导的无胸腺小鼠脑内D-54 MG胶质瘤异种移植瘤实验性间质放疗增敏作用

L-buthionine-sulfoximine-mediated radiosensitization in experimental interstitial radiotherapy of intracerebral D-54 MG glioma xenografts in athymic mice.

作者信息

Lippitz B E, Halperin E C, Griffith O W, Colvin O M, Honore G, Ostertag C B, Bigner D D, Friedman H S

机构信息

Department of Pathology, Duke University Medical Center, Durham, North Carolina.

出版信息

Neurosurgery. 1990 Feb;26(2):255-60. doi: 10.1097/00006123-199002000-00012.

DOI:10.1097/00006123-199002000-00012
PMID:2308673
Abstract

An intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-buthionine-S,R-sulfoximine (L-BSO)-mediated depletion of tumor glutathione levels. Administration of L-BSO [2.5 mmol/kg intraperitoneal injections x 4 doses plus concomitant availability in acidified (pH 3.0) drinking water at a concentration of 20 mM] resulted in depletion of tumor glutathione levels to 0.15 mumol/g wet weight (7.9% of control). The therapeutic activity of i.c. interstitial radiotherapy with an 125I seed was enhanced after L-BSO-mediated glutathione depletion, with increases in median survival of 13.4 to 30.5% over that seen with 125I seeds alone. These studies demonstrate a potential role for BSO in enhancing the therapeutic activity of interstitial radiotherapy.

摘要

建立了一种在携带颅内D-54 MG人胶质瘤异种移植瘤的无胸腺裸鼠中的颅内(i.c.)间质放疗模型,用于评估L-丁硫氨酸-S,R-亚砜亚胺(L-BSO)介导的肿瘤谷胱甘肽水平耗竭后所观察到的治疗益处。给予L-BSO[2.5 mmol/kg腹腔注射×4剂,同时在酸化(pH 3.0)饮用水中以20 mM的浓度提供]导致肿瘤谷胱甘肽水平耗竭至0.15 μmol/g湿重(对照组的7.9%)。L-BSO介导的谷胱甘肽耗竭后,用125I种子进行的颅内间质放疗的治疗活性增强,中位生存期比单独使用125I种子时增加了13.4%至30.5%。这些研究证明了BSO在增强间质放疗治疗活性方面的潜在作用。

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