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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Differential effects of buthionine sulphoximine in hypoxic and non-hypoxic regions of human cervical carcinoma xenografts.
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Differential effects of buthionine sulphoximine in hypoxic and non-hypoxic regions of human cervical carcinoma xenografts.

机译:丁硫氨酸亚砜亚胺在人宫颈癌异种移植物缺氧和非缺氧区域的差异作用。

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BACKGROUND AND PURPOSE: Recently we reported increased glutathione (GSH) levels in hypoxic regions of ME 180 and SiHa cervical cancer xenografts. Since this association might act synergistically to protect from radiotherapy, we examined the differential effects of the GSH depleting agent buthionine suiphoximine (BSO) in relation to tumor oxygenation. MATERIALS AND METHODS: The nitroimidazole EF5 was used to label tumor hypoxia. GSH levels were determined in cryostat sections using a sensitive HPLC assay and in parallel sections using fluorescence image analysis. Using a dual-labeling method, GSH levels were determined selectively in hypoxic and non-hypoxic tumor regions. RESULTS: GSH levels were higher in hypoxic than in non-hypoxic regions of cervical carcinoma xenografts. Treatment with BSO produced a more pronounced GSH depletion in regions of hypoxia, resulting in similar post-treatment levels in hypoxic and non-hypoxic areas. CONCLUSIONS: BSO effectively depletes GSH in hypoxic microregions of tumors. These findings suggest a potential role for BSO as an adjunct to radiotherapy in cervical cancer patients.
机译:背景与目的:最近,我们报道了ME 180和SiHa宫颈癌异种移植低氧区域的谷胱甘肽(GSH)水平升高。由于这种关联可能协同作用以保护免受放射疗法的影响,因此我们研究了GSH耗竭剂丁硫氨酸硫代磷酸亚胺(BSO)与肿瘤氧合的不同作用。材料与方法:硝基咪唑EF5用于标记肿瘤缺氧。使用敏感的HPLC分析法测定低温恒温器切片中的GSH水平,使用荧光图像分析测定平行切片中的GSH水平。使用双重标记方法,选择性地确定低氧和非低氧肿瘤区域的GSH水平。结果:缺氧宫颈癌异种移植物中的GSH水平高于非缺氧区域。 BSO治疗在缺氧区域产生了更明显的GSH耗竭,导致缺氧和非缺氧区域的治疗后水平相似。结论:BSO有效地耗尽了肿瘤低氧微区中的谷胱甘肽。这些发现表明,BSO作为宫颈癌患者放疗的辅助手段具有潜在的作用。

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