Multiparameter fluorescence mapping of nonprotein sulfhydryl status in relation to blood vessels and hypoxia in cervical carcinoma xenografts

Multiparameter fluorescence mapping of nonprotein sulfhydryl status in relation to blood vessels and hypoxia in cervical carcinoma xenografts
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DOI:
10.1016/s0360-3016(01)02716-x
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发表时间:
2002-03-01
影响因子:
7
通讯作者:
Hedley, DW
Hedley, DW
中科院分区:
医学1区
文献类型:
--
作者:
Vukovic, V;Nicklee, T;Hedley, DW

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目的:肿瘤血管的异常结构和血流的时间波动可导致肿瘤缺氧。本研究的目的是分类肿瘤缺氧的基础上的距离血管,并确定非蛋白巯基(NPSH)的水平位于近端和远端的肿瘤vessels.Methods和Materials的缺氧区域的生物学意义的特征:一个双重荧光方法开发的空间共定位的血管和缺氧的冷冻切片SiHa宫颈癌异种移植。平行切片用巯基汞橙子染色。通过成像和将各个视场平铺成2D图像阵列来生成复合荧光图像。结果:SiHa异种移植物的缺氧区域的NPSH水平较高(15.1 +/-0.5vs.13.5 +/-0.5积分光密度[IOD],p < 0.03)。当肿瘤缺氧被分类的距离最近的可见血管,显着更高的NPSH水平被发现在缺氧区域接近血管比在区域中的距离从vascular.Conclusion:本研究的结果表明,在SiHa肿瘤的近端或远端的血管缺氧区域的NPSH水平的差异表达。(C)2002年爱思唯尔科学公司
Purpose: Aberrant architecture of the tumor vasculature and temporal fluctuations in blood flow can result in tumor hypoxia. The aim of this study was to classify tumor hypoxia based on distance to blood vessels, and to characterize its biologic significance by determining levels of nonprotein sulfhydryls (NPSH) in hypoxic regions located proximally and distally to tumor blood vessels.Methods and Materials: A dual fluorescence method was developed for the spatial colocalization of the vasculature and hypoxia in frozen sections from SiHa cervical carcinoma xenografts. A parallel section was stained with the sulfhydryl stain mercury orange. Composite fluorescence images were generated by imaging and tiling individual fields of view into 2D image arrays. Image arithmetic techniques were combined with feature-based image segmentation to characterize expression of NPSH as a function of the hypoxic tumor microenvironment.Results: NPSH levels were higher in hypoxic areas of the SiHa xenografts (15.1 +/- 0.5 vs. 13.5 +/- 0.5 integrated optical density [IOD], p < 0.03). When tumor hypoxia was classified by distance to the nearest visible blood vessel, significantly higher NPSH levels were found in hypoxic regions close to blood vessels than in regions at a distance from blood vessels.Conclusion: The results of this study indicate differential expression of NPSH levels in regions of hypoxia that are proximal or distal to blood vessels in SiHa tumors. (C) 2002 Elsevier Science Inc.