Relations between non-protein sulfydryl levels in the nucleus and cytoplasm, tumor oxygenation, and clinical outcome of patients with uterine cervical carcinoma
Relations between non-protein sulfydryl levels in the nucleus and cytoplasm, tumor oxygenation, and clinical outcome of patients with uterine cervical carcinoma
复制标题
DOI：
10.1016/j.ijrobp.2004.02.020
复制
发表时间：
2005-01-01
影响因子：
7
通讯作者：
Hill, RP
中科院分区：
文献类型：
--
作者：
Hedley, DW;Nicklee, T;Hill, RP
目的：非蛋白巯基 (NPSH) 谷胱甘肽和半胱氨酸能够对辐射引起的 DNA 损伤进行化学修复，特别是在缺氧条件下，并且与辐射抗性有关。预计细胞核中的 NPSH 水平比细胞质中的更重要。因此，我们研究了核 NPSH 与根治性放射治疗 (RT) 临床结果之间的关系。 方法和材料：基于 SH 反应探针 1（4-氯汞苯基-偶氮-2-萘酚）和 DNA 染料 4,6-二脒基-2-苯基吲哚，开发了一种测量核 NPSH 的荧光图像分析技术。该方法用于测量 58 名接受根治性放疗的局部晚期宫颈癌患者的活检组织中的核和组织 NPSH 水平。结果：发现各个肿瘤之间的核和组织 NPSH 水平大约是两倍的范围，尽管肿瘤内异质性要小得多。在所有情况下，核和组织 NPSH 值密切相关。使用 Eppendorf pO(2) 探针进行活检时确定，NPSH 水平与肿瘤大小、分期或肿瘤缺氧之间没有统计学上的显着关联。对放疗的反应和患者生存率与肿瘤 NPSH 无关。结论：这些结果不支持独立调节的 NPSH 核库的存在，并表明组织和核 NPSH 不能预测接受放疗的局部晚期宫颈癌患者的结果。 (C) 2005 爱思唯尔公司。
Purpose: The non-protein sulfydryls (NPSH) glutathione and cysteine are able to effect chemical repair of radiation-induced DNA damage, particularly under hypoxic conditions, and are implicated in radioresistance. The levels of NPSH in the nucleus are predicted to be more important than those in cytoplasm. We, therefore, investigated the relation between nuclear NPSH and the clinical outcome of radical radiotherapy (RT).Methods and Materials: A fluorescence image analysis technique to measure nuclear NPSH was developed, based on the SH-reactive probe 1(4-chloromercuryphenyl-azo-2-naphthol) and the DNA dye 4,6-diamidino-2-phenylindole. This was used to measure nuclear and tissue NPSH levels in biopsies obtained from 58 patients with locally advanced uterine cervical carcinoma, treated with radical RT.Results: An approximately twofold range in the nuclear and tissue NPSH levels between individual tumors was found, although the intratumoral heterogeneity was much smaller. Nuclear and tissue NPSH values correlated closely in all cases. No statistically significant associations were noted between NPSH levels and tumor size, stage, or tumor hypoxia as determined at the time of biopsy using an Eppendorf pO(2) probe. The response to RT and patient survival did not correlate with tumor NPSH.Conclusion: These results did not support the existence of an independently regulated nuclear pool of NPSH and showed that tissue and nuclear NPSH are not predictive of the outcome of patients with locally advanced cervical carcinomas treated with RT. (C) 2005 Elsevier Inc.