Expression of Ku70 correlates with survival in carcinoma of the cervix.

Expression of Ku70 correlates with survival in carcinoma of the cervix.
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Ku70的表达与子宫颈癌的存活相关。

DOI:
10.1054/bjoc.2000.1510
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发表时间:
2000-12
影响因子:
8.8
通讯作者:
West, CML
West, CML
中科院分区:
医学1区
文献类型:
--
作者:
Wilson, CR;Davidson, SE;Margison, GP;Jackson, SP;Hendry, JH;West, CML

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在英国,宫颈癌每年影响大约3400名女性,晚期疾病通常接受放射治疗。作为建立快速和方便的预测肿瘤和患者对放射治疗反应的方法的计划的一部分,我们研究了宫颈癌患者治疗前DNA损伤识别复合体DNA-PK的Ku成分的表达与患者生存的关系。用福尔马林固定的肿瘤活检切片进行免疫组织化学染色,发现抗Ku70和Ku80的抗体在77个肿瘤中染色相同的区域,两种成分的平均染色阳性细胞数之间高度相关(r=0.82P<0.001)。在53个肿瘤中,肿瘤放射敏感性(2灰度处存活分数:SF2)与Ku70表达呈边缘显著相关(r=0.26,P=0.057),而Ku80无相关性(r=0.18,P=0.19)。然而,所有Ku70或Ku80阳性细胞数量较少的肿瘤都是放射敏感性的。此外,使用LOG-RANK分析,肿瘤Ku70低表达的患者的生存率显著较高(P=0.046)。这一差异也反映在Ku80上,但没有达到统计学意义(P=0.087)。这项研究表明,Ku蛋白的缺乏导致了一些肿瘤的放射敏感性,而其他因素也是导致Ku高表达的放射敏感性肿瘤的原因。很可能,对治疗结果最准确的预测将在于评估参与识别和修复DNA损伤的几种蛋白质的表达,其中之一将是Ku。©2000癌症研究活动http://www.bjcancer.com
Cervical carcinoma affects around 3400 women in the UK each year and advanced disease is routinely treated with radiation. As part of a programme to establish rapid and convenient methods of predicting tumour and patient responses to radiotherapy, we have examined the relationship between the pre-treatment expression of the Ku components of the DNA damage recognition complex DNA-PK and patient survival in cervical carcinoma. Using immunohistochemistry of formalin-fixed sections of tumour biopsies, antibodies to Ku70 and Ku80 stained identical regions of tumour and there was a high degree of correlation between the mean number of cells stained positive for the two components in 77 tumours (r = 0.82, P< 0.001). In 53 tumours there was a borderline significant correlation between measurements of tumour radiosensitivity (surviving fraction at 2 gray: SF2) and Ku70 expression (r = 0.26, P = 0.057) and no correlation for Ku80 (r = 0.18, P = 0.19). However, all tumours with a low number of Ku70 or Ku80 positive cells were radiosensitive. Furthermore, using log-rank analysis there was significantly higher survival in the patients whose tumours had a low Ku70 expression (P = 0.046). This difference was also reflected with Ku80, but did not reach statistical significance (P = 0.087). The study suggests that lack of Ku protein leads to radiosensitivity in some tumours and that other factors are responsible for radiosensitive tumours with high Ku expression. It is likely that the most accurate prediction of treatment outcome will lie in assessing the expression of several proteins involved in the recognition and repair of DNA damage, one of which will be Ku. © 2000 Cancer Research Campaign http://www.bjcancer.com
DOI: 10.1073/pnas.94.25.13588
发表时间: 1997-12-09
影响因子: 11.1
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Nussenzweig, A;Sokol, K;Li, GC
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