The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer.

The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer.
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DOI:
10.1038/bjc.2011.158
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发表时间:
2011-05-24
影响因子:
8.8
通讯作者:
Hareyama, M.
Hareyama, M.
中科院分区:
医学1区
文献类型:
--
作者:
Someya, M.;Sakata, K-I;Matsumoto, Y.;Kamdar, R. P.;Kai, M.;Toyota, M.;Hareyama, M.

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修复各种类型的DNA损伤对基因组的稳定性至关重要。DNA依赖性蛋白激酶(DNA- pk)在DNA双链断裂修复中起着重要作用。我们研究了不同癌症患者外周血淋巴细胞(pbl)中DNA-PK活性与生存率之间是否存在相关性。我们还研究了放射治疗后pbl中DNA-PK活性的变化。共有167名未经治疗的癌症患者参与了这项研究。收集外周血,分离,离心。采用dna下拉法测定DNA-PK活性。用细胞遗传学方法检测染色体畸变。晚期肿瘤患者pbl的DNA-PK活性明显低于早期。pbl中DNA-PK活性较低的患者在晚期比DNA-PK活性较高的患者有更低的疾病特异性生存和远端无转移生存。DNA-PK活性与多余片段呈负相关。大多数患者pbl的DNA-PK活性随着等效全身剂量的增加而降低。晚期肿瘤患者,pbl DNA-PK活性较低,远处转移率较高,预后较差。因此,pbl中DNA-PK活性可作为预测染色体不稳定性和预后不良的标志物。
Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy. A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods. DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased. Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.
DOI: 10.1016/0360-3016(93)90345-v
发表时间: 1993-01-15
影响因子: 7
作者:
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通讯作者: SUIT, H
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DOI: 10.1038/ng1409
发表时间: 2004-09-01
期刊: NATURE GENETICS
影响因子: 30.8
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DOI: 10.1139/o96-054
发表时间: 1996-01-01
期刊: BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
影响因子: --
作者:
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通讯作者: LeesMiller, SP