Clinical application of the methods to detect enzyme activities of proteins involved in repair of DNA double strand breaks
DNA双链断裂修复蛋白酶活性检测方法的临床应用
基本信息
- 批准号:16591215
- 负责人:
- 金额:$ 2.18万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2004
- 资助国家:日本
- 起止时间:2004 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The presence of genomic instability in cells is known to play an important role in the multistage carcinogenesis of various organs. The DNA double strand breaks (DSBs) repair pathway has been implicated in maintaining genomic integrity via suppression of chromosomal rearrangements. DNA-dependent protein kinase (DNA-PK) has an important role in DNA DSBs repair. The purpose of this study was to determine how DNA-PK activity varies among untreated cancer patients and cancer-free normal healthy volunteers and how this affects cancer risk. DNA-PK activities of peripheral blood lymphocytes (PBL) in normal volunteers were 15.84 ± 4.87 pmol and those of cancer patients were 12.28 ± 5.10 pmol. There was the significant difference between them (p=0.012). Age and smoking had no association with DNA-PK activity A relationship between DNA-PK acitvity and chromosome aberration in PBL was shown to exist. The frequency of excess fragment increased as the DNA-PK activity decreased.NBS1, a protein essential for DNA double strand break repair, re-localizes into subnuclear structures upon the induction of DNA damage by ionizing radiation, forming ionizing radiation-induced foci (IRIF). We compared NBS1 IRIF in PBL taken from 46 sporadic breast cancer patients and 30 cancer-free healthy volunteers. The number of persistent NBS1 IRIF per nucleus at 24 hours after irradiation in invasive cancer patients was significantly higher than in normal healthy volunteers. The frequency of spontaneous chromosome aberration increased as the number of persistent NBS1 IRIF increased, indicating that number of persistent NBS1 IRIF might be associated with chromosome instability. There was also an inverse correlation between NBS1 IRIF number and the activity of DNA-PK, which plays an important role in the non-homologous end-joining pathway (NHEJ), another mechanism of DNA DSB repair, indicating close interrelationship between HR and NHEJ in DNA DSB repair mechanism.
已知细胞中基因组不稳定性的存在在各种器官的多阶段癌变中起重要作用。DNA双链断裂(DSB)修复途径已经涉及通过抑制染色体重排来维持基因组完整性。DNA依赖性蛋白激酶(DNA-PK)在DNA双链断裂修复中具有重要作用。这项研究的目的是确定未经治疗的癌症患者和无癌症的正常健康志愿者之间的DNA-PK活性如何变化,以及这如何影响癌症风险。正常人外周血淋巴细胞DNA-PK活性为15.84 ± 4.87pmol,恶性肿瘤患者为12.28 ± 5.10pmol。两组间有显著性差异(p=0.012)。DNA-PK活性与外周血淋巴细胞染色体畸变之间存在一定的相关性。DNA双链断裂修复蛋白NBS 1在电离辐射诱导的DNA损伤中,重新定位于亚核结构,形成电离辐射诱导灶(IRIF)。我们比较了46例散发性乳腺癌患者和30例无癌健康志愿者PBL中的NBS 1 IRIF。照射后24小时,侵袭性癌症患者每个核中持续的NBS 1 IRIF的数量显著高于正常健康志愿者。自发染色体畸变的频率随着持续性NBS 1 IRIF数量的增加而增加,表明持续性NBS 1 IRIF的数量可能与染色体不稳定性有关。NBS 1 IRIF数目与DNA-PK活性呈负相关,而DNA-PK在DNA DSB修复的另一机制--非同源末端连接途径(NHEJ)中起重要作用,表明HR与NHEJ在DNA DSB修复机制中有密切的相互关系。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer
- DOI:10.1093/carcin/bgi175
- 发表时间:2006-01-01
- 期刊:
- 影响因子:4.7
- 作者:Someya, M;Sakata, K;Hareyama, M
- 通讯作者:Hareyama, M
The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer : Carcinogenesis.
DNA 依赖性蛋白激酶活性与染色体不稳定性和癌症风险的关联:癌发生。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Nakamura K;et al.;東 光太郎;M.Someya
- 通讯作者:M.Someya
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SAKATA Koh-ichi其他文献
SAKATA Koh-ichi的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SAKATA Koh-ichi', 18)}}的其他基金
Studies about gimeracil, a radiosensitizer
关于放射增敏剂吉美嘧啶的研究
- 批准号:
21591616 - 财政年份:2009
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Research of proteins involved in repair of DNA double strand breaks for individualization of radi ation therapy
DNA双链断裂修复相关蛋白质的研究用于个体化放射治疗
- 批准号:
19591462 - 财政年份:2007
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of the methods to detect enzyme activities of proteins involved in repair of DNA double strand breaks
开发检测参与 DNA 双链断裂修复的蛋白质酶活性的方法
- 批准号:
14570871 - 财政年份:2002
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of the practical methods to predict radiosensitivity of tumors with immunohistchemistry
开发免疫组织化学预测肿瘤放射敏感性的实用方法
- 批准号:
12670892 - 财政年份:2000
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Basic research for the gene therapy to the radioresistant tumors
抗放射肿瘤基因治疗的基础研究
- 批准号:
10670863 - 财政年份:1998
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Investigation of molecular mechanism of radiosensitivity of the tumor cell and its clinical application
肿瘤细胞放射敏感性分子机制研究及其临床应用
- 批准号:
08671043 - 财政年份:1996
- 资助金额:
$ 2.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
相似海外基金
Exploring the adaptive role of genomic instability in Trypanosoma cruzi.
探索克氏锥虫基因组不稳定性的适应性作用。
- 批准号:
MR/Y001338/1 - 财政年份:2024
- 资助金额:
$ 2.18万 - 项目类别:
Research Grant
Genomic Instability as A Driver of Stem Cell Exhaustion
基因组不稳定性是干细胞衰竭的驱动因素
- 批准号:
10722284 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
XRN2-DDX23 Cooperation in Avoiding R-loop-induced Genomic Instability
XRN2-DDX23 合作避免 R 环引起的基因组不稳定
- 批准号:
10654331 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
Exploiting markers of genomic instability in high-risk pre-invasive ovarian cancer
利用高风险浸润前卵巢癌基因组不稳定性标记
- 批准号:
10719535 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
Does inactivation of protein phosphatase PP2A contribute to genomic instability in RAS-mutant cancers?
蛋白磷酸酶 PP2A 失活是否会导致 RAS 突变癌症的基因组不稳定?
- 批准号:
2882281 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
Studentship
R-loops at the telomere as a toxic source of genomic instability
端粒上的 R 环是基因组不稳定的毒源
- 批准号:
10770896 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
Genomic instability and hypermutations in the pathogenesis of skin fibrosis in systemic scleroderma
系统性硬皮病皮肤纤维化发病机制中的基因组不稳定性和超突变
- 批准号:
485124 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
Operating Grants
Dissecting and targeting mechanisms of genomic instability-triggered immune evasion in RBM10-deficient non-small cell lung cancer
RBM10 缺陷型非小细胞肺癌基因组不稳定性触发免疫逃逸的剖析和靶向机制
- 批准号:
10658049 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
Characteristic cytosolic DNA patterns produced by genomic instability induce anti-tumour immunity via cGAS/STING in colorectal cancer
基因组不稳定性产生的特征性胞质 DNA 模式通过 cGAS/STING 在结直肠癌中诱导抗肿瘤免疫
- 批准号:
495184 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别:
Cytosolic DNA is the Link Between Genomic Instability and Cardiovascular Aging
细胞质 DNA 是基因组不稳定性与心血管衰老之间的联系
- 批准号:
10722123 - 财政年份:2023
- 资助金额:
$ 2.18万 - 项目类别: