[1]郭阳.错配修复系统缺陷对肿瘤放化疗的影响[J].国际放射医学核医学杂志,2011,35(6):363-365.[doi:10.3760,cma.j.issn.1673-4114.2011.06.011]
　GUO Yang.The effect of mismatch repair deficiency on chemotherapy and radiotherapy in tumors[J].International Journal of Radiation Medicine and Nuclear Medicine,2011,35(6):363-365.[doi:10.3760,cma.j.issn.1673-4114.2011.06.011]
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错配修复系统缺陷对肿瘤放化疗的影响(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
35
期数:
2011年第6期
页码:
363-365
栏目:
放射生物学
出版日期:
1900-01-01

文章信息/Info

Title:
The effect of mismatch repair deficiency on chemotherapy and radiotherapy in tumors
作者:
郭阳
天津市环湖医院放疗科, 天津 300060
Author(s):
GUO Yang
Department of radiotherapy, Tianjin Huanhu Hospital, Tianjin 300060, China
关键词:
碱基错配; DNA修复; 辐射耐受性; 抗药性; 肿瘤
Keywords:
Base pair mismatch; DNA repair; Radiation tolerance; Drug resistance; neoplasm
DOI:
10.3760,cma.j.issn.1673-4114.2011.06.011
摘要:
在肿瘤干细胞和增殖性肿瘤细胞中,广泛存在错配修复(MMR)系统的功能缺失。对于接受化疗的肿瘤,若MMR缺失,可导致细胞绕过细胞周期的G2/S期循环阻滞,产生对化疗药物的抗性。在I临床上,即使是06-甲基鸟嘌呤-DNA甲基转移酶阴性的胶质瘤细胞也会因MMR的缺失,对替莫唑胺产生抗性。对于接受放射治疗的肿瘤,MMR缺失的作用表现为相互矛盾的两个方面:首先,MMR缺失可导致肿瘤细胞对辐射挠陛的提高,细胞不出现凋亡和自吞噬;另一方面,预先给予放射增敏剂5-碘-2’-脱氧尿苷(IUdR)等药物后,MMR的缺失会导致DNA中掺杂大量未被修复的IUdR等基团,从而提高肿瘤细胞的辐射敏感性。
Abstract:
It is very common phenomenon that mismatch repair (MMR) deficiency in various tumors, both stem cells and proliferation cells.With MMR deficiency,the cells treated by chemotherapy drugs passed the G2/S arrest and became resistant to the drugs.In the clinical trial,even in the glioma with negative 06-methylguanine-DNA methyhransferase expression show the resistance to Temozolomide.The MMR deficiency cells treated by radiotherapy show two contradictory behaviors.MMR deficiency enhanced the cells resistance to radiation,for cells show less apoptosis or autophagy.On the other hand,pretreated with radiation enhancer,such as 5-iodo-2’-deoxyuridine (IUdR),resulting in more IUdR-DNA unrepaired cells and increasing the sensitivity to radiation.

参考文献/References:

[1] Kinsella TJ.Coordination of DNA mismatch repair and base excision repair processing of chenotherapy and radiation damage for targeting resistant cancers.Clin Cancer Res,2009,15(6):1853-1859.
[2] Vaish M.Mismatch repair deficiencies transforming stem cells into cancer stem cells and therapeutic implications.Mol Cancer,2007,6:26.
[3] Zeng X,Kinsella TJ.A novel role for DNA mismatch repair and the autophagic processing of chemotherapy drug in human tumor ceils.Autophagy,2007,3(4):368-370.
[4] O’Brien V,Brown R.Signalling cell cycle arrest and cell death through the MMR system.Carcinogenesis,2006.27(4):682-692.
[5] Yip S,Miao J,Cahill DP,et al.MSH6 mutation arise in glioblas-tomas during temozolomide therapy and mediated temozolomide resistance.Clin Cancer Res,2009,15(14):4622-4629.
[6] Hunter C,Smith R,Cahill DP,et al.A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy.Cancer Res,2006,66(8):3987-3991.
[7] Yan T,SeoY,Kinsella TJ.Differential cellular responses to pro-longed LDR-IR in MLHl-proficient and MLHl-deficient colorectal cancer HCTl 16 cells.Clin Cancer Res,2009,15(22):6912-6920.
[8] Shahi A,Lee JH,Kang Y,et al.Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair.Nucleic Acids Res,2011,39(6):2130-2143.
[9] Kinsella TJ,Kinsella MT,Seo Y,et al.5-iodo-2-pyrimidinone-2’-deoxyribose (IPdR)-mediated cytotoxicity and radiosensitization in U87 human glioblastoma xenografts.Int J Radiat Oncol Biol Phys,2007,69(4):1254-1261.
[10] Gerson SL,Reese J,Kenyon J.DNA repair in stem cell mainte-nance and conversion to cancer stem ceils.Ernst Schefing Found Symp Proc.2007.5:23l-244.
[11] Rodríquez-Jimémez FJ,Moreno-Manzano V,Lucas-Dominquez R,et al.Hypoxia causes downregulation of mismatch repair system and genomic instability in stem cell.Stem Cells,2008,26(8):2052-2062.
[12] Jificny J.The mihifaceted mismatch-repair system.Nat Rev Mol Cell Biol,2006,7(5):335-346.
[13] Adamson AW,Beardsley DI,Kim WJ,et al.Methylator-induced,mismatch repair-dependent G2 arrest is activated through Chkl and Chk2.Mol Biol Cell,2005,16(3):1513-1526.
[14] Yoshioka K,Yoshioka Y.Hsieh P.ATR kinase activation mediated by Mut Sα and Mut Lα in responseto cytotoxic 06-methylguanine adducts.Mol Cell,2006,22(4):501-510.
[15] Helleday T,Petermann E,Lundin C,et al.DNA repair pathways as targets for cancer therapy.Nat Rev Cancer,2008,8(3):193-204.
[16] Schulz CA,Mehta MP,Badie B,et al.Continuous 28-days iodo-deoxyuridineinfusion and hypeffractionated accelerated radiotherapy for malignant glioma:a phase I clinical study.Int J Radiat Oncol Biol Phys,2004,59(4):1107-1115

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　DONG Xiao-rong,WU Gang.The response of the brain tissue to DNA double strand breaks[J].International Journal of Radiation Medicine and Nuclear Medicine,2008,32(6):51.
[10]郭阳.DNA链间交联的修复与辐射敏感性[J].国际放射医学核医学杂志,2007,31(6):371.
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备注/Memo

备注/Memo:
收稿日期:2011-07-14。
更新日期/Last Update: 1900-01-01