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[人胶质瘤细胞系中DNA拓扑异构酶IIα表达与依托泊苷敏感性的相关性]

[Correlation between DNA topoisomerase II alpha expression and sensitivity to etoposide in human glioma cell lines].

作者信息

Hao Y J, Natsume A, Mizuno M, Taniguchi K, Wakabayashi T, Yoshida J

机构信息

Dept. of Neurosurgery, Nagoya University School of Medicine.

出版信息

Gan To Kagaku Ryoho. 2000 Aug;27(9):1403-9.

PMID:10969596
Abstract

The expression of topoisomerase II alpha (Topo II alpha) was investigated in six human glioma cell lines as a function of doubling time, cell cycle distribution, and sensitivity to an antineoplastic agent, etoposide (ETP). The Topo II alpha level was determined by immunohistochemical and flow cytometric studies using monoclonal antibody, 8D2, specific for Topo II alpha. In all cell lines, the Topo II alpha level correlated directly with sensitivity to ETP, but not with doubling time or percentage of cells in any phase of the cell cycle. These findings suggest that the cytocidal activity of ETP may be mediated by qualitative and quantitative changes in Topo II alpha in human glioma cells. We speculate that better knowledge of Topo II alpha expression in surgical specimens may lead to more individualized use of ETP in patients with malignant glioma.

摘要

研究了拓扑异构酶IIα(Topo IIα)在六种人类胶质瘤细胞系中的表达情况,该表达与倍增时间、细胞周期分布以及对抗肿瘤药物依托泊苷(ETP)的敏感性相关。使用针对Topo IIα的单克隆抗体8D2,通过免疫组织化学和流式细胞术研究确定Topo IIα水平。在所有细胞系中,Topo IIα水平与对ETP的敏感性直接相关,但与倍增时间或细胞周期任何阶段的细胞百分比无关。这些发现表明,ETP的杀细胞活性可能由人类胶质瘤细胞中Topo IIα的定性和定量变化介导。我们推测,更好地了解手术标本中Topo IIα的表达情况可能会使恶性胶质瘤患者更个体化地使用ETP。

相似文献

1
[Correlation between DNA topoisomerase II alpha expression and sensitivity to etoposide in human glioma cell lines].[人胶质瘤细胞系中DNA拓扑异构酶IIα表达与依托泊苷敏感性的相关性]
Gan To Kagaku Ryoho. 2000 Aug;27(9):1403-9.
2
Induction of resistance to etoposide and adriamycin in a human glioma cell line treated with antisense oligodeoxynucleotide complementary to the messenger ribonucleic acid of deoxyribonucleic acid topoisomerase II alpha.用与脱氧核糖核酸拓扑异构酶IIα信使核糖核酸互补的反义寡脱氧核苷酸处理人胶质瘤细胞系,诱导其对依托泊苷和阿霉素产生抗性。
Neurol Med Chir (Tokyo). 1997 Sep;37(9):655-61; discussion 661-2. doi: 10.2176/nmc.37.655.
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Changes in subcellular distribution of topoisomerase IIalpha correlate with etoposide resistance in multicell spheroids and xenograft tumors.拓扑异构酶IIα亚细胞分布的变化与多细胞球体和异种移植肿瘤中的依托泊苷耐药性相关。
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Drastic reduction of topoisomerase II alpha associated with major acquired resistance to topoisomerase II active agents but minor perturbations of cell growth.拓扑异构酶IIα的显著减少与对拓扑异构酶II活性剂的主要获得性耐药相关,但对细胞生长的干扰较小。
Oncol Res. 1995;7(7-8):407-16.
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Transfection of a human topoisomerase II alpha gene into etoposide-resistant human breast tumor cells sensitizes the cells to etoposide.将人拓扑异构酶IIα基因转染至依托泊苷耐药的人乳腺肿瘤细胞中可使细胞对依托泊苷敏感。
Oncol Res. 1996;8(3):101-10.
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[Expression of DNA topoisomerases (I, II alpha, II beta) mRNA in etoposide- and mAMSA-resistant cell lines].
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Decreased DNA topoisomerase II alpha expression and cold-sensitive growth in a mouse mammary cancer cell line resistant to etoposide and doxorubicin.在一株对依托泊苷和阿霉素耐药的小鼠乳腺癌细胞系中,DNA拓扑异构酶IIα表达降低及冷敏感生长。
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Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase IIalpha gene transfer is independent of topoisomerase IIbeta.腺病毒介导的人拓扑异构酶IIα基因转移后依托泊苷敏感性增强与拓扑异构酶IIβ无关。
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Topoisomerase II activities in AML and their correlation with cellular sensitivity to anthracyclines and epipodophyllotoxines.急性髓系白血病中的拓扑异构酶II活性及其与细胞对蒽环类药物和鬼臼毒素敏感性的相关性。
Leukemia. 1996 Jul;10(7):1177-80.
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Etoposide targets topoisomerase IIalpha and IIbeta in leukemic cells: isoform-specific cleavable complexes visualized and quantified in situ by a novel immunofluorescence technique.依托泊苷作用于白血病细胞中的拓扑异构酶IIα和IIβ:通过一种新型免疫荧光技术原位可视化并定量分析同工型特异性可切割复合物。
Mol Pharmacol. 1998 Jul;54(1):78-85. doi: 10.1124/mol.54.1.78.

引用本文的文献

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Higher topoisomerase 2 alpha gene transcript levels predict better prognosis in GBM patients receiving temozolomide chemotherapy: identification of temozolomide as a TOP2A inhibitor.拓扑异构酶 2α 基因转录水平较高的胶质母细胞瘤患者接受替莫唑胺化疗的预后较好:替莫唑胺是拓扑异构酶 2 抑制剂。
J Neurooncol. 2012 Apr;107(2):289-97. doi: 10.1007/s11060-011-0758-3. Epub 2011 Nov 19.
2
Immunohistochemical markers for prognosis of oligodendroglial neoplasms.少突胶质细胞瘤预后的免疫组化标志物
J Neurooncol. 2002 Jul;58(3):237-53. doi: 10.1023/a:1016270101321.