人脑膜瘤细胞对周期蛋白依赖性激酶抑制剂TG02的敏感性

IF 4.5 2区 医学 Q1 ONCOLOGY
C. von Achenbach, É. Le Rhun, F. Sahm, S. Wang, P. Sievers, M. Neidert, E. Rushing, T. Lawhon, Hannah Schneider, A. von Deimling, M. Weller
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引用次数: 4

摘要

脑膜瘤的护理标准包括手术切除和放疗,而药物治疗在这种疾病中几乎没有作用。我们从手术切除的脑膜瘤中产生了原代培养物,以探索一种新型细胞周期蛋白依赖性激酶抑制剂TG02在脑膜瘤细胞培养中的活性。肿瘤和细胞培养物通过突变谱和DNA甲基化谱进行表征。DNA甲基化数据用于将每个样本分配到六个先前建立的脑膜瘤甲基化类别中的一个:良性(ben)-1、2、3、中间(int)-A、B和恶性(mal)。被分配到甲基化类别ben-2的四个肿瘤在培养中显示出相同的类别,而来自五个非ben-2肿瘤的培养在四个患者中显示出更恶性的类别。细胞培养物在纳摩尔范围内对TG02均匀敏感。将细胞培养物分配给恶性程度更高的甲基化类似乎比分配给世界卫生组织级别更高的原发肿瘤与TG02敏感性更密切相关。脑膜瘤的原代细胞培养有助于研究新型药物的抗脑膜瘤活性。TG02是一种口服细胞周期蛋白依赖性激酶(CDK)抑制剂,值得进一步探索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sensitivity of human meningioma cells to the cyclin-dependent kinase inhibitor, TG02
Standards of care for meningioma include surgical resection and radiotherapy whereas pharmacotherapy plays almost no role in this disease. We generated primary cultures from surgically removed meningiomas to explore the activity of a novel cyclin-dependent kinase inhibitor, TG02, in meningioma cell cultures. Tumor and cell cultures were characterized by mutation profiling and DNA methylation profiling. DNA methylation data were used to allot each sample to one out of six previously established meningioma methylation classes: benign (ben)-1, 2, 3, intermediate (int)-A, B, and malignant (mal). Four tumors assigned to the methylation class ben-2 showed the same class in culture whereas cultures from five non-ben-2 tumors showed a more malignant class in four patients. Cell cultures were uniformly sensitive to TG02 in the nanomolar range. Assignment of the cell cultures to a more malignant methylation class appeared to be more closely associated with TG02 sensitivity than assignment to a higher WHO grade of the primary tumors. Primary cell cultures from meningioma facilitate the investigation of the anti-meningioma activity of novel agents. TG02, an orally available cyclin-dependent kinase (CDK) inhibitor, warrants further exploration.
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来源期刊
Translational Oncology
Translational Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
7.20
自引率
2.00%
发文量
314
审稿时长
6-12 weeks
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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