A new cancer diagnostic system based on a CDK profiling technology

A new cancer diagnostic system based on a CDK profiling technology
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DOI:
10.1016/j.bbadis.2005.06.001
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发表时间:
2005-09-25
影响因子:
6.2
通讯作者:
Sakai, T
Sakai, T
中科院分区:
生物学2区
文献类型:
--
作者:
Ishihara, H;Yoshida, T;Sakai, T

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对刺激细胞周期蛋白依赖性激酶(CDK 1、2、4和6)的分子的一系列分子病理学研究已经导致了这些分子对于癌症诊断的临床意义的知识的巨大积累。然而,这些分子尚未应用于临床癌症诊断,因为没有可用的技术用于在临床环境中应用这些知识。我们假设直接测量CDK活性和表达(CDK谱)可能会产生临床相关的诊断价值。本研究通过使用最初开发的表达和活性分析方法来研究胃肠道癌组织中CDK谱的临床相关性。我们已经建立了新的方法和装置,用于分析CDK分子的表达和活性的裂解物中的肿瘤组织在临床环境中,并检查了30例手术解剖的胃肠道癌和相应的正常粘膜标本。我们在这里证明,显着升高的CDK 2活性是明显的,在超过70%的癌组织。此外,G1-CDK活性谱准确地反映了肿瘤和正常结肠组织之间的增殖差异。我们的研究结果表明,CDK谱是一种有效的分子临床方法,以补充传统的病理诊断,并进一步协助个体化用药。(c)2005 Elsevier B. V.保留所有权利。
A series of molecular pathological investigations of the molecules that stimulate the cyclin dependent kinases (CDK1, 2, 4, and 6) have led to enormous accumulation of knowledge of the clinical significance of these molecules for cancer diagnosis. However, the molecules have yet to be applied to clinical cancer diagnosis, as there is no available technology for application of the knowledge in a clinical setting. We hypothesized that the direct measurement of CDK activities and expressions (CDK profiling) might produce clinically relevant values for the diagnosis. This study investigated the clinical relevance of CDK profiling in gastrointestinal carcinoma tissues by using originally developed expression and activity analysis methods. We have established novel methods and an apparatus for analyzing the expression and activities of the CDK molecules in lysate of tumor tissue in a clinical setting, and examined 30 surgically dissected gastrointestinal carcinomas and corresponding normal mucosal specimens. We demonstrate here that remarkably elevated CDK2 activity is evident in more than 70% of carcinoma tissues. Moreover, a G1-CDK activity profiling accurately mirrored the differences in proliferation between tumor and normal colonic tissues. Our results suggest that CDK profiling is a potent molecular-clinical approach to complement the conventional pathological diagnosis, and to further assist in the individualized medications. (c) 2005 Elsevier B.V. All rights reserved.