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用于个性化治疗的人类乳腺癌应用的多重细胞信号分析

Multiplexed cell signaling analysis of human breast cancer applications for personalized therapy.

作者信息

Wulfkuhle Julia D, Speer Runa, Pierobon Mariaelena, Laird Julie, Espina Virginia, Deng Jianghong, Mammano Enzo, Yang Sherry X, Swain Sandra M, Nitti Donato, Esserman Laura J, Belluco Claudio, Liotta Lance A, Petricoin Emanuel F

机构信息

Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia 20110, USA.

出版信息

J Proteome Res. 2008 Apr;7(4):1508-17. doi: 10.1021/pr7008127. Epub 2008 Feb 8.

Abstract

Phosphoprotein driven cellular signaling events represent most of the new molecular targets for cancer treatment. Application of reverse-phase protein microarray technology for the study of ongoing signaling activity within breast tumor specimens holds great potential for elucidating and profiling signaling activity in real-time for patient-tailored therapy. Analysis of laser capture microdissection primary human breast tumors and metastatic lesions reveals pathway specific profiles and a new way to classify cancer based on functional signaling portraits. Moreover, the data demonstrate the requirement of laser capture microdissection for analysis and reveal the metastasis-specific changes that occur within a new microenvironment. Analysis of biopsy material from clinical trials for targeted therapeutics demonstrates the feasibility and utility of comprehensive signal pathway activation profiling for molecular analysis.

摘要

磷酸化蛋白驱动的细胞信号转导事件代表了癌症治疗的大多数新分子靶点。应用反相蛋白质微阵列技术研究乳腺肿瘤标本中的持续信号活性,对于实时阐明和描绘信号活性以进行患者个体化治疗具有巨大潜力。对激光捕获显微切割的原发性人类乳腺肿瘤和转移灶的分析揭示了特定通路的特征以及基于功能信号图谱对癌症进行分类的新方法。此外,数据证明了激光捕获显微切割对于分析的必要性,并揭示了在新微环境中发生的转移特异性变化。对靶向治疗临床试验的活检材料进行分析,证明了综合信号通路激活图谱用于分子分析的可行性和实用性。

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