Immunohistochemical assessment of protein phosphorylation state: the dream and the reality.
Immunohistochemical assessment of protein phosphorylation state: the dream and the reality.
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DOI：
10.1007/s00418-008-0474-z
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发表时间：
2008-09
影响因子：
2.3
通讯作者：
Mandell, James W.
中科院分区：
文献类型：
--
作者：
Mandell, James W.
20世纪80年代磷酸化状态特异性抗体（PSSAs）的发展及其随后的增殖有望使复杂细胞内信号网络的激活状态的原位分析成为可能。这一承诺在多大程度上得到了履行，这就是本次审查的主题。我回顾了PSSAs的一些应用，主要是在评估实体瘤信号通路的激活状态。PSSA因其揭示细胞类型特异性活化状态、提供额外预后信息、帮助预测治疗反应以及最近证明激酶靶向化疗的疗效的潜力而受到相当大的关注。然而，尽管取得了一些成功，但许多研究未能证明PSSA相对于一般抗体免疫组织化学的附加值。此外，对于组织样品中复杂和异质染色模式的解释及其与体内实际磷酸化状态的关系，仍然存在很大程度的不确定性。PSSAs应用中的下一阶段转化研究将需要抗体验证、收集有关表位特异性不稳定性的详细信息以及实施标准化方法的艰苦工作。
The development of phosphorylation state-specific antibodies (PSSAs) in the 1980s, and their subsequent proliferation promised to enable in situ analysis of the activation states of complex intracellular signaling networks. The extent to which this promise has been fulfilled is the topic of this review. I review some applications of PSSAs primarily in the assessment of solid tumor signaling pathway activation status. PSSAs have received considerable attention for their potential to reveal cell type-specific activation status, provide added prognostic information, aid in the prediction of response to therapy, and most recently, demonstrate the efficacy of kinase-targeted chemotherapies. However, despite some successes, many studies have failed to demonstrate added value of PSSAs over general antibody immunohistochemistry. Moreover, there is still a large degree of uncertainty about the interpretation of complex and heterogeneous staining patterns in tissue samples and their relationship to the actual phosphorylation states in vivo. The next phase of translational research in applications of PSSAs will entail the hard work of antibody validation, gathering of detailed information about epitope-specific lability, and implementation of methods for standardization.
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
6.4
作者：
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通讯作者：
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