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从蛋白质-蛋白质相互作用到治疗反应:热休克蛋白的分子成像

From protein-protein interaction to therapy response: molecular imaging of heat shock proteins.

作者信息

Niu Gang, Chen Xiaoyuan

机构信息

The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, Stanford, CA 94305-5484, USA.

出版信息

Eur J Radiol. 2009 May;70(2):294-304. doi: 10.1016/j.ejrad.2009.01.052. Epub 2009 Mar 20.

Abstract

HSP70 promoter-driven gene therapy and inhibition of HSP90 activity with small molecule inhibitors are two shining points in a newly developed cohort of cancer treatment. For HSP70 promoters, high efficiency and heat inducibility within a localized region make it very attractive to clinical translation. The HSP90 inhibitors exhibit a broad spectrum of anticancer activities due to the downstream effects of HSP90 inhibition, which interfere with a wide range of signaling processes that are crucial for the malignant properties of cancer cells. In this review article, we summarize exciting applications of newly emerged molecular imaging techniques as they relate to HSP, including protein-protein interactions of HSP90 complexes, therapeutic response of tumors to HSP90 inhibitors, and HSP70 promoters-controlled gene therapy. In the HSPs context, molecular imaging is expected to play a vital role in promoting drug development and advancing individualized medicine.

摘要

热休克蛋白70(HSP70)启动子驱动的基因治疗以及使用小分子抑制剂抑制HSP90活性是新开发的癌症治疗方法中的两个亮点。对于HSP70启动子,局部区域内的高效性和热诱导性使其在临床转化方面极具吸引力。由于HSP90抑制的下游效应,HSP90抑制剂表现出广泛的抗癌活性,这些效应会干扰对癌细胞恶性特性至关重要的多种信号传导过程。在这篇综述文章中,我们总结了新出现的分子成像技术与热休克蛋白(HSP)相关的令人兴奋的应用,包括HSP90复合物的蛋白质 - 蛋白质相互作用、肿瘤对HSP90抑制剂的治疗反应以及HSP70启动子控制的基因治疗。在热休克蛋白的背景下,分子成像有望在促进药物开发和推进个体化医学方面发挥至关重要的作用。

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