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多胺与癌症

Polyamines and Cancer.

作者信息

Damiani Elisabetta, Wallace Heather M

机构信息

School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.

Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.

出版信息

Methods Mol Biol. 2018;1694:469-488. doi: 10.1007/978-1-4939-7398-9_39.

Abstract

This chapter provides an overview of how the polyamine pathway has been exploited as a target for the treatment and prevention of multiple forms of cancer, since this pathway is disrupted in all cancers. It is divided into three main sections. The first explores how the polyamine pathway has been targeted for chemotherapy, starting from the first drug to target it, difluoromethylornithine (DFMO) to the large variety of polyamine analogues that have been synthesised and tested throughout the years with all their potentials and pitfalls. The second section focuses on the use of polyamines as vectors for drug delivery. Knowing that the polyamine transport system is upregulated in cancers and that polyamines naturally bind to DNA, a range of polyamine analogues and polyamine-like structures have been synthesised to target epigenetic regulators, with encouraging results. Furthermore, the use of polyamines as transport vectors to introduce toxic/bioactive/fluorescent agents more selectively to the intended target in cancer cells is discussed. The last section concentrates on chemoprevention, where the different strategies that have been undertaken to interfere with polyamine metabolism and function for antiproliferative intervention are outlined and discussed.

摘要

本章概述了多胺途径如何被用作治疗和预防多种癌症的靶点,因为该途径在所有癌症中均被破坏。它分为三个主要部分。第一部分探讨了多胺途径如何成为化疗靶点,从首个靶向药物二氟甲基鸟氨酸(DFMO)到多年来合成并测试的各种多胺类似物,以及它们所有的潜力和缺陷。第二部分重点介绍了多胺作为药物递送载体的应用。鉴于多胺转运系统在癌症中上调,且多胺天然与DNA结合,人们已合成了一系列多胺类似物和多胺样结构来靶向表观遗传调节因子,取得了令人鼓舞的结果。此外,还讨论了使用多胺作为转运载体,将有毒/生物活性/荧光剂更有选择性地引入癌细胞中的预期靶点。最后一部分集中在化学预防方面,概述并讨论了为干扰多胺代谢和功能以进行抗增殖干预而采取的不同策略。

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