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靶向细胞死亡治疗 B 淋巴系恶性肿瘤。

Cell death targeting therapies in B lymphoid malignancies.

机构信息

Hematopathology Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Villarroel 170, Barcelona, Spain.

出版信息

Curr Drug Targets. 2010 Jul;11(7):769-80. doi: 10.2174/138945010791320863.

Abstract

Programmed cell death, commonly associated with the term apoptosis, is an integrated intracellular program that plays a critical role in lymphoid tissue homeostasis. Alterations in this highly regulated process is a common feature of most lymphoid malignancies, thus facilitating tumor escape from traditional chemotherapeutic agents whose main endpoint is the induction of tumor cell death. In the last years, enormous progress has been made in understanding the deregulated signals that could lead to ineffective apoptosis in B lymphoid tumors. Consequently, several new strategies have been designed to modulate the key molecules of life-and-death decisions. Numerous novel approaches are being validated and some of them have progressed to clinical testing or have even been approved in a record time. In this review we will focus on current therapies that have demonstrated to trigger efficiently cell death in B lymphoid neoplasms, either by directly targeting the intracellular apoptotic machinery or by modulating different factors involved in its regulation.

摘要

程序性细胞死亡,通常与细胞凋亡一词相关联,是一种整合的细胞内程序,在淋巴组织稳态中起着关键作用。这个高度调控过程的改变是大多数淋巴恶性肿瘤的共同特征,从而促进肿瘤逃避传统的化疗药物,其主要终点是诱导肿瘤细胞死亡。在过去的几年中,人们在理解导致 B 淋巴细胞肿瘤中无效凋亡的失调信号方面取得了巨大进展。因此,已经设计了几种新的策略来调节生死决策的关键分子。许多新的方法正在被验证,其中一些已经进展到临床测试,甚至在创纪录的时间内获得批准。在这篇综述中,我们将重点介绍目前已经证明能够有效地在 B 淋巴细胞肿瘤中引发细胞死亡的治疗方法,这些方法要么直接靶向细胞内凋亡机制,要么调节其调节中涉及的不同因素。

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