微信扫码关注“小狗文献”

即刻体验更多权益

文献多,下载快,翻译准

首页 > 医学词汇大全 > Histone deacetylase
Histone deacetylase

肿瘤

关键词肿瘤 临床研究术语 蛋白酶

词汇介绍

拓展阅读

解析

Histone   英 /'hɪstəʊn/   美 /'hɪston/

释    义   n. [生化] 组蛋白

例    句   The changes of epigenetics such as DNA methylation and histone modification can regulate the expression of genes and play an important role in the development of tumors. 表观遗传学改变,如DNA甲基化和组蛋白修饰改变可以调控基因的表达,在肿瘤的发生和发展中可能起关键作用。

 

Deacetylase

释    义   n. 脱乙酰酶;去乙酰酶

例    句   Indeed, HDAC6 deacetylates various substrates including α-tubulin and HSP90α, and is involved in protein trafficking and degradation, cell shape and migration. 事实上,HDAC6可以α-微管蛋白和HSP90α进行去乙酰化,与蛋白质转运、降解、细胞形状和迁移都有关系。

概述

组蛋白去乙酰化酶(HDAC)是一类蛋白酶,对染色体的结构修饰和基因表达调控发挥着重要的作用。一般情况下,组蛋白的乙酰化有利于DNA与组蛋白把具体的解离,核小体结构松弛,从而使各种转录因子和协同转录因子能与DNA结合位点特异性结合,激活基因的转录。在细胞核内,组蛋白乙酰化与去乙酰化过程处于动态平衡,并由组蛋白乙酰化转移酶和组蛋白去乙酰化酶共同调控。组蛋白乙酰化转移酶将乙酰辅酶A的乙酰基转移到组蛋白氨基末端特定的赖氨酸残基上,HDAC使组蛋白去乙酰化,与带负电荷的DNA紧密结合,染色质致密卷曲,

Selective Inhibition of Histone Deacetylases 1/2/6 in Combination with Gemcitabine: A Promising Combination for Pancreatic Cancer Therapy复制标题

选择性抑制组蛋白去乙酰化酶1/2/6联合吉西他滨: 胰腺癌治疗的一个有希望的组合

发表时间:2019-09-07

影响因子:6.2

作者: Richard S. Laschanzky

期刊:Cancers (Basel)

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of <10% due in part to a lack of effective therapies. Pan-histone deacetylase (HDAC) inhibitors have shown preclinical efficacy against PDAC but have failed in the clinic due to toxicity. Selective HDAC inhibitors may reduce toxicity while retaining therapeutic efficacy. However, their use requires identification of the specific HDACs that mediate the therapeutic effects of HDAC inhibitors in PDAC. We determined that the HDAC1/2/3 inhibitor Mocetinostat synergizes with the HDAC4/5/6 inhibitor LMK-235 in a panel of PDAC cell lines. Furthermore, while neither drug alone synergizes with gemcitabine, the combination of Mocetinostat, LMK-235, and gemcitabine showed strong synergy. Using small interfering (si)RNA-mediated knockdown, this synergy was attributed to inhibition of HDACs 1, 2, and 6. Pharmacological inhibition of HDACs 1 and 2 with Romidepsin and HDAC6 with ACY-1215 also potently synergized with gemcitabine in a panel of PDAC cell lines, and this drug combination potentiated the antitumor effects of gemcitabine against PDAC xenografts in vivo. Collectively, our data show that inhibition of multiple HDACs is required for therapeutic effects of HDAC inhibitors and support the development of novel strategies to inhibit HDACs 1, 2, and 6 for PDAC therapy.

译文

胰腺导管腺癌(PDAC)五年生存率<10%,部分原因是缺乏有效的治疗。Pan histone deacetylase(HDAC)抑制剂对PDAC具有临床前疗效,但由于毒性而在临床上失败。选择性HDAC抑制剂可以减少毒性,同时保留治疗效果。然而,它们的使用需要鉴定介导HDAC抑制剂在PDAC中的治疗作用的特定HDAC。我们测定了HDAC1/2/3抑制剂莫西汀与HDAC4/5/6抑制剂LMK-235在PDAC细胞系中的协同作用。此外,虽然两种药物都不能单独与吉西他滨协同作用,但莫西他汀、LMK-235和吉西他滨的联合应用显示出很强的协同作用。使用小干扰(si)RNA介导的敲除,这种协同作用归因于HDACs 1、2和6的抑制。吉西他滨对PDAC细胞株HDACs 1、HDAC6和ACY-1215的抑制作用也增强了吉西他滨对PDAC异种移植瘤的抑制作用。总之,我们的数据表明,抑制多个HDAC是HDAC抑制剂治疗效果所必需的,并支持开发新的策略来抑制PDAC治疗的HDACs 1、2和6。