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首页 > 医学词汇大全 > bruton tyrosine kinase
bruton tyrosine kinase

肿瘤

关键词肿瘤 临床研究术语 慢性淋巴细胞性白血病

词汇介绍

拓展阅读

解析

Bruton

释    义   n. (Bruton)人名;(英)布鲁顿;(法)布吕东

例    句   That year, I was giving the traditional Irish greeting, cad mle filte, a hundred thousand welcomes, to a new Irish prime minister, John Bruton, who was continuing the peace policy of his predecessor. 那一年,我给新任爱尔兰首相约翰.布鲁顿发出了“十万声欢迎”的爱尔兰传统祝福语,他正继续执行着前任的和平政策。

 

Tyrosine   英 /'taɪrəsiːn/   美 /'taɪrəsɪn/

释    义   n. [生化] 酪氨酸

例    句   Experts can not eat anything for depression, the problem was first set out the tyrosine content of foods and beverages, such as Chen cheese, canned meat, soy sauce, yeast extract, herring and salmon. 专家对于抑郁症不能吃什么这一问题首先罗列出了酪氨酸含量高的食物和饮料,如陈乳酪,罐头肉,酱油,酵母提取物,鲱鱼和鲑鱼等。

 

Kinase   英 /ˈkaɪneɪz/   美 /ˈkɪnneɪz/

释    义   n. [生化] 激酶;致活酶

例    句   However, the involvement of tyrosine kinase either directly or through the prostaglandins and nitric oxide synthase in response to inflammation during diabetes is not completely understood.不过,酪氨酸激酶是直接参与还是通过前列腺素和一氧化氮合酶对糖尿病炎症产生反应的,我们目前还不清楚。

概述

布鲁顿酪氨酸激酶(BTK),即非受体酪氨酸激酶Tec家族的一个成员,是在除了T淋巴细胞和自然杀伤细胞之外的所有造血细胞类型中表达的关键信号酶。BTK在将细胞表面B细胞受体(BCR)刺激连接到下游细胞内应答的B细胞信号途径中发挥至关重要的作用。BTK是B细胞发育、激活、信号传导和存活的关键调节剂;另外,BTK在众多其它造血细胞信号途径中起作用,例如,巨噬细胞中Toll样受体(TLR)和细胞因子受体介导的TNF-α产生,肥大细胞中IgE受体(FceRI)的信号传导,B系淋巴样细胞中Fas/ΑΡ0

Phase 1 study of selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL复制标题

选择性BTK抑制剂zanubrutinib治疗b细胞恶性肿瘤的1期研究及CLL的安全性和疗效评价

发表时间:2019-09-12

影响因子:16.6

作者: Constantine Tam

期刊:Blood

Zanubrutinib is a potent and highly selective inhibitor of Bruton tyrosine kinase (BTK). In this first-in-human, open-label, multicenter, phase 1 study, patients in part 1 (3 + 3 dose escalation) had relapsed/refractory B-cell malignancies and received zanubrutinib 40, 80, 160, or 320 mg once daily or 160 mg twice daily. Part 2 (expansion) consisted of disease-specific cohorts, including treatment-naive or relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The primary end points were safety and tolerability, and definition of the maximum tolerated dose (part 1). Additional end points included pharmacokinetics/pharmacodynamics and preliminary efficacy. Reported herein are results from 144 patients enrolled in the dose-finding and CLL/SLL cohorts. No dose-limiting toxicities occurred in dose escalation. Median BTK occupancy in peripheral blood mononuclear cells was >95% at all doses. Sustained complete (>95%) BTK occupancy in lymph node biopsy specimens was more frequent with 160 mg twice daily than 320 mg once daily (89% vs 50%; P = .0342). Consequently, 160 mg twice daily was selected for further investigation. With median follow-up of 13.7 months (range, 0.4-30.5 months), 89 CLL/SLL patients (94.7%) remain on study. Most toxicities were grade 1/2; neutropenia was the only grade 3/4 toxicity observed in >2 patients.

译文

Zanubrutinib是有效且高度选择性的Bruton酪氨酸激酶(BTK)抑制剂。在这项首次在人类中进行的,开放标签的,多中心的1期研究中,第1部分(3×+ 3剂量递增)的患者出现了复发/难治性B细胞恶性肿瘤,并接受了zanubrutinib 40、80、160或320 mg一次每日一次或每日两次160毫克。第2部分(扩展)由疾病特异性人群组成,包括初治或复发/难治性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(CLL / SLL)。主要终点是安全性和耐受性,以及最大耐受剂量的定义(第1部分)。其他终点包括药代动力学/药效学和初步疗效。本文报道的是来自144名患者的剂量查找和CLL / SLL研究组的结果。在剂量递增中没有发生剂量限制性毒性。在所有剂量下,外周血单核细胞中BTK的中位占有率均> 95%。淋巴结活检标本中持续完整(> 95%)的BTK占用比每天一次320 mg每天两次160 mg更为频繁(89%vs 50%; P = .0342)。因此,每天两次选择160毫克进行进一步研究。中位随访时间为13.7个月(范围0.4-30.5个月),仍有89名CLL / SLL患者(94.7%)仍在研究中。多数毒性为1/2级;中性粒细胞减少症是在> 2名患者中观察到的唯一的3/4级毒性。