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您的检索式：作者名="Thorsten Berg"
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| 1 | MCC1019,a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel,potent anticancer candidate显示文摘Polo-like kinase(PLK1) has been identified as a potential target for cancer treatment.Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain(PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethylbenzofuran-2-carboxylic acid ethyl ester(designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis.This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest—a phenomenon known as mitotic catastrophe, which is followed by immediate cell death via apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in vivo in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate. | Sara Abdelfatah Angela Berg Qi Huang Li Jun Yang Sami Hamdoun Anette Klinger Henry J.Greten Edmond Fleischer Thorsten Berg Vincent K.W.Wong Thomas Efferth | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 1 |
| 2 | Type A Botulinum Toxin for the Treatment of Hypertrophy of the Masseter and Temporal Muscles: An Alternative Treatment显示文摘 | Jens J. von Lindern Bernd Niederhagen Thorsten Appel Stefan Bergé Rudolf H. Reich | 2001 | Plastic and Reconstructive Surgery2001，，2： | 1 |
| 3 | 入院前开始使用替罗非班对拟行直接血管成形术的ST段抬高型心肌梗死患者的疗效(On-TIME2):一项多中心、双盲、随机对照试验显示文摘背景对于急性ST段抬高型心肌梗死(STEMI)患者来说,抗血小板治疗的最大有效程度和时间选择很重要。本研究探讨在救护车或转诊中心接诊患者的第一时间,及早使用糖蛋白Ⅱb/Ⅱa受体拮抗剂替罗非班是否能改善直接冠状动咏成形术(PCI)的效果.
方法该项双盲、随机、安慰剂对照试验在荷兰、德国和比利时的24个中心进行.从2006年6月29日至2007年11月13日期间,拟行PCI的984例4STEMI患者,按随机原则分组,一组接受大剂量替罗非班弹丸式注射(n=491),另一组接受安慰剂处理(n=493):两组患者都给予500mg阿司匹林、5000U肝素和600mg氯吡格雷,将研究药物置于密封箱内,4个一组,进行随机化,研究的主要终点是PCI后1h残留ST段偏移度:采用意向性治疗分析.本试验已注册,注册号ISRCTN06195297。
结果院前在救护车上诊断为心肌梗死后,936例患者(95%)随机接受了治疗:从患者症状发作到确诊为心肌梗死所花费的中位时间为76min(IQR35~150):与接受安慰剂的患者比较,早期大剂量使用替罗非班进行预处理的患者残留ST段偏移差值的平均值,在PCI前[10.9mm(S=9.2)vs12.1mm(5=9.4);P=0.0281和PCI后1h[3.6mm(s=4.6)vs4.8mm(s=613);P=0.003]均明显低于安慰剂组:两组之间主要出血事件的发生率没有明显差别[19例(4%)vs14例(3%);P=0.36]。
结论本研究表明,常规院前开始使用大剂量替罗非班,能够改善PCI后ST段偏移度和临床结局,特别是对于接受PCI的STEMI患者,除了应用大剂量氯吡格雷外还应进一步使用血小板聚集抑制剂。 | Arnoud W J van't Hal Jurrien ten Berg Ton Heestermans Thorsten Dill Reinhard C Funck Wouter van Werkum Jan-Henk E Dambrink Harry Suryapranata Gert van Houwelingen Jan Paul Ottervanger Pieter Stella Evangelos Giannitsis Christian Harem 张润峰(译) 李霞(校) | 2009 | 世界临床医学2009，3，1： | 0 |
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