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舒林酸衍生物K-80003与MEK抑制剂考比替尼联合用药对乳腺癌的效果研究 被引量:8
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作者 李宗熹 种姝伊 +3 位作者 古丽米然.阿里同别克 连宝环 蒋福全 张晓坤 《中国药理学通报》 CAS CSCD 北大核心 2019年第2期251-254,共4页
目的舒林酸衍生物K-80003是全球首个以类维甲酸受体的截断形式(该文简称tRXRα)为靶点的原创候选新药。本课题组前期研究发现,K-80003在抑制乳腺癌的同时,在乳腺癌细胞中可以激活p-ERK,因此该文试图将K-80003与已上市的MEK抑制剂考比替... 目的舒林酸衍生物K-80003是全球首个以类维甲酸受体的截断形式(该文简称tRXRα)为靶点的原创候选新药。本课题组前期研究发现,K-80003在抑制乳腺癌的同时,在乳腺癌细胞中可以激活p-ERK,因此该文试图将K-80003与已上市的MEK抑制剂考比替尼(cobimetinib,GDC-0973)联合使用,探究其对乳腺癌的抑制效果是否增强。方法采用Western blot法、MMTV-PyMT乳腺癌转基因小鼠模型、免疫组化染色等方法,检测K-80003与GDC-0973联合用药对乳腺癌细胞内ERK信号通路及肿瘤细胞凋亡水平的影响。结果 K-80003与GDC-0973联合使用可以更好地抑制p-ERK,并促进PARP切割,导致乳腺癌细胞凋亡,K-80003与GDC-0973联合使用相比于K-80003单药使用,对肿瘤细胞增殖的抑制作用有明显统计学意义。结论舒林酸衍生物K-80003与MEK抑制剂GDC-0973联合使用呈现一定的协同促进乳腺癌细胞凋亡作用。 展开更多
关键词 乳腺癌 舒林酸衍生物 P-ERK 信号通路 考比替尼 联合用药
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上市MEK抑制剂Ⅰ期临床试验数据总结
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作者 郭玉莹 田红旗 《中国医药导报》 CAS 2021年第20期193-196,共4页
丝裂原活化的细胞外信号调节激酶(MEK)是选择性磷酸化靶蛋白丝氨酸/苏氨酸和酪氨酸残基的双特异性蛋白激酶,抑制其活性可以阻止细胞增殖和诱导细胞凋亡,故MEK已经成为一个关键的抗癌靶点。抗肿瘤新药Ⅰ期临床试验风险大、致死率高,也是... 丝裂原活化的细胞外信号调节激酶(MEK)是选择性磷酸化靶蛋白丝氨酸/苏氨酸和酪氨酸残基的双特异性蛋白激酶,抑制其活性可以阻止细胞增殖和诱导细胞凋亡,故MEK已经成为一个关键的抗癌靶点。抗肿瘤新药Ⅰ期临床试验风险大、致死率高,也是影响药物上市的关键因素之一。目前已有4个MEK抑制剂已被美国食品药品监督管理局(FDA)批准用于癌症治疗,分别为曲美替尼,考比替尼,比美替尼和司美替尼。本文通过对其Ⅰ期临床试验的重要数据进行总结,希望能够对即将开展Ⅰ期临床试验或正在开展临床试验的其他MEK抑制剂提供一些借鉴。 展开更多
关键词 丝裂原活化的细胞外信号调节激酶抑制剂 Ⅰ期临床试验 曲美替尼 考比替尼 比美替尼 司美替尼
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在发挥政治工作功能作用中加快推进转变
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作者 宋涛 《政工学刊》 2012年第6期16-17,共2页
胡主席在十一届全国人大五次会议解放军代表团全体会议上强调,全军要坚持以推动国防和军队建设科学发展为主题、以加快转变战斗力生成模式为主线,不断增强履行新世纪新阶段我军历史使命的能力。这一重要论述,既给部队建设指明了方向、... 胡主席在十一届全国人大五次会议解放军代表团全体会议上强调,全军要坚持以推动国防和军队建设科学发展为主题、以加快转变战斗力生成模式为主线,不断增强履行新世纪新阶段我军历史使命的能力。这一重要论述,既给部队建设指明了方向、提供了遵循,也对部队思想政治建设提出了新的要求、 展开更多
关键词 政治 官兵 战斗力生成模式 军事训练 军事教育训练 主题主线 部队 考比
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Accurate and precise determination of lead isotope composition in selected geochemical reference materials 被引量:2
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作者 Guangliang Wu Jian-Ming Zhu +3 位作者 Decan Tan Guilin Han Lixing Zhang Kun Ren 《Acta Geochimica》 EI CAS CSCD 2017年第3期421-425,共5页
Lead(Pb)isotopes have been extensively employed in tracing sources of Pb and its transport pathways through the environment.However,Pb isotopic ratios in related geochemical reference materials are scarce.Here,we repo... Lead(Pb)isotopes have been extensively employed in tracing sources of Pb and its transport pathways through the environment.However,Pb isotopic ratios in related geochemical reference materials are scarce.Here,we report high-precision Pb isotopic ratios measured by Nu Plasma II MC-ICP-MS using calibrated ^(205)Tl/^(203)Tl=2.38865(NIST SRM 997)for mass discrimination correction.The long-term external precision(2SD)for NISTSRM 981 of Pb,BCR-2,and BHVO-2 are 0.31‰(n=105),0.42‰(n=11),and 0.25‰(n=5)for ^(208)Pb/ ^(206)Pb and 0.16‰,0.53‰,and 0.07‰for ^(206)Pb/ ^(207)Pb,both respectively,and their Pb isotopic ratios are in excellent agreement with the recommended values.Using this method,we report for the first time Pb isotopic compositions in shale SGR-1b(USGS);coal CLB-1(USGS);stream sediments GSD-17,-21,and-23(IGGE);soils GSS-12,-13,-14,-15,and-16(IGGE);plants GSV-1,-2,and-3(IGGE);and human hair GSH-1(IGGE). 展开更多
关键词 Lead isotopes Geochemical reference materials MC-ICP-MS
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Establish Albumin-creatinine Ratio Reference Value of Adults in the Rural Area of Hebei Province
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作者 Qiao-jing Liang Wen Huang +1 位作者 Guo-juan Zhang Ning-li Wang 《Chinese Medical Sciences Journal》 CAS CSCD 2016年第1期23-30,共8页
Objective To establish albumin-creatinine ratio (ACR) reference value of the rural population in Hebei province. Methods This study enrolled 5154 participants. By excluding subjects with hypertension, diabetes, dys... Objective To establish albumin-creatinine ratio (ACR) reference value of the rural population in Hebei province. Methods This study enrolled 5154 participants. By excluding subjects with hypertension, diabetes, dyslipidemia, cardiovascular and cerebrovascular diseases, kidney diseases, and overweight condition, as well as those with an estimated glomerular filtration rate (eGFR)(60 ml/(min· 1.73 m^2), apparently healthy subjects (1168) were selected. Urine albumin was measured by using the immunoturbidimetic method, serum creatinine was measured by using Jaffe's kinetic method on a morning spot-urine sample, and ACR was calculated. The 95th percentile of ACR in the healthy subjects was used as the normal upper limit. Results The normal upper limit of ACR was 28.71 mg/g (3.25 mg/retool) for males and 31.85 mg/g (3.60 rag/retool) for females. Based on this ACR reference value, the age-gender standardized prevalence of albuminuria in the rural areas of Hebei province was 12.9%. Conclusion The ACR reference value in the rural of Hebei province is higher than that of the Western population. 展开更多
关键词 albumin-creatinine ratio ALBUMINURIA chronic kidney disease
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Optical Fiber Pressure Sensor with Reference Channel 被引量:2
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作者 YUZhijing TIANWei 《Semiconductor Photonics and Technology》 CAS 1997年第4期311-317,共7页
The principle of optical fiber pressure sensing probe with common diaphragm and the method for stabilizing the laser diodes are described in this paper at first.Then we discussed the improvement in characteristics of ... The principle of optical fiber pressure sensing probe with common diaphragm and the method for stabilizing the laser diodes are described in this paper at first.Then we discussed the improvement in characteristics of the system by means of taking the techniques of reference light channel and ratio measurement. 展开更多
关键词 Accuracy Laser Diodes Ratio Measurement Reference Channel
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Evaluating the Performance of Investment Funds in Turkey
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作者 Hasan Ayaydm 《Journal of Modern Accounting and Auditing》 2013年第10期1392-1407,共16页
It is important to determine the most appropriate levels of risk and return for small investors. For that purpose, the investment funds are very important tools to create a portfolio for small investors, to deploy the... It is important to determine the most appropriate levels of risk and return for small investors. For that purpose, the investment funds are very important tools to create a portfolio for small investors, to deploy the potential risks in optimal proportions, and to direct investors. In this study, the performance of 83 pieces of investment funds will be evaluated which are treated in Turkey dates from January 1, 2010 to December 31, 2012 with performance evaluation methods such as Sharpe, Modigliani (M2) that is based on the standard deviation, and Treynor, T2, Jensen that is based on systematic risk (beta), and the highest and lowest performance investment funds will be presented. The aim of the study is to examine the success of the investment fund managers whether they could estimate the course of the market well or not regarding time period. The empirical results show that the investors who invest on the funds that have negative risk premium by investing in the investment funds getting under the risk cannot get more excess return than getting the return from the risk-free interest rate as treasury bills. The result implies that it could be said that the systematic and total risks of all investment funds are low and they are not sensitive to the developments in the market, and thus, regarding funds could be called as conservative funds. 展开更多
关键词 investment funds Sharpe ratio Treynor Jensen Modigliani (M2) BETA performance evaluation
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Filling Out Macbeth's Appraisal Form: A Deconstructive Re-reading of Shakespeare's Macbeth Through Management Studies
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作者 Aparajita Hazra 《Journalism and Mass Communication》 2014年第6期394-404,共11页
Macbeth was wary when he heard the witches out. He deliberated. He dithered. And Lady Macbeth puckered his courage up to the hilt and egged him on to murder. Macbeth murdered. Then he balked. He hallucinated himself o... Macbeth was wary when he heard the witches out. He deliberated. He dithered. And Lady Macbeth puckered his courage up to the hilt and egged him on to murder. Macbeth murdered. Then he balked. He hallucinated himself out of his wits. Then he went on a rampage to save his own skin. He destroyed in fear of being destroyed. Yet all he ended up doing is losing his peace, his composure, his wife, and finally, his life. The whole of Operation Kingship, if the author may so call the whole business of eliminating Duncan out of the way of the royal throne, failed miserably. Macbeth, on the lookout for power found himself terribly, fearfully beaten, crestfallen, devastated. The million-dollar question then is -what is it that went so very wrong in the whole process? Critics are often heard to cry his ambition--his "overvaulting ambition" down as his incorrigible hamartia. But living in the 21st century, one gets to hear that ambition is not bad after all--the higher the "ambi-horse" vaults, the higher the chances of success is. In this dissertation, the author proposes to analyze Macbeth's case from the perspective of management studies. This paper, more than setting forth a literary statement of Macbeth's predicament, aims at what management Gurus would love to call a candid SWOT (strength, weakness, opportunity, threat) and STEEPLED (social, technological, economic, educational, political, legal, environmental, and demographic factors) analysis of Macbeth's situation to find out where the shoe pinched, whether the whole project crashed because of inefficient leadership, or whether there was no leadership at all, whether organizational strategies were not properly formulated or whether the implementation capsized horribly, thereby making the whole business a rudderless wild goose chase. The discussion necessarily follows up with an insight into what Macbeth lacked as far as Maslow's Pyramid of Needs is concerned and what it could have been like, had it been rewritten with a corporate-friendly, management-savvy 21st century protagonist armed with well formulated action plans and stronger inter-personal skills, in the titular lead. 展开更多
关键词 Operation Kingship SWOT analysis STEEPLED analysis hamartia Maslow's pyramid of needs leadership
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已上市MEK抑制剂合成路线综述 被引量:1
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作者 李瑞鹏 赵建宏 +2 位作者 夏广新 谢建树 邓卫平 《中国医药工业杂志》 CAS CSCD 北大核心 2021年第10期1278-1290,共13页
丝裂原活化的细胞外信号调节激酶(MEK)抑制剂是重要的抗肿瘤药物,目前已上市4个产品,分别是曲美替尼、考比替尼、司美替尼和比美替尼。本文简要介绍了这4种药物,并对已报道的合成路线进行综述。
关键词 抗肿瘤药 丝裂原活化的细胞外信号调节激酶(MEK) 抑制剂 曲美替尼 考比替尼 司美替尼 比美替尼 合成
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