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Zhang Z Lee JC Lin L Olivas V Au V LaFramboise T Abdel-Rahman M Wang X Levine AD Rho JK Choi YJ Choi CM Kim SW Jang SJ Park YS Kim WS Lee DH Lee JS Miller VA Arcila M Ladanyi M Moonsamy P Sawyers C Boggon TJ Ma PC Costa C Taron M Rosell R Halmos B Bivona TG 《Nature genetics》2012,44(8):852-860
Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer. 相似文献
3.
固体颗粒强化泡状沸腾换热机理的研究 总被引:1,自引:0,他引:1
在液体中加入固体颗粒添加剂是强化沸腾换热的一项新技术,本文讨论了加热面附近颗粒-液体-蒸汽三相流动工况,着重分析了处于流化状态的固体颗粒强化沸腾的机理,获得了流化颗粒床泡状沸腾的计算式. 相似文献
4.
蒋良军 《四川师范大学学报(自然科学版)》1994,17(5):32-40
本文考虑一类非线性抛物型方程混合问题的解的爆破性质.通过引入爆破因子,证明了这个问题的解在有限时间的爆破.同时,用凸性方法,进一步研究了解的爆破性质,得到了与前人研究互为补充的结果. 相似文献
5.
研究了1-[(2-吡啶)]偶氮-2-萘酚-磺酸(简称PAN-S)与锰显色反应的最佳条件。在pH9硼砂-HC1介质中,锰与PAN-S形成1:2红色配合物,λmax=535um,ε535=2.66×104L·mol-1·cm-1.0~50μgMn/25mL符合比尔定律。本法可满意地用于测定碳素比色钢、低合金钢和碳素钢。 相似文献
6.
为使OPTO 22控制系统实现控制器热备份,需要解决主控制器与备份控制器之间的连接组织、数据交换、故障识别和自动切换等一系列问题.根据实践提出解决方案,对OPTO22控制系统的热备过程应注意的几个问题提出了解决方法并进行了分析. 相似文献
7.
A number of IDSs have been proposed for a networked or distributed environment. A modified D-IDS using federated peer-to-peer architecture, MCR (Multicast Reflector) and modified shaker protocol were proposed. The suggested scheme can be implemented easily and performs the information sharing between low-level IDS agents. As all users within a group monitor each other's, the common control server can perform detect intrusions with less cost and support the detection of the inside intruders. 相似文献
8.
Patten IS Rana S Shahul S Rowe GC Jang C Liu L Hacker MR Rhee JS Mitchell J Mahmood F Hess P Farrell C Koulisis N Khankin EV Burke SD Tudorache I Bauersachs J del Monte F Hilfiker-Kleiner D Karumanchi SA Arany Z 《Nature》2012,485(7398):333-338
Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. 相似文献
9.
B. C. Yoo S-H. Hong J-L. Ku Y-H. Kim Y-K. Shin S-G. Jang I-J. Kim S-Y. Jeong J-G. Park 《Cellular and molecular life sciences : CMLS》2009,66(2):350-364
Comparative analysis of proteomes using 5-fluorouracil (5-FU)-resistant human colon cancer cell line revealed that decreased
galectin-3 expression was significantly associated with retarded proliferation. However, in the presence of 5-FU proliferation
rate of cells with suppressed galectin-3 expression did not differ from that of cells with normal galectin-3 expression, even
galectin-3 suppression augmented apoptosis. Mechanism by which galectin-3 regulates cancer cell proliferation has been identified
in immunoprecipitates of the anti-galectin-3 antibody. Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) was identified
as a protein interacting with galectin-3. Interestingly, while galectin-3 protein was not affected by the hnRNP Q level, its
suppression was accompanied by a decrease in hnRNP Q expression. The present study demonstrates that galectin-3 stabilizes
hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
B.C.Yoo; S-H.Hong; These two authors contributed equally to this work.
Received 10 September 2008; received after revision 19 October 2008; accepted 07 November 2008 相似文献
10.
研究5-Br-PADN与铁(Ⅲ)的显色反应,在pH9.0~9.4范围内,当有10%SDS存在时,铁(Ⅲ)与5-Br-PADN形成1:4的稳定配合物。λ_(max)为534nm,ε为5.13×10 ̄4L·mol ̄(-1)·cm ̄(-1),铁(Ⅲ)浓度在0~12.5×10 ̄(-4)g/L范围内符合Beer定律,用双峰双波长法测定茶叶中痕量铁(Ⅲ),结果满意。 相似文献