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排序方式: 共有307条查询结果,搜索用时 78 毫秒
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Zeynep Eroglu Sheri L. Holmen Qing Chen Nikhil I. Khushalani Ravi Amaravadi Reena Thomas Kamran A. Ahmed Hussein Tawbi Sunandana Chandra Joseph Markowitz Inna Smalley James K. C. Liu Yian Ann Chen Yana G. Najjar Florian A. Karreth Daniel Abate‐Daga Isabella C. Glitza Jeffrey A. Sosman Vernon K. Sondak Marcus Bosenberg Meenhard Herlyn Michael B. Atkins Harriet Kluger Kim Margolin Peter A. Forsyth Michael A. Davies Keiran S. M. Smalley 《Pigment cell & melanoma research》2019,32(3):458-469
In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area. 相似文献
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Stephen W. Jarantow Barbara S. Bushey Jose R. Pardinas Ken Boakye Eilyn R. Lacy Renouard Sanders Manuel A. Sepulveda Sheri L. Moores Mark L. Chiu 《The Journal of biological chemistry》2015,290(41):24689-24704
The efficacy of engaging multiple drug targets using bispecific antibodies (BsAbs) is affected by the relative cell-surface protein levels of the respective targets. In this work, the receptor density values were correlated to the in vitro activity of a BsAb (JNJ-61186372) targeting epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET). Simultaneous binding of the BsAb to both receptors was confirmed in vitro. By using controlled Fab-arm exchange, a set of BsAbs targeting EGFR and c-MET was generated to establish an accurate receptor quantitation of a panel of lung and gastric cancer cell lines expressing heterogeneous levels of EGFR and c-MET. EGFR and c-MET receptor density levels were correlated to the respective gene expression levels as well as to the respective receptor phosphorylation inhibition values. We observed a bias in BsAb binding toward the more highly expressed of the two receptors, EGFR or c-MET, which resulted in the enhanced in vitro potency of JNJ-61186372 against the less highly expressed target. On the basis of these observations, we propose an avidity model of how JNJ-61186372 engages EGFR and c-MET with potentially broad implications for bispecific drug efficacy and design. 相似文献
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Scott E. Wolkenberg Zhijian Zhao David D. Wisnoski William H. Leister Julie O’Brien Wei Lemaire David L. Williams Marlene A. Jacobson Cyrille Sur Gene G. Kinney Doug J. Pettibone Philip R. Tiller Sheri Smith Christopher Gibson Bennett K. Ma Stacey L. Polsky-Fisher Craig W. Lindsley George D. Hartman 《Bioorganic & medicinal chemistry letters》2009,19(5):1492-1495
Glycine transporter 1 (GlyT1) represents a novel target for the treatment of schizophrenia via the potentiation of glutamatergic NMDA receptors. The discovery of 4,4-disubstituted piperidine inhibitors of GlyT1 which exhibit improved pharmacokinetic properties, including oral bioavailability, is discussed. 相似文献
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Matthew W. VanBrocklin James P. Robinson Todd Whitwam Adam R. Guilbeault Julie Koeman Pamela J. Swiatek George F. Vande Woude Joseph D. Khoury Sheri L. Holmen 《Pigment cell & melanoma research》2009,22(4):454-460
While many genetic alterations have been identified in melanoma, the relevant molecular events that contribute to disease progression are poorly understood. Most primary human melanomas exhibit loss of expression of the CDKN2A locus in addition to activation of the canonical mitogen‐activated protein kinase signaling pathway. In this study, we used a Cdkn2a‐deficient mouse melanocyte cell line to screen for secondary genetic events in melanoma tumor progression. Upon investigation, intrachromosomal gene amplification of Met, a receptor tyrosine kinase implicated in melanoma progression, was identified in Cdkn2a‐deficient tumors. RNA interference targeting Met in these tumor cells resulted in a significant delay in tumor growth in vivo compared with the control cells. MET expression is rarely detected in primary human melanoma but is frequently observed in metastatic disease. This study validates a role for Met activation in melanoma tumor progression in the context of Cdkn2a deficiency. 相似文献
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N Peter Reeves Jacek Cholewicki Sheri P Silfies 《Journal of electromyography and kinesiology》2006,16(3):264-272
There are conflicting findings in the literature regarding erector spinae activation imbalance in people with low-back pain (LBP). Some studies have found asymmetric recruitment between muscle pairs in people with LBP, whilst other studies have not; some reported people with LBP recruit more lumbar muscles whilst other have reported greater thoracic activity. Using 242 varsity athletes, EMG activity of thoracic and lumbar erector spinae pairs was recorded during an isometric trunk extension. Activation imbalance among muscle pairs and levels was compared between athletes with and without a history of low-back injury (HxLBI). There were no group differences in the imbalance between sides, but the HxLBI group had greater activation imbalance between lumbar and thoracic levels than the No HxLBI group. Activation imbalance between levels was similar for individuals with No HxLBI and those who sustained first time injury suggesting that imbalance does not cause LBI. There was no difference between the athletes with single and multiple episode LBI, nor between short and long symptom duration suggesting that the presence of imbalance is not an impairment. Interestingly, activation imbalance occurred in both directions, meaning more thoracic activity for some, and more lumbar activity for others, which might be a functional adaptation related to pathology. 相似文献
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Willem F. Wolkers Sheri A. Looper Ariane E. McKiernan Nelly M. Tsvetkova Fern Tablin John H. Crowe 《Molecular membrane biology》2013,30(3):201-210
Membrane properties and the overall protein secondary structure of freeze-dried trehalose-loaded mouse platelets were studied using steady state fluorescence anisotropy and Fourier transform infrared spectroscopy (FTIR). FTIR results showed that fresh control mouse platelets have a main phase transition at ~14°C, whereas, freeze-dried platelets exhibited a main phase transition ~12°C. However, the cooperativity of the transition of the rehydrated platelets was greatly enhanced compared to that of control platelets. Anisotropy experiments performed with 1,6 diphenyl-1,3,5 hexatriene (DPH) complemented FTIR results and showed that the lipid order in the core of the membrane was affected by freeze-drying procedures. Similar experiments with trimethyl ammonium 1,6 diphenyl-1,3,5 hexatriene (TMA-DPH), a membrane surface probe, indicated that membrane properties at the membrane/water interface were less affected by freeze-drying procedures than the core of the membrane. Lyophilization did not result in massive protein denaturation, but the overall protein secondary structure was altered, based on in situ assessment of the amide-I and amide-II band profiles. Lyophilization-induced changes to endogenous platelet proteins were further investigated by studying the protein's heat stability. In fresh control platelets, proteins denatured at 42°C, whereas proteins in the rehydrated platelets denatured at 48°C. 相似文献