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br Mechanisms of acquired resistance to st and nd
2020-11-06
Mechanisms of acquired resistance to 1st and 2nd generation EGFR inhibitors After treatment with first or second generation EGFR TKIs, virtually all patients after approximately 12 months develop acquired resistance (AR). Different mechanisms of AR to EGFR TKIs have been reported to date and may
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At the therapeutic level the logical approach to address
2020-11-06
At the therapeutic level, the logical approach to address the cooperation between FGFR4 and EGFR was the combined inhibition of both receptors. To explore the potential efficacy and specificity of this approach, we tested the effect of FGFR and EGFR inhibitors in monotherapy or in combination in syn
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The efficacy of A in the ob ob
2020-11-06
The efficacy of A-922500 in the ob/ob mouse model is of particular interest for two reasons. One of the most striking features of the DGAT-1 deficient mouse phenotype is the resistance to diet-induced obesity (Smith et al., 2000). However, HQNO of DGAT-1 in leptin deficient ob/ob mice failed to pro
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This work was supported by
2020-11-06
This work was supported by grants from the Institute of Cancer Research (ICR) and Biotechnology and Biological Sciences Research Council (BB/I014276/1 and BB/M013782/1). Main Text In 2006, Warburg et al. described an apparently distinct connective-tissue disorder characterized by blepharophimosi
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Preparation of the pyridyl ether analogs was
2020-11-05
Preparation of the 2-pyridyl ether analogs (–) was accomplished by alkylation of alcohol with 2-bromopyridines in the presence of NaH to afford the desired pyridyl ether analogs in low to moderate yield. Preparation of the 3-pyridyl analog was carried out by conversion of alcohol to the tosylate,
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The aim of the present study was
2020-11-05
The aim of the present study was to investigate the acute effects of THC on resting state Hydroxyurea neurophysiology, and to examine the impact of COMT genotype on these effects. Thirty-nine healthy volunteers participated in a randomised, placebo-controlled, crossover pharmacological MRI study. A
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Introduction Ewing sarcomas primitive neuroectodermal tumors
2020-11-05
Introduction Ewing sarcomas/primitive neuroectodermal tumors (ES/PNETs) are relatively infrequent but the second most common sarcoma of the bone next to osteosarcoma. Nearly 80% of them occur in persons younger than 20years. Most of them arise from the bone, but 10 to 20% of them from soft tissue.
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Herein we designed a strategy utilizing the target protectio
2020-11-05
Herein, we designed a strategy utilizing the target-protection method to produce a signal in a system involving fluorescence CuNPs stabilized by dumbbell template DNA (DT DNA) through a locked circle consisting of two poly T loops and a poly (ATTA) stem. In the presence of MTase, DT DNA was modified
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Ligand binding RTK activation induces
2020-11-05
Ligand binding (RTK activation) induces the endocytic internalization of RTKs, and this has been demonstrated for CSF-1R [15], [16], [17]. Endocytosed RTKs are targeted to the lysosome, which we and others have established to be dependent on ubiquitination via CBL-family and recognition by ESCRT com
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Cubic equations of state CEoS
2020-11-05
Cubic equations of state (CEoS) are particularly popular due to their simplicity and relatively good accuracy in predicting vapour-liquid equilibrium and liquid-liquid equilibrium for small, non-polar, non-associating molecules, such as light hydrocarbons. CEoS can match the phase boundaries (L/LL a
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Introduction Progesterone also known as
2020-11-05
Introduction Progesterone, also known as P4, is a steroid hormone acting as a key component in the complex regulation of female reproductive function. P4 plays major physiological roles in the uterus and ovary by releasing mature oocytes helping in implantation and maintenance of pregnancy, as wel
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EPAC induces SOCS gene expression in VECs resulting in
2020-11-05
EPAC1 induces SOCS3 gene expression in VECs, resulting in suppression of the JAK–STAT activation initiated by the sIL-6Rα/IL-6 trans-signalling complex [67]. EPAC1 regulates SOCS3 gene induction through the activation of C/EBP and c-Jun transcription factors, which interact directly with the SOCS3 p
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GW3965 br TRIM TIF A RNF TRIM contains a RING both
2020-11-04
TRIM24 (TIF1A, RNF82) TRIM24 contains a RING-both B-boxes-coiled coil conserved structure at the N-terminus with bromo and PHD domains prior to C-terminal end (Fig. 3). This transcriptional intermediary factor is well studied in the context of transcriptional activation of nuclear receptor via ac
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Present malarial chemotherapies mainly rely on a very
2020-11-04
Present malarial chemotherapies mainly rely on a very few chemotypes or their allied structures such as quinolines, anti-folates and some cyclic endo-peroxides (Nayyar et al., 2012). Over the last few decades, the extensive and repetitive deployment of these drugs has stimulated resistance in the pa
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kinesin inhibitor This structure guided the variation of the
2020-11-04
This structure guided the variation of the compounds aiming either at enhanced interaction with CK1 or to exclude interaction with CK1 (R=Me, 15). We chose the 5-cloro substituted oxoindole as backbone as it is supposed to show enhanced metabolic stability, which is commonly used in medicinal chemis
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