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In contrast irinotecan has shown
2020-12-24
In contrast, irinotecan has shown much less myelosuppression and may be more active in Ewing sarcoma both alone and in combination with temozolamide. One phase II study of 13 heavily pretreated Ewing sarcoma patients demonstrated a response rate of 38% including 2 complete responses (Bisogno et al.,
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Our previous high throughput screening HTS
2020-12-24
Our previous high-throughput screening (HTS) campaign using automated, robust, and sensitive fluorescence based Loratadine assay [10], [11] led to the identification of several EPAC specific inhibitors (ESIs), and was subsequently followed by extensive hit-to-lead optimizations [20], [21], [22], [2
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br Conflict of interest br Acknowledgments This
2020-12-24
Conflict of interest Acknowledgments This work was supported in part by grants from the , Spain (INCITE08PXIB203092PR). VGM was supported by a FPU pre-doctoral scholarship from the , Spain. MLR was supported in part by a crowdfunding campaign (PRECIPITA), coordinated by the Spanish Foundation
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br Results Patient disease and treatment characteristics of
2020-12-24
Results Patient, disease, and treatment characteristics of the study cohort are described in Table 1. All patients were stage IIIA with pathologically documented N2 disease per AJCC 7th edition. EP4 nuclear staining 0–1 versus 2+ was significantly associated with overall survival (OS) (44.3 vs.
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Future advances in the in
2020-12-24
Future advances in the in vivo molecular imaging of enzyme activity will greatly benefit from the progress towards the quantitative detection of enzymes. Quantitative imaging requires knowledge of both the location and concentration of a specific enzyme, which is dependent on the simultaneous measur
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Potential break through technology poised to overcome these
2020-12-24
Potential break-through technology poised to overcome these above-mentioned limitations is that of the “substrate mediated enzyme prodrug therapy”, SMEPT (Fig. 1). Learning from the previously established enzyme prodrug therapies (EPT) and specifically the antibody-directed EPT (ADEPT) [12], develop
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It is noteworthy that little is known as
2020-12-24
It is noteworthy that little is known as to the role of autophagy in regulation of eNOS phosphorylation and eNOS uncoupling. eNOS monomers, but not eNOS dimers could be degraded by ubiquitination [39], harbingering the existence of protein degradation pathways in modulation of eNOS turnover and acti
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A growing body of data indicates that endothelial NOS
2020-12-24
A growing body of data indicates that endothelial NOS (eNOS) is a rate-limiting enzyme for the synthesis of nitric oxide (NO), its downstream enolase molecule. High pathological concentrations of NO produced from inducible NO synthase (iNOS) induce apoptosis, whereas a reduction in the concentration
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The imaging and biochemical data presented here demonstrated
2020-12-24
The imaging and biochemical data presented here demonstrated that in T cells, AEP played a specific function in cleaving Foxp3 but not Tbet. These results are in accordance with previous AEP studies where it has been shown that AEP substrates in part are not amenable to other protease activity. In a
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Because of the important role of the DDB
2020-12-24
Because of the important role of the DDB1-CUL4B interaction for CUL4B-based E3 ligases, disruption of the DDB1-CUL4B interaction could be an effective approach to treat cancer. Therefore, we developed an in vitro HTS assay based on yeast cell growth inhibition to identify compounds that could disrup
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The possibility of harm with DPP inhibitors in patients with
2020-12-23
The possibility of harm with DPP-4 inhibitors in patients with clinically overt heart failure has been recently highlighted by the results of the VIVIDD (Vildagliptin in Ventricular Dysfunction Diabetes) trial (68), the only trial to date that has been designed to evaluate the effects of a DPP-4 inh
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The inhibition of NPY cleavage may also contribute to the
2020-12-23
The inhibition of NPY cleavage may also contribute to the effect of gliptins on blood pressure [123]: NPY is an agonist of Y1 receptor mediating peripheral vasoconstriction. Interestingly, blood pressure in adult SHRs was not affected by single dose administration of a specific DPP-4i whereas blood
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Acknowledgments We acknowledge the Danish Council for
2020-12-23
Acknowledgments We acknowledge the Danish Council for Independent Research (Grant no. 11-105250) and the Carlsberg Foundation (Grant no. 2011-01-0567) for funding this work. Introduction DNA is vital as a biological target to design diagnostic agents as well as therapeutic drugs. The recognitio
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Interest in DGKs increased as it became
2020-12-23
Interest in DGKs increased as it became clear that not only are they important for lipid homeostasis, they serve to modulate the relative levels of diacylglycerol (DAG) and phosphatidic inhibitor price (PtdOH) that play critical roles in a variety of signaling pathways (Eichmann and Lass, 2015; Liu
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ASC was reported as a potent antiviral
2020-12-23
ASC was reported as a potent antiviral and antifungal agent, and its derivatives could modulate a variety of physiological activities, such as anti-tumor, anti-metastatic, and anti-diabetic activities in animals. Mie Tsuruga et al. found that 4-o-methylascochlorin had immunosuppressive activity, but
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