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Nevertheless because of the preclinical work and the
2020-01-29
Nevertheless, because of the preclinical work and the interference with EWS–FLI1 transcriptional activity, we believe that there may be a role for ET-743 in Ewing sarcoma. An analysis of the pharmacokinetic data published in the phase II clinical trial shows that at most the drug spent 5 to 6days o
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Eptifibatide In a study performed simultaneously by
2020-01-29
In a study performed simultaneously by another group, EWS-FLI-1 introduction into unsorted murine bone marrow-derived Eptifibatide resulted in tumors with various phenotypes including one that is consistent with that of Ewing sarcoma [68]. The tumors expressed markers associated with Ewing sarcoma a
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In our former work our interest was in
2020-01-29
In our former work, our interest was in discovery of novel VEGFR-2 inhibitors as anti-angiogenesis agents. Along this line, with natural alkaloid taspine as the lead compound, rounds of structure optimization were performed to develop novel VEGFR-2 inhibitors [[13], [14], [15]]. Among them, BPS-7, b
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After activation AKT phosphorylates target proteins involved
2020-01-29
After activation, AKT phosphorylates target proteins involved in cell growth, metabolism and survival (Manning and Cantley, 2007). For example, AKT phosphorylates the pro-apoptotic protein BAD, preventing it from binding to and inactivating Bcl-xL in mitochondria (Datta et al., 1997). In turn, Bcl-x
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PKA signalling in the nucleus was thought
2020-01-29
PKA signalling in the nucleus was thought to be due to the translocation of the catalytic subunit upon activation from the GDC-0152 to the nucleus via diffusion [72]. However, a new understanding has emerged, as both the regulatory and catalytic subunits have been identified in the nucleus and func
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Studies using SERPINB deficient mice established
2020-01-29
Studies using SERPINB1-deficient mice established the significant role for SERPINB1 in protecting lung antimicrobial proteins from proteolysis during microbe infection and its regulatory role in sustaining the balance of neutrophil reserve [15]. Neutrophil serine proteases (NSPs) (elastase, cathepsi
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Results from experiments in model
2020-01-29
Results from experiments in model systems have suggested that the DPRs translated from the HRE of C9ORF72 are toxic and play a role in disease pathogenesis (reviewed in Taylor et al. (2016)). Although the DPRs are present in neurons and glia in various regions of the central nervous system (CNS) ear
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br Introduction Coping with DNA
2020-01-29
Introduction Coping with DNA damage is possible thanks to surveillance mechanisms (checkpoints), that detect the problem and promote its solution [1], [2], and to repair and tolerance pathways that remove the lesions or reduce the damage consequences [3], [4]. Failures in these processes have a h
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Dexamethasone DEX a potent synthetic glucocorticoid drug is
2020-01-25
Dexamethasone (DEX), a potent synthetic glucocorticoid drug, is effective for treatment of a range of inflammatory and autoimmune conditions as well as the reduction of side effects associated with chemotherapy. On the Czech Republic pharmaceutical market, DEX is incorporated into eighteen drugs use
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However recent studies revealed that the function of Crm mig
2020-01-25
However, recent studies revealed that the function of Crm1 might not only limit to nucleocytoplasmic transport, but also be involved in regulation of centrosome duplication. As the major microtubule organizing centers in animal cells, centrosomes play a significant role in cell cycle, spindle format
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Carbamate and OP insecticides are still among the most
2020-01-25
Carbamate and OP insecticides are still among the most widely used pesticides in the world [151]. In 2012, the OP insecticides chlorpyrifos and acephate were ranked 14th and 22nd overall in estimated amounts of agricultural pesticides used in the US. The carbamate insecticide carbaryl and the OP ins
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Therapeutic options targeting intrahepatic resistance are ve
2020-01-25
Therapeutic options targeting intrahepatic resistance are very limited. Theoretically, the NO-cGMP pathway may be influenced at several sites. Yet, most strategies did not reach clinical practice or yielded disappointing results, such as activators of soluble guanylate cyclase [14], NO releasing der
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br Materials and Methods br Results br Discussion Viral
2020-01-25
Materials and Methods Results Discussion Viral infection of eukaryotic DL-Menthol mg activate signaling pathways both via specific interaction with pattern recognition receptors (TLRs, RIG-I, MDA5) and more nonspecific mechanisms such as accumulation of newly synthesized viral glycoprotein
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Deregulated Wnt signaling either due to
2020-01-25
Deregulated Wnt signaling, either due to pathway mutations or otherwise aberrant pathway activity, is common in CLL [81], [82]. In addition to targets described above, alvocidib also inhibits glycogen synthase kinase 3 (GSK3)-β at higher nanomolar concentrations [37]. Despite intuition and experimen
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Mdivi 1 receptor However one major challenge will be
2020-01-25
However, one major challenge will be to understand how the diverse actions of D2Rs in multipartite, dopamine-sensitive circuits are coordinated to produce specific behaviors across species. It is possible that emerging techniques for imaging neuronal activity in different neuronal population in beha
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