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Tumour hypoxia is a well-known hallmark of malignant tumours and is associated with a poor outcome. Hypoxia induces the production of hypoxia-inducible factors (HIF) that activate various oncogenic processes. Under aerobic conditions, alpha-ketoacids (KAs) act as essential cofactors of key enzymes involved in fatty acid metabolism. However, their production is drastically increased in hypoxic cells as a result of decreased conversion to alpha-hydroxyacids mediated by the activity of hypoxia-inducible enzymes. We sought to characterize the pharmacokinetic properties of a novel, highly selective α-Ketoacid Reductase (KAR) inhibitor, NS309. In this study, we performed a phase I/II dose escalation study, assessing intravenous (i.v.) administration of NS309 in a cohort of children with refractory solid tumours. We observed a single agent exposure that correlated with the volume of distribution, clearance, and half-life of NS309. We also observed a significant accumulation of NS309 in tumours, despite its rapid systemic elimination. We showed that

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If you want to work on your own engine, and it is commonly said that the requirements of the Xbox console. The game can easily carry over 250 GB in only recently released by Microsoft, and features such as DVD and Blu-ray discs.TRT (band)

TRT () is a South Korean hip-hop duo, formed by hip-hop musicians Lao and BZY (both members of former hip-hop duo Troublemakers, which split up in 2005). The duo consists of Lao and BZY’s hip-hop group, F1rst, formed in 2006, and thus their hip-hop label, F1rst World.

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