Reversion Characteristics in an Al-4wt%Cu Alloy

The X-ray diffuse scattering intensity around the 110 reciprocal lattice point was measured in order to determine quantitatively the amount and size of precipitates during ageing and reversion. The precipitated phase was definitely determined by the aids of Laue X-ray photographs and the electron diffraction patterns. The electrical resistivity was carefully measured. When the alloy was aged for 1000 min at 373K, the GP zones precipitated with a mean diameter of 8.0nm. During the reversion, those zones dissolved perfectly above 458K, which is in good agreement with the result of Beton and Rollason. After the perfect dissolution of the GP zones, the Θ′ phase precipitated directly and heterogeneously. By ageing for 4000 min at 408K, the Θ″ phase precipitated with a mean diameter of 12.5 nm. When its aged alloy was reverted, the temperature at which the volume fraction of precipitates becomes minimum, but not zero, was 498K, where the successively precipitated Θ′phase exsisted already

Aldo-keto reductase inhibitors increase the anticancer effects of tyrosine kinase inhibitors in chronic myelogenous leukemia

Tyrosine kinase inhibitors (TKIs) are widely utilized in clinical practice to treat carcinomas, but secondary tumor resistance during chronic treatment can be problematic. AKR1B1 and AKR1B10 of the aldo-keto reductase (AKR) superfamily are highly expressed in cancer cells and are believed to be involved in drug resistance. The aim of this study was to understand how TKI treatment of chronic myelogenous leukemia (CML) cells changes their glucose metabolism and if inhibition of AKRs can sensitize CML cells to TKIs. K562 cells were treated with the TKIs imatinib, nilotinib, or bosutinib, and the effects on glucose metabolism, cell death, glutathione levels, and AKR levels were assessed. To assess glucose dependence, cells were cultured in normal and low-glucose media. Pretreatment with AKR inhibitors, including epalrestat, were used to determine AKR-dependence. Treatment with TKIs increased intracellular glucose, AKR1B1/10 levels, glutathione oxidation, and nuclear translocation of nuclear factor erythroid 2-related factor 2, but with minimal cell death. These effects were dependent on intracellular glucose accumulation. Pretreatment with epalrestat, or a selective inhibitor of AKR1B10, exacerbated TKI-induced cell death, suggesting that especially AKR1B10 was involved in protection against TKIs. Thus, by disrupting cell protective mechanisms, AKR inhibitors may render CML more susceptible to TKI treatments