Jet interaction in a hypersonic flow: a comparison between plif thermometry and computational simulation

Two-dimensional temperature measurements of the interaction between a sonic H2 jet injected into a hypersonic air-crossflow are compared to Reynolds-Averaged Navier-Stokes (RANS) simulations. The temperature measurements were obtained using the planar laser-induced fluorescence (PLIF) technique on the nitric oxide molecule. The experimental setup consists of a 9◦ compression ramp and a single, 1.6-mmdiameter fuel injector, angled at 81◦ to the crossflow. The RANS simulation shows good general agreement with the ensemble-averaged experimental data, but discrepancies are significant in regions where large-scale vortex structures dominate the unsteady flow

In pursuit of synergy: An investigation of the PI3K/mTOR/MEK co-targeted inhibition strategy in NSCLC

Clinical PI3K inhibition has been somewhat disappointing, due to both inadequate patient stratification and compensatory cell signalling through bypass mechanisms. As such, investigation of PI3K-MEK co-targeted inhibition has been recommended. With high mortality rates and a clear need for new therapeutic intervention strategies, non-small cell lung cancer (NSCLC) is an important setting to investigate the effectiveness of this approach.\ud \ud Here, 174 NSCLC tumours were screened for 150 mutations by Fluidigm technology, with 15 patients being profiled for phosphoprotein expression. The effects of GDC-0941 (a pan PI3K inhibitor), GDC-0980 (a dual PI3K/mTOR inhibitor) and GDC-0973 (a MEK inhibitor) alone and in combination were assessed in 3 NSCLC cell lines.\ud \ud PIK3CA was mutated in 5.17% of NSCLC patients. GDC-0941 and GDC-0980 treatment induced anti-proliferative and pro-apoptotic responses across all NSCLC cell lines, while GDC-0973 treatment induced only anti-proliferative responses. GDC-0980 and GDC-0973 combined treatment led to significant increases in apoptosis and synergistic reductions in proliferation across the panel of cell lines.\ud \ud This study found that the PI3K/MEK co-targeted inhibition strategy is synergistic in all 3 molecular subtypes of NSCLC investigated. Consequently, we would advocate clinical trials for NSCLC patients combining GDC-0980 and GDC-0973, each of which are separately under clinical investigation currently

DC BeadM1™: towards an optimal transcatheter hepatic tumour therapy

© 2015, The Author(s). Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1TM, 70–150 μm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and drug dose delivered. Both unloaded and drug loaded DC BeadM1 were shown to have a greater density of distal volume of penetration although the ultimate distal level of penetration was the same as that of the 100–300 µm beads in an in vitro penetration model. Elution of doxorubicin was slower than irinotecan elution, but it was similar when comparing the same drug elution from 70 to 150 µm compared to 100–300 µm beads. Radiopaque versions of 70–150 and 100–300 µm beads were prepared in order to evaluate distribution ex vivo using µ-CT and doxorubicin distribution using epifluorescent microscopy. Liver distribution of the radiopaque versions of the beads was shown to be more distal and efficient at filling smaller vessels with the DC BeadM1 and correspondingly more beads were found per vessel histologically with a larger area of drug coverage with the smaller size range. This study indicates that the smaller (70–150 μm) beads should permit an increased dose of drug to be administered to both hypervascular and hypovascular tumours as compared to 100–300 µm beads