In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells

INTRODUCTION: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells. METHODS: Human MCF-7 breast cancer cells were treated with up to 100 μM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation. RESULTS: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20 μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis. CONCLUSION: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma

Analysis and Control of Complex Flows in U-Bends using Computational Fluid Dynamics

Analysis and control of flow structure in U-bends are crucial since U-bends are used in many different engineering applications. As a flow parameter in U-bends, the ratio of inertial and centrifugal forces to viscous forces is called as Dean number. The increase of Dean number destabilizes the flow and leads to a three-dimensional flow consisting of stream wise parallel counter-rotating vortices (Dean vortices) stacked along the curved wall. Due to the curvature in U-bends, the flow development involves complex flow structures including Dean vortices and high levels of turbulence that are not seen in straight duct flows. These are quite critical in considering noise problems and structural failure of the ducts. In this work, computational fluid dynamic (CFD) models are developed using ANSYS FLUENT to simulate these complex flows patterns in square sectioned U-bend with a radius of curvature R-c/D=0.65. The predictions of mean velocity profiles on different angular positions of the U-bend are compared against the experimental results available in the literature and previous numerical studies. Performance of six different turbulence models are evaluated, namely: the standard k-epsilon, the k-epsilon Realizable, the k-epsilon RNG, the k-omega) SST, the Reynolds Stress Model (RSM) and the Scale-Adaptive Simulation Model (SAS), to propose the best numerical approach with increasing the accuracy of the solutions while reducing the computation time. Numerical results show remarkable improvements with respect to previous numerical studies and good agreement with the available experimental data. The best turbulence model for this application is proposed considering both the computation time and the result accuracy. In addition, different flow control techniques are still under investigation to eliminate Dean vortices and to reduce turbulence levels in U-bends