Normal living cells exhibit phosphatidylserine (PS) primarily within the intracellular leaflet of the plasma membrane. In contrast, viable cancer cells have high levels of PS on the external surface, and exhibit a broad range of surface PS, even within specific types of cancer. Agents that target surface PS have recently been developed to treat tumors and are expected to be more effective with higher surface PS levels. In this context, we examined whether surface PS is increased with irradiation. In vitro irradiation of cancer cell lines selected surviving cells that had higher surface PS in a dose- and time-dependent manner. This was more pronounced if surface PS was initially in the lower range for cancer cells. Radiation also increased the surface PS of tumor cells in subcutaneous xenografts in nude mice. We found an inverse relationship between steady state surface PS level of cancer cell lines and their sensitivity to radiation-induced cell death. In addition, serial irradiation, which selected surviving cells with higher surface PS, also increased resistance to radiation and to some chemotherapeutic drugs, suggesting a PS-dependent mechanism for development of resistance to therapy. On the other hand, fractionated radiation enhanced the effect of a novel anti-cancer, PS-targeting drug, SapC-DOPS, in some cancer cell lines. Our data suggest that we can group cancer cells into cells with low surface PS, which are sensitive to radiation, and high surface PS, which are sensitive to SapC-DOPS. Combination of these interventions may provide a potential new combination therapy.

Purpose: The purpose of this study is to determine the detector response function using Monte Carlo simulations of small radiation fields and simulations of detector responses to those fields. The results may be used to deconvolve the effect of finite size detectors on beam broadening in small field measurements. Method and Materials: A Monte Carlo model of a linear accelerator was generated to simulate the characteristics of a clinically used photon beam. These simulations were used to create a true beam profile. Three clinically available radiation detectors and two theoretical detectors were modeled in the beam. Detector specific models of measured beam profiles were generated from simulated detector responses. Detector response functions were deconvolved from the models of simulated measured profiles and the true beam profile. The results were then analyzed using curve fitting method. Results: The penumbra of the beam profiles generated by different cylindrical detectors demonstrated a significant linear relationship with detector radius. Detector response functions of cylindrical detectors can be approximately represented as a Gaussian curve dependent upon the radius of the detector. Fourier transform methods can be used to deconvolve the detector response function for the penumbral areas, but can introduce noise in the non‐penumbral areas. Deconvolution methods can reduce, but cannot remove the effects of detector size. Conclusions: Monte Carlo simulation can be used to model small radiation fields and detector responses. Detector response functions can be determined from the simulated fields and simulated detector responses. A deconvolution method based on a detector specific Gaussian response function can be used to reduce detector size effect in the penumbral areas.

Hemodialysis vascular access dysfunction as a result of venous neointimal hyperplasia in dialysis access grafts and fistulae is currently a huge clinical problem. The aim of this study was to assess the effects of paclitaxel and radiation, both singly and in combination on the proliferation of cell types present within the lesion of venous neointimal hyperplasia (vascular smooth muscle cells, fibroblasts and endothelial cells within the neointimal microvessels). Vascular smooth muscle cells, fibroblasts and endothelial cells were plated onto 96-well plates and exposed to different concentrations and doses of paclitaxel and radiation, respectively (both individually and in combination). Growth inhibition was assessed with an MTT assay. Both paclitaxel and radiation resulted in significant growth inhibition of all three cell types. However, even small doses of paclitaxel appeared to attenuate the antiproliferative effect of radiation on these cell types. Further experiments to elucidate the mechanism behind these findings could result in a better understanding of combination antiproliferative therapies.

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