The energy response of films in the energy range <100 keV can be improved by adjusting the active layer chemical composition. Removing bromine eliminated the over response at about 40 keV. The under response at energies ≤ 30 keV is improved by adding 7% Al to the active layer in the latest commercial EBT3 film models.
Background
Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high‐risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next‐generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy.
Methods
Using a number of androgen‐dependent (LNCaP, PC3‐T877A) and androgen‐independent (C4‐2, 22RV1, PC3, PC3‐AR V7) cell lines, the effect of ENZA as a radiosensitizer was studied alone or in combination with ADT and/or XRT. Cell viability and cell survival were assessed, along with determination of cell cycle arrest, DNA damage response and repair, apoptosis and senescence.
Results
Our results indicated that either ENZA alone (in AR positive, androgen‐dependent PCa cells) or in combination with ADT (in AR positive, hormone‐insensitive PCa cells) potentiates radiation response [Dose enhancement factor (DEF) of 1.75 in LNCAP and 1.35 in C4‐2] stronger than ADT + XRT conditions. Additionally, ENZA sensitized androgen dependent PCa cells to XRT in a schedule‐dependent manner, where concurrent administration of ENZA and radiation lead to a maximal radiosensitization when compared to either drug administration prior or after XRT. In LNCaP cells, ENZA treatment significantly prolonged the presence of XRT‐induced phospho‐γH2AX up to 24 h after treatment; suggesting enhanced DNA damage. It also significantly increased XRT‐induced apoptosis and senescence.
Conclusions
Our data indicates that ENZA acts as a much stronger radiosensitizer compared to ADT. We have also observed that its efficacy is schedule dependent and related to increased levels of DNA damage and a delay of DNA repair processes. Finally, the initial abrogation of DNA‐PKcs activity by AR inhibition and its subsequent recovery might represent an important mechanism by which PCa cells acquire resistance to combined anti‐androgen and XRT treatment. This work suggests a new use of ENZA in combination with XRT that could be applicable in clinical trial settings for patients with early and intermediate hormone responsive disease.
Results of our investigation revealed that the use of XR-QA2 GafChromic™ film is accompanied by a rather pronounced energy dependent response for beam qualities used for x-ray based diagnostic imaging purposes. The authors also found that the most appropriate function for the reference radiochromic film dosimetry would be the power function, while for the relative dosimetry one may use the exponential response function that can be easily linearized.
These results suggest that the TARGIT dose underestimates the physical dose to water from the INTRABEAM source. Understanding the correlation between the TARGIT and physical dose is important for any studies wishing to make dosimetric comparisons between the INTRABEAM and other radiation emitting devices.
[1] Statistical models of high-latitude plasma convection have been used in a wide range of studies pertaining to the ionosphere and thermosphere, and they are beginning to be used in various space weather applications. However, the statistical convection models only provide average, not instantaneous, convection patterns, and it is not clear if they are real convection patterns or blurred images of convection. It is also unclear how reliable these convection models are for applications involving ionosphere-thermosphere specifications and forecasts. To address these issues, a quantitative analysis was conducted of the Weimer [2001] empirical convection model, which is the most comprehensive model of high-latitude convection that has been constructed to date. First, criteria were established to determine whether or not a modeled convection pattern was correct for a given set of geophysical conditions. The criteria adopted were reasonable but stringent. Then the cross-track ion drift velocities obtained from Weimer [2001] were compared with the corresponding velocities measured by the DMSP F13 satellite. The comparisons were done for nearly a year (1998) of satellite crossings of the northern polar region (4430 successive crossings). The results indicate that the Weimer [2001] model is able to produce the gross structure in the convection pattern, i.e., it is good in a statistical sense. However, it does not adequately capture the mesoscale spatial structure and convection magnitudes observed by the DMSP satellite. Typically, it was able to capture real (instantaneous) convection features in only about 6% of the satellite crossings. Although empirical convection patterns are invaluable for scientific applications, these results have important implications for using empirical convection models in space weather applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.