Objective The present study evaluated the anti-cancer effects of irradiation (Ir) alone, Ir after heat shock protein 90 inhibitor; 17allylamino-17-demethoxygeldanamycin (17-AAG) and gold nanoparticle (GNP) treatments in human colorectal cancer cell line (HCT-116), with the targeting of related mechanisms. Methods Water-soluble tetrazolium salt-1 assay was utilized to study the cytotoxic effects of 17-AAG, GNP, Ir in single and combination cases on the cell viability of HCT-116 cells. The cells were examined with DNA fragmentation electrophoresis and evaluated for apoptosis induction. Caspase-3 expression as a critical apoptosis element in protein level was detected by western blotting.Results Treatment with 17-AAG in a dose dependent manner for 24 h inhibited the cellular viability of HCT-116 cells. GNP at a dose of 70 μM had the lowest cytotoxic effects and was thus selected for combination treatment studies. Based on the results, GNP at a dose of 70 μM did not have a significant effect on cellular viability of HCT-116. In contrast, the evaluation of double and triple combinations, GNP with Ir (2 Gy of 6 MV X-ray radiation) and 17-AAG in double combinations induced significant cytotoxicity. Both DNA damage pattern and caspase-3 protein upregulation were present in Ir,GNP/17-AAG,GNP and Ir,17-AAG combinations compared to single treatments. Furthermore, in the three combination of GNP,Ir,17-AAG, radiosensitization effects (increased caspase-3 expression) occurred with a minimum concentration of 17-AAG. Conclusion According to the results of this study, 17-AAG as chemotherapeutic agent in combination with Ir and GNP exerts noticeable anti-cancer effects, inhibited cell viability, and increased apoptosis occurrence by upregulating caspase-3 expression. It is suggested that these combinations should be more evaluated as a promising candidate for colorectal cancer treatment.
In this article, the optimum parameters of tuned mass dampers for suppressing the dynamic responses of multi degree-of-freedom structures induced by base excitations are proposed. The improved harmony search algorithm, which has been successfully applied in many fields, is used for tuning the tuned mass dampers under seismic loading. The parameters of tuned mass dampers including mass, damping coefficient, spring stiffness, and location are assumed as design variables and two objective functions have been considered. The results of the numerical simulations modeling of two 10-story shear structures show that tuned mass dampers are very effective in the reduction in energy responses of structures under recorded earthquakes. Also, the objective function offered in this article with better uniform distribution in transfer functions is more reliable than those which will be discussed in the following sections. Furthermore, in all earthquakes, the maximum displacement of tuned mass dampers and force exerted by tuned mass dampers on the structure for the offered objective function are considerably less. A discussion on the validity of the model used by Bekdaş and Nigdeli is also presented in detail. The results indicate that for developing reliable preliminary-design criteria, the proposed analysis-based approach presented herein has the potential to provide better calculation of the responses of such structures.
Gold nanoparticles (GNPs) are materials that make the tumor cells more radiosensitive when irradiated with ionizing radiation. The present study aimed to evaluate the impact of different physical interaction models on the dose calculations and radiochemical results around the GNP. By applying the Geant4 Monte Carlo (MC) toolkit, a single 50-nm GNP was simulated, which was immersed in a water phantom and irradiated with 5, 50, and 150 MeV proton beams. The present work assessed various parameters including the secondary electron spectra, secondary photon spectra, radial dose distribution (RDD), dose enhancement factor (DEF), and radiochemical yields around the GNP. The results with an acceptable statistical uncertainty of less than 1% indicated that low-energy electrons deriving from the ionization process formed a significant part of the total number of secondary particles generated in the presence of GNP; the Penelope model produced a larger number of these electrons by a factor of about 30%. Discrepancies of the secondary electron spectrum between Livermore and Penelope were more obvious at energies of less than 1 keV and reached the factor of about 30% at energies between 250 eV and 1 keV. The RDDs for Livermore and Penelope models were very similar with small variations within the first 6 nm from NP surface by a factor of 10%. In addition, neither the G-value nor the REF was affected by the choice of physical interaction models with the same energy cut-off. This work illustrated the similarity of the Livermore and Penelope models (within 15%) available in Geant4 for future simulation studies of GNP enhanced proton therapy with physical, physicochemical, and chemical mechanisms.
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