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.
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