OBJECTIVES To investigate the roles of glutathione and glutathione‐S‐transferase (GST) in cisplatin‐resistance mechanisms in human bladder cancer, by using glutathione‐depleting or GST‐blocking agents. MATERIALS AND METHODS Cisplatin‐resistant human bladder cancer cell lines were established by continuous exposure of T24 cells to increasing concentrations of cisplatin. Buthionine sulphoximine (BSO), ethacrynic acid and indomethacin were used to deplete glutathione or block GST. Intracellular glutathione content, GST activity and cisplatin cytotoxicity were determined after exposing parental and drug‐resistant cell lines to these agents. RESULTS Intracellular glutathione content and GST activity were significantly decreased, and cisplatin cytotoxicity significantly enhanced, in both parental and resistant cell lines by glutathione‐depleting or GST‐blocking agents. However, the resistance of cisplatin‐resistant cell lines did not fully recover to that of the parental cells with combined BSO and indomethacin. CONCLUSIONS Both increased glutathione content and GST activity are significant in the cisplatin resistance of human bladder tumour cells. Because BSO, ethacrynic acid and indomethacin caused a partial recovery of resistance in the cisplatin‐resistant cell line, further studies are needed to investigate their efficacy for treating patients with metastatic bladder carcinoma resistant to cisplatin.
This study evaluated the mechanical properties and bone regeneration ability of 3D-printed pure hydroxyapatite (HA)/tricalcium phosphate (TCP) pure ceramic scaffolds with variable pore architectures. A digital light processing (DLP) 3D printer was used to construct block-type scaffolds containing only HA and TCP after the polymer binder was completely removed by heat treatment. The compressive strength and porosity of the blocks with various structures were measured; scaffolds with different pore sizes were implanted in rabbit calvarial models. The animals were observed for eight weeks, and six animals were euthanized in the fourth and eighth weeks. Then, the specimens were evaluated using radiological and histological analyses. Larger scaffold pore sizes resulted in enhanced bone formation after four weeks (p < 0.05). However, in the eighth week, a correlation between pore size and bone formation was not observed (p > 0.05). The findings showed that various pore architectures of HA/TCP scaffolds can be achieved using DLP 3D printing, which can be a valuable tool for optimizing bone-scaffold properties for specific clinical treatments. As the pore size only influenced bone regeneration in the initial stage, further studies are required for pore-size optimization to balance the initial bone regeneration and mechanical strength of the scaffold.
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