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.
histological analysis including terminal deoxynucleotidyl transferase-mediated nickend labelling staining. The results were compared among normal control, salinetreated and glycine-treated rats.
OBJECTIVE
To investigate the effects of ovariectomy and oestrogen replacement on the function and expression of Rho‐kinase in rat bladder smooth muscle, as the actual effects of oestrogen deprivation on bladder smooth muscle are unclear.
MATERIALS AND METHODS
Female Sprague–Dawley rats were placed into one of three groups: sham‐operated, bilateral ovariectomy‐only, and bilateral ovariectomy plus oestrogen replacement groups. In the last group, oestrogen was replaced by weekly injection of β‐estradiol 17‐cypionate (250 µg/kg subcutaneously for 6 weeks) beginning at 1 week after ovariectomy, whereas the other groups received vehicle‐only injections for 6 weeks. After treatment, the bladder was removed for muscle strip studies to evaluate the effects of Y‐27632, a specific inhibitor of Rho‐kinase, on baseline tension and carbachol‐induced tonic contractions. Also, the protein expression of RhoA and Rho‐kinase isoenzymes was assessed by Western blot analysis.
RESULTS
Of the three groups, incubation with 10 µm Y‐27632 resulted in the largest decrease in baseline tension of strips from the bilateral ovariectomy‐only group, but this was not statistically significant (P > 0.05). For carbachol‐induced tonic contractions, strips from the bilateral ovariectomy‐only group were attenuated the most among the three groups after adding Y‐27632 (P < 0.05). However, there were no significant differences in the levels of RhoA and the two Rho‐kinase isoenzymes in bladder tissues from the three groups.
CONCLUSION
Our data show that oestrogen might inhibit the function of Rho‐kinase in bladder smooth muscle, while having no significant effect on its expression. This finding might help to explain the greater incidence of urinary tract symptoms suggestive of overactive bladder after the menopause in women.
This paper posits that arm's length buyer-supplier relationship as the intermediate type between market exchange relations and strategic partnership might be advisable, and information technology may have a role as a mechanism actualizing the effects of such arm's length relationship by strategic supply-line diversification.Based on the theoretical analysis on interactive feedback relationships among IT level, buyer-supplier relationships, and supply chain structure, we suggest a set of advisable buyer-supplier relationship type for efficient supply chain management. Also, doing so would be helpful in suggesting a dynamic IT investment and adoption model appropriate for the establishment of productive buyer-supplier relationship, and further in providing theoretical foundations and practical guidelines on the role and function of B-to-B E-commerce for efficient SC integration.
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