METHODS: Male SD rats at 8 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (Sham). Rats with prostatic inflammation were divided into COX-2 inhibitor (celecoxib) therapy (Treatment) and placebo groups (Placebo). Rats were treated with celecoxib at a dose of 10mg/kg daily from 2 days before induction of prostatic inflammation. Twenty-eight days later, conscious cystometry was performed to assess bladder function. After cystometry, the prostate and L6-S1 dorsal root ganglia (DRG) were excised for analysis of mRNA expression levels of IL1b and COX-2 in the prostate and a Kþ channel a-subunit, Kv1.4, in DRG as well as histological evaluation of prostate and bladder.RESULTS: In cystometry, intercontraction intervals (ICI) were significantly decreased in Placebo group compared to Sham group. mRNA expressions of IL1b and COX-2 in the prostate were significantly increased while mRNA expression of Kv1.4 in L6-S1 DRG was significantly decreased in Placebo group compared to Sham rats. However, these changes were normalized in Treatment group. Prostatic sections from Placebo group demonstrated infiltration of inflammatory cells, but not in Sham or Treatment group. There were no significant inflammatory changes in bladder sections from any groups.CONCLUSIONS: COX-2 inhibition improved not only prostatic inflammation evidenced by decreases of upregulated IL1b and COX-2 levels, but also bladder overactivity as shown by shorter ICI in association with decreased Kv1.4 expression in pelvic afferent pathways. These results suggest that prostatic inflammation mediated by COX-2 plays an important role in bladder overactivity possibly induced by prostate-to-bladder cross-talk through pelvic afferent pathways. Thus, these COX-2-dependent mechanisms might contribute to male LUTS due to BPH associated with prostatic inflammation.
Objective: Metastatic recurrence has been reported to occur in 20–30% of patients with clear cell renal cell carcinoma (ccRCC). Although the prognosis of these patients is poor, no marker has been established to predict metastatic potential and/or prognosis. Therefore, we investigated membrane expression of sialyl Lewis x (sLex) and sialyl Lewis a (sLea), which is generally considered to be associated with cancer metastasis. Materials and methods: We enrolled 117 patients who underwent curative surgery for RCC and were pathologically diagnosed as ccRCC. Immunohistochemistry for sLex and sLea was performed to evaluate the signal intensity on the cell membrane. We statistically analysed whether membrane expression of sLex/sLea is correlated with clinicopathological parameters and prognosis. Results: Of the 117 patients, 72 were classified as sLex-positive and 44 as sLea-positive. The sLex-positive group had significantly shorter progression-free survival (PFS) and overall survival (OS) than the negative group. Similarly, the sLea-positive group had significantly shorter PFS than the negative group, and it showed a trend towards a reduction of OS, although it did not reach statistical significance, a fact that could be due to the small sample size. Conclusion: Both sLex and sLea could be possible future prognostic indicators in ccRCC. Level of evidence: Level 3
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