In this study, we identified microRNAs (miRNAs) involved in cisplatin (CDDP) resistance in bladder cancer (BCa). After establishing CDDP-resistant BCa cell lines (T24RC and EJ138RC), TaqMan arrays revealed that members of the miR-200 family (miR-200b, miR-200a and miR-429) were downregulated in T24RC as compared to parental T24 cells. miR-200b was associated with CDDP sensitivity in BCa cells, and its downregulation was associated with CpG island hypermethylation. Pharmacological demethylation using 5-aza-2’-deoxycytidine restored miR-200b expression, and the combination of 5-aza-2’-deoxycytidine + CDDP strongly inhibited T24RC cell proliferation. Microarray analysis revealed that miR-200b + CDDP induced genes involved in CDDP sensitivity or cytotoxicity, including IGFBP3, ICAM1 and TNFSF10, in the resistant cells. Expression and DNA methylation of miR-200b were inversely associated in primary BCa, and low expression/high methylation was associated with poor overall survival. These results suggest downregulation of miR-200b is associated with CDDP resistance in BCa. Epigenetic silencing of miR-200b may be a marker of CDDP resistance and a useful therapeutic target for overcoming CDDP resistance in BCa.

Background Interstitial cystitis/bladder pain syndrome (IC/BPS) categorized with and without Hunner lesions is a condition that displays chronic pelvic pain related to the bladder with no efficacious treatment options. There are strong associations suggested between Hunner-type IC and autoimmune diseases. Recently, we established an animal model of Hunner-type IC using a Toll-like receptor-7 (TLR7) agonist. Intravenous infusion of mesenchymal stem cells (MSCs) can be used to treat injury via multimodal and orchestrated therapeutic mechanisms including anti-inflammatory effects. Here, we investigated whether infused MSCs elicit therapeutic efficacy associated with the TLR7-related anti-inflammatory pathway in our Hunner-type IC model. Methods Voiding behaviors were monitored 24 h prior to the Loxoribine (LX), which is a TLR7 agonist instillation in order to establish a Hunner-type IC model (from − 24 to 0 h) in female Sprague–Dawley rats. LX was instilled transurethrally into the bladder. At 0 h, the initial freezing behavior test confirmed that no freezing behavior was observed in any of the animals. The LX-instilled animals were randomized. Randomized LX-instilled rats were intravenously infused with MSCs or with vehicle through the right external jugular vein. Sampling tissue for green fluorescent protein (GFP)-positive MSCs were carried out at 48 h. Second voiding behavior tests were monitored from 72 to 96 h. After the final evaluation of the freezing behavior test at 96 h after LX instillation (72 h after MSC or vehicle infusion), histological evaluation with H&E staining and quantitative real-time polymerase chain reaction (RT-PCR) to analyze the mRNA expression levels of inflammatory cytokines were performed. Results Freezing behavior was reduced in the MSC group, and voiding behavior in the MSC group did not deteriorate. Hematoxylin–eosin staining showed that mucosal edema, leukocyte infiltration, and hemorrhage were suppressed in the MSC group. The relative expression of interferon-β mRNA in the bladder of the MSC group was inhibited. Numerous GFP-positive MSCs were distributed mainly in the submucosal and mucosal layers of the inflammatory bladder wall. Conclusion Intravenous infusion of MSCs may have therapeutic efficacy in a LX-instilled Hunner-type IC rat model via a TLR7-related anti-inflammatory pathway.

Objectives To clarify Japanese real‐world clinical data on the use of desmopressin 25 and 50 μg orally disintegrating tablets (ODT) for male patients with nocturia and evaluate the predictive factors to improve nighttime frequency. Methods We retrospectively accumulated real‐world clinical data from 27 institutions in Japan. Male patients with two or more episodes of nocturia who received desmopressin ODT for nocturnal polyuria (NP) from 2019 through 2021 were included. The primary endpoint was the change of nighttime frequency until 3 months after desmopressin administration. The secondary endpoints were to clarify the persistence rate, adverse events, and predictive factors of decreasing nighttime frequency. Results A total of 118 patients were eligible to participate in this study. The persistence rate of desmopressin on the Kaplan‐Meier curve at week 12 was 51.3. The reason for discontinuation was mainly the occurrence of adverse events in 67 patients (56.8%), particularly hyponatremia in 7 patients (5.9%). Nighttime frequencies at baseline, ‐ 1 month and 1 ‐ 3 months after desmopressin administration were 4.1 ± 1.3, 2.9 ± 1.4 (P < .01), and 2.6 ± 1.3 (P < .01), respectively. The mean nighttime urine volume voided at baseline was significantly larger in patients whose nighttime frequency decreased by two or more times than in those with a decrease of less than two times. Conclusions Desmopressin 25 and 50 μg ODT treatments are feasible for male patients with NP in Japanese real‐world clinical practice. Patients with higher voided volumes, particularly in the nighttime, may have great benefit from desmopressin.

Aims There have been few reports on whether long‐term oral phosphodiesterase 5 inhibitor administration can ameliorate bladder changes due to bladder outlet obstruction (BOO). Therefore, we clarified the chronological changes of the bladder using male BOO rats and evaluated the effects of tadalafil on these changes. Methods Eight‐week‐old male Sprague‐Dawley rats were used. BOO was created by placing a polyethylene catheter around the urethra. Then, the rats were orally treated with a vehicle, or tadalafil 2 or 10 mg/kg until each evaluation period. Cystometric measurements were performed and the degree of fibrosis in the smooth muscle layer was evaluated at 2, 4, and 16 weeks. Results In BOO rats, a significant increase in the number of non‐voiding contractions (NVCs) and a shortened intercontraction interval (ICI) were observed in the earlier phase (2 and 4 weeks) compared to Sham rats. In the chronic phase (16 weeks), markedly increased residual urine volume and an extended ICI were observed accompanied by enhanced smooth muscle fibrosis. These results indicated that the bladder in BOO rats represented the overactive phenotype in the earlier phase and changed into the underactive phenotype in the chronic phase. Even in Sham rats, an increased number of NVCs and enhanced fibrosis were observed with time. Tadalafil administration significantly prevented these bladder changes in both BOO and Sham rats. Conclusions Long‐term oral administration of tadalafil can prevent functional and histological changes in the BOO rat bladder. This agent is also effective for the bladder functional change even in non‐obstructed rats.

Risk factors for AS are thought to be multifactorial. Intraoperative blood loss was significantly associated with the development of anastomotic stricture. We should understand that anastomotic stricture following radical retropubic prostatectomy is not a rare morbidity and should inform patients about the possibility of postoperative AS.