Vectorial transport of organic cations (OCs) in renal proximal tubules is mediated by sequential action of human OC transporter 2 (hOCT2) and human multidrug and toxic extrusion protein 1 and 2K (hMATE1 and hMATE2K), expressed in the basolateral (hOCT2) and luminal (hMATE1 and hMATE2K) plasma membranes, respectively. It is well known that hOCT2 activity is subjected to rapid regulation by several signaling pathways, suggesting that renal OC secretion may be acutely adapted to physiological requirements. Therefore, in this work, the acute regulation of hMATEs stably expressed in human embryonic kidney cells was characterized using the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) as a marker. A specific regulation of ASP+ transport by hMATE1 and hMATE2K measured in uptake and efflux configurations was observed. In the example of hMATE1 efflux reduction by inhibition of casein kinase II, it was also shown that this regulation is able to modify transcellular transport of ASP+ in Madin–Darby canine kidney II cells expressing hOCT2 and hMATE1 on the basolateral and apical membrane domains, respectively. The activity of hMATEs can be rapidly regulated by some intracellular pathways, which sometimes are common to those found for hOCTs. Interference with these pathways may be important to regulate renal secretion of OCs.

Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival, especially those with pathological complete response (pCR). The response to NAC according to molecular subtypes has been discussed. Molecular targets such as estrogen receptor (ESR1) and human epidermal growth factor receptor 2 (ERBB2) play an important role in breast cancer management and have also been associated with urothelial bladder cancer. Hence, the association of Keratin 20 (KRT20) Keratin 5 (KRT5), ESR1, and ERBB2 mRNA expression in MIBC at transurethral resection (TUR-BT) with pCR after NAC was analyzed retrospectively. Formalin-fixed paraffin-embedded tumour tissue samples from TUR-BT of 54 patients (42 males, 12 females, median age of 64) with MIBC were analyzed for KRT20, KRT5, ESR1, and ERBB2 mRNA expression. After NAC, RC was performed, and the specimens were evaluated for pCR. Statistical analyses comprised nonparametric and chi2 testing, partition models, and Spearman correlation analyses. After NAC, 22 out of 54 patients (40.7%) had pCR. Tumours with an elevated expression of markers associated with luminal differentiation (KRT20, ERBB2, ESR1) were associated with a higher chance of pCR (55% vs. 15.8%, p = 0.009). Elevated ERBB2 expression was positively correlated with luminal expression features such as KRT20, and negatively with basal characteristics such as KRT5. Patients with MIBC showing a high expression of ERBB2, ESR1, or KRT20 have a significantly higher chance of pCR following NAC. These findings might improve patient selection for NAC in MIBC.

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To evaluate factors affecting the outcomes of short-term Mono-J insertion for 6 h following ureteroscopic stone removal. Patients treated with a Mono-J for 6 h after ureterorenoscopy and stone removal were analysed. FaST 1 and 2 (Fast Track Stent Studies), two consecutive single academic centre studies, were conducted between August 2014 and April 2018. In each study, we randomized patients with renal or ureteral calculi to two groups before ureterorenoscopy. FaST 1 compared a Mono-J insertion for 6 h versus Double-J insertion for 3–5 days after ureterorenoscopy. FaST 2 compared a Mono-J insertion to a tubeless procedure in the same clinical setting. All patients were pre-stented for 3–5 days before URS. The study endpoint was stent-related symptoms as assessed by a validated questionnaire (USSQ). Results were stratified by clinical parameters, stone characteristics and operation details. 108 of 156 initially randomized patients undergoing ureterorenoscopy were included. USSQ scores covering the time 3–5 weeks after stone removal showed a significantly reduced urinary symptoms and pain index compared to the scores before ureterorenoscopy. USSQ results before and after stone removal did not correlate with stone size or operation time and did not differ significantly depending on stone localization, the treating endourologist, or ureterorenoscopic device used (p > 0.05). Six patients (5%) required reintervention. Following secondary ureterorenoscopy and ureteral drainage with a Mono-J for 6 h, quality of life is independent of stone size and localization, operation time, the treating endourologist, and the URS device used.