Members of the miR-200 family of micro RNAs (miRNAs) have been shown to inhibit epithelial-mesenchymal transition (EMT). EMT of tubular epithelial cells is the mechanism by which renal fibroblasts are generated. Here we show that miR-200 family members inhibit transforming growth factor-beta (TGF-beta)-induced EMT of tubular cells. Unilateral ureter obstruction (UUO) is a common model of EMT of tubular cells and subsequent tubulointerstitial fibrosis. In order to examine the role of miR-200 family members in tubulointerstitial fibrosis, their expression was investigated in the kidneys of UUO mice. The expression of miR-200 family miRNAs was increased in a time-dependent manner, with induction of miR-200b most pronounced. To clarify the effect of miR-200b on tubulointerstitial fibrosis, we injected miR-200b precursor intravenously. A single injection of 0.5 nM miR-200b precursor was sufficient to inhibit the increase of collagen types I, III and fibronectin in obstructed kidneys, and amelioration of fibrosis was confirmed by observation of the kidneys with Azan staining. miR-200 family members have been previously shown to inhibit EMT by reducing the expression of ZEB-1 and ZEB-2 which are known repressors of E-cadherin. We demonstrated that expression of ZEB-1 and ZEB-2 was increased after ureter obstruction and that administration of the miR-200b precursor reversed this effect. In summary, these results indicate that miR-200 family is up-regulated after ureter obstruction, miR-200b being strongly induced, and that miR-200b ameliorates tubulointerstitial fibrosis in obstructed kidneys. We suggest that members of the miR-200 family, and miR-200b specifically, might constitute novel therapeutic targets in kidney disease.
Objectives Radical cystectomy is the gold‐standard treatment for muscle‐invasive bladder cancer and aggressive non‐muscle‐invasive bladder cancer. To enhance clinical decision‐making regarding patients with bladder cancer who underwent radical cystectomy, a recurrence prediction biomarker with high accuracy is urgently needed. In this study, we developed a model for the prediction of bladder cancer recurrence after radical cystectomy by combining serum microRNA and a pathological factor. Methods We retrospectively analyzed the clinical records of 81 patients with bladder cancer who underwent radical cystectomy between 2008 and 2016. The dataset was divided into two, and Fisher linear discriminant analysis was used to construct a prognostic model for future recurrence in the training set (n = 41). The performance of the model was evaluated in the validation set (n = 40). Results Thirty patients had recurrence after having undergone radical cystectomy. A prognostic model for recurrence was constructed by combining a pathological factor (i.e. positive pathological lymph node status) and three microRNAs (miR‐23a‐3p, miR‐3679‐3p, and miR‐3195). The model showed a sensitivity of 0.87, a specificity of 0.80, and an area under the receiver operating characteristic curve of 0.88 (0.77–0.98) in the validation set. Furthermore, Kaplan–Meier analysis revealed that patients with a low prediction index have significantly longer overall survival than patients with a high prediction index (P = 0.041). Conclusion A combination of serum microRNA profiles and lymph node statuses is useful for the prediction of oncological outcomes after radical cystectomy in patients with bladder cancer.
Background: Although radical prostatectomy is associated with good long-term oncological outcomes, approximately 30% of patients present biochemical recurrence, whereupon salvage treatments are required. Identification of novel molecular biomarkers to predict cancer behavior is clinically important. Here, we developed a novel microRNA (miRNA)-based prognostic model for patients who underwent radical prostatectomy. Methods: We retrospectively investigated the clinical records of 295 patients who underwent radical prostatectomy between 2009 and 2017. We randomly assigned these cases into training or validation sets. The prognostic model was constructed using Fisher linear discriminant analysis in the training set, and we evaluated its performance in the validation set.Results: Overall, 72 patients had biochemical recurrence. A prediction model was constructed using a combination of three miRNAs (miR-3147, miR-4513, and miR-4728-5p) and two pathological factors (pathological T stage and Gleason score). In the validation set, the predictive performance of the model was confirmed to be accurate (area under the receiver operating characteristic curve: 0.80; sensitivity: 0.78; specificity: 0.76). Additionally, Kaplan-Meier analysis revealed that the patients with a low prediction index had significantly longer recurrence-free survival than those with a high index (p < 0.001).Conclusions: Circulating miRNA profiles can provide information to predict recurrence after prostatectomy. Our model may be helpful for physicians to decide follow-up strategies for patients.
Introduction Clinical recurrence of prostate cancer after curative treatment with a limited number of metastases is often termed as oligorecurrence. We report a case of solitary recurrence of prostate cancer surrounded by epithelium of the seminal vesicle or vas deferens. Case presentation A 54‐year‐old man diagnosed with localized prostate cancer underwent radiation therapy. Six years later, imaging studies detected a solitary recurrence. We performed metastasectomy, and histopathological examination revealed the metastatic lesion surrounded by the epithelium of the seminal vesicle or vas deferens. Surgical resection achieved a complete biochemical response. Conclusion We presented with a case of prostate cancer metastasis surrounded by the epithelium of the seminal vesicle or vas deferens.
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