Dalsan You

miR‐140‐5p suppresses BMP2‐mediated osteogenesis in undifferentiated human mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) have self‐renewal and differentiation capabilities but the regulatory mechanisms of MSC fate determination remain poorly understood. Here, we aimed to identify microRNAs enriched in hMSCs that modulate differentiation commitments. Microarray analysis revealed that miR‐140‐5p is commonly enriched in undifferentiated hMSCs from various tissue sources. Moreover, bioinformatic analysis and luciferase reporter assay validated that miR‐140‐5p directly represses bone morphogenic protein 2 (BMP2). Furthermore, blocking miR‐140‐5p in hMSCs increased the expression of BMP signaling components and critical regulators of osteogenic differentiation. We propose that miR‐140‐5p functionally inhibits osteogenic lineage commitment in undifferentiated hMSCs.

The Value of Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy

PURPOSE We evaluated the value of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma in the targeted therapy era. MATERIALS AND METHODS We reviewed the records of 78 patients treated with targeted therapy for metastatic renal cell carcinoma between 2006 and 2009. A total of 45 patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 33 were treated with targeted therapy alone (noncytoreductive nephrectomy group). We estimated progression-free and overall survival using Kaplan-Meier curves. The prognostic significance of each variable was estimated with a Cox proportional hazards regression model. RESULTS Clinicopathological variables did not differ in the 2 groups except for Karnofsky performance status and sarcomatoid feature. The treatment response rate did not differ in the 2 groups (23.1% vs 30.3%, p = 0.488). Median progression-free survival was 11.7 and 9.0 months in the cytoreductive and noncytoreductive nephrectomy groups (p = 0.270), and median overall survival was 21.6 and 13.9 months, respectively (p = 0.128). On multivariate analysis Karnofsky performance status (HR 2.9, 95% CI 1.4-5.7, p = 0.003) and sarcomatoid features (HR 2.9, 95% 1.3-6.7, p = 0.013) were independent predictors of progression-free survival. Karnofsky performance status (HR 3.3, 95% 1.7-6.5, p = 0.001), sarcomatoid features (HR 2.7, 95% 1.2-6.2, p = 0.021) and liver metastasis (HR 2.7, 95% 1.0-7.1, p = 0.045) were independent predictors of overall survival. CONCLUSIONS We found no significant differences in tumor response or survival between the 2 groups. Prospective trials are needed to confirm our results.

Periprostatic Implantation of Human Bone Marrow-derived Mesenchymal Stem Cells Potentiates Recovery of Erectile Function by Intracavernosal Injection in a Rat Model of Cavernous Nerve Injury

OBJECTIVE To evaluate whether periprostatic implantation (PPI) of human bone marrow-derived mesenchymal stem cells (hBMSCs) potentiates recovery of erectile function after intracavernosal injection (ICI) of hBMSCs in a rat model of cavernous nerve (CN) injury. METHODS Sprague-Dawley rats that had undergone bilateral CN injury were treated by ICI with or without PPI of hBMSCs (10 rats per group). hBMSCs were harvested from healthy human donors. Fibrin scaffolds were used for PPI of hBMSCs. After 4 weeks, erectile responses to electric pelvic ganglion stimulation were studied. The expression of neuronal nitric oxide synthase (nNOS)-positive nerve fibers and smooth muscle/collagen ratio was evaluated in each penis. RESULTS ICI of hBMSCs slightly improved erectile function compared with the control group (maximal intracavernosal pressure/mean arterial pressure, 39.1% vs 21.7%; P=.060), but a combination of PPI and ICI significantly improved erectile function (45.0%, P=.007). After stem cell therapy, the number of nNOS-positive nerve fibers increased significantly in the PPI+ICI group (P=.017). The smooth muscle/collagen ratio increased significantly after stem cell therapy in the ICI and PPI+ICI groups (both P<.001). CONCLUSION ICI of hBMSCs in a rat model of CN injury results in recovery of penile erection by decreasing corporeal smooth muscle deterioration and collagen deposition. PPI of hBMSCs potentiates recovery of erectile function by ICI of hBMSCs via regeneration of nNOS-containing nerve fibers.

Comparative analysis of periprostatic implantation and intracavernosal injection of human adipose tissue‐derived stem cells for erectile function recovery in a rat model of cavernous nerve injury

We compared periprostatic implantation (PPI) and intracavernosal injection (ICI) of human adipose tissue‐derived stem cell (ADSC) to facilitate recovery of erectile function in a rat model of cavernous nerve (CN) injury.

Multilocular cystic renal cell carcinoma: clinicopathological features and preoperative prediction using multiphase computed tomography

Study Type – Diagnostic (exploratory cohort)

Effect of prostate size on pathological outcome and biochemical recurrence after radical prostatectomy for prostate cancer: is it correlated with serum testosterone level?

Study Type – Prognosis (case series)
Level of Evidence 4

Incremental Value of Magnetic Resonance Imaging for Clinically High Risk Prostate Cancer in 922 Radical Prostatectomies

PURPOSE We investigated the incremental value of magnetic resonance imaging in addition to clinical variables for predicting pathological outcomes and disease recurrence in patients with clinically high risk prostate cancer. MATERIALS AND METHODS A total of 922 consecutive patients with clinically high risk prostate cancer underwent magnetic resonance imaging before radical prostatectomy. We created multivariate logistic regression and Cox proportional hazards models with clinical variables only or combined with magnetic resonance imaging data to predict pathological outcomes and biochemical recurrence. The models were compared using ROC curves and the Harrell concordance index. RESULTS The proportion of patients with pathological extracapsular extension, seminal vesicle invasion and lymph node metastasis was 57.5%, 12.7% and 6.3%, respectively. The sensitivity and specificity of extracapsular extension, seminal vesicle invasion and lymph node metastasis detection were 43% and 84.2%, 34.9% and 93.8%, and 14.0% and 96.9%, respectively. The area under the ROC curve of the model with clinical variable and magnetic resonance imaging data was greater than that of the model with clinical variables alone to predict extracapsular extension and seminal vesicle invasion (0.734 vs 0.697, p=0.001 and 0.750 vs 0.698, p<0.001, respectively). The 5-year biochemical recurrence-free survival rate was 56.1%. To predict biochemical recurrence the concordance index of the multivariate model with clinical variables only and with clinical variables plus magnetic resonance imaging data was 0.563 and 0.599, respectively (p=0.003). CONCLUSIONS Magnetic resonance imaging findings have incremental value in addition to clinical variables for predicting pathological outcomes and disease recurrence.

Comparative Study of Autologous Stromal Vascular Fraction and Adipose-Derived Stem Cells for Erectile Function Recovery in a Rat Model of Cavernous Nerve Injury

The abilities of intracavernous injection of autologous stromal vascular fraction (SVF) and adipose‐derived stem cells (ADSCs) to facilitate recovery of erectile function in a rat model of cavernous nerve (CN) injury were compared. Forty male Sprague‐Dawley rats were randomly divided into four groups: sham and control groups (intracavernous injection of phosphate‐buffered saline), SVF group (intracavernous injection of SVF), and ADSC group (intracavernous injection of ADSCs). Rats in the latter three groups underwent bilateral CN injury prior to injection. The evaluation of erectile function and histomorphometric studies were performed 4 weeks after injection. The ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (0.18 vs. 0.56, p < .001). Intracavernous injection of SVF (0.36, p = .035) significantly improved erectile function compared with that in the control group, whereas the ADSC group (0.35, p = .052) showed marginally significant improvement. The smooth muscle/collagen ratio, smooth muscle content, number of neuronal nitric‐oxide synthase‐positive nerve fibers, and expression of von Willebrand factor were significantly higher in the SVF and ADSC groups than in the control group. Expression of endothelial nitric‐oxide synthase was significantly increased in the SVF group. The increases in the smooth muscle/collagen ratio and von Willebrand factor expression were larger in the SVF group than in the ADSC group. Intracavernous injection of SVF or ADSCs was equally effective in recovering penile erection in a rat model of CN injury.

Analysis of the late outcome of laparoscopic heminephrectomy in children with duplex kidneys

Study Type – Therapy (case series)
 Level of Evidence 4

Muscle-invasive bladder cancer developing after nephroureterectomy for upper urinary tract urothelial carcinoma

OBJECTIVES To evaluate the risk factors and prognosis of muscle-invasive bladder cancer (MIBC) developing after nephroureterectomy for upper urinary tract urothelial cell carcinoma (UUT-UC). MATERIALS AND METHODS We reviewed the medical records of 422 patients who underwent nephroureterectomy for UUT-UC between 1990 and 2010, and identified 173 (40.9%) with intravesical recurrence and 28 (6.6%) with MIBC. We evaluated the clinicopathologic features, risk factors, and cancer-specific survival (CSS) using the Kaplan-Meier method and the Cox proportional hazards regression models. RESULTS The median intervals from nephroureterectomy to intravesical recurrence and the development of MIBC were 8 and 17 months, respectively. On multivariate analysis, the pathologic stage (≥ pT3 vs. Ta/T1, HR 5.03, P = 0.001) and ureteral tumor location (HR 2.79, P = 0.011) were independent risk factors for the development of MIBC, whereas a history of previous or concomitant bladder tumor was the only significant risk factor for intravesical recurrence. The probability of developing MIBC 5 years after nephroureterectomy was 12.6% in patients with 1 risk factor and 20.6% in patients with both risk factors. Patients with MIBC had significantly worse CSS than those without MIBC (P = 0.004), whereas CSS rates were similar in patients with and without intravesical recurrence (P = 0.593). However, stratification analysis for matching pathology revealed that CSS rates were not significantly different in patients with pT2 or higher stage of UUT-UC. CONCLUSIONS Approximately 5% of the patients developed MIBC after nephroureterectomy with a median interval of 17 months. Patients with advanced pathologic stage (≥ pT3) and a ureteral tumor location are at increased risk of developing MIBC after nephroureterectomy.