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Introduction: Intravesical prostatic protrusion (IPP) has been reported to be associated with bladder outlet obstruction and is the main cause of lower urinary tract symptoms (LUTS) during the development of benign prostatic hyperplasia (BPH). However, the molecular mechanism of IPP remains unclear. Methods: Clinical data analysis was performed to analyze the association between IPP and long-term complications in patients with BPH. RNA sequencing was performed on prostate tissues (IPP or not). Stromal cells were obtained from IPP-derived primary cultures to explore the molecular mechanism of IPP formation. Cell proliferation was evaluated by a CCK-8 assay. Multiple proteins in the signaling pathway were assessed using Western blot. Results: First, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, we observed that FGF7 was upregulated in both IPP tissues and IPP primary stromal cells through immunohistochemistry, Western blot, and quantitative real-time PCR. Furthermore, FGF7 was significantly upregulated in high IPP-grade prostate tissues. The coculture experiments showed that the downregulation of FGF7 in IPP-derived stromal cells inhibited the proliferation and migration of the prostate epithelial cells. Additionally, FGF7 was bound to FGFR2 to induce the epithelial-mesenchymal transition process through binding to FGFR2. RNA sequencing analysis also revealed the activation of the MAPK/ERK1/2 signaling pathway. The MAPK/ERK1/2 was downregulated by a specific inhibitor affecting the FGF7 stimulation in vitro. Conclusions: Our data reveal a novel amplification effect, i.e., stromal cell-derived FGF7 promotes epithelial cell proliferation and stromal cell phenotype, ultimately inducing IPP formation. Targeting FGF7 can significantly reduce epithelial to stromal transition and provide a potential therapeutic target for BPH progression. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules. Methods: Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis. Results: The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis. Conclusion: These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules. [ABSTRACT FROM AUTHOR]

The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species–NLR family, pyrin domain‐containing 3 (ROS–NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70‐induced inflammation was explored in THP‐1 cells with or without N‐acetyl‐ l‐cysteine (NAC) pretreatment. The function of NLRP3 and Caspase‐1 was determined by Western blot analysis, enzyme‐linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3–5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase‐1, and interleukin‐18 (IL‐18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL‐1β and IL‐18 could be inhibited by NLRP3 or Caspase‐1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase‐1, IL‐1β, and IL‐18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS–NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a common disease in elderly men, and transurethral laser prostatectomy (TULP) has been widely used in the clinic to remove bladder outlet obstruction caused by BPH. Previous animal models for wound repair after prostatectomy have many limitations, and there have been no previous reports of a mouse model of TULP. Therefore, this study aimed to establish a novel mouse model of TULP. Twelve healthy adult Kunming (KM) mice received transurethral laser vaporization prostatectomy with a 200-μm thulium laser. The mice were sacrificed, and wound specimens from the prostatic urethra and bladder neck were harvested at 1 day, 3 days, 5 days, and 7 days after surgery. Hematoxylin-eosin (HE) and immunohistochemistry were applied to confirm the establishment of the mouse TULP model. One day after the surgery, urothelium expressing uroplakin (UPK) was absent in the urethral wound site, and a large number of necrotic tissues were found in the wound site. There was no UPK-positive urothelium in the wound 3 days after surgery. At 5 days after surgery, monolayer urothelium expressing UPK was found in the wound site, indicating that the re-epithelization of the wound had been completed. On the 7th day after surgery, there were multiple layers of urothelium with UPK expression, indicating that the repair was completed. It is feasible to establish a mouse TULP model by using a microcystoscope system and a 200-μm thulium laser. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. The erectile function was evaluated at 4 weeks, as well as the expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS), and insulin-like growth factor 1 (IGF1). STZ-induced diabetic rats showed impaired ICP, which was significantly improved by hWJ-MSC treatment. VEGF, eNOS, IGF1, and bFGF expression levels were higher in hWJ-MSC injection sites than those in control ones in STZ-induced diabetic rats. These results suggest that hWJ-MSC transplantation might improve diabetic erectile dysfunction through increased production of paracrine growth factors, highlighting a novel potential therapeutic option for erectile dysfunction. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the effects of an imbalance in the estrogen/androgen ratio on prostate fibrosis. Methods: Different concentrations of dihydrotestosterone (DHT) or estradiol (E2) dissolved in corn oil were injected subcutaneously into the nape of the castrated Sprague–Dawley (SD) rats over 28 consecutive days. Masson's trichrome staining and immunohistochemical staining were performed to detect the content of collagen fibers and the expression of collagen I, fibronectin, and elastin in the rat prostate of each group, respectively. DHT + E2 at different concentrations was administered to human normal prostate stromal immortalized cells (WPMY-1 cells) for 1 week. The expression of collagen I, fibronectin, elastin, transforming growth factor-β1 (TGF-β1), Smad3, and Smad7 was detected by Western blotting (WB). Then, WPMY-1 cells treated with 10 nM DHT + 5 pM E2 were incubated with the TGF-β/Smad pathway inhibitor SD208 for 1 week, after which collagen I, fibronectin, and elastin expression was detected by WB. Results: Compared with the uncastrated control and corn oil injection groups, the collagen fiber content and collagen I and fibronectin expression were increased and elastin expression was decreased in the castrated rat prostate with corn oil injection group (p < 0.01). Compared to castrated corn oil injection group, collagen fiber content, collagen I, and fibronectin expression were significantly decreased, and elastin expression was significantly increased in the castrated rat prostate 0.15 mg/kg DHT treatment group (p < 0.01). Following treatment with 0.15 mg/kg DHT, the content of collagen fibers, and the expression of collagen I and fibronectin were increased, and the expression of elastin was decreased in the rat prostate with increasing concentrations of E2 treatment group compared to the 0.15 mg/kg DHT group (p < 0.05, p < 0.01). Following treatment with 0.05 mg/kg E2, the collagen fiber content and the expression of collagen I and fibronectin were decreased, and the expression of elastin was increased in the rat prostate with increasing DHT concentration treatment group compared to the 0.05 mg/kg E2 group (p < 0.05, p < 0.01). Compared with the Control group, the expression of collagen I, fibronectin, TGF-β1 and Smad3 was decreased, and the expression of elastin and Smad7 was increased in WPMY-1 cells after treatment with 10 nM DHT (p < 0.01). Following treatment with 10 nM DHT, the expression of collagen I, fibronectin, TGF-β1, and Smad3 was increased, and the expression of elastin and Smad7 was decreased in WPMY-1 cells with increasing E2 concentration treatment compared to the 10 nM DHT group (p < 0.05, p < 0.01). Following treatment with 5 pM E2, the expression of collagen I, fibronectin, TGF-β1, and Smad3 was decreased, and elastin and Smad7 expression was increased with increasing DHT concentration compared to the 5 pM E2 group (p < 0.05, p < 0.01). Compared to the 10 nM DHT + 5 pM E2 group, the expressions of collagen I and fibronectin were decreased; the expression of elastin was increased in WPMY-1 cells after the supplement of TGF-β/Smad pathway inhibitor SD208 group (p < 0.05, p < 0.01). Conclusions: An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E2 may activate the degree of prostate fibrosis. In contrast to the effect of E2, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-β/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro; promote stem cell proliferation, differentiation, and migration; maintain stem cell activity; alleviate the problems of insufficient seed cell source, differentiation, and maturation; and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application. [ABSTRACT FROM AUTHOR]

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0–10.0 ng ml−1, 10.1–20.0 ng ml−1, and >20.0 ng ml−1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml−2, 0.297 ng ml−2, and 1.180 ng ml−2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies. [ABSTRACT FROM AUTHOR]

We conducted the present study to assess the correlation of the prostatic anatomical parameters, especially the ratio of peripheral zone thickness and transitional zone thickness, with clinical and uroflowmetry characteristics suggestive of benign prostate hyperplasia (BPH). A total of 468 consecutive patients with a detailed medical history were identified. All patients were evaluated by scoring subjective symptoms with the International Prostate Symptom Score (IPSS) and quality of life (QoL). The prostatic anatomical parameters were measured using transrectal ultrasonography, and postvoid residual urine and maximum flow rate (Qmax) values were also determined. Pearson's correlation analysis revealed that both total prostate volume (TPV; r = 0.160, P < 0.001) and transitional zone volume (TZV; r = 0.104, P = 0.016) increased with patients' age; however, no correlations were observed of TPV, TZV, transitional zone index (TZI), and transitional zone thickness (TZT) with IPSS or QoL (all P >0.05). Peripheral to transitional zone index (PTI) was found negatively correlated with total IPSS (r = −0.113, P = 0.024), storage IPSS (r = −0.103, P = 0.041), and voiding IPSS (r = −0.123, P = 0.014). As regards the uroflowmetry characteristics, PTI (r = 0.157, P = 0.007) was indicated to be positively correlated with Qmaxand negatively correlated with TZI (r = −0.119, P = 0.042) and TZT (r = −0.118, P = 0.045), but not correlated with TPV, TZV, or peripheral zone thickness (PZT) (all P > 0.05). Postvoid residual urine (PVR) had not correlated with all the prostatic anatomical variables (all P > 0.05). This is the first study that formally proposed the concept of PTI, which is an easy-to-measure prostate anatomical parameter which significantly correlates with total IPSS, storage IPSS, voiding IPSS, and Qmax, suggesting that PTI would be useful in evaluating and managing men with lower urinary tract symptoms (LUTS)/BPH. However, well-designed studies are mandatory to verify the clinical utility of PTI. [ABSTRACT FROM AUTHOR]

Erectile dysfunction attributable to testosterone deficiency is less common in young males, and the effect of estradiol on erectile function in eugonadal young males is unclear. We analyzed data from 195 male participants, including 143 eugonadal patients with erectile dysfunction and 52 healthy men. To distinguish psychogenic and organic erectile dysfunction, penile rigidity was measured using the nocturnal penile tumescence rigidity test. Serum levels of sexual hormones were quantified by electrochemiluminescence, and penile vascular status was assessed by penile color Doppler ultrasound. Both serum estradiol levels and the ratio of estradiol to testosterone were higher in patients with organic erectile dysfunction than in patients with psychogenic erectile dysfunction or healthy controls. Organic erectile dysfunction was negatively associated with estradiol levels and the ratio of estradiol to testosterone, and estradiol was the only significant risk factor for organic erectile dysfunction (odds ratio: 1.094; 95% confidence interval: 1.042–1.149, P = 0.000). Moreover, serum estradiol levels were negatively correlated with penile rigidity. Serum estradiol levels were higher and penile rigidity was lower in patients with venous erectile dysfunction than in patients with nonvascular erectile dysfunction. We conclude that elevated serum estradiol levels may impair erectile function and may be involved in the pathogenesis of organic erectile dysfunction in eugonadal young men. [ABSTRACT FROM AUTHOR]

Background: Sirtuin-7 (SIRT7) is associated with the maintenance of tumorigenesis. However, its functional roles and oncogenic mechanisms in prostate cancer (PCa) are poorly understood. Here, we investigated the roles and underlying molecular mechanisms of SIRT7 in PCa cell growth and androgen-induced autophagy. Methods: The LNCap and 22Rv1 PCa cell lines were subjected to quantitative reverse transcription (RT)-PCR to characterize their genes encoding SIRT7, AR, and SMAD4. The proteins produced from these genes were quantified by western blotting and immunoprecipitation analysis. SIRT7-depleted cells were produced by transfection with plasmid vectors bearing short hairpin RNAs against SIRT7. The proliferation of each cell line was assessed by CCK8 and EdU assays. Autophagic flux was tracked by mRFP–GFP–LC3 adenovirus under an immunofluorescence microscope. Apoptosis was evaluated by flow cytometry. Tumors were induced in mouse axillae by injection of the cell lines into mice. Tumor morphology was examined by immunohistochemistry and relative tumor growth and metastases were compared by a bioluminescence-based in vivo imaging system. Results: SIRT7 depletion significantly inhibited cell proliferation, androgen-induced autophagy, and invasion in LNCap and 22Rv1 cells (in vitro) and mouse xenograft tumors induced by injection of these cells (in vivo). SIRT7 knockdown also increased the sensitivity of PCa cells to radiation. Immunohistochemical analysis of 93 specimens and bioinformatic analysis revealed that SIRT7 expression was positively associated with androgen receptor (AR). Moreover, the AR signal pathway participated in SIRT7-mediated regulation of PCa cell proliferation, autophagy, and invasion. SIRT7 depletion downregulated the AR signal pathway by upregulating the level of SMAD4 protein in PCa cells. Conclusion: SIRT7 plays an important role in the development and progression of human PCa and may be a promising prognostic marker for prostate cancer. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development; however, after 18‐24 months of AR blocking therapy, patients invariably progress to castration‐resistant prostate cancer (CRPC), which remains an urgent problem to be solved. Therefore, finding key molecules that interact with AR as novel strategies to treat prostate cancer and even CRPC is desperately needed. In the current study, we focused on the regulation of RNA‐binding proteins (RBPs) associated with AR and determined that the mRNA and protein levels of AR were highly correlated with Musashi2 (MSI2) levels. MSI2 was upregulated in prostate cancer specimens and significantly correlated with advanced tumor grades. Downregulation of MSI2 in both androgen sensitive and insensitive prostate cancer cells inhibited tumor formation in vivo and decreased cell growth in vitro, which could be reversed by AR overexpression. Mechanistically, MSI2 directly bound to the 3′‐untranslated region (UTR) of AR mRNA to increase its stability and, thus, enhanced its transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2‐AR axis and provide novel evidence towards a strategy against prostate cancer. [ABSTRACT FROM AUTHOR]

This study compared the diagnostic efficacy of transrectal ultrasound (TRUS)-guided prostate biopsy (TRBx) and transperineal prostate biopsy (TPBx) in patients with suspected prostate cancer (PCa). We enrolled 2962 men who underwent transrectal (n = 1216) or transperineal (n = 1746) systematic 12-core prostate biopsy. Clinical data including age, prostate-specific antigen (PSA) level, and prostate volume (PV) were recorded. To minimize confounding, we performed propensity score-matching analysis. We measured and compared PCa detection rates between TRBx and TPBx, which were stratified by clinical characteristics and Gleason scores. The effects of clinical characteristics on PCa detection rate were assessed by logistic regression. For all patients, TPBx detected a higher proportion of clinically significant PCa (P < 0.001). Logistic regression analyses illustrated that PV had a smaller impact on PCa detection rate of TPBx compared with TRBx. Propensity score-matching analysis showed that the detection rates in TRBx were higher than those in TPBx for patients aged >– 80 years (80.4% vs 56.5%, P = 0.004) and with PSA level 20.1–100.0 ng ml−1 (80.8% vs 69.1%, P = 0.040). In conclusion, TPBx was associated with a higher detection rate of clinically significant PCa than TRBx was; however, because of the high detection rate at certain ages and PSA levels, biopsy approaches should be optimized according to patents' clinical characteristics. [ABSTRACT FROM AUTHOR]

Quaking homolog (QKI) is a member of the RNA‐binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'‐untraslated region (3'‐UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI‐6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI‐6 overexpression or knockdown. QKI‐6 down‐regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI‐6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI‐6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI‐6 expression had opposite effects in vitro and in vivo. QKI‐6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'‐UTR, whereas E2F3 induced QKI‐6 transcription by binding to the QKI‐6 promoter in negative feedback mechanism. QKI‐6 expression also suppressed activity and expression of nuclear factor‐κB (NF‐κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI‐6. In conclusion, QKI‐6 down‐regulation contributes to bladder cancer development and progression. [ABSTRACT FROM AUTHOR]

Objectives: 5α‐reductase inhibitor (5‐ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment. Materials and Methods: Prostate specimens from patients were collected. Insulin‐like growth factor 1 (IGF‐1), Beclin‐1, LC3 levels, was analysed by immunohistochemistry. The role IGF‐1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated. Results: We demonstrated that IGF‐1 expression is down‐regulated in prostate fibroblasts after long‐term 5‐ARI application. A decrease in IGF‐1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF‐1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long‐term 5‐ARI application reduces IGF‐1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression. Conclusions: Focusing on the autophagy induced by low levels of IGF‐1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development. [ABSTRACT FROM AUTHOR]

Ureteric stenting is an effective drainage method in patients with acute urinary tract infection caused by ureteral calculi; however, the optimal ureteral stent indwelling time has not been clearly defined. The aim of this study was to evaluate the effect of ureteric stent indwelling time on the treatment of acute infection secondary to urinary tract calculi. A total of 142 patients with acute infection caused by urinary tract calculi were identified retrospectively from January 2011 to August 2015 at our institution. 63 patients were with ureteric stenting for 7 days (A group) and 79 patients with ureteric stenting for more than 7 days (B group). The patient characteristics of two groups were analyzed and the clinical data before and after stenting were compared. The postoperative complication outcomes were collected and analyzed. Effective drainage obtained from ureteral stenting clearly abated the infection after stenting for 7 days; WBC count, WBCs in urine, and positive rate of urine culture were significantly decreased compared with the condition of immediate stenting. Both groups showed similar stone clearance rates (96.8% vs. 96.2%, p = 0.841), and there was no significant difference in the rate of postoperative complications, especially related to urinary tract infection (6.3% vs. 6.3%, p = 1.000). It is safe and effective for patients with acute urinary tract infection secondary to urinary tract calculi to be treated by ureteroscopic lithotripsy after stenting for one week. Prolonging the stenting period achieves no added benefit for patients. [ABSTRACT FROM AUTHOR]

The aim of this study is to compare the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy (RPLU) and ureteroscopic holmium laser lithotripsy (UHLL) as two minimally invasive procedures in managing obstructive upper ureteral calculi with concurrent urinary tract infections (UTI). The retrospective study included 189 patients who underwent unilateral obstructive upper ureteral stones with concurrent UTI from January 2007 to November 2014 at our institution. Patients received RPLU (81 cases) or UHLL (108 cases). All patients received preoperative anti-infection treatment (indwelling ureteral stent and/or preoperative antibiotics). Collected data, including sex, age, stone size, success rate, operation duration, post-operation hospitalization time, and post-operation complications, were compared. All patients were followed up for more than 6 months after surgeries, and no ureterostenosis occurred. The study included 189 patients, 41 (21.7 %) females and 148 (78.3 %) males with a medium age of 52 years (range 22-81 years). All surgeries were successfully performed without conversion to open surgery. Stone size in the RPLU group was larger than that of the UHLL group (16.1 ± 1.4 vs. 10.4 ± 1.6 mm, P = 0.012). Operative duration (P = 0.009) and hospitalization time (P < 0.001) in the UHLL group were significantly shorter than those in the RPLU group, whereas stone clearance rate was significantly higher in the RPLU group (100 vs. 88.9 %, P = 0.002). Of note, postoperative fever was more common in patients treated with UHLL (15 cases) versus RPLU (4 cases) (13.9 vs. 4.9 %, P = 0.043). Moreover, in the UHLL group, three patients without a preoperative indwelling ureteral stent were complicated with sepsis, which was not seen in RPLU group. In our study, the safety and stone clearance rate of RPLU are better than those of UHLL in the treatment of unilateral upper ureteric calculi with concurrent UTI. Preoperative antibiotics and indwelling ureteral stent may reduce the risk of postoperative infections. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility and effectiveness of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping (3D-LPNSSAC) comparing with the conventional two-dimensional laparoscopic partial nephrectomy (2D-LPN). Methods: Between November 2012 and March 2014, 90 patients with cT1 renal tumor at Shanghai General Hospital were enrolled in our study, which were randomly divided into two groups: the 3D-LPNSSAC group ( n = 45) and 2D-LPN group ( n = 45). The perioperative variables, including operative time, dissecting time, suturing time, blood loss, warm ischemia time (WIT), preoperative and postoperative renal functions, were recorded and analyzed. In addition, the oncological outcomes and complications were also evaluated. Results: All the LPNs were performed successfully without conversion to radical nephrectomy or open surgery, only three cases were converted to total renal artery clamping during 3D-LPNSSAC. There were no significant differences in operative time and dissecting time between the groups, while the suturing time was shorter during 3D-LPNSSAC ( P < 0.01). The technique was associated with higher blood loss ( P < 0.01). The technique of 3D-LPNSSAC significantly reduced WIT ( P = 0.04), and better postoperative ipsilateral renal function could be obtained during 3D-LPNSSAC ( P < 0.01). During a mean follow-up time of 16.8 months (range 5.5-22.5 months), the complication rate was 8.8 % (8/90) and no tumor reoccurrence was detected. Conclusions: 3D-LPNSSAC is a feasible and safe technique for treating selective renal tumors, presenting with the beneficial clinical outcomes of reduced suturing time, shorter WIT and better postoperative ipsilateral renal function. [ABSTRACT FROM AUTHOR]

ABSTRACT This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di( n-butyl) phthalate (DBP). DBP was administered to timed-pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart-lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen-related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen-related signaling networks might play an important role in the occurrence of ARMs. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 261-268, 2016. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of urgent percutaneous nephrolithotomy (PNL) for acute kidney injury secondary to bilateral upper urinary stones in infants. Methods: A total of seven infants (five boys and two girls), aged from 5 to 12 months, underwent urgent PNL for calculus anuria from September 2011 to March 2013. The initial blood test revealed acute renal injury in all infants. After correcting electrolyte imbalance and acid-base status through medical treatment in a short time without dialysis, all urgent PNL procedures were performed with 16F percutaneous access and small-diameter nephroscopes designed specifically for pediatric surgery on the side with the more dilated pelvis. Stones were fragmented with a pneumatic lithotripter. Results: Stones were completely removed from the operative side kidneys. The operating time ranged from 35 to 57 min. Blood BUN, serum creatinine, and electrolyte levels returned to normal on postoperative 36 h. There were no major perioperative or postoperative complications and deaths. Conclusions: When performed by experienced endourologists, urgent PNL is a safe and effective procedure in infants for acute kidney injury secondary to bilateral upper urinary stones. [ABSTRACT FROM AUTHOR]

Mounting evidence has indicated the crucial role of Wnt5a in the embryonic development including guts. However, the Wnt5a involvement in the process of anorectal malformations (ARMs) remains unclear. In this study, we examined the expression of Wnt5a during ARMs development in the offspring of di(n-butyl) phthalate (DBP)-treated pregnant rats. During the neonatal period, Wnt5a expression was evaluated in the terminal rectum of ARM offspring, non-ARM littermates and controls. Using real-time polymerase chain reaction (real-time PCR), western-blot analysis and immunohistochemistry approaches, we found a significant decrease of Wnt5a expression in DBP-induced ARMs rats. Collectively, our results demonstrate the aberrant expression of Wnt5a during anorectal development, which suggests that Wnt5a might be involved in DBP-induced ARMs. [ABSTRACT FROM AUTHOR]

Two-micrometer thulium laser resection of the prostate-tangerine technique (TmLRP-TT) has been introduced as a minimally invasive treatment for benign prostatic hyperplasia (BPH). Acute urinary retention (AUR) is a common and serious complication of BPH. The study was undertaken to assess the clinical efficacy and safety of TmLRP-TT in the treatment of patients with AUR secondary to BPH. A prospective evaluation of 52 patients undergoing TmLRP-TT from December 2011 to November 2012 was carried out. Preoperative status, surgical details, and perioperative complications were recorded. The follow-up outcome was evaluated with subjective and objective tests at 1 and 6 months. Mean age was 70.3 ± 7.8 years old. Mean prostate volume was 69.6 ± 31.6 ml, and mean residual volume with retention was 274.5 ± 150.7 ml. Mean operative time was 64.1 ± 30.4 min. Mean catheterization duration was 5.4 ± 1.1 days. The mean International Prostate Symptom Score, quality of life score, and postvoid residual urine volume decreased significantly at 6-month follow-up (21.6 ± 6.8 vs. 6.8 ± 3.2, 4.4 ± 1.2 vs. 0.9 ± 0.8, 274.5 ± 150.7 vs. 40.6 ± 22.5 ml). The mean maximum urinary flow rate was 18.7 ± 6.9 ml/s postoperative. Two (3.8 %) of the patients required blood transfusion in operation. Five (9.6 %) of the patients had transient hematuria postoperative, and two (3.8 %) of them received 3 days recatheterization due to clot retention. The early clinical results suggest that the TmLRP-TT is a promising safe, effective, and minimally invasive treatment for patients with AUR secondary to BPH. The incidence of complications was low. [ABSTRACT FROM AUTHOR]

Thulium laser resection of the prostate-tangerine technique (TmLRP-TT) dissects whole prostatic lobes off the surgical capsule, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of TmLRP-TT for older symptomatic benign prostatic hyperplasia patients with large prostates during 18 months of follow-up. A prospective analysis of 95 consecutive patients with large prostates (>80 ml) who underwent surgical treatment using TmLRP-TT was carried out. All patients were evaluated preoperatively and at 1, 6, 12, and 18 months postoperatively by the International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate ( Q), postvoid residual urine volume (PVR), International Index of Erectile Function 5 (IIEF-5), urine analysis, and urine culture. Perioperative complications were recorded and graded by the modified Clavien classification system (CCS). Mean preoperative prostate volume was 106.81 ± 24.79 ml. TmLRP-TT was successfully completed in all patients. The mean operative duration, catheterization time, and hospital stay were 95.36 ± 27.06 min, 2.25 ± 0.9 days, and 5.39 ± 1.18 days, respectively. The decrease in mean hemoglobin level was 1.23 ± 0.72 g/dl, and that in mean serum sodium level was 0.71 ± 2.56 mmol/l. Within the observation period of 18 months, the patients showed an improvement in IPSS (20.01 ± 7.08 vs. 4.96 ± 3.68), QoL (4.10 ± 1.16 vs. 1.23 ± 1.30), Q (8.14 ± 3.81 ml/s vs. 18.33 ± 2.56 ml/s) and PVR (102.70 ± 70.64 ml vs. 20.28 ± 30.02 ml), compared with baseline values ( P < 0.001). IIEF-5 remained stable. Minor complications occurred in 10 (10.52 %) of 95 patients (Clavien grade 1, 9.47 % and grade 2, 1.05 %). There were no severe complications requiring reintervention (Clavien grade 3, 0 % and grade 4, 0 %). TmLRP-TT is a safe and effective surgical endoscopic technique associated with a low complication rate in large prostates as assessed during an 18-month follow-up period. It is a promising technology, which may be considered as one of the alternatives to open simple prostatectomy (OP) for large prostates in the future. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the biological functions of miR-96 in the processes of proliferation and clonogenicity in the prostate cancer cells. miR-96 was identified to be markedly up-regulated in prostate cancer cell and cancer tissues compared with normal prostate cell and normal prostate tissues by microarray method and RT-PCR analysis. Down-regulation of miR-96 expression reduced the proliferation and colony formation ability of PC3 prostate cancer cells, while over-expression of miR-96 induced proliferation and colony formation ability of LNCaP prostate cancer cells. Forkhead box protein O1 (FOXO1) is key tumor suppressors and has been shown to play key roles in the regulation of diverse cellular processes, including cell proliferation, differentiation, cell cycle progression and apoptosis. The expression level of FOXO1 was strikingly up-regulated in PC3 cells after transfected with miR-96 inhibitor, and FOXO1 expression was down-regulated in LNCaP cells after transfected with miR-96 mimics. miR-96 may play a vital role in promoting cell proliferation in human prostate cancer cells. Inhibition of miR-96 caused expression increase of tumor suppressor gene FOXO1, thus manipulating miR-96 expression may be a promising approach in treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

The thulium laser (Tm-laser) technique has been used in the management of many urologic conditions. The present study aimed to evaluate the use of this technique for distal ureter and bladder cuff (DUBC) excision during nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Fifty-eight patients with UUT-UC who underwent radical nephroureterectomy were included in this retrospective study. DUBC was managed by open excision in 24 cases, by transurethral electrosurgery in 17 cases, and by transurethral Tm-laser in 17 cases. Perioperative measures and oncologic outcomes were compared among the three groups. Furthermore, 11 human ureteral segments were collected to measure the burst pressure and show physical pressure tolerance, and six ureteral segments were assessed histologically to investigate the sealing effect. Operative time and hospital stay were significantly longer, and intraoperative blood loss was significantly greater in the open excision group than in the electrosurgery and Tm-laser groups ( P < 0.05 for all). There were no significant differences in these parameters between the electrosurgery and Tm-laser groups. In addition, there were no significant differences in the incidences of bladder tumors and retroperitoneal recurrence of urothelial carcinoma among the three groups. The coagulation time and resection time were significantly shorter in the Tm-laser group than in the electrosurgery group. The mean burst pressure did not differ significantly between the tissues sealed by electrosurgery and by Tm-laser. Histopathological analyses showed that distal ureters were completely sealed by both electrosurgery and Tm-laser. The Tm-laser technique is superior to open excision and comparable to transurethral electrosurgery in the management of DUBC during nephroureterectomy for UUT-UC, offering an alternative treatment option for this condition. [ABSTRACT FROM AUTHOR]

Aging is a major risk factor for prostate cancer (PCa), and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors (ARs) by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA (shRNA), matrix metalloproteinase (MMP) expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males. [ABSTRACT FROM AUTHOR]

Objective.The aim of this study was to report the authors' experience with percutaneous intrarenal marsupialization of symptomatic peripelvic renal cysts. Material and methods. Thirty-one patients (16 male and 15 female, with a mean age of 49 years) with a peripelvic renal cyst associated with chronic flank or lumbar pain or urinary infection were selected for percutaneous intrarenal marsupialization with a 2 μm laser in the authors' centre from January 2005 to December 2010. Cyst size ranged from 4.5 to 10.5 (mean 6.0) cm. The cysts were punctured by a percutaneous technique guided by ultrasonography, a 20.8 F nephroscope was introduced and the whole internal surface of the cyst was inspected. Methylene blue was injected through the ureteral catheter to help identify the collecting system. A 1.5-4 cm incision was made at the avascular area of the cystic wall by the 2 μm laser to achieve intrarenal marsupialization of the cyst into the renal collecting system. One or two 6 F double-J stents were placed with the proximal end in the cyst for 2-3 months. Results.The mean operation time was 50 (25-120) min. No serious complications such as massive bleeding, urine leak or infected haematoma occurred. The patients were followed up for a mean of 12 (range 3-36) months. All patients were relieved of their symptoms. Eighteen cysts disappeared after surgery, while 13 cysts reduced in size by over one-third and communicated with the renal collecting system. No enlargement of cysts was observed. Conclusions.Percutaneous intrarenal marsupialization with a 2 μm laser is an effective and safe procedure and may offer a minimally invasive alternative for the management of symptomatic peripelvic renal cysts. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to investigate whether mesothelial cells could function as seed cells to construct tissue-engineered peritoneum-like tissue for urethral reconstruction in a rabbit model. Materials and Methods: Bladder acellular matrices were prepared and trimmed to 1.5 × 1 cm. Nine male rabbits underwent omentum biopsy and autologous mesothelial cells were isolated. After in vitro expansion, the cells were seeded onto the matrices and incubated for 7 days. In 18 rabbits, a pendulous urethral segment 1.5 cm long was totally excised and urethroplasty was performed with tubularized matrices seeded with cells in 9 animals and without cells in 9 as controls. Urethrography was performed at 1, 2 and 6 months postoperatively. Meanwhile, the neourethras were harvested and analyzed grossly and histologically. Results: Histological analysis of the cell-seeded grafts revealed a loose collagen matrix covered with a single layer of mesothelim. Serial urethrography indicated a wide urethral caliber without stricture formation in animals implanted with cell-seeded matrices, while all animals of the control group developed stricture. Histological analysis of the implanted cell-seeded matrices demonstrated a normal urethral architecture by 1 month, composed of multilayers of urothelium surrounded by smooth muscle bundles, which became increasingly organized with time. By 6 months, the neourethra could be hardly distinguished from native urethra both grossly and histologically. Conclusions: Autologous mesothelial cells could be successfully used as seed cells for tubularized urethral reconstruction in male rabbits. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate fluid-electrolyte and renal pelvic pressure (RPP) changes during ureteroscopic lithotripsy. Fifteen patients were detected with residual ureteral calculi after minimally invasive percutaneous nephrolithotomy (MPCNL), distal ureter calculi in three, midureter calculi in four, proximal calculi in eight. RPP was measured via the percutaneous nephrostomy tube by urodynamic study at irrigation pressures of 50, 100 and 200 mmHg. Haemoglobin (Hb), haematocrit (Hct), blood urea mitrogen (BUN), creatinine (Cre), serum sodium (Na+), potassium (K+), chlorine (Cl-) were recorded before and after ureteroscopic lithotripsy. There were no significant differences between Hb, Hct, BUN, Cre, Na+, K+, Cl- values. Baseline RPP was (16.37 ± 3.14) cmH2O, RPPs were 46.06 ± 6.85 cmH2O, 99.07 ± 14.62 cmH2O and 166.27 ± 33.08 cmH2O at irrigation pressures of 50, 100 and 200 mmHg, they were much higher than baseline RPP (p < 0.0001). RPP in the proximal ureter was much higher than in the distal and middle ureter, 50.98 ± 4.52 cmH2O versus 40.44 ± 4.07 cmH2O (p = 0.0004), 110.26 ± 2.39 cmH2O versus 86.29 ± 11.60 cmH2O (p = 0.0014), 193.21 ± 5.88 cmH2O versus 135.47 ± 20.95 cmH2O (p = 0.0002) at irrigation pressures of 50, 100 and 200 mmHg. There were no significant changes in fluid-electrolyte. RPP was significantly increased during ureteroscopic lithotripsy, it was correlated with the irrigation pressure and the position in the ureter. [ABSTRACT FROM AUTHOR]

In this paper, we reviewed the features of common prostate diseases, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and chronic prostatitis (CP) that are specific to Asian men. Compared to the Westerners, Asians exhibit particular characteristics of prostate diseases. Through summarizing the epidemiology, symptomatology, diagnostics and therapeutics of these diseases, we find that Asians have a lower incidence of PCa than whites, but the incidences of BPH and CP are similar. Asian men with CP often suffer from fewer disease sites, but have a higher frequency of pain during urination rather than after sexual climax. Prostate-specific antigen (PSA) is a widely used marker for the diagnosis of PCa in both Asian and Western countries. Although the PSA level may be lower in Asians, the threshold used is based on whites. After reviewing the treatments available for these diseases, we did not find a fundamental difference between Asians and whites. Furthermore, the selection for the most appropriate treatment based on the individual needs of patients remains a challenge to urologists in Asia. After considering the traits of prostate diseases that are specific to Asian men, we hope to pave the way for the development of specific diagnostic and therapeutic strategies targeted specifically to Asian men. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the association between immune inflammation and androgen receptor (AR) expression in benign prostatic hyperplasia (BPH). We retrospectively analyzed 105 prostatectomy specimens. An immune inflammation score for each specimen was defined by combining three immunohistochemical markers (CD4, CD8 and CD20). The immunohistochemical markers were CD4 and CD8 for T lymphocytes, CD20 for B lymphocytes and AR antibody for the AR in BPH samples. Rates of CD4, CD8, CD20 and AR expression in BPH were 20 (19.0%), 21 (20.0%), 101 (96.2%) and 48 (45.7%), respectively. Total prostate volume (TPV) was higher in the immune inflammation group than in the non-immune inflammation group (62.7 ml vs. 49.2 ml, t=2.482, P<0.05). Patients in the immune inflammation group had a higher serum prostate-specific antigen (PSA) than those in the non-inflammation group (7.5 ng ml−1 vs. 5.4 ng ml−1, t=2.771, P<0.05). Specifically, the immune inflammation group showed a higher rate of AR expression than the non-inflammation group (56.1% vs. 28.2%, χ2=7.665, P<0.05). Our study revealed a strong association between immune inflammation and TPV, serum PSA and AR expression in BPH tissue. Prostate hyperplasia caused by an immune inflammatory process may contribute to BPH progression over time. Therefore, the inflammatory response involved in BPH may be a prime therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the peritoneal cavity could function as a bioreactor to produce autologous tubular grafts for ureteral reconstruction in beagles. Materials and Methods: 8-Fr Silastic tubes were implanted into the peritoneal cavities of 6 female beagles. At 3 weeks, the tubes were harvested and the tubular tissue covering the tubes was gently everted. A segment 3 cm in length of the right mid-ureter, involving two thirds of its diameter, was removed parallel to the ureteral axis, leaving a third of the ureteral wall. A 5-Fr double-J stent was inserted into the ureter through the created defect, and two thirds of the graft were anastomosed to both edges of the ureteral defect. One third of the graft was overlapped with the retained normal ureter and anastomosed to the external surface of the lumens. Thus, the graft was partly encapsulated by the remainder of ureteral wall. The stent was maintained for 6 weeks and removed. Excretory urography was performed at 8 (n = 3) and 12 weeks (n = 3), postoperatively. Meanwhile, the neoureter was harvested and analyzed. The left ureter served as the control and a simple intubated ureterotomy was performed. Results: Histological analysis of the tubular tissue demonstrated transversely arranged myofibroblasts and an outer layer of mesothelium. The tissue was easily everted and transplanted as a ureteral graft. Eight weeks postoperatively, the neoureter demonstrated normal ureteral architecture, composed of multilayers of urothelium surrounded by smooth muscle bundles, which became increasingly organized with time. Excretory urography indicated no stenosis or hydronephrosis. Conclusions: These results show that autologous tubular tissue grown within the recipients' peritoneal cavity can be used for ureteral reconstruction in the beagle model. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and β-oestradiol (E2) (P<0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P<0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-β1 (TGF-β1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l−1 DHT plus 10 nmol l−1 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone (PZ) of donors of varying ages and found that cultured stromal cells from old donors (PZ-old) were more enlarged and polygonal than those from young donors (PZ-young). Furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage(>100) and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor (HGF), fibroblast growth factor 5 (FGF5), insulin-like growth factor 2 (IGF2), insulin-like growth factor-binding protein 4 (IGFBP4), IGFBP5 and matrix metallopeptidase 1 (MMP1). Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction (PCR), Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent epithelial cells. This finding hints at a new potential strategy for the prevention of PCa. [ABSTRACT FROM AUTHOR]

The purpose of the current ex vivo study was to compare the speed of vaporesection of human prostatic tissue with benign prostatic hyperplasia (BPH) and the depth of tissue damage using 70- and 120-W 2-µm laser devices. Fresh prostatic tissue specimens were obtained from five patients by open prostatectomy, and were divided into separate groups (70 and 120 W) based on the energy of the laser output (70 and 120 W, respectively). The vaporesection speed, coagulation zone depth and the necrotic tissue layer in the prostatic tissue were evaluated. The current result showed that the speeds (mean±s.d.) of vaporesection were 5.21±0.66 and 10.39±1.15 g/5 min for the 70 and 120 W groups, respectively (P=0.000). There was no difference in the depth of necrosis/coagulation (0.98±0.13/0.30±0.09 and 0.99±0.12/0.31±0.08 mm) for the 70 and 120 W groups, respectively. In conclusion, both 70- and 120-W 2-µm laser devices had superficial tissue damage during the vaporesection of human prostate tissue; moreover, the 120-W laser offers a higher vaporesection speed than the 70-W laser. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone (TZ) or peripheral zone (PZ) in the carcinogenesis of prostate cancer (PCa) epithelial cells (PC-3) in vitro and in vivo co-culture models. Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis. In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established. We assessed tumor growth and weight in the in vivo nude mice model. There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate. In all, 514 differentially expressed genes were selected by microarray analysis; 483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ. Co-culture with PZ stromal cells and transforming growth factor-β1 (TGF-β1) increased the tumor growth of PC-3 cells in vitro and in vivo, as well as Bcl-2 expression. On the other hand, stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model. We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate, and stroma–epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation.Asian Journal of Andrology (2009) 11: 176–182. doi: 10.1038/aja.2008.33; published online 5 January 2009. [ABSTRACT FROM AUTHOR]

Post-translational degradation of protein plays an important role in cell life. We employed chimeric molecules (dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]) to facilitate androgen receptor (AR) degradation via the ubiquitin–proteasome pathway (UPP) and to investigate the role of AR in cell proliferation and viability in androgen-sensitive prostate cancer cells. Western blot analysis and immunohistochemistry were applied to analyse AR levels in LNCaP cells after DHT-PROTAC treatment. Cell counting and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay were used to evaluate cell proliferation and viability after AR elimination in both LNCaP and PC-3 cells. AR was tagged for elimination via the UPP by DHT-PROTAC, and this could be blocked by proteasome inhibitors. Degradation of AR depended on DHT-PROTAC concentration, and either DHT or an ALAPYIP-(arg)8 peptide could compete with DHT-PROTAC. Inhibition of cell proliferation and decreased viability were observed in LNCaP cells, but not in PC-3 or 786-O cells after DHT-PROTAC treatment. These data indicate that AR elimination is facilitated via the UPP by DHT-PROTAC, and that the growth of LNCaP cells is repressed after AR degradation.Asian Journal of Andrology (2009) 11: 119–126. doi: 10.1038/aja.2008.26; published online 15 December 2008. [ABSTRACT FROM AUTHOR]

The critical role played by stroma–epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-β, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-1, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR), and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.Asian Journal of Andrology (2009) 11: 28–35. doi: 10.1038/aja.2008.39; published online 22 December 2008. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) plays an important role in the development and progression of prostate cancer (PCa). Androgen deprivation therapy is initially effective in blocking tumor growth, but it eventually leads to the hormone-refractory state. The detailed mechanisms of the conversion from androgen dependence to androgen independence remain unclear. Several PCa cell lines were established to study the role of AR in PCa, but the results were often inconsistent or contrasting in different cell lines, or in the same cell line grown under different conditions. The cellular and molecular alteration of epithelial cells and their microenvironments are complicated, and it is difficult to use a single cell line to address this important issue and also to study the pathophysiological effects of AR. In this paper, we summarize the different effects of AR on multiple cell lines and show the disadvantages of using a single human PCa cell line to study AR effects on PCa. We also discuss the advantages of widely used epithelium–stroma co-culture systems, xenograft mouse models, and genetically engineered PCa mouse models. The combination of in vitro cell line studies and in vivo mouse models might lead to more credible results and better strategies for the study of AR roles in PCa.Asian Journal of Andrology (2009) 11: 39–48. doi: 10.1038/aja.2008.44; published online 22 December 2008. [ABSTRACT FROM AUTHOR]

Aim: To investigate the antitumor immunity by a dendritic cell (DC) vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods: DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine (SLC) cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC+lysate–DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results: We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC+lysate–DC inhibited tumor growth most significantly when compared with SLC–DC, lysate–DC, DC or phosphate buffer solution (PBS) counterparts ( P < 0.01). Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4+, CD8+ T cell and CD11c+ DC within established tumor treated by SLC +lysate–DC vaccine than other DC vaccines ( P < 0.01). Conclusion: DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4+, CD8+ T cell and DC, which might provide a potential immunotherapy method for prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Bladder carcinoma is the most common urological malignancy in China. Gene mutation may be one of causes of carcinogenesis in the cancer. We therefore investigated the mRNA expression of RTKN gene in clinic malignant bladder carcinoma and explored the relationship between the novel gene and the cancer. Methods: Total RNA was extracted from 33 surgically resected specimens of bladder carcinoma and 19 specimens of tumor-free bladder tissues. After the optimal reverse-transcription polymerase chain reaction condition was established, the mRNA expression levels of the RTKN gene in the lesions and tumor-free bladder tissues were examined semiquantitatively, and the relationships between expression levels of RTKN and clinical patho- logical features were analyzed. Results: The expression of RTKN gene mRNA in 33 human bladder carcinoma tissues was significantly higher than that in 19 human tumor-free bladder tissues (0.93 7 ± 0.103 vs. 0.350 ± 0.082). The average ratio of RTKN expression in neoplasms to that in tumor-free bladder tissues was 0.350 ± 0.164. Based on this ratio the 33 patients were divided into three groups: a downregulated expression group (n 2), an up regulated expression group (n 22), and an unchanged group (n = 9). Although the x2 test demonstrated a statistically nonsignificant differences in RTKN expression between tumor stages Ta, T1, and T2 overall in the 33 human bladder carcinoma, the t test showed that there were statistically significant differences between solitary and multiple tumors, between the paired group aged younger or older than 70 years in 27 de novo bladder carcinoma patients, and between the groups with tumor larger or smaller than 2.25 cm3. Conclusions: These results suggest that the RTKN gene is involved in bladder carcinogenesis and progression in bladder carcinoma, indicating that RTKN gene could be a molecular target in cancer therapy. [ABSTRACT FROM AUTHOR]