OBJECTIVE To reveal the potential role of the basic helix-loop-helix myogenic transcription regulator MyoD in the regulation of castration-resistant prostate cancer. METHODS Expression level of MyoD was assessed in prostate cancer tissues using quantitative reverse transcription polymerase chain reaction and immunohistochemistry and in experimentally induced castration-resistant LNCaP/R cells using quantitative reverse transcription polymerase chain reaction and immunoblotting. Effect of MyoD knockdown on LNCaP/R cell progression was determined by assessing cell proliferation, apoptosis, and colony formation rate. The effect of MyoD knockdown on the oxidative stress state in PC3 cells was determined by assessing antioxidant response gene expression and glutathione synthetase-to-glutathione ratio. Finally, the functional link between the nuclear factor erythroid-derived 2-related factor 1 (NRF1) and the regulation of antioxidant response element-driven transcription by MyoD was studied at both molecular and functional levels. RESULTS MyoD expression was significantly upregulated in hormone-refractory prostate cancer tissues and in experimentally induced castration-resistant LNCaP/R cells, and MyoD knockdown effectively impaired LNCaP/R cell proliferation and promoted apoptosis under androgen-depleted condition. Moreover, MyoD enhanced the glutathione production and protected against oxidative stress by positively regulating a cluster of antioxidant genes known to be the downstream targets of NRF1. Mechanistically, MyoD could augment the antioxidant response element-driven transcription in an NRF1-dependent manner, and the stimulatory effect of MyoD on the antioxidant response was substantially compromised in the presence of NRF1 small interfering RNA treatment. CONCLUSION We have identified an unexpected collaboration between MyoD and NRF1 under androgen-depleted condition, which may serve as an important adaptive mechanism during the pathogenesis of castration-resistant prostate cancer. (C) 2018 Elsevier Inc.
OBJECTIVE To investigate whether ischemic postconditioning (IPO) and ozone postconditioning (OP) could synergistically attenuate renal ischemia-reperfusion (I/R) injury and its possible mechanism. MATERIALS AND METHODS An in vivo rat model of renal I/R injury was established, and the serum and kidneys were harvested after reperfusion to assess renal function and histologic changes. For the in vitro study, the cultured NRK-52E cells were subjected to 3 hours of hypoxia (5% CO2, 1% O-2, and 94% N-2) followed by 24 hours of reoxygenation (5% CO2, 21% O-2, and 74% N-2). The mRNA expression levels were analyzed by real-time polymerase chain reaction, and the protein expression levels were analyzed by using Western blot, immunofluorescence staining and enzyme-linked immunosorbent assay. RESULTS Kidneys undergone I/R showed characteristic renal dysfunction and pyroptosis. IPO or OP could prevent the elevated blood urea nitrogen and creatinine, renal damage, as well as pyroptosis, however, the combined application of them had more obvious protection. Oxidative stress and pyroptosis were increased in hypoxia and reoxygenation (H/R) model using NRK-52E cells. The combination of hypoxic postconditioning and OP had more protective effects on oxidative abnormalities and pyroptosis compared with the single application of hypoxic postconditioning or OP. CONCLUSION Our in vivo and in vitro studies show the combination of IPO and OP synergistically protected the kidney from I/R by attenuating pyroptosis in kidney cells. (C) 2018 Elsevier Inc.
Type 2 papillary renal cell carcinoma (PRCC) is a malignant tumor originated from renal tubular epithelial cells. Here we present a rare case of extrarenal type 2 PRCC which is located at the right lateral side of the retroperitoneal inferior vena cava. No suspicious lesions were detected in the bilateral kidneys. The diagnosis was confirmed by histopathological examination after complete excision of the tumor. No recurrence was observed in 5 months of follow-up after surgery. (C) 2018 Elsevier Inc.
OBJECTIVE To assess the expression profile and functional mechanism of long noncoding RNA (lncRNA) insulin growth factor 2 antisense (IGF2AS) in human prostate cancer (PCa). METHODS Quantitative reverse transcriptase-polymerase chain reaction was applied to assess IGF2AS expression in immortal PCa cell lines and in situ human PCa tumors. IGF2AS was overexpressed in VCaP and PC3 cells to assess its effect on PCa cell proliferation and invasion in vitro, and xenograft in vivo. The effect of IGF2AS overexpression on IGF2 was also assessed in PCa cells. Then, IGF2 was upregulated in IGF2AS-overexpressed PCa cells to assess the functional involvement of IGF2 in IGF2AS-mediated PCa cell development. RESULTS IGF2AS was downregulated in both PCa cell lines and human PCa tumors. In VCaP and PC3 cells, lentivirus-induced IGF2AS overexpression suppressed cancer cell proliferation and invasion in vitro, and xenograft development in vivo. IGF2 was downregulated by IGF2AS overexpression. Conversely, IGF2 upregulation revered the suppressing function of IGF2AS on PCa proliferation and invasion. CONCLUSION LncRNA IGF2AS is acting as an epigenetic tumor suppressor in human PCa, likely through inverse regulation on IGF2. IGF2AS/IGF2 axis may be a future therapeutic target for PCa treatment.(C) 2018 Elsevier Inc.
OBJECTIVE To illustrate our technique to construct the Institute of Urology Peking University (IUPU) orthotopic ileal bladder and present our initial experience. METHODS From August 2017 to April 2018, 12 patients with bladder cancer underwent radical cystectomy (RC), pelvic lymph node dissection and extracorporeal construction of an IUPU neobladder (IUPUB) by an experienced surgeon. We present the demographic, clinicopathologic, perioperative, and follow-up data. We also describe our step-by-step surgical technique for the IUPUB in this article. RESULTS Laparoscopic RC with an extracorporeal IUPUB was successfully accomplished in 11 patients, and 1 patient was converted to open RC with an IUPUB. The median total operative time and median time spent suturing the pouch were 248 minutes and 23 minutes, respectively. The median estimated blood loss was 150 mL. The median time to recovery of bowel function (tolerance of a liquid diet) was 31/2 days. The urinary catheter was removed on post-operative day 21 in 10 patients. The ureteral stents and stoma catheter were removed on day 7 after cystography. At a median followup of 71/2 months, 2 patients had early complications (<30 days), and no major complications (grade >= 3) occurred. The follow-up outcomes were satisfactory. The limitations included the small sample size and short-term outcomes. CONCLUSION Our technique of constructing the IUPUB is feasible and safe. The operative time and early complication rates are acceptable. (C) 2018 Elsevier Inc.
OBJECTIVE To explore the clinical significance of the fused renal pyramid (FRP) in establishing percutaneous renal access, and the anatomic basis for avoiding vascular injury caused by puncturing through this renal pyramid with the aim of achieving accurate puncture in percutaneous nephrolithotomy. MATERIALS AND METHODS Sixty-two cadaveric kidneys and 105 porcine kidneys were selected for the assessment of regional anatomy, to explore the anatomic structure of the FRP and determine its frequency. Then, we compared the effects of 4 different puncture paths on the occurrence of renal vascular injury when respectively punctured through the normal renal pyramid (group A), the centerline of one side pyramid of the FRP (group B), the center of the entire FRP (group C) and the renal column (group D). RESULTS The incidence of FRP in human kidneys is not low. The artery in the kidney can be divided into 6 grades. The grade IV branch-interlobar artery courses through the FRP. There was significant difference in the degree of arterial injury between the group A and C (P = .003), while no significant difference between the group A and B (P = .151). There was significant difference in the proportion of interlolar artery injury between group A and C (P <.001), while no significant difference between group A and B (P = .239). CONCLUSION It is necessary to carefully identify and bypass the FRP when establishing a percutaneous renal access. If unavoidable, the puncture path should be on the centerline of one side pyramid of the FRP. (C) 2018 Elsevier Inc.
OBJECTIVE To evaluate the use of a new single-port robotic system, da Vinci SP (Intuitive Surgical, Sunnyvale, CA) in performing retzius-sparing radical prostatectomy in a cadaveric model. METHODS A cadaver was placed in supine position on operating table. A 4-cm skin incision was made above the umbilicus for insertion of the robotic port via a GelPoint Mini Advanced Access Platform (Applied Medical, Rancho Santa Margarita, CA). An additional 10-mm assistant port was inserted in the right lower quadrant. The operating table was then placed at a 30 degrees Trendelenburg position and the robotic system was docked. The robotic endoscopic camera was set to pass in at the 6 o'clock to facilitate upward viewing during surgery. The parietal peritoneum was incised at the anterior surface of the rectovesical pouch. Vas deferens and seminal vesicles were dissected. Posterior dissection was performed till the prostatic apex. Lateral dissection was then performed with division of the prostatic pedicles. The dissection was continued distally and anteriorly until reaching the apical region. The lateral contour of the prostate was defined. The vesicoprostatic junction was identified by careful dissection of the perivesical fat and following the contour of the lateral prostatic surface. Bladder neck was identified and incised. Prostate was then retracted downward and the anterior prostatic surface was dissected. Finally, urethra was divided just distal to prostatic apex after urethra catheter withdrew. The vesicourethral anastomosis was completed with 2 barbed sutures. RESULT The procedure was completed without conversion and the total robotic surgical time was 146 minutes. CONCLUSION The use of da Vinci SP system (Intuitive Surgical, Sunnyvale, CA) for retzius sparing radical prostatectomy was feasible. The flexible robotic camera provides additional benefit in viewing the operating field, in particular during the posterior dissection, bladder dissection, and anastomosis. (c) 2018 Elsevier Inc.
OBJECTIVE To explore new therapies for castration-resistant prostate cancer to improve patients' quality of life and extend life. MATERIALS AND METHODS The synthesis, morphology analysis, phase analysis, spectral analysis, and photothermal conversion test were referenced to our previous articles. Then near-infrared light-driven copper sulfide (CuS) nanoplates to inhibit the growth of prostate cancer cells in vivo and in vitro was carried out. Transmission electron microscope, mCherry-LC3 syncytial virus labeling, acridine orange staining, and autophagy protein were used to detect the autophagy caused by CuS nanoplates and chloroquine was used to inhibit the process of autophagy. RESULTS The CuS nanoplates prepared in this study feature low cytotoxicity, simple preparation, and high photothermal conversion efficiency. Driven by 980 nm near-infrared light, CuS nanoplates could inhibit the growth of prostate cancer cells in vivo and in vitro, while triggering the autophagy and cytoprotection of prostate cancer cells. CONCLUSION CuS nanoplates are a kind of commendable photothermal therapy agent in castration-resistant prostate cancer treating. Autophagy inhibition enhances the photothermal efficiency of CuS nanoplates, which indicates favorable application prospects in the treatment of advanced prostate cancer. (C) 2018 Elsevier Inc.
OBJECTIVE To describe a modified technique for easily locating cystic wall during flexible ureteroscopic surgery for treatment of parapelvic renal cysts. METHODS Nineteen patients with symptomatic/asymptomatic parapelvic renal cyst were treated with modified or conventional flexible ureteroscopic surgery between February 2015 and March 2017, and the differences of the 2 techniques were compared. The detailed surgical procedures and results, postoperative complications, and patients' follow-ups were evaluated. RESULTS All the patients received endoscopic management by flexible ureteroscope successfully, without requiring another complicated surgery. The cysts were seen clearly in 9 patients with modified method. Two of ten patients who underwent conventional ureteroscopic surgery changed to the modified surgery intra-operatively since it was difficult to identify the cyst. The total time of search and incision of cysts was 24.2 +/- 6.2 minutes and 17.7 +/- 2.5 minutes for conventional and modified technique respectively (P = .01), of which 11.4 +/- 4.8 minutes and 5.1 +/- 1.1 minutes to search the cysts, respectively (P = .002), and the mean time of the procedure of puncture was 8 +/- 2.3 minutes. Duration of pure incising the cystic wall was 12.8 +/- 3.3 minutes and 12.6 +/- 2.5 minutes for patients who underwent conventional and modified technique, respectively (P = .859). All patients acquired relief from the presentation of flank discomfort after surgery. All of the patients were followed-up over 12 months and no serious complications and recurrence was observed. CONCLUSION The modified technique can decrease time of searching the renal cyst and decrease the total time in flexible ureteroscopic treatment of parapelvic cysts. The limitations of our study were also observed and further studies are needed. (C) 2018 Elsevier Inc.
OBJECTIVE To evaluate the feasibility and safety of reproductive organ preserving radical cystectomy (ROPRC) compared to radical cystectomy (RC) for elderly female patients with muscle-invasive bladder cancer. METHODS We retrospectively studied 135 elderly female patients (aged >= 75 years) who underwent RC followed by cutaneous ureterostomies at our center between January 1, 2007 and December 31, 2017. Eighty-four patients treated with RC, and 51 patients treated with ROPRC, were grouped into 45 pairs. Patient demographics, extensive pen-operative, and oncological data were then recorded and evaluated. RESULTS In the matched group, the incidence of short-term and long-term complications in the ROPRC group were lower than the RC group (18.0% vs 28.0%, P = .035; 12.0% vs 22.0%, P = .030). Furthermore, operative time was shorter, estimated blood loss was lower, and bowel recovery was quicker in the ROPRC group (207.5 minutes vs 267.9 minutes, P < .001; 500 mL vs 600 mL, P = .024; 3.0 days vs 4.0 days, P < .001, respectively) compared to the RC group. The recurrence free survival (P = .658), overall survival (P = .604), and cancer-specific survival (P = .361) were all equivalent when compared between the 2 groups with a median follow-up period of 34.0 and 38.0 months, respectively. The surgical approach (RC vs ROPRC) was an independent risk factor for short-term complications (P = .045), duration of operative time (P < .001), estimated blood loss (P = .004), and bowel recovery (P < .001). CONCLUSION This propensity score-matched cohort study showed that ROPRC was both feasible and safe for elderly female patients with muscle-invasive bladder cancer compared to RC, and also had comparable oncological outcomes after a lengthy follow-up period. (C) 2018 Elsevier Inc.
OBJECTIVES To assess the feasibility of a novel functional perfusion model based on enhanced computed tomography (CT) for the evaluation of split renal function and orientation of segmental renal artery clamping during laparoscopic partial nephrectomy (LPN). MATERIALS AND METHODS From December 2016 to November 2017, functional perfusion model was applied in 91 patients with T1a renal tumors who had undergone LPN with segmental renal artery clamping. Split computed tomographic-glomerular filtration rate (CT-GFR) was calculated using the 2-point Patlak plot technique. Parenchymal perfusion areas of segmental renal arteries were marked, and target segmental arteries were determined by the perfusion areas wherein tumors were confined. LPN with precise segmental renal artery clamping was performed based on the novel model. Correlations between CT-GFR and estimated GFR and radioisotope GFR were analyzed using Pearson's method. Intraoperative ischemic status and surgical outcomes were assessed. RESULTS Mean tumor size was 2.9 cm. Large tumors were accompanied by more feeding lobar arteries than segmental arteries. CT-GFR was strongly correlated with estimated GFR (r = 0.70) and radioisotope GFR (r = 0.88). All LPNs were successful without converting to main renal artery clamping. Mean operation time was 81.8 minutes; median estimated blood loss was 120 mL. The actual parenchymal ischemic region observed during the operation was consistent with the prediction of the perfusion model in all patients. No arterial bleeding or other uncontrollable defect bleeding occurred during tumor resection. CONCLUSION This model is a reliable method for the determination of split renal function and orientation of segmental artery clamping during LPN. (C) 2018 Elsevier Inc.
OBJECTIVE To investigate the relationship between the upregulated expression of sphingostne-1-phosphate receptor 1 (S1P1) in the corpus cavernosum and erectile function in spontaneously hypertensive rats (SHRs). METHODS Twelve-week-old healthy male Wistar-Kyoto rats (WKY) and SHR rats were randomly divided into 4 groups: WKY, SHR, WKY transfection, and SHR transfection (n = 5). A lentiviral vector carrying the S1P1 gene was injected into the corpus cavernosum penis of rats in the transfection groups (1 x 10(9) TU/mu L, 20 mu L). After 1 week, the maximum penile intracavernous pressure/mean arterial pressure (ICPmax/MAP), nitric oxide (NO) content, and the expression of eNOS, P-eNOS, ROCK1, ROCK2, and S1P1 in the corpus cavernosum penis of rats in each group were measured. RESULTS The ICPmax/MAP value was significantly higher in the SHR transfection group than in the SHR group under 3-V and 5-V electrical stimulations (P <.01). The expression of S1P1 and P-eNOS proteins significantly increased (P <.01), while that of ROCK1 and ROCK2 proteins significantly decreased (P <.01) in the SHR transfected group compared with the SHR group. The NO content was significantly higher in the SHR transfection group than in the SHR group (P <.01). CONCLUSION The upregulated expression of S1P1 in SHR corpus cavernosum penis may improve the SHR erectile function by upregulating the P-eNOS/eNOS ratio and inhibiting the RhoA/Rho kinase signaling pathway. (C) 2019 Elsevier Inc.