[Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy].

OBJECTIVE: Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters. METHODS: In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA). RESULTS: The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) µg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711). CONCLUSION: Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.

VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR.

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

[Management of calyceal diverticular calculi with stenotic infundibulum by flexible ureteroscopic holmium laser infundibulectomy and lithotripsy].

OBJECTIVE: To evaluate the efficacy and safety of flexible ureteroscopic holmium laser lithotripsy in treating calyceal diverticular calculi with stenotic infundibulum and to present our initial experience. METHODS: From Nov. 2012 to Nov. 2014, 10 patients with stone-bearing calyceal diverticulum and stenotic infundibulum underwent flexible ureteroscopic holmium laser lithotripsy in our hospital, including 3 female patients and 7 male patients with an average age of 36.9 years (range: 20 to 62 years). There were 6 patients with right side while 4 patients with left side calyceal diverticular calculi. The average cumulative stone size was (1.33±0.43) cm. Five patients underwent extracorporeal shock wave lithotripsy (ESWL) before hospital admission but no stone was discharged. All the patients received intravenous urography (IVU) and CT-urography (CTU) preoperatively and underwent double-J stents placement 2 weeks before operations. A digital-fiber flexible ureteroscopy and 200 µm holmium laser fiber were used for treatment. Surgeries began with routine flexible ureteroscopy and methylene blue injection was used to identify the small ostium of infundibulum. Then infundibulectomy followed by lithotripsy was performed. All the patients receive double-J stents placement and traditional Chinese medicine for 1 to 3 months after operations. The stone clearance was estimated by kidney ureter bladder (KUB) within 3 months' follow up. RESULTS: The locations of calyceal diverticulum were upper pole in 7 patients, and interpolar regions in 4 patients. The average operation time was (123.7±59.6) min, and the average estimated blood loss was (29.3±32.1) mL. Successful flexible ureteroscopic holmium laser infundibulectomies were performed in all the 10 patients. Success rate was 100%. The stone clearance rates for 1 and 3 months after surgery were 50.0% and 80.0%, respectively, which were observed by KUB follow-up. Two patients had serious post-operative fever (>38.0 °C) in coexistence with chills. The mobidity of urosepsis was 20.0%. No major complications were identified. CONCLUSION: In selected patients, calyceal diverticular calculi with stenotic infundibulum can be treated safely and efficiently with flexible ureteroscopic homium laser lithotripsy. CTU and IVU should be completed preoperatively for calyceal diverticulum location and technique difficulty prediction. Retrograde methylene blue injection can be used to identify the ostium during surgery. And prolonged post-operation stone clearance was observed.

[Expression and clinical significance of glycoprotein non-metastatic melanoma protein B in human renal cell carcinoma].

OBJECTIVE: To investigate the role of glycoprotein non-metastatic melanoma protein B (GPNMB) in renal cell carcinoma (RCC). METHODS: The method of immunohistochemistry (IHC) and Western blot were utilized to examine the expression of GPNMB in RCC and the normal adjacent tissues matched. RESULTS: The expression of GPNMB was lower in RCC than in the matched normal adjacent tissues (P=0.022). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of RCC and the detection of GPNMB may be useful for the early diagnosis of tumor and its development.

[Free fatty acids induce proliferation of human renal carcinoma 786-O cell line via integrin-linked kinase].

OBJECTIVE: To investigate the effects of free fatty acids on cell proliferation and integrin-linked kinase (ILK) expression in human renal carcinoma 786-O cell line. METHODS: The 786-O cells were exposed to normal medium and different concentrations of oleic acid (OA) carried by de-fatty bovine serum albumin (d-BSA). The MTT assay and the flow cytometry assay were performed respectively for cell proliferation and apoptosis after the treatment with OA for 48 h. The expressions of ILK, Akt and p-Akt were detected by Western blot. RESULTS: The MTT assay showed that the cell viabilities of 0.05 mmol/L, 0.1 mmol/L and 0.2 mmol/L OA groups were increased gradually, as compared with the blank control (absorbance: 0.657 ± 0.056, 0.682 ± 0.028, 0.718 ± 0.042 vs. 0.495 ± 0.034; all P<0.001). The effects of OA on cells apoptosis were not significant (apoptotic rates: 2.42% ± 0.25% vs. 2.33% ± 0.87% vs. 2.25%± 0.51%, P=0.082). After being treated with OA, the expressions of ILK and p-Akt were increased in 786-O cells. CONCLUSION: The results suggested that free fatty acids could promote the development of renal cell carcinoma via up-regulating ILK/Akt pathway, which may reveal the relations between metabolic disturbance and renal carcinoma to a certain extent.

[Inhibitory effect of CMTM5 on xenografted human prostatic cancer in nude mice].

OBJECTIVE: To investigate the inhibitory effect of CKLF-like MARVEL transmembrane domain containing 5 (CMTM5) on xenografted human prostatic cancer in nude mice and its action mechanism. METHODS: We established a model of xenografted prostatic cancer by inoculating PC-3 cells subcutaneously into nude mice, and 3 weeks later injected CMTM5 adenovirus locally into the tumor followed by daily observation of the tumor volume and body weight of the experimental animals. All the rats were killed 2 weeks after CMTM5 injection and the tumor tissue harvested for detection of the inhibitory effect of CMTM5 on the expressions of VEGF and NF-kappaB proteins by immunohistochemistry. RESULTS: The tumor volume was significantly smaller and body weight of the CMTM5-treated mice were (573.39 +/- 175.24) mm3 and (0.55 +/- 0.11) g, respectively, significantly decreased as compared with those of the controls ([1482.50 +/- 327.86] mm3 and [1.31 +/- 0.29] g) (P = 0.03 and P = 0.027). Immunohistochemistry showed that the expressions of VEGF and NF-kappaB were obviously down-regulated in the CMTM5 group in comparison with the control group. CONCLUSION: CMTM5 suppresses the growth of prostate cancer by down-regulating the expressions of VEGF and NF-kappaB.

[Expression of glycoprotein non-metastatic melanoma protein B in prostate cancer and its significance].

OBJECTIVE: To investigate the expression of glycoprotein non-metastatic melanoma protein B (GPNMB) in prostate cancer and its clinical significance. METHODS: The expression of GPNMB was analysed in 63 prostate cancer and 3 heterosexual hyperplasia prostate tissue and 8 benign prostatic hyperplasia samples by immunohistochemical staining, with integral optical density(IOD) value representing expression level of positive cells. RESULTS: The expression of GPNMB was lower in benign prostatic hyperplasia (BPH, IOD=70 017.49) than in Atypical hyperplasia (IOD=101 547.33, P=0.000 1) . The expression of GPNMB in tumor (IOD= 162 027.54) was higher than in non-tumor group (IOD=79 290.97), which included BPH and atypical hyperplasia (P=0.000 1). But GPNMB expression level was not positively elevated with degree of malignancy of prostate cancer. However, the expression of GPNMB in low pathological grading(IOD=177 944.30) was higher than that in high pathological grading(IOD=150 885.81, P=0.013). CONCLUSION: The abnormal expression of GPNMB may play an important role in the development of prostate cancer and its detection may be useful for the early diagnosis of prostate cancer.

[Effect of integrin-linked kinase on the growth of prostate cancer in nude mice].

OBJECTIVE: To investigate the effect of the integrin-linked kinase (ILK) small interfering RNA (siRNA) on prostate cancer in nude mice by orthotopic injection of human cell line DU145. METHODS: The cultured human cell line DU145 was knocked down for ILK using a siRNA .Cellular ILK expression was quantified by RT-PCR and Western blot analysis. Moreover, cell attachment, invasiveness and microfilament dynamics assays were performed. Furthermore, the impact of the ILK siRNA on the prostate cancer was tested using a nude mice model in which prostate cancer was induced by orthotopic injection of human prostate cancer cell line DU145.Gross tumor volume of prostate in nude mice,cell differentiation,the state of apoptosis and proliferation were tested after 5 weeks of injection. RESULTS: The expression of ILK was suppressed significantly by siRNA, cellular mRNA and protein of ILK decreased 87% and 81% separately. The knockdown of ILK also induced the attachment and invasiveness of DU145 cell growing down. The tumor volume, cell differentiation, apoptosis index and proliferation index of prostate in nude mice of ILK siRNA orthotopic injection model were significantly smaller, better, increased and decreased separately than those in control group. CONCLUSION: Targeting inhibition of ILK not only decreases attachment and invasiveness of human DU145 cells, but also suppresses the growth and development of prostate cancer of orthotopic injection human DU145 cell line model in nude mice.