GTSE1 promotes prostate cancer cell proliferation via the SP1/FOXM1 signaling pathway.

G2 and S phase-expressed-1 (GTSE1) has been implicated in the pathogenesis of several malignant tumors. However, its specific role in prostate cancer (PCa) remains unclear. In this study, RNA-Seq data from patients with PCa and controls were downloaded from the FIREBROWSE database, and it was found that the GTSE1 mRNA level was significantly upregulated in PCa. Moreover, patients with higher GTSE1 mRNA levels had higher Gleason scores (P < 0.001), a more advanced pT stage (P = 0.011), and a more advanced pN stage (P = 0.006) as well as a shorter time to biochemical recurrence (P = 0.005). In addition, overexpression of GTSE1 could promote proliferation in LNCaP cells, whereas silencing GTSE1 could inhibit the growth of C4-2 cells in vitro and in vivo. Mechanistically, GTSE1 enhanced the expression of FOXM1 by upregulating the SP1 protein level, a transcription factor of FOXM1, which ultimately promoted PCa cell proliferation. In summary, GTSE1 is a new candidate oncogene in the development and progression of PCa, and it can promote PCa cell proliferation via the SP1/FOXM1 signaling pathway.

[Video endosopic inguinal lymphadenectomy for penile cancer].

Inguinal lymph node metastasis is one of the important factors affecting the prognosis of penile cancer. Conventional open inguinal lymphadenectomy, with a high rate of complications, seriously affects the effect of surgery and the patient's quality of life, and therefore is rarely employed nowadays as a treatment option. Video endosopic inguinal lymphadenectomy (VEIL), however, can significantly reduce the incidence rate of surgery-related complications, achieve a desirable control of the tumor, and markedly improve the prognosis. This review focuses on the application, development, indications, effectiveness and complications of VEIL in the treatment of penile cancer.

Survival Analysis and a Novel Nomogram Model for Progression-Free Survival in Patients with Prostate Cancer.

Background: This study sought to perform a survival analysis and construct a prognostic nomogram model based on the Gleason grade, total prostate-specific antigen (tPSA), alkaline phosphate (ALP), and TNM stage in patients with prostate cancer (PCa). Methods: The progression-free survival (PFS) of 255 PCa patients was analyzed in this study. The prognostic value of tPSA and ALP was evaluated using the Kaplan-Meier survival curves and Cox regression analysis, and a nomogram model based on the Gleason grade, tPSA, ALP, and TNM stage was further established for PFS prediction in PCa patients. Results: PCa patients with different Gleason grades, tPSA and ALP levels, and TNM stages presented distinct PFS. The Gleason grade, tPSA, ALP, and TNM stage were four independent prognostic indicators. The C-index of the established nomogram was 0.705 for PFS in the test cohort and 0.687 for the validation cohort, and the calibration curves indicated a good consistency between predicted and actual PFS in PCa patients. Conclusion: The data of this study demonstrated that the Gleason grade, tPSA, ALP, and TNM stage of PCa patients are independently correlated with PFS, and a nomogram model based on these indicators may be valuable for the PFS prediction in PCa patient.

Biparametric MRI-based radiomics classifiers for the detection of prostate cancer in patients with PSA serum levels of 4∼10 ng/mL.

Purpose: To investigate the predictive performance of the combined model by integrating clinical variables and radiomic features for the accurate detection of prostate cancer (PCa) in patients with prostate-specific antigen (PSA) serum levels of 4-10 ng/mL. Methods: A retrospective study of 136 males (mean age, 67.3 ± 8.4 years) with Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 category ≤3 lesions and PSA serum levels of 4-10 ng/mL were performed. All patients underwent multiparametric MRI at 3.0T and transrectal ultrasound-guided systematic prostate biopsy in their clinical workup. Radiomic features were extracted from axial T2-weighted images (T2WI) and apparent diffusion coefficient (ADC) maps of each patient using PyRadiomics. Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were implemented to identify the most significant radiomic features. Independent clinic-radiological factors were identified via univariate and multivariate regression analyses. Seven machine-learning algorithms were compared to construct a single-layered radiomic score (ie, radscore) and multivariate regression analysis was applied to construct the fusion radscore. Finally, the radiomic nomogram was further developed by integrating useful clinic-radiological factors and fusion radscore using multivariate regression analysis. The discriminative power of the nomogram was evaluated by area under the curve (AUC), DeLong test, calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC). Results: The transitional zone-specific antigen density was identified as the only independent clinic-radiological factor, which yielded an AUC of 0.592 (95% confidence interval [CI]: 0.527-0.657). The ADC radscore based on six features and Naive Bayes achieved an AUC of 0.779 (95%CI: 0.730-0.828); the T2WI radscore based on 13 features and Support Vector Machine yielded an AUC of 0.808 (95%CI: 0.761-0.855). The fusion radscore obtained an improved AUC of 0.844 (95%CI: 0.801-0.887), which was higher than the single-layered radscores (both P<0.05). The radiomic nomogram achieved the highest value among all models (all P<0.05), with an AUC of 0.872 (95%CI: 0.835-0.909). Calibration curve showed good agreement and DCA together with CIC confirmed the clinical benefits of the radiomic nomogram. Conclusion: The radiomic nomogram holds the potential for accurate and noninvasive identification of PCa in patients with PI-RADS ≤3 lesions and PSA of 4-10 ng/mL, which could reduce unnecessary biopsy.

Comparison of intravesical instillation of hyaluronic acid with intradetrusor botulinum toxin A injection or cystoscopic hydrodistention for ketamine-associated cystitis.

OBJECTIVE: This study aimed to compare the therapeutic effect of intravesical instillation hyaluronic acid with intradetrusor botulinum toxin A (BTX-A) injection or cystoscopic hydrodistention for ketamine-associated cystitis. METHODS: Thirty-six patients were evenly randomly divided into the BTX-A group or the hydrodistention group. Patients received 200 U BTX-A detrusor injections in the BTX-A group and cystoscopic hydrodistention in the hydrodistention group. Intravesical instillation of hyaluronic acid was administrated in both groups for eight times. Patients with involuntary detrusor contraction were divided into the persistent involuntary detrusor contraction group and resolved involuntary detrusor contraction group after treatment in 6 months. The predictors of persistent involuntary detrusor contraction were analyzed. RESULTS: Twelve months after treatment, the daytime frequency, Interstitial Cystitis Symptom Index, maximal capacity, and maximal cystometric capacity in the BTX-A group were significantly better than those in the hydrodistention group. Patients with resolution of involuntary detrusor contraction had a significantly shorter duration of ketamine, lower amount of fibrosis in pathology, and higher maximal capacity than those with persistent involuntary detrusor contraction 6 months after therapy. CONCLUSION: Intravesical instillation of hyaluronic acid with intradetrusor BTX-A injection appears to be a preferable option for long-term effectiveness compared with cystoscopic hydrodistention.

Microstructures of the spermatic cord with three-dimensional reconstruction of sections of the cord and application to varicocele.

The aim of the study was to investigate the micro-structures of the spermatic cord using histological examination with three-dimensional (3D) reconstruction of the serial tissue sections of the cord for clinical application in microscopic varicocelectomy. Human spermatic cord specimens obtained from 13 adult male cadavers were used to prepare serial transverse sections. The sections were stained to allow observation of the spermatic cord microstructures. The 3D reconstruction was performed with digitized serial sections by Mimics software. The microscopic varicocelectomy was performed based on the anatomical results of 3D reconstruction of the spermatic cord. The results showed the number of small spermatic veins, large spermatic veins, arteries, lymphatics or nerves were not markedly different between the subinguinal and inguinal regions or between the right and left sperm cord. The number of medium spermatic veins in the subinguinal region was obviously higher than at the inguinal level. The internal spermatic vessels and the vas deferens together with other associated vessels within the cremaster were separately enclosed by two thin and translucent sheaths, the internal spermatic fascia and the vas deferens fascia. We conclude that internal spermatic vessels and the vas deferens together with the associated neurovascular vessels are wrapped by two distinct sheaths separating them from the surrounding tissues. Microscopic varicocelectomy based on the anatomical results of 3D reconstruction of the spermatic cord is feasible. ABBREVIATIONS: 3D: three-dimensional; ISF: internal spermatic fascia; ESF: external spermatic fascia; MHIV: High inguinal microsurgical varicocelectomy; MSIV: subinguinal microsurgical varicocelectomy; CAAD: computer-assisted anatomic dissection; HE: hematoxylin-eosin.

MicroRNA-488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3.

Prostate cancer (PCa) remains the second leading cause of cancer-related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. By analyzing the Gene Expression Omnibus dataset, we found lower expression for miR-488 in PCa than in normal tissues. Moreover, CCK-8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR-488 in PCa cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis. In contrast, downregulation of miR-488 expression promoted proliferation and glycolysis in PCa cells. Using a bioinformatic approach and dual-luciferase reporter assays, we identified 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform3 (PFKFB3), as a direct target of miR-488. Inhibition of PFKFB3 also suppressed PCa cell glycolysis and proliferation. Our study suggests that miR-488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and thus, miR-488 may be a novel therapeutic candidate for PCa.

Hyperglycaemia-induced miR-301a promotes cell proliferation by repressing p21 and Smad4 in prostate cancer.

Hyperglycaemia promotes the development of Prostate cancer (PCa). However, the roles of miRNAs in this disease process and the underlying mechanisms are largely unknown. In this study, we recruited 391 PCa patients in China and found that PCa patients with high level blood glucose (≥100 mg/dL) trended to have high Gleason score (GS ≥ 7). miRNA-301a levels were significantly higher in prostate cancer than that in normal prostate tissues. Hyperglycaemia or high glucose treatment induced miR-301a expression in prostate tissues or PCa cell lines. miR-301a suppressed the expression of p21 and Smad4, and subsequently promoted G1/S cell cycle transition and cell proliferation in vitro and xenograft growth in nude mice in vivo. Furthermore, knockdown of p21 and Smad4 mimicked the effects of miR-301a overexpression. Restoration of p21 and smad4 could interrupt the effects of miR-301a overexpression. Importantly, inhibition of miR-301a severely blocked high glucose-induced PCa cell growth both in vitro and in vivo. These results revealed a novel molecular link between hyperglycaemia and PCa. The miR-301a plays an important role in the hyperglycaemia-associated cancer growth, and represents a novel therapeutic target for PCa.