Leye He

Clinical Significance of IL-2, IL-10, and TNF-α in Prostatic Secretion of Patients With Chronic Prostatitis

OBJECTIVES To explore the clinical significance of interleukin-2 (IL-2), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha) in expressed prostatic secretions (EPS) of patients with different types of chronic prostatitis (CP). METHODS Fifty-seven CP patients and 12 healthy males (controls) were investigated. The CP patients were evaluated through routine examination of urine, EPS, 2 glasses urine culture, and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score and classified by the NIH prostatitis diagnostic criteria. The levels of cytokines TNF-alpha, IL-10, and IL-2 in the EPS were measured by two-antibody enzyme-linked immunosorbent assay. RESULTS CP patients fell into 3 groups: type II (n = 10), type IIIa (n = 26), and type IIIb (n = 21). EPS TNF-alpha and IL-10 levels were significantly higher in type II and type IIIa than in type IIIb and control groups. The levels of IL-2 were lower than control in all CP groups, but only type II was statistically different from the controls. In the CP patients, the level of TNF-alpha was positively related to the white blood cell counts (r = .77; P <.01), and the level of IL-10 was positively related to the NIH-CPSI scores (r = .55; P <.01). CONCLUSIONS Determination of variety expression of TNF-alpha, IL-10, and IL-2 in the EPS of CP patients may provide a potential indicator for clinical diagnosis classification and an indicator to evaluate the effect of treatment of CP.

The prognostic role of preoperative serum albumin/globulin ratio in patients with bladder urothelial carcinoma undergoing radical cystectomy

OBJECTIVE To date, only a few studies have demonstrated the prognostic value of pretreatment serum albumin in bladder urothelial carcinoma (BUC). The aim of this study was to evaluate the association between the pretreatment albumin/globulin ratio (AGR) and the survival of patients with BUC treated with radical cystectomy (RC). MATERIALS AND METHODS Data from 296 patients with BUC who underwent RC between June 2000 and June 2013 were analyzed. The AGR was calculated as follows: albumin/(total protein-albumin). The AGR was divided into 2 groups for receiver operating characteristics curve analysis. Survival was estimated using Kaplan-Meier analysis and compared using the log rank test. Cox proportional hazards models were used for univariate and multivariate survival analyses. RESULTS Patients in the high AGR group (AGR≥1.60) had a lower 5-year recurrence-free mortality rate compared with those in the low AGR group (AGR<1.60) (87.0% vs. 48.0%, P<0.001). The median cancer-specific survival (CSS) time was 71.1 months for low AGR patients and 156.0 months for the high AGR patients (P<0.001). After adjusting for confounding variables, the AGR remained an independent predictor of recurrence-free survival (RFS) (hazard rate = 0.356; 95% CI: 0.170-0.748; P = 0.006) and CSS (hazard rate = 0.280; 95% CI: 0.115-0.683; P = 0.005). Moreover, in the subset of 167 patients with normal serum albumin (albumin of≥40.0g/l), serum AGR continues to be an independent predictor of RFS (P = 0.012) and CSS (P = 0.008). CONCLUSIONS High AGR is a strong independent predictor of long-term RFS and CSS in patients with BUC undergoing RC. Additionally, among patients with normal albumin (≥40g/l) levels, patients with higher globulin, but lower AGR have worse survival. The pretreatment AGR is an easily accessible and cheap to use for predicting mortality in patients with BUC treated by RC.

The effect of immediate surgical bipolar plasmakinetic transurethral resection of the prostate on prostatic hyperplasia with acute urinary retention

In the present study, we evaluated the safety and efficacy of immediate surgical bipolar plasmakinetic transurethral resection of the prostate (PK-TURP) for patients with benign prostatic hyperplasia (BPH) with acute urinary retention (AUR). We conducted a retrospective analysis of clinical data of BPH patients who received PK-TURP. A total of 1126 BPH patients were divided into AUR (n = 348) and non-AUR groups (n = 778). After the urethral catheters were removed, the urine white blood cell (WBC) count in the AUR group significantly increased compared with the non-AUR group (P < 0.01). However, there was no significant difference in international prostate symptom score, painful urination, and maximal urinary flow rate. The duration of hospitalization of the AUR group was longer than that of the non-AUR group (P < 0.001). A total of 87.1% (303/348) patients in the AUR group and 84.1% (654/778) patients in the non-AUR group completed all of the postoperative follow-up visits. The incidence of urinary tract infection in the AUR group within 3 months after surgery was significantly higher than that in the non-AUR group (P < 0.01). The incidence of temporary urinary incontinence in the AUR group did not exhibit significant difference. During 3-12 months after surgery, there were no significant differences in major complications between the two groups. Multivariate regression analyses showed that age, postvoid residual, maximal urinary flow rate, diabetes, and hypertension, but not the presence of AUR, were independent predictors of IPSS post-PK-TURP. In conclusion, immediate PK-TURP surgery on patients accompanied by AUR was safe and effective.

SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival

Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo. Moreover, SPAG5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models was confirmed via immunohistochemical analysis of a cohort of human BUC specimens that underwent RC. Collectively, our data suggested that in patients with BUC who underwent RC, high SPAG5 expression is associated with poor survival. In addition, targeting SPAG5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.

Knockdown of HMGN5 increases the chemosensitivity of human urothelial bladder cancer cells to cisplatin by targeting PI3K/Akt signaling

High-mobility group nucleosome-binding domain 5 (HMGN5) is the latest member of the HMGN family of proteins. Numerous studies have confirmed the carcinogenic role of HMGN5 in cancer, but its function in the regulation of chemosensitivity is largely unknown and controversial. A previous study by the authors of the present study demonstrated that HMGN5 contributes to the progression of urothelial bladder cancer (UBC) through regulating the expression of E-cadherin and vascular endothelial growth factor (VEGF)-C, which are associated with the sensitivity of tumor cells to cisplatin. Therefore, the present study aimed to elucidate the mechanisms underlying the regulation of HMGN5 and investigate the involvement of HMGN5 in cisplatin treatment. The results of the present study revealed that HMGN5 is able to positively regulate the expression of phosphorylated (p-)Akt in UBC cells. In addition, HMGN5 expression was negatively associated with the response of UBC cells to cisplatin. The findings indicated that HMGN5 may be a potential therapeutic target of cisplatin treatment, since cisplatin treatment reduced HMGN5 expression in a dose-dependent manner. It was also confirmed that the knockdown of HMGN5 decreased the viability, colony formation and invasion of 5637 cells but increased apoptosis under cisplatin treatment. The changes caused by HMGN5 knockdown in 5637 cells were able to be reversed by treatment with insulin-like growth factor-1 (IGF-1), which is a phosphoinositide 3-kinase (PI3K)/Akt signaling activator. Additionally, with the decreased expression of HMGN5, the expression of p-Akt, slug, E-cadherin and VEGF-C was subsequently inhibited. By contrast, the expression of cytochrome c, cleaved-caspase-3 and cleaved-poly ADP ribose polymerase was increased following HMGN5 knockdown. Consistently, these changes in protein expression were able to be reversed by IGF-1 treatment. In conclusion, findings from the in vitro experiments indicate that HMGN5 may a target of cisplatin treatment and that the inhibition of HMGN5 increases the chemosensitivity of UBC cells by inhibiting PI3K/Akt signaling.

Renal Calculus Complicated with Squamous Cell Carcinoma of Renal Pelvic: Report of Two Cases

Squamous cell carcinoma (SCC) of the renal pelvis is an uncommon tumor, which is usually associated with infection and long standing renal calculus. The neoplasm is highly aggressive, so it is at advanced stage and has a poor outcome when diagnosed. We present two cases who had diseases of kidney stone complicated with mass of renal pelvis. Both patients were operated with radical nephrectomy subsequently. The histopathology report showed that the tumors of renal pelvis were SCC. When come across a case of chronic renal calculi, we should pay attention to whether it exists neoplasm because the co-existing latent mass may bring about misdiagnosing and effect the patient’s treatment plan and prognosis.

Rural and Urban Differences in Stage at Diagnosis of Prostate Cancer in Hunan Province, China

This study set out to investigate whether patients in rural areas tend to have more advanced prostate cancer (PCa) than urban areas in Hunan province, define possible factors related to the stage at diagnosis of PCa between rural and urban areas, and to determine the potential correlations between these factors and PCa stage at time of diagnosis. Data were used from a retrospective database of 490 PCa patients from the Third XiangYa hospital. Rural and urban differences in PCa stage, age, delay in diagnosis, prostate specific antigen (PSA) values, PSA screening, and metabolic syndrome were described and analyzed. Pearson correlation, Spearman correlation, and multiple linear regression were performed to examine the correlations between factors which may attribute to regional differences and stage. The percentage of advanced stage in rural cases was higher than in urban cases. Moreover, younger age, longer delay in diagnosis, less metabolic syndrome, and fewer PSA screening prior to diagnosis were observed in rural patients compared with the urban patients. Current study revealed that rural patients were more likely to have advanced PCa stage and PSA values at time of diagnosis. Perhaps, most importantly, these data demonstrated that both rural and urban patients in Hunan province suffered from an unacceptable frequency of advanced PCa, presumably from lack of routine PSA screening.

MicroRNA‑124 inhibits cell proliferation, invasion and migration by targeting CAV1 in bladder cancer

MicroRNAs (miRs) may have promotive or suppressive roles in various human cancers types, but the molecular mechanisms underlying the role of miR-124 in bladder cancer (BC) progression have remained largely elusive. In the present study, it was observed that miR-124 was significantly downregulated in BC tissues compared with that in adjacent non-neoplastic tissues. Furthermore, its expression was also reduced in several human BC cell lines (T24, HT-1376 and 5637) compared with that in the normal bladder epithelial SV-HUC-1 cell line. A low expression of miR-124 in BC patients was significantly associated with advanced malignancy and a poor prognosis. Caveolin 1 (CAV1) was identified as a novel target gene of miR-124, and the expression of CAV1 was negatively regulated by miR-124 in T24 cells. Furthermore, CAV1 was identified to be significantly upregulated in BC tissues and cell lines, and a negative correlation was observed between the expression of miR-124 and CAV1 in BC tissues. Furthermore, restoration of miR-124 expression significantly inhibited the proliferation, migration and invasion of T24 cells, and these effects were impaired following overexpression of CAV1. Taken together, the present results demonstrate that miR-124 has a suppressive role in the proliferation, migration and invasion of BC cells by targeting CAV1, which suggests that miR-124 is a potential therapeutic candidate for BC.

TRIM65 supports bladder urothelial carcinoma cell aggressiveness by promoting ANXA2 ubiquitination and degradation

Clinically, most of human urothelial carcinoma of the bladder (UCB)-related deaths result from tumor metastasis, but the underlying molecular mechanisms are largely unknown. Recently, a growing number of tripartite motif (TRIM) family members have been suggested to be important regulators for tumorigenesis. However, the impact of most TRIM members on UCB pathogenesis is unclear. In this study, TRIM65 was first screened as an important oncogenic factor of UCB from the Cancer Genome Atlas (TCGA) database and was validated by a large cohort of clinical UCB tissues. By in vitro and in vivo experiments, we demonstrated that TRIM65 promotes UCB cell invasive and metastatic capacities. Notably, we showed that TRIM65 modulates cytoskeleton rearrangement and induces UCB cells epithelial-mesenchymal transition by the ubiquitination of ANXA2, ultimately leading to an enhanced invasiveness of UCB cells. Importantly, UCBs with high expression of TRIM65 and low expression of ANXA2 showed the poorest outcome. Collectively, our results suggest that the overexpression of TRIM65 has an essential oncogenic role via ubiquitination of ANXA2 in UCB pathogenesis, and that such could be used as a novel prognostic marker and/or therapeutic target for UCB.

RIPK4 promotes bladder urothelial carcinoma cell aggressiveness by upregulating VEGF-A through the NF-κB pathway

BackgroundConstitutively activated nuclear factor kappa B (NF-κB) signalling plays vital roles in bladder urothelial carcinoma (BC) progression. We investigate the effect of receptor-interacting protein kinase 4 (RIPK4) on NF-κB activation and BC progression.MethodsThe expression of RIPK4 was examined in 25 cryopreserved paired bladder samples and 112 paraffin BC specimens. In vivo and in vitro assays were performed to validate effect of RIPK4 on NF-κB pathway-mediated BC progression.ResultsHigh expression of RIPK4 was observed in BC tissues and was an independent predictor for poor overall survival. Up or downregulating the expression of RIPK4 enhanced or inhibited, respectively, the migration and invasion of BC cells in vitro and in vivo. Mechanistically, RIPK4 promoted K63-linked polyubiquitination of tumour necrosis factor receptor-associated factor 2 (TRAF2), receptor-interacting protein (RIP) and NF-κB essential modulator (NEMO). RIPK4 also promoted nuclear localisation of NF-κB-p65, and maintained activation of NF-κB substantially, leading to upregulation of VEGF-A, ultimately promoting BC cell aggressiveness.ConclusionsOur data highlighted the molecular aetiology and clinical significance of RIPK4 in BC: upregulation of RIPK4 contributes to NF-κB activation, and upregulates VEGF-A, and BC progression. Targeting RIPK4 might represent a new therapeutic strategy to improve survival for patients with BC.