Changwen Zhang

CtBP2 could promote prostate cancer cell proliferation through c-Myc signaling.

C-terminal binding protein-2 (CtBP2) is a CtBP-family member which plays a significant role in tumor initiation, progression and response to therapy. However, little has been known about the potential oncobiological role of CtBP2 and its mechanism in human prostate cancer. In this study, we observed the overexpression of CtBP2 in prostate cancer and demonstrated that its expression was closely correlated with several malignant behaviors, e.g., increased serum PSA level, advanced tumor stage (T3), higher Gleason scores and poor outcome. Furthermore, downregulation of CtBP2 expression in prostate cancer PC3 cells could markedly inhibit their proliferation by inducing apoptosis in vitro. Additionally, CtBP2 inhibition could decrease the level of c-Myc and its direct transcriptional target, HSPC111. Taken together, our investigations demonstrated that low-expression of CtBP2 could highly inhibit proliferation of prostate cancer by c-Myc induced signaling, suggesting that targeting CtBP2 may yield a viable anti-tumor strategy by restraining tumor progression in prostate cancer.

Lymphovascular invasion, ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes

PURPOSE To identify predictive factors underlying recurrence and survival after partial cystectomy for pelvic lymph node-negative muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) and to report the results of partial cystectomy among select patients. METHODS We retrospectively reviewed 101 cases that received partial cystectomy for MIBC (pT2-3N0M0) between 2000 and 2010. The log-rank test and a Cox regression analyses were performed to identify factors that were predictive of recurrence and survival. RESULTS With a median follow-up of 53.0 months (range 9-120), the 5-year overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were 58%, 65% and 50%, respectively. A total of 33 patients died of bladder cancer and 52 patients survived with intact bladder. Of the 101 patients included, 55 had no recurrence, 12 had non-muscle-invasive recurrence in the bladder that was treated successfully, and 34 had recurrence with advanced disease. The multivariate analysis showed that prior history of urothelial carcinoma (PH.UC) was associated with both CSS and RFS and weakly associated with OS; lymphovascular invasion (LVI) and ureteral reimplantation (UR) were associated with OS, CSS and RFS. CONCLUSIONS Among patients with pelvic lymph node-negative MIBC, PH.UC and UR should be considered as contraindications for partial cystectomy, and LVI is predictive of poor outcomes after partial cystectomy. Highly selective partial cystectomy is a rational alternative to radical cystectomy for the treatment of MIBC with negative pelvic lymph nodes.

Prognostic significance of GPC5 expression in patients with prostate cancer

The objective of this study was to evaluate the protein level of glypican-5 (GPC5) and its relationship with clinicopathologic significance in prostate cancer. The protein level of GPC5 in 160 prostate cancer tissues and 60 adjacent normal samples was examined by immunohistochemistry analysis, and the results were correlated with clinicopathologic parameters. The level of GPC5 in prostate cancer tissues was markedly lower than that in normal cases, especially in high-risk prostate cancer. Additionally, the low expression of GPC5 was closely associated with increased serum prostate-specific antigen (PSA), higher Gleason scores, advanced tumor stage (T3), positive lymph node metastasis, and biochemical recurrence. Moreover, GPC5 low expression was an independent prognostic factor for overall survival of patients with prostate cancer. GPC5 protein expression showed a close correlation with the tumorigenesis and tumor progression of prostate cancer, and that might be applied as a novel biomarker for the prediction of diagnosis and prognosis of prostate cancer.

Metformin Prevents Renal Stone Formation through an Antioxidant Mechanism In Vitro and In Vivo.

Oxidative stress is a causal factor and key promoter of urolithiasis associated with renal tubular epithelium cell injury. The present study was designed to investigate the preventive effects of metformin on renal tubular cell injury induced by oxalate and stone formation in a hyperoxaluric rat model. MTT assays were carried out to determine the protection of metformin from oxalate-induced cytotoxicity. The intracellular superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured in vitro. Male Sprague-Dawley rats were divided into control group, ethylene glycol (EG) treated group, and EG + metformin treated group. Oxidative stress and crystal formations were evaluated in renal tissues after 8-week treatment. Metformin significantly inhibited the decrease of the viability in MDCK cells and HK-2 cells induced by oxalate. Besides, metformin markedly prevented the increased concentration of MDA and the decreased tendency of SOD in oxalate-induced MDCK cells and HK-2 cells. In vivo, the increased MDA levels and the reduction of SOD activity were detected in the EG treated group compared with controls, while these parameters reversed in the EG + metformin treated group. Kidney crystal formation in the EG + metformin treated group was decreased significantly compared with the EG treated group. Metformin suppressed urinary crystal deposit formation through renal tubular cell protection and antioxidative effects.

CtBP2 Overexpression is associated with tumorigenesis and poor clinical outcome of prostate cancer

Introduction The aim of the study was to evaluate the expression of CtBP2 in prostate cancer and to determine its relationship with clinicopathologic parameters. Material and methods The expression of CtBP2 in 119 prostate cancer tissues and 41 normal tissues was examined by qPCR and Western blot analysis, and the results were correlated with clinicopathologic parameters. Results CtBP2 expression in prostate cancer tissues was higher than that in normal samples. CtBP2 overexpression was closely correlated with serum prostatic specific antigen (PSA) (p = 0.018), advanced tumor stage (T3) (p = 0.025), higher Gleason scores (p = 0.019), positive extraprostatic extension (p = 0.012), positive vascular invasion (p = 0.011) and perineural invasion (p = 0.035). However, no significant association was found between CtBP2 abnormal expression and other parameters, including age (p = 0.776), positive lymph node (p = 0.872) and positive surgical margin (p = 0.37). Moreover, CtBP2 overexpression was significantly associated with poor clinical outcome of prostate cancer (p = 0.0168). Conclusions CtBP2 is overexpressed in prostate cancer, and its increased expression is closely associated with tumor progression and the outcome of prostate cancer.

Laparoscopic simple enucleation and coagulation on tumor bed using argon beam coagulator for treating small renal cell carcinomas: An animal study followed by clinical application

Summary Background The aim of our study was to evaluate the feasibility and clinical effect of laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator for treating small renal cell carcinomas. Material/Methods The animal experiments of coagulation therapy on the wound tissue bed during partial nephrectomy with an argon beam coagulator were performed on 16 rabbits, which were randomly divided into 4 groups. Groups A and B had renal artery occlusion; the treatment time of coagulation was 4 seconds and 6 seconds, respectively. Groups C and D did not have renal artery occlusion; the treatment time of coagulation was 2 seconds and 4 seconds, respectively. Then 30 clinical operations of laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator were performed. Results All 16 rabbits successfully underwent the operation. By the histological examination, the scab depth of the wound tissue bed in groups A, B, C, and D were 2.76±0.17 mm, 3.15±0.15 mm, 2.28±0.16 mm and 2.75±0.06 mm, respectively. Group A differed significantly from groups B and C (P=0.012, 0.007), and group D differed significantly from groups B and C (P=0.002, 0.002). In the clinical study, all 30 patients successfully underwent the operation. The mean operative time was 182 minutes, and the mean blood loss was 280 ml. With a median follow-up time of 37 months, neither local recurrence nor distant metastasis was found by computerized tomography scan. Conclusions Laparoscopic simple enucleation and coagulation on tumor bed using an argon beam coagulator can be considered for treating small renal cell carcinomas. However, the indication of this procedure should be highly selected.

Elevated expression of ZNF217 promotes prostate cancer growth by restraining ferroportin-conducted iron egress

Although we and other studies indicated ZNF217 expression was increased in prostate cancer (PCa), the factors mediating its misregulated expression and their oncogenic activity remain largely unexplored. Recent evidence demonstrated that ferroportin (FPN) reduction lead to decreased iron export and increased intercellular iron that consequently aggravates the oncogenic effects of iron. In the present study, ZNF217 was identified as a transcriptional repressor that inhibits FPN expression. Increased of ZNF217 expression led to decreased FPN concentration, coupled with resultant intracellular iron retention, increased iron-related cellular activities and enhanced tumor cell growth. In contrast, decreased of ZNF217 expression restrained tumor cell growth by promoting FPN-driven iron egress. Mechanistic investigation manifested that ZNF217 facilitated the H3K27me3 levels of FPN promoter by interacting with EZH2. Besides, we also found that MAZ increased the transcription level of ZNF217, and subsequently inhibited the FPN expression and their iron–related activities. Strikingly, the expression of MAZ, EZH2 and ZNF217 were concurrently upregulated in PCa, leading to decreased expression of FPN, which induce disordered iron metabolism. Collectively, this study underscored that elevated expression of ZNF217 promotes prostate cancer growth by restraining FPN-conducted iron egress.

Pim-3 is a Critical Risk Factor in Development and Prognosis of Prostate Cancer.

Background Pim-3 kinase is a highly homologous serine/threonine kinase that is overexpressed in hematological malignancies and solid tumors. Few studies have been conducted to define the role of Pim-3 in solid tumors, especially in prostate cancer. The aim of this study was to define the role of Pim-3 in development and prognosis of prostate cancer. Material/Methods We collected specimens from 160 patients with prostate cancer, as well as 100 patients with benign prostatic hyperplasia. Realtime polymerase chain reaction was used for the assessment of Pim-3 expression at the RNA level and Western blot was used to quantify the Pim-3 protein synthesis in 3 different cell lines. Results We found that Pim-3 mRNA expression in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (p<0.05). Accordingly, the protein level expression of Pim-3 in prostate cancer cell lines was also significantly higher than that in control cells. In addition, the expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. High expression of Pim-3 also significantly decreased the survival rate of patients after surgery. Conclusions Pim-3 expression is an important risk factor for prostate cancer; we are the first team to report Pim-3 as a valuable biomarker in Chinese.

The promotion on cell growth of androgen-dependent prostate cancer by antimony via mimicking androgen activity

Antimony is a widely used heavier pnictogens in industry, and its toxicity has been a matter of concern. Although previous studies have suggested that antimony may have the function as either a tumor suppressor or an oncogene in several cancers, the molecular basis underlying antimony-mediated transformation is still unclear. In the current study, we attempt to elucidate the potential role of antimony in the development of prostate cancer. Our results showed that the concentration of antimony was much higher in serum of prostate cancer patients, and was closely associated with poor outcome of patients who underwent radical prostatectomy. Additionally, low dose of antimony could promote proliferation and invasion of androgen-dependent prostate cancer cell line LNCaP cells in vitro and in vivo. The mechanistic studies demonstrated that exposure to antimony triggered the phosphorylation of androgen receptor (AR), which transcriptionally regulates the expression of androgen-related targets, including PSA and NKX3.1. Overall, our results unearthed that antimony could promote tumor growth by mimicking androgen activity in androgen-dependent prostate cancer cells. Therefore, these findings expanded our understanding on the molecular mechanism of antimony in tumorigenesis and tumor progression of prostate cancer, and it appears to be an inspiring strategy to restrain prostate cancer by inhibiting antimony-induced androgen-like effects.

Low expression of TMEM67 is a critical predictor of poor prognosis in human urothelial carcinoma of the bladder

OBJECTIVES The aim of the study was to evaluate the expression of TMEM67 in urothelial carcinoma of the bladder (UCB) tissues and to determine the potential relevance between the expression of TMEM67 and prognosis of UCB. MATERIAL AND METHODS In this study, the expression of TMEM67 mRNA was performed by quantitative real-time PCR in 80 UCB and 54 noncancerous tissues. The expression of TMEM67 protein was identified by immunohistochemistry and western blotting. Chi-square test was conducted to verify the relevance between the expression of TMEM67 and clinical parameters. Kaplan-Meier survival analysis was demonstrated between high or low expression level of TMEM67 mRNA and recurrence-free survival probability. Cox regression analysis was conducted to evaluate the relevance between the expression of TMEM67 and the prognosis in UCB. RESULTS Low expression of TMEM67 mRNA and protein was detected in most of UCB tissues using quantitative real-time polymerase chain reaction and western blotting, compared with noncancerous tissues. Low expressions of TMEM67 were associated with TNM stage, grade, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that the low expression of TMEM67 mRNA had significantly shorter recurrence-free survival probability (P = 0.018). Cox regression analysis confirmed that low expression of TMEM67 mRNA predicted poor prognosis of patients with UCB (HR = 2.950, P = 0.029, 95% CI: 1.116-7.796). CONCLUSIONS TMEM67 expression is low in UCB tissues, and the TMEM67 low expression predicted poor prognosis of patients with UCB.