Decreased expression of TCF12 contributes to progression and predicts biochemical recurrence in patients with prostate cancer.

As a member of helix-loop-helix protein family, transcription factor 12 functions as either an oncogene or a tumor suppressor in various human cancers. However, there are no reports on its involvement in prostate cancer. To investigate clinical relevance of transcription factor 12 in prostate cancer and to evaluate its roles in malignant phenotypes of this cancer in vitro and in vivo, we here examined expression patterns of transcription factor 12 protein in 50 prostate cancer tissue specimens by immunohistochemistry. Then, associations of transcription factor 12 expression with various clinicopathological characteristics and patients' prognosis of prostate cancer were evaluated. Its involvements in cancer cell proliferation, migration, invasion, and tumor growth were determined by in vitro and in vivo experiments. As a result, the positive immunostaining of transcription factor 12 protein was localized in cytoplasm and/or nucleus of prostate cancer cells. Its expression levels were decreased with prostate cancer Gleason score increased. Statistically, the decreased expression of transcription factor 12 protein more frequently occurred in prostate cancer patients with high Gleason score, positive metastasis, prostate-specific antigen failure, and short biochemical recurrence-free survival (all p < 0.05). Importantly, multivariate analysis showed that the status of transcription factor 12 expression was an independent predictor of biochemical recurrence-free survival in prostate cancer. Functionally, enforced expression of transcription factor 12 suppressed cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. In conclusion, transcription factor 12 protein may be a novel molecule which plays a critical role in prostate cancer progression and patients' prognosis, suggesting it might be a promising therapeutic target for prostate cancer therapy.

Expression of CD147 is associated with prostate cancer progression.

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate-specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure-free, metastasis-free and overall survival. Kaplan-Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure-free, metastasis-free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure-free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa.

Mannose inhibits the growth of prostate cancer through a mitochondrial mechanism.

The limited treatment options for advanced prostate cancer (PCa) lead to the urgent need to discover new anticancer drugs. Mannose, an isomer of glucose, has been reported to have an anticancer effect on various tumors. However, the anticancer effect of mannose in PCa remains unclear. In this study, we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro, and mannose was observed to have an anticancer effect in mice without harming their health. Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential, increased mitochondrial and cellular reactive oxygen species (ROS) levels, and reduced adenosine triphosphate (ATP) production in PCa cells. Mannose treatment of PCa cells induced changes in mitochondrial morphology, caused dysregulated expression of the fission protein, such as fission, mitochondrial 1 (FIS1), and enhanced the expression of proapoptotic factors, such as BCL2-associated X (Bax) and BCL2-antagonist/killer 1 (Bak). Furthermore, lower expression of mannose phosphate isomerase (MPI), the key enzyme in mannose metabolism, indicated poorer prognosis in PCa patients, and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose. This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.

Protein regulator of cytokinesis 1 overexpression predicts biochemical recurrence in men with prostate cancer.

BACKGROUND: Protein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer-specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy. MATERIALS AND METHODS: PRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed. RESULTS: PRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P<0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P<0.001). CONCLUSION: These findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy.

miR-195 Inhibits Tumor Progression by Targeting RPS6KB1 in Human Prostate Cancer.

PURPOSE: To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer. EXPERIMENTAL DESIGN: qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems. RESULTS: miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xenograft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195-RPS6KB1 axis. CONCLUSION: The newly identified miR-195-RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment.

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer.

AIM: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. METHODS: EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p=0.006), the grade (p=0.002), carcinoma in situ (p=0.01), the recurrence (p=0.009), the progression (p=0.009), and the death (p=0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p=0.008) and OS (p=0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p=0.03) and OS (p=0.03). CONCLUSION: EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer.

Pathogen incidence and antibiotic resistance patterns of catheter-associated urinary tract infection in children.

The aim of this study was to characterize the pathogens and their antibiotic susceptibilities in children with catheter-associated urinary tract infection (CAUTI) in order to optimize empirical antibiotic therapy and prophylaxis. from 2001 to 2006, 895 children with an indwelling catheter from 3 hospitals in China were included in this study, of whom 335 (37.4%) had CAUTI. Antimicrobial susceptibility testing of 450 bacterial isolates was performed using the ClSi broth and Kirby-bauer agar dilution methods. Escherichia coli was the most frequently isolated pathogen, followed by Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus spp. E. coli had higher susceptibility to ceftazidime (87.4%), cefuroxime (85.1%) and cefatrizine (76.6%) than to sulfamethoxazole (SMZ) (8.0%), amoxicillin (21.7%), ampicillin (17.1%) and cefazolin (37.7%). Isolates of Klebsiella pneumoniae and Proteus species had similar patterns as E. coli. S. aureus had lower susceptibility to SmZ (6.8%), ampicillin (8.2%), and amoxicillin (24.7%); the trend of S. epidermidis was similar. This study demonstrates that the Gram-negative species are the predominating uropathogens of CAUti in children. it is important to know the bacterial spectrum and the susceptibility patterns to various classes of antibiotic agents to improve empiric antibiotic therapy of children with CAUTI in China.