circPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma.

Background: Circular RNAs (circRNAs) have been identified as essential regulators in a plethora of cancers. Nonetheless, the mechanistic functions of circRNAs in Renal Cell Carcinoma (RCC) remain largely unknown. Methods: In this study, we aimed to identify novel circRNAs that regulate RCC epithelial-mesenchymal transition (EMT), and to subsequently determine their regulatory mechanisms and clinical significance. Results: circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both in vitro and in vivo. We found that increased expression of circPRRC2A is positively associated with advanced clinical stage and worse survivorship in RCC patients. Mechanistically, our results indicate that circPRRC2A prevents the degradation of TRPM3, a tissue-specific oncogene, mRNA by sponging miR-514a-5p and miR-6776-5p. Moreover, circPRRC2A promotes tumor EMT and aggressiveness in patients with RCC. Conclusions: These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.

Retrospective analysis of fosfomycin combinational therapy for sepsis caused by carbapenem-resistant Klebsiella pneumoniae.

The aim of the present study was to compare the efficacy and safety of fosfomycin combinational therapy with other antibiotics for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective cohort study examined 104 cases of sepsis caused by CRKP occurring between January 2012 and November 2014 in Shanghai Tenth People's Hospital. Three categories of patient outcome were assessed: Survival/mortality, duration of intensive care unit stays and duration of medical ventilation. Univariate ordinal analyses were adopted to evaluate the correlations between outcome and treatment. A total of 104 patients with physician-diagnosed CRKP were involved in the study. The overall mortality rate was 25.0%. The majority of the infections (84; 80.8%) were hospital acquired. Critical infections received more than one active antibiotic as therapy. Patients treated with fosfomycin combinational therapy were less likely to fail therapy (OR: 4.71, 95% CI: 1.03-21.65, P=0.034) and tended to have a shorter duration of mechanical ventilation. Gender (OR: 4.35, 95% CI: 1.08-3.60, P=0.037), history of chronic obstructive pulmonary disease (OR: 9.35, 95% CI: 0.06-0.19, P=0.007) and peripheral catheter use (OR: 3.00, 95% CI: 0.07-0.19, P=0.002) are risk factors for clinical outcome. Therefore, the use of fosfomycin combinational therapy for treatment of infection due to CRKP appears to be associated with improved survival rate.

Decreased expression of long non-coding RNA NBAT-1 is associated with poor prognosis in patients with clear cell renal cell carcinoma.

OBJECTIVE: accumulating evidence suggest that long non-coding RNAs (lncRNAs) may play important roles in human cancers. LncRNA neuroblastoma associated transcript-1 (NBAT-1) was initially identified to be involved in the progression of neuroblastoma. However, there is no report about the role of NBAT-1 in clear cell renal cell carcinoma (ccRCC). The purpose of this study is to investigate the clinical significant of NBAT-1 in ccRCC. METHODS: the expression pattern of NBAT-1 in ccRCC patients and renal cancer cell lines was detected by using quantitative real-time PCR (qRT-PCR), and its correlation with clinicopathologic features and prognosis of patients with ccRCC was assessed by Kaplan-Meier method and Cox proportional hazards model, respectively. Small interfering RNA (siRNA) was transfected into 786-O and ACHN cells to determine the effect of NBAT-1 knockdown on renal cancer cells. RESULT: NBAT-1 expression is significantly decreased in ccRCC tissues and renal cancer cells compared with adjacent normal tissues and normal human proximal tubule epithelial cell line HK-2, and its low level is associated with advanced features and poor prognosis. Also, multivariate analysis identified NBAT-1 expression as an independent prognostic factor for ccRCC. In vitro assays indicated that knockdown of NBAT-1 expression increased renal cancer cell proliferation, migration and invasion. CONCLUSIONS: NBAT-1 is a novel molecular correlated with ccRCC progression; and it may represent a prognostic biomarker and therapeutic target in renal cancer diagnosis and treatment.

Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels.

Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.

Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA­21.

Previous studies have reported that hyperoside and quercetin in combination (QH; 1:1) inhibited the growth of human leukemia cells. The aim of the present study was to investigate the anti­cancer effect of QH on prostate cancer cells. The results demonstrated that QH decreased the production of reactive oxygen species (ROS) and increased antioxidant capacity in PC3 cells at various concentrations (2.5­60 µg/ml) with peak inhibition and augmentation changes of 3.22­ and 3.00­fold, respectively. Following treatment with QH for 48 and 72 h, the IC50-values on PC3 cells were 19.7 and 12.4 µg/ml, respectively. Western blot analysis revealed that QH induced apoptosis in human prostate cancer cells via activation of caspase­3 and cleavage of poly(adenosine diphosphate ribose) polymerase. In addition, QH significantly inhibited the invasion and migration of PC3 cells as well as reduced the expression of numerous prostate tumor­associated microRNAs (miRs), including miR­21, compared to that of untreated human prostate cancer cells. QH was also found to enhance the expression of tumor suppressor programmed cell death protein 4, which was negatively regulated by miR­21. Furthermore, induced overexpression of miR­21 using pre­miR­21 oligonucleotides attenuated the beneficial effect of QH on prostate cancer cells. In conclusion, the results of the present study indicated that QH exerted an anti­cancer effect on human prostate cancer cells, the mechanism of which proceeded, at least in part, via the inhibition of the miR­21 signaling pathway.

Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells.

Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P < 0.05). As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene.

High expression of long non-coding RNA SPRY4-IT1 predicts poor prognosis of clear cell renal cell carcinoma.

INTRODUCTION: Long non-coding RNAs (lncRNAs) play a key role in cellular processes, such as cell growth, apoptosis, and carcinogenesis. lncRNAs SPRY4-IT1 has recently been identified to be involved in tumorigenesis of several cancers such as non-small cell lung cancer and esophageal squamous cell carcinoma. However, the role of SPRY4-IT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. METHODS: The expression of SPRY4-IT1 was examined in ccRCC patients and renal cancer cell lines by using quantitative real-time PCR (qRT-PCR). The relationship between SPRY4-IT1 level and clinicopathological parameters of ccRCC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in renal cancer cell line 786-O. In vitro assays were performed to further explore its role in renal cancer progressio. RESULTS: The relative level of SPRY4-IT1 was significantly higher in ccRCC tissues compared to the adjacent normal renal tissues. And higher expression of SPRY4-IT1 was found in renal cancer cell lines compared with the normal human proximal tubule epithelial cell line HK-2. The ccRCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. Multivariate analyses by Cox's proportional hazard model revealed that expression of SPRY4-IT1 was an independent prognostic factor in ccRCC. In vitro assays, our results indicated that knockdown of SPRY4-IT1 reduced renal cancer cell proliferation, migration, and invasion. CONCLUSIONS: Our data suggested that lncRNA SPRY4-IT1 might be considered as a potential prognostic indicator and a potential target for therapeutic intervention in RC.

Metastatic prostate adenocarcinoma posing as urothelial carcinoma of the right ureter: a case report and literature review.

This is a case report of a 67-year-old patient with distant metastasis of prostate cancer to the right ureter which caused hydronephrosis. At the beginning, both of the cytology of the morning urine and imaging findings were consistent with urothelial carcinoma. Nephroureterectomy was subsequently performed. Interestingly, the pathological examination of the excised ureter revealed that the malignancy was derived from the prostate. No skeletal metastasis was detected. However, after four months of follow-up, several abnormal signal shadows were reported in skeletal scintigraphy and the prostate specific antigen (PSA) was gradually increasing. We present such a case for its unique presentation. A review of the literature is also provided.

Prophylactic effects of quercetin and hyperoside in a calcium oxalate stone forming rat model.

Quercetin and hyperoside (QH) are the two main constituents of the total flavone glycosides of Flos Abelmoschus manihot, which has been prescribed for treating chronic kidney disease for decades. This study aimed to investigate the effect of QH on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. Rats were divided into three groups: an untreated stone-forming group, a QH-treated stone-forming group (20 mg/kg/day) and a potassium citrate-treated stone-forming group (potassium citrate was a worldwide-recognized calculi-prophylactic medicine). Ethylene glycol (0.5 %) was administered to the rats during the last week, and vitamin D3 was force-fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. 24 h urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope for semi-quantification of the crystal-formation. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. QH and potassium citrate have the ability to alkalinize urine. The number of crystal deposits decreased significantly in the QH-treated stone-forming group as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the QH-treated stone-forming group, as compared with the untreated stone-forming group. QH administration has an inhibitory effect on the deposition of CaOx crystal in EG-fed rats and may be effective for preventing stone-forming disease.

Protective effects of quercetin and hyperoside on renal fibrosis in rats with unilateral ureteral obstruction.

Prevention of renal fibrosis is an important therapeutic strategy in the treatment of obstructive nephropathy. The purpose of the present study was to identify whether the combination of two natural plant-derived flavanoids, quercetin and hyperoside (QH), could inhibit renal fibrosis in the model of unilateral ureteral obstruction (UUO) in rats. QH mixtures (1:1) were fed to Wistar rats, and UUO ligation was performed on all the rats with the exception of the sham group. Masson's trichrome staining was used for interstitial fibrosis, while immunohistochemistry and western blot analysis were used to detect the expression of α-smooth muscle actin (SMA) and fibronectin (FN). In the QH group, the expression of SMA and FN was significantly lower than that in the untreated UUO group. In addition, QH administration significantly inhibited the SMA and FN expression of mesangial cells induced by interleukin-1ß. Consequently, it was evident that combinational QH therapy prevented UUO-induced renal fibrosis. Based on these findings, the combinatorial intervention of phytomedicine may present an improved treatment strategy for renal fibrotic disease.

Bromodomain 4 protein is a predictor of survival for urothelial carcinoma of bladder.

BACKGROUND: Bromodomain 4 (BRD4) protein is a double bromodomain-containing protein that binds preferentially to acetylated chromatins. BRD4 is essential for cellular growth and has been implicated in cell cycle control, DNA replication and carcinogenesis. However, its expression profile and prognostic value in urothelial carcinoma of the bladder (UCB) have not been investigated. METHODS: Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore BRD4 expression in UCBs and normal bladder tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of BRD4 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of BRD4 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blot when compared with their paired normal bladder tissues. Clinicopathological analysis was showed a significant correlation existed between the higher expression of BRD4 protein with the histological grade, lymph node metastasis and distant metastasis (P < 0.05); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated BRD4 expression in bladder cancer tissue predicted poorer overall survival (OS) compared with group in lower expression. Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of BRD4 was an independent prognostic factor in UCB. CONCLUSIONS: These results suggest that the aberrant expression of BRD4 in human UCB is possibly involved in the tumorigenesis and development, and the BRD4 protein could act as a potential biomarker for prognosis assessment of bladder cancer. Further studies on the cellular functions of BRD4 need to address these issues.

Fibrinogen alpha chain precursor and apolipoprotein A-I in urine as biomarkers for noninvasive diagnosis of calcium oxalate nephrolithiasis: a proteomics study.

UNLABELLED: Calcium oxalate nephrolithiasis is the most common urological disease, but noninvasive and convenient methods of diagnosis are rarely available. OBJECTIVE: The present study aimed to identify potential urine biomarkers for noninvasive diagnosis of CaOx nephrolithiasis. METHODOLOGY: Urine samples from 72 patients with CaOx nephrolithiasis and 30 healthy controls were collected and proteomics analysis was performed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometer (MALDI-TOF-MS). RESULTS: Thirteen proteins/peptides displayed statistically significant differences. The peptides of m/z 1207.23 and 2773.86 were selected by the genetic algorithm (GA) to build a possible diagnostic model. The area under the curve of m/z 1207.23 and 2773.86 was 0.936 and 0.987, respectively. The diagnostic model in distinguishing patients and healthy subjects showed 100% sensitivity and specificity. The peak at m/z 2773.86 was identified as fibrinogen alpha chain (FGA) with the sequence G.EGDFLAEGGGVR.G, and the peak at m/z 2773.86 was identified as apolipoprotein A-I (apoA-I) with the sequence L.PVLESFKVSFLSALEEYTKKLNTQ. CONCLUSION: The study results strongly suggested that urinary FGA and apoA-I are highly sensitive and specific biomarkers for noninvasive diagnosis of CaOx nephrolithiasis.

Dietary fiber intake and risk of renal cell carcinoma: evidence from a meta-analysis.

The aim of this study was to investigate the possible relationships between dietary fiber intake and risk of renal cell carcinoma (RCC). Electronic databases including MEDLINE, EMBASE and Web of Science were searched to find eligible studies. Random-effects relative risk (RR) and its corresponding 95 % confidence interval (CI) were used. Besides, random-effects dose-response analyses were also performed to clarify the dose-response relations. Finally, publication bias was assessed by Egger's test and Begg's test. All p values were two tailed. Seven studies, including two cohort studies and five case-control studies, were eligible and included in this meta-analysis. Overall analysis in highest versus lowest level revealed that total dietary fiber intake was associated with reduced RCC risk (RR 0.84, 95 % CI 0.74-0.96). In addition, pooled estimated data showed that risk of RCC was significantly associated with vegetable and legume fiber intake (RR 0.70, RR 0.80, respectively), but not with fruit and cereal fiber intake (RR 0.92, RR 1.04, respectively). However, in dose-response analysis, no significant association was reported. Finally, no publication bias was detected by Egger's or Begg's test. The dietary fiber intake, especially vegetable and legume fiber, may be associated with reduced RCC risk. Considering the limitations of the included studies, more well-designed prospective studies will be needed to confirm our findings.

Foxl1 inhibits tumor invasion and predicts outcome in human renal cancer.

UNLABELLED: The Forkhead Box L1 (Foxl1) transcription factor regulates epithelial proliferation and development of gastrointestinal tract, and has been implicated in gastrointestinal and pancreatic tumorigenesis. However, the role of Foxl1 in renal cancer development and progression remains to be elucidated. The study was conducted to investigate the expression of Foxl1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of Foxl1 in human ccRCC was further investigated in cell culture models. METHODS: Real-time quantitative PCR, western-blot, immunohistochemistry were used to explore Foxl1 expression in primary ccRCC clinical specimens and ccRCC cell lines. Foxl1 expression was up-regulated by over-expression vector in 786-O and ACHN cells, proliferation, cell cycle, migration and invasion were assayed. RESULTS: Foxl1 expression was down-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that Foxl1 expression was significantly correlated with tumor stage, lymph node metastasis, distant metastasis, clinical TNM stage (cTNM) and histological grade of renal cancer. The Kaplan-Meier survival curves revealed that low Foxl1 expression was associated with poor prognosis in ccRCC patients. Foxl1 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis. Mechanistic analyses demonstrated that over-expression of Foxl1 inhibits tumor cell growth, migration and invasion in renal cancer cells. CONCLUSIONS: These results suggest that Foxl1 expression is a candidate predictor of clinical outcome in patients with resected ccRCC and it plays an inhibitory role in renal tumor progression.

Argonaute 2 is up-regulated in tissues of urothelial carcinoma of bladder.

UNLABELLED: Argonaute 2 proteins (Ago2) have been demonstrated to be widely expressed and involved in post-transcriptional gene silencing and play key roles in carcinogenesis. However, its expression profile and prognostic value in urothelial carcinoma of the bladder (UCB) have not been investigated. METHODS: Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore Ago2 expression in UCBs and normal bladder tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of Ago2 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of Ago2 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blot when compared with their paired normal bladder tissues. Clinic pathological analysis was showed a significant correlation existed between the higher expression of Ago2 protein with the Histological grade, lymph node metastasis and Distant metastasis (P<0.05); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated Ago2 expression in cancer tissue predicted poorer overall survival (OS) compared with group in lower expression (62.2% VS 86.3%, P<0.05). Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of Ago2 was an independent prognostic factor in UCB. CONCLUSIONS: These results suggest that the aberrant expression of Ago2 in human UCB is possibly involved with tumorigenesis and development, and the Ago2 protein could act as a potential biomarker for prognosis assessment of bladder cancer. Further studies on the cellular functions of Ago2 need to address these issues.

Urinary neutrophil gelatinase-associated lipocalin, a biomarker for systemic inflammatory response syndrome in patients with nephrolithiasis.

BACKGROUND: The objective of this study was to determine the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL), C-reactive protein (CRP), and procalcitonin (PCT) in the prognosis of patients presenting with the systemic inflammatory response syndrome (SIRS) with nephrolithiasis. METHODS: Urine NGAL protein levels were measured by enzyme-linked immunosorbent assay in 87 patients presenting with nephrolithiasis who were diagnosed as SIRS. Additionally, 52 patients presenting with nephrolithiasis but without urinary tract infection and 30 healthy controls were also included in the study. Levels of serum CRP and PCT were also taken into consideration. RESULTS: Median urinary NGAL levels were significantly increased in the SIRS cohorts compared with nephrolithiasis without urinary tract infection patients (4.28 ng/mL versus 2.69 ng/mL, P < 0.001), and NGAL was markedly elevated even in the early stage of SIRS (3.23 ng/mL versus 2.69 ng/mL, P < 0.001). According to the receiver-operating characteristic analysis, NGAL demonstrated a high diagnostic value compared with either PCT or CRP. In the later stage of SIRS, NGAL remained a highly sensitive (76.8%) and specific (86.5%) diagnostic marker compared with either PCT or CRP. Moreover, the area under the curves of NGAL (0.822) were also superior to those seen in either PCT (0.657) or CRP (0.761). CONCLUSION: Urinary NGAL is a highly sensitive and specific predictor of SIRS for patients presenting with nephrolithiasis. Further study of NGAL as a reliable biomarker of SIRS is required.

Combination of quercetin and hyperoside has anticancer effects on renal cancer cells through inhibition of oncogenic microRNA-27a.

Quercetin and hyperoside (QH) in combination (1:1 ratio) have previously been shown to inhibit the growth of human leukemia cells. Here, we investigated the anticancer activity of the same mixture in 786-O renal cancer cells. QH decreased the generation of reactive oxygen species (ROS) by up to 2.25-fold and increased the antioxidant capacity by up to 3-fold in 786-O cells (3.8-60 µg/ml), whereas IC50 values for viability were 18.2, 18.7 and 11.8 µg/ml, respectively. QH also induced caspase-3 cleavage (2-fold) and increased PARP cleavage. Specificity protein (Sp) transcription factors are overexpressed in cancer cells and regulate genes required for cell proliferation, survival and angiogenesis. QH treatment decreased the expression of Sp1, Sp3 and Sp4 mRNA and this was accompanied by decreased protein expression. Moreover, expression of the Sp-dependent anti-apoptotic survival gene survivin was also significantly reduced, both at the mRNA and protein levels. QH decreased microRNA-27a (miR-27a) and induced the zinc finger protein ZBTB10, an Sp-repressor, suggesting that interactions between QH and the miR-27a-ZBTB10 axis play a role in Sp downregulation. This was confirmed by transfection of cells with a specific mimic for miR-27a, which partially reversed the effects of QH. These findings are consistent with previous studies on botanical anticancer agents in colon cancer cells.

Preventive effect of phosphodiesterase 5 inhibitor tadalafil on experimental post-pyelonephritic renal injury in rats.

BACKGROUND: To evaluate the effects of Tadalafil, a phosphodiesterase 5 enzyme inhibitor, on Escherichia coli-induced renal damage in an acute pyelonephritis (PN) rat model. METHODS: Experimental PN was induced in 32 Wistar rats, and four groups were formed: group 1 (no treatment), group 2 (antibiotic), group 3 (Tadalafil), and group 4 (antibiotic + Tadalafil). Antibiotic was given on days 3 to 8, and Tadalafil was administered between days 0 and 28 of bacterial inoculation. Half of the rats were killed on the ninth day (early period) and histopathological parameters, immunohistochemical renal fibrosis markers, and oxidant/antioxidant system activities were evaluated. The rest of the rats were killed at the sixth week of the study and evaluated for histopathological parameters and renal fibrosis markers. RESULTS: Inflammatory activity was significantly milder in rats treated with antibiotic + Tadalafil versus no treatment group both in the early and late periods. In the late period, interstitial fibrosis or tubular atrophy was lower in the antibiotic + Tadalafil group versus the no treatment and antibiotic groups, and in Tadalafil versus antibiotic group. Tadalafil administration significantly reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. In addition, circulating tumor necrosis factor α, interleukin 1ß was greatly reduced in Tadalafil group versus the no treatment group. CONCLUSIONS: We have provided the first evidence that phosphodiesterase 5 enzyme inhibitor Tadalafil ameliorates circulating inflammatory cytokines, reverses oxidant/antioxidant dysfunction and eventually possesses an overall protective effect on renal tissue from Escherichia coli-induced PN-related kidney injury. Phophodieterase 5 inhibitor might be a novel therapeutic target for PN.

Statin use and risk of kidney cancer: a meta-analysis of observational studies and randomized trials.

AIM: Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject. METHODS: A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of 12 (two randomized controlled trials, five cohort, and five case-control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results. CONCLUSION: The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.

Expression and clinical significance of the nin one binding protein and p38 MAPK in prostate carcinoma.

BACKGROUND: Prostate carcinoma is a major cause of morbidity and mortality. The MAPK Signaling Pathway plays an important role in multiple tumors, including prostate carcinoma. MAPK signaling is mediated by ERK1/2, JNK and p38 MAPK, which are important in the control of cell proliferation, differentiation and apoptosis. However, relatively little is known about the regulatory mechanism of p38 MAPK in prostate cancers. NOB1 is among the most novel topic in MAPK studies currently. Recent studies found its vital role in tumor metastasis in glioblastoma proliferation, however, its expression profile and its prognostic value in prostate carcinoma have not been investigated. METHODS: To determine the relationship between NOB1 and p38 MAPK expressions, a population-based study was conducted for immunohistochemical staining analysis of tumor tissues, in matched malignant and nonmalignant prostatectomy samples from 132 PCa patients. Moreover, Western blot analysis and NOB1 interference studies of prostate cancer cell lines. To evaluate the diagnostic and prognostic between NOB1 and p38 MAPK in prostate cancer (PCa) tissue after radical prostatectomy, the hypothesis that prostate cancers with NOB1 expression have distinct clinical, prognostic and molecular attributes was tested. RESULTS: Among 132 prostate cancers, NOB1 expression was detected in 117 (88.7%) tumors by immunohistochemistry. NOB1 and p38 MAPK expression had significant positive correlation with carcinogenesis, tumor progression and patient survival. Immunohistochemically, NOB1 expression in prostate cancer was independently associated with p38 MAPK activation (P=0.0002). Furthermore, p38 MAPK expression was completely suppressed by NOB1 interference in the prostate cancer cell lines DU-145 and PC-3. CONCLUSIONS: NOB1 expression status was closely correlated with important histopathologic characteristics and the recurrence and metastasis of prostate carcinomas. These data support a potential link between NOB1 and p38 MAPK, and suggest that NOB1 may identify a subset of prostate cancer patients with a poor prognosis. This study proved that NOB1 in PCa tissue can be used, in combination with traditional clinicopathological factors, as promising diagnostic and prognostic tools.