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OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.

Background: C-reactive protein (CRP), considered as a prototypical inflammatory cytokine, has been proposed to be involved in tumor progression through inflammation. Recent studies have indicated CRP as a progostic predictor for urological cancers, but the results remain controversial. Materials and Methods: A systematic search of Medline, Scopus and the Cochrane Library was performed to identify eligible studies published between Jan 1, 2001 and Sep 1, 2013. Outcomes of interest were collected from studies comparing overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratio (HR) of CRP with its 95% confidence interval (CI) for survival were used for the effect size estimate. Results: A total of 43 studies (7,490 patients) were included in this meta-analysis (25 for RCC, 10 for UC, and 8 for PC). Our pooled results showed that elevated serum CRP level was associated with poor OS (HR: 1.26, 95%CI: 1.22-1.30) and RFS (HR: 1.38 95%CI: 1.29-1.47), respectively. For CSS the pooled HR (HR: 1.33, 95%CI: 1.28-1.39) for higher CRP expression could strongly predict poorer survival in urological cancers. Simultaneously, elevated serum CRP was also significantly associated with poor prognosis in the subgroup analysis. Conclusions: Our pooled results demonstrate that a high serum level of CRP as an inflammation biomarker denotes a poor prognosis of patients with urological cancers. Further large prospective studies should be performed to confirm whether CRP, as a biomarker of inflammation, has a prognostic role in urological cancer progression.

Immediate intravesical instillation of chemotherapeutic agents after transurethral resection (TUR) of nonmuscle invasive transitional cell bladder cancer has recently been suggested and has been proven to decrease the tumor recurrence rate significantly. This study is to evaluate the efficacy and safety of immediate intravesical instillation combined with regular instillations of Pirarubicin (THP(®)) as prophylaxis compared to regular instillations only after TUR operation.This was a prospective, randomized, multi-center, clinical study. Patients diagnosed with non-muscle invasive bladder cancer (Ta and T1) pathologically and suitable for TUR were enrolled randomly into two groups. In the study group, the patients received intravesical instillation within 24-hour post TURBT, followed by regular intravesical therapy using 30 mg/50 ml of THP(®) once a week for 8 weeks, and then once a month to 1 year postoperatively Among the patients. In the control group, patients received regular instillation only.A total of 403 patients were enrolled into this study from 26 institutions in China. Among the potients, 210 were enrolled into the study group and 193 were enrolled into the control group. At the median follow-up of 18 months, the recurrence rate was 7.8% in the study group, significantly lower than that in the control group (14.3%; P = 0.042). Subgroup analysis showed that the recurrence rate in low and intermediate-risk patients was significantly lower in the study group (6.8%) than in the control group (14.0%; P = 0.047), although no significant differences were found in high-risk patients.One immediate dose of THP(®) 30 mg after TURBT followed by regular intravesical therapy appears well tolerated and more effective than regular intravesical therapy for preventing tumor recurrence, especially in low and intermediate-risk patients.

To explore the relationship between occupational factors and the incidence of bladder cancer.The present research was based on a hospital-based case-control study. The cases were frequency matched. The non-conditional Logistic regression was used to calculate the odds ratio (OR) of each occupation.The OR of business and administration professionals, male electricians and electronic workers were 3.88 and 7.40; the OR of janitors and helpers was 0.21; the OR of handcrafted and printing clerks was 0.71, but there was no significant difference.Business and administration professionals, male electricians and electronic workers tend to have bladder cancer. The occupation of janitors and helpers has a protective effect on bladder cancer while the occupation of printing clerks shows no statistical significance on bladder cancer.

Bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial. To optimize the management of young patients with bladder cancer, we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients.From 1994 to 2008, a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed. The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinic outcomes.Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis. Tumors in young bladder cancer patients tended to be less multifocal at diagnosis. In addition, young patients had a lower recurrence rate and longer recurrence interval than older patients. The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients. The univariate and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients.Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients. These findings argue for more conservative management approaches for young patients with bladder cancer.

Idiopathic hyperoxaluria (IH) may be caused by increased endogenous formation or exogenous absorption of oxalic acid. Characterization of the molecular pathogenesis of IH has been hampered by the lack of an ideal animal model. We therefore established a stabile rat IH model in order to analyze variation in gene expression profile in the jejunum and to investigate the association between IH pathogenesis and exogenous absorption of oxalic acid.A rat model of IH was established and three female rats with IH were assigned to the study group, while three normal rats served as controls. Total RNA was isolated from the jejunum of rats in the two groups and mRNA was purified, reversely transcribed, labeled with Cy5 or Cy3 and hybridized to 27K Rat Genome Array. Differences in gene expression profile between the 2 groups were analyzed by bioinformatics methods.Comparative analysis revealed that the expression of 517 genes was up-regulated and that of 203 genes was down-regulated by at least two-fold in the jejunum of rats with idiopathic hyperoxaluria. These genes are related to many functions including cell signal transduction, DNA binding and transcription, ATP binding, ion binding and transport, cell receptors, immunity, cyclins, cytoskeleton structure, and metabolic proteins. Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis revealed that the variations of 239 pathway functional changes are statistically significant (P0.05).cDNA microarray can be used effectively to screen differentially expressed genes in the jejunum of rats with idiopathic hyperoxaluria. These differentially expressed genes may underlie idiopathic hyperoxaluria pathophysiology and provide a platform for further studying molecular pathogenetic mechanisms.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a clinical syndrome characterized by pain in the perineum, pelvis, suprapubic area, or external genitalia and variable degrees of voiding and ejaculatory disturbance. The analgesic effect of extracorporeal shock wave treatment (ESWT) was an interesting phenomenon with an unclear mechanism discovered by chance in the applications for urolithiasis, on which ESWT has become an increasingly popular therapeutic approach as an alternative option for the treatment of a number of soft tissue complaints. In this study, we aimed to evaluate the feasibility and efficacy of ESWT in non-inflammatory (IIIB) CP/CPPS.Men diagnosed with IIIB CP/CPPS were randomized to either ESWT (group 1, n = 40) or the control (group 2, n = 40). Group 1 received 20 000 shock wave impulses in 10 sessions over a two-week period, whereas group 2 received only a sham procedure. The total scores and sub-domain scores of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) for both groups were assessed at baseline, mid-treatment, end-point, and 4-week and 12-week follow-up visits.The mean total NIH-CPSI score of group 1 was significantly decreased from baseline at all post-treatment time points (P0.01 for all). Decreases in pain domain and quality of life (QOL) scores were also significant. In group 2, no significant decreases of total NIH-CPSI score and pain domain score were found at all post-treatment time points. At the end-point of treatment, 71.1% of group 1 exhibited perceptible improvement in total NIH-CPSI compared with 27.0% of group 2 (P0.001); additionally, 28.9% of group 1 exhibited clinically significant improvement compared with 10.8% of group 2 (P0.01). Moreover, a greater number of patients in group 1 at 4-week and 12-week follow-up were rated as responders (perceptible and clinically significant response) compared with group 2.ESWT exhibits a potentially therapeutic role in the treatment of CP/CPPS.

To explore the clinical, pathological features and prognosis of patients with chromophobe renal cell carcinoma.From January 1998 to January 2008, clinical data of 29 patients with chromophobe renal cell carcinoma including clinical manifestations, imaging examinations, treatment models, pTNM stages and follow-up results, were summarized to investigate its features and prognosis.All cases had no obvious clinical and preoperative imaging presentation. There were 23 patients underwent radical nephrectomy, and 6 cases underwent nephron sparing surgery. Postoperative pathological findings confirmed the diagnosis of chromophobe renal cell carcinoma. Macroscopically, the cut surface of the tumors were generally beige in color. Histologically, it showed polygonal chromophobe cells and small round eosinophilic cells with eccentric hyaline degeneration. These tumor cells had a clear and sharp membrane, lightly stained abundant cytoplasm with a fine reticular translucent pattern and irregular nuclei. And a perinuclear halo was often seen in these cells. Histochemically, the tumor cells generally show a diffuse and strong reaction for CK-8 with a negative expression of Vimentin. The pTNM stages of the tumor were as follows, pT1N0M0 in 11 cases, pT2N0M0 in 8 cases, pT3aN0M0 in 5 cases, pT1N1M0 in 3 cases, pT2N1M0 in 2 cases. Twenty-six cases of patients were followed up (24 to 144 months, with an average of 90 months), 3 cases died of cardio-cerebrovascular disease, and local recurrence involved in 6 cases with reoperation in 4 cases, as well as distant metastasis in 1 case. Twenty-one cases survived with tumor-free. The statistical results indicated that the survival rates of the patients with chromophobe renal cell carcinoma in five years and ten years were 83.9%, 77.9%, respectively, compared with renal cell carcinoma of the same stage 63.8% and 49.9% at the same periods, and there is no difference in the survival rate of five years (P0.05) but significant difference in that of ten years (P0.01).Chromophobe renal cell carcinoma is a morphologically uncommon subtype of renal cell carcinoma with the good prognosis. Definite diagnosis depends on its typical pathological feature. Radical nephrectomy is the first choice for the treatment of chromophobe renal cell carcinoma.

The oxalate-degradation genes of Oxalobacter formigenes (Ox.F)-frc gene and oxc gene-were cloned and transfected into intestinal stem cell population of the mouse to make the latter obtain oxalate-degradation function.(1) The dicistronic eukaryotic expression vector, which could express oxc gene and frc gene in the same time, pIRES-oxc-frc was constructed. (2) The intestinal stem cell population of the mouse were isolated and cultured, and the function of the cell growth and differentiation was identified. (3) The cells were transfected with pIRES-oxc-frc. After selection by G418, the function of the cell growth and differentiation and the the expression of the objective genes were identified. (4) The concentration of the oxalate in the culture medium which was used to culture the transgenic cells was determined by ion chromatography to explore the oxalate-degradation function of the cells.Ox.F could be isolated and cultured from the feces of Chinese people. Compared with the foreign reports, a certain morphologic variation of the Ox.F existed. But the oxc gene and frc gene showed high homology with the sequence reported in GenBank. The recombinant plasmid containing oxc gene and frc gene could successfully be transfected into the intestinal stem cell population of the mouse. The expression of the objective genes was normal. The concentration of the oxalate in the culture fluid of the transgenic intestinal stem cell population [(2.48 +/- 0.03 g/L)] was lower than those of the normal group [(2.69 +/- 0.01) g/L] and the control group [(2.69 +/- 0.01) g/L, P0.01].The oxc gene and the frc gene could be transfected into the intestinal stem cell population of the mouse, and the cells could be given oxalate-degrading function. The gene of prokaryocyte could be introduced into the eukaryocyte for a successful expression.

To investigate the effect of inversion-table in the treatment of lower pole renal stones.From March 2006 to September 2008, 36 patients with lower pole renal calculi were treated by inversion-table, 13 cases with stone diameter from 4 mm to 20 mm received extracorporeal shock wave lithotripsy (ESWL) combined with inversion-table treatment and other 23 cases with stone diameter from 2 mm to 4mm received inversion-table treatment alone.All of 36 cases underwent inversion-table treatment successfully and no one had cardio-cerebral accident. After following up 3 months, the radiologically documented complete stone clearance rate at 3 months group was 83.3%.Inversion-table treatment is a safe and valuable adjunct in assisting passage of lower pole renal stone fragments after mini-invasive treatment of stone and can improve stone-free rate.

To investigate the clinical efficacy, surgical indications and postoperative complications of mid urethral sling procedures in treatment of female stress urinary incontinence.A multicenter clinical trial was conducted from April 2002 to April 2008 in five hospitals, 304 cases of genuine stress urinary incontinence and 8 cases of mixed incontinence were included. TVT procedures were carried out in 134 patients, TVTO procedures in 167 patients, Monarc procedures in 11 patients. Perioperative evaluations included: operating time, bleeding volume, and perioperative complications. Operative efficacy was classified into three categories: cure, improved and failure and evaluated before discharge, 3 months after surgery and then every year.TVT group had longer operating time [(18.5 + or - 9.6) min] and more bleeding volume [(32.2 + or - 12.6) ml] than those in TVTO group [(11.5 + or - 3.1) min, (12.8 + or - 8.5) ml] and in Monarc group [(11.1 + or - 2.6) min, (12.3 + or - 3.5) ml] with P0.05. Monarc and TVTO procedures had higher cure rates and improve rates comparing with TVT, but the differences were of no significance. The cure rate (95.7%) in patients with genuine stress incontinence were significantly higher than that in patients with mixed incontinence (37.5%). No significant differences of total intra- and postoperative complications were noted for all of the three procedures. However, bladder injury tended to occur in TVT group and obturator nerve injury and vaginal injury tended to occur in TVTO group. Transient voiding dysfunction and urinary retention were the most common complications.Mid urethral sling procedures have excellent clinical outcomes in the treatment of female stress urinary incontinence.

To study the expression level of calbindin-D28k, a kind of calcium binding protein, in the kidneys of genetic hypercalciuric stone-forming (GHS) rats and to investigate its role in idiopathic hypercalciuria (IH).Kidneys were taken out from 16 GHS rats and 6 normal control (NC) rats. Western blotting and real time quantitative PCR were used to detect the protein and mRNA expression levels of calbindin-D28k respectively.Western blotting showed that the A value of calbindin-D28k of the GHS rats was 0.49 +/- 0.02, significantly higher than that of the NC rats (0.20 +/- 0.01, P0.05). The 2(-(delta delta CT)) value of mRNA of calbindin-D28k of the GHS rats was 1.21, remarkably higher than that of the NC rats [with the of 2(-(delta delta CT)) value of 1.0]. There was not significant difference in the delta CT value between the two groups (P0.05).The up-regulation of calbindin-D28k in the GHS rats is possibly caused by hyperexpression of VDR and hypercalcinuria, and plays an important role in urine calcium reabsorption; however, it is not the key protein that results in IH.

To evaluate the value of quantitative examination of MUC 1 in the urine of patients with bladder transitional cell carcinoma (BTCC).Urine samples were obtained from 31 patients with BTCC for quantification of MUC 1 content by immunoradiometric analysis. The urine samples were also examined in 10 patients with cystitis glandularis, 10 with benign urine disease and 10 healthy volunteers. The differences in urine MUC1 content were statistically measured between the groups, between cancer patients of different clinical stages and classes, between primary and recurrent cancer patients, and between measurements taken before and after operation.Urine MUC 1 was detected in all the patients. No significant differences were found between the groups, nor between patients with BTCC in all stages (P0.05), or between primary and recurrent cancer patients (P0.05). But MUC 1 contents showed significant difference before and after the operation in the cancer patients (P0.05).Urine MUC 1 can not serve as the marker to screen and diagnose BTCC, but it can be useful in therapeutic effect and prognostic evaluation. Specific oncogene markers are more significant than oncogene phenotype markers in clinical diagnosis and screen of BTCC.

To explore the feasibility of muscle-derived cell autotransplantation in the treatment of post-prostatectomy urinary incontinence.Skeletal muscle-derived cells (MDC) were isolated and purified by replate technique from 6 female SD rats, and then transduced with adenovirus carrying Lac-Z gene. About 5 x 10(6) of the transduced cells were injected autologously into the bladder neck of the animals. Tissues were harvested after 5 and 15 days for histological examination and X-gal staining.At 5 and 15 days after the autologous MDC transplantation, histological examination revealed no apparent sign of inflammation and inflammatory cell invasion, and X-gal staining showed a large number of cells dyed blue, indicating the survival of the autologous cells.Autotransplanted MDCs can survive permanently. Autologous muscle stem cell injection can be an effective treatment for post-prostatectomy urinary incontinence.

To evaluate retroperitoneal laparoscopic partial or total adrenalectomy for primary aldosteronism.From February 2000 to September 2003, 130 patients (76 women and 54 men) with a confirmed diagnosis of primary aldosteronism underwent retroperitoneal laparoscopic operation. Of the 130 cases, there were 119 cases with Aldosterone-producing Adenoma and 11 cases with Idiopathic Adrenal Hyperplasia (unilateral of 2 cases). Eleven cases with Idiopathic Adrenal Hyperplasia underwent unilateral adrenalectomy. Of the 119 cases with Aldosterone-producing Adenoma, 61 cases underwent total adrenalectomy, and 58 cases underwent partial adrenalectomy. All cases were with preoperatively high plasma aldosterone, low plasma rennin and hypokalemia and arterial hypertension.Operations were successfully performed in all cases. The operative time ranged from 15 to 225 min (mean 52 +/- 40 min, Md = 43 min) and the operative bleeding ranged from 0 to 200 ml (mean 23 +/- 34 ml, Md = 20 ml, zero bleeding means that less than 5 ml) without blood transfusion. The hospital length of stay was ranged from 3 to 9 d (mean 5.1 +/- 1.3 d). No major complication occurred. Kalemia was normalized within one month and aldosterone/PRA ratio was decreased obviously in all cases. Postoperatively blood pressure was normalized within 2 month in 88 cases without using any drug.It is safe and practical to perform retroperitoneal laparoscopic partial on total adrenalectomy on the patients with primary aldosteronism.

Background The development of vectors for cell-specific gene delivery is a major goal of gene therapeutic strategies. Transferrin receptor (TfR) is an endocytic receptor and identified as tumor relative specific due to its overexpression on most tumor cells or tissues, and TfR binds and intakes of transferrin-iron complex. We have previously generated an anti-TfR single-chain variable fragments of immunoglobulin (scFv) which were cloned from hybridoma cell line producing antibody against TfR linked with a 20 aa-long linker sequence (G4S)4. In the present study, the anti-TfR single-chain antibody (TfRscFv) was fused to DNA-binding domain of the yeast transcription factor GAL4. The recombinant fusion protein, designated as TfRscFv-GAL4, is expected to mediate the entry of DNA-protein complex into targeted tumor cells. Results Fusion protein TfRscFv-GAL4 was expressed in an E. coli bacterial expression system and was recovered from inclusion bodies with subsequent purification by metal-chelate chromatography. The resulting proteins were predominantly monomeric and, upon refolding, became a soluble biologically active bifunctional protein. In biological assays, the antigen-binding activity of the re-natured protein, TfRscFv-GAL4, was confirmed by specific binding to different cancer cells and tumor tissues. The cell binding rates, as indicated by flow cytometry (FCM) analysis, ranged from 54.11% to 8.23% in seven different human carcinoma cell lines. It showed similar affinity and binding potency as those of parent full-length mouse anti-TfR antibody. The positive binding rates to tumor tissues by tissue microarrays (TMA) assays were 75.32% and 63.25%, but it showed weakly binding with hepatic tissue in 5 cases, and normal tissues such as heart, spleen, adrenal cortex blood vessel and stomach. In addition, the re-natured fusion protein TfRscFv-GAL4 was used in an ELISA with rabbit anti-GAL4 antibody. The GAL4-DNA functional assay through the GAL4 complementary conjugation with the GAL4rec-GFP-pGes plasmid to verify the GLA4 activity and GAL4rec-recognized specificity functions. It also shows the complex, TfRscFv-GAL4-GAL4rec-GFP-pGes, could be taken into endochylema to express the green fluorescent protein (GFP) with 8 to 10-fold transfection efficiency. Conclusions Results of our study demonstrated that the biofunctianality of genetically engineered fusion protein, TfRscFv-GAL4, was retained, as the fusion protein could both carry the plasmid of GAL4rec-pGes and bind TfR on tumour cells. This product was able to transfect target cells effectively in an immuno-specific manner, resulting in transient gene expression. This protein that can be applied as an effective therapeutic and diagnostic delivery to the tumor using endogenous membrane transport system with potential widespread utility.