Diagnostic value of the combination of DAPK methylation in urinary sediment and B ultrasound for recurrent urinary bladder cancer.

BACKGROUND: Urinary bladder cancer (UBC) is the most common malignancy affecting the urinary system. This study aimed to investigate the diagnostic value of combining DAPK methylation in urinary sediment and B ultrasound in the detection of recurrent UBC. METHODS: A total of 1021 cases with primary UBC who underwent electrocision of bladder tumor through urethra were included in this study and followed up. Various parameters including B ultrasound, DAPK methylation in urinary sediment, examination of exfoliated cells in the urine, and cystoscopy were performed. The data collected was analyzed using the Kappa test, and receiver operating characteristic (ROC) curve was constructed to assess the diagnostic role in recurrent UBC. RESULTS: Among the 1021 patients, 115 patients experienced recurrence confirmed by cystoscopy and biopsy within two years and were excluded from the study, resulting in an effective sample size of 906 primary UBC cases. The results of cystoscopy showed agreement with B ultrasound (Kappa = 0.785, P < 0.05), as well as with DAPK methylation in urinary sediment, and the combination of B ultrasound and DAPK methylation (Kappa = 0.517, P < 0.05, Kappa = 0.593, P < 0.05). The combination of B ultrasound with DAPK methylation yielded an area under the curve of 0.922, with a sensitivity of 92.86%, specificity of 91.63%, and a negative predictive value of 99.4%, suggesting that a negative result indicates a low risk of recurrence. CONCLUSION: The combination of DAPK methylation in urinary sediment with B ultrasound demonstrates high diagnostic performance for recurrent UBC.

Sarcopenia as an independent predictor for venous thromboembolism events in bladder cancer patients undergoing radical cystectomy.

BACKGROUND: Sarcopenia has been proved to be related to the prognosis of patients with bladder cancer (BC) after radical cystectomy (RC). The relationship between sarcopenia and the occurrence of venous thromboembolism (VTE) after RC is unclear. METHODS: We collected data of 252 BC patients treated with RC at our institution. Data was obtained from the electronic medical record database. Sarcopenia was defined by the third lumbar vertebra skeletal muscle index (SMI) which was measured using preoperative computed tomography. The primary outcome was the incidence of VTE within 30 days after the surgery in sarcopenia and non-sarcopenia groups. Outcomes between the two cohorts were compared using univariate analysis. Multivariate logistic regression was used to control for differences between cohorts. RESULTS: Two hundred fifty-two patients were enrolled, of which 85 (33.7%) patients were in sarcopenia group, while 167 (66.3%) patients were not in sarcopenia group. The incidence of total VTE in sarcopenia group was higher than that in the extended group (10.6% vs. 1.8%, p = 0.005). Sarcopenia did not cause an increase in other postoperation 30 days complications (all p > 0.05). Multivariate analysis confirmed sarcopenia was independently associated with increased odds of VTE (OR = 4.18, 95% CI [1.01-17.27]; p = 0.048). Subgroup analysis showed that patients with VTE tended to be older (76.5 vs 66.0, p = 0.025) and have higher proportion of diabetes (58.3% vs 14.2%, p < 0.001) as well as lower level of serum albumin (35.0 g/L vs 40.4 g/L, p = 0.023) compared with those without VTE. CONCLUSIONS: Sarcopenia was an independent predictor for VTE with patients undergoing RC for BC.

The CUSUM curve combined with comprehensive complication index for assessing short-term complications of radical cystectomy.

OBJECTIVE: To evaluate the comprehensive complication index(CCI) and Clavien-Dindo classification(CDC) for short-term postoperative complications in radical cystectomy and assess cumulative surgical morbidity to compare sufficient surgical skill. METHODS: From September 30, 2010, to October 1, 2020, clinical data of patients with urothelial carcinoma who underwent radical cystectomy with urinary diversion were gathered, patients who had only a urinary diversion, bladder sparing surgery, additional abdominal surgeries at the same time were all excluded. The CDC and CCI were utilized to evaluate 30-d complications after radical cystectomy and the relevance of hospital stay was compared between CCI and CDC. The cumulative sum control models (CUSUM) were used to evaluate the overall surgical morbidity of radical cystectomy in our facility and for comparisons between surgeons. RESULTS: This study enrolled a total of 635 individuals, 548 (86.3%) of whom had 1124 problems. The incidence of severe complications (CDC≥ Grade III) was 10.2%. The average CCI was 20.2 ± 14.7. Gender, urinary diversion subtype, procedure method, and surgeon were significantly correlated with the increase of CCI (p < 0.05). The CCI demonstrated a better relationship with hospital stay (R2  = 0.429) than the CDC (R2  = 0.361). The CUSUM-CCI model demonstrated a difference and growth distribution in dynamic time between individual surgeons. CONCLUSIONS: CCI can better reflect the incidence of complications for radical cystectomy than CDC, and CCI is more strongly correlated with postoperative hospital stay. The CUSUM-CCI model can reflect the quality of surgical skill for each surgeon instantaneously.

Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer.

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT-qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.

RAB38 promotes bladder cancer growth by promoting cell proliferation and motility.

BACKGROUND: Bladder cancer is the most common malignancy of urinary system with high morbidity and mortality. In general, the development and progression of bladder cancer are complicated pathological processes, and the treatment methods mainly include surgical resection, radiotherapy, chemotherapy, and combined therapy. In recent years, targeted therapy has made progress in the treatment of bladder cancer. Therefore, to improve survival rates of patients with advanced bladder cancer, novel therapeutic targets are still urgently needed. METHODS AND RESULTS: In this study, we found that RAB38 expressed in tumor tissues of patients with bladder cancer was linked to clinical features including pTNM stage and tumor recurrence, and positively correlated with the poor prognosis of bladder cancer. Notably, further results indicated that depletion of RAB38 could significantly inhibit the proliferation and motility of two types of human bladder cancer cells, T24 and 5637 cells. In addition, RAB38 ablation obviously blocked tumor growth and development in mice compared with control. CONCLUSION: In conclusion, this study provides significant evidence that RAB38 promotes the development of bladder cancer and provides a novel therapeutic target of bladder cancer.

Molecular analysis of dominant species in Listeria monocytogenes-positive biofilms in the drains of food processing facilities.

Listeria monocytogenes exhibits symbiotic codependence with the dominant commensal bacteria, which may help it avoid being removed or inactivated by disinfectants in local environments. In this study, we investigated L. monocytogenes-positive biofilms at food production facilities, and the dominant bacterial species of the biofilms were identified to determine the properties of the microbiological background. For this purpose, the ISO 11290 method was used for the detection and isolation of L. monocytogenes, and the species were further identified based on 16S rRNA and hly genes. 16S rRNA gene-based cloning, terminal restriction fragment length polymorphism, and denaturing gradient gel electrophoresis were combined to evaluate the dominant bacteria of the drain biofilms. Out of 100 drain samples, 8 were naturally contaminated with L. monocytogenes. Three molecular methods consistently showed that Pseudomonas psychrophila, Pseudomonas sp., and Klebsiella oxytoca were dominant species in 3Q, 5Q, and 6Q samples; Aeromonas hydrophila and Klebsiella sp. were significantly dominant in 1-2, 1-3, and 3-2 samples; A. hydrophila and K. oxytoca were dominant in the 2-3 sample; and A. hydrophila and Pseudomonas sp. were prominent in the 3-3 sample. Different biofilms from the same plant shared common bands, suggesting that similar bacteria can be found and can be dominant in different biofilms. This study provides a better understanding of the dominant compositions in these bacterial communities. Further studies to determine the mechanism of co-culture with L. monocytogenes will be of critical importance in predicting effective disinfection strategies.

The comparison of perioperative outcomes of robot-assisted and open partial nephrectomy: a systematic review and meta-analysis.

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) has been widely used worldwide, to determine whether RAPN is a safe and effective alternative to open partial nephrectomy (OPN) via the comparison of RANP and OPN. METHODS: A comprehensive literature search was performed within the databases including PubMed, Cochrane Library, and Embase updated on 30 September 2015. Summary data with their corresponding 95 % confidence intervals (CIs) were calculated using a random effects or fixed effects model. Heterogeneity and publication bias were also evaluated. RESULTS: A total of 16 comparative studies including 3024 cases were used for this meta-analysis. There are no significant differences in the demographic characteristic between the two groups, but the age was lower and the tumor size was smaller for the RAPN group. RAPN had a longer operative time and warm ischemia time but which showed less estimated blood loss, hospital stay, and perioperative complications. No differences existed in the margin status, the change of glomerular filtration rate, transfusion rate, and conversion rate between the two groups. There was no significant publication bias. CONCLUSIONS: RAPN offered a lower rate of perioperative complications, less estimated blood loss, and shorter length of hospital stay than OPN, suggesting that RAPN can be an effective alternative to OPN. Well-designed prospective randomized controlled trials will be helpful in validating our findings.

Expression of long noncoding RNA lncRNA-n336928 is correlated with tumor stage and grade and overall survival in bladder cancer.

Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n = 3). Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P < 0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P < 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to the patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Collectively, our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer.

Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population.

Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.

[Establishment and application of Chinese Pediatric Evaluation of Disability Inventory norms in Chongqing, China].

OBJECTIVE: To establish the Chinese Pediatric Evaluation of Disability Inventory (PEDI) norms in Chongqing, China. METHODS: PEDI (English version) was translated into Chinese and proof read by back-translation. A total of 1 140 children stratified by age were randomly selected from Chongqing and evaluated by the Chinese version of the PEDI. The obtained data were statistically analyzed. RESULTS: Of 1 140 questionnaires, 1 075 (94.3%) were valid. The data showed that the raw and scale scores of PEDI increased with age, but the standard scores did not increase with age. The raw, scale, and standard scores on self-care and social function scales were significantly lower than American PEDI norms in some age periods (P<0.05), but the raw, scale, and standard scores on mobility scale were not significantly different from American norms (P>0.05). CONCLUSIONS: The PEDI norms in Chongqing have been successfully established, and can be used to assess the daily function in children, judge the degree of daily function impairment, evaluate the effect of rehabilitation training, and make the rehabilitation plan for disabled children.

Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression.

BACKGROUND: Special AT rich sequence binding protein 1 (SATB1) plays a crucial role in the biology of various types of human cancer. However, the role of SATB1 in human nasopharyngeal carcinoma (NPC) remains unknown. In the present study, we sought to investigate the contribution of aberrant SATB1 expression in the progression of NPC and its association with the Epstein Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1). METHODS: Immunohistochemical analysis was performed to detect SATB1 and LMP-1 protein in clinical samples, and the association of SATB1 protein expression with patient clinicopathological characteristics and LMP-1 expression were analyzed. SATB1 expression profiles were evaluated in well-differentiated NPC cell line CNE1, poorly-differentiated CNE2Z, undifferentiated C666-1 and immortalized nasopharyngeal epithelia NP-69 cells using quantitative RT-PCR, western blotting and fluorescent staining. After inhibition the SATB1 expression by using SATB1 specific small interfering RNA in these cell lines, the change of cell proliferation was investigated by western blotting analysis of PCNA (proliferating cell nuclear antigen) expression and CCK-8 assay, and the cell migration was assessed by Transwell migration assay. Finally, the expressions of SATB1 and PCNA were examined in CNE1 cells that forced LMP-1 expression by fluorescent staining and RT-PCR. RESULTS: Immunohistochemical analysis revealed that SATB1 protein expression was elevated in NPC tissues compared to benign nasopharyngeal tissues (P = 0.005). Moreover, high levels of SATB1 protein expression were positively correlated with clinical stage (P = 0.025), the status of lymph node metastasis (N classification) (P = 0.018), distant metastasis (M classification) (P = 0.041) and LMP-1 expression status (r = 2.35, P < 0.01) in NPC patients. In vitro experiments demonstrated that an inverse relationship between SATB1 expression and NPC differentiation status, with SATB1 weakly expressed in NP-69 cells and CNE1 cells, and significant increasingly expressed in CNE-2Z and C666-1 cells. Targeted knockdown of SATB1 expression obviously attenuated the proliferation and migration of highly SATB1-expressing CNE2Z and C666-1 cells, but not NP-69 and CNE1 cells. Interestingly, forced LMP-1 expression in CNE1 cells led to a surprisingly increasing SATB1 expression and nuclear location, companying with an up-regulated PCNA expression. CONCLUSIONS: Our results reveal that EBV LMP-1-mediated over-expression of SATB1 is associated with NPC progression, suggesting SATB1 may represent a promising biomarker and therapeutic target for NPC.

[Diagnosis and treatment of xanthogranulomatous prostatitis: a case report and review of the literature].

OBJECTIVE: To explore the diagnosis and treatment of xanthogranulomatous prostatitis. METHODS: A 75-year-old man presented with a 3-month history of difficult urination and frequent micturition, which was exacerbated for 2 days. Digital rectal examination indicated an enlarged prostate size of II degrees with hard texture but no tenderness. Serum total PSA was 172.5 microg/L. TRUS revealed 200 ml of post-micturition residual urine, thickened bladder wall, prostate size of 4.3 cm x 3.8 cm x 5.0 cm and no isochrones. MRI showed an enlarged prostate gland, with marked enlargement of the central zones and low-signal intensity of the peripheral gland, part of the prostate gland protruding to the bladder with no clear dividing line. It was diagnosed as prostate cancer initially, and confirmed by needle biopsy. RESULTS: Histopathological examination revealed large numbers of "foamy macrophages" in the lesion, with a few multinucleated giant cells, leukocytes, mononuclear, plasmocytes and fibroplasia. Immunohistochemistry showed CD68 (+) and PSA (-). The patient was treated with oral Tamsulosin and glucocorticoid and by temporary catheterization, and followed up for 20 months. Urination symptoms began to alleviate and serum PSA to decrease at 4 months. The PSA level was 9.2 microg/L at 13 months and 3.6 microg/L at 17 months. CONCLUSION: Xanthogranulomatous prostatitis is a rare clinically, which can be confirmed by histopathological examination. It is treated mainly by supportive therapy and, for the cases with severe lower urinary tract obstruction, TURP can be employed. Follow-up must be performed by possible examination of PSA and necessary needle biopsy of the prostate.

The impact of histological variants in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

OBJECTIVE: To investigate the impact of histological variants (HV) in patients with upper tract urothelial carcinoma (UTUC) and analyze the potential association between HV and postoperative bladder recurrence. MATERIALS AND METHODS: The medical records of UTUC patients treated with RNU at our center from January 2012 to December 2019 were retrospectively analyzed. Patients were grouped according to the types of HV. Clinicopathological features and prognostic factors were compared among groups. RESULTS: A total of 629 patients were included in the study: 458 (73%) patients had pure urothelial carcinoma (PUC) and 171 (27%) patients had UTUC with HV. Squamous differentiation was the most common type (124 cases, 19%), followed by glandular differentiation (29 cases, 5.0%). Patients with HV had a higher proportion of T3 and T4 pathologic stages (P < 0.001) as well as high-grade disease (P = 0.002). In the univariate analysis, squamous differentiation and glandular differentiation were significantly associated with worse cancer-specific survival (CSS) (HR 2.22, 95% CI 1.62-3.04, P < 0.001; HR 1.90, 95% CI 1.13-3.20, P = 0.016). However, the multivariate analysis showed that this association became non-significant. We found that HV were associated with recurrent muscle-invasive bladder cancer (MIBC) after RNU and all patients had T2 and T3 initial tumor stages (P = 0.008, P < 0.001). CONCLUSION: We found that UTUC patients with HV were associated with biologically aggressive disease and recurrent MIBC after RNU. The detection of bladder recurrence following surgery needs to be given more attention in advanced UTUC patients with HV.

NONO regulates multiple cytokine production in sepsis via the ERK1/2 signaling pathway.

The massive release of pro-inflammatory cytokines is a crucial step in triggering the inflammatory cascade in sepsis. Exploring the key molecules regulating the expression and release of multiple cytokines has important value for revealing the mechanism of the cytokine storm in sepsis. This study aimed to investigate the role of multifunctional nuclear protein non-POU domain containing octamer-binding protein (NONO) in the sepsis cytokine storm and to elucidate the underlying mechanism. We found that NONO expression in tissues and cells of sepsis mice was significantly upregulated. Downregulation of NONO expression inhibited the mRNA expression of multiple cytokines, including IL-6, IL-1ß, MCP-1, MIP-1α, and MIP-1ß in inflammatory cells from mice and human leukemic monocyte-THP1 cells challenged with lipopolysaccharide (LPS), and significantly decreased the level of these cytokines and TNF-α in the supernatant of THP1 cells challenged by LPS. Nono knockout also reduced the levels of TNF-α, IL-6, MIP-1α, and MIP-1ß in serum, alleviated hepatocyte edema, and improved the survival rate of sepsis mice. Reduced NONO expression decreased the phospho-ERK1/2 level in inflammatory cells from sepsis mice or THP1 cells challenged by LPS. Phospho-ERK1/2 inhibitor decreased the mRNA expression and concentration of cytokines in the culture supernatant of LPS-induced THP1 cells, similar to the effect of NONO knockdown. After LPS challenge, the levels of phospho-ERK1/2 and NONO were increased, with obvious colocalization in the nucleus and vesicular-like organelles in macrophages. NONO knockdown decreased nuclear translocation of phospho-ERK1/2 in LPS-challenged THP1 cells. These results suggest that NONO is a potentially critical molecule involved in multiple cytokine production in sepsis. Upregulated NONO in sepsis may promote the expression and release of multiple cytokines to participate in a sepsis cytokine storm by promoting ERK1/2 phosphorylation.

[Tail-suspended model simulating mouse oocytes maturation inhibited with microgravity].

We studied the effects of simulated microgravity on mouse oocytes maturation, and analyzed whether the tail-suspended model can be applied to investigate simulated microgravity effects on reproductive processes in female mice. Mouse oocytes were cultured in vitro with microgravity simulated by a rotating wall vessel bioreactor and by tail-suspended model, and the maturation rate of the mouse oocytes in the two models were examined in vivo. The maturation rate of mouse oocytes cultured in simulated microgravity was 8.93%, and that was 72.33% in 1g gravity. In ratio, oocyte maturation rate had no significant difference between the rotational group and control group. Microgravity simulated by the tail-suspended model inhibited mouse oocytes maturation and increased the rate of oocytes abnormity. The maturation rate of tail-suspended mouse oocytes was 14.54%, which was significantly lower than that of control group. Tail-suspended model should be an ideal model to investigate simulated microgravity effects on reproductive processes of female mice.

Flexible cystoscopy can improve anxiety and subjective feelings of bladder cancer patients during follow-up.

INTRODUCTION: The effect of repeated cystoscopy on bladder cancer (BC) patient anxiety and feelings is rarely evaluated. AIM: To compare the difference of patients' anxiety and subjective feelings caused by different cystoscopes. MATERIAL AND METHODS: We prospectively included 192 BC patients who accepted regular cystoscopy follow-up after transurethral resection of bladder tumor (TURBT): 93 in the flexible group and 99 in the rigid group. The method of anesthesia and the order of examinations were consistent between different groups. We analyzed the anxiety level before cystoscopy, the maximum pain during the examination and the change of lower urinary tract symptoms (LUTS) before and after cystoscopy. Meanwhile, we analyzed the rate of gross hematuria and pyuria after cystoscopy. The anxiety and pain levels were evaluated by the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and visual analogue scale (VAS). LUTS was reflected by the Core Lower Urinary Tract Symptom Score (CLSS). We distinguished gender during analysis. RESULTS: The median APAIS score of male patients undergoing flexible or rigid cystoscopy was 8 vs. 12 (p < 0.01), and this result for females was 8 vs. 9 (p = 0.048). The median pain scores for men in the two groups was 1 vs. 2 (p < 0.01), respectively, and this outcome in female patients was 0 vs. 1 (p < 0.01). Patients in the rigid group had more CLSS change (0 vs. 1, p < 0.01). There was no difference in pyuria or gross hematuria rate after examination. Analysis in respective groups showed that men have more severe pain than women, 1 vs. 0 (p = 0.001) in the flexible group and 2 vs. 1 (p = 0.009) in the rigid group. CONCLUSIONS: A flexible cystoscope can improve anxiety and subjective feelings of BC patients during cystoscopy follow-up.

BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway.

BACKGROUND: The incidence of bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is approximately three times higher in men than in women. High expression of the mitotic kinase BUB1 is associated with the occurrence and development of several cancers, although the relationship between BUB1 and bladder tumorigenesis remains unclear. METHODS: Using a microarray approach, we found increased BUB1 expression in human BCa. The association between BUB1 and STAT3 phosphorylation was determined through molecular and cell biological methods. We evaluated the impact of pharmacologic inhibition of BUB1 kinase activity on proliferation and BCa progression in vitro and in vivo. RESULTS: In this study, we found that BUB1 expression was increased in human bladder cancer (BCa). We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727. In addition, the findings that pharmacologic inhibition of BUB1 kinase activity significantly suppressed BCa cell proliferation and the progression of bladder cancer in vitro and in vivo were further verified. Finally, we found that the BUB1/STAT3 complex promoted the transcription of STAT3 target genes and that depletion of BUB1 and mutation of the BUB1 kinase domain abrogated this transcriptional activity, further highlighting the critical role of kinase activity in the activation of STAT3 target genes. A pharmacological inhibitor of BUB1 (2OH-BNPP1) was able to significantly inhibit the growth of BCa cell xenografts. CONCLUSION: This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.

ECRG4 Represses Cell Proliferation and Invasiveness via NFIC/OGN/NF-κB Signaling Pathway in Bladder Cancer.

Bladder cancer (BCa) is a malignant tumor in the urinary system with high cancer-related mortality worldwide. However, the molecular mechanisms of many genes dysregulated in BCa are still unclear. Herein, we showed that esophageal cancer-related gene-4 (ECRG4), which is downregulated in BCa tissues and cell lines, has a positive correlation with osteoglycin (OGN). Further functional experimental studies suggested that both ECRG4 and OGN inhibit cell proliferation, migration, and invasion in BCa cells. Moreover, ECRG4 acts as a tumor repressor and promotes the expression of OGN via the upregulation of nuclear factor 1 C-type (NFIC), which can bind to the promoter region of OGN and regulate its transcription. Bioinformatics analysis revealed that NFIC is downregulated in BCa tissues and has a positive correlation with ECRG4 or OGN. Esophageal cancer-related gene-4 could positively regulate the protein levels of NFIC in BCa cells. In addition, we demonstrated for the first time that ECRG4 inhibits the nuclear factor (NF)-κB signaling pathway via the upregulation of OGN in BCa cells. Overall, these findings provide evidence that both ECRG4 and OGN function as tumor repressors and that overexpression of ECRG4 inhibits the NF-κB signaling pathway by promoting NFIC/OGN signaling in BCa cells. Our results reveal the molecular regulatory mechanisms of the ECRG4-mediated repression of the NFIC/OGN/NF-κB signaling pathway in BCa and provide potential biomarkers or therapeutic targets for BCa.

Small cell carcinoma of the upper urinary tract and factors associated with progress survival: a systematic review and pooled analysis.

INTRODUCTION: Little is known about small cell carcinoma of the upper urinary tract (UUT-SCC), the aim of this study is to identify the risk factors in relation to survival of patients with UUT-SCC. EVIDENCE ACQUISITION: Literature search on UUT-SCC was performed in databases including MEDLINE, EMBASE, Wangfang, and CNKI. Studies were eligible for inclusion if outcomes of patients with histopathologically confirmed UUT-SCC were reported. The relevant data on clinic, pathology, and therapy were collected. Progress survival was evaluated using the Cox regression model with the robust sandwich estimates of the covariance matrix. EVIDENCE SYNTHESIS: There were 55 eligible publications identified, contributing 76 patients in total. The median of overall survival (OS) was 14 months. In univariable analyses, pathological stage and platinum-based chemotherapy regimen were associated with OS (pT3-pT4 versus pT1-pT2, HR=3.228, P=0.005; other chemotherapies versus platinum-based, HR=6.249, P=0.035). The median of cancer-specific survival (CSS) was 15 months. In univariable analyses, pathological stage and platinum-based chemotherapy regimen were associated with CCS (pT3-pT4 versus pT1-pT2, HR=3.332, P=0.004; non-platinum based versus platinum-based, HR=7.784, P=0.025). CONCLUSIONS: In multivariable analyses, no variables were associated with OS and CSS. UUT-SCC is a rare tumor characterized by an aggressive clinical course. Pathological stage and platinum-based chemotherapy regimen are the most important factors related to OS and CSS.

KIF5A Promotes Bladder Cancer Proliferation In Vitro and In Vivo.

BACKGROUND: Bladder cancer is a common malignancy with uncontrolled and rapid growth. Although lots of the important regulatory networks in bladder cancer have been found, the cancer-relevant genes remain to be further identified. METHODS: We examined the KIF5A expression levels in bladder cancer and normal bladder tissue samples via immunohistochemistry and observed the effect of KIF5A on bladder tumor cell proliferation in vitro and in vivo. Additionally, a coexpression between KIF5A and KIF20B in tumor tissues was explored. RESULTS: KIF5A expression level was higher in the bladder cancer tissues than in the adjacent nontumor tissues. Patients with higher KIF5A expression displayed advanced clinical features and shorter survival time than those with lower KIF5A expression. Moreover, KIF5A knockdown inhibited bladder cancer cell proliferation, migration, and invasion demonstrated in vivo and in vitro. In addition, coexpression was found between KIF5A and KIF20B in tumor tissues. CONCLUSION: The results demonstrated that KIF5A is a critical regulator in bladder cancer development and progression, as well as a potential target in the treatment of bladder cancer.