Purpose: This study aimed to investigate the associations between the preoperative prognostic nutritional index (PNI), systemic immune-inflammation index (SII) and overall survival (OS) and cancer-specific survival (CSS) in high-risk non-muscle-invasive bladder cancer (NMIBC) patients who received intravesical instillation of Bacillus Calmette-Guerin (BCG) after transurethral resection of bladder tumour (TURBT). Patients and Methods: We retrospectively collected data from 387 high-risk NMIBC patients between January 2004 and December 2014. PNI was calculated as total lymphocyte count (10⁹/L)× 5+albumin concentration (g/L). SII was calculated as neutrophil count (10⁹/L)×platelet count (10⁹/L)/lymphocyte count (10⁹/L). The cutoff values of PNI and SII were determined through receiver operating characteristic (ROC) analysis. OS and CSS were estimated by Kaplan–Meier analysis. The Log rank test was used to compare differences between the groups. Univariate and multivariate Cox regression analyses were performed to assess the predictive values of PNI and SII for OS and CSS. Additionally, highest-risk NMIBC patients were also divided into low or high groups according to PNI and SII. The OS and CSS of highest-risk NMIBC patients were estimated using Kaplan-Meier analysis with the Log rank test. Results: The patients were divided into two groups according to the cutoff values of PNI (< 50.17 vs ≥ 50.17) and SII (< 467.76 vs ≥ 467.76). Kaplan–Meier analysis revealed that low PNI and high SII were associated with poorer OS and CSS in high-risk NMIBC patients. Univariate and multivariate Cox regression analyses revealed that PNI and SII were independent predictive factors for OS and CSS. Kaplan–Meier analysis also revealed that low PNI and high SII were related to poorer OS and CSS in highest-risk NMIBC patients. Conclusion: These results suggest that preoperative PNI and SII, based on standard laboratory measurements, may be useful noninvasive, inexpensive and simple tools for predicting the long-term survival of high-risk NMIBC patients who received intravesical instillation of BCG after TURBT.

Background: Epidemiological evidences regarding the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of prostate cancer (PC) is still controversial. Therefore, we conducted a meta-analysis to explore the controversy that exists. Methods: Electronic databases including Medline, EMBASE, Web of Science, Cochrane Library, BIOSIS, Scopus, CBM, CNKI, WANFANG, and CQVIP were used to search for and identify eligible studies published until December 31, 2017. Pooled effect estimates for the relative risk (RR) were computed through fixed-effects or random-effects models as appropriate. Publication bias was evaluated by Egger's and Begg's tests and potential sources of heterogeneity were investigated in subgroup analyses. Results: A total of 43 observational studies were eligible for this meta-analysis. A protective effect was identified for the intake of any NSAIDs on the risk of PC (pooled RR = 0.89, 95% CI = 0.81–0.98). Moreover, the long-term intake of NSAIDs (≥5 years rather than ≥4 years) was associated with reduced PC incidence (pooled RR = 0.882, 95% CI = 0.785–0.991). Aspirin intake was also associated with a 7.0% risk reduction of PC (pooled RR = 0.93, 95% CI = 0.89–0.96). The inverse association became stronger for advanced PC and PC with a Gleason score ≥7 compared to the association with total PC. Interestingly, it was the daily dose (≥1 pill/day) rather than, long-term aspirin intake (≥4 or ≥5 years) that was associated with reduced PC incidence (pooled RR = 0.875, 95% CI = 0.792–0.967). The pooled effects for non-aspirin NSAIDs demonstrated no significantly adverse or beneficial effects on total PC, advanced PC, or PC with Gleason score ≥7, though all pooled RRs were >1. Conclusions: Our findings suggested a protective effect of the intake of any NSAIDs on the risk of PC, especially in those who took the NSAIDs for a long period. Moreover, aspirin intake was also associated with a decreased risk of PC, and there was a dose related association between aspirin intake and the risk of PC, while no significant effects of long-term aspirin intake were found on the PC incidence.

Chemotherapy is the main treatment for bladder cancer, but drug resistance and side effects limit its application and therapeutic effect. Herein, we constructed doxorubicin (DOX)/COOH-mesoporous silica nanoparticle/polyethylenimine (PEI)/nucleic acid chimeras (DOX/MSN/Chimeras) to reduce the toxicity of chemotherapy drugs and the resistance of bladder cancer cells. Transmission electron microscopy showed that PEI was coated on the DOX/MSN/BSA nanoparticles with a diameter of about 150 nm. DOX/MSN/PEI could control DOX release for over 48 h, and the sudden release rate was significantly lower than DOX/MSN. Immunohistochemical results showed that DOX/MSN/Chimera specifically bound to bladder cancer cells, and markedly inhibited PI3K expression and proliferation of DOX-resistant bladder cancer cells. DOX/MSN/Chimera promoted the apoptosis of drug-resistant bladder cancer cells, which was superior to DOX/MSN/Aptamer or DOX/MSN. We further carried out animal experiments and found that DOX/MSN/Chimera could reduce the volume of transplanted tumors in vivo. Compared with DOX/MSN/Aptamer group, the proliferation rate was significantly decreased and the proportion of apoptotic cells was highly increased. Through the histological observation of kidneys and lungs, we believed that DOX/MSN/Chimera can effectively reduce the damage of chemotherapy drugs to normal tissues. In conclusion, we constructed a COOH-MSN/nucleic acid chimera conjugate for the targeted delivery of siRNA and anti-cancer drugs. Our study provides a new method for personalized and targeted treatment of drug-resistant bladder cancer.

Introduction: Krüppel-like factors (KLFs), which comprise 17 family members, exert important functions during the development of cancer. The role of KLF16 seems controversial in carcinogenesis because both tumor suppressive and promoting effects have been reported. Methods: The expression level of KLF16 was analyzed based on public data sets from The Cancer Genome Atlas (TCGA) and evaluated by immunohistochemical (IHC) staining. CCK8 assay, colony formation analysis, transwell assays and the PI/Annexin V-APC assay kit were performed to detect cell growth, colony formation, cell migration and apoptosis of BC cells. Xenograft tumorigenesis assay was performed to detect the KLF16 expression on BC growth in vivo. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay were performed to analyze the interaction between KLF16 and its target. Results: In this study, we explored the role of KLF16 in bladder cancer (BC). We demonstrated that KLF16 was overexpressed in human BC tissues. The high expression of KLF16 was a potential predictor of a poor prognosis in patients with BC. Interference with KLF16 expression in 563 cells, having relatively higher levels of KLF16, repressed cell proliferation and migration. In contrast, upregulation of KLF16 in T24 cells enhanced cellular function, including cell growth and migration. KLF16 also suppressed the apoptosis of BC cells. Additionally, KLF16 inhibited the expression of the TGF-type III receptor (TGFBR3) by binding to its promoter sequence and reducing transcriptional activity. There was a negative correlation between KLF16 and TGFBR3 in human BC tissues. Furthermore, TGFBR3 was revealed to be a negative regulator of BC cell proliferation and migration. KLF16 also supported BC tumorigenesis by downregulating TGFBR3 expression in vivo. Discussion: These results suggested that KLF16 acts as an oncogene in BC through transcriptional inactivation of TGFBR3. This study provides evidence that targeting the KLF16/TGFBR3 axis may be beneficial for BC patients.

Introduction: The aim of this study was to elucidate the association between apolipoprotein A-I (Apo A-I) and overall survival (OS) as well as cancer-specific survival (CSS) in non-muscle-invasive bladder cancer (NMIBC) patients undergoing transurethral resection of bladder tumor (TURBT). Patients and methods: We retrospectively collected data of 470 eligible patients diagnosed with NMIBC and who received TURBT between January 2004 and December 2011. Pretreatment blood indexes were examined. The association of Apo A-I with clinicopathological characteristics was further analyzed by dichotomizing our sample into those with Apo A-I ≤ 1.19 g/L (low Apo A-I group) and those with Apo A-I > 1.19 g/L (high Apo A-I group). OS and CSS were estimated by Kaplan–Meier analysis and the log-rank test was used to compare differences between groups. Univariate and multivariate Cox regression analyses were plotted to assess the prognostic value of Apo A-I in NMIBC patients. In addition, subgroup analyses were performed according to the risk classification of the International Bladder Cancer Group. Results: In the overall population, patients in the high Apo A-I group had greater 5-year OS and 5-year CSS rates as compared to those in the low Apo A-I group. Kaplan–Meier survival analysis revealed that higher albumin, Apo A-I, and hemoglobin levels were associated with greater OS and CSS while elevated neutrophil–lymphocyte ratio was associated with worse OS and CSS in the overall and high-risk population rather than low- and intermediate-risk population. Furthermore, Apo A-I was shown to be an independent predictor in the overall population (for OS, hazard ratio [HR], 0.364, 95% confidence interval [CI], 0.221–0.598, p < 0.001; for CSS, HR, 0.328, 95% CI, 0.185–0.583, p < 0.001) and high-risk patients (for OS, HR, 0.232, 95% CI 0.121–0.443, p < 0.001; for CSS, HR, 0.269, 95% CI, 0.133–0.541, p < 0.001). Conclusion: These results suggest that Apo A-I level could potentially serve as a useful prognostic indicator for therapeutic decision making in NMIBC patients.