Erlin Sun

Preoperative peripheral plasma fibrinogen level is an independent prognostic marker in penile cancer.

Background and aim: High levels of peripheral plasma fibrinogen have recently been revealed that related to poor clinical prognosis in various types of malignant tumors. The purpose of this research was to identify the prognostic significance of the preoperative peripheral serum fibrinogen level in patients with penile cell carcinoma. Methods: This retrospective research included 72 penile cancer patients with date about their serum fibrinogen value before surgery who undergone either partial or radical penectomy at The 2nd Hospital of Tianjin Medical University between January 2002 to January 2012. They had a mean follow-up of 30.8 months. To determine the factors that were significant in predicting a patients prognosis, univariate and multivariate analyses were performed according to the Cox proportional hazards regression model. Results: The 5-year cancer specific survival (CSS) rate was 62.4% of patients with preoperative fibrinogen levels below 340 mg/dl and 41.9% for those with higher levels (p = 0.001). Multivariate analysis revealed that the pathological T stage (p < 0.001), tumor grade (p = 0.036), postoperative chemotherapy (p = 0.041), nodal metastasis(p < 0.001), pathological type (p < 0.001) and fibrinogen (p = 0.023) were independent prognostic factors for survival. Patients with low fibrinogen level (<340mg/dl) had significantly longer CSS and the different survival rate were defined using the log-rank test. Conclusions: The high preoperative peripheral serum fibrinogen level was related to poor survival in penile cancer patients. Fibrinogen may serve as a powerful predictor of CSS in penile cancer patients.

RETRACTED ARTICLE: Down-regulation of Sphk2 suppresses bladder cancer progression

Bladder cancer is the second most common urological malignancy around the world and is by far the most frequent urological malignancy in China. The abnormal expression of sphingosine kinase 2 (SphK2) is associated with tumor progression and a poor patient survival rate, however, the effect of SphK2 on the bladder cancer cells remains unclear. The aim of the paper was to study the expression of SphK2 in bladder cancer and the role of SphK2 on the cell proliferation, metastasis, and apoptosis in bladder cancer in vitro. Our results showed that SphK2 is up-regulated in bladder cancer tissues compared with the corresponding adjacent non-neoplastic tissues, and the expression level of SphK2 was significantly higher in human bladder cancer cells in comparison with normal bladder epithelial cells. Silencing of SphK2 could inhibit the proliferation ability of T24 cells in vitro. In addition, SphK2 knockdown could induce a significant increase in the number of apoptotic cells. Furthermore, the transwell assay also showed significant cell migration inhibition in SphK2 siRNA transfectant compared with cell lines transfected with NC. Thus, this study suggested that SphK2 inhibition may provide a promising treatment for bladder cancer patients.

Graphene oxide/DNA-decorated electrode for the fabrication of microRNA biosensor

We fabricate a sensitive biosensor for miRNA quantification using a graphene oxide/DNA-decorated electrode. AgNPs are modified on DNA probe, which is the complementary sequence of target miRNA. Since the hybridization between DNA and miRNA releases DNA, electrochemical signals from AgNPs are declined, which indicates the concentration of miRNA.

Preoperative neutrophil–lymphocyte ratio and fibrinogen level in patients distinguish between muscle-invasive bladder cancer and non-muscle-invasive bladder cancer

Introduction The aim of this study was to explore if the preoperative neutrophil–lymphocyte ratio (NLR) and fibrinogen level can help in distinguishing between muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Methods We identified 669 patients who underwent surgery at our institution, and evaluated their preoperative NLRs and fibrinogen levels. Patients were divided into two groups, NMIBC (group-I) and MIBC (group-II), according to the postoperative pathology. For the intergroup comparison, data obtained from the two groups were evaluated using independent samples t-test. The cutoff value of the NLR, fibrinogen level, and integrated NLR and fibrinogen level was determined with receiver operating characteristic (ROC) curve. Results The mean NLRs of group-I and group-II were found as 2.71±2.46 and 4.66±8.00, respectively (P<0.001). The fibrinogen levels of the two groups were ~3.13±0.70 g/L and 3.41±0.84 g/L, respectively (P=0.001). Whether the NLR, fibrinogen level, and integrated NLR and fibrinogen level can help in distinguishing between MIBC and NMIBC was evaluated with ROC curve. The cutoff value of NLR was estimated as 2.01 according to the Youden index. With this value, sensitivity was found as 67.1%, specificity was 52.7%, and area under receiver operating characteristic (ROC) curve (AUC) was 0.601 (P=0.031). The cutoff value of fibrinogen level was estimated as 3.17 g/L according to the Youden index. Accordingly, sensitivity was found as 58%, specificity was 58%, and AUC was 0.60 (P=0.001). The cutoff value of integrated NLR and fibrinogen level was found as 0.166; the sensitivity was found as 86%, specificity was 42%, and AUC was 0.801 (P=0.01). Conclusion The data obtained in this study suggested that 67.1% of Ta-T1 tumors were likely to be invasive if the NLR was >2.01 and 58% were likely to be invasive if the fibrinogen level was >3.17 g/L. When we used both the NLR and fibrinogen level to distinguish between the MIBC and NMIBC, sensitivity was found to be 86%, and specificity was 42%.

Clinicopathological and prognostic significance of survivin expression in renal cancer patients: a meta-analysis

Background Survivin has been reported to play a role in the diagnosis and prognosis of renal cell carcinoma (RCC); however, published data on this subject are conflicting. Aim To conduct a meta-analysis to evaluate the impact of survivin as a prognostic marker and its association with clinicopathological variables in patients with RCC. Method Comprehensive searches of electronic databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the Cochrane Library) were updated to June 2016 to retrieve eligible studies. The association strength was measured with relative risks (RRs) and pooled HRs with 95% CIs, which were extracted and pooled to determine the association between survivin expression and patient survival and clinicopathological features. Results Ten studies with 1063 cases of RCC were included. Positive survivin expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07 to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The correlation between survivin expression and gender was not significant (pooled RR 0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found between survivin expression and overall survival for patients with RCC (pooled HR 1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17 (univariate model)). Conclusions Our results indicate that survivin is of prognostic significance in patients with RCC.

Giant bladder stone in a male patient: A case report.

Background:In recent years, bladder stones are increasing in China. However, a giant bladder stone is rarely found nowadays. Methods:A case of a 54-year-old man who presented with a >9-year history of urinary frequency and urgency and macrohematuria for the past 3 days, was examined by ultrasound scan, kidney–ureter–bladder x-ray, and computed tomography. Then, the patient received a cystolithotomy. Results:His suprapubic area was hard when palpated. An ultrasound scan showed hydronephrosis of both kidneys and expanded ureters. A kidney–ureter–bladder x-ray showed a large stone within the bladder, and computed tomography revealed that the stone occupied most of the bladder. A large bladder stone composed of magnesium ammonium phosphate, weighing 1048 g, and measuring 13.3*8.0*9.7cm in size was removed. Conclusion:This rare case is, to the best of our knowledge, the largest bladder stone case reported to date in China. For patients with only Lower urinary tract symptoms, bladder stone should be taken into consideration when other signs occur, such as recurrent urinary tract infection and hematuria.

Gene therapy of renal cancer using recombinant adeno‑associated virus encoding human endostatin

Renal cell carcinoma (RCC) is characterized by robust angiogenesis during tumor development. Various therapies are not able completely eradicated tumor relapse. The present study targeted angiogenesis and developed a recombinant adeno-associated virus (rAAV) vector containing human endostatin gene for human kidney cancer gene therapy. Prophylactic and therapeutic RCC models were established in nude mice by subcutaneous inoculation of RCC cells and intra-muscular or intra-tumor injection of rAAV-Endostatin. The growth of xenograft tumors was evaluated by tumor volume and weight. The microvessel density (MVD) was used to measure the anti-angiogenesis effect of rAAV-Endostatin. The toxic effect of rAAV-Endostatin was also examined. In the therapeutic model, tumor-bearing mice with rAAV-Endostatin intra-tumor injection demonstrated slow tumor growth (32.63±9.75) compared with control groups with intratumoral rAAV-enhanced yellow florescent protein (EYFP) injections (21.50±11.42) and the RPMI-1640 group (21.75±10.48 days, for tumors to reach ~300 mm3). MVD of the xenografts treated with rAAV-Endostatin was 8.30±3.14/0.739 mm2 whereas that of control groups was 13.87±4.09/0.739 mm2 (rAVV-EYFP) and 13.76±3.50/0.739 mm2 (RPMI-1640). No significant side effects associated with rAAV-endostatin use were identified in the vital organs. rAAV-Endostatin demonstrated significant anti-angiogenesis and antitumor activities. It may serve as an effective agent for renal cancer gene therapy.

Antimicrobial susceptibility of hospital acquired Stenotrophomonas maltophilia isolate biofilms

AIMS We sought to characterize the antibiotic susceptibility of strains of Stenotrophomonas maltophilia isolated from clinical samples, and the role of Stenotrophomonas maltophilia biofilm in antibiotic resistance. METHODS Fifty-one clinical Stenotrophomonas maltophilia isolates were obtained from patients with nosocomial infection in the surgical wards and ICUs of six general hospitals in Tianjin, China. In vitro models of Stenotrophomonas maltophilia biofilms were established and confirmed by scanning electron microscopy and fluorescence microscopy with silver staining. The minimal inhibitory concentrations and biofilm inhibitory concentrations of commonly used antibiotics were determined. RESULTS 47 of 51 strains were resistant to three or more antibiotics. 42 of 51 strains formed Stenotrophomonas maltophilia biofilms in vitro. Stenotrophomonas maltophilia biofilm formation greatly reduced sensitivity to most tested antibiotics, but not to levofloxacin. However, in the presence of erythromycin scanning electron microscopy revealed that levofloxacin inhibited Stenotrophomonas maltophilia biofilm formation. Factorial ANOVA revealed that erythromycin enhanced susceptibility to levofloxacin, cefoperazone/sulbactam, and piperacillin (p<0.05), and an ΔE model revealed that levofloxacin and erythromycin acted synergistically in biofilms, suggesting specific use of combined macrolide therapy may represent an effective treatment for Stenotrophomonas maltophilia infection. CONCLUSIONS Antibiotics could act synergistically to combat the protection conferred to clinical isolates of Stenotrophomonas maltophilia by biofilms. Macrolide antibiotics may be effective where used in combination.

Recombinant hIFN-α2b-BCG inhibits tumor growth in a mouse model of bladder cancer

Bacillus Calmette-Guérin (BCG) reduces the recurrence and progression of non-muscle invasive bladder cancer. The present study aimed to investigate the impact of a recombinant hIFN-α2b-secreting BCG (rBCG) on the mouse bladder MB49 cell line and an orthotopic mouse model of bladder cancer. MB49 cells were cultivated in the presence or absence of rBCG, BCG or BCG+hIFN-α2b. Cellular morphology and viability were assessed by microscopy and CCK-8 assay, respectively. Apoptosis was assessed by acridine orange, Hoechst 33258 staining and flow cytometry. MHC-I expression was assessed by flow cytometry. MB49 cells were transplanted into the bladders of C57BL/6 mice administered BCG, rBCG or BCG+hIFN-α2b. Local tissue Fas expression and T cell subsets were assessed by immunohistochemistry. Peripheral blood TNF-α and IL-12 levels were measured by ELISA, and circulating T lymphocyte subsets by flow cytometry. BCG, rBCG and BCG+hIFN-α2b increased the distortion and death of MB49 cells, yet rBCG reduced the proliferation and enhanced apoptosis most substantially. Apoptosis was increased after a 24-h co-culture with rBCG or BCG+hIFN-α2b. Mice administered rBCG survived longer than mice administered BCG (p<0.001), yet this result was not significantly different from mice administered BCG+hIFN-α2b. The average bladder weight was reduced by administration of rBCG (p<0.001). Fas expression and peripheral blood mTNF-α and mIL-12, cell counts of polymorphonuclear leukocytes, monocytes, T lymphocytes and CD4+/CD8+ ratios were significantly increased by all BCG treatments (p≤0.05), yet monocyte and T lymphocyte counts were higher in mice administered rBCG than in mice treated with BCG or BCG+hIFN-α2b (p=0.000). These results indicate that in an orthotopic murine bladder cancer model rBCG possesses superior antitumor activity to BCG+hIFN-α2b.