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.

Primitive neuroectodermal tumor of the prostate in a 58-year-old man: A case report.

BACKGROUND: Primitive neuroectodermal tumor (PNET), especially located in the prostate, is a rare tumor that mainly occurs in young men. Bladder or rectum invasion and distant metastasis are strongly associated with a poor prognosis. Combination therapy, including radical surgery, adjuvant chemotherapy, and radiotherapy, is available. We present a case of prostatic PNET and a review of 17 cases identified in the literature. CASE SUMMARY: A 58-year-old man was admitted complaining of dysuria for 2 years. Computed tomography and magnetic resonance imaging showed a large cystic-solid mass in the pelvic cavity compressing the surrounding bladder and rectum. The mass was iso- to hyperintense on T1-weighted imaging (WI) and heterogeneously hyperintense on T2WI. Cystic degeneration and necrosis were seen in the tumor, and solid tissues within the mass enhanced on contrast-enhanced scan. The patient underwent robot-assisted laparoscopic pelvic tumor resection. Histologically, the presence of many small round cells that were positive for expression of CD99, vimentin, and synaptophysin established the diagnosis of PNET in the prostate after surgery. The patient underwent adjuvant chemotherapy. During 34 mo of follow-up, the patient had no signs or symptoms of recurrence or residual disease. CONCLUSION: We present the case of the oldest prostatic PNET patient, who has a good prognosis. This illustrates how older men with prostatic PNET may also benefit from the combination therapy, like younger adults, and achieve a long-term survival. As always, PNET should be considered in the differential diagnosis of aggressive prostatic tumors in young men.

Functional analysis and application of the cryptic plasmid pBSG3 harboring the RapQ-PhrQ system in Bacillus amyloliquefaciens B3.

This work sequenced and characterized a cryptic plasmid called pBSG3 from wild-type Bacillus amyloliquefaciens B3--a powerful agent for suppression of plant pathogenic organisms. It is an 8439 bp circular molecule, with G+C content of 40.3%. We provide evidence that pBSG3 replicates via the rolling-circle (RC) mechanism and, sequence comparisons place it in the pC194 family of rolling-circle-replicons. The plasmid contains seven putative open reading frames (ORFs), including genes repB3, mobB3, rapQ, phrQ, pgsR, and two unknown ORFs (orf1c and orf2). Our observations reveal that the RapQ-PhrQ (response regulator aspartate phosphatase-phosphatase regulator) system is involved in sporulation and RapQ can delay the onset of sporulation. Two Escherichia coli and Bacillus potential shuttle vectors, pTRD (containing the minimal replicon) and pTRDS (containing the minimal replicon and the single-strand origin) were developed from pBSG3 and tested the stability. Moreover, HpaG(xooc) protein, which can induce disease and insect resistance in plants, was tried to express with the stable vector pTRDS in Bacillus subtilis. In summary, the pBSG3 plasmid containing various genes is not only a candidate tool for vector development in Bacillus genus research but also a potential vehicle for the exchange of genetic elements among Bacillus populations that contributes to the survival of bacilli in natural environments.

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.

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.

Prognostic significance of urothelial carcinoma with divergent differentiation in upper urinary tract after radical nephroureterectomy without metastatic diseases: A retrospective cohort study.

To evaluate the impact of urothelial carcinoma with divergent differentiation (UCDD) on the prognosis of patients for primary upper urinary tract urothelial carcinoma (UTUC) with pN0/x status treated with radical nephroureterectomy (RNU) and to evaluate the prognostic value of UCDD in different tumor locations (renal pelvis and ureter).Data from a total of 346 patients with UTUC who received RNU between January 2012 and March 2016 in the institution were retrospectively analyzed. Clinicopathological features and prognostic factors age, sex, complaint, height, weight, blood pressure, tumor grade, stage, smoking status, history of adjuvant chemotherapy, tumor location, history of bladder cancer, tumor necrosis, degree of hydronephrosis, tumor size, tumor focality, and preoperative anemia were compared between patients with pure UTUC and patients with UCDD. The endpoints were cancer-specific survival (CSS), overall survival (OS), and intraluminal recurrence-free survival (IRFS).Overall, divergent differentiation was present in 50 patients (14.5%). UCDD was related to different tumor location (P = .01), smoking (P = .04), higher body mass index (P = .02), and advanced tumor grade (P = .01). By Kaplan-Meier analysis, UCDD was found to be significantly correlated with worse IRFS, CSS, and OS (all P < .01). Multivariate analysis demonstrated that UCDD was an independent predictor of IRFS (P < .01), CSS (P = .01), and OS (P = .01). However, 40 patients died for various reasons and the 5-year OS rates were 91.9% in UCDD- group and 68.0% in UCDD+ group, respectively. In patients with ureteral tumors, UCDD was the significant predictor for IRFS, CSS, and OS. However, the prognostic value of UCDD was not observed in pyelocaliceal tumors.The presence of divergent differentiation is associated with inferior survival. UCDD may identify patients at high risks for poor prognosis especially in patients with ureteral tumors. As a result, more attention and follow-up should be given to patients with ureteric urothelial carcinoma.

Biological effects of eukaryotic recombinant plasmid pReceiver-M61-BAI-1 transfection on T24 cells and HUVECs.

The aim of the current study was to investigate the biological effect on T24 cells and human umbilical vein endothelial cells (HUVECs) of transfection with brain-specific angiogenesis inhibitor-1 (BAI-1). The recombinant plasmid pReceiver-M61-BAI-1 was transfected into human superficial bladder tumor cells (T24) and HUVECs, in parallel with the vector control. mRNA and protein expression levels of BAI­1 were then detected by quantitative polymerase chain reaction (qPCR) and western blotting, respectively. Cell apoptosis of T24 cells and HUVECs prior and subsequent to transfection with BAI­1 was analyzed by flow cytometric analysis. Proliferation of T24 cells and HUVECs prior and subsequent to transfection of BAI-1 was assessed by the MTT method. T24 cells and HUVECs transfected with pReceiver­M61­BA1­1 were classed as the experimental group; T24 cells and HUVECs transfected with p­Receiver­M61 were the control group. qPCR and western blotting methods confirmed that there was positive expression of BAI­1 in T24 cells and HUVECs transfected with pReceiver­M61­BAI­1, however BAI­1 was not expressed in T24 cells and HUVECs transfected with pReceiver­M61. The results of the MTT assay demonstrated that absorbance was markedly reduced in HUVECs at 12, 48 and 72 h subsequent to transfection with pReceiver-M61-BAI-1 when compared with that of the control group and in T24 cells transfected with p­Receiver-M61-BAI-1. Furthermore, flow cytometry results also indicated that the apoptotic rate of HUVECs transfected with p­Receiver­M61­BAI­1 was significantly increased compared with that of the control group and T24 cells transfected with p­Receiver­M61­BAI­1. BAI­1 was observed to markedly inhibit the proliferation of vascular endothelial cells in vitro, however, no direct inhibition by BAI­1 was observed in T24 cells. In conclusion, BAI-1 is suggested to be a potential novel therapautic target for the inhibition of tumor neovascularization.

The evaluation of the association between the metabolic syndrome and tumor grade and stage of bladder cancer in a Chinese population.

OBJECTIVE: The objective of this article was to summarize the relationship between some components of metabolic syndrome (MetS) and the histopathologic findings in bladder cancer in a Chinese population. METHODS: We retrospectively analyzed data of 323 patients from the Department of Urology, Second Hospital of Tianjin Medical University between January 2012 and January 2014. All the patients were diagnosed with bladder cancer for the first time. Age, height, weight, histologic stage, grade, the presence of hypertension, diabetes mellitus, and body mass index were evaluated. The 2009 American Joint Committee on Cancer TNM staging system was used, with Ta and T1 tumors accepted as lower stage and T2, T3, and T4 tumors as higher stage bladder cancers. Also, pathologists assigned tumor grade according to the 1973 World Health Organization grading system. Noninvasive papillary urothelial neoplasms of low malignant potential were regarded as low grade. Analyses were completed using chi-square tests and logistic regression analysis. RESULTS: Of the 323 patients, 164 had hypertension, 151 had diabetes mellitus, and 213 had a body mass index ≥25 kg/m(2). MetS was significantly associated with histologic grade (P<0.001) and stage (P=0.006) of bladder cancer. Adjusted for age in binary logistic regression analysis, the presence of MetS predicts the risk of higher T stage (odds ratio =4.029, P<0.001) and grade (odds ratio =3.870, P<0.001) of bladder cancer. CONCLUSION: The patients with MetS in the People's Republic of China were found to have statistically significant higher T stage and grade of bladder cancer.

Identification of a Novel Rat NR2B Subunit Gene Promoter Region Variant and Its Association with Microwave-Induced Neuron Impairment.

Microwave radiation has been implicated in cognitive dysfunction and neuronal injury in animal models and in human investigations; however, the mechanism of these effects is unclear. In this study, single nucleotide polymorphism (SNP) sites in the rat GRIN2B promoter region were screened. The associations of these SNPs with microwave-induced rat brain dysfunction and with rat pheochromocytoma-12 (PC12) cell function were investigated. Wistar rats (n = 160) were exposed to microwave radiation (30 mW/cm(2) for 5 min/day, 5 days/week, over a period of 2 months). Screening of the GRIN2B promoter region revealed a stable C-to-T variant at nucleotide position -217 that was not induced by microwave exposure. The learning and memory ability, amino acid contents in the hippocampus and cerebrospinal fluid, and NR2B expression were then investigated in the different genotypes. Following microwave exposure, NR2B protein expression decreased, while the Glu contents in the hippocampus and CSF increased, and memory impairment was observed in the TT genotype but not the CC and CT genotypes. In PC12 cells, the effects of the T allele were more pronounced than those of the C allele on transcription factor binding ability, transcriptional activity, NR2B mRNA, and protein expression. These effects may be related to the detrimental role of the T allele and the protective role of the C allele in rat brain function and PC12 cells exposed to microwave radiation.

[Case-control study on midterm follow-up effects of the extended release of posterior clearance in total knee arthroplasty].

OBJECTIVE: To evaluate the midterm follow-up results of extended release of posterior clearance in total knee arthroplasty. METHODS: A total of 120 patients with knee osteoarthritis were equally randomly assigned to the experimental group and control group, and underwent unilateral TKA from March 2010 to March 2012. In experimental group, there were 21 males and 39 females with an average age of (62.2±10.9) years old. In the control group, there were 25 males and 35 females with an average age of (64.9±11.4) years old. All the patients were performed using the anterior knee approach. During operation, after osteotomy of the tibia and the femoral condyle, extended release of the posterior knee clearance were taken in experimental group, while only the clearance of osteophyte in the posterior condyle were performed in the control group. The KSS scores including knee functional score and knee clinical score,as well as the range of motion (ROM) of patients, were compared between the two groups at midterm follow-up. RESULTS: Totally 49 patients in the experimental group and 54 patients in the control group were followed up, and the median follow-up time was 46 months. The knee functional score of patients in the experimental group was 91.3±3.4, which was better than 86.4±3.9 of patients in the control group; initiative ROM of flexion of patients in the experimental group was (133.2±5.9)°, which was better than (126.9±7.4)° of patients in the control group. There were no significant difference of knee clinical score between 86.9±4.6 of patients in the experimental group and 85.7±5.1 of patients in the control group, and the initiative ROM of extension between (0.5±1.1)° and (0.3±1.2)°. CONCLUSION: Extended release of the posterior knee clearance contributes to the knee function and initiative flexion ROM during a midterm follow-up and patients benefit.