BackgroundUpper tract urothelial carcinoma (UTUC) is a rare malignancy. The management of metastatic or unresectable UTUC is mainly based on evidence extrapolated from histologically homologous bladder cancer, including platinum-based chemotherapy and immune checkpoint inhibitor alone, whereas UTUC exhibits more invasiveness, worse prognosis, and comparatively inferior response to treatments. First-line immunochemotherapy regimens have been attempted in clinical trials for unselected naïve-treated cases, but their efficacies relative to standard chemo- or immuno-monotherapy still remain controversial. Here, we present a case of highly aggressive UTUC for whom comprehensive genetic and phenotypic signatures predicted sustained complete response to first-line immunochemotherapy.Case presentationA 50-year-old man received retroperitoneoscopic nephroureterectomy and regional lymphadenectomy for high-risk locally advanced UTUC. Postoperatively, he developed rapid progression of residual unresectable metastatic lymph nodes. Pathologic analysis and next-generation sequencing classified the tumor as highly aggressive TP53/MDM2-mutated subtype with features more than expression of programmed death ligand-1, including ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state. Immunochemotherapy combining gemcitabine, carboplatin, and off-label programmed death-1 inhibitor sintilimab was initiated, and sintilimab monotherapy was maintained up to 1 year. Retroperitoneal lymphatic metastases gradually regressed to complete response. Blood-based analyses were performed longitudinally for serum tumor markers, inflammatory parameters, peripheral immune cells, and circulating tumor DNA (ctDNA) profiling. The ctDNA kinetics of tumor mutation burden and mean variant allele frequency accurately predicted postoperative progression and sustained response to the following immunochemotherapy, which were mirrored by dynamic changes in abundances of ctDNA mutations from UTUC-typical variant genes. The patient remained free of recurrence or metastasis as of this publishing, over 2 years after the initial surgical treatment.ConclusionImmunochemotherapy may be a promising first-line option for advanced or metastatic UTUC selected with specific genomic or phenotypic signatures, and blood-based analyses incorporating ctDNA profiling provide precise longitudinal monitoring.

Accumulating studies have confirmed that PIWI-interacting RNAs (piRNAs) are considered epigenetic effectors in cancer. We performed piRNA microarray expression analysis on renal cell carcinoma (RCC) tumor tissues and paired normal tissues and performed a series of in vivo and in vitro experiments to explore piRNAs associated with RCC progression and investigate their functional mechanisms. We found that piR-1742 was highly expressed in RCC tumors and that patients with high piR-1742 expression had a poor prognosis. Inhibition of piR-1742 significantly reduced tumor growth in RCC xenograft and organoid models. Mechanistically, piRNA-1742 regulates the stability of USP8 mRNA by binding directly to hnRNPU, which acts as a deubiquitinating enzyme that inhibits the ubiquitination of MUC12 and promotes the development of malignant RCC. Subsequently, nanotherapeutic systems loaded with piRNA-1742 inhibitors were found to effectively inhibit the metastasis and growth of RCC in vivo. Therefore, this study highlights the functional importance of piRNA-related ubiquitination in RCC and demonstrates the development of a related nanotherapeutic system, possibly contributing to the development of therapeutic approaches for RCC.

This study was conducted to investigate the prognostic significance of a combination of fibrinogen and neutrophil-to-lymphocyte ratio (NLR) named the F-NLR score as a novel indicator and further create nomograms for predicting the prognosis of patients with renal cell carcinoma (RCC) treated with laparoscopic nephrectomy. A total of 425 patients with RCC who underwent laparoscopic nephrectomy were included in this study. Then, we divided the patients based on the cut-off values of their F-NLR score into three categories: F-NLR 2 (both high fibrinogen and NLR), F-NLR 0 (both low fibrinogen and NLR), and F-NLR 1 (remaining patients). Cox regression analysis was performed to investigate the predictive performance of the F-NLR score on overall survival (OS) and cancer-specific survival (CSS). Predictive nomograms of F-NLR were established and internally validated. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to assess the predictive accuracy of the nomogram, NLR, and fibrinogen as prognostic markers. The F-NLR 0, 1, and 2 groups included 226 (53.2%), 147 (34.6%), and 52 (12.2%) patients, respectively. Cox regression analysis showed that a high F-NLR score was significantly associated with poor prognosis and acted as an independent prognostic factor for OS and CSS (all P < 0.05). Predictive nomograms with F-NLR for OS (C-index: 0.773) and CSS (C-index: 0.838) were well developed. Time-dependent ROC results showed that nomograms containing F-NLR had better predictive performance than NLR and fibrinogen. F-NLR score was a novel effective prognostic biomarker for patients with RCC undergoing laparoscopic nephrectomy.

Mucin 1 (MUC1) is a heterodimeric transmembrane glycoprotein that protects epithelial cells in mammals. The transmembrane C-terminal subunit (MUC1-C) plays a crucial role in oncogenesis. As an oncoprotein, MUC1-C regulates a number of proteins that are associated with tumorigenesis by interacting with oncoproteins, transcription factors, coactivators, etc., inducing proliferation, epithelial-mesenchymal transition (EMT), invasion, stemness, immune evasion, and drug resistance. Moreover, MUC1-C modulates the expression of non-coding RNAs (ncRNAs), which further regulate carcinogenesis by directly binding to specific proteins. ncRNAs can also affect MUC1 protein expression by targeting the MUC1 mRNA 3' untranslated region (UTR). A series of ncRNAs can modulate cancer development by regulating MUC1-C. This review focuses on the interaction of MUC1-C with proteins and ncRNAs in cancer progression. We also summarize the recent advances in immunotherapy with a focus on therapeutic approaches based on MUC1-C and nanocarrier complexes for cancer treatment.

The accumulating evidence confirms that long non-coding RNAs (lncRNAs) play a critical regulatory role in the progression of renal cell carcinoma (RCC). But, the application of lncRNAs in gene therapy remains scarce. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA-SLERCC (SLERCC) in RCC cells. We performed lncRNAs expression profiling in paired cancer and normal tissues through microarray and validated in our clinical data and TCGA dataset. The Plasmid-SLERCC@PDA@MUC12 nanoparticles (PSPM-NPs) were tested in vivo and in vitro, including cellular uptake, entry, CCK-8 assay, tumor growth inhibition, histological assessment, and safety evaluations. Furthermore, experiments with nude mice xenografts model were performed to evaluate the therapeutic effect of PSPM-NPs nanotherapeutic system specific to the SLERCC. We found that the expression of SLERCC was downregulated in RCC tissues, and exogenous upregulation of SLERCC could suppress metastasis of RCC cells. Furthermore, high expression DNMT3A was recruited at the SLERCC promoter, which induced aberrant hypermethylation, eventually leading to downregulation of SLERCC expression in RCC. Mechanistically, SLERCC could directly bind to UPF1 and exert tumor-suppressive effects through the Wnt/β-catenin signaling pathway, thereby inhibiting progression and metastasis in RCC. Subsequently, the PSPM-NPs nanotherapeutic system can effectively inhibit the growth of RCC metastases in vivo. Our findings suggested that SLERCC is a promising therapeutic target and that plasmid-encapsulated nanomaterials targeting transmembrane metastasis markers may open a new avenue for the treatment in RCC.

The aim of the present study was to investigate the expression of spalt like transcription factor 4 (SALL4) in the three most common types of renal cell carcinomas (RCC) [clear cell RCC (ccRCC), papillary renal cell carcinoma (pRCC) and chromophobe RCC (chRCC)], and the association with the overall survival (OS) of patients. The Cancer Genome Atlas (TCGA) database and RCC samples were used to investigate the expression levels of the SALL4 gene and its association with the OS in the three types of RCC based on the analysis of the transcriptome, copy number and survival data. It was found that SALL4 was highly expressed in ccRCC and pRCC tumor tissue, and low mRNA expression level of SALL4 indicated a prolonged survival in both ccRCC and pRCC. This mRNA expression level was associated with pathological Tumor‑Node‑Metastasis stage, M and T stages in both ccRCC and pRCC. The analysis of the enriched pathway results suggested that SALL4 may act via translation initiation, and that the related genes promoted the progression of RCC. Moreover, the high expression level of SALL4 was detected in RCC samples and serum from patients. It was demonstrated that SALL4 promotes increased viability in RCC cells. Therefore, the present results suggest that SALL4 may be a sensitive and specific cancer biomarker in ccRCC and pRCC. Furthermore, targeting of SALL4 may improve RCC therapy and prolong the survival of patients with ccRCC or pRCC.

BACKGROUND Hypoxia is common in solid tumor masses that has functional consequences for tumor progression. Previous studies demonstrated that nearly 80% renal cell carcinoma (RCC) are under hypoxia. However, effect and its mechanism of hypoxia on RCC cell invasion remains to be defined. METHODS The shRNA expression vectors, which were constructed to express a short hairpin RNA against lncRNA and overexpression of lncRNA, were transfected into the RCC cell lines (SW839 and OSRC-2). Levels of lncRNA-ENST00000574654.1, VEGF-A and VEGF-C mRNA and protein were examined by real-time quantitative-fluorescent PCR and Western blot analysis, respectively. The effects of lncRNA silencing and overexpression on cell invasion of SW839 and OSRC-2 cells were evaluated with cell migration assay. RESULTS Hypoxia significantly stimulated cell invasion in both RCC cell lines (SW839: 2.38 ± 0.19 of normoxia vs 7.83 ± 0.38 of hypoxia, P < 0.05; and OSRC-2: 1.00 ± 0.08 of normoxia vs 5.88 ± 0.32 of hypoxia, P < 0.05). LncRNA microarray analysis found that lncRNA-ENST00000574654.1 was down-regulated under hypoxia. Consistently, over-expression of lncRNA-ENST00000574654.1 resulted in significant blockade of hypoxia-induced RCC migration. Furthermore, expression of lncRNA-ENST00000574654.1 was regulated by HIF-1α and VEGA-A through interacting with hnRNP, which in turn regulated the RCC cell invasion. CONCLUSIONS These findings suggested that hypoxia promoted RCC cell invasion through HIF-1α/lncRNA (ENST00000574654.1)/hnRNP/VEGF-A pathway. Targeting this pathway could potentially improve therapeutic outcomes of renal cell carcinoma.

Background: Circular RNAs (circRNAs) have been identified as essential regulators in a plethora of cancers. Nonetheless, the mechanistic functions of circRNAs in Renal Cell Carcinoma (RCC) remain largely unknown. Methods: In this study, we aimed to identify novel circRNAs that regulate RCC epithelial-mesenchymal transition (EMT), and to subsequently determine their regulatory mechanisms and clinical significance. Results: circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both in vitro and in vivo. We found that increased expression of circPRRC2A is positively associated with advanced clinical stage and worse survivorship in RCC patients. Mechanistically, our results indicate that circPRRC2A prevents the degradation of TRPM3, a tissue-specific oncogene, mRNA by sponging miR-514a-5p and miR-6776-5p. Moreover, circPRRC2A promotes tumor EMT and aggressiveness in patients with RCC. Conclusions: These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.

The objective of the present study was to assess the expression of CD105 and its association with overall survival in three subtypes of renal cell carcinoma (RCC), namely clear cell (cc)RCC, papillary (p)RCC and chromophobe (ch)RCC. Data regarding the transcriptome and copy number of genes in RCC tumor samples and survival were obtained from The Cancer Genome Atlas. Bioinformatics analysis revealed that CD105 is overexpressed in ccRCC tumor tissue vs. normal renal tissue, and a higher CD105 copy number in ccRCC tissues was significantly associated with longer patient survival. The effect of the mRNA expression of CD105 in all three types of RCC and the copy number in pRCC and chRCC on patient survival was insignificant, but certain trends were observed. In addition, CD105 mRNA expression was associated with the metastasis and tumor stage, as well as pathological stage in ccRCC and pRCC. Pathway enrichment analysis revealed that CD105 may, through translation initiation of associated genes, promote RCC progression. The results of the present study suggest that in RCC tumors, the association of CD105 with different stages is complex. To evaluate the role of CD105 in RCC, its function should be assessed in addition to its expression. The exact influence of CD105 mRNA expression and copy number in RCC tumors on patient survival and the underlying mechanisms require further elucidation.

// Min Liu 1 , Guang-Chun Wang 1 , Yuan Feng 2 , Jian-Ping Che 1 , Hai-Min Zhang 1 , Yang Yan 1 , Jian-Hua Huang 1 , Xu-Dong Yao 1 and Jun-Hua Zheng 1 1 Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, China 2 Department of Nephrology, Nanjing University Affiliated Drum Tower Hospital, Nanjing, Jiangsu, 210093, China Correspondence to: Xu-Dong Yao, email: fibrosis744@126.com Jun-Hua Zheng, email: junhuazheng006@163.com Keywords: renal fibrosis, GAS5, rs145204276, miR-21, SMAD/TGFB1 Received: January 02, 2017 Accepted: April 19, 2017 Published: January 11, 2018 ABSTRACT Background: Growth arrest-specific 5 (GAS5), a long non-coding RNA (lncRNA), has been identified as a key gene expression regulator in multiple cancers. The polymorphism of the promoter region of GAS5 promotes the transcription level of GAS5, and then supervises its downstream signal pathway. This study was designed to investigate the mechanism between GAS5 and renal fibrosis. Results: rs145204276 polymorphism (INS or DEL allele) located in promoter of GAS5. The DEL/DEL of GAS5 promotes the transcription of GAS5 and lower Histological score of kidneys disease samples. QRTPCR of clinical sample show that the DEL/DEL genotype group displayed higher levels of GAS5 and SMAD7 mRNA, and lower levels of miR-21 and TGFB1 protein than INS/INS group. Further mechanism study show that GAS5 inhibits the expression level of miR-21 and then the miR-21/SMAD7/SMAD3 feedback loop. Our further study confirmed that the expression of GAS5 supervised the expression of miR21, SMAD7 and TGFB1. Meanwhile, SMAD7 is a directly target gene of miR-21. Materials and Methods: Bioinformatics analysis and luciferase assay were employed to investigate the role of rs145204276 polymorphism in gene expression regulation. Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and western-blot were employed to study the expression level. Hematoxylin-eosin staining was performed to explore role of rs145204276 polymorphism of GAS5 in renal fibrosis. Conclusions: our study shows that GAS5 (lncRNAs) supervises SMAD/TGF- β 1 -mediated renal fibrosis via miR-21. In addition, rs145204276 polymorphism (INS or DEL allele) of GAS5 contributes to renal fibrosis via transcription of the GAS5, and then serves as a potential therapeutic target for renal fibrosis.

The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.

The aim of the present study was to compare the efficacy and safety of fosfomycin combinational therapy with other antibiotics for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective cohort study examined 104 cases of sepsis caused by CRKP occurring between January 2012 and November 2014 in Shanghai Tenth People's Hospital. Three categories of patient outcome were assessed: Survival/mortality, duration of intensive care unit stays and duration of medical ventilation. Univariate ordinal analyses were adopted to evaluate the correlations between outcome and treatment. A total of 104 patients with physician-diagnosed CRKP were involved in the study. The overall mortality rate was 25.0%. The majority of the infections (84; 80.8%) were hospital acquired. Critical infections received more than one active antibiotic as therapy. Patients treated with fosfomycin combinational therapy were less likely to fail therapy (OR: 4.71, 95% CI: 1.03-21.65, P=0.034) and tended to have a shorter duration of mechanical ventilation. Gender (OR: 4.35, 95% CI: 1.08-3.60, P=0.037), history of chronic obstructive pulmonary disease (OR: 9.35, 95% CI: 0.06-0.19, P=0.007) and peripheral catheter use (OR: 3.00, 95% CI: 0.07-0.19, P=0.002) are risk factors for clinical outcome. Therefore, the use of fosfomycin combinational therapy for treatment of infection due to CRKP appears to be associated with improved survival rate.

Previous studies have reported that hyperoside and quercetin in combination (QH; 1:1) inhibited the growth of human leukemia cells. The aim of the present study was to investigate the anti‑cancer effect of QH on prostate cancer cells. The results demonstrated that QH decreased the production of reactive oxygen species (ROS) and increased antioxidant capacity in PC3 cells at various concentrations (2.5‑60 µg/ml) with peak inhibition and augmentation changes of 3.22‑ and 3.00‑fold, respectively. Following treatment with QH for 48 and 72 h, the IC50-values on PC3 cells were 19.7 and 12.4 µg/ml, respectively. Western blot analysis revealed that QH induced apoptosis in human prostate cancer cells via activation of caspase‑3 and cleavage of poly(adenosine diphosphate ribose) polymerase. In addition, QH significantly inhibited the invasion and migration of PC3 cells as well as reduced the expression of numerous prostate tumor‑associated microRNAs (miRs), including miR‑21, compared to that of untreated human prostate cancer cells. QH was also found to enhance the expression of tumor suppressor programmed cell death protein 4, which was negatively regulated by miR‑21. Furthermore, induced overexpression of miR‑21 using pre‑miR‑21 oligonucleotides attenuated the beneficial effect of QH on prostate cancer cells. In conclusion, the results of the present study indicated that QH exerted an anti‑cancer effect on human prostate cancer cells, the mechanism of which proceeded, at least in part, via the inhibition of the miR‑21 signaling pathway.

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2015MP47-12 MIR-646 IN CLEAR CELL RENAL CARCINOMA CORRELATED WITH TUMOUR METASTASIS BY TARGETING THE NIN ONE BINDING PROTEIN Wei Li, Yuanyuan Zhang, Min Liu, Jianping Che, and Junhua Zheng Wei LiWei Li More articles by this author , Yuanyuan ZhangYuanyuan Zhang More articles by this author , Min LiuMin Liu More articles by this author , Jianping CheJianping Che More articles by this author , and Junhua ZhengJunhua Zheng More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1532AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renal cell carcinoma (RCC) is a common urologic malignancy and accounts for 3% of adult malignancies and causes 90 000 deaths worldwide annually. Biomarkers for early detection and followup of the disease are not available at present. Previous studies have found that nin one binding protein (NOB1) was identified as a potential oncogene in human glioma and miR-646 plays an important role in human growth and development. However, the underlying molecular mechanisms of NOB1 in tumorigenicity and its correlation with miR-646 in renal cell carcinoma (RCC) have not been investigated. METHODS We performed bioinformatic analysis to explore miRNA targeting NOB1. The expression of NOB1 and miR-646 from 100 cases of clear cell RCC (ccRCC) and 30 cases of adjacent non-tumour tissues were detected by quantitative real-time PCR. The expression of miR-646 was correlated with NOB1 expression, tumour features and patient metastasis-free survival. The effect of overexpression of mir-646 on renal cancer cell proliferation was detected by colony formation in soft agar. Using a xenograft tumour model, we observed the in vivo tumorigenesis effect of miR-646 and NOB1. RESULTS miR-646 negatively regulated NOB1 and inhibited the proliferation and migration of renal cancer cells. There was a significant upregulation of NOB1 in ccRCC and it was further increased in metastatic cases, while miR-646 was downregulated in tumour tissues and further decreased in metastatic ccRCC. Additionally, expression of miR-646 was inversely correlated with the expression of NOB1. The downregulation of miR-646 also indicated a higher probability of developing metastasis. Most importantly, miR-646 expression was an independent predictor of ccRCC metastasis by the univariate analysis and binary logistic regression model (both P≤0.05). Colony formation in soft agar and xenograft tumour model suggested that miR-646 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, suppression of NOB1 increased the phosphorylation of several proteins in MAPK pathway. CONCLUSIONS Our findings suggest that NOB1 as a novel target of miR-646. Overexpression of miR-646 decreased tumorigenesis of renal cancer cells through the modulation of MAPK pathway. Clinically, NOB1 expression might be associated with tumour grade as well as the prognosis of ccRCC. Our findings suggest that exogenous overexpression of miR-646 may be considered as a promising strategy for targeted therapies in renal cancer. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e556 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei Li More articles by this author Yuanyuan Zhang More articles by this author Min Liu More articles by this author Jianping Che More articles by this author Junhua Zheng More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

目的 研究Argonaute-2蛋白在膀胱移行上皮癌组织中的表达及临床意义.方法 通过实时荧光定量PCR、免疫组化法测定88例经病理确诊的膀胱移行上皮癌患者配对的肿瘤组织、癌旁组织中Argonaute-2蛋白的表达,分析该蛋白表达与预后和其他临床病理参数的相关性.结果 膀胱移行上皮癌组织中Argonaute-2 mRNA表达明显高于癌旁组织(P＜0.05);Argonaute-2蛋白表达明显高于癌旁组织(P＜0.05).高表达Argonaute-2与肿瘤的病理分级、临床分期以及淋巴结转移情况显著相关.利用Kaplan-Meier生存曲线和Log-Rank检验分析显示,肿瘤组织中Argonaute-2蛋白高表达组患者的5年生存率较低表达组患者明显降低(62.2％ vs.86.3％,P＜0.05).结论 Argonaute-2蛋白的异常表达可能参与膀胱移行上皮癌的发生、发展,可作为膀胱癌预后评估的一个重要生物学指标.

Objective To describe the security and validity of retrograde extraperitoneal approach of resection of prostate and bladder to radical cystectomy.Methods From May 2010 to May 2014,total 165 cases,aged 33-85 years,were treated with retrograde extraperitoneal radical cystectomy.There were 87 cases of Ta-T1,65 cases of T2,and 13 cases of T3-T4 ; Urinary diversion:50 cases of Studer orthotopic neobladder,73 cases of Bricker operation,42 cases of ureterocutaneostomy.General anesthesia and hip elevation hyperextension were taken,the skin and fascial layers were incised from pubic symphysis to subumbilical incision,extraperitoneal bladder wall and prostate bladder structure were visualized.Pelvic iliac artery lymphadenectomy was performed,followed with bladder artery ligated and incision of pelvic fascia.Both sides of the prostate were dissociated,dorsal vein complex was sutured,prostatic urethra was dissociated and cut off.The indwelling urethral catheter of the apex of the prostate was raised,rectourethral muscle was dissociated and cut off,the bottom and sides of the prostate were dissociated,Denonvillier fascia at the seminal vesicle was incised,the lateral ligament of bladder was separated.LigaSure system was used to cut hemostasis and gradually seperete the prostate and bladder from rectal peritoneum.Regional peritoneum was excised if peritoneal invasion was suspected.Results The amount of operative bleeding was 30-160 ml,average 100 ml; operation time was 45-120 min,average 80 min.Postoperative pathologic results:157 cases of urothelial carcinoma,5 cases of adenocarcinoma of bladder,1 cases of squamous cell carcinoma,and 2 cases of prostate carcinoma invading the bladder; lymph node metastasis was found in 16 cases.The period of follow-up was 3-32 months (median,13 months).No peritoneal metastasiswas found.Conclusions Radical retrograde extraperitoneal cystectomy is based on a finer knowledge of anatomy and requires accurate dissection.It is safe,effective,and minimally invasive,especially in the neobladder.

Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.

Objective To explore a safe treatment for renal cell carcinoma in patients with horseshoe kidneys.Methods Clinical data of 5renal cell carcinoma patients with horseshoe kidneys treated in our hospital were retrospectively analyzed.The right kidney was involved in one patients and the left was involved in 4patients.Tumors invaded the isthmus in 2patients.Clinical manifestation,diagnosis and treatment of the five patients were analyzed.Results The five patients were correctly diagnosed and surgically treated in time.Two patients received retroperitoneal laparoscopic radical nephrectomy and three underwent transperitoneal radical nephrectomy.Satisfactory clinical outcomes were obtained in all patients.Conclusion Radical nephrectomy is an optimal treatment for renal cell carcinoma in horseshoe kidney.Preoperative evaluation of vascular malformation and minimally-invasive dissection of the isthmus are keys for surgical treatment.Retroperitoneal laparoscopic radical nephrectomy may be a good choice for patients with small tumors in the upper and middle pole of the kidneys.

Objective: To investigate the risk factors of postoperative fever in percutaneous nephrolithotomy (PCNL) and explore optimal treatment strategy.Methods: A total of 369 patients who underwent PCNL in our center from September 2009 to June 2013 were retrospectively analyzed and divided into two groups: fever group (T >38.5℃) and non-fever group (T ≤38.5℃). Analyses for the risk factors of fever were performed.Results: Of 369 PCNL patients, 45 (12.2%) cases suffered from postoperative fever. Urinary tract infection, pyonephrosis, stone surface area > 6 cm2, bleeding volume >400 mL, operation time >2 min, irrigation lfuid volume >30 L and inadequate drainage were risk factors of postoperative fever (P<0.05).Conclusion: Fever is the common postoperative complication of PCNL. Effective control of urinary tract infections, rational use of prophylactic antibiotics, optimal timing of surgery, aseptic processing and unobstructed drainage should be performed to prevent and treat the PCNL postoperative fever.

OBJECTIVE:accumulating evidence suggest that long non-coding RNAs (lncRNAs) may play important roles in human cancers. LncRNA neuroblastoma associated transcript-1 (NBAT-1) was initially identified to be involved in the progression of neuroblastoma. However, there is no report about the role of NBAT-1 in clear cell renal cell carcinoma (ccRCC). The purpose of this study is to investigate the clinical significant of NBAT-1 in ccRCC.METHODS:the expression pattern of NBAT-1 in ccRCC patients and renal cancer cell lines was detected by using quantitative real-time PCR (qRT-PCR), and its correlation with clinicopathologic features and prognosis of patients with ccRCC was assessed by Kaplan-Meier method and Cox proportional hazards model, respectively. Small interfering RNA (siRNA) was transfected into 786-O and ACHN cells to determine the effect of NBAT-1 knockdown on renal cancer cells.RESULT:NBAT-1 expression is significantly decreased in ccRCC tissues and renal cancer cells compared with adjacent normal tissues and normal human proximal tubule epithelial cell line HK-2, and its low level is associated with advanced features and poor prognosis. Also, multivariate analysis identified NBAT-1 expression as an independent prognostic factor for ccRCC. In vitro assays indicated that knockdown of NBAT-1 expression increased renal cancer cell proliferation, migration and invasion.CONCLUSIONS:NBAT-1 is a novel molecular correlated with ccRCC progression; and it may represent a prognostic biomarker and therapeutic target in renal cancer diagnosis and treatment.