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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.

// Guanghui Hu 1 * , Binbin Dong 2, * , Jingwei Zhang 1, * , Wei Zhai 1, 3 , Tiancheng Xie 1 , Bisheng Huang 1 , Chi Huang 4 , Xudong Yao 1 , Junhua Zheng 1 , Jianping Che 1, 4 and Yun-Fei Xu 1 1 Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China 2 Department of Urology, Yancheng Third People’s Hospital, Yancheng, Jiangsu, China 3 Department of Urology, Renji Hospital, Shanghai Jiaotong University, Shanghai, China 4 Department of Urology, Shanghai Tenth People’s Hospital, Nanjing Medical University, Nanjing, Jiangsu, China * These authors have contributed equally to this work Correspondence to: Yun-Fei Xu, email: xuyunfeibb@sina.com Jianping Che, email: chejianping77@126.com Wei Zhai, email: jacky_zw2002@hotmail.com Keywords: renal cell carcinoma, HOTAIR, hippo pathway, SAV1 Received: December 31, 2016 Accepted: March 14, 2017 Published: April 25, 2017 ABSTRACT 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.

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.

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.

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.

Quercetin and hyperoside (QH) are the two main constituents of the total flavone glycosides of Flos Abelmoschus manihot, which has been prescribed for treating chronic kidney disease for decades. This study aimed to investigate the effect of QH on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. Rats were divided into three groups: an untreated stone-forming group, a QH-treated stone-forming group (20 mg/kg/day) and a potassium citrate-treated stone-forming group (potassium citrate was a worldwide-recognized calculi-prophylactic medicine). Ethylene glycol (0.5 %) was administered to the rats during the last week, and vitamin D3 was force-fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. 24 h urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope for semi-quantification of the crystal-formation. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. QH and potassium citrate have the ability to alkalinize urine. The number of crystal deposits decreased significantly in the QH-treated stone-forming group as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the QH-treated stone-forming group, as compared with the untreated stone-forming group. QH administration has an inhibitory effect on the deposition of CaOx crystal in EG-fed rats and may be effective for preventing stone-forming disease.

Flotillin-2 (FLOT2) is a highly conserved protein isolated from caveolae/lipid raft domains that tether growth factor receptors linked to signal transduction pathway. FLOT2 has recently been identified to be involved in tumorigenesis of several cancers such as breast cancer, melanoma, and gastric cancer. However, the role of FLOT2 in renal cell carcinoma (RCC) remains unclear. The expression levels of FLOT2 in RCC patients and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot. FLOT2 protein expression was also analyzed in archived paraffin-embedded RCC tissues using immunohistochemistry (IHC), and its association with overall survival of patients was analyzed by statistical analysis. Small-interfering RNA (siRNA) was used to suppress FLOT2 expression in RCC cell lines. In vitro assays were performed to further explore its role in tumor progression. The expression level of FLOT2 was higher in RCC tissues and cell lines than in corresponding adjacent normal tissues and normal human proximal tubule epithelial cell line HK-2. IHC analysis revealed high expression levels of FLOT2 in RCC specimens. The RCC patients with higher FLOT2 expression had an advanced clinical stage and poorer prognosis than those with lower FLOT2 expression. FLOT2 expression was an independent prognostic marker of overall RCC patient survival in a multivariate analysis. In vitro assays indicated that knockdown of FLOT2 reduced cell proliferation, migration, and invasion. Our data suggest that FLOT2 is a novel molecule involved in RCC progression, which provide a potential prognostic biomarker and therapeutic target.

Prevention of renal fibrosis is an important therapeutic strategy in the treatment of obstructive nephropathy. The purpose of the present study was to identify whether the combination of two natural plant-derived flavanoids, quercetin and hyperoside (QH), could inhibit renal fibrosis in the model of unilateral ureteral obstruction (UUO) in rats. QH mixtures (1:1) were fed to Wistar rats, and UUO ligation was performed on all the rats with the exception of the sham group. Masson's trichrome staining was used for interstitial fibrosis, while immunohistochemistry and western blot analysis were used to detect the expression of α-smooth muscle actin (SMA) and fibronectin (FN). In the QH group, the expression of SMA and FN was significantly lower than that in the untreated UUO group. In addition, QH administration significantly inhibited the SMA and FN expression of mesangial cells induced by interleukin-1β. Consequently, it was evident that combinational QH therapy prevented UUO-induced renal fibrosis. Based on these findings, the combinatorial intervention of phytomedicine may present an improved treatment strategy for renal fibrotic disease.

Background: 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

Introduction The MHC class I chain-related molecule A (MICA) is a ligand for the natural killer group 2, member D (NKG2D) immunoreceptor activation. The engagement of tumor cell surface MICA to NKG2D stimulates the NK and T cell antitumor immunity. Shedding of MICA by tumor cells facilitates tumor immune evasion, which might partially contribute to tumor progression. Material and methods Inmunohistochemistry was performed on both normal and neoplastic renal tissues. Human renal carcinoma cell lines 786-0 and ACHIN were transfected and target sequences to silence human MMP2 by shRNA expression were established. The degree of MICA shedding was measured and quantitative real-time PCR and Western-blot analysis were performed. Results The membrane type matrix metalloproteinase 2 (MMP2) mediated the MICA shedding, which was blocked by suppression of MMP2 expression. Concomitantly, MMP2 overexpression enhanced the MICA shedding, indicating that MMP2 was involved in the renal cell carcinoma-associated proteolytic release of soluble MICA (sMICA), which facilitated the tumor immune escape. Conclusions These findings suggested that MMP2 might be a new potential target for tumor immune therapy. Elucidation of the mechanisms by which tumors shed MICA could be of a great importance for cancer treatment in order to reinforce the NK and T cell antitumor immunity.

Resumen Introduccion La molecula A relacionada con la cadena de clase i del CMH (MICA) es un ligando del grupo 2 de celulas asesinas naturales, y miembro D (NKG2D) de la activacion de inmunorreceptores. La union de la superficie de la celula tumoral MICA con NKG2D estimula las celulas asesinas (NK) y la inmunidad de las celulas T antitumorales. La eliminacion de MICA por las celulas tumorales facilita la evasion inmune del tumor, lo cual podria contribuir en parte a la progresion tumoral. Materiales y metodos Se aplico inmunohistoquimica tanto en tejidos renales normales como neoplasicos. Se transfectaron las lineas de celulas tumorales de rinon humano 786-O y ACHIN, y se establecieron secuencias objetivo para silenciar la MMP2 humana a traves de la expresion ARNhc. Se midio el grado de eliminacion de MICA y se llevo a cabo una PCR cuantitativa en tiempo real, asi como el analisis de Western blot. Resultados La membrana de tipo metaloproteinasa de matriz-2 (MMP2) media en la eliminacion de MICA, que se bloquea por la supresion de la expresion de MMP2. Simultaneamente, la sobreexpresion de MMP2 aumenta la eliminacion de MICA, lo cual indica que MMP2 interviene en la liberacion proteolitica de MICA soluble (sMICA) asociada al carcinoma de celulas renales, que facilita el escape tumoral inmune. Conclusiones Dichos resultados sugieren que MMP2 podria ser un nuevo objetivo potencial para la terapia inmune de tumores. Un esclarecimiento de los mecanismos por los que los tumores eliminan MICA podria ser de gran importancia para el tratamiento del cancer, para asi reforzar las NK y la inmunidad antitumoral de las celulas T.

The objective of this study was to determine the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL), C-reactive protein (CRP), and procalcitonin (PCT) in the prognosis of patients presenting with the systemic inflammatory response syndrome (SIRS) with nephrolithiasis.Urine NGAL protein levels were measured by enzyme-linked immunosorbent assay in 87 patients presenting with nephrolithiasis who were diagnosed as SIRS. Additionally, 52 patients presenting with nephrolithiasis but without urinary tract infection and 30 healthy controls were also included in the study. Levels of serum CRP and PCT were also taken into consideration.Median urinary NGAL levels were significantly increased in the SIRS cohorts compared with nephrolithiasis without urinary tract infection patients (4.28 ng/mL versus 2.69 ng/mL, P0.001), and NGAL was markedly elevated even in the early stage of SIRS (3.23 ng/mL versus 2.69 ng/mL, P0.001). According to the receiver-operating characteristic analysis, NGAL demonstrated a high diagnostic value compared with either PCT or CRP. In the later stage of SIRS, NGAL remained a highly sensitive (76.8%) and specific (86.5%) diagnostic marker compared with either PCT or CRP. Moreover, the area under the curves of NGAL (0.822) were also superior to those seen in either PCT (0.657) or CRP (0.761).Urinary NGAL is a highly sensitive and specific predictor of SIRS for patients presenting with nephrolithiasis. Further study of NGAL as a reliable biomarker of SIRS is required.

Aim Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta-analysis of published studies regarding this subject. Methods A literature search was carried out using MEDLINE, EMBASE and the Cochrane database between January 1966 and October 2012. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Fixed effect and random effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. Results A total of 12 (two randomized controlled trials, five cohort, and five case–control) studies contributed to the analysis. There was heterogeneity among the studies but no evidence of publication bias. Pooled results indicated a non-significant decrease of total kidney cancer risk among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83, 1.22). In our subgroup analyses, the results were not substantially affected by study design, confounder adjustment and gender. Furthermore, sensitivity analysis confirmed the stability of the results. Conclusion The findings of this meta-analysis suggested that there was no association between statin use and risk of kidney cancer. More studies, especially randomized controlled trials and high quality cohort studies with larger sample size and well controlled confounding factors, are needed to confirm this association in the future.

Background To evaluate the effects of Tadalafil, a phosphodiesterase 5 enzyme inhibitor, on Escherichia coli –induced renal damage in an acute pyelonephritis (PN) rat model. Methods Experimental PN was induced in 32 Wistar rats, and four groups were formed: group 1 (no treatment), group 2 (antibiotic), group 3 (Tadalafil), and group 4 (antibiotic + Tadalafil). Antibiotic was given on days 3 to 8, and Tadalafil was administered between days 0 and 28 of bacterial inoculation. Half of the rats were killed on the ninth day (early period) and histopathological parameters, immunohistochemical renal fibrosis markers, and oxidant/antioxidant system activities were evaluated. The rest of the rats were killed at the sixth week of the study and evaluated for histopathological parameters and renal fibrosis markers. Results Inflammatory activity was significantly milder in rats treated with antibiotic + Tadalafil versus no treatment group both in the early and late periods. In the late period, interstitial fibrosis or tubular atrophy was lower in the antibiotic + Tadalafil group versus the no treatment and antibiotic groups, and in Tadalafil versus antibiotic group. Tadalafil administration significantly reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. In addition, circulating tumor necrosis factor α, interleukin 1β was greatly reduced in Tadalafil group versus the no treatment group. Conclusions We have provided the first evidence that phosphodiesterase 5 enzyme inhibitor Tadalafil ameliorates circulating inflammatory cytokines, reverses oxidant/antioxidant dysfunction and eventually possesses an overall protective effect on renal tissue from Escherichia coli –induced PN-related kidney injury. Phophodieterase 5 inhibitor might be a novel therapeutic target for PN.

Aims: The aim of this study was to screen several novel genes associated with renal cell carcinoma (RCC), and analyze the gene functions and signal pathways which were critical to RCCs with DNA microarray. Methods: The gene expression profile of GSE781 was downloaded from Gene Expression Omnibus database, including 9 RCC samples and 9 healthy controls. Compared with the control samples, differentially expressed genes (DEGs) of RCC was identified the by packages in R. The selected DEGs were further analyzed using bioinformatics methods. Gene ontology (GO) enrichment analysis was performed using Gene Set Analysis Toolkit and protein-protein interaction (PPI) network was constructed with prePPI. Then, pathway enrichment analysis to PPI network was performed using WebGestalt software. Results: A total of 429 DEGs were down-regulated and 418 DEGs were up-regulated in RCC samples compared to healthy controls. A total of 11 remarkable enhanced functions and 13 suppressed functions were identified. PPI nodes of high degrees, such as JAK2, IL8, BMPR2, FN1 and NCR1, were obtained. The DEGs were classified and significantly enriched in cytokine and cytokine receptor pathway. Conclusion: The hub genes we find from RCC samples are not only bio-markers, but also may provide the groundwork for a combination therapy approach for RCCs.

Objective To investigate the correlation of histological prostatitis with sexual function (erectile dysfunction [ED]) and lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). Methods A retrospective analysis of patients with BPH who received surgical treatment (from May 1, 2012 to November 30, 2012) was conducted, consisting of 80 patients with uncomplicated BPH and 80 patients with BPH plus histological prostatitis. The International Index of Erectile Function (IIEF-5) symptom score and the International Prostate Symptom Score (IPSS) before surgery were calculated. Preoperative sexual functions were compared between the 2 groups. Results Differences between both groups in age (72.56 ± 7.36 vs 71.98 ± 7.33) and IPSS score (18.65 ± 5.72 vs 20.50 ± 7.12) were not statistically significant (P >.05). Meanwhile, comparison in erectile function symptom score (14.80 ± 5.93 vs 7.35 ± 4.38) demonstrated significant differences (P

Resumen Antecedentes GATA-3 es un factor de transcripcion implicado en el crecimiento y desarrollo humano. Estudios recientes han demostrado su asociacion con el cancer de mama, sin embargo, su perfil de expresion en el carcinoma de celulas renales (CCR) no se ha investigado. Material y metodo El estudio incluyo a 35 pacientes sometidos a nefrectomia radical con diagnostico patologico confirmado de CCR. Se obtuvieron tejidos renales de control normales de 25 donantes vivos de rinon y los tejidos se biopsiaron antes de la implantacion. La mayoria de las muestras de CCR fueron diagnosticadas como carcinoma renal de celulas claras (94,3%), excepto para un caso de CCR papilar y otro caso de carcinoma del sistema colector. La expresion de GATA-3 se evaluo por PCR cuantitativa y Western blot (WB) en muestras de CCR y rinones normales, respectivamente; tambien se realizo tincion inmunohistoquimica. Mientras tanto, la expresion de GATA-3 en 2 lineas celulares de cancer (786-O, ACHN) y celulas epiteliales de rinon normales (HK-2) se detecto por PCR y WB. Ademas, las celulas renales cancerosas y las celulas HK-2 se cultivaron y se detectaron por microscopia confocal para la exacta localizacion intracelular de GATA-3. Resultados Los datos mostraron una importante subregulacion de la expresion de GATA-3 presente en los tejidos neoplasicos en comparacion con los tejidos normales; de manera similar, GATA-3 se atenuo significativamente en todas las lineas celulares de cancer renal en comparacion con las celulas HK-2 normales. La confocal mostro una fuerte actividad citoplasmica inmuno-fluorescente de GATA-3 con la zona perinuclear en HK-2, mientras que la intensidad en las celulas cancerosas fue notablemente mas debil que la de HK-2. Conclusiones En resumen, nuestro estudio aclara que el perfil de expresion aberrante de GATA-3 en el CCR humano esta posiblemente involucrado en la tumorogenesis, y el complicado mecanismo es digno de mayor investigacion.

Background GATA-3 is a transcription factor involved in human growth and development. Recent studies found its association with breast cancer, however, its expression profile in renal cell carcinoma (RCC) has not been investigated. Material and method The study included 35 patients submitted to radical nephrectomy with confirmed pathological diagnosis of RCC. Normal control kidney tissues were obtained from 25 living kidney donors and tissues were biopsied before implantation. The majority of RCC samples were diagnosed as clear cell renal cell carcinoma (94.3%) except for 1 case of papillary RCC and 1 case of collecting duct carcinoma. GATA-3 expression was evaluated by quantitative PCR and Western blotting (WB) in RCC samples and normal kidneys respectively, immunohistochemical staining was performed as well. Meanwhile, the GATA-3 expression in two cancer cell lines (786-O, ACHN) and normal kidney epithelial cells (HK-2) was detected by PCR and WB. In addition, renal cancer cells and HK-2 cells were cultivated and detected by confocal microscopy for the exact intra-cellular localization of GATA-3. Results Data showed a significant down-regulation of GATA-3 expression present in neoplastic tissues compared with normal tissues; similarly, GATA-3 was significantly attenuated in all renal cancer cell lines compared with normal HK-2 cells. Confocal displayed a strong cytoplasmic immuno-fluorescence activity of GATA-3 with peri-nuclear zone in HK-2, whereas the intensity in cancer cells was markedly weaker than that of HK-2. Conclusions In summary, our present study clarifies that the aberrant expression profile of GATA-3 in human RCC is possibly involved with tumorigenesis, and the complicated mechanism is worthy of further investigation.

What's known on the subject? and What does the study add? Thulium laser is a new generation of surgical laser. It is a minimally invasive technology with several advantages, including rapid vaporization and minimal tissue damage and bleeding. However, details regarding the safety and efficacy of thulium laser in treating BPH remains unknown. We performed a comparative study in 100 patients with BPH of the safety and efficacy of thulium laser resection of the prostate (TMLRP, n = 50) and bipolar transurethral plasmakinetic prostatectomy (TUPKP, n = 50). We found that the efficacy and indications were the same in TMLRP and TUPKP. In TUPKP, the morbidity of urethrostenosis was low, and was nearly bloodless in surgery and had higher safety. Nevertheless, TUPKP is more suitable for patients with larger prostate volume. Objective To compare the safety and short-term efficacy of thulium laser resection of the prostate (TMLRP) and bipolar transurethral plasmakinetic prostatectomy (TUPKP) for the treatment of patients with benign prostatic hyperplasia (BPH). Methods A total of l00 patients diagnosed with BPH were randomly divided into two groups, treated with either TMLRP (50, group 1) or TUPKP (50, group 2). There was no significant difference in preoperative variables such as age, prostate volume, prostate-specific antigen (PSA) level, International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) between the two groups. The perioperative parameters and therapeutic effects were recorded and compared between the two groups. Results There were significant differences in the following parameters between the two groups (TMLRP vs TUPKP [mean ± SD]): operation duration, 61.2 ± 24.2 vs 30.14 ± 15.9 min; catheterization time, 1.8 ± 0.4 vs 3.2 ± 0.6 d; postoperative hospital stay, 3.3 ± 0.8 vs 4.1 ± 1.3 d. The volume of blood loss and postoperative bladder irrigation were significantly lower in TMLRP group than in the TUPKP group. At 1 month after the operation, there were four cases of urethral stricture in the TUPKP group. At 3 months after the operation, IPSS, quality of life (QoL), Qmax and PVR were significantly improved, with no significant difference between the two groups. Conclusions TMLRP is superior to TUPKP in terms of safety, blood loss, recovery time and complication rate, and is as efficacious as TUPKP for treating BPH. Operation duration was significantly longer in the TMLRP group than in the TUPKP group.

To determine whether photoselective vaporization has advantages over transurethral resection of the prostate (TURP) in terms of effectiveness and safety for treatment of patients with benign prostatic hyperplasia.MEDLINE, EMBASE, and the Cochrane Controlled Trial Register were searched for randomized controlled trials. The risk ratio, mean difference, and their corresponding 95% confidence intervals were calculated for dichotomous and continuous outcomes, respectively. Risk of bias of enrolled trials was assessed according to Cochrane Handbook.A total of five trials were enrolled. There was no significant difference in the International Prostate Symptom Score and maximum flow rate between photoselective vaporization and TURP at 6-, 12-, and 24-month follow-up. Photoselective vaporization was associated with significantly lower risk of capsule perforation, transurethral resection syndrome, and clot retention, significantly lower transfusion requirements, a shorter catheterization time, and a shorter length of hospital stay. TURP was associated with a shorter operative time and a lower risk of reoperation. In addition, there was no difference in risk of acute urinary retention and urethral/bladder neck sclerosis between photoselective vaporization and TURP.Photoselective vaporization and TURP provide comparable improvements in functional results, including International Prostate Symptom Score and maximum flow rate at 6-, 12-, and 24-month follow-up. Photoselective vaporization offers advantages over TURP in terms of intraoperative safety; however, TURP is found to have a shorter operative time and lower reoperative risk.

MED19 is a member of the Mediator that plays a key role in the activation and repression of signal transduction or the regulation of transcription in carcinomas. To tested the functional role of MED19 in human prostate cancer, we downregulated MED19 expression in prostate cancer cells (PC-3 and DU145) by lentivirus-mediated short hairpin (shRNA), and analyzed the effect of inhibition of MED19 on prostate cancer cell proliferation and tumorigenesis. The in vitro prostate cancer cell proliferation, colony formation, and in vivo tumor growth in nude mice xenografts was significantly reduced after the downregulation of MED19. Knockdown of MED19 caused S-phase arrest and induced apoptosis via modulation of Bid and Caspase 7. It was suggested that MED19 serves as a novel proliferation regulator that promotes growth of prostate cancer cells.

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.

expression profiles for miR-10a and 10b in the nephrectomy and RMB specimens, binary logistic regression models were created for differentiation between local and aggressive disease. From the biopsy samples, the area under the curve, sensitivity, and specificity of this model were 0.818, 63.6, and 76.9, respectively. Decreased cancer specific survival was shown for patients with lower levels of miR-10b at 5 years follow up. CONCLUSIONS: We have identified a panel of 7 miRNA whose expression profiles are statistically different between local and aggressive ccRCC. This is the first study to stratify patients with ccRCC using biopsy tissue alone. The future utility of RMB may be in stratification and prognosis in addition to its current primary use of histologic diagnosis.

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.

Long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, pancreatic cancer, and cervical cancer. However, the role of lncRNA MALAT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Expression levels of lncRNA MALAT1 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress MALAT1 expression in renal cancer cells. In vitro assays were conducted to further explore its role in tumor progression. The expression level of MALAT1 was higher in ccRCC tissues and renal cancer cells compared to adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. The ccRCC patients with higher MALAT1 expression had an advanced clinical features and a shorter overall survival time than those with lower MALAT1 expression. And multivariate analysis showed that the status of MALAT1 expression was an independent predictor of overall survival in ccRCC. Additionally, our data indicated that knockdown expression of MALAT1 decreased renal cancer cell proliferation, migration, and invasion. Our data suggested that lncRNA MALAT1 was a novel molecule involved in ccRCC progression, which provided a potential prognostic biomarker and therapeutic target.

Calcium oxalate nephrolithiasis is the most common urological disease, but noninvasive and convenient methods of diagnosis are rarely available.Objective.The present study aimed to identify potential urine biomarkers for noninvasive diagnosis of CaOx nephrolithiasis.Methodology.Urine samples from 72 patients with CaOx nephrolithiasis and 30 healthy controls were collected and proteomics analysis was performed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometer (MALDI-TOF-MS).Results.Thirteen proteins/peptides displayed statistically significant differences. The peptides of m/z 1207.23 and 2773.86 were selected by the genetic algorithm (GA) to build a possible diagnostic model. The area under the curve of m/z 1207.23 and 2773.86 was 0.936 and 0.987, respectively. The diagnostic model in distinguishing patients and healthy subjects showed 100% sensitivity and specificity. The peak at m/z 2773.86 was identified as fibrinogen alpha chain (FGA) with the sequence G.EGDFLAEGGGVR.G, and the peak at m/z 2773.86 was identified as apolipoprotein A-I (apoA-I) with the sequence L.PVLESFKVSFLSALEEYTKKLNTQ.Conclusion.The study results strongly suggested that urinary FGA and apoA-I are highly sensitive and specific biomarkers for noninvasive diagnosis of CaOx nephrolithiasis.

The aim of this study was to investigate the possible relationships between dietary fiber intake and risk of renal cell carcinoma (RCC). Electronic databases including MEDLINE, EMBASE and Web of Science were searched to find eligible studies. Random-effects relative risk (RR) and its corresponding 95 % confidence interval (CI) were used. Besides, random-effects dose-response analyses were also performed to clarify the dose-response relations. Finally, publication bias was assessed by Egger's test and Begg's test. All p values were two tailed. Seven studies, including two cohort studies and five case-control studies, were eligible and included in this meta-analysis. Overall analysis in highest versus lowest level revealed that total dietary fiber intake was associated with reduced RCC risk (RR 0.84, 95 % CI 0.74-0.96). In addition, pooled estimated data showed that risk of RCC was significantly associated with vegetable and legume fiber intake (RR 0.70, RR 0.80, respectively), but not with fruit and cereal fiber intake (RR 0.92, RR 1.04, respectively). However, in dose-response analysis, no significant association was reported. Finally, no publication bias was detected by Egger's or Begg's test. The dietary fiber intake, especially vegetable and legume fiber, may be associated with reduced RCC risk. Considering the limitations of the included studies, more well-designed prospective studies will be needed to confirm our findings.

Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P < 0.05). As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene.