Comparison of novel flexible and traditional ureteral access sheath in retrograde intrarenal surgery.

OBJECTIVES: To compare the efficiency and safety of a novel flexible ureteral access sheath (f-UAS) and traditional ureteral access sheath (UAS) during retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Between January 2022 and September 2022, a total of 152 consecutive cases with renal stones underwent RIRS with the f-UAS. Their outcomes were compared with those of another 152 consecutive cases undergoing RIRS with traditional UAS using a 1:1 scenario matched-pair analysis, with matching parameters including age and stone size. The f-UAS is a novel UAS with a 10-cm-long tube at the tip that can follow the bends of flexible ureteroscope (f-URS). RESULTS: Baseline characteristics were found to be similar between the two groups. The f-UAS group demonstrated significantly higher SFR (76.3% vs. 7.2%; P < 0.001) at 1 day postoperatively and a higher clearance rate of stone volume (98.11% vs. 91.78%; P < 0.001). The f-UAS group also had lower total complications rate (9.9% vs. 22.4%; P = 0.003), lower incidence of fever (5.9% vs 11.9%; P = 0.001), shorter operative times (56.5 min vs. 59.9 min; P = 0.047), and lower usage rate of baskets (17.1% vs. 100%; P < 0.001). There was no significant difference in SFR at 1 month postoperatively (P = 0.627) and in the length of postoperative hospital stay between the two groups (P = 0.225). CONCLUSION: Compared to the traditional UAS during RIRS, the f-UAS showed several advantages, including higher SFR at 1 day postoperatively, shorter operative times, lower incidence of complications, and less use of basket.

Flexible ureteroscopy with novel flexible ureteral access sheath versus mini-percutaneous nephrolithotomy for treatment of 2-3 cm renal stones.

OBJECTIVES: To assess and compare the effectiveness and safety of flexible ureteroscopy (f-URS) with a novel flexible ureteral access sheath (f-UAS) versus mini-percutaneous nephrolithotripsy (mini-PCNL) in treating 2-3 cm renal stones. METHODS: Retrospectively analyzed consecutive cases that underwent f-URS with f-UAS (12/14 Fr) from January 29, 2022, to November 30, 2022. Consecutive cases that underwent mini-PCNL (18 Fr) from June 5, 2021, to January 26, 2022, were selected as controls. The f-UAS is a novel device with a 10 cm anterior tip that passively bends along with the f-URS to enter the renal calyx. We analyzed demographic characteristics, stone parameters, operative time, stone-free rates (SFR), hospitalization time, and complication. RESULTS: A total of 96 consecutive cases that underwent f-URS with f-UAS and 96 consecutive cases that underwent mini-PCNL were included in the study. There were no significant differences between the two groups in terms of operative time (p = 0.06), stone volume clearance (p = 0.533) and complete SFR (p = 0.266) on the first postoperative day or residual Stone after 1 month (p = 0.407). We observed a significantly shorter postoperative hospital stay (1.4 days vs. 2.1 days; p < 0.001) and a lower decrease in hemoglobin levels (0.39 g/dL vs. 0.68 g/dL; p < 0.001) in the f-UAS group. The mini-PCNL group had a significantly higher overall complication rate (13.5%) compared with the f-UAS group (5.2%; p = 0.048). CONCLUSIONS: In the treatment of 2-3 cm renal stones, f-URS with a novel f-UAS may provide a superior alternative to mini-PCNL, potentially challenging its established status.

IGF2BP3 overexpression predicts poor prognosis and correlates with immune infiltration in bladder cancer.

BACKGROUND: IGF2BP3 expression is associated with poor prognosis in cancers of multiple tissue origins. However, the precise mechanism of its co-carcinogenic action in bladder cancer is unknown. METHODS: We aimed to demonstrate the relationship between IGF2BP3 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. We next validated IGF2BP3 expression in the Gene Expression Omnibus (GEO) database (GSE3167). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic values of IGF2BP3. Cox and logistic regression were used to explore the factors affecting the prognosis. Protein-protein interactions (PPIs) network was constructed by STRING. Enrichment analyses were performed to infer involved pathways and functional categories of IGF2BP3 using the cluster Profiler package. We applied single-sample gene set enrichment analysis (ssGSEA) algorithm and TIMER database to evaluate the expression level of immune genes. RESULTS: Pan-cancer analyses reveal that IGF2BP3 was higher in most cancer types, including bladder cancer, and the same results were found in GSE3167. The area under the ROC curve of IGF2BP3 was 0.736, which indicated that IGF2BP3 may be a potential diagnostic biomarker. High IGF2BP3 expression was associated with poorer overall survival (OS) (P = 0.015). For validation, we collected 95 bladder cancer samples and found that IGF2BP3 expression was higher in bladder cancer tissues than that in non-tumor bladder tissues by immunohistochemistry staining. We found a positive correlation between the expression level of IGF2BP3 and the clinical stage of bladder cancer. Immunocyte infiltration analysis showed that high IGF2BP3 expression was correlated with regulating the infiltration level of immune cell, including neutrophil cells and macrophages. IGF2BP3 promotes migration and invasion of bladder cancer cells, while IGF2BP3 inhibition had the opposite effects. Higher IGF2BP3 expression was closely associated with advanced TNM stage. CONCLUSION: IGF2BP3 overexpression was related to disease progression and poor prognosis, as well as infiltration of immune cells in bladder cancer. IGF2BP3 can be a promising independent prognostic biomarker and potential treatment target for bladder cancer.

Novel cuproptosis-related long non-coding RNA signature to predict prognosis in prostate carcinoma.

BACKGROUND: Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function. METHODS: RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships. RESULTS: The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan-Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed. CONCLUSIONS: A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.

MAPK8IP2 is a potential prognostic biomarker and promote tumor progression in prostate cancer.

BACKGROUND: MAPK8IP2 is one of the JNK-interacting proteins (JIPs) family members, and is involved in the regulation of the JNK and P38 MAPK signaling pathways. MAPK8IP2 has been reported to be closely associated with several cancers. However, the biological function of MAPK8IP2 in prostate cancer (PCa) remains unclear. METHODS: MAPK8IP2 expression in PCa and subgroups of PCa was analyzed by public databases. The prognostic role of MAPK8IP2 in prostate cancer was analyzed using the Cox regression method. The potential mechanism by which MAPK8IP2 affects PCa progression was investigated by utilizing public data, including genetic alteration, DNA methylation, m6A methylation, and immune infiltration data. We further performed in vitro assays to validate the effect of MAPK8IP2 on PCa cell proliferation, migration and invasion. RESULTS: MAPK8IP2 is highly expressed in PCa tissues. Overexpression of MAPK8IP2 is associated with adverse clinicopathological factors and a poor prognosis in PCa. Receiver operating curve analysis showed that MAPK8IP2 can distinguish PCa tissues from non-PCa tissues with a certain accuracy (AUC = 0.814). The MAPK8IP2 genetic alteration rate was 2.6% and MAPK8IP2 alterations correlated with a poor prognosis. We also found that CDK12 and TP53 mutations were associated with MAPK8IP2 expression. The DNA methylation level of MAPK8IP2 was higher in primary tumors than in normal tissues, and the high MAPK8IP2 DNA methylation group of PCa patients had poor survival. Enrichment analysis indicated that MAPK8IP2 was involved in the MAPK signaling pathway. In vitro, knockdown of MAPK8IP2 inhibited PCa cell proliferation, migration and invasion. CONCLUSION: MAPK8IP2 is a potential target for PCa treatment and can serve as a novel biomarker for PCa diagnosis and prognosis evaluation.

Identification of a novel signature based on unfolded protein response-related gene for predicting prognosis in bladder cancer.

BACKGROUND: The unfolded protein response (UPR) served as a vital role in the progression of tumors, but the molecule mechanisms of UPR in bladder cancer (BLCA) have been not fully investigated. METHODS: We identified differentially expressed unfolded protein response-related genes (UPRRGs) between BLCA samples and normal bladder samples in the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and the least absolute shrinkage and selection operator penalized Cox regression analysis were used to construct a prognostic signature in the TCGA set. We implemented the validation of the prognostic signature in GSE13507 from the Gene Expression Omnibus database. The ESTIMATE, CIBERSORT, and ssGSEA algorithms were used to explore the correlation between the prognostic signature and immune cells infiltration as well as key immune checkpoints (PD-1, PD-L1, CTLA-4, and HAVCR2). GDSC database analyses were conducted to investigate the chemotherapy sensitivity among different groups. GSEA analysis was used to explore the potential mechanisms of UPR-based signature. RESULTS: A prognostic signature comprising of seven genes (CALR, CRYAB, DNAJB4, KDELR3, CREB3L3, HSPB6, and FBXO6) was constructed to predict the outcome of BLCA. Based on the UPRRGs signature, the patients with BLCA could be classified into low-risk groups and high-risk groups. Patients with BLCA in the low-risk groups showed the more favorable outcomes than those in the high-risk groups, which was verified in GSE13507 set. This signature could serve as an autocephalous prognostic factor in BLCA. A nomogram based on risk score and clinical characteristics was established to predict the over survival of BLCA patients. Furthermore, the signature was closely related to immune checkpoints (PD-L1, CTLA-4, and HAVCR2) and immune cells infiltration including CD8+ T cells, follicular helper T cells, activated dendritic cells, and M2 macrophages. GSEA analysis indicated that immune and carcinogenic pathways were enriched in high-risk group. CONCLUSIONS: We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of patients with bladder cancer.

Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is a malignant tumor with a dismay outcome. Increasing evidence has confirmed that chromatin regulators (CRs) are involved in cancer progression. Therefore, we aimed to explore the function and prognostic value of CRs in BLCA patients. METHODS: Chromatin regulators (CRs) were acquired from the previous top research. The mRNA expression and clinical information were downloaded from TCGA and GEO datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to select the prognostic gene and construct the risk model for predicting outcome in BLCA. The Kaplan-Meier analysis was used to assess the prognosis between high- and low-risk groups. We also investigated the drug sensitivity difference between high- and low-risk groups. CMAP dataset was performed to screen the small molecule drugs for treatment. RESULTS: We successfully constructed and validated an 11 CRs-based model for predicting the prognosis of patients with BLCA. Moreover, we also found 11 CRs-based model was an independent prognostic factor. Functional analysis suggested that CRs were mainly enriched in cancer-related signaling pathways. The CR-based model was also correlated with immune cells infiltration and immune checkpoint. Patients in the high-risk group were more sensitive to several drugs, such as mitomycin C, gemcitabine, cisplatin. Eight small molecule drugs could be beneficial to treatment for BLCA patients. CONCLUSION: In conclusion, our study provided novel insights into the function of CRs in BLCA. We identified a reliable prognostic biomarker for the survival of patients with BLCA.

Development and validation of a novel lipid metabolism-related gene prognostic signature and candidate drugs for patients with bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is a common cancer associated with an unfavorable prognosis. Increasing numbers of studies have demonstrated that lipid metabolism affects the progression and treatment of tumors. Therefore, this study aimed to explore the function and prognostic value of lipid metabolism-related genes in patients with bladder cancer. METHODS: Lipid metabolism-related genes (LRGs) were acquired from the Molecular Signature Database (MSigDB). LRG mRNA expression and patient clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a signature for predicting overall survival of patients with BLCA. Kaplan-Meier analysis was performed to assess prognosis. The connectivity Map (CMAP) database was used to identify small molecule drugs for treatment. A nomogram was constructed and assessed by combining the signature and other clinical factors. The CIBERSORT, MCPcounter, QUANTISEQ, XCELL, CIBERSORT-ABS, TIMER and EPIC algorithms were used to analyze the immunological characteristics. RESULTS: An 11-LRG signature was successfully constructed and validated to predict the prognosis of BLCA patients. Furthermore, we also found that the 11-gene signature was an independent hazardous factor. Functional analysis suggested that the LRGs were closely related to the PPAR signaling pathway, fatty acid metabolism and AMPK signaling pathway. The prognostic model was closely related to immune cell infiltration. Moreover, the expression of key immune checkpoint genes (PD1, CTLA4, PD-L1, LAG3, and HAVCR2) was higher in patients in the high-risk group than in those in the low-risk group. The prognostic signature based on 11-LRGs exhibited better performance in predicting overall survival than conventional clinical characteristics. Five small molecule drugs could be candidate drug treatments for BLCA patients based on the CMAP dataset. CONCLUSIONS: In conclusion, the current study identified a reliable signature based on 11-LRGs for predicting the prognosis and response to immunotherapy in patients with BLCA. Five small molecule drugs were identified for the treatments of BLCA patients.

Preoperative aspartate transaminase/alanine transaminase ratio as a prognostic biomarker in primary non-muscle-invasive bladder cancer: a propensity score-matched study.

PURPOSE: To evaluate the prognostic value of the aspartate transaminase/alanine transaminase (AST/ALT) ratio in primary non-muscle-invasive bladder cancer (NMIBC) using propensity score matching (PSM) analysis. METHODS: We retrospectively collected the clinical and pathological data from 314 patients with primary NMIBC who underwent transurethral resection of bladder tumor. The full cohorts were divided into a low AST/ALT ratio group and a high AST/ALT ratio group according to the optimal cut-off value which was obtained based on the analysis of the receiver operating characteristic curve for the 3-year recurrence-free survival (RFS). After 1:1 PSM, the correlation between preoperative AST/ALT ratio and survival prognosis was evaluated by Kaplan-Meier analysis with log-rank tests. The independent prognostic factors for RFS and progression-free survival (PFS) were also analyzed. RESULTS: The optimum cutoff value of the preoperative AST/ALT ratio was 1.40. Before PSM, a high AST/ALT ratio was correlated with the larger proportion of age > 60 years (P = 0.007) and the worse pathological T stage (P < 0.001). After PSM, patients with a high AST/ALT ratio had poorer RFS and PFS than patients with a low AST/ALT ratio (all P < 0.001). In addition, multivariate Cox regression analysis indicated that preoperative AST/ALT ratio was considered as an independent prognostic factor of RFS (HR 2.865; 95%CI 1.873-4.381; P < 0.001) and PFS (HR 4.771; 95%CI 2.607-8.734; P < 0.001) in patients with primary NMIBC. CONCLUSIONS: The high AST/ALT ratio group tended to have poorer RFS and PFS than the low AST/ALT ratio group. Our results also indicated that the elevated preoperative AST/ALT ratio could be seen as a useful prognostic biomarker for predicting early disease recurrence and progression in patients with primary NMIBC.

IGF2BP3 facilitates cell proliferation and tumorigenesis via modulation of JAK/STAT signalling pathway in human bladder cancer.

Insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) has been reported to contribute to tumorigenesis in several human cancers. However, the biological functions of IGF2BP3 in bladder cancer are poorly understood. We investigated the relation between IGF2BP3 expression and prognosis of bladder cancer patients. Cell proliferation, cell cycle and cell apoptosis assays were performed to assess IGF2BP3 functions. The results showed that IGF2BP3 was overexpressed in bladder cancer tissues compared with that in normal bladder tissues, and its higher expression was closely correlated with poor prognosis in bladder cancer patients. Overexpression of IGF2BP3 markedly promoted cell proliferation and cell cycle progression and inhibited cell apoptosis, while knockdown of IGF2BP3 notably suppressed the proliferation, promoted cell apoptosis and induced cell cycle arrest at the G0/G1 phase. Mechanistically, we revealed that IGF2BP3 promotes the activation of the JAK/STAT pathway in bladder cancer cells. Moreover, the JAK/STAT inhibitor dramatically blocked the tumour-promoting activity of IGF2BP3. Tumour growth in vivo was also suppressed by knocking down of IGF2BP3. Hence, IGF2BP3 facilitated bladder cancer cell proliferation by activating the JAK/STAT signalling pathway. These findings suggest that IGF2BP3 exhibits an oncogenic effect in human bladder cancer progression.

Transvesical robot-assisted radical prostatectomy: initial experience and surgical outcomes.

OBJECTIVES: To describe in detail the techniques for transvesical robot-assisted radical prostatectomy (RARP) using the da Vinci Si/Xi system (Intuitive Surgical, Sunnyvale, CA, USA) and to evaluate functional and oncological outcomes in 35 patients with prostate cancer. PATIENTS AND METHODS: Thirty-five patients with localized prostate cancer were enrolled for transvesical RARP. The patients' preoperative data (mean ± sd age 63.4 ± 8.1 years, body mass index 28.6 ± 5.3 kg/m2 , total prostate-specific antigen 10.8 ± 4.9 ng/mL and prostate volume 30.6 ± 14.4 mL, and median [interquartile range {IQR}] biopsy Gleason score 6 [6-7], and International Index of Erectile Function [IIEF]-5 score 18 [16-20]) were collected. Preoperative assessment revealed 28 cases of cT2a and seven cases of cT2b disease. All patients were continent preoperatively (defined as no pad required or one dry pad per day as a precaution). Surgical results and peri-operative complications were assessed. All patients were followed up for at least 12 months postoperatively. RESULTS: The mean operating time was 150 ± 35 min. Estimated blood loss was 100 ± 45 mL. Urinary infection was noted in one patient and managed with levofloxacin. Another patient complained of nocturia on postoperative day 14, which was relieved with solifenacin succinate. Urethral catheters were removed on postoperative day 7. Thirty-two patients achieved immediate urinary continence, with three patients returning to full continence on postoperative day 14. Postoperative pathology confirmed 24 pT2a cases, nine pT2b cases and two pT2c cases (median [IQR] Gleason score 6 [6-7]). Positive surgical margins were found in four patients (11.4%). No urethral stricture or urinary leakage was noted on urethrocystography taken 3 months after surgery. Urodynamic studies were performed preoperatively and 6 months after surgery: median (IQR) maximum urinary flow 12.2 (10.2-14.9) vs 13.7 (10.1-15.0) mL/s; bladder capacity 385.3 (351.3-410.2) vs 370.2 (330.1-395.4) mL; and voiding phase detrusor contractility 38.5 (27.8-42.3) vs 35.6 (28.3-41.3) mmH2 O, respectively. During a minimum of 12 months of follow-up, no biochemical recurrence was noted in any patient. The median (IQR) IIEF-5 score was 17 (16-19). CONCLUSIONS: The transvesical approach is a valid alternative to RARP in selected patients, providing promising postoperative urinary continence. Long-term functional and oncological results require further investigation.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Blockage of neddylation modification stimulates tumor sphere formation in vitro and stem cell differentiation and wound healing in vivo.

MLN4924, also known as pevonedistat, is the first-in-class inhibitor of NEDD8-activating enzyme, which blocks the entire neddylation modification of proteins. Previous preclinical studies and current clinical trials have been exclusively focused on its anticancer property. Unexpectedly, we show here, to our knowledge for the first time, that MLN4924, when applied at nanomolar concentrations, significantly stimulates in vitro tumor sphere formation and in vivo tumorigenesis and differentiation of human cancer cells and mouse embryonic stem cells. These stimulatory effects are attributable to (i) c-MYC accumulation via blocking its degradation and (ii) continued activation of EGFR (epidermal growth factor receptor) and its downstream pathways, including PI3K/AKT/mammalian target of rapamycin and RAS/RAF/MEK/ERK, via inducing EGFR dimerization. Finally, MLN4924 accelerates EGF-mediated skin wound healing in mouse and stimulates cell migration in an in vitro culture setting. Taking these data together, our study reveals that neddylation modification could regulate stem cell proliferation and differentiation and that a low dose of MLN4924 might have a therapeutic value for stem cell therapy and tissue regeneration.

The Comparison Study of Flexible Ureteroscopic Suctioning Lithotripsy With Intelligent Pressure Control Versus Minimally Invasive Percutaneous Suctioning Nephrolithotomy in Treating Renal Calculi of 2 to 3 cm in Size.

Purpose. To compare the efficacy and safety of flexible ureteroscopic suctioning lithotripsy (FURS) using patented designed intelligent irrigation and suctioning intraluminal pressure-control platform and integrated pressure-measuring suctioning ureteral access sheath versus minimally invasive suctioning percutaneous nephrolithotomy (MPCNL) in treating renal calculi at 2 to 3 cm in size. Methods. Ninety-one patients who met the criteria were included in the study. Among these, 46 patients underwent transurethral flexible ureteroscopic lithotripsy and the other 45 patients underwent MPCNL. We retrospectively analyzed the clinical data for the 2 groups and parameters including stone clearance rate, complication rate, average operative time, average postoperative hospitalization duration, and average postoperative hemoglobin level decrease were compared. Results. The hospitalization time for the FURS group was 3.53 ± 1.25 days, which was statistically shorter than that of the MPCNL group, which was 6.54 ± 2.36 days. There was significantly more patients needing pain medication postoperatively in the MPCNL group with statistical difference between the 2 groups (P = .015). Also, there was more significant hemoglobin level drop in the MPCNL group with statistical difference between the 2 groups. However, there were no statistical differences between the 2 groups on average operative time and stone clearance rate. Conclusion. Both the operative methods are safe and efficacious in treating solitary renal calculus at 2 to 3 cm in size. However, FURS has more advantages including shorter hospital stay, less complication, and less bleeding.

Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

Contrast-Enhanced Ultrasound Differentiation Between Low- and High- Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density.

OBJECTIVES: Time-intensity curves (TICs) of contrast-enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low-grade and high-grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD). METHODS: The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low-grade and 50 high-grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one-half the signal intensity (TPH) and the corresponding descending slope (DS) of the low-grade and high-grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34. RESULTS: Based on conventional ultrasound, the low-grade and high-grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high-grade group was significantly longer than that of the low-grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low-grade and high-grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high-power field of the low-grade and high-grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01). CONCLUSIONS: Contrast-enhanced ultrasound can be used to differentiate low from high-grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis.

WITHDRAWN: IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to CXC195-induced apoptosis in human bladder carcinoma T24 cells.

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IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to CXC195-induced apoptosis in human bladder carcinoma T24 cells.

Bladder urothelial carcinoma (UC) accounts for approximately 5% of all cancer deaths in humans. Current treatments extend the recurrence interval but do not significantly alter patient survival. The objective of the present study was to investigate the anti-cancer effect and the underlying mechanisms of CXC195 against human UC cell line T24 cells. CXC195 inhibited the cells growth and induced caspase- and mitochondrial-dependent apoptosis in T24 cells. In addition, CXC195 triggered activation of proteins involved in ER stress signaling including GRP78, CHOP, IRE1α, TRAF2, p-ASK1 and p-JNK in T24 cells. Co-immunoprecipitation experiments showed that activation of JNK was induced by the activation of IRE1α through formation of an IRE1α-TRAF2-ASK1 complex. Knockdown of IRE1α by siRNA dramatically abrogated CXC195-induced activation of TRAF2, ASK and JNK, formation of an IRE1α-TRAF2-ASK1 complex and caspase- and mitochondrial-dependent apoptosis in T24 cells. These findings provided new insights to understand the mode of action of CXC195 in treatment of human UC.

Survivin and PSMA Loaded Dendritic Cell Vaccine for the Treatment of Prostate Cancer.

Dendritic cell (DC)-based vaccines are a promising therapeutic modality for cancer. Results from recent trials and approval of the first DC vaccine by the U.S. Food and Drugs Administration for prostate cancer have paved the way for DC-based vaccines. A total of 21 hormone refractory prostate cancer (HRPC) patients with a life expectancy >3 months were randomised into two groups. DC loaded with recombinant Prostate Specific Membrane Antigen (rPSMA) and recombinant Survivin (rSurvivin) peptides was administered as an subcutaneous (s.c.) injection (5×10(6) cells). Docetaxel (75 mg/m(2) intravenous (i.v.)) and prednisone (5 mg, bis in die (b.i.d.)) served as control. Clinical and immunological responses were evaluated. Primary endpoints were safety and feasibility; secondary endpoint was overall survival. Responses were evaluated on day 15, day 30, day 60, and day 90. DC vaccination was well tolerated with no signs of grade 2 toxicity. DC vaccination induced delayed-type hypersensitivity reactivity and an immune response in all patients. Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumours (RECIST) was 72.7% (8/11) versus 45.4 (5/11) in the docetaxel arm and immune related response criteria (irRC) was 54.5% (6/11) compared with 27.2% (3/11) in the control arm. The DC arm showed stable disease (SD) in 6 patients, progressive disease (PD) in 3 patients, and partial remission (PR) in two patients compared to SD in 5 patients, PD in 6 patients, and PR in none in the docetaxel arm. There was a cellular response, disease stabilization, no adverse events, and partial remission with the rPSMA and rSurvivin primed DC vaccine.