Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial.

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Ivermectin Inhibits Bladder Cancer Cell Growth and Induces Oxidative Stress and DNA Damage.

BACKGROUND: Bladder cancer is the most common malignant tumor of the urinary system. Nevertheless, current therapies do not provide satisfactory results. It is imperative that novel strategies should be developed for treating bladder cancer. OBJECTIVES: To evaluate the effect of a broad-spectrum anti-parasitic agent, Ivermectin, on bladder cancer cells in vitro and in vivo. METHODS: CCK-8 and EdU incorporation assays were used to evaluate cell proliferation. Apoptosis was detected by flow cytometry, TUNEL assay, and western blotting. Flow cytometry and DCFH-DA assay were used to analyze the reactive oxygen species (ROS) levels. DNA damage was determined by Neutral COMET assay and γ H2AX expression. Proteins related to apoptosis and DNA damage pathways were determined by WB assay. Xenograft tumor models in nude mice were used to investigate the anti-cancer effect of Ivermectin in vivo. RESULTS: Our study showed that in vitro and in vivo, Ivermectin inhibited the growth of bladder cancer cells. In addition, Ivermectin could induce apoptosis, ROS production, DNA damage, and activate ATM/P53 pathwayrelated proteins in bladder cancer cells. CONCLUSIONS: According to these findings, Ivermectin may be a potential therapeutic candidate against bladder cancer due to its significant anti-cancer effect.

Perioperative outcomes and continence following robotic-assisted radical cystectomy with mainz pouch II urinary diversion in patients with bladder cancer.

PURPOSE: To present the widely unknown perioperative outcomes and continence status of bladder cancer patients following robotic-assisted radical cystectomy (RARC) with Mainz pouch II urinary diversion (UD). MATERIALS AND METHODS: From November 2020 to December 2023, 37 bladder cancer patients who underwent RARC with Mainz pouch II UD were retrospectively assessed (ChiCTR2300070279). The results, which included patient demographics, perioperative data, continence, and complications (early ≤ 30 days and late ≤ 30 days) were reported using the RC-pentafecta criteria. RC-pentafecta criteria included ≥ 16 lymph nodes removed, negative soft tissue surgical margins, absence of major (Grade III-IV) complication at 90 days, absence of clinical recurrence at ≤ 12 months, and absence of long-term UD-related sequelae. A numeric rating scale assessed patient satisfaction with urinary continence 30 days after surgery. The validated Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire was used to evaluate bowel function. The Kaplan-Meier curve was used to evaluate overall survival (OS). RESULTS: Of the 37 patients evaluated over a median (range) follow-up period of 23.0 (12.0-36.5) months. The median (range) age was 65 (40-81) years. The median (range) time to urinary continence after surgery was 2.3 (1.5-6) months. Of the 37 patients, 31 (83.8%) were continent both during the day and at night, 34 (91.9%) were continent during the day, 32 (86.5%) were continent at night, 35 (94.6%) were satisfied with their urinary continence status, and 21 (56.8%) were very satisfied. The mean (range) voiding frequency was 6 (4-10) during the day and 3 (2-5.5) at night. The mean (range) PAC-SYM total score was 9.50 (4.00-15.00). In 12 (32.4%) of the patients, RC-pentafecta was achieved, and achieving RC-pentafecta was linked to better satisfaction scores (7.3 vs. 5.5, p = 0.034). There was no significant difference between RC-pentafecta and No RC-pentafecta groups in terms of OS (25.6 vs. 21.5 months, p = 0.16). 7 (19.4%) patients experienced late complications. CONCLUSIONS: Mainz pouch II UD following RARC in bladder cancer patients results in a satisfactory continence rate. Achieving RC-pentafecta was correlated with better satisfaction scores. The intracorporeal approach to Mainz pouch II UD is beneficial for female patients due to its reduced invasiveness. TRIAL REGISTRATION: ChiCTR2300070279; Registration: 07/04/2023, Last updated version: 01/06/2023. Retrospectively registered.

Formin-related protein 1 facilitates proliferation and aggressive phenotype of clear cell renal cell carcinoma through MAPK/MMP2 pathway.

BACKGROUND: Formin-related protein-1(FRL1) has reportedly been overexpressed in a variety of malignancies, such as clear cell renal cell carcinoma (ccRCC). However, the clinical value and molecular mechanisms underlying ccRCC tumorigenesis and progression in association with FRL1 remain poorly understood. METHODS: Immunohistochemical analysis was performed on 119 paraffin-embedded RCC tissue samples to detect FRL1 expression and analyze its prognostic value. Colony formation, the CCK-8 assay, flow cytometry, and in vivo nude mice subcutaneous experiments were used to identify the effects of FRL1 on growth and proliferation. In vitro tests for wound healing, migration, and invasion were used to assess the involvement of FRL1 in invasion and metastatic potential. The process of epithelial-mesenchymal transition process (EMT) and the MMP2 expression were detected in stably transfected RCC cells via western blotting, as well as in tumor tissue paraffin sections from xenograft model. RESULTS: Both FRL1 mRNA and protein levels were noticeably elevated in ccRCC cell lines and samples. Aberrant overexpression of FRL1 was associated with unfavorable clinicopathological features of ccRCC and indicated poor prognosis. Ectopic overexpression of FRL1 increased the growth-promoting traits of ccRCC cells as well as the migratory and invasive capacity of RCC cells, whereas FRL1-silencing caused the opposite results. In addition, FRL1 promoted epithelial-mesenchymal transition (EMT) and upregulated the expression of matrix metalloproteinase 2 (MMP2). Finally, overexpression of FRL1 upregulated phosphorylation level of ERK1/2 with no effect on total level of ERK1/2 in the RCC cells. MAPK/ERK inhibitor reversed the promotional effects of FRL1. CONCLUSION: FRL1 was overexpressed in ccRCC tissues and predicted poor prognosis. FRL1 contributes to invasion and aggressive phenotype of ccRCC by facilitating EMT through MAPK/MMP2 axis.

Perioperative, functional, and oncologic outcomes of minimally-invasive surgery for highly complex renal tumors (RENAL or PADUA score ≥ 10): an evidence-based analysis.

The primary objective of the current study is to undertake a comparative analysis of the effectiveness and safety of minimally-invasive partial nephrectomy (MIPN; including laparoscopic and robotic approaches) and open partial nephrectomy (OPN) for the treatment of highly complex renal tumors (defined as PADUA or RENAL score ≥ 10). A comprehensive search was conducted in four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) to identify relevant studies published in the English language up to April 2023. The current study employed Review Manager 5.4 and encompassed controlled trials of both MIPN and OPN for the treatment of highly complex renal tumors. This study comprised a total of eight comparative trials involving 1161 patients. MIPN demonstrated a significant reduction in length of hospital stay (weighted mean difference [WMD] - 2.08 days, 95% confidence interval [CI] - 2.48, - 1.68; p < 0.00001), blood loss (WMD - 39.86 mL, 95% CI - 75.32, - 4.39; p = 0.03), transfusion rates (odds ratio [OR] 0.30, 95% CI 0.13, 0.71; p = 0.006), and overall complications (OR 0.46, 95% CI 0.31, 0.70; p = 0.0003). However, there were no significant differences between MIPN and OPN in terms of operative time, warm ischemia time, conversion to radical nephrectomy rates, renal functional and oncologic outcomes. This study reveals that MIPN presents several benefits in comparison to OPN, including decreased length of hospital stay, blood loss, transfusion rates, and complications, while still offering renal functional and oncological outcomes that are comparable to those of OPN in patients with highly complex renal tumors.

Clinical application and efficacy analysis of partial cystectomy combined with intravesical chemotherapy in muscle-invasive bladder cancer.

OBJECTIVES: Comparing the long-term tumor control results of partial cystectomy(PC)and radical cystectomy(RC)in the treatment of muscle-invasive bladder cancer, and to explore the feasible method of bladder preservation therapy (BPT)in patients with MIBC. METHODS: We retrospectively analyzed the clinical data of 102 patients with muscle-invasive bladder cancer in our hospital between January 2012 and December 2018, of whom 32 cases in the partial cystectomy group and 70 cases in the radical cystectomy group. We performed a comparative analysis of patient general information, perioperative-related indicators and postoperative follow-up data, comparing OS, PFS, and DSS at 1, 2, 3, 4, and 5 years in both groups, and comparing tumour recurrence and metastasis in postoperative patients. RESULTS: All the 102 cases in this study were successfully completed. Partial cystectomy group and Radical cystectomy group median operating time (169.50(130.00 ~ 225.25) min and 420.00(343.75 ~ 483.75) min, p < 0.001), median intraoperative blood loss was (100(50 ~ 100)ml and 400(200 ~ 1000)ml, p < 0.001), median perioperative blood transfusion volume (0(0 ~ 0)ml and 600(150.00 ~ 906.25)ml, p < 0.001), median total hospital stay (18(14.25 ~ 20.00) and 24.5(20.00 ~ 34.25) days, p < 0.001), median preoperative preparation time (7(4.25 ~ 8.00) and 10(8.00 ~ 13.00) days, p < 0.001), median postoperative hospital stay (9(8.00 ~ 13.50) and 14(11.00 ~ 21.25) days, p < 0.001), the incidence of perioperative blood transfusion was (15.6% and 75.7%, p < 0.001), the incidence of surgical complications was(28.1%(9/32) and 50.0%(35/70), p = 0.033), average hospitalization cost ((26435.76 ± 9877.82) yuan and (58464.36 ± 19753.13) yuan, p < 0.001), the differences were statistically significant (p < 0.05). Perioperative mortality (0 vs. 2.9%(2/70), p = 1), and OS at 1, 2, 3, 4, and 5 years after surgery were (80.0%, 59.8%, 56.1%, 51.0%, 44.6% vs. 76.5%, 67.4%, 64.9%, 57.9%, 52.6%, p = 0.524), PFS (68.2%, 64.6%, 60.3%, 54.8%, 54.8% vs. 82.7%, 78.3%, 75.4%, 67.3%, 62.1%, p = 0.259). DSS (89.9%, 72.4%, 68.6%, 68.6%, 62.4% vs. 87.3%, 83.4%, 80.9%, 73.6%, 68.0%, p = 0.424), and the incidence of tumor recurrence or metastasis was (40.0%(12/30) vs. 25.4%(16/63), p = 0.151), the differences were not statistically significant (p > 0.05). CONCLUSION: In patients with limited solitary T2N0M0 and T3N0M0 muscle-invasive bladder cancer, partial cystectomy plus bladder instillations treatment can achieve comparable tumour control to radical cystectomy. However, patients in the PC group have significant advantages in terms of operative time, intraoperative bleeding, intraoperative and postoperative blood transfusion, preoperative preparation time, total hospital stay, postoperative recovery time, operative costs and operative complications. This option may be considered for such patients with a need for bladder preservation.

Retroperitoneal laparoscopic radical nephrectomy (RLRN) is associated with poor integrity of Gerota's fascia and perirenal fat: A prospective comparative study.

Purpose: To figure out the difference of integrity of Gerota's fascia and perirenal fat between Retroperitoneal Laparoscopic Radical Nephrectomy (RLRN) and Transperitoneal Laparoscopic Radical Nephrectomy (TLRN). Methods: This is a prospective comparative study of patients with Renal Cell Carcinoma (RCC) from a designated tertiary center in Lanzhou, China. We have developed and propose a scoring tool to quantify the integrity of nephrectomy specimens from both approaches. The integrity score is based on 6 common conditions of nephrectomy specimens. Specimens are scored on a 1 to 6-point scale according to the integrity of Gerota's fascia and perirenal fat. We applied the integrity score to 142 consecutive patients. Integrity scores were compared between RLRN and TLRN groups. Factors associated with low integrity score were assessed by logistic regression. Results: Among 142 patients, 79 (55.6%) patients and 63 (44.4%) patients, respectively, underwent RLRN and TLRN. There was a significant difference in the distribution of integrity score between the two groups (P < 0.001). RLRN (odds ratio 10.65, 95%CI 4.29-26.45, P < 0.001), tumor size (odds ratio 1.22, 95%CI 1.04-1.42, P = 0.015) and Body Mass Index (BMI) (odds ratio 0.83, 95%CI 0.72-0.96, P = 0.010) were significantly associated with low integrity score. The logistic regression equation showed good power to predict low integrity score. Conclusion: RLRN has poor integrity of Gerota's fascia and the perirenal fat. The integrity score can be used to evaluate the extent of resection and specimen completeness in LRN. Postoperative evaluation of the integrity score is of great value for urologists to evaluate the risk of tumor residue.

TAGLN2 Promotes the Proliferation, Migration, Invasion, and EMT of Clear Cell Renal Cell Carcinoma Through the PI3K/Akt Signaling Pathway.

The effect of Transgelin 2 (TAGLN2) on clear cell renal cell carcinoma (ccRCC) is unknown. This study explored the potential role and mechanism of ccRCC. The expression of TAGLN2 in Pan-cancers was analyzed using the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. TCGA-KIRC database was used to analyze subsequent prognostic survival, pathway enrichment, and immune infiltration. Relevant experimental methods could explain the effect of TAGLN2 expression on tumor cell proliferation, migration, invasion, and apoptosis. Apoptosis, proliferation, Epithelial-to-Mesenchymal Transition (EMT), and PI3K/AKT signaling pathway-related protein expression were determined through western blotting. In the TCGA + GTEx database, mRNA-TAGLN2 expression was clearly increased in pan-cancer tissues, and the same result was found in ccRCC patients based on KIRC analysis results. In addition, TAGLN2 was associated with poor clinical stage, pathological grade, and survival prognosis. TAGLN2 is highly expressed in ccRCC tissues and in vitro TAGLN2 silencing of cells inhibits the proliferation, migration, invasion, and EMT of ccRCC cancer cells. Furthermore, TAGLN2-related differential genes enriched in the PI3K/AKT signaling pathway were negatively regulated after TAGLN2 silencing. Moreover, TAGLN2 may promote tumor immune escape and increase the risk of distant metastasis in immune infiltration-related analyses. TAGLN2 can be used as a single indicator to explain the survival probability of patients with ccRCC. In vitro TAGLN2 silencing inhibited the malignant properties of ccRCC by blocking the PI3K/AKT signaling pathway. In addition, TAGLN2 contributes to tumor immune escape and may be a potential therapeutic target for ccRCC.

Identification of stemness index-related long noncoding RNA SNHG12 in human bladder cancer based on WGCNA.

BACKGROUND: Cancer stem cells (CSCs) have an key role in the beginning, progression and treatment of bladder cancer. In the current study, our target was to identify CSCS-related genes in bladder cancer. METHODS: Bladder cancer (BLCA) transcriptome data were acquired from The Cancer Genome Atlas (TCGA) database. WGCNA was used to screen genes connected with the mRNA expression-based stemness index (mRNAsi).Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the biological function of mRNAsi-related genes. Univariate Cox regression and LASSO Cox regression algorithms were applied to build a risk score model. Additionally, a ceRNA regulatory netwok based on key mRNAsi-related genes was established via TargetScan, miRDB, miRTarBas and miRcode database,and lncRNA SNHG12 was selected for further in vitro and invivo functional assays. RESULTS: Between BLCA and normal samples were identified 1560 differentially expressed genes (DEGs).845 DEGs were most significantly associated with mRNAsi according to WGCNA analysis, which were mainly enriched in GO terms and KEGG pathways related to cell proliferation. Univariate Cox regression and LASSO Cox regression algorithms screened 25 mRNAsi-related genes to construct the risk score model with the significant ability to estimate prognosis of BLCA patients. A ceRNA network, including 8 lncRNA, 11 miRNA and 9 mRNAsi-related mRNA, was constructed.We found that lncRNAs ADAMTS9-AS1 and SNHG12 were observably related to the survival of BLCA patients. To verify this finding, we selected SNHG12 for further study. RT-PCR experiments revealed that SNHG12 was high expression in both bladder cancer tissues and cells.SNHG12 promoted proliferation, invasion, migration, apoptosis and stemness of bladder cancer cells in vitro and tumour proliferation in vivo. CONCLUSION: Our study identified 25 biomarkers associated with stemness indices in BLCA and established a ceRNA network based on key mRNAsi-related genes.SNHG12 promoted BLCA proliferation, invasion, migration, apoptosis and stemness in vitro. It was also showed that SNHG12 promoted tumour growth.

High expression of eIF4A1 predicts unfavorable prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a worldwide malignancy with high morbidity and mortality. Translation initiation factor 4A1 (eIF4A1), which is an ATP-dependent RNA helicase as a part of eIF4F complex, has been linked to malignant transformation and progression, and a variety of cancers display dysregulation of this enzyme. However, its role in ccRCC remains unclear. In our study, we examined its potential effects in ccRCC. METHODS: Based on Proteomic data, TCGA and ONCOMINE database, RCC cell lines and tissues, the expression of eIF4A1 between ccRCC and normal tissues were investigated. A correlation was evaluated between the prognostic model for OS and ccRCC progression. Analysis of functional enrichment and PPI network were performed. After examining differentially expressed genes between the eIF4A1 high and low-expression groups, we performed GSEA analysis. Furthermore, we investigated immune cell infiltration of eIF4A1. Then we determined eIF4A1 functions in the establishment and maintenance of cell viability, migration and invasion of cell lines. Flow cytometry was utilized to detect cell cycle. RESULTS: The eIF4A1 was up-regulated in ccRCC tissues and cell lines. An increased level of eIF4A1 was linked to lower survival rates and impaired immunity. Depletion of eIF4A1 could arrest tumor cells in G1 phase, so as to seriously limit cell proliferation and weaken the capacity of cell migration. CONCLUSION: ccRCC patients with high eIF4A1 expression are at increased risk of poor prognosis, furthermore eIF4A1 plays a prominent role in facilitating tumor cell proliferation and migration which may further be a potential prognostic biomarker and therapeutic target.

Quantitative proteomic analysis reveals sophisticated metabolic alteration and identifies FMNL1 as a prognostic marker in clear cell renal cell carcinoma.

Purpose: In this study, we have undertaken the whole proteomic analysis and got a better understanding of biological processes involved in the development and progression of ccRCC. We hope promising biomarkers can be uncovered to facilitate early diagnosis, predict the prognosis and progression, more importantly, to be applied as potential therapeutic targets. Experimental design: Fresh frozen tissue samples were surgically resected from patients with local or locally advanced ccRCC. Trypsin digested proteins were analyzed using TMT-based LC-MS/MS proteomic approach, followed by bioinformatic analysis. A potential prognostic marker FMNL1 was chosen to be validated in TCGA_KIRC datasets (n=525 and 72), further validation sets (n=10 and 10) and expanded validation sets (n=81 and 16). The effects of FMNL1 on proliferation, migration and invasion were determined by colony formation, wound healing, and transwell assays in 786-O and Caki-1 cells in vitro study. Results: A total of 657 differentially expressed proteins were identified and quantified between ccRCC and adjacent normal tissues (p-value<0.05, FC>2 or<1/2), of which 186 proteins were up-regulated and 471 proteins were down-regulated. Bioinformatic analysis showed enriched metabolic biological processes and pathways. Univariate and multivariate analysis defined FMNL1 as an independent negative prognostic marker in the TCGA datasets. High expression of FMNL1 correlated significantly with tumor stage and distant metastasis (P<0.05) both in the TCGA-KIRC datasets and expanded validation sets. Kaplan-Meier survival curve illustrated that the patients with high FMNL1 protein level had shorter OS time in the expanded validation sets (p=0.0273). In vitro experiments presented the functional effects of FMNL1 knockdown on the inhibition of proliferation, migration and invasion in cancer cell lines. Conclusion and clinical relevance: The proteomic results uncovered sophisticated metabolic reprogramming of ccRCC and indicated that the upregulation of rate-limiting enzymes in glycolysis and mitochondrial impairment may be the cause of metabolic reprogramming in ccRCC. Moreover, FMNL1 has been identified as a promising prognostic marker, and knockdown of FMNL1 could inhibit ccRCC cell proliferation, migration and invasion, which might be used as a new effective therapeutic strategy to inhibit the progression of ccRCC.

Li-ESWT treatment reduces inflammation, oxidative stress, and pain via the PI3K/AKT/FOXO1 pathway in autoimmune prostatitis rat models.

BACKGROUND: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated. OBJECTIVE: To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS. MATERIALS AND METHODS: According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li-ESWT group (LPS-induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis. RESULTS: Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1ß, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all p < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both p < 0.05). Moreover, the Li-ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway. DISCUSSION AND CONCLUSIONS: Li-ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity-induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.

Comparison of open and intracorporeal modified ureterosigmoidostomy (Mainz II) after laparoscopic radical cystectomy with bladder cancer.

OBJECTIVE: To compare perioperative and oncologic outcomes of open modified ureterosigmoidostomy urinary diversion (OMUUD) and intracorporeal modified ureterosigmoidostomy urinary diversion (IMUUD) following laparoscopic radical cystectomy (LRC). PATIENTS AND METHODS: We retrospectively reviewed our single institutional collected database patients undergoing LRC from October 2011 to October 2019. The perioperative characteristics were compared between OMUUD and IMUUD, and overall survival (OS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. RESULTS: Overall, 84 patients were included. OMUUD and IMUUD were performed in 63 (75%) and 21 (25%) patients, respectively. IMUUD patients demonstrated shorter postoperative length of stay (16.24 ± 3.91 days vs. 18.98 ± 7.41 days, P = 0.033), similar operation time (498.57 ± 121.44 vs. 462.24 ± 99.71, P = 0.175), similar estimated blood loss [400 (200-475) ml vs. 400 (200-700) ml, P = 0.095], and similar overall complication rate within 30 days (19.05% vs. 25.40%, P = 0.848) and 90 days (23.81% vs. 17.46%, P = 0.748). Complete urinary control rate was 87.3% (55/63) in the OMUUD group. In IMUUD, the complete urinary control rate was 90.5% (19/21). There was no significant difference in OS (χ2 = 0.015, P = 0.901) and PFS (χ2 = 0.107, P = 0.743) between the two groups. CONCLUSION: IMUUD postoperative recovery is faster; other perioperative outcomes and oncology results are not significantly different with OMUUD. It is indicated that IMUUD can be utilized safely and effectively in the urinary diversion after LRC.

A novel tetrapeptide fluorescence sensor for early diagnosis of prostate cancer based on imaging Zn2+ in healthy versus cancerous cells.

Zinc as a biomarker can be used to diagnose the early stage prostate cancer, while ZIP1 protein, a zinc transporter is significantly down-regulated in prostate cancer cells. This behavior leads to the apparent alteration of the enrichment ability for zinc between early prostate cancer tissues and healthy tissues. This difference inspires us to develop a novel Zn2+ sensor that applies to the clinic diagnosis of early prostate cancer. We designed a tetrapeptide sensor H2L (Dansyl-Gly-Pro-Trp-Gly-NH2) according to the photo-induced electron transfer principle (PET), and it performed adequately in Zn2+ imaging of prostate cell lines. Based on the assessment of Zn2+ enrichment ability, there was distinctly lower Zn2+ concentrate in prostate cancer cell lines than healthy prostate epithelial cells. Furthermore, H2L displayed high sensitivity with a detection limit as low as 49.5 nM, and high specificity for Zn2+ detection. Also the low toxicity and the superior cell permeability of H2L made the imaging of Zn2+ ions detection safe and rapid. We expect that H2L to be a powerful tool for early diagnosis of prostate cancer and a good indicator for the precise resection of cancer tissue during surgery.

Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA.

BACKGROUND: Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Urothelial cancer associated 1 (UCA1) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the molecular mechanism of UCA1 in renal cancer is still needed to further explore. METHODS: The relative expression level of UCA1 was determined by Real-Time qPCR in a total of 88 patients with urothelial renal cancer and in different renal cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of UCA1 and miR-182-5p on renal cancer cell proliferation, migration, apoptosis and tumorigenicity. Comprehensive transcriptional analysis, dual-luciferase reporter assay and western blot etc. were performed to explore the molecular mechanisms underlying the functions of UCA1. RESULTS: In this study, we found that UCA1 was significantly up-regulated in renal cancer. Moreover, increased UCA1 expression was positively correlated with differentiation and advanced TNM stage. Further experiments demonstrated that knockdown of UCA1 inhibited malignant phenotypes and Notch signal path of renal cancer cells, and miR-182-5p was reverse function as UCA1. UCA1 functioned as a miRNA sponge to positively regulate the expression of Delta-like ligand 4(DLL4) through sponging miR-182-5p and subsequently promoted malignant phenotypes of renal cancer cells, thus UCA1 playing an oncogenic role and miR-182-5p as an antioncogenic one in renal cancer pathogenesis. CONCLUSION: UCA1-miR-182-5p-DLL4 axis is involved in proliferation and progression of renal cancer. Thus, this study demonstrated that UCA1 plays a critical regulatory role in renal cancer cell and UCA1 may serve as a potential diagnostic biomarker and therapeutic target of renal cancer.

MicroRNA-508 is downregulated in clear cell renal cell carcinoma and targets ZEB1 to suppress cell proliferation and invasion.

Recent studies have identified several microRNAs (miRNAs/miRs) that are dysregulated in clear cell renal cell carcinoma (ccRCC), and their dysregulation may serve important roles in the occurrence and development of ccRCC. Therefore, understanding the expression pattern and functional roles of miRNAs in ccRCC may facilitate the identification of novel therapeutic targets for the treatment of ccRCC. In the current study, reverse transcription-quantitative polymerase chain reaction was used to determine miR-508 expression levels in ccRCC tissue samples and cell lines. The cell counting kit-8 and in vitro Transwell invasion assays were used to examine the effects of miR-508 overexpression on ccRCC cell proliferation and invasion, respectively. In addition, bioinformatics analysis and dual-luciferase reporter gene assays were used to investigate the underlying mechanism of miR-508 in ccRCC cells. Furthermore, the regulatory role of miR-508 on zinc finger E-box-binding homeobox 1 (ZEB1) mRNA and protein expression in ccRCC cells was investigated using RT-qPCR and western blot analysis, respectively. Additionally, the association between miR-508 and ZEB1 expression in ccRCC tissue samples was examined. Rescue experiments were performed to determine whether the tumor suppressive effects of miR-508 may be mediated by ZEB1 in ccRCC cells. The results of the current study demonstrated that miR-508 expression was significantly downregulated in ccRCC tissue samples and cell lines. In addition, miR-508 overexpression significantly decreased the proliferation and invasion of ccRCC cells. ZEB1 was identified as a direct target gene of miR-508 in ccRCC cells and the relative expression level of ZEB1 mRNA was significantly increased in ccRCC tissue samples. Furthermore, a negative correlation between miR-508 and ZEB1 expression was identified in ccRCC tissues. ZEB1 knockdown exhibited a functional role similar to miR-508 overexpression in ccRCC cells, and restoration of ZEB1 expression significantly reversed the inhibitory effects of miR-508 on the malignant phenotype of ccRCC cells. Taken together, the results of the current study demonstrated that miR-508 may serve a tumor suppressive role in ccRCC via direct targeting of ZEB1. MiR-508 may present a novel and efficient therapeutic target for the treatment of patients with ccRCC.

A sequential and reversibility fluorescent pentapeptide probe for Cu(II) ions and hydrogen sulfide detections and its application in two different living cells imaging.

In this study, we report a sequential and reversibility fluorescent probe (DP5) based on pentapeptide conjugated with dansyl groups using the solid phase peptide synthesis (SPPS) technology. DP5 showed immediate "turn off" response toward Cu2+ ions at an excitation wavelength of 330 nm with detection limits of 23.5 nM. The 2:1 binding ratio between DP5 and Cu2+ were confirmed using Job's plot method and fluorescence titration study, and DP5-Cu complex was observed with an association constant of 6.76 × 108 M-2. As designed, DP5-Cu complex as a promising analytical probe exhibited highly selective for H2S detection in aqueous solutions. The detection limit for H2S was obtained to be 17.2 nM, and lower than EPA and WHO guidelines. In addition, the reversibility and cyclicity were imparted to the DP5 during the detection of Cu2+ and H2S, and cycle effect is very good. Furthermore, DP5 displayed better biocompatibility and low biotoxicity, and sequential fluorescence "on-off-on" responses of DP5 to Cu2+ and H2S were successfully applied in two different living cells.

Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis.

OBJECTIVE: This study investigated the association between abnormal matrix metalloproteinase-9 (MMP-9) expression and bladder cancer (BC) development. MATERIALS AND METHODS: In a retrospective analysis, this study used tissue samples derived from 92 patients pathologically diagnosed with BC (experimental group), who were hospitalized between September 2012 and June 2014 at the Urinary Surgery of Department of Urology, Lanzhou University Second Hospital. As controls (control group), 63 normal pericancerous bladder mucosal tissues (3 cm distant form edge of BC foci) with confirmed pathology were selected from the same time period. Immunohistochemistry was employed to detect MMP-9 protein expression in the tissues and enzyme-linked immunosorbent assay was performed to measure MMP-9 protein levels in tissue samples of patients and control subjects. Finally, a meta-analysis was conducted to understand the overall impact of MMP-9 on BC pathogenesis. STATA 12.0 software (Stata Corp, College Station, TX, USA) was used for all statistical analyses. RESULTS: The MMP-9 positive expression rate in tissue samples and MMP-9 levels were significantly greater in the experimental group compared to the control group (both P < 0.001). The frequency of MMP-9 positive status showed statistically significant differences between G1 (low-grade) and G3 (high-grade) (P < 0.001), between G2 and G3 (P < 0.05), and between G1/G2 and G3 (P = 0.001). Our meta-analysis findings provided further evidence that MMP-9 positive expression status and MMP-9 levels in the experimental group were significantly higher than the control group (positive expressions: Odds ratio [OR] = 18.59, 95% confidence interval [95% CI] = 11.63-29.71, P < 0.001; expression levels: Standard mean difference = 1.51, 95%CI = 0.63-2.39, P = 0.001). The positive expression status of MMP-9 was notably lower in G1/G2 compared to G3 (OR = 0.24, 95%CI = 0.15-0.36, P < 0.001). CONCLUSION: Our study demonstrated that both positive expression status in tumor tissue and expression levels of MMP-9 are significantly elevated in BC patients and correlate with disease progression. Thus, MMP-9 can serve as a biomarker to determine the degree of BC malignancy.

Melamine Poisoning Pediatric Urolithiasis Treatment in Gansu, China 5-Year Follow-up Analysis.

OBJECTIVE: To investigate the clinical characteristics of urolithiasis, retrospectively, in children who ingested melamine-poisoned formula as infants, and report a 5-year follow-up analysis. MATERIALS AND METHODS: Clinical data on 207 patients (mean ± standard deviation, 13.6 ± 8.0 months) with melamine-induced urolithiasis were retrospectively analyzed. Patients were subdivided into 2 groups according to treatment. A 5-year follow-up study was conducted with 95.7% (198 of 207) of the children. Ultrasonography, renal function evaluation, and urinalysis were analyzed. RESULTS: A total of 149 (72.0%) patients accepted conservative treatment. Fifty-eight (28.0%) patients accepted surgical intervention after conservative treatment proved ineffective. Of the 48 patients in whom retrograde ureteral catheterization was performed, 33 discharged the stone successfully, 4 had residual stones, 2 were switched to percutaneous nephrolithotripsy, and 9 underwent ureteroscopic lithotripsy. Six patients underwent extracorporeal shock wave lithotripsy, and other 4 patients underwent ureteral lithectomy. The age of onset, clinical presentations, size and location of stones, renal function, and mean time of hospitalization in patients with surgical intervention were significantly different from those of patients who accepted conservative treatment only (P < .001). The main component of the 12 melamine-contained stone samples was urate. The results of 5-year follow-up (mean ± standard deviation, 72.7 ± 4.1 months) study in 198 children did not show any significant difference of stone residue, renal function, and urinalysis between 2 groups. CONCLUSION: If the stones were treated appropriately in patients with melamine-induced urolithiasis, there is no medium-term risk for stone formation. Still, a longer time follow-up study is required to determine if there is any long-term poisonous effect on these patients.