Velocity and Temperature Simulation for a Cylindrical Regenerative Thermal Oxidizer.

The cylindrical regenerative thermal oxidizer (CRTO) came into being later than the three-chamber regenerative thermal oxidizer (TRTO). Compared with TRTO, CRTO has a smaller size and a larger regenerator volume for absorbing and releasing heat. There are few studies on CRTO despite its numerous applications. A CRTO was selected in industrial applications for simulation research. The velocity and temperature of the CRTO were investigated after error analysis of industrial and simulated data. It was found that the velocity and temperature in the regenerative chamber had obvious stratification and gradients after homogenization by the regenerator unit. The velocity and temperature distribution in the oxidation chamber were independent of the position of the CRTO inlet and outlet or the structure below the regenerator, and there were identical periodic changes in each period. A TRTO with primary parameters as those of the CRTO was employed for comparison. The time of the intake and exhaust periods of a CRTO regenerative chamber were 30 s longer than those of a TRTO. The regenerator volume of heat storage used by CRTO for heat exchange increased by 1/6 compared to that of TRTO at the same total regenerator volume. Simulation shows that CRTO had a more uniform velocity and temperature in the regenerative chamber compared to those in TRTO, increasing by approximately 2%; the thermal efficiency is higher, with an average increase of about 3%.

GALNT12 suppresses the bone-specific prostate cancer metastasis by activating BMP pathway via the O-glycosylation of BMPR1A.

Bone metastasis caused the majority death of prostate cancer (PCa) but the mechanism remains poorly understood. In this present study, we show that polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) suppresses bone-specific metastasis of PCa. GALNT12 suppresses proliferation, migration, invasion and cell division ability of PCa cells by activating the BMP pathway. Mechanistic investigations showed that GALNT12 augments the O-glycosylation of BMPR1A then actives the BMP pathway. Activated BMP signaling inhibits the expression of integrin αVß3 to reduce the bone-specific seeding of PCa cells. Furthermore, activated BMP signaling remolds the immune microenvironment by suppressing the STAT3 pathway. Our results of this study illustrate the role and mechanism of GALNT12 in the process of bone metastasis of PCa and identify GALNT12 as a potential therapeutic target for metastatic PCa.

Small ankyrin 1 (sANK1) promotes docetaxel resistance in castration-resistant prostate cancer cells by enhancing oxidative phosphorylation.

Docetaxel (DTX) plays an important role in treating advanced prostate cancer (PCa). However, nearly all patients receiving DTX therapy ultimately progress to DTX resistance. How to address DTX resistance in PCa remains a key challenge for all urologists. Small ankyrin 1 (sAnk1) is an integral membrane protein in the endoplasmic reticulum. In the present study, we identified that sAnk1 is upregulated in PCa tissues and is positively associated with DTX therapy resistance in PCa. Further investigation demonstrated that overexpression of sAnk1 can significantly increase the DTX-resistant ability of PCa cells in vitro and in vivo. In addition, overexpression of sAnk1 could enhance oxidative phosphorylation (OXPHOS) levels in PCa cells, which was consistent with the higher OXPHOS levels observed in DTX-resistant PCa cells as compared to DTX-sensitive PCa cells. sAnk1 was also found to interact with polypyrimidine-tract-binding protein (PTBP1), an alternative splicing factor, and suppressed PTBP1-mediated alternative splicing of the pyruvate kinase gene (PKM). Thus, overexpression of sAnk1 decreased the ratio of PKM2/PKM1, enhanced the OXPHOS level, and ultimately promoted the resistance of PCa cells to DTX. In summary, our data suggest that sAnk1 enhances DTX resistance in PCa cells.

Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies.

Microcystin-leucine-arginine (MC-LR) is positively linked with multiple cancers in humans. However, the association between MC-LR and the risk and prognosis of prostate cancer has not been conducted in epidemiological studies. No reported studies have linked MC-LR exposure to the poor prognosis of prostate cancer by conducting experimental studies. The content of MC-LR was detected in most of the aquatic food in wet markets and supermarkets in Nanjing and posed a health risk for consumers. MC-LR levels in both prostate cancer tissues and serum were significantly higher than controls. The adjusted odds ratio (OR) for prostate cancer risk by serum MC-LR was 1.75 (95%CI: 1.21-2.52) in the whole subjects, and a positive correlation between MC-LR and advanced tumor stage was observed. Survival curve analysis indicated patients with higher MC-LR levels in tissues exhibited poorer overall survival. Human, animal, and cell studies confirmed that MC-LR exposure increases the expression of estrogen receptor-α (ERα) and promotes epithelial-mesenchymal transition (EMT) in prostate cancer. Moreover, MC-LR-induced decreased E-cadherin levels, increased vimentin levels, and increased migratory and invasive capacities of prostate cancer cells were markedly suppressed upon ERα knockdown. MC-LR-induced xenograft tumor growth and lung metastasis in BALB/c nude mice can be effectively alleviated with ERα knockdown. Our data demonstrated that MC-LR upregulated vimentin and downregulated E-cadherin through activating ERα, promoting migration and invasion of prostate cancer cells. Our findings highlight the role of MC-LR in prostate cancer, providing new perspectives to understand MC-LR-induced prostatic toxicity.

Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p.

The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer stemness in RCC. Further investigation revealed that CAFs could enhance cancer stemness through delivering exosomes to RCC cells, and miR-181d-5p was identified as the critical exosomal miRNA in CAF-secreted exosomes by small RNA sequencing and subsequent screening assays. Mechanistically, exosomal miR-181d-5p transferred from CAFs to RCC cells directly suppressed the expression of ring finger protein 43 (RNF43) and activated Wnt/ß-catenin signaling pathway, thus promoted cancer stemness and tumor progression. Overexpression of RNF43 strongly suppressed stemness properties and the effects could be reverted by miR-181d-5p. Overall, our findings revealed a crucial mechanism by which CAF-secreted exosomal miRNAs to enhance cancer stemness and thus promote RCC progression, suggesting a new avenue based on CAF-secreted miRNAs for more effective targeted therapies.

Environmental exposure to microcystin-LR increases the risks of urinary bladder proliferation and carcinogenesis: Evidence from case control, animal, and in vitro studies.

To date, no reported studies have explored the impacts of microcystin-LR (MC-LR) on bladder tissues, and even the occurrence of bladder cancer. The current study explores the role of MC-LR in the development of bladder cancer through human observation and experimental research. In the population study, the odds ratio of bladder cancer for MC-LR was 6.073 (95 % CI, 2.117-17.422) after adjusting interference confounders. MC-LR is mainly located in the nucleus of epithelial cells in bladder cancer tissues instead of normal tissues. A positive association was observed between MC-LR and advanced tumor stage in serum and tissues. The animal study confirmed that prolonged MC-LR treatment promoted the bladder cancer phenotype accompanied by urinary bladder proliferation. In vitro, we indicated that MC-LR activated the PI3K/AKT/GSK3ß/Cyclin D1 and JAK2/STAT3/Bcl2 signaling pathways to induce the growth of SV-HUC-1 cells. Moreover, MC-LR promoted the angiogenesis of SV-HUC-1 cells through PI3K/AKT/mTOR/HIF-1α/VEGF pathway. Our study provided the first evidence that prolonged MC-LR treatment increases the incidence of bladder cancer from human investigations, mice models, and in vitro studies, implying the profound importance of the investigation of MC-LR for public health.

circCYP24A1 promotes Docetaxel resistance in prostate Cancer by Upregulating ALDH1A3.

BACKGROUND: Docetaxel (DTX) is the most widely prescribed first-line chemotherapy for advanced prostate cancer (PCa). Unfortunately, DTX resistance invariably emerges, leading to worse prognosis of PCa. Growing evidence has shown that circRNAs had complex spatiotemporal specificity during the tumor development and oncogenesis. This study was designed to investigate the biological functions and possible molecular mechanisms of circRNAs in DTX resistance of PCa. METHODS: circRNAs in established DTX-resistant DU145 cell line were identified by RNA sequencing. Biological function of circCYP24A1 was verified in vitro and in vivo. The potential role of circCYP24A1 in the development of DTX-resistant PCa was investigated via dual-luciferase reporter assays, RIP assays and RNA pull-down assays. Univariate and multivariate logistic regression analyses was used to predict DTX-chemotherapy response based on patients' clinical and biological information. RESULTS: CircCYP24A1 was identified to be upregulated in DTX-resistant DU145 cells. Upregulated circCYP24A1 was found to suppress the DTX chemosensitivity in vitro and in vivo. Furthermore, we found that circCYP24A1 promoted DTX resistance in PCa via regulating ALDH1A3 expression by sponging miR-1301-3p and activating PI3K/AKT/mTOR signaling pathway. Statistical analyses elucidated that circCYP24A1 was an independent risk factor to predict DTX response (OR = 0.165; 95% CI: 0.038-0.723; P = 0.017). CONCLUSIONS: This study demonstrated that circCYP24A played an essential role in DTX resistance in PCa, suggesting that circCYP24A1 could be a promising biomarker to predict DTX response and a potential therapeutic target in PCa patients resistant to DTX chemotherapy.

Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation.

Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific metastasis in renal cancer. LAPTM5 sustains self-renewal and cancer stem cell-like traits of renal cancer cells by blocking the function of lung-derived bone morphogenetic proteins (BMPs). Mechanistic investigations showed that LAPTM5 recruits WWP2, which binds to the BMP receptor BMPR1A and mediates its lysosomal sorting, ubiquitination and ultimate degradation. BMPR1A expression was restored by the lysosomal inhibitor chloroquine. LAPTM5 expression could also serve as an independent predictor of lung metastasis in renal cancer. Lastly, elevation of LAPTM5 expression in lung metastases is a common phenomenon in multiple cancer types. Our results reveal a molecular mechanism underlying lung-specific metastasis and identify LAPTM5 as a potential therapeutic target for cancers with lung metastasis.

Pan-cancer analysis identifies LMNB1 as a target to redress Th1/Th2 imbalance and enhance PARP inhibitor response in human cancers.

BACKGROUND: Emerging evidence suggests that LMNB1 is involved in the development of multiple cancer types. However, there is no study reporting the potential role of LMNB1 in a systematic pan-cancer manner. METHODS: The gene expression level and potential oncogenic roles of LMNB1 in The Cancer Genome Atlas (TCGA) database were analyzed with Tumor Immune Estimation Resource version 2 (TIMER2.0), Gene Expression Profiling Interactive Analysis version 2 (GEPIA2), UALCAN and Sangerbox tools. Pathway enrichment analysis was carried out to explore the possible mechanism of LMNB1 on tumorigenesis and tumor progression. The therapeutic effects of LMNB1 knockdown combined with PARP inhibition on human cancers were further investigated in vitro. RESULTS: LMNB1 upregulation is generally observed in the tumor tissues of most TCGA cancer types, and is verified in kidney renal clear cell carcinoma using clinical specimens of our institute. High level of LMNB1 expression usually predicts poor overall survival and disease free survival for patients with tumors. Mechanically, LMNB1 level is positively correlated with CD4+ Th2 cell infiltration and DNA homologous recombination repair gene expression. In vitro experiments reveal that targeting LMNB1 has a synergistic effect on prostate cancer with PARP inhibitor treatment. CONCLUSIONS: LMNB1 is a biomarker of CD4+ Th2 cell infiltration and DNA homologous recombination repair in human cancers. Blockage of LMNB1 combined with PARP inhibitor treatment could be a promising therapeutic strategy for patients with cancers.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

KLF2 inhibits cancer cell migration and invasion by regulating ferroptosis through GPX4 in clear cell renal cell carcinoma.

The metastatic dissemination and underlying mechanisms of clear cell renal cell carcinoma (ccRCC) remain insufficiently understood. In this study, we identified the essential role of KLF2 in suppressing the metastasis of ccRCC. Downregulation of KLF2 detected by immunohistochemistry in primary metastatic ccRCC was remarkably related to poor clinical outcomes. Overexpression of KLF2 in vitro inhibited growth, migration and invasion of RCC cells. Analysis of clinical specimens revealed that there is a close correlation between KLF2 and GPX4 in ccRCC. Mechanistically, KLF2 deficiency is sufficient to inhibit ferroptosis on account of the impairment of transcriptional repression of GPX4 and thus promotes the migration and invasion of RCC cells. Reverting KLF2 expression in vivo decreased pulmonary metastatic lesions and prolonged life span of mice, whereas GPX4 overexpression reversed these properties. Overall, our results established a novel critical pathway that drives human ccRCC invasion and metastasis, which could be a promising target regarding to the therapies of advanced ccRCC in the clinic.

SOX9 in prostate cancer is upregulated by cancer-associated fibroblasts to promote tumor progression through HGF/c-Met-FRA1 signaling.

Transcription factor SOX9 was a biomarker for prostate cancer (Pca) with poor prognosis. Nevertheless, the regulatory mechanism underlying SOX9 upregulation still remains unclear. Several cytokines have been reported to be involved in the regulation of SOX9, suggesting that cancer-associated fibroblasts (CAFs), one of the main sources of secreted factors in the tumor microenvironment (TME), may play a role in regulating SOX9 expression. Herein, an in vitro model of paracrine interaction between primary CAFs and Pca cells was applied to investigate the molecular mechanism of SOX9 upregulation during Pca progression. The regulatory axis was validated by in vivo experiments and The Cancer Genome Atlas data. Conditional medium of CAFs (CAF-CM) upregulated the expression of SOX9, which was mutually proved to be essential for CAF-induced tumor progression. Further analysis showed that hepatocyte growth factor (HGF) secreted by CAFs was responsible for SOX9 elevation in Pca cells, via the activation of c-Met signaling. Mechanistically, HGF/c-Met signaling specifically activated MEK1/2-ERK1/2 pathway, which induced phosphorylation and upregulation of FRA1, which then transcriptionally upregulated SOX9 by binding to the promoter of SOX9 gene. Moreover, we identified that HGF/c-Met-ERK1/2-FRA1-SOX9 axis was relatively conserved between human and mouse species by validating in mouse Pca cells. Our results reveal a novel insight into the molecular mechanism that SOX9 in Pca cells is promoted by CAFs through HGF/c-Met-ERK1/2-FRA1 axis. Furthermore, SOX9 may serve as an alternative marker for the activated HGF/c-Met signaling to enroll the optimal Pca patients for HGF/c-Met inhibition treatment, since it is much more stable and easier to detect.

Chronic exposure to microcystin-LR increases the risk of prostate cancer and induces malignant transformation of human prostate epithelial cells.

Microcystins-LR (MC-LR) acts as a possible carcinogen for humans and causes a serious risk to public environmental health. The current study aimed to evaluate the interaction between MC-LR exposure and prostate cancer development and elucidate the underlying mechanism. In this study, mice were exposed to MC-LR at various doses for 180 days. MC-LR was able to induce the progression of prostatic intraepithelial neoplasia (PIN) and microinvasion. Furthermore, MC-LR notably increased angiogenesis and susceptibility to prostate cancer in vivo. In vitro, over 25 weeks of MC-LR exposure, normal human prostate epithelial (RWPE-1) cells increased secretion of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and colony formation, features typical for cancer cells. These MC-LR-transformed prostate epithelial cells displayed increased expression of forkhead box M1 (FOXM1) and cyclooxygenase-2 (COX-2); abrogation of FOXM1 or COX-2 activity by specific inhibitors could abolish the invasion and migration of MC-LR-treated cells. In conclusion, we have provided compelling evidence demonstrating the induction of a malignant phenotype in human prostate epithelial cells and the in vivo development of prostate cancer by exposure to MC-LR, which might be a potential tumor promoter in the progression of prostate cancer.

Internal cross-linked polymeric nanoparticles with dual sensitivity for combination therapy of muscle-invasive bladder cancer.

BACKGROUND: Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment. METHODS: The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated. RESULTS: The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment. CONCLUSION: A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.

Unbiased enrichment of urine exfoliated cells on nanostructured substrates for sensitive detection of urothelial tumor cells.

BACKGROUND: Early detection of urothelial carcinoma (UC) by noninvasive diagnostic methods with high accuracy is still underscored. This study aimed to develop a noninvasive assay incorporating both enrichment of urine exfoliated cells and immunoassays for UC detection. METHODS: Polystyrene dishes were exposed to oxygen plasma and modified with 3-aminopropyltriethoxysilane to prepare amine-functionalized nanostructured substrates (NS). Performance characterization of NS was evaluated by atomic force microscope and X-ray photoelectron spectroscopy. Urine exfoliated cells were captured by NS and then immunostained to detect urinary tumor cells (UTCs), which was called UTC assay. The receiver operating characteristic (ROC) curve, area under ROC curve (AUC), and Youden index were used to find the cutoff value of UTC assay. ROC analysis and McNemar test were used to compare the diagnostic accuracy of UTC assay with cytology. Kappa test was used to analyze the agreement of UTC assay and cytology with pathological diagnosis. RESULTS: Nanostructured substrates had good cell binding yields of nucleated cells and tumor cells. CK20+ CD45- CD11b- cells were considered as UTCs. UTC number ≥ 1 per sample could be considered as a positive result. By AUC and Kappa analysis, UTC assay showed good performance in UC detection. McNemar test demonstrated that UTC assay had a superior sensitivity even in low-grade subgroup and a similar specificity compared to cytology in UC diagnosis. CONCLUSIONS: Nanostructured substrates could be used to enrich the exfoliated cells from urine samples. UTC assay with NS has the potential to play a role in UC detection. The value of this assay still needs additional validation by large, multi-center studies.

Circular RNA circSLC8A1 acts as a sponge of miR-130b/miR-494 in suppressing bladder cancer progression via regulating PTEN.

BACKGROUND: Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs formed by a covalently closed loop, and increasing evidence has revealed that circRNAs play crucial functions in regulating gene expression. CircSLC8A1 is a circRNA generated from the SLC8A1 gene. Currently, the role and underlying molecular mechanisms of circSLC8A1 in bladder cancer remain unknown. METHODS: The differentially expressed circRNAs were identified from RNA-sequencing data, and circSLC8A1 was determined as a new candidate circRNA. qRT-PCR was used to detect the expression of circRNAs, miRNAs and mRNAs in human tissues and cells. RNA pull-down assay and luciferase reporter assay were used to investigate the interactions between the specific circRNA, miRNA and mRNA. The effects of circSLC8A1 on bladder cancer cells were explored by transfecting with plasmids in vitro and in vivo. The expression of PTEN was detected by Western blot. The biological roles were measured by wound healing assay, transwell assay, and CCK-8 assay. RESULTS: In the present study, we found that circSLC8A1 was down-regulated in bladder cancer tissues and cell lines, and circSLC8A1 expression was associated with the pathological stage and histological grade of bladder cancer. Over-expression of circSLC8A1 inhibited cell migration, invasion and proliferation both in vitro and in vivo. Mechanistically, circSLC8A1 could directly interact with miR-130b/miR-494, and subsequently act as a miRNA sponge to regulate the expression of the miR-130b/miR-494 target gene PTEN and downstream signaling pathway, which suppressed the progression of bladder cancer. CONCLUSIONS: CircSLC8A1 acts as a tumor suppressor by a novel circSLC8A1/miR-130b, miR-494/PTEN axis, which may provide a potential biomarker and therapeutic target for the management of bladder cancer.

miR-30e-5p suppresses cell proliferation and migration in bladder cancer through regulating metadherin.

Recent studies have suggested that miR-30e-5p is dysregulated in several human carcinomas; however, the mechanism of miR-30e-5p in bladder cancer (BCa) remains unknown. Here, we confirmed that the expression of miR-30e-5p was decreased in human BCa specimens and cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Upregulation of miR-30e-5p decreased the proliferation and migration in T24 and UM-UC-3 cells. Metadherin (MTDH) was a potential target for miR-30e-5p through bioinformatics analysis. Dual-luciferase assays were conducted to validate the interaction between miR-30e-5p and MTDH, which demonstrates that the relative luciferase activity was significantly downregulated after transfected miR-30e-5p mimic compared with control mimic in 293T cells. We also detected that whether silencing of MTDH by using small interfering(si)-MTDH matched effects caused by miR-30e-5p overexpression in BCa cells lines by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assay, and we found the effects of silencing of MTDH same as miR-30e-5p overexpression. Furthermore, we verified that the restoration of MTDH in miR-30e-5p-overexpressed BCa cells rescued the inhibitory effects of miR-30e-5p. In conclusion, these results demonstrated that miR-30e-5p may inhibit BCa cells growth and invasiveness by targeting MTDH and may be a promising therapeutic agent for treating clinical BCa patients.

Preoperative C-reactive protein/albumin ratio predicts outcome of surgical papillary renal cell carcinoma.

Aim: To evaluate the prognostic values of some preoperative inflammation-based factors including C-reactive protein/albumin ratio (CRP/Alb) and platelet level in papillary renal cell carcinoma (PRCC). Materials & methods: A total of 108 PRCC patients underwent partial or radical nephrectomy were retrospectively analyzed. The prognostic values were determined with Kaplan-Meier analysis, univariate and multivariate COX regression models. Results: CRP/Alb and platelet level were both significantly associated with subtype, Fuhrman grade, tumor stage, lymph node invasion, perinephric fat extension, shorter overall survival (OS) and disease-free survival (all p < 0.01). Further, CRP/Alb was an independent prognostic factor for OS (hazard ratio: 9.64, 95% CI: 2.17-23.78; p = 0.003). Conclusion: Relatively higher CRP/Alb independently predicted poorer OS of surgical PRCC patients.

Predictors for immediate recovery of continence following Retzius-sparing robot-assisted radical prostatectomy: a case-control study.

PURPOSE: We evaluated urinary continence in a series of consecutive patients who underwent Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) to identify the preoperative predictors of the return to immediate urinary continence. METHODS: 110 consecutive patients who underwent RS-RARP for clinically localized prostate cancer were retrospectively collected. Patients reported freedom from using safety pad (0 pad/day) within 7 days after removal of urinary catheter were defined as immediate urinary continent. RESULTS: A total of 85 patients (77.27%) were immediate urinary continent after RS-RARP. Patients with immediate urinary continence were significantly younger (66.92 ± 5.73 vs. 69.68 ± 4.99 years, p = 0.031) than those who were incontinent. Furthermore, the prostate volume was significantly smaller (30.90 vs. 44.60 ml, p = 0.001) and preoperative international prostate symptom score (IPSS) was significantly lower (Mild 76.5% vs. 24.0%, Moderate 20.0% vs. 32.0%, and Severe 3.5% vs. 44.0%, p = 0.000) in patients with immediate urinary continence compared with those who were not. On univariable regression analysis, patient's age (OR 0.907, p = 0.035), prostate volume (OR 0.935, p = 0.000), moderate (OR 0.196, p = 0.007), and severe IPSS (OR 0.025, p = 0.000) (compared with mild IPSS) were independent adverse predictors of immediate urinary continence. On multivariable analysis, prostate volume (OR 0.955, p = 0.032) and severe preoperative IPSS (OR 0.044, p = 0.000) (compared with mild IPSS) were independent adverse predictors of immediate urinary continence after RS-RARP. CONCLUSIONS: RS-RARP hastens the recovery of urinary continence after surgery. Prostate volume and severe preoperative IPSS were independent adverse predictors of the return to immediate urinary continence.

TOX3 inhibits cancer cell migration and invasion via transcriptional regulation of SNAI1 and SNAI2 in clear cell renal cell carcinoma.

Studies on the mechanism of clear cell renal cell carcinoma (ccRCC) progression are lacking. In this study, TOX3 was identified as a novel cancer suppressor gene in ccRCC. Hypermethylation of CpG probes in the promoter region was associated with the functional loss of TOX3 in ccRCC cancer tissues. Downregulation of TOX3 mRNA was strongly associated with poor clinical outcomes in ccRCC. Immunohistochemistry confirmed TOX3 was downregulated in primary tumors without metastasis (n = 126) and further downregulated in primary metastatic tumors (n = 23) compared with adjacent noncancerous tissues (n = 92). In vitro, overexpression of TOX3 inhibited RCC cell growth, migration and invasion. Mechanistic investigations showed that TOX3 deficiency facilitates the epithelial-mesenchymal transition due to impairment of transcriptional repression of SNAIL members SNAI1 and SNAI2 and promotes cancer cell migration and invasion. In vivo, restoring TOX3 expression reduced lung metastatic lesions and prolonged survival of mice. TOX3 combined with SNAI1 or SNAI2 predicted overall survival in ccRCC patients. Blockage of this pathway could be a promising therapeutic target for advanced ccRCC.