Interaction between Wnt/ß-catenin signaling pathway and EMT pathway mediates the mechanism of sunitinib resistance in renal cell carcinoma.

BACKGROUND: Targeted drugs are the main methods of RCC treatment. However, drug resistance is common in RCC patients, in-depth study of the drug-resistant mechanism is essential. METHODS: We constructed sunitinib resistant and Twist overexpressed A498 cells, and studied its mechanisms in vitro and in vivo. RESULTS: In cell research, we found that either sunitinib resistance or Twist overexpression can activate Wnt/ß-catenin and EMT signaling pathway, and the sunitinib resistance may work through ß-catenin/TWIST/TCF4 trimer. In zebrafish research, we confirmed the similarity of Twist overexpression and sunitinib resistance, and the promoting effect of Twist overexpression on drug resistance. CONCLUSIONS: Sunitinib resistance and Twist overexpression can activate Wnt/ß-catenin signaling pathway and EMT to promote the growth and metastasis of RCC cells.

LINC00460 Enhances Bladder Carcinoma Cell Proliferation and Migration by Modulating miR-612/FOXK1 Axis.

INTRODUCTION: LincRNA (long intergenic noncoding RNA) has been indicated as a mediator in tumorigenesis of bladder carcinoma. This study was performed to evaluate the role of LINC00460 in bladder carcinoma progression. METHODS: Expression levels of LINC00460 in bladder carcinoma tissues and cell lines were analyzed via qRT-PCR. MTT, EdU (5-ethynyl-2'-deoxyuridine) staining, and colony formation assays were utilized to evaluate cell viability and proliferation. The wound healing assay was performed to evaluate bladder cancer cell migration, and the transwell assay was used to evaluate cell invasion. The microRNA (miRNA) target of LINC00460 and the corresponding target gene were validated via the dual luciferase activity assay. The tumorigenic function of LINC00460 was determined via establishment of a xenotransplanted tumor model. RESULTS: LINC00460 was elevated in bladder carcinoma tissues and cell lines. Elevated LINC00460 was associated with shorter overall survival of bladder carcinoma patients. Overexpression of LINC00460 promoted cell viability, proliferation, invasion, and migration, while silencing of LINC00460 indicated the opposite effect on bladder carcinoma progression. LINC00460 could directly bind to miR-612 and inhibit miR-612 expression. Moreover, LINC00460 expression was negatively correlated with miR-612 in patients with bladder carcinoma. FOXK1 (Forkhead Box K1) was identified as the target of miR-612 and upregulated in patients with bladder carcinoma. Overexpression of FOXK1 attenuated interference of LINC00460-inhibited bladder carcinoma progression. Knockdown of LINC00460 suppressed in vivo bladder carcinoma growth. CONCLUSIONS: LINC00460 promoted bladder carcinoma progression via sponging miR-612 to facilitate FOXK1 expression, suggesting that LINC00460 might have the potential of being explored as a therapeutic target for treatment of bladder carcinoma.

Rubimaillin suppresses proliferation, migration and invasion of prostate cancer cells via the Notch-1/MMP signaling pathway.

This study was aimed to explore the effect of Rubimaillin on the survival, migration, and invasion of prostate cancer cell lines DU145 and PC3, and its mechanism. CCK-8 method was used to detect the effects of different concentrations of rubs (0, 5, 10, 20, 40 and 80 µM) on the activity of DU145 cells and PC3 cells. Transwell cell lab test was used to detect the migration and invasion of cells. Western blot was used to detect Notch-1, MMP-2, MMP-9 and Hes-1 protein levels. The CCK-8 assay showed that Rub inhibited the activity of Du145 and PC3 cells in a concentration dependent manner. When the concentration reached 40 µM, the inhibition reached the maximum. After Rub intervention, the migration and invasion ability of Du145 and PC3 cells decreased significantly, while the expression levels of Notch-1, MMP-2, MMP-9 and Hes-1 protein decreased significantly. Rub can inhibit the growth, migration and invasion of prostate cancer cell line DU145 and PC3. The mechanism may be related to the inhibition of Notch-1, MMP-2, MMP-9 and Hes-1 by Rub.

ALDOLASE A regulates invasion of bladder cancer cells via E-cadherin-EGFR signaling.

Glycolysis and glycogenesis are known to be tightly associated with cancer cell migration. However, their roles in bladder cancer have not been reported. In this study, ALDOLASE A (ALDOA) was identified in a coexpression network generated using glycolysis- and glycogenesis-related genes in Kyoto Encyclopedia of Genes and Genomes. ALDOA was located in the central region in the network, and the cancer genome atlas (TCGA) data suggest that ALDOA expression levels are associated with viability in patients with cancer at the middle and late stages. Bladder cancer cell lines, T24 and RT4, were used to knockdown (sh) or overexpress (OE) ALODA to analyze its role. The sh-ALDOA reduced cell viability, colony formation rate, and invasion cell number; while OE had an opposite effect compared with sh-ALDOA. Further, the sh-ALDOA expression induced E-cadherin level while reduced N-cadherin and vimentin levels. The OE cells reduced E-cadherin and induced N-cadherin and vimentin levels. In addition, epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), and AKT serine/threonine kinase (AKT) phosphorylation levels are all reduced in sh-ALODA while activated in OE cells compared with the control group. But either sh-ALODA or OE did not change total protein levels of EGFR, MAPK, and AKT. To further analyze E-cadherin function in ALDOA regulation on bladder cancer cells, sh-ALDOA and sh-E-cadherin were cotransfected in T24 and RT4 cells. The results indicated that sh-ALDOA and sh-E-cadherin expressions eliminated sh-ALDOA function, resulting similar cell viability, colony formation rate, and invasion cell number with control group. Also, sh-ALDOA and shE-cadherin expressions increased EGFR, MAPK, and AKT phosphorylation levels; and the levels were similar to the control group. But, sh-ALDOA and sh-E-cadherin expressions did not change N-cadherin and vimentin levels, which maintain similar levels with sh-ALDOA-expressing cells. Taken together, these results suggest that ALDOA might play an important function in bladder cancer and its action may be though E-cadherin-EGFR signaling.

Blood cell indices and inflammation-related markers with kidney cancer risk: a large-population prospective analysis in UK Biobank.

Background: Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk. Methods: We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses. Results: During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results. Conclusion: Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals.

Knockdown of Circ_CCNB2 Sensitizes Prostate Cancer to Radiation Through Repressing Autophagy by the miR-30b-5p/KIF18A Axis.

Background: Circular RNAs (circRNAs) have recently emerged as crucial regulatory molecules in prostate cancer (PCa), but few researches focus on the effects of circRNAs on PCa radiosensitivity. The issue will be addressed in this study using circRNA Cyclin B2 (circ_CCNB2) as an object. Materials and Methods: All RNA and protein levels were severally examined using quantitative real-time polymerase chain reaction and Western blot. Colony formation assay and flow cytometry were implemented for detecting cell colony capacity and apoptotic cells, respectively. Cellular migration and invasion abilities were evaluated by transwell assay. The combination between potential target molecules was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The effect of circ_CCNB2 on PCa radiosensitivity in vivo was explored using xenograft models in mice. Results: Circ_CCNB2 was upregulated in irradiation-resistant PCa tissues and cells. Circ_CCNB2 knockdown had promoted effect on the radiosensitivity of irradiation-resistant PCa cells by inhibiting autophagy. Besides, circ_CCNB2 could directly sponge miR-30b-5p, and the promotion of circ_CCNB2 knockdown on PCa radiosensitivity was achieved by elevating miR-30b-5p. MiR-30b-5p enhanced the radiosensitivity of irradiation-resistant PCa cells through repressing the expression of its target kinesin family member 18A (KIF18A). Furthermore, circ_CCNB2 regulated the KIF18A level through targeting miR-30b-5p. Circ_CCNB2 downregulation facilitated PCa radiosensitivity in vivo through inhibiting autophagy by miR-30b-5p/KIF18A. Conclusions: In this study, knockdown of circ_CCNB2 was shown to promote PCa radiosensitivity through autophagy repression by miR-30b-5p/KIF18A axis, developing a molecular resistance mechanism of PCa radiotherapy and a feasible strategy to increase radiosensitivity.

Application of the Improved Clustering Algorithm in Operating Room Nursing Recommendation under the Background of Medical Big Data.

The nursing work in the operating room has the characteristics of long time, strong technicality, and heavy work, which have an important influence on the quality of the operation. Operating room nursing recommendations based on data mining technology can solve a series of practical problems in clinical nursing and nursing management. This paper selects the clustering algorithm in commonly used data mining technology as the research object and actually analyzes the impact of this algorithm in operating room nursing recommendations. At this stage, there is little research on data mining technology in the field of nursing in China. This paper aims to provide new ideas for the field of nursing research by exploring the actual application in the field of nursing.

Isorhamnetin inhibited the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the mitochondrion-dependent intrinsic apoptotic and PI3K/Akt/mTOR pathway.

The present study investigated the effects of Isorhamnetin on two types of prostate cancer cells (androgen-independent and androgen-dependent) and explored its possible mechanisms underlying such effects. Treatment with Isorhamnetin significantly inhibited cell growth and induced lactate dehydrogenase (LDH) release of androgen-independent DU145 and PC3 prostate cancer cells, but exhibited almost no toxicity effect on androgen-dependent LNCaP prostate cancer cell line or normal human prostate epithelial PrEC cells, which was achieved by the induction of apoptosis in a mitochondrion-dependent intrinsic apoptotic pathway. Furthermore, Isorhamnetin inhibited cell migration and invasion in concentration-dependent manners by enhancing mesenchymal-epithelial transition (MET) and inhibiting matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9 overexpression. In addition, Isorhamnetin also down-regulated the expression of phosphorylated PI3K (p-P13K), Akt (p-Akt), and mTOR (p-mTOR) proteins in both cancer cells, revealing Isorhamnetin to be a selective PI3K-Akt-mTOR pathway inhibitor. In summary, these findings propose that Isorhamnetin might be a novel therapeutic candidate for the treatment of androgen-independent prostate cancer.

Upregulation of miR-543-3p promotes growth and stem cell-like phenotype in bladder cancer by activating the Wnt/ß-catenin signaling pathway.

The Wnt/ß-catenin signaling pathway, which is strictly controlled by multiple negative regulators, has been reported commonly hyper activated and closely related to the progression of bladder cancer. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/ß-catenin signaling is still unclear. In the current study, we demonstrated that upregulation of miR-543-3p in bladder cancer activated Wnt/ß-catenin signaling by directly targeting Wnt inhibitory factor 1 (WIF1) and Dickkopf 1 (DKK1), which are important antagonist molecules of the Wnt/ß-catenin pathway. Expression of miR-543-3p was upregulated in both bladder cancer tissues and cells, and positively correlated with high-grade bladder cancer. Furthermore, ectopic overexpression of miR-543-3p promoted proliferation and inhibited apoptosis in bladder cancer cells. Notably, overexpression of miR-543-3p enhanced, while silencing miR-543-3p reduced, stem cell-like phenotype of bladder cancer cells. Therefore, our results suggest that miR-543-3p plays a significant role in promoting proliferation and stem cell-like phenotype in bladder cancer, which might be a potential target for anti-bladder cancer therapy.

[Staged retrograde flexible ureteroscopic lithotripsy versus miniaturized percutaneous nephrolithotomy for renal stones of 2-4 cm in diameter: a randomized controlled trial].

OBJECTIVE: To compare the efficacy and safety of staged retrograde flexible ureteroscopic lithotripsy (FURS) and miniaturized percutaneous nephrolithotomy (m-PCNL) for treatment of renal stones of 2-4 cm in diameter. METHODS: This randomized controlled trial was conducted in 70 patients with renal stones of 2-4 cm in diameter admitted in our hospital between January 2013 and December 2015. The patients were randomized to receive staged FURS (35 cases) or m-PCNL (35 cases), and the total treatment time, total hospital stay after procedure, total medical cost, treatment success, decrease in hemoglobin level and complications were compared between the two groups. RESULTS: The treatment success rate was 100% in both groups, but the complete stone-free rate was significantly lowered in FURS group than m-PCNL group (65.71% vs 94.29%, P<0.01). The average decrease in hemoglobin level was 3.37∓1.56 g/L in FURS group and 11.93∓2.24 g/L in m-PCNL group (P<0.01). The overall complication rates in the two groups were 6.25% and 9.37%, respectively (P>0.05). Minor complications (grade I by Clavien-Dindo classification) occurred in one case in FURS group (fever) and two cases in m-PCNL group (self-limiting hematuria); major complications (grade II) occurred in one case in FURS group (steinstrase) and one case in m-PCNL group (blood transfusion). In staged FURS and m-PCNL groups, the mean total treatment time was 4.06∓1.11 vs 1.26∓0.47 weeks (P<0.01), the mean hospital stay after procedure was 3.66∓1.29 vs 5.13∓0.43 days (P<0.01), and the mean total medical cost was 54 291.00 RMB ∓6149.00 vs 23 482.00 RMB ∓2317.00 (P<0.01), respectively. CONCLUSION: FURS is safe and effective for treatment of renal stones of 2-4 cm in diameter, and a staged procedure is necessary to achieve a stone-free status for large calculi. Both sophisticated equipment and rich surgical experience are essential to ensure treatment success.

[Application of Clavien-Dindo classification for comparing complications of three endoscopic procedures for benign prostatic hyperplasia].

OBJECTIVE: To compare the incidences of complications associated with 3 different endoscopic procedures, namely transurethral resection of prostate (TURP), bipolar plasmakinetic resection of the prostate (PKRP), and holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) and assess the clinical value of the Clavien-Dindo classification system for standardizing the evaluation of the complications. METHODS: Between January 2010 and December 2013, a total of 625 patients with BPH scheduled for endoscopic surgery underwent TURP (214 cases), PKRP (207 cases), or HoLEP (204 cases). The complications were recorded in each group and analyzed using the Clavien-Dindo classification system. RESULTS: There was no significant difference in the baseline data among the 3 groups (P>0.05). TURP was associated with a higher total incidence rate of complications than PKRP and HoLEP, and the incidences of electrolyte disturbance, massive intraoperative hemorrhage, urinary irritation symptom, urinary blockage, transurethral resection syndrome (TRUS), and erectile dysfunction (ED) differed significantly among the 3 groups (P<0.05). According to Clavien-Dindo classification, the incidence of grade II complications was significantly higher in TURP group than in PKRP and HoLEP groups (P<0.05), and that of grades III and IV complications was significantly higher in TURP group than in HoLEP group (P<0.05); no significant difference was found in grade I or V complications among the 3 groups (P>0.05). CONCLUSION: According to the results of Clavien-Dindo classification analysis, PKRP and HoLEP are associated with fewer complications with a better safety profile in the treatment of BPH. The current Clavien-Dindo classification system can contribute to standardized evaluation of surgical complications but still needs further modifications for better performance.