ABSTRACT
Stanniocalcin1 (STC1) is a secreted glycoprotein, which is highly expressed in prostate cancer cells. However, the biological functions of STC1 in modulating ferroptosis and glycolysis in prostate cancer are still not clear. The viability of PC-3 and DU145 cells was detected by CCK-8 assay. The relative Fe2+ level was detected by an Iron Assay Kit. MDA level was detected by Lipid Peroxidation MDA Assay Kit. Glucose uptake and lactate product were measured by Glycolysis Assay Kit and Lactate Assay Kit. In this study, STC1 was highly expressed in prostate cancer tissue specimens and cells. STC1 knockdown suppressed prostate cancer cell proliferation, and upregulated Fe2+ level, reduced glutathione (GSH) level, downregulated GPX4 and SLC7A11 protein expressions in PC-3 cells and DU145 cells. Besides, STC1 knockdown decreased glucose uptake, lactate product, and ATP level, as well as downregulated glycolysis-related protein HK2 and LDHA protein expressions. In addition, STC1 knockdown repressed the Nrf2/HO-1/NQO1 pathway. Nrf2 pathway activator, Oltipraz, upregulated Nrf2, total NQO1, and HO-1 expressions in PC-3 cells and DU145 cells. Moreover, Nrf2 pathway activator Oltipraz reversed the effect of STC1 knockdown on Fe2+ level and GPX4, SLC7A11, HK2, LDHA protein expressions in PC-3 cells and DU145 cells. Finally, STC1 knockdown restrained the tumor volume, tumor weight, and glycolysis in prostate cancer in vivo. Thus, STC1/Nrf2 pathway is a vital pathway to induce ferroptosis and suppress glycolysis in prostate cancer.
Subject(s)
Prostatic Neoplasms , Humans , Male , Ferroptosis/genetics , Glucose , Glycolysis , Lactates , NF-E2-Related Factor 2/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathologyABSTRACT
Bladder cancer is the ninth most diagnosed cancer in the world. This study aims to investigate the role and mechanisms of the taurine-upregulated gene 1 (TUG1)/miR-140-3p/annexin A8 (ANXA8) axis in bladder cancer. Western blotting and qRT-PCR determined the expression levels of ANXA8, miR-140-3p, TUG1, and epithelial-mesenchymal transition (EMT) markers. RNA immunoprecipitation (RIP), luciferase assay, and RNA pull-down assay validated the association among ANXA8, miR-140-3p, and TUG1. The biological functions were determined by colony formation, Annexin V-fluorescein isothiocyanate (FITC)/propidium (PI) staining, and transwell assays. Xenograft tumorigenesis detected tumor growth and metastasis in vivo. Pathological analysis was examined by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) analyses. ANXA8 was elevated in bladder tumors and cells. Knockdown of ANXA8 suppressed cell growth, migration, invasion, and EMT in UMUC-3 and T24 cells. ANXA8 was determined as a miR-140-3p target gene. Overexpression of miR-140-3p suppressed cell proliferation, migration, invasion, and EMT via targeting ANXA8. TUG1 promoted ANXA8 expression via sponging miR-140-3p. Silencing of miR-140-3p or ANXA8 overexpression abrogated the tumor-suppressive effects of TUG1 silencing on bladder cancer cell growth and metastasis. The TUG1/miR-140-3p/ANXA8 axis was also implicated in tumor growth and lung metastasis in vivo. TUG1 promotes bladder cancer progression and metastasis through activating ANXA8 by sponging miR-140-3p, which sheds light on the mechanisms of bladder cancer pathogenesis.
ABSTRACT
OBJECTIVES: To compare two different treatment strategies, one-stage and two-stage multi-tract mini-percutaneous nephrolithotomy (mt-mPCNL), for pediatric complex renal calculus disease. METHODS: Between the period of July 2016 and July 2018, a total of 36 children aged 15 years and younger, with complex renal calculi disease, who underwent total ultrasound-guided mt-mPCNL by a single experienced urologist were enrolled in our study. All patients were assigned either to Group 1 (n = 18) who received one-stage mt-mPCNL or Group 2 (n = 18) who received planned two-stage mt-mPCNL. RESULTS: The demographic data were comparable between the two groups. There were no serious complications (Modified Clavien Grade ≥ III) observed in either group. The stone -free rate (SFR), operation time, postoperative creatinine increase, and perioperative complication rates were similar in both groups (P = 0.603, 0.818, 0.161, and 0.402, respectively). The postoperative hospital stay (5.8 days vs. 7.4 days) and cost (17373.3 CNY vs. 23717.1 CNY) were statistically less in Group 1. Group 2 had significantly less total estimated blood loss (70.6 ml vs. 130.0 ml, P < 0.001). The operation time of two cases in Group 1 with perioperative sepsis or systemic inflammatory response syndrome (SIRS) was more than two hours. CONCLUSIONS: Our preliminary results indicated that both one-stage and two-stage mt-mPCNL were safe and effective for pediatric complex renal calculi. Two-stage mt-mPCNL could significantly reduce blood loss; while one-stage mt-mPCNL could significantly decrease the length and costs of hospitalization. We also suggest that the planned two-stage mt-mPCNL should be applied in children with estimated operation time more than two hours.
Subject(s)
Blood Loss, Surgical , Kidney Calculi , Nephrolithotomy, Percutaneous , Postoperative Complications , Systemic Inflammatory Response Syndrome , Adolescent , Blood Loss, Surgical/prevention & control , Blood Loss, Surgical/statistics & numerical data , Child , China/epidemiology , Comparative Effectiveness Research , Female , Humans , Kidney Calculi/diagnosis , Kidney Calculi/physiopathology , Kidney Calculi/surgery , Length of Stay/statistics & numerical data , Male , Nephrolithotomy, Percutaneous/adverse effects , Nephrolithotomy, Percutaneous/methods , Operative Time , Outcome and Process Assessment, Health Care , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/etiology , Ultrasonography, Interventional/methodsABSTRACT
PURPOSE: To describe our technique and experience with retroperitoneoscopic upper pole nephroureterectomy in duplex kidney, focusing on the role of dilated upper ureter. MATERIALS AND METHODS: From November 2004 to August 2011, retroperitoneoscopic upper pole nephroureterectomy was performed in 31 patients with a duplex kidney by a single, experienced laparoscopic surgeon. We developed our own surgical technique to suit this technically challenging procedure. Follow-up studies were performed using renal ultrasonography, intravenous urography (IVU) and/or dimercaptosuccinic acid (DMSA) renal scan in all patients at 3 months postoperatively and annually thereafter. RESULTS: All procedures were completed laparoscopically without conversion to open surgery and blood transfusion. The mean operative time was 106 (90-157) min. The estimated blood loss was < 50 mL in all cases. The mean postoperative hospital stay was 4.2 (3-7) days. Perioperative complications were limited to 1 case of peritoneal tear during a procedure and 1 case of transient postoperative fever. No major intraoperative and postoperative complication occurred. With the mean follow-up period of 41 months (range 3 to 80), no case was observed to have functional loss of the remaining lower moiety on postoperative IVU or DMSA renal scan. CONCLUSION: Retroperitoneoscopic upper pole nephroureterectomy using our technique is safe and effective.