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Cisplatin-induced acute kidney injury (AKI) is commonly seen in the clinical practice, and ferroptosis, a type of non-apoptotic cell death, plays a pivotal role in it. Previous studies suggested that protein arginine methyltransferase 4 (PRMT4) was incorporated in various bioprocesses, but its role in renal injuries has not been investigated. Our present study showed that PRMT4 was highly expressed in renal proximal tubular cells, and it was downregulated in cisplatin-induced AKI. Besides, genetic disruption of PRMT4 exacerbated, while its overexpression attenuated, cisplatin-induced redox injuries in renal proximal epithelia. Mechanistically, our work showed that PRMT4 interacted with NCOA4 to inhibit ferritinophagy, a type of selective autophagy favoring lipid peroxidation to accelerate ferroptosis. Taken together, our study demonstrated that PRMT4 interacted with NCOA4 to attenuate ferroptosis in cisplatin-induced AKI, suggesting that PRMT4 might present as a new therapeutic target for cisplatin-related nephropathy.
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Injúria Renal Aguda , Cisplatino , Humanos , Cisplatino/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Rim/metabolismo , Fatores de Transcrição/metabolismo , Autofagia , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismoRESUMO
Cisplatin-induced acute kidney injury (CP-AKI) is a common complication in cancer patients. Although ferroptosis is believed to contribute to the progression of CP-AKI, its mechanisms remain incompletely understood. In this study, after initially processed individual omics datasets, we integrated multi-omics data to construct a ferroptosis network in the kidney, resulting in the identification of the key driver TACSTD2. In vitro and in vivo results showed that TACSTD2 was notably upregulated in cisplatin-treated kidneys and BUMPT cells. Overexpression of TACSTD2 accelerated ferroptosis, while its gene disruption decelerated ferroptosis, likely mediated by its potential downstream targets HMGB1, IRF6, and LCN2. Drug prediction and molecular docking were further used to propose that drugs targeting TACSTD2 may have therapeutic potential in CP-AKI, such as parthenolide, progesterone, premarin, estradiol and rosiglitazone. Our findings suggest a significant association between ferroptosis and the development of CP-AKI, with TACSTD2 playing a crucial role in modulating ferroptosis, which provides novel perspectives on the pathogenesis and treatment of CP-AKI.
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Injúria Renal Aguda , Cisplatino , Ferroptose , Cisplatino/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Humanos , Animais , Camundongos , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Simulação de Acoplamento Molecular , Masculino , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Lipocalina-2/genética , Lipocalina-2/metabolismo , Antineoplásicos/efeitos adversos , MultiômicaRESUMO
BACKGROUND: A prognostic model of bladder cancer was constructed based on costimulatory molecules, and its stability and accuracy were verified in different datasets. METHOD: The expression profile of bladder cancer RNA and the corresponding clinical data in The Cancer Genome Atlas (TCGA) database were analyzed employing computational biology, and a prognostic model was constructed for costimulating molecule-related genes. The model was applied in GSE160693, GSE176307, Xiangya_Cohort, GSE13507, GSE19423, GSE31684, GSE32894, GSE48075, GSE69795 and GSE70691 in TCGA dataset and Gene Expression Omnibus database. The role of costimulating molecules in bladder cancer tumor subtypes was also explored. By consistent cluster analysis, bladder cancer in the TCGA dataset was categorized into two subtypes: C1 and C2. The C1 subtype exhibited a poor prognosis, high levels of immune cell infiltration and significant enrichment of natural killer cells, T cells and dendritic cells in the C1 subtype. In addition, the ImmuneScore calculated by the ESTIMATE algorithm differed greatly between the two subtypes, and the ImmuneScore of the C1 subtype was greater than the C2 subtype in a significant manner. RESULTS: This study also assessed the relationship between costimulating molecules and immunotherapy response. The high-risk group responded poorly to immunotherapy, with significant differences in the amount of most immune cells between the two groups. Further, three indices of the ESTIMATE algorithm and 22 immune cells of the CIBERSORT algorithm were significantly correlated with risk values. These findings suggest the potential value of costimulating molecules in predicting immunotherapy response. CONCLUSION: A costimulatory molecule-based prognostic model for bladder cancer was established and validated across multiple datasets. This model introduces a novel mode for tailoring treatments to each individual with bladder cancer, and offers valuable insights for informed clinical choices. Simultaneously, this research also delved into the significance of costimulating molecules within distinct bladder cancer subtypes, shedding novel insights into improving immunotherapy strategies for the treatment of bladder cancer.
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Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Algoritmos , Análise por ConglomeradosRESUMO
INTRODUCTION: Bladder cancer (BLCA) is a prevalent and deadly form of urinary cancer, and there is a need for effective therapies, particularly for muscle-invasive bladder cancer (MIBC). Cell cycle inhibitors show promise in restoring control of the cell cycle in BLCA cells, but their clinical prognosis evaluation is limited. METHODS: Transcriptome and scRNA-seq data were collected from the Cancer Genome Atlas Program (TCGA)-BLCA and GSE190888 cohort, respectively. R software and the Seurat package were used for data analysis, including cell quality control, dimensionality reduction, and identification of differentially expressed genes. Genes related to the cell cycle were obtained from the genecards website, and a protein-protein interaction network analysis was performed using cytoscape software. Functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular docking were conducted using various tools and packages. BLCA cell lines were cultured and transfected for in vitro experimental assays, including RT-qPCR analysis, and CCK-8 cell viability assays. RESULTS: We identified 32 genes as independent risk or protective factors for BLCA prediction. Functional enrichment analysis revealed their involvement in cell cycle regulation, apoptosis, and various signaling pathways. Using these genes, we developed a nomogram for predicting BLCA survival, which displayed high prognosis stratification efficacy in BLCA patients. Four cell cycle associated key genes identified, including NCAM1, HBB, CKD6, and CTLA4. We also identified the main cell types in BLCA patients and investigated the functional differences between epithelial cells based on their expression levels of key genes. Furthermore, we observed a high positive correlative relationship between the infiltration of cancer-associated fibroblasts and the risk score value. Finally, we conducted in vitro experiments to demonstrate the suppressive role of NCAM1 in BLCA cell proliferation. CONCLUSION: These findings suggest that cell cycle associated genes could serve as potential biomarkers for predicting BLCA prognosis and may represent therapeutic targets for the development of more effective therapies. Hopefully, these findings provide valuable insights into the molecular mechanisms and potential therapeutic targets in BLCA from the perspective of cell cycle. Moreover, NCAM1 was a novel cell proliferation suppressor in the BLCA carcinogenesis.
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Bladder cancer is a malignant tumor of the urinary system and is one of the most common cancers worldwide. Lipoxygenases are closely related to the development of various cancers. However, the relationship between lipoxygenases and p53/SLC7A11-dependent ferroptosis in bladder cancer has not been reported. Here, we aimed to investigate the roles and internal mechanisms of lipid peroxidation and p53/SLC7A11-dependent ferroptosis in the development and progression of bladder cancer. First, ultraperformance liquid chromatography-tandem mass spectrometry was performed to measure the metabolite production of lipid oxidation in patients' plasma. The metabolic changes in patients with bladder cancer were discovered, revealing that stevenin, melanin, and octyl butyrate were upregulated. Then, the expressions of lipoxygenase family members were measured to screen out candidates with significant changes in bladder cancer tissues. Among various lipoxygenases, ALOX15B was significantly downregulated in bladder cancer tissues. Moreover, p53 and 4-hydroxynonenal (4-HNE) levels were decreased in bladder cancer tissues. Next, sh-ALOX15B, oe-ALOX15B, or oe-SLC7A11 plasmids were constructed and transfected into bladder cancer cells. Then, the p53 agonist Nutlin-3a, tert-butyl hydroperoxide, iron chelator deferoxamine, and the selective ferroptosis inhibitor ferr1 were added. The effects of ALOX15B and p53/SLC7A11 on bladder cancer cells were evaluated by in vitro and in vivo experiments. We revealed that knockdown of ALOX15B promoted bladder cancer cell growth, which was also found to protect bladder cancer cells from p53-induced ferroptosis. Furthermore, p53 activated ALOX15B lipoxygenase activity by suppressing SLC7A11. Taken together, p53 activated the lipoxygenase activity of ALOX15B via inhibiting SLC7A11 to induce ferroptosis in bladder cancer cells, which provided insight into the molecular mechanism of the occurrence and development of bladder cancer.
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Ferroptose , Neoplasias da Bexiga Urinária , Humanos , Proteína Supressora de Tumor p53/genética , Lipoxigenase , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária , Sistema y+ de Transporte de Aminoácidos/genéticaRESUMO
We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).
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Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antígeno Prostático Específico , Tioidantoínas/efeitos adversos , Antagonistas de Receptores de Andrógenos , Resultado do TratamentoRESUMO
Growing evidence suggest that circular RNAs (circRNAs) are critical mediators in renal diseases. However, there have been very few reports about the role of circRNAs in renal fibrosis. In this study, circRNA_33702 was found to be upregulated, both in unilateral ureteral obstruction (UUO) mice and in TGF-ß1-treated Boston University mouse proximal tubule cells. Furthermore, hsa_circ_0026331, homologous with mmu_circ_33702, was found to be upregulated in TGF-ß1-treated HK-2 cells. Although knockdown of circRNA_33702 or hsa_circ_0026331 was shown to relieve the TGF-ß1-induced expression of collagen I, collagen III, and fibronectin, overexpression of circRNA_33702 was found to exert an inhibitory effect on the expression of the same genes. Mechanistically, circRNA_33702 was demonstrated to bind directly with miR-29b-3p and inhibit its expression. MiR-29b-3p mimic was shown to inhibit the TGF-ß1-induced expression of collagen I, collagen III, and fibronectin. Moreover, WNT1-inducible signaling pathway protein 1 (WISP1) was identified as a target of miR-29b-3p, and the expression of WISP1 was observed to be repressed by miR-29b-3p. Notably, knockdown of circRNA_33702 was found to attenuate the expression of collagen I, collagen III, and fibronectin by inhibiting the expression of WISP1, and the observed inhibitory effect can be reversed by miR-29b-3p inhibitor. Finally, inhibition of circRNA_33702 was shown to attenuate interstitial fibrosis in UUO mice via the miR-29b-3p/WISP1 axis. In general, our data show that circRNA_33702 may promote renal fibrosis via the miR-29b-3p/WISP1 axis, which may potentially be developed as a new therapeutic target. SIGNIFICANCE STATEMENT: This study's findings suggested that circRNA_33702 plays a profibrosis role and that circRNA_33702 with the homologous human hsa_circ_0026331 may be a novel therapeutic target of renal fibrosis.
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Nefropatias , MicroRNAs , Humanos , Animais , Camundongos , RNA Circular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fibronectinas/genética , Fibrose , Nefropatias/genética , Transdução de Sinais/genética , Proliferação de CélulasRESUMO
OBJECTIVE: Prostate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase-like 3 (METTL3) in affecting PCa development by regulating miR-148a-3p expression via N6-methyladenosine (m6A) modification was investigated. METHODS: METTL3, miR-148a-3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT-qPCR and Western blotting. The m6A modification level of miR-148a-3p was observed by Me-RIP assay. Bioinformatics website predicted miR-148a-3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual-luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK-8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry. RESULTS: METTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up-regulated miR-148a-3p by promoting the m6A modification of pri-miR-148a-3p in PCa cells. miR-148a-3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR-148a-3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down-regulating miR-148a-3p and up-regulating TXNIP. CONCLUSION: METTL3 promoted miR-148a-3p by mediating the m6A modification of pri-miR-148a-3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice.
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MicroRNAs , Neoplasias da Próstata , Humanos , Masculino , Animais , Camundongos , Camundongos Nus , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Próstata , Proliferação de Células/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Proteínas de Transporte/genéticaRESUMO
BACKGROUND: Venous thromboembolism (VTE) is the second leading cause for death of radical prostatectomy. We aimed to establish new nomogram to predict the VTE risk after robot-assisted radical prostatectomy (RARP). METHODS: Patients receiving RARP in our center from November 2015 to June 2021, were enrolled in study. They were randomly divided into training and testing cohorts by 8:2. Univariate and multivariate logistic regression (model A) and stepwise logistic regression (model B) were used to fit two models. The net reclassification improvement (NRI), integrated discrimination improvement (IDI), and receiver operating characteristic (ROC) curve were used to compare predictive abilities of two new models with widely used Caprini risk assessment (CRA) model. Then, two nomograms were constructed and received internal validation. RESULTS: Totally, 351 patients were included. The area under ROC of model A and model B were 0.967 (95% confidence interval: 0.945-0.990) and 0.978 (95% confidence interval: 0.960-0.996), which also were assayed in the testing cohorts. Both the prediction and classification abilities of the two new models were superior to CRA model (NRI > 0, IDI > 0, p < 0.05). The C-index of Model A and Model B were 0.968 and 0.978, respectively. For clinical usefulness, the two new models offered a net benefit with threshold probability between 0.08 and 1 in decision curve analysis, suggesting the two new models predict VTE events more accurately. CONCLUSIONS: Both two new models have good prediction accuracy and are superior to CRA model. Model A has an advantage of less variable. This easy-to-use model enables rapid clinical decision-making and early intervention in high-risk groups, which ultimately benefit patients.
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Nomogramas , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Tromboembolia Venosa , Humanos , Masculino , Próstata , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Distribuição Aleatória , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Tromboembolia Venosa/etiologiaRESUMO
Bladder cancer (BC) has an unpredictable prognosis. Pyroptosis is a novel form of programmed cell death. However, whether the pyroptosis-related genes have a prognostic value remains unknown. In this study, we downloaded the mRNA expression and clinical data of BC patients and used the LASSO Cox analysis was employed to build a signature. High-risk patients had a significantly lower overall survival (OS) (p < .0001). Single-sample gene set enrichment analysis (ssGSEA) indicated that the tumor immune microenvironment was different between the two risk groups. In conclusion, a pyroptosis-related signature can be used for OS prediction of patients with BCs.
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Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Piroptose , Neoplasias da Bexiga Urinária/genética , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Prognóstico , Análise de Sequência de RNA , Análise de Sobrevida , Microambiente TumoralRESUMO
Regulated cell death (RCD), distinct from accidental cell death, refers to a process of well-controlled programmed cell death with well-defined pathological mechanisms. In the past few decades, various terms for RCDs were coined, and some of them have been implicated in the pathogenesis of various types of acute kidney injury (AKI). Cisplatin is widely used as a chemotherapeutic drug for a broad spectrum of cancers, but its usage was hampered because of being highly nephrotoxic. Cisplatin-induced AKI is commonly seen clinically, and it also serves as a well-established prototypic model for laboratory investigations relevant to acute nephropathy affecting especially the tubular compartment. Literature reports over a period of three decades have indicated that there are multiple types of RCDs, including apoptosis, necroptosis, pyroptosis, ferroptosis, and mitochondrial permeability transition-mediated necrosis, and some of them are pertinent to the pathogenesis of cisplatin-induced AKI. Interestingly, myo-inositol metabolism, a vital biological process that is largely restricted to the kidney, seems to be relevant to the pathogenesis of certain forms of RCDs. A comprehensive understanding of RCDs in cisplatin-induced AKI and their relevance to myo-inositol homeostasis may yield novel therapeutic targets for the amelioration of cisplatin-related nephropathy.
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Injúria Renal Aguda/induzido quimicamente , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Inositol/metabolismo , Necroptose/efeitos dos fármacos , Injúria Renal Aguda/patologia , Animais , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Camundongos Endogâmicos C57BL , Necrose/metabolismo , Necrose/patologia , Morte Celular Regulada/efeitos dos fármacosRESUMO
BACKGROUD: To evaluate the relationship between omentin-1 and benign prostatic hyperplasia (BPH). BPH is the most common urological disease in elderly men worldwide. Lower serum omentin-1 levels were reported to be negatively associated with the incidence of inflammation, diabetes, obesity and metabolic syndrome, which all play a role in the development of BPH. To the best of our knowledge, the relationship between omentin-1 and BPH has not been investigated previously. METHODS: A total of 70 males participated in this study, including forty patients diagnosed with BPH and thirty healthy males. The anthropometric measurements and the biochemical parameters were measured in this study. We evaluated serum omentin-1 levels and the correlation with those data. We also test the gene expression of IL-8, IL-18 in BPH group using the TURP tissues. RESULTS: The serum omentin-1 levels were lower in the BPH patients than in the control group (27.95 ± 4.18 versus 32.03 ± 5.46, p < 0.001). The general characteristics and biochemical parameters were investigated, and a negative correlation was found between serum omentin-1 levels and BMI in the BPH group (r = - 0.391, p = 0.013) as well as the whole group (r = - 0.457, p < 0.001). Multiple-factor binary regression analysis revealed that serum omentin-1was a protective factor of BPH development. Furthermore, lower serum omentin-1 levels were associated with higher mRNA expression of IL-8 or IL-18 in the BPH group. CONCLUSION: Omentin-1 may suppress the development of BPH and Lower serum omentin-1 levels in BPH patients might associated with higher prostate volume and higher IL-8 and IL-18 expression levels in their prostatic cells.
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Citocinas/sangue , Lectinas/sangue , Hiperplasia Prostática/sangue , Correlação de Dados , Proteínas Ligadas por GPI/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the application of the deep dorsal vein complex (DVC) ligation-free technique in robot-assisted radical prostatectomy (RARP) and its effects on the intraoperative blood loss, incidence of positive surgical margin (PSM) and urinary continence of the patient. METHODS: Totally 154 PCa patients underwent RARP between October 2015 and June 2019, 40 with the DVC ligation-free technique (group A) and the other 114 by conventional DVC ligation (group B). We compared the baseline characteristics, operation time, intraoperative blood loss, blood transfusion rate, and postoperative incidences of PSM and urinary incontinence immediately and at 1 and 3 months after catheter removal between the two groups. RESULTS: There were no statistically significant differences between the groups A and B in age, body mass index, PCa risk levels or American Scoiety of Anesthesiology (ASA) tumor grades (P > 0.05), nor in intraoperative blood loss (ΔZ: ï¼»2.11 ± 8.88ï¼½ vs ï¼»1.24 ± 14.70ï¼½ g/L, P > 0.05), blood transfusion rate (10.0% vs 15.8%, P > 0.05), overall PSM incidence (15.0% vs 15.8%, P > 0.05) or apical PSM rate (7.5% vs 8.8%, P > 0.05). The mean operation time was remarkably shorter in group A than in B (107.20 min vs 113.25 min, P < 0.05) and the postoperative incidence rate of urinary incontinence was markedly lower in the former than in the latter group immediately after (2.5% vs 17.5%, P < 0.05) and at 1 month after catheter removal (0 vs 14.0%, P < 0.05), but with no statistically significant difference between the two groups at 3 months (0 vs 7.9%, P > 0.05). CONCLUSIONS: The DVC ligation-free technique in RARP can reduce the operation time and promote the recovery of urinary continence in PCa patients without increasing intraoperative blood loss and the incidence of PSM.
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Prostatectomia/métodos , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Ligadura , Masculino , Neoplasias da Próstata/cirurgia , Resultado do TratamentoRESUMO
In recent years, circular RNAs (circRNAs) have been identified to be essential regulators of various human cancers. However, knowledge of the functions of circRNAs in prostate cancer remains very limited. The correlation between circABCC4 and human cancer is largely unknown. This study aims to investigate the biological functions of circABCC4 in prostate cancer progression and illustrate the underlying mechanism. We found that circABCC4 was remarkably up-regulated in prostate cancer tissues and cell lines and promoted FOXP4 expression by sponging miR-1182 in prostate cancer cells. CircABCC4 knockdown markedly suppressed prostate cancer cell proliferation, cell-cycle progression, migration and invasion in vitro. Furthermore, silencing of the circRNA also delayed tumor growth in vivo. Taken together, our findings indicated that circABCC4 facilitates the malignant behaviour of prostate cancer by promoting FOXP4 expression through sponging of miR-1182. The circABCC4-miR-1182-FOXP4 regulatory loop may be a promising therapeutic target for prostate cancer intervention.
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Fatores de Transcrição Forkhead/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , RNA Circular/genética , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVE: To identify risk factors for early complications in patients after robot-assisted laparoscopic radical cystectomy (RARC) and a standardized reporting model to predict complications precisely and recommend reasonable prophylaxis.â© Methods: A total of 90 patients with bladder cancer, who underwent RARC in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2016 to January 2018, were enrolled for this study. Their clinical information, preoperative examination and follow-up data within 90 d after RARC were collected. Univariable and multivariable logistic regressions were performed to identify risk factors for early complications after RARC.â© Results: The overall incidence of complications within 90 d after RARC was 48.9% (44/90), including 9 cases of Clavien grade 1, 17 cases of Clavien grade 2, 4 cases of Clavien grade 3, 12 cases of Clavien grade 4, and 2 cases of Clavien grade 5. Acute renal injury (22.2%), intestinal obstruction (16.7%), urinary tract infection (14.4%) and lymphatic leakage (10.0%) were the most common complications within 90 d after the operation. Two patients (2.2%) died within 90 d after the operation. Preoperative BMI (OR=1.16, 95% CI 1.02 to 1.32), postoperative instant (≤30 min) serum creatinine (OR=1.02, 95% CI 1.00 to 1.03), and pT stage (OR=1.67, 95% CI 1.05 to 2.68) were the risk factors for early complications after RARC. â© Conclusion: The incidence of early complications after RARC is high. Preoperative hemodialysis, correction of anemia, intraoperative protection of renal function, and early recovery after surgery are helpful to prevent early complications after RARC.
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Cistectomia , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária/cirurgia , Humanos , Complicações Pós-Operatórias , Fatores de Risco , Robótica , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. METHODS: The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. RESULTS: The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. CONCLUSIONS: our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients.
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Linfócitos/citologia , Neutrófilos/citologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia , Bases de Dados Factuais , Intervalo Livre de Doença , Humanos , Linfócitos/imunologia , Metástase Neoplásica , Neutrófilos/imunologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/mortalidadeRESUMO
Prostate cancer has the highest incidence among malignant tumors of the urinary system in China. Radical prostatectomy (RP) is the most effective treatment for localized prostate cancer with a good long-term prognosis. Erectile dysfunction (ED) is a common complication after RP, which seriously affects the patient's quality of life. With the rising incidence and early diagnosis of prostate cancer, the proportion of young cases of RP is increasing, and so is the importance of the treatment of post-RP ED. The restoration of erectile function after RP is closely related to the timing of penile rehabilitation as well as to pre- and intra-operative measures such as surgical strategies and methods. Common options for the treatment of post-RP ED include oral medication of phosphodiesterase type 5 inhibitors, application of vasoactive substances in the urethra or corpus cavernosum, use of vacuum erection devices, and implantation of penile prosthesis. Stem cell therapy, nerve transplantation, low-intensity extracorporeal shockwave therapy, and erythropoietin have shown great potential in penile rehabilitation after RP. At present, the stress is placed on the remission of symptoms in the treatment of ED. Stem cell therapy may reverse the cause of disease or cure ED by reversing its pathophysiological changes. A series of clinical trials of stem cell therapy are underway and have preliminarily confirmed the safety of stem cell therapy and proved that it can improve erectile function in patients with post-RP ED. This review focuses on the progress in the prevention and treatment of ED after RP.
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Disfunção Erétil/terapia , Prótese de Pênis , Inibidores da Fosfodiesterase 5/uso terapêutico , Complicações Pós-Operatórias/terapia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Vasodilatadores/uso terapêutico , China , Disfunção Erétil/prevenção & controle , Humanos , Masculino , Ereção Peniana , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Transplante de Células-Tronco , Resultado do Tratamento , VácuoRESUMO
BACKGROUND: Radical nephroureterectomy is considered as the gold standard for the surgical treatment of upper urinary tract urothelial carcinoma (UTUC). Laparoscopic radical nephroureterectomy (LNU) can be performed via the transperitoneal (TLNU) or retroperitoneal (RLNU) approach, and each one has its own advantages and limitations. Our study was conducted to describe the difference between TLNU and RLNU by comparing the perioperative outcomes. METHODS: From January 2009 to October 2014, 68 patients underwent TLNU or RLNU at our center were retrospectively collected and 1:1 matched for age, body mass index and tumor side. Baseline characteristics and perioperative outcomes were evaluated and compared, respectively. RESULTS: There were no significant differences between the TLNU and RLNU group in terms of baseline characteristics, operating time, estimated blood loss, visual analogue pain scale, cosmetic results, intraoperative and postoperative complication rate. Compared to TLNU approach, RLNU was associated with a quicker time to first oral intake (2.9 vs 2.0 days, p = 0.02) and hospital discharge (6.7 vs 5.6 days, p = 0.02). CONCLUSION: Both transperitoneal and retroperitoneal laparoscopic approaches are safe and effective methods for treatment of UTUC. Retroperitoneal approach has the advantage in terms of quicker bowel recovery and shorter hospital discharge.
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Carcinoma de Células de Transição/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Ureter/cirurgia , Neoplasias Ureterais/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Peritônio/cirurgia , Espaço Retroperitoneal/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To evaluate the effect and safety of phloroglucinol combined with parecoxib on cystospasm after transurethral resection of the prostate (TURP). METHODS: We conducted a prospective randomized case-control study on 98 patients treated by TURP. After operation, the patients were randomly assigned to a treatment (n=50) and a control group (n=48), the former treated by intravenous injection of 80 mg phloroglucinol qd plus 40 mg parecoxib bid while the latter given 80 mg phloroglucinol only, both for 3 successive days. Then we recorded the frequency and duration of cystospasm, visual analogue scales (VAS), adverse reactions, post-operative bladder irrigation time, catheter-indwelling time, and hospital stay and compared them between the two groups of patients. RESULTS: Compared with the controls, the patients in the treatment group showed a significantly lower frequency of cystospasm (ï¼»1.95±0.14ï¼½ vs ï¼»0.70±0.65ï¼½ times, P<0.01), duration of cystospasm (ï¼»0.44±0.21ï¼½ vs ï¼»0.12±0.14ï¼½ min, P<0.01), and VAS score (2.70±1.80 vs 1.90±1.30, P<0.01) at 48ï¼72 hours after TURP, but no statistically significant differences were found between the control and treatment groups in the post-operative bladder irrigation time (ï¼»2.75±0.87ï¼½ vs ï¼»2.64±0.83ï¼½ d, P>0.05), catheter-indwelling time (ï¼»3.52±0.32ï¼½ vs ï¼»3.44±0.42ï¼½ d, P>0.05), and hospital stay (ï¼»5.23±0.81ï¼½ vs ï¼»5.10±0.73ï¼½ d, P>0.05), and no obvious adverse reactions were observed in either of the two groups. CONCLUSIONS: Phloroglucinol combined with parecoxib is more effective and safer than phloroglucinol alone in relieving postoperative cystospasm after TURP.
Assuntos
Isoxazóis/uso terapêutico , Floroglucinol/uso terapêutico , Espasmo/tratamento farmacológico , Ressecção Transuretral da Próstata , Bexiga Urinária/efeitos dos fármacos , Idoso , Estudos de Casos e Controles , Quimioterapia Combinada , Humanos , Isoxazóis/administração & dosagem , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Floroglucinol/administração & dosagem , Período Pós-Operatório , Estudos Prospectivos , Hiperplasia Prostática , Irrigação Terapêutica , Resultado do Tratamento , Bexiga Urinária/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the safety and effectiveness of GreenLight 120-W laser photoselective vaporization of the prostate (PVP) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). METHODS: We searched PubMed, Medline, Embase, Cochrane Library, Wanfang, CNKI, and VIP for randomized control trials and their references addressing 120-W PVP versus TURP in the treatment of BPH. Based on the inclusion and exclusion criteria, two reviewers independently accomplished the screening, quality assessment, and data extraction of the identified studies and performed meta-analyses using RevMan 5.2. RESULTS: Totally, 6 randomized control trials were included in this analysis, involving 703 cases, 351 treated by PVP and 352 by TURP. Compared with TURP, PVP showed significantly decreased time of catheterization (by 32. 55 hours, 95% CI 15.3 -49.8, P < 0.01), hospital stay (by 1.85 days, 95% CI 1.2-2.5, P < 0.01), and intraoperative blood loss (by 15.6 g/L, 95% CI 10.0-21.2, P < 0.01), but increased time of operation (by 9.37 minutes, 95% CI 5. 1-13.6, P < 0.01). There was also a significant reduction in blood transfusion, TUR syndrome, and capsular perforation in the PVP group. At 12 months after surgery, no statistically significant differences were found between the two groups in the improvement of maximum urinary flow rate, IPSS, postvoid residual, and sexual function. CONCLUSION: GreenLight 120-W laser PVP is a safe and effective procedure for the treatment of BPH, with similar effectiveness to TURP but less blood loss, shorter time of catheterization and hospital stay, and lower incidences of blood transfusion, TUR syndrome and capsular perforation.