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1.
J Biol Chem ; : 107598, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39059495

RESUMEN

In recent years, a surge in studies investigating N6-methyladenosine (m6A) modification in human diseases has occurred. However, the specific roles and mechanisms of m6A in kidney disease remain incompletely understood. This study revealed that m6A plays a positive role in regulating renal fibrosis (RF) by inducing epithelial-to-mesenchymal phenotypic transition (EMT) in renal tubular cells. Through comprehensive analyses, including m6A sequencing, RNA sequencing, and functional studies, we confirmed the pivotal involvement of zinc finger E-box binding homeobox 2 (ZEB2) in m6A-mediated RF and EMT. Notably, the m6A-modified coding sequence (CDS) of ZEB2 mRNA significantly enhances its translational elongation and mRNA stability by interacting with the YTHDF1/eEF-2 complex and IGF2BP3, respectively. Moreover, targeted demethylation of ZEB2 mRNA using the dm6ACRISPR system substantially decreases ZEB2 expression and disrupts the EMT process in renal tubular epithelial cells. In vivo and clinical data further support the positive influence of m6A/ZEB2 on RF progression. Our findings highlight the m6A-mediated regulation of RF through ZEB2, revealing a novel therapeutic target for RF treatment and enhancing our understanding of the impact of mRNA methylation on kidney disease.

2.
Lancet Oncol ; 24(4): 360-370, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36893772

RESUMEN

BACKGROUND: Accurate lymph node staging is important for the diagnosis and treatment of patients with bladder cancer. We aimed to develop a lymph node metastases diagnostic model (LNMDM) on whole slide images and to assess the clinical effect of an artificial intelligence-assisted (AI) workflow. METHODS: In this retrospective, multicentre, diagnostic study in China, we included consecutive patients with bladder cancer who had radical cystectomy and pelvic lymph node dissection, and from whom whole slide images of lymph node sections were available, for model development. We excluded patients with non-bladder cancer and concurrent surgery, or low-quality images. Patients from two hospitals (Sun Yat-sen Memorial Hospital of Sun Yat-sen University and Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China) were assigned before a cutoff date to a training set and after the date to internal validation sets for each hospital. Patients from three other hospitals (the Third Affiliated Hospital of Sun Yat-sen University, Nanfang Hospital of Southern Medical University, and the Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China) were included as external validation sets. A validation subset of challenging cases from the five validation sets was used to compare performance between the LNMDM and pathologists, and two other datasets (breast cancer from the CAMELYON16 dataset and prostate cancer from the Sun Yat-sen Memorial Hospital of Sun Yat-sen University) were collected for a multi-cancer test. The primary endpoint was diagnostic sensitivity in the four prespecified groups (ie, the five validation sets, a single-lymph-node test set, the multi-cancer test set, and the subset for a performance comparison between the LNMDM and pathologists). FINDINGS: Between Jan 1, 2013 and Dec 31, 2021, 1012 patients with bladder cancer had radical cystectomy and pelvic lymph node dissection and were included (8177 images and 20 954 lymph nodes). We excluded 14 patients (165 images) with concurrent non-bladder cancer and also excluded 21 low-quality images. We included 998 patients and 7991 images (881 [88%] men; 117 [12%] women; median age 64 years [IQR 56-72]; ethnicity data not available; 268 [27%] with lymph node metastases) to develop the LNMDM. The area under the curve (AUC) for accurate diagnosis of the LNMDM ranged from 0·978 (95% CI 0·960-0·996) to 0·998 (0·996-1·000) in the five validation sets. Performance comparisons between the LNMDM and pathologists showed that the diagnostic sensitivity of the model (0·983 [95% CI 0·941-0·998]) substantially exceeded that of both junior pathologists (0·906 [0·871-0·934]) and senior pathologists (0·947 [0·919-0·968]), and that AI assistance improved sensitivity for both junior (from 0·906 without AI to 0·953 with AI) and senior (from 0·947 to 0·986) pathologists. In the multi-cancer test, the LNMDM maintained an AUC of 0·943 (95% CI 0·918-0·969) in breast cancer images and 0·922 (0·884-0·960) in prostate cancer images. In 13 patients, the LNMDM detected tumour micrometastases that had been missed by pathologists who had previously classified these patients' results as negative. Receiver operating characteristic curves showed that the LNMDM would enable pathologists to exclude 80-92% of negative slides while maintaining 100% sensitivity in clinical application. INTERPRETATION: We developed an AI-based diagnostic model that did well in detecting lymph node metastases, particularly micrometastases. The LNMDM showed substantial potential for clinical applications in improving the accuracy and efficiency of pathologists' work. FUNDING: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, and the Guangdong Provincial Clinical Research Centre for Urological Diseases.


Asunto(s)
Inteligencia Artificial , Metástasis Linfática , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/patología , Metástasis Linfática/diagnóstico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos
3.
Funct Integr Genomics ; 23(4): 291, 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37676513

RESUMEN

Folate metabolism is critical for the maintenance of genomic stability due to its regulatory ability to methylation, nucleotide metabolism, and reduction capabilities in cancer cells. However, the prognostic value of folate metabolism-related genes has not been clarified, especially in bladder cancer (BLCA). 91 folate metabolism-related genes were retrieved from the public database. TCGA-BLCA cohort, obtained from the Cancer Genome Atlas, was selected for training, while GSE13507, GSE31684, and GSE32894, downloaded from the Gene Expression Omnibus, and 35 BLCA samples collected from the local hospital were used for external validation. Through genomic difference detection, protein-protein interaction network analysis, LASSO regression, and Cox regression, a three-gene signature, including ATIC, INS, and MTHFD1L, was constructed. The signature was a reliable prognosis predictor across multiple independent cohorts (pooled hazard ratio = 2.79, 95% confidence interval = 1.79-4.33). The signature was associated with the BLCA malignant degree, which was validated in the local clinical samples (P < 0.01) and multiple cell lines (all P < 0.05). Additionally, the TIDE algorithm, GSE111636 cohort, and IMvigor210 cohort indicated that the signature was a promising tool to evaluate the immunotherapeutic response. Collectively, a folate metabolism-related gene signature was constructed to predict the prognosis and immunotherapeutic sensitivity in BLCA, which was verified in multiple large-scale cohorts, clinical samples, and cellular experiments, providing novel insights into the biological mechanisms.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Algoritmos , Línea Celular , Inmunoterapia , Ácido Fólico
4.
World J Urol ; 41(3): 865-872, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36757468

RESUMEN

INTRODUCTION: Ureteral access sheath (UAS) and irrigation are used in flexible ureteroscopy (fURS). Both conventional UAS (cUAS) and vacuum-assisted UAS (vaUAS) are currently available. Irrigation increases the intrarenal pressure (IRP). Our objectives were to study the effects of various irrigation rates on IRP using different sizes of fURS in different sizes and functions of UAS. MATERIALS AND METHODS: Ten freshly harvested porcine kidneys served as the study subjects. 11/13F and 12/14F cUAS and vaUAS with 2.8 mm and 3.2 mm fURS were experimented on in various scope/sheath combinations. 6F pressure monitor catheters were placed into upper, middle, and lower calyces. IRPs were recorded under different irrigation rates in cUAS and vaUAS, with either 150 or 300 mmHg aspiration pressures, and with air vent either open or closed. RESULTS: 12/14F cUAS with 2.8 mm fURS could maintain IRPs below 35 mmHg with irrigation rates up to 200 cc/min. With 3.2 mm fURS, the rate dropped to 110-120 cc/min. With 12/14F vaUAS and vent closed, the IRP remained less than 5 mmHg at 200 cc/min irrigation for both fURS. For 11/13F cUAS, the < 35 mmHg threshold for 2.8 mm fURS was 80-90 cc/min; for 3.2 mm fURS, it was 30-40 cc/min. For 11/13F vaUAS with vent closed, IRPs remained < 5 mmHg at 200 cc/min irrigation for both scopes. CONCLUSION: Both 12F cUAS and vaUAS can be used safely with 2.8 mm fURS up to 200 cc/min irrigation. With either a smaller sheath or a larger scope, vaUAS with vent closed can maintain IRP in a safe range up 200 cc/min irrigation. vaUAS with vent open performed marginally better than cUAS.


Asunto(s)
Cálculos Renales , Ureteroscopios , Porcinos , Animales , Ureteroscopía , Presión , Irrigación Terapéutica , Riñón , Cálculos Renales/terapia
5.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(2): 156-161, 2023 Apr 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-37283099

RESUMEN

OBJECTIVES: To investigate the effect of progressive pre-disconnection of urethral mucosal flap during transurethral plasmakinetic enucleation of prostate (TUPEP) on early recovery of urinary continence. METHODS: Clinical data of patients with benign prostatic hyperplasia (BPH) admitted in Zhujiang Hospital of Southern Medical University during February and May 2022 were collected. All the patients underwent TUPEP, and the progressive pre-disconnection of urethral mucosal flap was performed in the procedure. The total operation time, enucleation time, postoperative bladder irrigation time and catheter indwelling time were recorded. Urinary continence was evaluated 24 h, 1 week, and 1, 3, 6 months after the removal of urinary catheter. RESULTS: All surgeries were successfully completed at one time with less intraoperative bleeding, and there were no complications such as rectal injury, bladder injury or perforation of prostate capsule. The total operation time was (62.2±6.5) min, the enucleation time was (42.8±5.2) min, the postoperative hemoglobin decrease by (9.5±4.5) g/L, the postoperative bladder irrigation time was (7.9±1.4) h, and the postoperative catheter indwelling time was 10.0 (9.2, 11.4) h. Only 2 patients (3.6%) had transient urinary incontinence within 24 h after catheter removal. No urinary incontinence occurred at 1 week, and 1, 3, 6 months after operation, and no safety pad was needed. The Qmax at 1 month after operation was 22.3 (20.6, 24.4) mL/s, international prostate symptom scores were 8.0 (7.0, 9.0), 5.0 (4.0, 6.0) and 4.0 (3.0, 4.0) at 1, 3 and 6 months after surgery, and quality of life scores at 1, 3 and 6 months after surgery were 3.0 (2.0, 3.0), 2.0 (1.0, 2.0) and 1.0 (1.0, 2.0), all of these indicators were better than those before surgery (all P<0.01). CONCLUSIONS: In the treatment of BPH, the application of progressive pre-disconnection of urethral mucosal flap in TUPEP can completely remove the hyperplastic glands and promote early recovery of postoperative urinary continence with less perioperative bleeding and decreased surgical complications.


Asunto(s)
Hiperplasia Prostática , Resección Transuretral de la Próstata , Incontinencia Urinaria , Masculino , Humanos , Próstata , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Calidad de Vida , Vejiga Urinaria , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & control , Incontinencia Urinaria/cirugía , Resultado del Tratamiento
6.
Zhonghua Nan Ke Xue ; 29(10): 904-909, 2023 Oct.
Artículo en Zh | MEDLINE | ID: mdl-38639660

RESUMEN

OBJECTIVE: To explore the application prospect and clinical efficacy of transurethral plasmakinetic enucleation of the Giant prostatic hyperplasia. METHODS: The clinical data of 5 patients with Giant prostatic hyperplasia treated by transurethral plasmakinetic enucleation in our department from december 2021 to january 2023 were retrospectively analyzed. RESULTS: All 5 patients successfully completed the operation, aged 69-80 years (73.2±4.32),PSA level was 8.07~42.90ng/ml (22.81±13.97), prostate volume was 321.05-534.26g (388.34±84.26), enucleation time was 120-240 min (174±61.48), Gland processing time 40-120 min(63±32.71). There were 1 case of perforation of prostate capsule and severe hematuria,3 cases of blood transfusion. 2 cases of transient urinary incontinence were improved after 2 weeks and 4 months postoperative respectively. International Prostate Symptom Score (IPSS),and quality of life score (QoL) and Maximum urine flow rate(Qmax) were significantly improved compared with preoperative parameters. CONCLUSION: It is safe and effective to treat GPH with plasma enucleation through urethra with skilled plasma enucleation technique.


Asunto(s)
Hiperplasia Prostática , Resección Transuretral de la Próstata , Humanos , Masculino , Próstata/cirugía , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/diagnóstico , Calidad de Vida , Estudios Retrospectivos , Resección Transuretral de la Próstata/métodos , Resultado del Tratamiento , Anciano , Anciano de 80 o más Años
7.
Int J Med Sci ; 19(2): 377-392, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35165523

RESUMEN

Background: Necroptosis, a cell death of caspase-independence, plays a pivotal role in cancer biological regulation. Although necroptosis is closely associated with oncogenesis, cancer metastasis, and immunity, there remains a lack of studies determining the role of necroptosis-related genes (NRGs) in the highly immunogenic cancer type, kidney renal clear cell carcinoma (KIRC). Methods: The information of clinicopathology and transcriptome was extracted from TCGA database. Following the division into the train and test cohorts, a three-NRGs (TLR3, FASLG, ZBP1) risk model was identified in train cohort by LASSO regression. The overall survival (OS) comparison was conducted between different risk groups through Kaplan-Meier analysis, which was further validated in test cohort. The Cox proportional hazards regression model was introduced to assess its impact of clinicopathological factors and risk score on survival. ESTIMATE and CIBERSORT algorithms were introduced to evaluate immune microenvironment, while enrichment analysis was conducted to explore the biological significance. Correlation analysis was applied for the correlation assessment between checkpoint gene expression and risk score, between gene expression and therapeutic response. Gene expressions from TCGA were verified by GEO datasets and immunohistochemistry (IHC) analysis. Results: This NRGs-related signature predicted poorer OS in high-risk group, which was also verified in test cohort. Risk score could also independently predict survival outcome of KIRC. Significant changes were also found in immune microenvironment and checkpoint gene expressions between different risk groups, with immune functional enrichment in high-risk group. Interestingly, therapeutic response was correlated with the expressions of NRGs. The expressions of NRGs from TCGA were consistent with those from GEO datasets and IHC analysis. Conclusion: The NRGs-related signature functions as a novel prognostic predictor of immune microenvironment and therapeutic response in KIRC.


Asunto(s)
Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Necroptosis/genética , Transcriptoma/genética , Microambiente Tumoral/genética , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/mortalidad , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Regresión , Factores de Riesgo
8.
Mol Hum Reprod ; 27(1)2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33543289

RESUMEN

Accumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wnt ligands, Wnt receptors, Wnt intracellular signals and Wnt regulators. By sorting out and integrating relevant functions, as well as underlining the controversies among different reports, our review aims to offer an overview of Wnt signaling in male reproductive physiology and pathology for further mechanistic studies.


Asunto(s)
Reproducción/fisiología , Proteínas Wnt/farmacología , Vía de Señalización Wnt/fisiología , Animales , Humanos , Infertilidad Masculina/metabolismo , Masculino , Receptores Wnt/fisiología
9.
Acta Med Okayama ; 75(4): 415-421, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34511607

RESUMEN

Human RAD17, as an agonist of checkpoint signaling, plays an essential role in mediating DNA damage. This hospital-based case-control study aimed to explore the association between RAD17 rs1045051, a missense sin-gle nucleotide polymorphism (SNP), and prostate cancer risk. Subjects were 358 prostate cancer patients and 314 cancer-free urology patients undergoing treatment at the Zhujiang Hospital of Southern Medical University in China. RAD17 gene polymorphism rs1045051 was evaluated by the SNaPshot method. Compared with the RAD17 gene polymorphism rs1045051 AA genotype, there was a higher risk of prostate cancer for the CC gen-otype (adjusted odds ratio [AOR] = 1.731, 95% confidence interval [95%CI] = 1.031-2.908, p = 0.038). Compared with the A allele, the C allele was significantly associated with the disease status (AOR = 1.302, 95%CI = 1.037-1.634, p = 0.023). All these findings indicate that in the SNP rs1045051, both the CC genotype and C allele may have a substantial influence on the prostate cancer risk.


Asunto(s)
Puntos de Control del Ciclo Celular/genética , Proteínas de Ciclo Celular , Neoplasias de la Próstata/genética , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Daño del ADN/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/sangre
10.
Cancer Control ; 27(1): 1073274820976665, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33356494

RESUMEN

In recent years, immune checkpoint inhibitors (ICIs) targeting CTLA-4 or PD1/PDL1 have achieved remarkable success in the treatment of bladder cancer (BLCA), but only a few patients have shown durable clinical benefits. The prognostic role of a mutant form of the tumor suppressor gene TP53 (TP53-MT) in predicting the efficacy of ICIs is highly controversial; therefore, in this study, we obtained data for 210 patients from an immunotherapy cohort, 412 patients from The Cancer Genome Atlas (TCGA)-BLCA cohort and 18 BLCA cell lines from Genomics of Drug Sensitivity in Cancer (GDSC), and we performed integrated bioinformatic analysis to explore the relationships between TP53-MT and clinical benefits derived from ICI treatment and the underlying mechanisms. We conclude that TP53-MT is a potential indicator of a relatively good response to ICIs and associated with prolonged overall survival (OS) (log-rank test, hazard ratio (HR) = 0.65 [95% confidence interval (CI), 0.44-0.99], p = 0.041). Through integrated analysis with several platforms, we found that TP53-MT patients were more likely to benefit from ICIs than wild-type P53 (TP53-WT) patients, which may be the result of 2 major mechanisms. First, the patients with TP53-MT showed stronger tumor antigenicity and tumor antigen presentation, as indicated by a higher tumor mutational load, a higher neoantigen load and increased expression of MHC; second, the antitumor immunity preexisting in tumors was stronger in samples with TP53-MT than in those with TP53-WT, including enrichment of interferon-gamma, positive regulation of TNF secretion pathways and increased expression of some immunostimulatory molecules, such as CXCL9 and CXCL10. This study provided some clues for identifying patients who would potentially benefit from ICIs at the somatic genomic level, developing new indications for targeted second-generation sequencing and promoting the development of precision medicine.


Asunto(s)
Biomarcadores de Tumor/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Recurrencia Local de Neoplasia/epidemiología , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Presentación de Antígeno/genética , Antígenos de Neoplasias/inmunología , Quimiocina CXCL10/genética , Quimiocina CXCL9/genética , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Conjuntos de Datos como Asunto , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/inmunología , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/genética , Medicina de Precisión/métodos , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/mortalidad
11.
Acta Med Okayama ; 74(2): 175-178, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32341594

RESUMEN

Urolithiasis, a common condition in patients with spinal deformity, poses a challenge to surgical procedures and anesthetic management. A 51-year-old Chinese male presented with bilateral complex renal calculi. He was also affected by severe kyphosis deformity and spinal stiffness due to ankylosing spondylitis. Dr. Li performed the percutaneous nephrolithotomy under local infiltration anesthesia with the patient in a kneeling prone position, achieving satisfactory stone clearance with no severe complications. We found this protocol safe and effective to manage kidney stones in patients with spinal deformity. Local infiltration anesthesia may benefit patients for whom epidural anesthesia and intubation anesthesia are difficult.


Asunto(s)
Anquilosis/complicaciones , Cálculos Renales/cirugía , Cifosis/complicaciones , Nefrolitotomía Percutánea/métodos , Posicionamiento del Paciente , Anestesia Local/métodos , Humanos , Cálculos Renales/complicaciones , Cálculos Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
12.
World J Urol ; 36(7): 1117-1126, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29459994

RESUMEN

PURPOSE: Bipolar endoscopic enucleation of the prostate (BEEP) was recommended by the 2016 EAU guidelines as the first choice of surgical treatment in men with a substantially enlarged prostate and moderate-to-severe lower urinary tract symptoms. The main aim of this study was to compare a modified diode laser enucleation of the prostate (DiLEP) to BEEP. METHODS: A total of 114 patients with prostate (20-160 mL) were randomized 1:1 into either DiLEP or BEEP in a dual-centre, non-inferiority-design randomized-controlled trial. The primary outcomes included Qmax and IPSS at 12 months. Non-inferiority was evaluated by comparing the two-sided 95% CI for the mean differences of Qmax and IPSS. Secondary endpoints included other perioperative parameters, postoperative micturition variables, and complication rate. RESULTS: A total of 111 patients (97%) had completed the intent-to-treat analysis, The results showed that DiLEP was comparable to BEEP regarding Qmax (28.0 ± 7.0 vs. 28.1 ± 7.2 mL/s) and IPSS (3.0 ± 2.2 vs. 2.9 ± 2.6) at 12 months, the non-inferiority was met for both Qmax and IPSS. There were also no significant difference between two groups regarding tissue removal rate (71.8 vs. 73.8%), hemoglobin decrease (0.33 ± 0.66 vs. 0.36 ± 0.75 g/dL), sodium decrease (1.0 ± 2.7 vs. 0.3 ± 2.9 mmol/L), and Clavien III complications (5.3 vs. 1.8%) at 12 months. CONCLUSIONS: This DiLEP is an anatomical endoscopic enucleation technique for the treatment of benign prostatic hyperplasia, it is non-inferior to BEEP regarding Qmax and IPSS at 12 months postoperatively.


Asunto(s)
Terapia por Láser/métodos , Síntomas del Sistema Urinario Inferior/cirugía , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Anciano , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Láseres de Semiconductores , Tiempo de Internación , Síntomas del Sistema Urinario Inferior/etiología , Masculino , Hiperplasia Prostática/complicaciones , Calidad de Vida , Factores de Tiempo , Resultado del Tratamiento
13.
Biochem Biophys Res Commun ; 483(1): 197-202, 2017 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-28042037

RESUMEN

Lycorine, an alkaloid extracted from Amaryllidaceae genera, exhibits antitumor activities against several human solid-tumor and leukemia cells with extensive influence on various cell signaling molecules. However, the effect of lycorine on bladder cancer has not yet been investigated. In this study, we demonstrated that lycorine induced apoptosis in human bladder cancer T24 cells, an effect that is mediated via inhibition of phospho-Akt expression and the consequent activation of caspase-3 and Bax in vitro. In an in vivo experiment, T24 cells were subcutaneously implanted in the right rear flank of nu/nu mice. Lycorine treatment for 14 days significantly inhibited tumor growth compared with that in controls. Collectively, our findings suggest that lycorine suppressed the Akt pathway and activated the intrinsic apoptotic cascade, leading to the apoptosis of bladder cancer cells. We suggest that lycorine can be a viable therapeutic option for bladder cancer patients.


Asunto(s)
Alcaloides de Amaryllidaceae/farmacología , Apoptosis/efectos de los fármacos , Fenantridinas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/farmacología , Caspasa 3/metabolismo , Línea Celular , Línea Celular Tumoral , Femenino , Humanos , Ratones Desnudos , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Vejiga Urinaria/citología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de Xenoinjerto
14.
BJU Int ; 120(4): 530-536, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28370930

RESUMEN

OBJECTIVES: To investigate the long-term functional outcomes and complications after continent cutaneous diversion with the Lundiana pouch. PATIENTS AND METHODS: Complications, re-operations, renal function, and continence were ascertained from patient charts. Outcome variables were validated by a second and independent review of the patient files. RESULTS: A complication of Clavien-Dindo grade ≥III, including unscheduled re-admissions, occurred in 45/193 patients (23%) at ≤90 days of surgery. At a median follow-up of 13 years, 105/193 patients (54%) had undergone at least one re-operation, with uretero-intestinal stricture being the most prevalent cause [28 patients (15%)]. Re-operations were more prevalent in patients operated during the first half of the study period than during the second half (2000-2007; 62% vs 47%; P = 0.03), and they were also more frequent in patients who underwent surgery for benign causes than in patients who underwent surgery for malignancy (60% vs 51%; P = 0.04). Continence was achieved in 172/188 patients (91%). In all, 16% of all patients required revisional surgery of the outlet to remain continent with an easily catheterisable pouch or to address stomal stenosis. The mean decrease in estimated glomerular filtration rate was more pronounced in patients with benign indications for urinary diversion than in those with malignancies, even after adjusting for younger age at surgery and longer follow-up in the former group (22 vs 11 mL/min/1.73 m2 ; P < 0.006). A disinterested third-party assessment revealed 10 postoperative complications, 17 re-operations during follow-up, and seven occasions of hospitalisation due to pyelonephritis (included in data above) not recorded at the primary data review. CONCLUSIONS: The Lundiana pouch is associated with a high risk of re-operation, although the functional results are good. Independent review by a third party increased the validity of the outcome data.


Asunto(s)
Carcinoma de Células Transicionales/cirugía , Reoperación/estadística & datos numéricos , Neoplasias de la Vejiga Urinaria/cirugía , Reservorios Urinarios Continentes/efectos adversos , Anciano , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Estudios de Cohortes , Cistectomía/métodos , Femenino , Estudios de Seguimiento , Hospitales Universitarios , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/cirugía , Reoperación/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Tasa de Supervivencia , Suecia , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Incontinencia Urinaria/prevención & control
15.
World J Urol ; 35(3): 395-402, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27380209

RESUMEN

OBJECTIVE: To illustrate a ligation-free technique and compare perioperative and postoperative outcomes of this technique versus the standard suture method. PATIENTS AND METHODS: This study is a retrospective review of 233 consecutive patients with localized prostate cancer who underwent ligation-free technique (n = 180, Group 1) or standard ligation (n = 53, Group 2) at an academic institution from February 2010 to January 2014. RESULTS AND LIMITATIONS: Operative time was significantly shorter in Group 1 than in Group 2 (148.47 vs. 164.25 min, p = 0.000). No difference in EBL was noted between the groups (191.11 vs. 185.06 mL, p = 0.055). Postoperative continence rates at 3, 6, and 12 months in Groups 1 and 2 were 40.0 versus 24.5, 54.4 versus 37.7, and 73.9 versus 71.7 %, respectively. These differences were statistically significant. No patient in either group had a positive apical surgical margin. During follow-up, tumor recurrence or metastasis was not observed in any patient. Limitations of the study include this retrospective study of a single-center experience and lack of potency appraisal. CONCLUSIONS: This present ligation-free technique showed a statistically significant shorter interval to recovery of continence and higher continence rates in short-term postoperative results by contrast to conventional suture ligation, but no significant difference was revealed in long-term urinary control. We offer this technique and the correlative data to provide more information for deeply understanding the precise construction of the dorsal vascular complex and the mechanism of urinary control.


Asunto(s)
Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Próstata/irrigación sanguínea , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Incontinencia Urinaria/epidemiología , Anciano , Pérdida de Sangre Quirúrgica , China , Estudios de Seguimiento , Humanos , Ligadura , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Estadificación de Neoplasias , Tempo Operativo , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Técnicas de Sutura
16.
Urol Int ; 98(2): 169-176, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27602571

RESUMEN

INTRODUCTION: FK506 binding proteins (FKBPs) function as oncogenes or tumor suppressors by interacting with steroid hormone receptors, kinases, or other cellular factors in addition to intracellular ligands FK506 and rapamycin. In this study, we aimed at evaluating the expression and function of FKBPs in renal cell carcinoma (RCC). MATERIALS AND METHODS: Thirty-four RCC specimens were analyzed by whole transcriptome sequencing. Small interfere RNA was employed to knockdown FKBP10 in 786-O and A-704 cells, and cell proliferation, cell cycle progression, invasion and migration were evaluated. RESULTS: FKBP10 was different from other members of FKBPs with most significant upregulation in almost all RCC specimens, compared to normal mucosa. FKBP10 expression was high in additional 38 RCC specimens and RCC cell lines compared to paired non-tumor tissues and normal renal tubule cells. FKBP10 knockdown led to cell cycle arrest at G0/G1 phase, and reduced cell proliferation, invasion, and migration in 786-O and A-704 cells. In addition, heat shock protein 90 was significantly downregulated after FKBP10 knockdown. CONCLUSIONS: FKBP10 is overexpressed and promotes RCC and is a new promising biomarker and therapy target for RCC.


Asunto(s)
Carcinoma de Células Renales/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/metabolismo , Proteínas de Unión a Tacrolimus/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Perfilación de la Expresión Génica , Humanos , Ligandos , Masculino , Persona de Mediana Edad , ARN Interferente Pequeño/metabolismo , Análisis de Secuencia de ARN
17.
Tumour Biol ; 37(9): 12843-12854, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27449037

RESUMEN

The biological role of miR-26a involved in the carcinogenesis of prostate cancer (PC) has been controversial. Besides, the underlying mechanism by which miR-26a plays a role in PC has been unclear. To investigate the role of miR-26a-5p in the PC, miR-26a-5p was detected and statistically analyzed in clinical PC tissues and a panel of PC cell lines. Using bioinformatics analysis, we found that serpine1 messenger RNA (mRNA) binding protein 1 (SERBP1) was a potential downstream target of miR-26a-5p. Using luciferase reporter and western blot, we identified that miR-26a-5p negatively regulated SERBP1 on the PC cell line level. It was confirmed that miR-26a-5p was markedly downregulated in PC tissues compared with normal controls whose reduced expression was significantly associated with metastasis and poor overall prognosis and found that miR-26a-5p was able to prevent proliferation and motility of PC cells in vitro. Additionally, SERBP1 was identified as a downstream target of miR-26a-5p. Moreover, it was observed that SERBP1 was markedly upregulated in prostate cancer tissues and was significantly associated with tissue metastasis and Gleason score. Taken together, our results for the first time demonstrate that the loss of miR-26a-5p promotes proliferation, migration, and invasion through targeting SERBP1 in PC, supporting the tumor-suppressing role of miR-26a-5p in PC.


Asunto(s)
Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , MicroARNs/genética , Neoplasias de la Próstata/genética , Proteínas de Unión al ARN/genética , Regiones no Traducidas 3'/genética , Secuencia de Bases , Línea Celular , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Modelos de Riesgos Proporcionales , Prostatectomía , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/cirugía , Interferencia de ARN , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico
18.
Tumour Biol ; 37(5): 6653-9, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26646562

RESUMEN

In this study, we aimed to identify the influence of exonuclease 1 (EXO1) single-nucleotide polymorphism rs9350, which is involved in DNA mismatch repair, on prostate cancer risk in Chinese people. In our hospital-based case-control study, 214 prostate cancer patients and 253 cancer-free control subjects were enrolled from three hospitals in China. Genotyping for rs9350 was performed by the SNaPshot(®) method using peripheral blood samples. Consequently, a significantly higher prostate cancer risk was observed in patients with the CC genotype [odds ratio (OR) = 1.678, 95 % confidence interval (CI) = 1.130-2.494, P = 0.010] than in those with the CT genotype. Further, the CT/TT genotypes were significantly associated with increased prostate cancer risk (adjusted OR = 1.714, 95 % CI = 1.176-2.500, P = 0.005), and the C allele had a statistically significant compared with T allele (P = 0.009) of EXO1 (rs9350). Through stratified analysis, significant associations were revealed for the CT/TT genotype in the subgroup with diagnosis age >72 (adjusted OR = 1.776, 95 % CI = 1.051-3.002, P = 0.032) and in patients with localized disease subgroup (adjusted OR = 1.798, 95 % CI = 1.070-3.022, P = 0.027). In addition, we observed that patients with prostate-specific antigen (PSA) levels of ≤10 ng/mL were more likely to have the CT/TT genotypes than those with PSA levels of >10 ng/mL (P = 0.006). For the first time, we present evidence that the inherited EXO1 polymorphism rs9350 may have a substantial influence on prostate cancer risk in Chinese people. We believe that the rs9350 could be a useful biomarker for assessing predisposition for and early diagnosis of prostate cancer.


Asunto(s)
Reparación de la Incompatibilidad de ADN , Exodesoxirribonucleasas/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Anciano , Alelos , Estudios de Casos y Controles , China/epidemiología , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Oportunidad Relativa , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Factores de Riesgo
19.
World J Urol ; 34(9): 1207-19, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26699627

RESUMEN

PURPOSE: To evaluate the efficacy and safety of transurethral enucleation of the prostate (TUEP) versus transvesical open prostatectomy (OP) for the management of large benign prostatic hyperplasia (BPH). METHODS: Randomized controlled trials (RCTs) comparing TUEP and OP were identified from PubMed, Embase and Web of Science up to February 28, 2015. A meta-analysis was conducted with the STATA 12.0 software. RESULTS: Nine RCTs including 758 patients were enrolled in our meta-analysis. There were no significant differences between the two groups in the maximum urinary flow rate at 1, 3, 6 months, 1 and 2 years: postvoiding residual urinary volume, prostate-specific antigen, international prostate symptom score and quality of life score at 1, 3, 6 months and 1 year; or international index of erectile function at 3, 6 months and 1 year. Perioperative outcomes including hemoglobin level drop, catheter period, irrigation length and hospital stay favored TUEP, while operative time and resected prostate weight favored OP. There was significantly less blood transfusion with TUEP, but no significant differences were found in other complications such as recatheterization, urinary tract infection, reintervention for clots and bleeding control, incidence of pneumonia and infarction, transient incontinence, bladder neck contracture, urethral stricture and recurrent adenoma. CONCLUSIONS: TUEP can be performed effectively and safely with functional outcomes and complications similar to OP for large BPH, whereas it has the advantages of a shorter catheter period, shorter hospital stays and less blood transfusion. These findings seem to support TUEP as the next-generation "gold standard" of surgery for large BPH.


Asunto(s)
Prostatectomía/métodos , Hiperplasia Prostática/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Masculino , Hiperplasia Prostática/patología , Uretra , Vejiga Urinaria
20.
Cell Mol Biol Lett ; 21: 27, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28536629

RESUMEN

Immunoglobulin G (IgG) has been implicated in the progression of various cancers. This study explored the role of IgG in the proliferation, apoptosis, cell cycle and in vitro invasive properties of LNCaP prostate cancer cells. We used IGHG1 small interfering RNA to silence IgG1 expression in LNCaP cells. The efficacy of IgG1 gene knockdown was confirmed using qPCR and western blotting. The colony formation, proliferation, migration and invasion abilities of LNCaP cells after transfection were assessed using colony-forming, flow cytometry and transwell assays. The expressions of PCNA and caspase-3 proteins in LNCaP cells after transfection were detected with immunofluorescence staining and western blotting. IgG1 silencing significantly decreased the colony formation, survival, cell cycle progression, migration and invasion of LNCaP cells (p < 0.05). IgG1 silencing also reduced the amount of the proliferation marker PCNA and induced formation of the apoptotic marker caspase-3 (p < 0.05). Our results show that IgG1 produced by LNCaP cells confers advantages for tumor cell survival, proliferation, migration and invasion, suggesting that IgG1 is a potential target for prostate cancer treatment.


Asunto(s)
Apoptosis , Movimiento Celular , Proliferación Celular , Inmunoglobulina G/genética , Invasividad Neoplásica , Neoplasias de la Próstata/metabolismo , Interferencia de ARN , Caspasa 3 , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Antígeno Nuclear de Célula en Proliferación , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
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