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1.
Urol J ; 21(2): 114-120, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38581150

RESUMO

PURPOSE: To assess outcomes of bilateral single-session percutaneous nephrolithotomy (PCNL) with minimally invasive techniques in pediatric population. MATERIALS AND METHODS: From August 2015 to July 2021, 45 children (including 12 infants) were treated with bilateral single-session PCNL, which included miniPCNL (12-16-Fr) and Microperc (4.8-Fr). Patient, stone and operation-related characteristics, stone-free rate (SFR) and complication rate (CR) were compared using ANOVA. Independent predictors were determined using multivariate linear regression. RESULTS: The mean stone burden was 3.2 cm in sum diameter for both kidneys. For bilateral kidneys, the mean operative time was 61.6min and SFR was 93.3%; CR was 53.3%, of which complications of Clavien grade 1 and 2 accounted for 46.7%. Bilateral Microperc, bilateral miniPCNL and Microperc plus miniPCNL was performed in 19, 14 and 12 children respectively. Both irrigation volume and postoperative stay were less in groups with Microperc. Both SFRs and CRs were satisfactory for the three groups. Self-limiting hematuria represented the most common complication of all cases (33.3%), especially in groups with miniPCNL. The stone burden was the only independent predictor for operative time (P < .001) and the postoperative complication (P = .008). Children with older age (P = .009), higher body mass index (P = .016) or a higher stone burden (P < .001) received larger irrigated fluid volume. Microperc was associated with less irrigated fluid volume (P = .001). Children with Clavien grade 3 complications (P = .004) spent prolonged postoperative hospital stay. CONCLUSION: With favourable SFR and acceptable CR, bilateral single-session PCNL with minimally invasive techniques might be an effective and safe procedure for pediatric nephrolithiasis.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Lactente , Criança , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/métodos , Cálculos Renais/cirurgia , Resultado do Tratamento , Rim/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Nefrostomia Percutânea/métodos
2.
BMC Urol ; 24(1): 52, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443863

RESUMO

BACKGROUND: The forgotten ureteral stents (FUS) is one of the late complications of stent placement. This systematic review summarized different aspects of FUS and focused on the problems and solutions related to FUS. METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. PubMed® and Embase® were searched from inception until October 1st, 2022. Eligible studies were those defining FUS as a stent unintentionally left in situ longer than at least 2 months. RESULTS: Total 147 studies with 1292 patients were finally included. The mean indwelling time of FUS was 33.5 months (range from 3 months to 32 years). The most common initial cause for stent placement was adjunct treatment to urolithiasis (79.2%). The major forgetting reasons were patient-related (83.9%), which included poor compliance, lapse in memory, and misconceptions about the necessity of timely removal. Primary presenting complaints were flank pain (37.3%), lower urinary tract symptoms (33.3%), and hematuria (22.8%). Encrustation (80.8%) and urinary tract infections (40.2%) were the most common complications detected in patients with FUS. Computed tomography evolving as a preferred imaging test (76.1%) was indispensable for evaluating encrustation, migration, fracture and other complicated situations in patients with FUS. Besides, evaluation of kidney function and infection status was also of great importance. Multiple and multimodal procedures (59.0%) were often necessitated to achieve the stent-free status, and were mostly endoscopic procedures. Cystoscope was most commonly used (64.8%). Retrograde ureteroscopy (43.4%) and antegrade stent removal (31.6%) were often used when dealing with more complicated situations. Extracorporeal shockwave lithotripsy (30.4%) was often used as adjunctive to other endoscopic procedures, but it sometimes failed. The decision regarding the choice of treatment is based on the volume and site of encrustation, the direction of migration, the site of fracture, kidney function and other urinary comorbidities. CONCLUSIONS: FUS not only pose hazard to patients' health, but also impose a huge economic burden on medical care. Thorough preoperative evaluation is fundamental to developing the treatment strategy. The management of FUS should be individualized using different treatment modalities with their advantages to minimize patients' morbidities. Prevention is better than cure. Strengthening health education and setting a tracking program are of great importance to the prevention of FUS.


Assuntos
Corpos Estranhos , Fraturas Ósseas , Litotripsia , Stents , Urolitíase , Humanos , Cistoscópios , Hematúria , Ureteroscopia , Stents/efeitos adversos
3.
J Endourol ; 36(11): 1502-1508, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35670260

RESUMO

Objectives: To evaluate learning curves in pediatric flexible ureteroscopy (FURS) and pediatric prone percutaneous nephrolithotomy (PCNL) by a single surgeon with experience in adult endourologic procedures. Materials and Methods: Children who were found to have nephrolithiasis and treated with PCNL or FURS from June 2014 to April 2019 were analyzed. Patient demographics, stone characteristics, stone-free rate (SFR), and complication rate (CR) were reported. Learning curves were generated to estimate the effect of a surgeon's experience on outcomes. Results: Seventy-three children underwent PCNL on 86 sides in 77 operations and 275 children underwent FURS on 320 sides in 288 operations. The SFRs were 88.1% (282/320) for FURS procedures and 89.5% (77/86) for PCNL procedures. CRs were 19.8% (57/288) and 35.1% (27/77), respectively. Learning curves showed that the SFRs of the two procedures increased with the accumulation of cases. There was an apparent improvement of SFR for PCNL procedures after ∼60 surgeries. A favorable SFR of FURS could be achieved at the start of learning. No apparently decreased CRs were observed for either PCNL or FURS. Conclusions: Both PCNL and FURS could achieve satisfactory SFRs and accepted CRs in pediatric stones. Increased surgical experience was associated with improved SFRs of both PCNL and FURS procedures, and the surgeon's experience of adult FURS translating to that of pediatric FURS was better than adult PCNL translating to pediatric PCNL. A surgeon needs ∼60 cases of PCNL to achieve competence. For FURS, a favorable SFR could be achieved at the start of learning.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Adulto , Humanos , Criança , Nefrolitotomia Percutânea/métodos , Ureteroscopia/métodos , Curva de Aprendizado , Resultado do Tratamento , Ureteroscópios , Cálculos Renais/cirurgia , Estudos Retrospectivos
4.
World J Surg Oncol ; 19(1): 18, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472645

RESUMO

BACKGROUND: To evaluate the predictive performance of age for the risk of Gleason score change and pathologic upstaging. EVIDENCE ACQUISITION: Ovid MEDLINE, Ovid Embase, and the Cochrane Library were searched from inception until May 2020. Quality of included studies was appraised utilizing the Newcastle-Ottawa Quality Assessment Scale for case-control studies. The publication bias was evaluated by funnel plots and Egger's tests. EVIDENCE SYNTHESIS: Our search yielded 27 studies with moderate-to-high quality including 84296 patients with mean age of 62.1 years. From biopsy to prostatectomy, upgrading and upstaging occurred in 32.3% and 9.8% of patients, respectively. Upgrading from diagnostic biopsy to confirmatory biopsy was found in 16.8%. Older age was associated with a significant increased risk of upgrading (OR 1.04, 95% CI 1.03-1.05), and similar direction of effect was found in studies focused on upgrading from diagnostic biopsy to confirmatory biopsy (OR 1.06, 95% CI 1.04-1.08). For pathologic upstaging within older men compared with younger, the pooled odds was 1.03 (95% CI 1.01-1.04). CONCLUSION: Thorough consideration of age in the context of effect sizes for other factors not only prompts more accurate risk stratification but also helps providers to select optimal therapies for patients with prostate cancer.


Assuntos
Neoplasias da Próstata , Idoso , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
5.
BMC Urol ; 21(1): 3, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407381

RESUMO

BACKGROUND: To explore the rate of Gleason sum upgrading (GSU) from biopsy to radical prostatectomy pathology and to develop a nomogram for predicting the probability of GSU in a Chinese cohort. METHODS: We retrospectively reviewed our prospectively maintained prostate cancer (PCa) database from October 2012 to April 2020. 198 patients who met the criteria were enrolled. Multivariable logistic regression analysis was performed to determine the predictors. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination. Calibration curve was used to assess the concordance between predictive probabilities and true risks. RESULTS: The rate of GSU was 41.4%, whilst GS concordance rate was 44.4%. The independent predictors are prostate specific antigen (PSA), greatest percentage of cancer (GPC), clinical T-stage and Prostate Imaging Reporting and Data System (PI-RADS) score. Our model showed good discrimination (AUC of 0.735). Our model was validated internally with good calibration with bias-corrected C-index of 0.726. CONCLUSIONS: Utilization of basic clinical variables (PSA and T-stage) combined with imaging variable (PI-RADS) and pathological variable (GPC) could improve performance in predicting actual probabilities of GSU in the 24-core biopsy scheme. Our nomogram could help to assess the true risk and make optimal treatment decisions for PCa patients.


Assuntos
Nomogramas , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Biópsia , China , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia/métodos , Estudos Retrospectivos
6.
World J Surg Oncol ; 18(1): 310, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243261

RESUMO

BACKGROUND: Bladder cancer displays a broad mutational spectrum and intratumor heterogeneity (ITH), which results in difference in molecular phenotypes and resistance to therapies. However, there are currently no clinically available measures to predict patient prognosis using ITH. We aimed to establish a clinically relevant biomarker by using ITH for informing predictive of outcomes. METHODS: We used the Bioconductor R package Maftools to efficiently and comprehensively analyze somatic variants of muscle-invasive bladder cancer (MIBC) from The Cancer Genome Atlas (TCGA). We then used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters as well as mutational subtypes. RESULTS: We observed a broad range of somatic mutations in MIBC from TCGA. MATH value was higher for the high-grade group than for the low-grade group (p < 0.05). There was a strong correlation between higher MATH value and presence of TP53 mutations (p = 0.008), as well as between lower MATH value and presence of FGFR3 mutations (p = 0.006). Patients with FGFR3 mutation and low MATH value exhibit longer overall survival time than that of all BLCA patients (p = 0.044), which was replicated in another bladder cancer database composed of 109 BLCA patients. CONCLUSION: Measures of tumor heterogeneity may be useful biomarkers for identifying patients with bladder cancer. Low MATH value was an independent risk factor that predicted better prognosis for patients with FGFR3 mutation compared to all BLCA patients.


Assuntos
Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Neoplasias da Bexiga Urinária , Alelos , Biomarcadores Tumorais/genética , Humanos , Mutação , Prognóstico , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética
7.
Urol J ; 18(5): 477-484, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084002

RESUMO

PURPOSE: To examine the correlation between prostate specific antigen (PSA) and the risk of Gleason sum upgrading (GSU) from biopsy Gleason sum (bGS) to prostatectomy Gleason sum (pGS). MATERIALS AND METHODS: Five electronic databases (Web of Science, Ovid Medline, Ovid Embase, SCOPUS and the Cochrane Library) were searched from inception until March 2020. Studies were included if they focused on the relationship between PSA and GSU analyzed in multivariable analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. Quality of included studies was appraised utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies. The publication bias was evaluated by funnel plot and Egger's test. RESULTS: Our search yielded 19 studies with high quality including 42193 patients. GSU was found in 28.2% of patients. Higher PSA level was associated with a significant increased risk of GSU (pooled OR = 1.14, 95% CI: 1.10-1.18; P < .05; I2 = 92%). For the definition of upgrading from bGS ≤ 6 to pGS ≥ 7, the odds of upgrading with higher PSA level as opposed to lower PSA level was 1.12 (95% CI: 1.11-1.14; P < .05; I2 = 13%), while the odds of upgrading with other definitions were 1.11 (95% CI: 1.05-1.18; P < .05; I2 = 89%). CONCLUSION: Patients with high level of serum PSA are at high risk of undergoing pathologic upgrading at prostatectomy. Combined with other risk factors, PSA prompts risk reclassification and improve confidence of urologists in management decisions for optimal therapy. Nevertheless, further robust studies are necessitated to confirm these results.


Assuntos
Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Gradação de Tumores , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Medição de Risco
8.
Environ Sci Pollut Res Int ; 27(21): 26163-26171, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361974

RESUMO

Cardiovascular diseases are related to vascular endothelial cell injury; our previous studies showed that endosulfan could cause hypercoagulation of blood by inducing endothelial cell injury. To clarify the mechanism of it, we treated human umbilical vein endothelial cells (HUVECs) with 0, 1, 5, and 10 µg/mL endosulfan, while in the inhibition groups, reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC, 3 mmol) and endoplasmic reticulum (ER) stress inhibitor (STF-083010, 10 µmol) were incubated prior to endosulfan. The results showed that endosulfan could induce inflammatory response and dysfunction by increasing the release of inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET-1), and inducing ROS production in HUVECs. We also found that endosulfan could cause ER damage, remarkably increase the expressions of inositol-requiring enzyme 1α (IRE1α), phosphorylated IRE1α (p-IRE1α), GRP78, XBP1, nuclear factor-kappa B (NF-κB), and phosphorylated NF-κB (p-NF-κB) in HUVECs. The presence of NAC antagonized the ROS production, expressions of IRE1α and p-IRE1α; however, STF-083010 could decrease the expression levels of GRP78, XBP1, NF-κB, and p-NF-κB and attenuate IL-1ß, IL-6, TNF-α, VCAM-1, and ET-1 release induced by endosulfan. These results demonstrated that endosulfan-induced endothelial inflammation and dysfunction through the IRE1α/NF-κB signaling pathway may be triggered by oxidative stress. The study provided experimental basis for the correlation between environmental pollutants (endosulfan) and cardiovascular diseases.


Assuntos
Endossulfano , NF-kappa B , Chaperona BiP do Retículo Endoplasmático , Endorribonucleases , Humanos , Inflamação , Inositol , Proteínas Serina-Treonina Quinases , Espécies Reativas de Oxigênio , Transdução de Sinais , Fator de Necrose Tumoral alfa
9.
Int Urol Nephrol ; 52(6): 1049-1055, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32026308

RESUMO

INTRODUCTION: Genistein is recognized as a potent anti-oxidant in soybean-enriched foods, which is a kind of phytoestrogen involved in anticancer activity in various cancers. OBJECTIVE: The objective of this study was to investigate the molecular mechanism of CDKN2a hypomethylation involved in the anti-tumor effect of genistein on kidney cancer. METHODS: The CDKN2a expression was measured using qRT-PCR. The level of CDKN2a methylation was detected using methylation-specific PCR. The apoptosis was detected via flow-cytometric analysis. The cell viability was detected using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Our results indicated that genistein induced cell apoptosis and inhibited the cell proliferation of kidney cancer cells. Moreover, genistein increased the expression of CDKN2a and decreased CDKN2a methylation. CONCLUSIONS: Our results demonstrated that the anti-tumor effect of genistein might induce cell apoptosis and inhibit the proliferation of kidney cancer cells via regulating CDKN2a methylation.


Assuntos
Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Genisteína/farmacologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Humanos , Metilação , Células Tumorais Cultivadas
10.
J Surg Oncol ; 119(8): 1145-1154, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30887516

RESUMO

BACKGROUND AND OBJECTIVES: Bladder cancer is one of the most common and highly recurrent cancers worldwide. Recurrence-associated genes may potentially predict cancer recurrence. We aimed to construct a recurrence-associated gene panel to improve the prognostic prediction of bladder cancer. METHODS: Based on DNA sequencing and clinical data from the TCGA-BLCA project, we identified 10 potential driver genes significantly associated with recurrence of bladder cancer. We performed multivariable logistic regression analysis to construct an optimized recurrence prediction model with nine recurrence-associated genes (EME1, AKAP9, ZNF91, PARD3, STAG2, ZFP36L2, METTL3, POLR3B, and MUC7) and clinical information as the independent variables. RESULTS: The area under the receiver operating characteristic (ROC) curve was 0.80 in this model, much higher than that of the baseline model (AUC = 0.73) and the same trend was also validated in its subset. Decision curve analysis also revealed that there is a significant net benefit gained by adding nine genes mutation to the baseline model. Furthermore, Kaplan-Meier survival analysis showed that eight out of the nine genes (excluding MUC7) had good effects on the overall prognosis of patients. CONCLUSIONS: This nine-gene panel will most likely be a useful tool for prognostic evaluation and will facilitate the personalized management of patients with bladder cancer.


Assuntos
Recidiva Local de Neoplasia/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Genéticas , Feminino , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Transcriptoma , Neoplasias da Bexiga Urinária/patologia
11.
Neurourol Urodyn ; 37(8): 2502-2509, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30070388

RESUMO

AIMS: Sacral spinal cord injury (SCI) could induce underactive bladder (UAB). Malfunction of connexin 43 (CX43) regulated by TGF-ß1 might involve in urinary bladder dysfunction. We studied the changes of CX43 and TGF-ß1/Smad3 signaling in detrusor of neurogenic bladder (NB) in sacral SCI rats. METHODS: Sacral SCI was produced by hemisection (SSCH) or transection (SSCT) of spinal cord between L4 and L5 in female Wistar rats. BBB scores, residual urine volume and bladder weight as well as characteristic cystometric parameters at 6th week were used to confirm the successful establishment of NB. Western blotting and qRT-PCR were used to exam the protein and mRNA expression levels of CX43, CX45, TGF-ß1, and Smad3 in detrusor. RESULTS: BBB scores were significantly decreased, with the lowest in SSCT rats (P < 0.01). The residual urine volume, mean bladder weight, and cystometric parameters were increased, with the highest in SSCT rats. CX43 and phospho-CX43 protein levels were significantly decreased, but those of TGF-ß1, Smad3, and phospho-Smad3 were significantly increased. It was the protein and mRNA levels of CX43 but not those of CX45 which were decreased in negative accordance with those of TGF-ß1 and Smad3. Those changes were more significant in SSCT than in SSCH rats. CONCLUSIONS: This study indicates that voiding dysfunction is related to the decreased CX43 function in detrusor from NB. TGF-ß1/Smad3 signaling might be involved in the down-regulation of CX43 in SCI rats. Early regulation of CX43 might be beneficial to patients with voiding dysfunction.


Assuntos
Conexina 43/biossíntese , Traumatismos da Medula Espinal/fisiopatologia , Fator de Crescimento Transformador beta1/biossíntese , Bexiga Urinaria Neurogênica/fisiopatologia , Animais , Conexina 43/genética , Estado de Descerebração/fisiopatologia , Feminino , Tamanho do Órgão , Ratos , Ratos Wistar , Proteína Smad3/biossíntese , Proteína Smad3/genética , Traumatismos da Medula Espinal/complicações , Fator de Crescimento Transformador beta1/genética , Bexiga Urinária/patologia , Bexiga Urinaria Neurogênica/etiologia , Urodinâmica
12.
Dalton Trans ; 46(30): 9959-9968, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28726908

RESUMO

Currently, the shortage of red components and easy aging of organic silicone still remain challenges for high-power phosphor-converted warm white light-emitting diodes (w-LEDs). Aiming to alleviate these issues, phosphor-in-glass (PiG), fabricated by co-sintering red- and yellow-emitting phosphors and low-melting glass, has been regarded as a promising color converter for w-LEDs. In this study, a Li+,Mn4+ co-doped SrMgAl10O17 red phosphor was synthesized via a conventional solid-state reaction. The as-prepared phosphor exhibits a deep red emission, ascribed to Mn4+:2Eg→4A2g spin-forbidden transition in the range of 600-700 nm with a narrow-band full width at half maximum of 55 nm, and provides an ideal broadband excitation extending from 250 to 530 nm. Impressively, the Li+ additive used as charge compensation was beneficial to enhance the Mn4+ luminescence by allowing more Mn4+ to replace Al3+. Furthermore, the developed SrMgAl10O17:Mn4+,Li+ red phosphor and commercial YAG:Ce3+ yellow phosphor co-doped inorganic PiG were successfully fabricated as color converters to substitute organic silicone. The w-LED was fabricated by combining an InGaN blue LED chip with a PiG plate. Importantly, the constructed w-LEDs exhibited superior optical performance and tuned chromaticity feature with the correlated color temperature evolved from bluish cool white (6903 K) to yellowish warm white (3717 K), and the color rendering index increased from 69.4 to 85.5, meeting the requirements for indoor lighting.

13.
Sci Rep ; 6: 29267, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27383411

RESUMO

Bilateral renal cell carcinomas (RCCs) pose a challenge for clinical treatment and management. Most bilateral RCCs are sporadic, and do not show a hereditary pattern indicative of VHL syndrome or other inherited cancers. The origin and evolution of these sporadic bilateral RCCs remains elusive. We obtained normal and tumor samples from two male patients suffering from early stage synchronous bilateral clear cell RCC (ccRCC), and analyzed genomic DNA using whole exome sequencing and bisulfite pyrosequencing. We detected distinct 3p loss of heterozygosity (LOH) in both tumors in each patient. Two tumors within the same patient harbored distinct driver mutations and different CpG hypermethylation sites in the VHL promoter. Moreover, tumors exhibit independent evolutionary trajectories. Therefore, distinct 3p LOH, combined with contingent driver gene mutations and independent VHL hypermethylation, led to independent tumor origin and parallel evolution of bilateral ccRCC in these two patients. Our results indicate that tumors in these two cases were not due to common germline oncogenic mutations. They were results of multiple de novo mutations in each kidney, rather than primary ccRCC with contralateral renal metastasis. Therefore, histopathologic and genetic profiling from single tumor specimen may underestimate the mutational burden and somatic heterogeneity of bilateral ccRCCs.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Genes Neoplásicos/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Metilação de DNA/genética , Feminino , Humanos , Perda de Heterozigosidade/genética , Masculino , Mutação/genética , Regiões Promotoras Genéticas/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/patologia
14.
Drug Des Devel Ther ; 10: 745-55, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26937175

RESUMO

INTRODUCTION: mTOR and MDM2 signaling pathways are frequently deregulated in cancer development, and inhibition of mTOR or MDM2 independently enhances carcinoma-cell apoptosis. However, responses to mTOR and MDM2 antagonists in renal cell carcinoma (RCC) remain unknown. MATERIALS AND METHODS: A498 cells treated with MDM2 antagonist MI-319 and/or mTOR inhibitor rapamycin were employed in the present study. Cell apoptosis and Western blot analysis were performed. RESULTS AND CONCLUSION: We found that the MDM2 inhibitor MI-319 induced RCC cell apoptosis mainly dependent on p53 overexpression, while the mTOR antagonist rapamycin promoted RCC cell apoptosis primarily through upregulation of HIF1α expression. Importantly, strong synergistic effects of MI-319 and rapamycin combinations at relatively low concentrations on RCC cell apoptosis were observed. Depletion of p53 or HIF1α impaired both antagonist-elicited apoptoses to differential extents, corresponding to their expression changes responding to chemical treatments, and double knockdown of p53 and HIF1α remarkably hindered MI-319- or rapamycin-induced apoptosis, suggesting that both p53 and HIF1α are involved in MDM2 or mTOR antagonist-induced apoptosis. Collectively, we propose that concurrent activation of p53 and HIF1α may effectively result in cancer-cell apoptosis, and that combined MDM2 antagonists and mTOR inhibitors may be useful in RCC therapy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos/química , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Indóis/química , Indóis/farmacologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/genética
15.
Tumour Biol ; 36(7): 5537-41, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25682287

RESUMO

Multiple studies have shown that CC-chemokine receptor 7 (CCR7) promotes cell proliferation in several human cancers. We investigated the expression and clinical significance of CCR7 in our large collection of prostate cancer (PCa) samples and explored its function on the proliferation and migration of PCa cells. In this study, the expression of CCR7 was examined by immunohistochemical staining and quantitative RT-PCR in primary PCa tissues from 60 patients who underwent radical prostatectomy. Then, we investigated the functional role of CCR7 in PCa cell proliferation and migration by small interfering RNA-mediated depletion. The positive rate of CCR7 staining was 88.33 % (53/60) in the PCa group and 16.67 % (10/60) in cases of benign prostate hyperplasia (BPH); the difference of CCR7 expression between PCa and BPH was statistically significant. The results were confirmed by quantitative real-time PCR. CCR7 was significantly elevated in all five PCa cell lines when compared to the RWPE-1 cells. Silencing of CCR7 inhibited the proliferation of PC3 cells which have a relatively high level of CCR7 in a time-dependent manner, and the invasion and migration of PC3 cells were distinctly suppressed. Our data suggest that the pathogenesis of human PCa maybe mediated by the CCR7, and thus CCR7 could represent selective targets for the molecularly targeted treatments of PCa.


Assuntos
Proliferação de Células/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Receptores CCR7/biossíntese , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica/genética , Prostatectomia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Receptores CCR7/genética
16.
Urol Int ; 86(1): 90-4, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20881362

RESUMO

INTRODUCTION: We estimated the diagnostic accuracy of Abrams-Griffiths number (AG), urethral resistance factor (URA) and detrusor-adjusted mean passive urethral resistance relation factor (DAMPF) for bladder outlet obstruction (BOO) in benign prostate hyperplasia (BPH) patients. MATERIALS AND METHODS: AG, URA and DAMPF were obtained by pressure-flow studies from BPH patients. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic accuracy of the AG, URA and DAMPF in the diagnosis of BOO. RESULTS: Among the 172 cases there were 154 classified as obstructed (89.5%) and 18 as unobstructed (10.5%). There were statistically significant differences in AG, URA and DAMPF between the obstructed and the unobstructed cases. The ROC curve demonstrated a similar diagnostic accuracy in the diagnosis of BOO for AG and URA values, and the least was seen for the DAMPF value. An AG cutoff of >33 provided a sensitivity of 89.61% and a specificity of 100%. A URA cutoff of >28 provided a sensitivity of 91.56% and a specificity of 100%. A sensitivity of 93.51% and the weakest specificity of 77.78% were recorded for DAMPF values of >52. AG and URA had a similar accuracy, while the efficacy of DAMPF is significantly lower in the diagnosis of BOO. CONCLUSIONS: AG or URA appeared to be the best discriminating parameters of BOO in BPH patients. The DAMPF could be used to aid the BOO diagnosis. Lower cutoff values were suggested for these BOO parameters.


Assuntos
Hiperplasia Prostática/complicações , Obstrução do Colo da Bexiga Urinária/diagnóstico , Urodinâmica , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Obstrução do Colo da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia
17.
Zhonghua Nan Ke Xue ; 16(4): 341-4, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20626164

RESUMO

OBJECTIVE: It is controversial whether unilateral interruption of the arteria iliaca interna distal end affects penile hemodynamics and erectile function. The purpose of this study was to prospectively evaluate this influence by detecting the blood flow of the penile artery before and after renal transplantation. METHODS: Thirty-three patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) received renal transplantation, the grafts revascularized by end-to-end anastomosis to the right internal iliac artery. Six months before and after the surgery, we obtained the IIEF scores of the patients, recorded their penile blood flow on color Doppler ultrasonography and the levels of serum creatinine, hemoglobin and serum cholesterol, and analyzed post-transplantation immunosuppressive medication. RESULTS: The patients ranged in age from 21 to 55 years, of whom 36% had erectile dysfunction (ED) during MHD, and 33% after renal transplantation. A total of 67% of the renal transplant recipients (RTR) complained of unchanged and 15% deteriorated ED, while 18% admitted improved erectile function. The patients showed a significantly stronger sexual desire after the transplantation than before it (6.2 +/- 1.6 vs 8.9 +/- 0.9, P < 0.01). There was a significant decrease in peak systolic velocity (PSV) in the cavernous arteries after transplantation as compared with pre-transplantation (P < 0.01). Penile arterial blood flow insufficiency was found in none of the RTRs. CONCLUSION: Unilateral interruption of the internal iliac artery decreases penile arterial blood flow, but not to such a degree as to result in ED. Unilateral interruption of the arteria iliaca interna distal end does not affect the erectile function of RTRs.


Assuntos
Transplante de Rim , Ereção Peniana , Pênis/irrigação sanguínea , Priapismo/etiologia , Adulto , Anastomose Cirúrgica , Humanos , Artéria Ilíaca/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Artéria Renal/cirurgia , Adulto Jovem
18.
Zhonghua Yi Xue Za Zhi ; 88(40): 2842-4, 2008 Nov 04.
Artigo em Chinês | MEDLINE | ID: mdl-19080494

RESUMO

OBJECTIVE: To summarize the clinical experience in living related donor kidney transplantation. METHODS: 117 patients with different nephropathies underwent transplantation of kidneys donated by their collateral relative in three generations. All donor kidneys were removed by open nephrectomy. Immunosuppressive protocols which consisting of cyclosporine A/tacrolimus, mycophenolate mofetil/azathioprine/rapamycin, and steroid were used in all patients as immunosuppressors. Follow-up was conducted for 1-44 months. RESULTS: Delayed graft function recovery occurred in 2 patients. Acute rejection episodes occurred in 18 patients, and the condition was reversed by high intravenous dose of methyl-prednisolone or polyclonal anti-T-cell antibodies. Follow-up showed that all the patients survived with normal kidney function, and the donors kept good kidney function with normal life quality. Hypertension was found in 2 donors and diabetes mellitus was found in 1 donor. CONCLUSION: Careful evaluation of both psychological and physical status of the donors and optimal physical status of recipients before operation are critical for successful kidney transplantation. Injury of graft kidney should be reduced and recipients should be treated with sufficient immunosuppressive regimen in early stage after transplantation.


Assuntos
Transplante de Rim , Doadores Vivos , Adulto , Família , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade
19.
Chin Med J (Engl) ; 121(9): 795-9, 2008 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-18701044

RESUMO

BACKGROUND: Renal transplants can improve the quality of life for recipients, but the quality of their sexual life might not be improved. This study was conducted to research the prevalence of erectile dysfunction (ED) and the influential factors in male renal transplant recipients (RTRs). METHODS: A cross-sectional survey was conducted in three renal transplantation centers. Structured questionnaires were administrated by trained interviewers to 824 male renal transplant patients, who had active sexual lives in the last 6 months. RESULTS: Complaints of ED were reported by 75.5% of the 809 RTRs (age range 19 - 75 years, mean age (45 +/- 10) years), whose questionnaires were completed. Mild, moderate and severe ED were reported at 53.6%, 8.3% and 13.6%, respectively. The mean age and the graft duration were significantly higher in male RTRs with ED compared to potent graft recipients (P = 0.00 and 0.04, respectively). The prevalence of ED increased with the increase in age. It was 60.7%, 65.8%, 75.2%, 87.5% and 92.2% in patients with age below 30 years, 31 - 40 years, 41 - 50 years, 51 - 60 years and over 60 years, respectively (P = 0.000). Moreover, the severity of ED increased with aging. The percentage of moderate and severe cases of ED increased from 6.7% in patients below 40 years to 28.9% in those over 40 years (P = 0.000). The prevalence of ED in the RTR who had no occupation was higher than in those who were holding a position (P = 0.001). The prevalence of ED decreased with the increase in the education level. The prevalence of ED was 94.3%, 86.4%, 74.0% and 67.8% in men with elementary school or lower, middle school, high school, and college or higher degrees, respectively (P = 0.000). Patients, whose distal end of arteria iliaca interna was interrupted and underwent iterative transplantation, worried transplanted kidney function was impacted by sexual life, and received cyclosporine (CsA)-based immunosuppressive regimens, were more likely to have ED (P = 0.000, 0.001, 0.000, 0.000, respectively). After Logistic regression analysis, only five factors, age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life and CsA-based immunosuppressive regimens sustained their significance. CONCLUSIONS: Renal transplant has varying effects on erectile function. ED is highly prevalent among RTRs and its influential factors are multiple. Age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life, CsA-based immunosuppressive regimens are the main influential factors of ED in male RTRs.


Assuntos
Disfunção Erétil/etiologia , Transplante de Rim/efeitos adversos , Adulto , Idoso , Estudos Transversais , Ciclosporina/uso terapêutico , Disfunção Erétil/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
20.
Zhonghua Nan Ke Xue ; 13(4): 360-3, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17491275

RESUMO

The quality of sexual life is important for renal transplantation recipients. With the increase of survival rate of renal transplantation, the quality of the male recipients' sexual life, especially their erectile function, has been generally remarked. The prevalence of ED is 35.8%-78.3% in male allograft renal transplantation recipients. And it can be caused by various factors, such as age, dialysis time, modus operandi, hemoglobin level, deprementia, immunosuppressant, and diabetes. We give an overview of the therapeutic options for ED in this special population. Sildenafil is effective and safe. If the oral drug fails, we can choose intracavernosal injection and penile prosthesis implantation. Nevertheless, three-piece prostheses should be avoided.


Assuntos
Disfunção Erétil/terapia , Transplante de Rim , Disfunção Erétil/epidemiologia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Prevalência , Qualidade de Vida , Transplante Homólogo/efeitos adversos
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