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1.
J Mol Diagn ; 26(7): 613-623, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38677548

RESUMO

The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube. The detection limitation of the test was approximately two genome copies of methylated PENK per milliliter of urine. In the retrospective training set (n = 105), an optimal cutoff value was determined to distinguish BC from non-BC, resulting in a sensitivity of 87.3% and a specificity of 95.2%. In the prospective validation set (n = 210, 122 Korean and 88 American patients), the overall sensitivity for detecting all stages of BC was 81.0%, with a specificity of 91.5% and an area under the curve value of 0.889. There was no significant difference between the two groups. The test achieved a sensitivity of 100% in detecting high-grade Ta and higher stages of BC. The negative predictive value of the test was 97.7%, and the positive predictive value was 51.5%. The findings of this study demonstrate that EarlyTect BCD is a highly effective noninvasive diagnostic tool for identifying BC among patients with hematuria.


Assuntos
Metilação de DNA , Hematúria , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/urina , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/diagnóstico , Hematúria/urina , Hematúria/diagnóstico , Hematúria/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Sensibilidade e Especificidade , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/genética , Estudos Retrospectivos , Curva ROC , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer/métodos , Adulto
2.
Investig Clin Urol ; 65(1): 69-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38197753

RESUMO

PURPOSE: To investigate the prevalence of lower urinary tract symptoms/benign prostatic hyperplasia in a Korean population. MATERIALS AND METHODS: The Korean Prostate & Voiding Health Association provided free prostate-related community health care and conducted surveys in all regions of Korea from 2001 to 2022 with the cooperation of local government public health centers. A total of 72,068 males older than 50 were surveyed and analyzed. History taking, International Prostate Symptom Score (IPSS), transrectal ultrasonography, prostate-specific antigen (PSA) testing, uroflowmetry, and urine volume testing were performed. RESULTS: The mean prostate volumes in males in their 50s, 60s, 70s, and 80s or above were 24.7 g, 27.7 g, 31 g, and 33.7 g, respectively. The proportion of males with high PSA greater than 3 ng/mL was 3.8% among males in their 50s, 7.7% among males in their 60s, 13.1% among males in their 70s, and 17.9% among males 80 years of age or older. The mean IPSS total scores in males in their 50s, 60s, 70s, and 80s or above were 10.7, 12.7, 14.5, and 16, respectively. Severe symptoms were reported by 27.3% of males, whereas 51.7% reported moderate symptoms. The mean Qmax in males in their 50s, 60s, 70s, and 80s or above were 20 mL/s, 17.4 mL/s, 15.4 mL/s, and 13.8 mL/s, respectively. CONCLUSIONS: In this population-based study, mean prostate volume, IPSS, PSA, and Qmax were 30.6±15.1 g, 14.8±8.2, 1.9±4.7 ng/mL, and 15.6±6.5 mL/s, respectively. Aging was significantly associated with increased prostate volume, PSA levels, and IPSS scores, and with decreased Qmax and urine volume.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Antígeno Prostático Específico , Próstata , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , República da Coreia/epidemiologia
3.
J Mol Diagn ; 25(9): 646-654, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37330048

RESUMO

Hematuria is a prevalent symptom associated with bladder cancer (BC). However, the invasiveness and cost of cystoscopy, the current gold standard for BC diagnosis in patients with hematuria, necessitate the development of a sensitive and accurate noninvasive test. This study introduces and validates a highly sensitive urine-based DNA methylation test. The test improves sensitivity in detecting PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR. In a case-control study comprising 175 patients with BC and 143 patients without BC with hematuria, the test's optimal cutoff value was determined by distinguishing between two groups, achieved an overall sensitivity of 86.9% and a specificity of 91.6%, with an area under the curve of 0.892. A prospective validation clinical study involving 366 patients with hematuria scheduled for cystoscopy assessed the test's performance. The test demonstrated an overall sensitivity of 84.2% in detecting 38 cases of BC, a specificity of 95.7%, and an area under the curve of 0.900. Notably, the sensitivity for detecting Ta high grade and higher stages of BC reached 92.3%. The test's negative predictive value was 98.2%, and the positive predictive value was 68.7%. These findings highlight the potential of the PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR test in urine as a promising molecular diagnostic tool for detecting primary BC in patients with hematuria, which may reduce the need for cystoscopy.


Assuntos
Hematúria , Neoplasias da Bexiga Urinária , Humanos , Hematúria/etiologia , Hematúria/genética , Metilação de DNA/genética , Estudos de Casos e Controles , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/urina , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina
4.
Int Neurourol J ; 27(1): 70-76, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37015727

RESUMO

PURPOSE: In this paper, we propose an optimal ureter stone detection model utilizing multiple artificial intelligence technologies. Specifically, the proposed model of urinary tract stone detection merges an artificial intelligence model and an image processing model, resulting in a multimethod approach. METHODS: We propose an optimal urinary tract stone detection algorithm based on artificial intelligence technology. This method was intended to increase the accuracy of urinary tract stone detection by combining deep learning technology (Fast R-CNN) and image processing technology (Watershed). RESULTS: As a result of deriving the confusion matrix, the sensitivity and specificity of urinary tract stone detection were calculated to be 0.90 and 0.91, and the accuracy for their position was 0.84. This value was higher than 0.8, which is the standard for accuracy. This finding confirmed that accurate guidance to the stones area was possible when the developed platform was used to support actual surgery. CONCLUSION: The performance evaluation of the method proposed herein indicated that it can effectively play an auxiliary role in diagnostic decision-making with a clinically acceptable range of safety. In particular, in the case of ambush stones or urinary stones accompanying ureter polyps, the value that could be obtained through combination therapy based on diagnostic assistance could be evaluated.

5.
BMC Cancer ; 22(1): 1195, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36403035

RESUMO

BACKGROUND: Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa. METHODS: CpG methylation microarray analysis was conducted on primary tumors with varying stages (T1-T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0. RESULTS: CpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 - 95.5%), a specificity of 92.5% (95% CI: 85.7 - 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 - 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa. CONCLUSIONS: In this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Detecção Precoce de Câncer , DNA
6.
Int J Urol ; 29(6): 503-509, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35297106

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: A prospective, randomized, double-blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health-Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate-specific antigen were performed. RESULTS: In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub-score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs. CONCLUSION: Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add-on treatments in patients with storage symptoms with alpha-blocker monotherapy.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Prostatite , Método Duplo-Cego , Quimioterapia Combinada , Medicina Herbária , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Dor , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Prostatite/complicações , Prostatite/tratamento farmacológico , Qualidade de Vida , Sulfonamidas/efeitos adversos , Tansulosina/uso terapêutico , Resultado do Tratamento
7.
J Exerc Rehabil ; 17(1): 59-65, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33728290

RESUMO

We studied the long-term efficacy and safety of cystocele operation by polypropylene mesh. A total of 198 women with stage ≥2 cystocele who had anterior vaginal wall repair with transobturator four-arm polypropylene mesh during 2003 to 2015 were evaluated. Outcomes including clinical characteristics and complications were reviewed by extracting patient data from electronic medical records. In addition, telephone interviews were conducted using a validated questionnaire along with physical examination. The follow-up period was 9.3±0.3 years. The cystocele stage in patients was significantly decreased post-operation compared to that preoperation. The anatomical cure rate for cystocele was 93.4%, and that for stress urinary incontinence was 95%. Comparing the three questionnaires indicated overall average score was improved significantly, except for Female Sexual Function Index Assessment. Early complications were either resolved spontaneously or controlled medically in four cases of hematoma or abscess, three cases of vaginal infection and urinary tract infection, and four cases of difficult micturition. In late complications, four cases of pain were managed, five cases of recurrence were observed and two cases of mesh exposure were treated with ointment and local excision. Transobturator four-arms mesh is an effective and safe method for cystocele repair with low rate of recurrence and complications. We suggest that the use of transobturator four-arm mesh is a still good choice for the old patients with cystocele who are not suitable for general anesthesia and reside in areas where laparoscopy and robots are not available.

8.
J Inflamm Res ; 14: 367-378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33623409

RESUMO

BACKGROUND: Interstitial cystitis (IC) is a chronic disorder that indicates bladder-related pain or discomfort. Patients with IC often experience urination problems, such as urinary frequency and urgency, along with pain or discomfort in the bladder area. Therefore, new treatments based on IC etiology are needed. Polydeoxyribonucleotide (PDRN) is a biologic agonist of the adenosine A2A receptor, and PDRN has anti-inflammatory effect and inhibits apoptosis. In the current study, the effect of PDRN on cyclophosphamide-induced IC animal model was investigated using rats. METHODOLOGY: To induce the IC animal model, 75 mg/kg of cyclophosphamide was injected intraperitoneally once every 3 days for 10 days. The rats in the PDRN-treated groups were intraperitoneally injected with 0.5 mL physiological saline containing 8 mg/kg PDRN, once a day for 10 days after IC induction. RESULTS: Induction of IC by cyclophosphamide injection caused voiding dysfunction, bladder edema, and histological damage. Cyclophosphamide injection increased secretion of pro-inflammatory cytokines and enhanced apoptosis. In contrast, PDRN treatment alleviated voiding dysfunction, bladder edema, and histological damage. Secretion of pro-inflammatory cytokines and expressions of apoptotic factors were suppressed by PDRN treatment. These changes indicate that treatment with PDRN improves voiding function by ultimately promoting the repair of damaged bladder tissue. CONCLUSION: The conclusion of this experiment suggests the possibility that PDRN could be used as an effective therapeutic agent for IC.

9.
Investig Clin Urol ; 61(3): 297-303, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32377606

RESUMO

Purpose: Many patients with benign prostatic hyperplasia require treatment for persistent storage symptoms, even when the obstruction is successfully relieved by surgery. Previous studies identified a characteristic increase in α1D-adrenoceptor levels in the bladder in a bladder outlet obstruction (BOO) model. Here, we investigated the expression of α1-adrenoceptor subtypes in the bladder after relief of partial BOO (pBOO) in a rat model. Materials and Methods: A total of 60 female Sprague-Dawley rats were randomly divided into three groups (sham-operated, pBOO, and pBOO relief groups), and the expression of α1-adrenoceptor subtypes in the urothelium and detrusor muscle tissues was examined by western blot. Results: The expression of the α1D-adrenoceptor was significantly higher in the urothelium and detrusor muscle tissue of the pBOO and pBOO relief groups than in the corresponding tissue of the sham-operated group. Additionally, the α1A-adrenoceptor was predominant in the sham-operated group but significantly decreased in the urothelium in the pBOO group. No significant differences were found in α1A-adrenoceptor levels in detrusor muscle or whole bladder. Conclusions: Our results showed that α1D-adrenoceptor levels were consistently increased with pBOO, even after relief, suggesting that the α1D-adrenoceptor might be a cause of persistent storage symptoms after relief of pBOO.


Assuntos
Receptores Adrenérgicos alfa 1/biossíntese , Obstrução do Colo da Bexiga Urinária/metabolismo , Bexiga Urinária/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Obstrução do Colo da Bexiga Urinária/cirurgia
10.
Urol J ; 16(1): 44-49, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30120758

RESUMO

PURPOSE: It remains unclear whether laparoscopic radiofrequency ablation (RFA) for primary treatment of small renal masses is similar to partial nephrectomy (PN) in terms of long-term oncological and renal function outcomes. We reviewed the long-term outcomes for patients with T1a renal masses treated with either laparoscopic RFA orPN. MATERIALS AND METHODS: This retrospective single-center study on 115 patients who were treated by laparoscopic RFA or PN for small (<4 cm) renal masses between January 2005 and October 2014 at Chungnam National University Hospital. Estimated glomerular filtration rate (eGFR) was measured before and 1-2 weeks after surgery and at last follow-up. The laparoscopic RFA and PN groups were compared in terms of clinical characteristics data and change in eGFR after surgery using the Chi-squared test or Student's t-test. Survival data were analyzed using theKaplan-Meier method and the log-rank test. RESULTS: Of the 115 patients, 62 and 53 underwent laparoscopic RFA and PN, respectively. Their mean (range) follow-up duration was 60 (30-104) and 68 (30-149) months, respectively (P = 0.092). The RFA patients were older (P = 0.023) and had smaller tumors (P = 0.000). RFA associated with shorter operation and hospitalization times and less perioperative blood loss (all P<0.001). The groups did not differ in terms of change in eGFR 1-2 weeks after surgery (P = 0.252) or at the last follow-up (P = 0.395) or 5 year survival rates (P = 0.360). CONCLUSION: Laparoscopic RFA for small renal masses was comparable to PN in terms of oncological and functional outcomes and associated with shorter operative and hospitalization times and less perioperative bleeding.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia , Ablação por Radiofrequência , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Carcinoma de Células Renais/fisiopatologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Neoplasias Renais/fisiopatologia , Laparoscopia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
11.
Anticancer Res ; 38(4): 2429-2437, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29599373

RESUMO

BACKGROUND/AIM: Microtubule-associated protein 1 light chain 3B (LC3B), an autophagy marker, has been used as a promising marker in various cancer types. However, the expression of LC3B in muscle-invasive bladder cancer (MIBC) and its prognostic significance have not been investigated. Recent studies pointed to the involvement of ESRRA in regulating autophagy via both transcriptional and post-translational control. In the current study, prognostic importance of LC3B and ESRRA in MIBC was investigated. PATIENTS AND METHODS: We immunohistochemically studied the expression of LC3B and ESRRA in 56 MIBC samples. RESULTS: LC3B was stained high in 16 patients (28.6%) and low or negative in 40 patients (71.4%). ESRRA expression was high for 20 patients (35.7%) and low for 36 patients (64.3%). Both LC3B (p=0.003) and ESRRA (p=0.026) expression correlated significantly with disease-free survival rates. Double-positive LC3B and ESRRA correlated with poor overall survival (p=0.007) and disease-free survival (p=0.001) in MIBC patients. CONCLUSION: LC3B and ESRRA might be a useful prognostic factor in patients with MIBC. The co-expression of LC3B and ESRRA might be a prognostic and therapeutic target for patients with bladder cancer.


Assuntos
Autofagia , Biomarcadores Tumorais/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/secundário , Receptores de Estrogênio/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/metabolismo , Invasividade Neoplásica , Prognóstico , Análise Serial de Tecidos , Neoplasias da Bexiga Urinária/metabolismo , Receptor ERRalfa Relacionado ao Estrogênio
12.
Urol J ; 13(3): 2684-9, 2016 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-27351323

RESUMO

PURPOSE: This study was conducted to evaluate lower urinary tract symptoms (LUTS) change in patients with localized prostate cancer after radical retropubic prostatectomy (RRP) and examine the efficacy of anticholinergic drugs to treat patients suffering from storage symptoms. MATERIALS AND METHODS: Among 50 patients who underwent RRP for prostate cancer, 40 who did not undergo additional treatment that might affect their urination pattern were included in the analysis. The International Prostate Symptom Score (IPSS), quality of life (QoL) score, and uroflowmetry were analyzed prior to RRP and 12 months after RRP. Twelve months after RRP, patients desiring improvement of storage symptoms were administered anticholinergic drugs for 6 months; the effects of such treatments were analyzed 3 and 6 months later. RESULTS: Preoperatively and at 12 months after surgery, the mean IPSS for patients were 10.9 ± 6.7 and 9.2 ± 5.7, respectively. The mean IPSS for patients desiring improvement of storage symptoms before and after administration of medication were 9.7 ± 5.9 and 9.0 ± 4.4, respectively. In particular, the mean storage symptom composites improved significantly after administration of medication. There were no statistically significant differences in frequency between baseline and 3-month, but frequency was improved significantly after 6 months. Urgency and nocturia were improved significantly after 3 months. CONCLUSION: In patients undergoing RRP, urinary symptoms change over time, with worsening storage symptoms. Our results suggest that, in patients who had discomfort with storage symptoms after RRP, anticholinergic drugs significantly improved symptoms and QoL. .


Assuntos
Antagonistas Colinérgicos/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Prostatectomia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prostatectomia/métodos , Fatores de Tempo , Resultado do Tratamento
13.
Dis Markers ; 2016: 7276502, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27057081

RESUMO

Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 µL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.


Assuntos
Biomarcadores Tumorais/urina , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Regulação para Cima , Neoplasias da Bexiga Urinária/urina
14.
Oxid Med Cell Longev ; 2015: 906787, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26491537

RESUMO

Bladder ischemia-reperfusion (I/R) injury results in the generation of reactive oxygen species (ROS) and markedly elevates the risk of lower urinary tract symptoms (LUTS). Allopurinol is an inhibitor of xanthine oxidase (XO) and thus can serve as an antioxidant that reduces oxidative stress. Here, a rat model was used to assess the ability of allopurinol treatment to ameliorate the deleterious effects of urinary bladder I/R injury. I/R injury reduced the in vitro contractile responses of longitudinal bladder strips, elevated XO activity in the plasma and bladder tissue, increased the bladder levels of tumor necrosis factor-α (TNF-α), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase, reduced the bladder levels of extracellular regulated kinase (ERK), and decreased and increased the bladder levels of Bcl-2 and Bax, respectively. I/R injury also elevated lipid peroxidation in the bladder. Allopurinol treatment in the I/R injury was generated significantly ameliorating all I/R-induced changes. Moreover, an in situ fluorohistological approach also showed that allopurinol reduces the generation of intracellular superoxides enlarged by I/R injury. Together, the beneficial effects of allopurinol reducing ROS production may be mediated by normalizing the activity of the ERK, JNK, and Bax/Bcl-2 pathways and by controlling TNF-α expression.


Assuntos
Alopurinol/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Bexiga Urinária/patologia , Animais , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Bexiga Urinária/metabolismo , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
BMC Urol ; 15: 37, 2015 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-25951823

RESUMO

BACKGROUND: We designed this experiment to elucidate the relationship between the expression of brain derived-neurotrophic factor (BDNF), the expression of granulocyte-colony stimulating factor (G-CSF), and the development of overactive bladder (OAB). In our previous study, the urothelium was observed to be more than a simple mechanosensory receptor and was found to be a potential therapeutic target for OAB. Moreover, neuregulin-1 and BDNF were found to be potential new biomarkers of OAB. Here, we investigated the relationship between changes in the voiding pattern and the expression of BDNF and G-CSF in the urothelium and evaluated the effects of 5-hydroxymethyl tolterodine (5-HMT) on rats with bladder outlet obstruction (BOO). METHODS: A total of 100 Sprague-Dawley rats were divided into the following groups: 20 control rats; 40 BOO rats; and 40 BOO rats administered 5-HMT (0.1 mg/kg). After BOO was induced for 4 weeks, the rats were assessed by cystometrography. The changes in BDNF and G-CSF expression were examined in both separated urothelial tissues and in cultured urothelial cells by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: BOO rats showed increased non-voiding activity [NVA; (number/10 voidings)] and bladder weight and decreased micturition volume (MV), micturition interval (MI), and micturition time (MT) relative to the controls. Moreover, the 5-HMT administration rats showed decreased NVA and bladder weight and increased MV and MI in comparison to the BOO rats. BDNF and G-CSF expression was increased in BOO rats and decreased following 5-HMT administration. In this model, voiding dysfunction developed as a result of BOO. As a therapeutic agent for OAB, the administration of 5-HMT improved the voiding dysfunction. CONCLUSIONS: BDNF and G-CSF might modulate voiding patterns through micturition pathways and might be involved only in the urothelium. Moreover, the expression of both genes in the urothelium might be related to voiding dysfunction in OAB patients. Thus, the urothelium has an important role in the manifestation of voiding symptoms.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Bexiga Urinária Hiperativa/fisiopatologia , Micção/fisiologia , Urotélio/metabolismo , Animais , Modelos Animais de Doenças , Ratos Sprague-Dawley , Bexiga Urinária Hiperativa/metabolismo
16.
Cancer Res Treat ; 47(4): 823-33, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25672588

RESUMO

PURPOSE: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that shows elevated expression in a number of cancers. We attempted to determine whether serum APE1/Ref-1 is elevated in patients with bladder cancer. MATERIALS AND METHODS: Serum APE1/Ref-1 levels were determined using enzyme-linked immunosorbent assay in serum from patients with bladder cancer who had not received chemotherapy or radiotherapy (n=51) and non-tumor controls (n=55). The area under the receiver operating characteristic area under the curve was applied to determine the correlation between clinical factors and the serum levels of APE1/Ref-1. RESULTS: Serum levels of APE1/Ref-1 in bladder cancer patients were significantly elevated compared to those of the control group (3.548 ± 0.333 ng/100 µL [n=51] for bladder cancer vs. 1.547 ± 0.319 ng/100 µL [n=55] for the control group), with a sensitivity and specificity of 93% and 59%, respectively. Serum APE1/Ref-1 levels are associated with tumor stage, grade, muscle invasion, and recurrence. CONCLUSION: Serum APE1/Ref-1 might be useful as a potential serologic biomarker for bladder cancer.


Assuntos
Biomarcadores Tumorais/sangue , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/sangue , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Sorológicos
17.
J Korean Med Sci ; 29(9): 1271-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25246747

RESUMO

This multicenter study was undertaken to determine the efficacy of antibiotic prophylaxis and identify the risk factors for infectious complications after prostate surgery in Korean patients. A total of 424 patients who underwent surgery of the prostate were reviewed. All patients underwent urinalysis and urine culture preoperatively and postoperatively. Efficacy of antibiotic prophylaxis and risk factors for infectious complications were investigated. Infectious complications were observed in 34.9% of all patients. Factors independently associated with infectious complications were diabetes mellitus (adjusted OR, 1.99; 95% CI, 1.09-3.65, P=0.025) and operation time (adjusted OR, 1.08; 95% CI, 1.03-1.13, P=0.004). Clinicians should be aware of the high risk of infectious complications in patients with diabetes and those who undergo a prolonged operation time. Neither the type nor duration of prophylactic antibiotics resulted in differences in infectious complications.


Assuntos
Neoplasias da Próstata/cirurgia , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Diabetes Mellitus Tipo 2/complicações , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Escherichia coli/isolamento & purificação , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Neoplasias da Próstata/complicações , Quinolonas/farmacologia , Fatores de Risco , Fatores de Tempo , Ressecção Transuretral da Próstata , Urinálise , Infecções Urinárias/microbiologia
18.
Urology ; 83(4): 875-81, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24529580

RESUMO

OBJECTIVE: To show the noninferiority of silodosin 8-mg once-daily (QD) to 4-mg twice-daily (BID) in efficacy and safety in patients with lower urinary tract symptoms or benign prostatic hyperplasia in the Korean population. METHODS: A prospective, multicenter, double-blind, randomized, comparative study was conducted. A total of 532 male patients aged ≥50 years with lower urinary tract symptoms or benign prostatic hyperplasia were included. All patients received silodosin QD or BID for 12 weeks. The primary end point was the change from baseline in total International Prostate Symptom Score (IPSS) at 12 weeks. Adverse drug reactions, vital signs, and laboratory tests were recorded. RESULTS: A total of 424 patients were randomized to the silodosin QD or BID groups. These groups were not significantly different in baseline characteristics. The mean total IPSS change in QD group was not inferior to that in BID group (-6.70 and -6.94, respectively; 95% confidence interval, -0.88 to 1.36). The QD and BID groups did not significantly differ in the following: percentages of patients with ≥25% (63.41% and 67.82%, respectively; P = .349) or ≥4-point improvement in total IPSS (65.85% and 69.31%, respectively; P = .457), maximum urinary flow rate improvement ≥30% (47.32% and 40.59%, respectively; P = .172), changes in IPSS voiding subscore (-4.42 ± 4.93 and -4.65 ± 4.77; P = .641), IPSS storage subscore (-2.05 ± 3.07 and -2.52 ± 2.97; P = .117), quality of life (-1.19 ± 1.49 and -1.40 ± 1.42; P = .136), maximum urinary flow rate (3.55 ± 5.93 and 3.74 ± 6.79 mL/s; P = .768), International Continence Society male questionnaire score, Patient Goal Achievement Score, or Treatment Satisfaction Question. The 2 groups had similar frequencies of adverse drug reactions. CONCLUSION: QD administration of silodosin was not inferior to BID in efficacy. The 2 groups had similar adverse drug reaction profiles.


Assuntos
Indóis/administração & dosagem , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Agentes Urológicos/administração & dosagem , Idoso , Método Duplo-Cego , Esquema de Medicação , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Inquéritos e Questionários , Resultado do Tratamento , Micção/efeitos dos fármacos , Agentes Urológicos/uso terapêutico
19.
Cell Biochem Funct ; 32(1): 24-30, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23589085

RESUMO

Ischemia/reperfusion (I/R) injury represents an important cause of bladder contractile dysfunction. One of the major causes leading to this dysfunction is thought to be reactive oxygen species formation. In this study, we investigated the potential benefit of N-acetylcysteine (NAC), a potent antioxidant that neutralizes free radicals, in a rat model of urinary bladder injury. NAC treatment rescues the reduction of contractile response to I/R injury in a dose-dependent manner. In addition, all levels of reactive oxygen species, lipid peroxidation, and NADPH-stimulated superoxide production in the I/R operation+NAC (I/R+NAC) group also decreased compared with a marked increase in the I/R operation+saline (I/R+S) group. Moreover, an in situ fluorohistological approach also showed that NAC reduces the generation of intracellular superoxides enlarged by I/R injury. Together, our findings suggest that NAC has a protective effect against the I/R-induced bladder contractile dysfunction via radical scavenging property.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Acetilcisteína/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Masculino , Contração Muscular , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Bexiga Urinária/fisiopatologia
20.
Korean J Urol ; 54(9): 603-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24044094

RESUMO

PURPOSE: We have performed both open partial nephrectomy (OPN) and laparoscopic radiofrequency ablation (RFA) on selected patients since January 2007 and have been following these patients through serial laboratory assessments and computed tomography (CT). The purpose of the present study was to evaluate long-term oncologic outcomes and renal function status for laparoscopic RFA versus OPN at a minimum follow-up of 3 years. MATERIALS AND METHODS: A total of 55 patients with exophytic, single small renal masses were treated with either OPN (n=14) or laparoscopic RFA (n=41) by a single surgeon. The indications for laparoscopic RFA were as follows: 1) cases with the greatest dimension of the renal mass <3 cm, and 2) cases in which the collecting system, renal calyx, and great vessels were free from the tumor margins by 1 cm. RESULTS: The estimated blood loss (EBL), the operation time, and the mean number of hospital days was significantly lower in the laparoscopic RFA group than in the OPN group. Oncologic data did not differ significantly between the two groups. Creatine clearance levels did not differ significantly compared with those before the operation in either group. CONCLUSIONS: Our data suggest excellent therapeutic outcomes with laparoscopic RFA with achievement of effective operative times, hospital stays, and EBL compared with OPN. According to our indications for laparoscopic RFA, laparoscopic RFA is an effective minimally invasive therapy for the treatment of small renal masses, yielding oncologic outcomes and renal function equivalent to those of OPN.

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