RESUMO
ABSTRACT Background In order to induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy for bladder cancer, various tumor antigens can be loaded onto DCs. Objective The aim of this study was to establish a method of immunotherapy for male patients with non-muscle invasive bladder cancer (NMIBC), using bladder cancer-specific CTLs generated in vitro by DCs. Materials and Methods Monocyte-derived DCs from bladder cancer patients were induced to mature in a standard cytokine cocktail (IL-1β, TNF-α, IL-6, and PGE2: standard DCs, sDCs) or anα-type 1-polarized DC (αDC1) cocktail (IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated bladder cancer cell line, T24. Antigen-loaded αDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay. Results The αDC1s significantly increased the expression of several molecules pertaining to DC maturation, regardless of whether or not the αDC1s were loaded with tumor antigens, relative to sDCs. The αDC1s demonstrated increased production of interleukin-12 both during maturation and after subsequent stimulation with CD40L that was not significantly affected by loading with tumor antigens as compared to that of sDCs. Bladder cancer-specific CTLs targeting autologous bladder cancer cells were successfully induced by αDC1s loaded with dying T24 cells. Conclusion Autologous αDC1s loaded with an allogeneic bladder cancer cell line resulted in increased bladder cancer-specific CTL responses as compared to that with sDCs, and therefore, may provide a novel source of DC-based vaccines that canbe used in immunotherapy for male patients with NMIBC.
Assuntos
Humanos , Masculino , Idoso , Neoplasias da Bexiga Urinária/terapia , Células Dendríticas/imunologia , Linfócitos T Citotóxicos/imunologia , Citocinas/uso terapêutico , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/imunologia , Diferenciação Celular/imunologia , Resultado do Tratamento , Linhagem Celular Tumoral , Imunoterapia/efeitos adversos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In order to induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy for bladder cancer, various tumor antigens can be loaded onto DCs. OBJECTIVE: The aim of this study was to establish a method of immunotherapy for male patients with non-muscle invasive bladder cancer (NMIBC), using bladder cancer-specific CTLs generated in vitro by DCs. MATERIALS AND METHODS: Monocyte-derived DCs from bladder cancer patients were induced to mature in a standard cytokine cocktail (IL-1ß, TNF-α, IL-6, and PGE2: standard DCs, sDCs) or anα-type 1-polarized DC (αDC1) cocktail (IL-1ß, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated bladder cancer cell line, T24. Antigen-loaded αDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay. RESULTS: The αDC1s significantly increased the expression of several molecules pertaining to DC maturation, regardless of whether or not the αDC1s were loaded with tumor antigens, relative to sDCs. The αDC1s demonstrated increased production of interleukin-12 both during maturation and after subsequent stimulation with CD40L that was not significantly affected by loading with tumor antigens as compared to that of sDCs. Bladder cancer-specific CTLs targeting autologous bladder cancer cells were successfully induced by αDC1s loaded with dying T24 cells. CONCLUSION: Autologous αDC1s loaded with an allogeneic bladder cancer cell line resulted in increased bladder cancer-specific CTL responses as compared to that with sDCs, and therefore, may provide a novel source of DC-based vaccines that canbe used in immunotherapy for male patients with NMIBC.
Assuntos
Citocinas/uso terapêutico , Células Dendríticas/imunologia , Imunoterapia/métodos , Linfócitos T Citotóxicos/imunologia , Neoplasias da Bexiga Urinária/terapia , Idoso , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Humanos , Imunoterapia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologiaRESUMO
OBJECTIVE: To investigate whether prostate-specific antigen (PSA) fluctuation correlates with a prostate cancer and to assess whether PSA fluctuation could be used for diagnosis of prostate cancer. MATERIALS AND METHODS: Our study included 229 patients who were performed a prostate biopsy (non-cancer group, 177; prostate cancer group, 52). Enrolled patients were provided twice PSA tests within 6 months. PSA fluctuation (%/month) was defined as a change rate of PSA per a month. Independent t test was used to compare between two groups. Receiver operator characteristic curve was used to assess the availability as a differential diagnostic tool and the correlation. Simple linear regression was performed to analyze a correlation between PSA fluctuation and other factors such as age, PSA, PSA density, and prostate volume. RESULTS: There were significant differences in PSA, PSA density, percentage of free PSA, and PSA fluctuation between two groups. PSA fluctuation was significantly greater in non-cancer group than prostate cancer group (19.95 ± 23.34%/month vs 9.63 ± 8.57%/ month, P=0.004). The most optimal cut-off value of PSA fluctuation was defined as 8.48%/month (sensitivity, 61.6%; specificity, 59.6%; AUC, 0.633; P=0.004). In a simple linear regression model, only PSA level was significantly correlated with PSA fluctuation. CONCLUSION: Patients with wide PSA fluctuations, although baseline PSA levels are high, might have a low risk of diagnosis with prostate cancer. Thus, serial PSA measurements could be an option in patients with an elevated PSA level.
Assuntos
Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Estatísticas não ParamétricasRESUMO
Objective To investigate whether prostate-specific antigen (PSA) fluctuation correlates with a prostate cancer and to assess whether PSA fluctuation could be used for diagnosis of prostate cancer. Materials and Methods Our study included 229 patients who were performed a prostate biopsy (non-cancer group, 177; prostate cancer group, 52). Enrolled patients were provided twice PSA tests within 6 months. PSA fluctuation (%/month) was defined as a change rate of PSA per a month. Independent t test was used to compare between two groups. Receiver operator characteristic curve was used to assess the availability as a differential diagnostic tool and the correlation. Simple linear regression was performed to analyze a correlation between PSA fluctuation and other factors such as age, PSA, PSA density, and prostate volume. Results There were significant differences in PSA, PSA density, percentage of free PSA, and PSA fluctuation between two groups. PSA fluctuation was significantly greater in non-cancer group than prostate cancer group (19.95±23.34%/month vs 9.63±8.57%/month, P=0.004). The most optimal cut-off value of PSA fluctuation was defined as 8.48%/month (sensitivity, 61.6%; specificity, 59.6%; AUC, 0.633; P=0.004). In a simple linear regression model, only PSA level was significantly correlated with PSA fluctuation. Conclusion Patients with wide PSA fluctuations, although baseline PSA levels are high, might have a low risk of diagnosis with prostate cancer. Thus, serial PSA measurements could be an option in patients with an elevated PSA level. .
Assuntos
Adolescente , Criança , Feminino , Humanos , Modelos Estatísticos , Fatores Etários , Asma/etiologia , Índice de Massa Corporal , Causalidade , Interpretação Estatística de Dados , Menarca , Razão de Chances , Tamanho da AmostraRESUMO
Purpose Endoscopic urethrotomy is an alternative method in treatment of urethral stricture. However, it have high recurrence rate because of the remained fibrotic tissue. Removal of the fibrotic tissue can maintain the patency of the urethral lumen after the procedure. We report the therapeutic efficacy of our initial experience using pediatric resectoscope for treating anterior urethral stricture in 16 cases. Materials and Methods From January 2009 to April 2011, transurethral resection with pediatric resectoscope was primarily performed on 16 patients with anterior urethral stricture. Retrograde urethrography, uroflowmetry, postvoid residual volume, IPSS score and QoL score were performed preoperatively. We used 11.5Fr pediatric resectoscope (Wolf) and monopolar electrosurgical generator. The stricture was incised under vision at the 12 o'clock location or the site of maximum scar tissue or narrowing in asymmetric strictures for working space. After incision, transurethral resection with pediatric resectoscope was performed to all scar tissues. Monopolar cutting current was set on 45 watt and coagulation current was set on 30 watt, fulgurate mode. Postoperatively, drainage of the bladder was performed for 7 days using an 18F latex catheter. Patients were followed up by IPSS score, QoL score, uroflowmetry and postvoid residual volume. Results Successful results without recurrence were achieved in 11 of 16patients. Postoperative urethral dilation had been performed average 2.4 times (0∼6 times). When we classified the results by etiology, the number of successful results in strictures with a trauma, iatrogenic, or unknown cause was 5 (7/11), 3 (3/4) and 1 (1/1), respectively. In 5 patients who failed treatment, we repeated transurethral resection with pediatric resectoscope in 1 patient, and periodic urethral dilation in 4 patients. No operative complications occurred in any patients. Conclusions Transurethral resection with ...