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1.
Masui ; 64(1): 70-6, 2015 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-25868205

RESUMO

BACKGROUND: Anesthetic management for cesarean section of patients with placenta previa accreta is challenging. The aim of this retrospective study was to review past placenta previa accreta cases in our hospital to propose a better strategy for anesthetic management for this difficult condition. METHODS: Cases of placenta previa accreta were identified in our anesthesia database. The diagnosis, surgical procedure, amount of blood loss and anesthetic management were reviewed. RESULTS: Eight cases of placenta previa accreta were identified. Four of the eight cases underwent stepwise treatment, and in one of the four cases, intra-aortic balloon occlusion (IABO) was performed. The amount of blood loss in the four cases ranged from 840 to 1,150 ml. The remaining four cases underwent cesarean hysterectomy. The amount of blood loss in the four cases ranged from 2,400 to 5,200 ml. Neuraxial anesthesia alone was planned in four cases, but in two of which anesthesia was converted to general anesthesia due to massive bleeding. CONCLUSIONS: The present retrospective study showed that stepwise treatment and using IABO could be an effective aid for management of plasenta previa accreta. It is necessary to compare the effectiveness of IABO with that of common iliac artery occlusion in reducing the amount of blood loss.


Assuntos
Anestesia Obstétrica/métodos , Anestésicos/uso terapêutico , Cesárea , Placenta Prévia/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Feminino , Humanos , Histerectomia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
2.
Int J Urol ; 21(7): 658-63, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24650159

RESUMO

OBJECTIVE: To analyze clinical and dosimetric factors involved in prostate-specific antigen bounce in patients who underwent permanent implant brachytherapy for localized prostate cancer, and to study the relationships among prostate-specific antigen bounce, age and sexual function. METHODS: Between March 2007 and April 2012, 116 patients with localized prostate cancer underwent permanent implant, iodine-125 brachytherapy. Patients receiving external-beam radiotherapy or who used phosphodiesterase-5 inhibitor pre- or post-treatment were excluded. Prostate-specific antigen bounce was defined as an increase of ≥0.2 ng/mL and ≥0.4 ng/mL above an initial prostate-specific antigen nadir followed by a subsequent decline to or below the initial nadir without treatment. Clinical and dosimetric factors involved in prostate-specific antigen bounce were analyzed using multivariate logistic regression analysis with the forced entry method. RESULTS: The median age was 66 years (range 51-80 years), and prostate-specific antigen bounce on a prostate-specific antigen rise of ≥0.2 ng/mL occurred in 47 of the 116 participants (40.5%). The median period before the prostate-specific antigen bounce was 17.5 months (range 8-36 months). Patients with prostate-specific antigen bounce were younger and had higher sexual function before treatment (P = 0.003) than those who not show prostate-specific antigen bounce. Regression analysis results showed that young age and a high level of pretreatment sexual function were significant predictive factors for prostate-specific antigen bounce (P = 0.028 and P = 0.048). CONCLUSION: Sexual function seems to be associated with a prostate-specific antigen bounce in patients undergoing permanent implant brachytherapy for localized prostate cancer, and it can be preserved after treatment if it is well present before treatment. Highly maintained sexual function after treatment might influence prostate-specific antigen bounce.


Assuntos
Braquiterapia/métodos , Radioisótopos do Iodo/uso terapêutico , Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/radioterapia , Comportamento Sexual/fisiologia , Disfunções Sexuais Fisiológicas/sangue , Idoso , Idoso de 80 Anos ou mais , Ejaculação/fisiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Valor Preditivo dos Testes , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Doses de Radiação , Disfunções Sexuais Fisiológicas/diagnóstico
3.
Prostate ; 72(8): 834-45, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21932426

RESUMO

BACKGROUND: Docetaxel-based chemotherapy (DBC) showed limited clinical efficacy for castration-resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC-resistant CRPC patients. METHODS: Twenty DBC-resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC-resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV. RESULTS: Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC-resistant CRPC patients and patients with no prior DBC (log-rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC-resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL-6 levels before vaccination was an unfavorable factor for OS of DBC-resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001-0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068-0.661) by multivariable analysis. CONCLUSIONS: Further clinical study of PPV is recommended for DBC-resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL-6 by combined therapy may provide much better clinical outcome.


Assuntos
Antineoplásicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Orquiectomia , Medicina de Precisão , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Citocinas/sangue , Progressão da Doença , Docetaxel , Humanos , Imunidade Humoral , Interleucina-6/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/mortalidade , Falha de Tratamento , Resultado do Tratamento
4.
Cancer ; 118(12): 3208-21, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22071976

RESUMO

BACKGROUND: Because only a subset of patients show clinical responses to peptide-based cancer vaccination, it is critical to identify biomarkers for selecting patients who would most likely benefit from this treatment. METHODS: The authors characterized the gene expression profiles in peripheral blood of vaccinated patients to identify biomarkers to predict patient prognosis. Peripheral blood was obtained from advanced castration-resistant prostate cancer patients, who survived for >900 days (long-term survivors, n = 20) or died within 300 days (short-term survivors, n = 20) after treatment with personalized peptide vaccination. Gene expression profiles in prevaccination and postvaccination peripheral blood mononuclear cells (PBMCs) were assessed by DNA microarray. RESULTS: There were no statistically significant differences in the clinical or pathological features between the 2 groups. Microarray analysis of prevaccination PBMCs identified 19 genes that were differentially expressed between the short-term and long-term survivors. Among the 15 up-regulated genes in the short-term survivors, 13 genes, which were also differentially expressed in postvaccination PBMCs, were associated with gene signatures of granulocytes. When a set of 4 differentially expressed genes were selected as the best combination to determine patient survival, prognosis was correctly predicted in 12 of 13 patients in a validation set (accuracy, 92%). CONCLUSIONS: These results suggested that abnormal granulocytes present in the PBMC faction may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination. Gene expression profiling in peripheral blood might thus be informative for devising better therapeutic strategies by predicting patient prognosis after cancer vaccines.


Assuntos
Vacinas Anticâncer/uso terapêutico , Perfilação da Expressão Gênica , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Granulócitos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Seleção de Pacientes , Prognóstico , Neoplasias da Próstata/sangue
5.
J Infect Chemother ; 18(5): 753-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22203121

RESUMO

Although many treatments have been applied to treat hormone-refractory prostate cancer (HRPC), therapeutic outcome is not altogether satisfactory. In the case of locally recurring HRPC, uncontrolled gross hematuria, dysuria, and scalding are often experienced. We report a patient who improved following intra-arterial infusion of cisplatin (CDDP) and ifosfamide (IFM) to treat urinary retention caused by locally recurring HRPC. After chemotherapy, cancer volume was remarkably reduced and symptoms improved.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Retenção Urinária/tratamento farmacológico , Cisplatino/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia
6.
Cancer Immunol Immunother ; 59(7): 1001-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20146063

RESUMO

Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Anticâncer/imunologia , Peptídeos/imunologia , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Vacinas Anticâncer/administração & dosagem , Estudos Cross-Over , Relação Dose-Resposta a Droga , Estramustina/administração & dosagem , Estramustina/efeitos adversos , Seguimentos , Humanos , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Orquiectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/cirurgia , Dermatopatias/induzido quimicamente , Análise de Sobrevida , Resultado do Tratamento , Vômito/induzido quimicamente
7.
Endocr J ; 57(10): 873-80, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20733268

RESUMO

Sunitinib is a multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma. However, sunitinib often causes hypothyroidism. In this study, we report eight cases with thyroid dysfunction that occurred during sunitinib treatment for advanced renal cell carcinoma. In seven cases, mild hypothyroidism developed early in the first treatment cycle, and recovered spontaneously. Transient hyperthyroidism was observed during the second or third treatment cycles and was preceded by a rapid increase in thyroglobulin levels. (99m)Tc scintigraphy in the hyperthyroid state showed decreased thyroidal uptake of (99m)TcO(4)(-), suggesting destructive thyroiditis. Hypothyroidism subsequently developed, requiring levothyroxine replacement therapy. Ultrasonography showed a hypoechogenic pattern of the parenchyma and decreased intrathyroidal blood flow. The thyroid glands ultimately became atrophic, which may progress to permanent hypothyroidism. These findings suggest that sunitinib-induced hypothyroidism may occur frequently and may be a consequence of thyroiditis with transient thyrotoxicosis. The marked decrease in thyroid size due to reduced capillary blood flow induced by VEGF receptor inhibition may cause delayed and/or permanent hypothyroidism. Therefore, thyroid function should be monitored in all patients treated with sunitinib.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Indóis/efeitos adversos , Pirróis/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Atrofia , Progressão da Doença , Feminino , Humanos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/patologia , Hipertireoidismo/fisiopatologia , Hipotireoidismo/patologia , Indóis/uso terapêutico , Japão , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirróis/uso terapêutico , Fluxo Sanguíneo Regional/efeitos dos fármacos , Sunitinibe , Glândula Tireoide/irrigação sanguínea , Glândula Tireoide/patologia , Tireoidite/induzido quimicamente , Tireotoxicose/induzido quimicamente , Tireotoxicose/patologia , Tireotoxicose/fisiopatologia
8.
Prostate ; 68(16): 1753-62, 2008 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-18767041

RESUMO

BACKGROUND: To evaluate the immunological responses of personalized peptide vaccination combined with low-dose glucocorticoids for advanced hormone refractory prostate cancer (HRPC) patients (pts). METHODS: Eleven pts with advanced HRPC were treated with the vaccination and low-dose glucocorticoids; 6 pts with 10 mg/day of prednisolone (PDL) followed by 1 mg/day of dexamethasone at the time of progression, 1 pt with PDL, and 4 pts with dexamethasone. Peptide-specific cellular and humoral responses were employed to monitor pre- and post- (6th) vaccination samples. RESULTS: The vaccination combined with glucocorticoids was well tolerated with no severe adverse effects. Increments of IgG responses were observed in 1 of 4 or 8 of 10 pts tested who received PDL or dexamethasone, respectively, increment of cytotoxic T lymphocyte activity was observed in 2 of 4 or 5 of 7 pts tested, respectively. Vaccination with PDL or dexamethasone resulted in a decline of PSA (at least 50%) in 1 of 7 or 6 of 10 pts with significantly longer median TTP in the dexamethasone group, respectively. CONCLUSION: Vaccination combined with dexamethasone could be recommended for further clinical trials from both immunological and clinical points of view.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Antineoplásicos Hormonais/farmacologia , Vacinas Anticâncer/farmacologia , Dexametasona/farmacologia , Neoplasias da Próstata/terapia , Idoso , Formação de Anticorpos/imunologia , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/uso terapêutico , Terapia Combinada , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Masculino , Prednisolona/efeitos adversos , Prednisolona/farmacologia , Prednisolona/uso terapêutico , Neoplasias da Próstata/imunologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Int J Oncol ; 33(4): 647-55, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18813777

RESUMO

We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) alone and PEG-IFN-alpha2b plus 5-fluorouracil (5-FU) in vitro on the proliferation of renal cell carcinoma (RCC) cell lines. After the transplantation of RCC cells into nude mice, we administered IFN (PEG-IFN-alpha2b or IFN-alpha2b) alone, 5-FU alone, or IFN (PEG-IFN-alpha2b or IFN-alpha2b) plus 5-FU; and investigated tumor volume, tumor weight, the numbers of apoptotic cells and artery-like blood vessels, relative mRNA expression levels of enzymes which relate to 5-FU metabolism, angiogenesis factor, and type I interferon receptor. RCC cells in vitro were generally and relatively resistant to the anti-proliferative effects of PEG-IFN-alpha2b, but the addition of 5-FU augmented IFN-induced anti-proliferative effects with the induction of apoptosis. PEG-IFN-alpha2b in vivo presented stronger anti-tumor effects than IFN-alpha2b, and its combination with 5-FU augmented the effects. The significant anti-tumor effect of the combination treatment was the increase in apoptotic cell number, but there were no significant differences in the suppression of angiogenesis, expression of IFN receptor, and the actions of metabolic enzymes of 5-FU. In conclusion, PEG-IFN-alpha2b presents stronger anti-tumor effects than non-pegylated IFN, and the effects are augmented in the combination with 5-FU. Our findings suggest the clinical usefulness of PEG-IFN-alpha2b in the treatment of RCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Fluoruracila/farmacologia , Interferon-alfa/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Transplante de Células , Feminino , Humanos , Técnicas In Vitro , Interferon alfa-2 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neovascularização Patológica , Polietilenoglicóis/química , Proteínas Recombinantes
10.
BJU Int ; 102(8): 958-63, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18485031

RESUMO

OBJECTIVE: To evaluate, in a prospective, single-blind, randomized trial, the safety and efficacy of a suspension technique for improving early recovery of continence after radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: We randomly assigned 60 men with clinically localized prostate cancer to RRP; 30 were treated with the suspension technique and the remaining 30 were not. All patients had RRP by the same surgeon followed by early catheter removal on the third day after RRP. The primary outcome measures were the interval to recovery of continence, and the positive margin rates. The continence status was evaluated by a third party using validated questionnaires at baseline before RRP and at 4 and 7 days, and 2 weeks, 1, 3, 6 and 12 months after RRP. RESULTS: The suspension technique resulted in significantly greater continence rates at 1, 3 and 6 months after RRP of 53% vs 20%, 73% vs 47% and 100% vs 83%. Kaplan-Meier curves also showed that patients in the suspension group had a significantly earlier recovery of continence than in the no-suspension group; the median (95% confidence interval) interval for recovery was 31 (12-74) days in the suspension group and 90 (65-150) days in the no-suspension group (log rank test, P = 0.002). The groups had no significant differences in their histological status. CONCLUSIONS: The suspension technique had a significant effect on the earlier recovery of urinary continence within 6 months after RRP, without compromising the oncological outcome of RRP.


Assuntos
Complicações Pós-Operatórias/prevenção & controle , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Incontinência Urinária/prevenção & controle , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prostatectomia/métodos , Método Simples-Cego , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Cateterismo Urinário/métodos
11.
Asian J Androl ; 10(4): 651-8, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18097503

RESUMO

AIM: To conduct a double-blind, placebo-controlled randomized and dose-ranging study to evaluate the safety and efficacy of the extract of Ganoderma lucidum (G. lucidum) in men with lower urinary tract symptoms (LUTS). METHODS: We enrolled male volunteers (> or = 50 years) with an International Prostate Symptom Score (IPSS; questions 1-7) > or = 5 and a prostate-specific antigen (PSA) value < 4 ng/mL. Volunteers were randomized into groups of placebo (n = 12), G. lucidum of 0.6 mg (n = 12), 6 mg (n = 12) or 60 mg (n = 14), administered once daily. Efficacy was measured as a change from baseline in IPSS and the peak urine flow rate (Q(max)). Prostate volume and residual urine were estimated by ultrasonography, and blood tests, including PSA levels, were measured at baseline and at the end of the treatment. RESULTS: The overall administration was well tolerated, with no major adverse effects. Statistical significances in the magnitude of changes between the experimental groups were observed at weeks 4 and 8. No changes were observed with respect to Q(max), residual urine, prostate volume or PSA levels. CONCLUSION: The extract of G. lucidum was well tolerated and an improvement in IPSS was observed. The recommended dose of the extract of G. lucidum is 6 mg in men with LUTS.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Reishi , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia/métodos , Projetos Piloto , Próstata/patologia , Antígeno Prostático Específico/sangue , Resultado do Tratamento
12.
Asian J Androl ; 10(5): 777-85, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18097505

RESUMO

AIM: To evaluate the safety and efficacy of an extract of Ganoderma lucidum that shows the strongest 5alpha-reductase inhibitory activity among the extracts of 19 edible and medicinal mushrooms by a double-blind, placebo-controlled, randomized and dose-ranging study in men with lower urinary tract symptoms (LUTS). METHODS: In this trial, we randomly assigned 88 men over the age of 49 years who had slight-to-moderate LUTS to 12 weeks of treatment with G. lucidum extract (6 mg once a day) or placebo. The primary outcome measures were changes in the International Prostate Symptom Score (IPSS) and variables of uroflowmetry. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, laboratory values and the reported adverse effects. RESULTS: G. lucidum was effective and significantly superior to placebo for improving total IPSS with 2.1 points decreasing at the end of treatment (mean difference, -1.18 points; 95% confidence interval, -1.74 to -0.62; P < 0.0001). No changes were observed with respect to quality of life scores, peak urinary flow, mean urinary flow, residual urine, prostate volume, serum prostate-specific antigen or testosterone levels. Overall treatment was well tolerated with no severe adverse effects. CONCLUSION: The extract of G. lucidum was well tolerated and improved IPSS scores. These results encouraged a further, large-scale evaluation of phytotherapy for a long duration using the extract of G. lucidum on men with LUTS.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Fitoterapia , Reishi , Transtornos Urinários/tratamento farmacológico , Urodinâmica/efeitos dos fármacos , Idoso , Medicamentos de Ervas Chinesas/efeitos adversos , Etanol , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Solventes , Resultado do Tratamento
13.
Cancer Sci ; 98(12): 1965-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17919310

RESUMO

The aim of this clinical trial was to investigate the toxicity and immunological responses of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients. Patients were confirmed to be human leukocyte antigen (HLA)-A24 or HLA-A2 positive and had histologically confirmed renal cell carcinoma. Ten patients were enrolled in the present study. The peptides to be administered were determined based on the presence of peptide-specific cytotoxic T lymphocyte precursors in peripheral blood mononuclear cells (PBMC) and peptide-specific IgG in the plasma of cancer patients. Patients received subcutaneous injections of four different peptides (3 mg/peptide) every 2 weeks. Vaccinations were well tolerated without any major adverse events. A minimal increase in peptide-specific interferon-gamma production in postvaccination PBMC was observed, regardless of higher levels of cytotoxic T lymphocyte activity in prevaccination PBMC. In contrast, an increase in peptide-specific IgG levels of postvaccination (sixth) plasma was observed in the majority of patients. After progression, five patients received interleukin-2 therapy and continuous vaccination, with survival of 31, 25, 23, 17, and 15 months, but interleukin-2 did not impede humoral responses boosted by the vaccination. These results encourage further clinical trials of personalized peptide vaccinations.


Assuntos
Vacinas Anticâncer/toxicidade , Carcinoma de Células Renais/imunologia , Neoplasias Renais/imunologia , Vacinas de Subunidades Antigênicas/toxicidade , Carcinoma de Células Renais/patologia , Terapia Combinada , Citocinas/uso terapêutico , Antígenos HLA-A/imunologia , Antígeno HLA-A2/imunologia , Antígeno HLA-A24 , Humanos , Imunoglobulina G/sangue , Neoplasias Renais/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Seleção de Pacientes
14.
Oncol Res ; 16(7): 341-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17518272

RESUMO

The aim of this study was to investigate prognostic factors of patients with metastatic hormone refractory prostate cancer (HRPC) under combined administration of personalized peptide vaccination and low-dose estramustine phosphate (EMP). From February 2001 to July 2004, 58 men with metastatic HRPC received the combination therapy of personalized peptide vaccination and low-dose EMP. Conducted immune monitorings for those patients were peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production and peptide-reactive immunoglobulin G (IgG) by an enzyme-linked immunosorbent assay. Clinical responses and survival times were also evaluated. The combination therapy was well tolerated with no major adverse effects. Increased levels of CTL precursors and IgG responses to the vaccinated peptides were observed in 29 of 37 (78%) patients and in 36 of 41 (88%) patients tested, respectively. A prostate-specific antigen decline of at least 50% occurred in 24% of patients. The median survival time was 17 months (95% confidence interval, 12-25 months). Cox proportional hazards analysis showed that a low number of lymphocytes (p = 0.0075, odds ratio 2.700), a negative immunological activity response after the vaccination (p = 0.0185, odds ratio 2.658), and poor performance status (p = 0.0347, odds ratio 2.569) were independent predictors of disease death. These encouraging results show the need for further evaluation of the combination of personalized peptide vaccination and low dose of EMP for metastatic HRPC patients.


Assuntos
Vacinas Anticâncer/uso terapêutico , Epitopos de Linfócito T/uso terapêutico , Estramustina/uso terapêutico , Imunoterapia Ativa/métodos , Peptídeos/uso terapêutico , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Formação de Anticorpos/imunologia , Vacinas Anticâncer/imunologia , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Humanos , Imunidade Celular/imunologia , Imunoglobulina G/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/terapia , Peptídeos/química , Peptídeos/imunologia , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento
15.
Oncol Rep ; 18(6): 1463-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17982631

RESUMO

The human leukocyte antigen (HLA)-G molecule can exert immunoregulatory functions. However, its limited tissue distribution and preferential expression in a variety of malignancies suggest the possibility that it could be a target in anti-cancer immunotherapy. In the present study, we tested this possibility by focusing on renal cell carcinoma (RCC) patients, especially those with HLA-A24 alleles. Four HLA-G-derived peptides were prepared based on the binding motif to the HLA-A24 alleles. After a stabilization assay confirmed the binding of these peptides to HLA-A24 molecules, they were screened for the capacity to induce peptide-specific cytotoxic T lymphocytes (CTLs) from peripheral blood mononuclear cells (PBMCs) of HLA-A24+ RCC cancer patients. As a result, the HLA-G(146-154) peptide was found to effectively induce peptide-specific CTLs, and HLA-G(146-154) peptide-stimulated PBMCs exhibited cytotoxic activity against HLA-G-expressing HLA-A24+ RCC cells. Antibody blocking and cold inhibition experiments confirmed that the cytotoxicity was partially ascribed to peptide-specific and HLA class I-restricted CD8+ T cells. These results indicate that HLA-G-associated immunoregulation can be overcome and that HLA-G peptide-based anti-cancer immunotherapy is feasible.


Assuntos
Carcinoma de Células Renais/imunologia , Antígenos HLA/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Imunoterapia/métodos , Neoplasias Renais/imunologia , Sequência de Aminoácidos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Citometria de Fluxo , Antígenos HLA-A/genética , Antígeno HLA-A24 , Antígenos HLA-G , Humanos , Interferon gama/farmacologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Fragmentos de Peptídeos , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
16.
Transl Oncol ; 10(6): 998-1007, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29096248

RESUMO

Patients who undergo surgical extirpation of a primary liver carcinoma followed by radiotherapy and chemotherapy leading to complete remission are nevertheless known to develop cancerous metastases 3-10 years later. We retrospectively examined the blood sera collected over 8 years from 30 patients who developed bone metastases after the complete remission of liver cancer to identify serum proteins showing differential expression compared to patients without remission. We detected a novel RGD (Arg-Gly-Asp)-containing peptide derived from the C-terminal portion of fibrinogen in the sera of metastatic patients that appeared to control the EMT (epithelial-mesenchymal transition) of cancer cells, in a process associated with miR-199a-3p. The RGD peptide enhanced new blood vessel growth and increased vascular endothelial growth factor levels when introduced into fertilized chicken eggs. The purpose of this study was to enable early detection of metastatic cancer cells using the novel RGD peptide as a biomarker, and thereby develop new drugs for the treatment of metastatic cancer.

17.
Int J Oncol ; 29(6): 1555-60, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17088996

RESUMO

We have previously identified numerous tumor-rejection antigens and their epitope peptides having the potential to induce cancer-reactive cytotoxic T lymphocytes (CTLs) in patients with various types of cancer. In the present study, we attempted to determine which antigens and their peptides are useful in specific immunotherapy for bladder carcinoma (BC) patients, especially those with human leukocyte antigen (HLA)-A24+ alleles. The mRNA expression of a panel of cancer-associated antigens was examined regarding four BC cell lines. As a result, three candidate antigens, including SART3, multidrug resistance-associated protein 3 (MRP3), and polycomb group protein enhancer of zeste homolog 2 (EZH2), were expressed in three of four BC cell lines. Thereafter, antigen-derived peptides which we reported to induce cancer-reactive CTLs from HLA-A24+ patients with various types of cancer were examined for their potential to induce CTLs from peripheral-blood mononuclear cells of HLA-A24+ BC patients. Among these antigen-derived six peptides, SART3109-118, MRP31293-1301, and EZH2735-742 peptides efficiently induced peptide-specific and BC cell-reactive CTLs from HLA-A24+ BC patients. The cytotoxicity against BC cells was dependent on peptide-specific CD8+ T cells. IgG reactive to the SART3109-118 peptide was frequently detected in the plasma of BC patients. This information could facilitate the development of effective peptide-based immunotherapy for HLA-A24+ BC patients.


Assuntos
Vacinas Anticâncer/imunologia , Antígenos HLA-A/imunologia , Imunoterapia Ativa/métodos , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/uso terapêutico , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/imunologia , Proteína Potenciadora do Homólogo 2 de Zeste , Antígeno HLA-A24 , Humanos , Imunoglobulina G/imunologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/imunologia , Complexo Repressor Polycomb 2 , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas de Ligação a RNA/imunologia , Linfócitos T Citotóxicos/imunologia , Fatores de Transcrição/imunologia
19.
Low Urin Tract Symptoms ; 8(1): 55-61, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26789544

RESUMO

OBJECTIVES: To understand the mechanisms underlying ejaculation dysfunction caused by α1A-adrenocetor (AR) antagonists, the effects of α1A-AR antagonists on the contractile responses of the seminal vesicle were investigated. METHODS: Isolated seminal vesicles from guinea pigs were cannulated and pressurized, and the changes in the intraluminal pressure were recorded. Periodic applications of electrical stimulation (ES) caused biphasic increase in the intraluminal pressure, that is, initial and subsequent contractions. The effects of silodosin and tamsulosin, α1A-AR antagonists, on the contractile responses were examined. RESULTS: The ES-induced biphasic contractions were blocked by tetrodotoxin (TTX). Silodosin and tamsulosin suppressed the initial contractions in a dose-dependent manner, while also exerting various inhibitory effects on the subsequent contractions. Increases in the intraluminal pressure facilitated spontaneous phasic contractions. The spontaneous contractions were not affected by TTX or α1A-AR antagonists, but were abolished by nifedipine. CONCLUSIONS: The initial contractions triggered by neuronal excitations were suppressed by silodosin and tamsulosin, suggesting that the ejaculation dysfunction may be attributed to the α1A-AR antagonist-mediated suppression of nerve-evoked contractions in the seminal vesicle. The subsequent contractions may be induced by mechanical stimulation associated with the initial, nerve-evoked contractions. Alternatively, other transmitters may be involved to various degrees in the neuromuscular transmission of the seminal vesicle.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Indóis/farmacologia , Contração Muscular/efeitos dos fármacos , Glândulas Seminais/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Cobaias , Masculino , Tansulosina
20.
Kurume Med J ; 62(1-2): 9-16, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26935441

RESUMO

We investigated the influence of nocturia and sleep disturbance on health-related quality of life(HRQOL) using the Medical Outcomes Study 8-item Short Form Health Survey (SF-8) in patients with nocturia. We also assessed the effect of therapeutic intervention by means of an anticholinergic agent on the results of the SF-8. One hundred and eighty-four patients who voided at least once per night were surveyed using the SF-8, Overactive Bladder Symptom Score (OABSS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). These parameters were also evaluated before and after 12 weeks of imidafenacin treatment in 51 patients with OAB accompanied by nocturia. The SF-8 physical component summary score (PCS) showed a significant decrease as nighttime voiding frequency increased. The mental health component summary score was 47.1 and 47.6 (which were lower than the standard value of 50) in the group with a nighttime frequency of once and ≥3/night, respectively. The SF-8 PCS and 6 subscales were negatively associated with nighttime voiding frequency, while the PSQI global score was positively associated with it. Imidafenacin significantly improved the OABSS, PSQI, and ESS, as well as the SF-8 score. This is the first study using the SF-8 to show that nocturia and sleep disturbance have a major influence on comprehensive HRQOL and that the SF-8 can be used to monitor HRQOL in OAB patients receiving treatment for nocturia.


Assuntos
Noctúria/psicologia , Qualidade de Vida , Transtornos do Sono-Vigília/psicologia , Sono , Inquéritos e Questionários , Bexiga Urinária Hiperativa/psicologia , Bexiga Urinária/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas Colinérgicos/uso terapêutico , Feminino , Nível de Saúde , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Noctúria/diagnóstico , Noctúria/tratamento farmacológico , Noctúria/fisiopatologia , Valor Preditivo dos Testes , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/fisiopatologia , Urodinâmica
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