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1.
Hinyokika Kiyo ; 47(5): 349-61, 2001 May.
Artículo en Japonés | MEDLINE | ID: mdl-11433759

RESUMEN

Pharmacodynamics (PD), anti-tumor effects, safety and pharmacokinetics of a 3-month formulation of goserelin (Zoladex LA 10.8 mg depot: "10.8 mg depot") were investigated in a collaborative multicenter study. Study participants were 40 Japanese patients with prostate cancer comprising 20 untreated patients and 20 switch patients who had been receiving Zoladex 3.6 mg depot for 3 months or longer. Serum testosterone levels, serum LH levels, prostate-specific antigen (PSA) levels and drug concentrations were measured until 12 weeks after a single subcutaneous dose of 10.8 mg depot. Anti-tumor effects were evaluated by means of changes in the tumor lesions and the PSA levels at 12 weeks. After administration to the untreated patients, 10.8 mg depot reduced serum testosterone to the castrate range within 4 weeks and the reduction was maintained for up to 12 weeks. In the switch patients, serum testosterone suppression that had been produced by previous treatment with Zoladex 3.6 mg depot was maintained for up to 12 weeks following 10.8 mg depot administration. The anti-tumor effect at 12 weeks was 90.0% including partial response cases. The ratio of PSA normalization at 12 weeks was 75.0%. Fifty-seven adverse reactions were observed in 27 of the 40 patients (67.5%), but none were clinically significant. Although a disease flare presented as urinary retention in 1 of the untreated patients, all patients completed the study. Serum goserelin was detected up to 12 weeks after the administration of 10.8 mg depot. In conclusion a single dose of 10.8 mg depot showed a satisfactory PD-effect and brought about clinical efficacy persisting for at least 12 weeks and was well tolerated in patients with prostate cancer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Hormonales/uso terapéutico , Hormona Liberadora de Gonadotropina/agonistas , Goserelina/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/metabolismo , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/farmacocinética , Preparaciones de Acción Retardada , Esquema de Medicación , Goserelina/administración & dosificación , Goserelina/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/metabolismo , Testosterona/sangre
2.
Anal Sci ; 17(1): 107-12, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11993644

RESUMEN

A highly sensitive and selective fluorometric determination method for ornithine and lysine has been developed. This method is based on an intramolecular excimer-forming fluorescence derivatization with a pyrene reagent, 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester (PSE), followed by reversed-phase liquid chromatography (LC). The analytes, containing two amino moieties in a molecule, were converted to the corresponding dipyrene-labeled derivatives by reaction with PSE. The derivatives afforded intramolecular excimer fluorescence (450-550 nm) which can clearly be discriminated from the normal fluorescence (370-420 nm) emitted from PSE and monopyrene-labeled derivatives of monoamines. The structures of the derivatives and the emission of excimer fluorescence were confirmed by LC with mass spectrometry and with three-dimensional fluorescence detection system, respectively. The PSE derivatives of ornithine and lysine could be separated by reversed-phase LC on ODS column with isocratic elution. The detection limits (signal-to-noise ratio = 3) for ornithine and lysine were 3.5 and 3.7 fmol, respectively, for a 20-microl injection. Furthermore, this method had enough selectivity and sensitivity for the determination of ornithine and lysine in normal human urine.


Asunto(s)
Lisina/análisis , Ornitina/análisis , Calibración , Cromatografía Liquida , Colorantes Fluorescentes/química , Humanos , Indicadores y Reactivos , Lisina/orina , Espectrometría de Masas , Ornitina/orina , Pirenos/química , Reproducibilidad de los Resultados , Espectrometría de Fluorescencia
3.
Anal Chem ; 72(17): 4199-204, 2000 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-10994984

RESUMEN

We introduce a novel approach in highly selective and sensitive fluorescence derivatization of polyamines. This method is based on an intramolecular excimer-forming fluorescence derivatization with a pyrene reagent, 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester (PSE), followed by reversed-phase high-performance liquid chromatography (HPLC). Polyamines, having two to four amino moieties in a molecule, were converted to the corresponding dipyrene- to tetrapyrene-labeled derivatives by reaction (100 degrees C, 20 min) with PSE. The derivatives afforded intramolecular excimer fluorescence (450-520 nm), which can clearly be discriminated from the monomer (normal) fluorescence (360-420 nm) emitted from PSE, its hydrolysate and monopyrene-labeled derivatives of monoamines. The structures of the derivatives were confirmed by HPLC with mass spectrometry, and the emission of excimer fluorescence could be proved by spectrofluorometry and time-resolved fluorometry. The PSE derivatives of four polyamines [putrescine (Put), cadaverine (Cad), spermidine (Spd), and spermine (Spm)] could be separated by reversed-phase HPLC on a C8 column with linear gradient elution. The detection limits (signal-to-noise ratio of 3) for the polyamines were 1 (Put), 1 (Cad), 5 (Spd), and 8 (Spm) fmol on the column. Furthermore, the present method was so selective that biogenic monoamines gave no peak in the chromatogram.


Asunto(s)
Poliaminas/análisis , Cromatografía Líquida de Alta Presión , Fluorometría , Espectrometría de Masas , Pirenos
4.
Hinyokika Kiyo ; 46(11): 791-7, 2000 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-11193299

RESUMEN

This study was conducted to examine the efficacy of administration of tamsulosin hydrochloride alone or in combination with chlormadinone acetate (CMA) against lower urinary tract symptoms for a period of 52 weeks in 33 patients with benign prostatic hyperplasia. The patients were randomly allocated into a group administered tamsulosin alone and a group administered tamsulosin in combination with CMA. Based on the assessment of the total I-PSS (International Prostate Symptom Score), significant symptomatic improvement was noted 4 weeks after the commencement of drug administration in the tamsulosin + CMA group, whereas no significant improvement was observed in the tamsulosin group. Both irritative and obstructive bladder symptoms improved significantly at any time of assessment after 4 weeks of drug administration in the tamsulosin + CMA group; however, significant improvement was noted only at week 16 and week 52 for irritative symptoms and at week 16 for obstructive symptoms in the tamsulosin group. In particular, obstructive symptoms showed significant improvement at week 4 in the tamsulosin + CMA group, as compared with that in the tamsulosin group. The average value of peak urinary flow rate was significantly increased in the tamsulosin + CMA group (10.4 ml/s to 15.6 ml/s) as compared with that in the tamsulosin group (8.5 ml/s to 10.5 ml/s). These findings indicate that combined administration of tamsulosin and CMA resulted in early improvement of lower urinary tract symptoms in these patients. Long-term combined administration of tamsulosin and CMA thus appears to be a promising treatment strategy for the improvement of obstructive symptoms and peak urinary flow rate, particularly, 16 weeks onward after administration in patients with benign prostatic hyperplasia.


Asunto(s)
Antagonistas Adrenérgicos alfa/uso terapéutico , Antagonistas de Andrógenos/uso terapéutico , Acetato de Clormadinona/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Sulfonamidas/uso terapéutico , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/fisiopatología , Tamsulosina , Factores de Tiempo , Resultado del Tratamiento , Urodinámica
5.
Int J Urol ; 6(4): 173-7, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10226833

RESUMEN

PURPOSE: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. METHODS: Patients with microscopic hematuria detected at a health examination, who were advised by a consulted urologist to have a cystoscopical examination, were asked to enter this study. Urine samples were collected before cystoscopy and divided into two portions for NMP22 test and voided urine cytology. RESULTS: Of the 309 patients with microscopic hematuria, 22 cases (7.1%) of urothelial cancer and one case of prostate cancer were detected. For the other cases, 128 (41.4%) were of benign diseases and 158 (51.1%) were designated as having no evidence of disease (NED). The median NMP22 values for urothelial cancer, other diseases and NED were 35.5, 6.7 and 6.0 U/mL, respectively, with 95% confidence intervals of 19.9-228.2, 5.1-9.3 and 5.4-7.2, respectively. The sensitivity of the NMP22 test for urothelial cancer was 90.9% (20/22), whereas the sensitivity of voided urine cytology was only 54.5% (12/22). CONCLUSIONS: The present study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.


Asunto(s)
Biomarcadores de Tumor/orina , Hematuria/diagnóstico , Tamizaje Masivo/métodos , Proteínas Nucleares/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Cistitis/diagnóstico , Diagnóstico Diferencial , Femenino , Hematuria/orina , Humanos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/orina , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/orina , Urinálisis , Neoplasias de la Vejiga Urinaria/orina , Cálculos Urinarios/diagnóstico , Cálculos Urinarios/orina , Urotelio/química
6.
Jpn J Clin Oncol ; 29(2): 87-91, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10089949

RESUMEN

BACKGROUND: Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed. METHODS: CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion. RESULTS: Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P < 0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P < 0.0001). CONCLUSION: A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.


Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Granisetrón/uso terapéutico , Náusea/prevención & control , Vómito Precoz/prevención & control , Adolescente , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Esquema de Medicación , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico
7.
Jpn J Clin Oncol ; 29(11): 562-70, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10678560

RESUMEN

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.


Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Acetato de Clormadinona/administración & dosificación , Dietilestilbestrol/administración & dosificación , Goserelina/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Supervivencia sin Enfermedad , Esquema de Medicación , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/mortalidad , Tasa de Supervivencia
8.
Eur Urol ; 34(5): 441-7, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9803008

RESUMEN

The number of nucleolar organizer regions (NOR) of human bladder cancers was evaluated at the light- and electron-microscopic level. The average number of argyrophilic NOR (AgNOR), stained by the one-step silver colloid method, was measured in benign and malignant urothelial cells in the human urinary bladder using a light microscope. The average number of nucleolar fibrillar centers (FC) per nucleus was also calculated by quantitative ultrastructural morphometry in the specimens from the same patients. Statistical evaluations revealed that the average number of AgNOR per nucleus was significantly correlated with the elevation of tumor grade and stage (p < 0.05). An average FC number per nucleus also increased in association with tumor grade and stage (p < 0.05). Although the average number of FC was 5.6 times higher than that of AgNOR, the correlation between the average number of FC and AgNOR was statistically significant. In conclusion, these results suggested that the silver staining method was a useful and convenient tool for the evaluation of the differentiation and invasive potential of bladder cancer cells at the light-microscopic level.


Asunto(s)
Carcinoma de Células Transicionales/ultraestructura , Región Organizadora del Nucléolo/ultraestructura , Neoplasias de la Vejiga Urinaria/ultraestructura , Cálculos Urinarios/ultraestructura , Biopsia con Aguja , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Núcleo Celular/ultraestructura , Femenino , Marcadores Genéticos , Humanos , Masculino , Microscopía Electrónica , Estadificación de Neoplasias , Sensibilidad y Especificidad , Plata/análisis , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Cálculos Urinarios/genética , Cálculos Urinarios/patología
9.
Gan To Kagaku Ryoho ; 25(8): 1179-87, 1998 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-9679581

RESUMEN

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.


Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Transicionales/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Tegafur/administración & dosificación , Uracilo/administración & dosificación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Oral , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Carcinoma de Células Transicionales/radioterapia , Carcinoma de Células Transicionales/cirugía , Quimioterapia Adyuvante , Dietilestilbestrol/administración & dosificación , Dietilestilbestrol/análogos & derivados , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/cirugía
11.
Gan To Kagaku Ryoho ; 24(7): 829-36, 1997 May.
Artículo en Japonés | MEDLINE | ID: mdl-9170521

RESUMEN

This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the surveillance of bladder cancer, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 144 patients with histologically diagnosed bladder cancer, 65 patients with other urological cancers, and 171 healthy volunteers by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All bladder cancer patients were evaluated for urinary NMP22 values and voided urine cytology simultaneously from the same urine samples. Based on the data from the bladder cancer patients and the healthy volunteers, the cut-off value was set at 12 U/ml. The median urinary NMP22 value for the bladder cancer patients was 17.8 U/ml (95% CI: 13.1-29.0). The sensitivities of urinary NMP22 and voided urine cytology were 61.1% (88/144) and 33.8% (48/144), respectively, a significant difference (p < 0.00001). Multivariate analysis revealed that tumor size affected the urinary NMP22 values. The positive rate by tumor size was 42.3%, 59.1%, and 85.0% for tumors of < 10 mm, 10-30 mm, and > 30 mm, respectively. Urinary NMP22 values decreased postoperatively in 82.9% of the patients. The median NMP22 values for prostate cancer and renal cancer were 4.4 U/ml (95% CI: 2.2-6.7) and 6.2 U/ml (95% CI: 3.6-12.5). The positive rates were 24.2% and 31.3%, respectively, both of which were significantly lower than for bladder cancer. Our multicenter study indicates that urinary NMP22 test is more sensitive than voided urine cytology test for the surveillance of bladder cancer.


Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/diagnóstico , Proteínas Nucleares/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Femenino , Humanos , Neoplasias Renales/diagnóstico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias de la Próstata/diagnóstico
12.
Gan To Kagaku Ryoho ; 24(7): 837-42, 1997 May.
Artículo en Japonés | MEDLINE | ID: mdl-9170522

RESUMEN

This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 183 patients with microscopic hematuria by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All patients were entered in this study before cystoscopy was performed, and were evaluated for NMP22 values and voided urine cytology simultaneously from the same urine samples. Of the 183 patients with microscopic hematuria, 14 cases of urothelial cancer were detected. For the other cases, 65 were of benign diseases and 104 were designated NED (No Evidence of Disease). The median NMP22 values for urothelial cancer, benign diseases, and NED were 26.5 U/ml (95% CI: 18.5-228.2; 4.9 U/ml (95% CI: 3.6-8.3), and 5.9 U/ml (95% CI: 4.8-6.5), respectively. The urinary NMP22 value for urothelial cancer was significantly higher than for benign diseases and NED. When the cut-off value of urinary NMP22 was set at 12 U/ml, the positive rate of NMP22 for urothelial cancer was 85.7%, significantly higher than the 50% positive rate by voided urine cytology. This study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.


Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/diagnóstico , Hematuria/orina , Proteínas Nucleares/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Renales/diagnóstico , Pelvis Renal , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Neoplasias Uretrales/diagnóstico
13.
Eur Urol ; 31(3): 360-4, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9129932

RESUMEN

OBJECTIVE: It has been reported that blocking of testosterone production inhibits bladder carcinogenesis in various animal models. We investigated how testosterone acts on rat bladder carcinogenesis using an antiandrogen, flutamide, and a 5 alpha-reductase inhibitor, finasteride. METHODS: Experiment 1: we administered 0.05% BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] orally to 117 Wistar rats for 10 weeks, divided them into seven groups-control, surgical castration, finasteride (2 mg/kg), luteinizing hormone releasing hormone (LH-RH) agonist (1 mg/kg) flutamide (50 mg/kg), LH-RH agonist plus finasteride, and LH-RH agonist plus flutamide-, and then cystectomized them to investigate the incidence of bladder cancer on week 21; experiment 2: we administered 0.05% BBN to 154 Wistar rats for 7 weeks, divided them into seven groups-control, finasteride 2, 4, and 8 mg/kg, and flutamide 50, 100, and 200 mg/kg-, and then we cystectomized them to investigate the dose-dependent influence on bladder carcinogenesis of these drugs on week 20, and experiment 3: we investigated the presence of androgen receptors in rat and mouse normal bladder mucosa using a monoclonal antibody. RESULTS AND CONCLUSIONS: Experiment 1: Surgical castration and LH-RH agonist treatment significantly reduced the occurrence of carcinomas. There was no significant additive effect of coadministered finasteride or flutamide with LH-RH agonist. Finasteride or flutamide monotherapy showed no statistically significant effects on the results of experiment 1 at the doses used. Experiment 2: Flutamide showed a dose-dependent effect on reducing the number of rats with bladder cancer, and at a dosis of 200 mg/kg twice a week, the difference was statistically significant when compared with the control group, whereas finasteride had no statistically significant suppressing effect at any dose. Experiment 3: Mouse and rat bladder urothelium expressed the androgen receptor. Our results indicate that testosterone itself might have a more potent action on bladder carcinogenesis rather than its converting form, 5 alpha-dihydrotestosterone.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Finasterida/uso terapéutico , Flutamida/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Oral , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/farmacología , Animales , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Butilhidroxibutilnitrosamina , Carcinógenos , Carcinoma/tratamiento farmacológico , Carcinoma/metabolismo , Colestenona 5 alfa-Reductasa , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Finasterida/administración & dosificación , Finasterida/farmacología , Flutamida/administración & dosificación , Flutamida/farmacología , Hormona Liberadora de Gonadotropina/agonistas , Inmunohistoquímica , Leuprolida/administración & dosificación , Leuprolida/farmacología , Leuprolida/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C3H , Oxidorreductasas/antagonistas & inhibidores , Ratas , Ratas Wistar , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/metabolismo
14.
Eur Urol ; 31(2): 163-8, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9076459

RESUMEN

OBJECTIVES: This study was undertaken to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a novel urine marker for urothelial cancer, particularly, to substitute for voided-urine cytology. METHODS: NMP22 values were determined for 280 patients and 20 healthy volunteers by NMP22 Test Kit based on an enzyme-linked immunosorbent assay. RESULTS: When the cut-off value was set at 10 U/ml, the positive rate of urinary NMP22 for urothelial cancer was 80.9% (38/47), whereas that for posttreatment cases and benign diseases was 35.7% (74/207). When urinary NMP22 and voided-urine cytology were compared, the test for urinary NMP22 showed higher sensitivity than cytology in patients with urothelial cancer. When urinary NMP22 values were determined pre- and postoperatively in patients with urothelial cancer, the postoperative value decreased in all patients, and were below the cut-off value in all except one patient. CONCLUSIONS: Urinary NMP22 is a useful diagnostic marker as a substitute for voided-urine cytology for the surveillance of urothelial cancer.


Asunto(s)
Adenocarcinoma/orina , Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/orina , Proteínas Nucleares/orina , Neoplasias Urológicas/orina , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales , Biomarcadores de Tumor/sangre , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Niño , Ritmo Circadiano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/orina , Estadificación de Neoplasias , Proteínas Nucleares/sangre , Proyectos Piloto , Estudios Retrospectivos , Orina/citología , Neoplasias Urológicas/patología , Neoplasias Urológicas/cirugía , Urotelio/patología
15.
Int J Urol ; 4(6): 557-60, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9477183

RESUMEN

BACKGROUND: The BTA test is a latex agglutination assay for the qualitative detection in the urine of analytes that are associated with bladder tumor. We compared the results of the BTA test with those of voided urine cytology (VUC) in patients with bladder cancer. METHODS: A multicenter trial was performed at 6 institutions. A total of 132 patients with histologically diagnosed bladder cancer were enrolled. Urine samples were split for BTA and VUC testing. RESULTS: The sensitivities of the BTA test and VUC were 57.6% and 37.9%, respectively; this difference was significant (P < 0.001). The BTA test had much higher sensitivity for small, solitary, superficial tumors than did VUC. CONCLUSION: The BTA test is simple to perform, gives rapid results, and is far more sensitive than VUC for detection of bladder cancer. The BTA test has the potential to become an additional tool for detecting bladder cancer.


Asunto(s)
Antígenos de Neoplasias/orina , Carcinoma de Células Transicionales/orina , Neoplasias de la Vejiga Urinaria/orina , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/diagnóstico , Cistoscopía , Femenino , Humanos , Pruebas de Fijación de Látex/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/diagnóstico , Orina/citología
16.
J Clin Pharmacol ; 36(11): 1029-38, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8973992

RESUMEN

The pharmacokinetics of tamsulosin hydrochloride in patients with renal impairment were compared with those in healthy volunteers, and the factors that influenced plasma levels of tamsulosin were elucidated. A single oral dose of 0.2 mg of tamsulosin was given and blood and urine samples were obtained for 36 hours after administration. Unbound plasma concentration of tamsulosin was measured by a combination of equilibrium dialysis and liquid chromatography tandem mass spectrometry methods to examine the effect of protein binding on the pharmacokinetics of tamsulosin. Mean values for maximum concentration (Cmax) and area under the concentration-time curve (AUC) of total drug (Cmax,t and AUC1) in patients with renal impairment were 73% and 211% greater, respectively, than those in healthy volunteers. Mean Cmax and AUC of unbound drug (Cmax,u and AUCu), however, were almost the same in the two groups. A high correlation was found between alpha 1-acid glycoprotein (alpha 1-AGP) concentration and AUCt, but no correlation was found between alpha 1-AGP concentration and AUCu,0-36) or between creatinine clearance (ClCR) and AUCu,0-36). These results show that in patients with renal impairment, the pharmacokinetics of tamsulosin are affected by the change in protein binding that is associated with alteration of plasma alpha 1-AGP concentration, but are not largely affected by the decrease in the renal excretion. Although total tamsulosin levels increased as plasma protein binding increased, unbound tamsulosin levels (which are directly associated with the pharmacologic effects) remained unchanged in these patients.


Asunto(s)
Antagonistas Adrenérgicos alfa/farmacocinética , Enfermedades Renales/metabolismo , Orosomucoide/metabolismo , Sulfonamidas/farmacocinética , Antagonistas Adrenérgicos alfa/sangre , Anciano , Proteínas Sanguíneas/metabolismo , Interacciones Farmacológicas , Humanos , Enfermedades Renales/sangre , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Unión Proteica , Valores de Referencia , Sulfonamidas/sangre , Tamsulosina
17.
Int J Urol ; 3(6): 468-71, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9170575

RESUMEN

BACKGROUND: In a recent study by the Casodex Combination Study Group, USA, patients in a flutamide (750 mg/day) plus LH-RH agonist group showed a high treatment failure rate, mainly due to flutamide-induced diarrhea and hepatotoxicity. Our current study was conducted to determine the optimal dose of flutamide for use in this type of combination therapy. METHODS: In a randomized, multicenter study, 30 patients (hormone untreated; stage C or D) were divided into 2 groups: flutamide 250 mg (125 mg x 2; 14 patients) and flutamide 375 mg (125 mg x 3; 16 patients, and each dose combined with either goserelin acetate (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin and leuprolide were administered to patients in a 1:1 ratio. Flutamide monotherapy at a daily dose of 375 mg was determined to be the optimal dose in Japan in our previous phase II study. The endpoints of this pilot study were the objective response and adverse events during the 12-week treatment. RESULTS: The objective response rate was 83.3% in the flutamide 250 mg group and 85.7% in the flutamide 175 mg group according to the Japanese response criteria for prostate cancer. Elevated PSA levels fell to within the normal range in 83.3% of the patients in the former group and in 93.3% of the patients in the latter group. One patient administered 250 mg of flutamide experienced diarrhea, while the serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide and 4 patients administered 375 mg of flutamide. CONCLUSIONS: Based on the findings of this pilot study of maximal androgen-depletion therapy for advanced prostate cancer, 375 mg/day of flutamide is recommended in combination with an LH-RH agonist. Assessment of the effects of our recommended regimen on longer term survival, quality of life and antiandrogen withdrawal syndrome of patients treated requires additional patients and time for follow-up.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Flutamida/administración & dosificación , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos Hormonales/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Flutamida/efectos adversos , Estudios de Seguimiento , Goserelina/administración & dosificación , Humanos , Leuprolida/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Prospectivos
18.
Cancer Res ; 56(18): 4154-8, 1996 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-8797585

RESUMEN

Loss of E-cadherin-mediated adhesion is an important step in the progression of many carcinomas. In model systems, it has been shown that cadherin function requires not only proper E-cadherin expression but also its linkage to the cytoskeleton through catenins. Hence, defects in catenins may cause defective E-cadherin function, and catenins as well as E-cadherin might constitute prognostic indicators. Here, we extend our previous study on E-cadherin in bladder cancer (Cancer Res., 53: 3241-3245, 1993). We have evaluated the expression of E-cadherin-associated cytoplasmic molecules (alpha-, beta-, and gamma-catenins and p120cas) to clarify whether or not the pattern of their expression could provide additional prognostic information beyond that from E-cadherin alone. Forty-eight frozen bladder tumor specimens and 9 samples of normal urothelium were studied by immunohistochemistry. A discrepancy between the E-cadherin and catenin expression pattern was seen in 20.8% of cases. Abnormal expression of each molecule is significantly correlated with tumor grade (P < 0.01) and stage (P < 0.01). Reduced expression of all of the molecules correlates with poor survival (P < 0.01 for each variable). Proportional hazard regression analysis showed that beta-catenin, E-cadherin, and alpha-catenin have strong predictive value, whereas plakoglobin and p120cas have a somewhat lower predictive value. Within patients with invasive tumors, those with a normal staining for either E-cadherin, alpha-catenin, or beta-catenin show a trend toward better survival. However, the difference in survival is significant only for E-cadherin (P < 0.05). Thus, beta-catenin, E-cadherin, and alpha-catenin have similar prognostic values. Therefore, from a practical point of view, the expression of any of these proteins can be of prognostic value for patients with bladder cancer.


Asunto(s)
Biomarcadores de Tumor/análisis , Moléculas de Adhesión Celular/análisis , Proteínas del Citoesqueleto/análisis , Fosfoproteínas/análisis , Transactivadores , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Cadherinas/análisis , Cateninas , Moléculas de Adhesión Celular/biosíntesis , Terapia Combinada , Proteínas del Citoesqueleto/biosíntesis , Desmoplaquinas , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fosfoproteínas/biosíntesis , Pronóstico , Tasa de Supervivencia , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugía , alfa Catenina , beta Catenina , gamma Catenina , Catenina delta
19.
Hinyokika Kiyo ; 42(8): 557-61, 1996 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-8889562

RESUMEN

We performed mass screening for prostate diseases in the village of Satomi-mura, in Ibaraki Prefecture for males between 40 and 79 years old (participation rate; 21%). The findings were compared to those obtained by mass screening in the village of Shimamaki-mura, in Hokkaido Prefecture, conducted by the same examiners in a consistent manner (participation rate; 47%). When we considered the difference in biopsy rates between the two sites, the detection rate of prostate cancer in Satomi-mura was similar to that in Shimamaki-mura. There were no apparent differences in distribution of prostate volume, the International Prostate Symptom Score (I-PSS) and maximum flow rate between the two sites for each 10-year-age group. Our findings suggested that there was little site difference in the detection rate of prostate cancer and voiding condition between the two villages.


Asunto(s)
Tamizaje Masivo , Neoplasias de la Próstata/prevención & control , Micción , Urodinámica , Adulto , Factores de Edad , Anciano , Humanos , Japón , Masculino , Persona de Mediana Edad , Próstata/patología , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/fisiopatología , Neoplasias de la Próstata/fisiopatología
20.
Int J Urol ; 3(3): 234-6, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8776624

RESUMEN

Leiomyosarcoma arising from the ovarian vein is extremely rare: only one case was found in the literature. We report a case in a sixty-one-year-old woman who had unexplained attacks of pain in her left lower abdomen and flank for two years.


Asunto(s)
Leiomiosarcoma/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Ovario/irrigación sanguínea , Dolor/etiología , Venas/patología , Femenino , Humanos , Persona de Mediana Edad , Flebografía , Tomografía Computarizada por Rayos X
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