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1.
Int J Clin Oncol ; 29(5): 602-611, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38418804

RESUMEN

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.


Asunto(s)
Anticuerpos Monoclonales , Enfermedades del Sistema Nervioso Periférico , Humanos , Masculino , Femenino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anciano de 80 o más Años , Conducción Nerviosa/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/tratamiento farmacológico , Supervivencia sin Progresión , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología
2.
BMC Urol ; 21(1): 45, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33765999

RESUMEN

BACKGROUND: The advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system. METHODS: We carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated. RESULTS: A total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS). CONCLUSIONS: Our results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system. TRIAL REGISTRATION: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803-002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205).


Asunto(s)
Carcinoma de Células Transicionales/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Pelvis Renal , Neoplasias Ureterales/diagnóstico por imagen , Ureteroscopía/métodos , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Grabación en Video
3.
Jpn J Clin Oncol ; 49(2): 183-189, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30452662

RESUMEN

OBJECTIVE: In several cancers, the loss of skeletal muscle is well associated with oncological outcome. However, its effect is unknown in testicular cancer. This study evaluated the prognostic impact of psoas major muscle volume loss during systemic chemotherapy. METHODS: This was a retrospective study of patients who underwent chemotherapy from 2008 to 2017. Psoas major muscle volume was calculated by volume analyzer software, and its loss was calculated during systemic chemotherapy. The patients were divided according to muscle volume loss: Group 1 (<20%) and Group 2 (≥20%). The losses were compared with Kaplan-Meier curves, and a Cox proportional hazard model was applied to test predictors of poor prognosis. RESULTS: Fifty patients were included. Seventeen were classified into Group 1, and 33 into Group 2. The Kaplan-Meier curves revealed that the progression-free and the overall survival of Group 1 were significantly better than those of Group 2 (P = 0.002, P = 0.03, respectively). A multivariate analysis identified psoas major muscle volume loss as a significant and independent predictor of poor prognosis. CONCLUSIONS: Patients with psoas major muscle volume loss during chemotherapy had a significantly worse prognosis than those without loss.


Asunto(s)
Músculos Psoas/patología , Neoplasias Testiculares/tratamiento farmacológico , Adolescente , Adulto , Anciano , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tamaño de los Órganos , Pronóstico , Modelos de Riesgos Proporcionales , Músculos Psoas/diagnóstico por imagen , Curva ROC , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/patología , Adulto Joven
4.
Clin Exp Nephrol ; 23(3): 415-424, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30191414

RESUMEN

BACKGROUND: Excessive visceral fat may decrease renal function because of metabolic derangements. The aim of this study was to evaluate the impact of abdominal fat distribution on renal function of recipients after kidney transplantation using the visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) ratio. METHODS: Seventy-nine patients underwent living kidney transplantation from 2009 to 2017. Patients without a correct measurement of VAT and SAT, follow-up of < 6 months, or with kidney transplant rejection or a virus infection were excluded. VAT and SAT were calculated automatically by 3-D volume analyzer software in recipients prior to living kidney transplantation. Our primary aim was to identify abdominal fat distribution measured by CT associated with renal dysfunction (estimate glomerular filtration rate; eGFR < 45) at 6 month post renal transplantation in recipient. RESULTS: Fifty-eight living kidney recipients were included in this retrospective study: 30 for the high VAT/SAT ratio group; 28 for the VAT/SAT low group. Multiple logistic regression analysis showed the VAT/SAT ratio and pre-donor eGFR were associated with eGFR < 45 ml/min/1.73 m2. An increase in VAT/SAT ratio was associated independently with the incidence of decreased renal function. CONCLUSION: This finding indicates that adipose tissue distribution is an important predictor of the outcome of living kidney transplantation in recipients.


Asunto(s)
Grasa Abdominal/anatomía & histología , Imagenología Tridimensional/métodos , Trasplante de Riñón , Donadores Vivos , Tomografía Computarizada por Rayos X/métodos , Grasa Abdominal/diagnóstico por imagen , Adulto , Anciano , Tasa de Filtración Glomerular , Humanos , Lípidos/sangre , Persona de Mediana Edad , Estudios Retrospectivos
5.
J Infect Chemother ; 25(4): 247-252, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30583958

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the efficacy of single-dose perioperative antimicrobial therapy as infection prophylaxis in recipients of living-donor renal transplants in the rituximab era. PATIENTS AND METHODS: Between 2009 and 2017, 84 recipients underwent living-donor renal transplantation (LDRT) at Okayama University Hospital; 3 with vascular/urinary complications requiring additional surgery were excluded from this analysis. Data including recipient characteristics, antimicrobial prophylaxis and administration of rituximab were retrospectively examined for an association with perioperative infections. Prophylactic antimicrobial agents, selected according to the Results of preoperative urine cultures, were administered just before incision. Perioperative infections, which consisted of surgical site infections, remote infections, and urinary tract infections, were defined as a positive culture indicating required administration of additional antimicrobial agents. RESULTS: Among the 81 recipients, prophylactic cefazolin, ampicillin/sulbactam, and others were administered to 66 (82%), 13 (16%), and 2 (3%) recipients, respectively. Twenty-one (26%) received single-dose antimicrobial prophylaxis, while 60 (74%) received multiple doses up to 7 days. Rituximab was used in 59 (72.8%) recipients. The incidence of urinary tract infection, surgical site infection and remote infection was 13 (16%), 1 (1%), and 0, respectively. Univariate analysis could not demonstrate any significant risk factors for postoperative urinary tract infections, including a single dose vs multiple doses of antimicrobial therapy (P = 0.069) and administration of rituximab (P = 0.717). CONCLUSIONS: Our data suggest that the use of single-dose perioperative antimicrobial therapy is acceptable for prophylaxis of infections in patients undergoing LDRT, even in the rituximab era.


Asunto(s)
Antibacterianos/administración & dosificación , Profilaxis Antibiótica/métodos , Trasplante de Riñón/efectos adversos , Infección de la Herida Quirúrgica/prevención & control , Infecciones Urinarias/prevención & control , Adulto , Esquema de Medicación , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/métodos , Incidencia , Donadores Vivos , Masculino , Persona de Mediana Edad , Atención Perioperativa/métodos , Estudios Retrospectivos , Factores de Riesgo , Rituximab/efectos adversos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Resultado del Tratamiento , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología
6.
World J Urol ; 36(6): 889-895, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29387931

RESUMEN

PURPOSE: Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC. METHODS: Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266. RESULTS: Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence. CONCLUSIONS: Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.


Asunto(s)
Antineoplásicos/administración & dosificación , Doxorrubicina/análogos & derivados , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Administración Intravesical , Anciano , Análisis de Varianza , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Cuidados Posoperatorios/métodos , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía
7.
Clin Exp Nephrol ; 22(2): 453-458, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28741049

RESUMEN

BACKGROUND: Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. METHODS: Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for <12 months were excluded leaving 34 patients' data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor's postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. RESULTS: Strong correlations were observed preoperatively in a Bland-Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. CONCLUSION: Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.


Asunto(s)
Corteza Renal/diagnóstico por imagen , Corteza Renal/trasplante , Pruebas de Función Renal/métodos , Trasplante de Riñón/métodos , Donadores Vivos , Nefrectomía , Tejido Parenquimatoso/diagnóstico por imagen , Tejido Parenquimatoso/trasplante , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Selección de Donante , Femenino , Tasa de Filtración Glomerular , Humanos , Imagenología Tridimensional , Corteza Renal/fisiopatología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Tejido Parenquimatoso/fisiopatología , Valor Predictivo de las Pruebas , Interpretación de Imagen Radiográfica Asistida por Computador , Radiofármacos/administración & dosificación , Reproducibilidad de los Resultados , Estudios Retrospectivos , Programas Informáticos , Tecnecio Tc 99m Mertiatida/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento
8.
Acta Med Okayama ; 72(3): 241-247, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29926001

RESUMEN

We retrospectively analyzed the factors related to postoperative cardiovascular (CV) events in patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1 renal cell carcinoma (RCC). We identified 570 patients who underwent PN or RN for T1 renal cell carcinoma between January 1998 and December 2009 at our institution and related hospitals. We determined the cumulative incidence rate of CV events and overall survival (OS) using Kaplan-Meier survival curves with a log-rank test, and we evaluated the risk for an increase in CV events and OS using Cox proportional hazard regression. Of the 570 patients, 171 underwent PN and 399 underwent RN. The type of surgery was not significantly related with CV events. The only factor that significantly increased the risk of CV events in both the univariate (HR 2.67, p=0.006) and multivariate analyses (HR 2.14, p=0.044) was a postoperative estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Postoperative eGFR was also a significant risk factor for OS in the univariate analysis (HR 2.38, p=0.0104), but not in the multivariate model. Postoperative renal function was a significant independent predictor of the incidence of subsequent CV events.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Tasa de Filtración Glomerular , Nefrectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Anciano , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Nefrectomía/mortalidad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo
9.
Acta Med Okayama ; 72(6): 605-609, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30573917

RESUMEN

Metastatic prostate cancer (PCa) cases that cannot be detected on repeat prostate biopsy are extremely rare. Our patient was a 51-year-old Japanese man diagnosed as metastatic PCa by histopathological examination of lesions obtained bone biopsy and lymph node dissection. The primary tumor was not detected after repeated prostate biopsy. Metastatic PCa was diagnosed based on immunohistochemical staining: PSA, AR, P504S, and NKX3.1 of bone and lymph node with metastasis. We speculate that the primary PCa was "burned-out," demonstrating remote metastases with no apparent primary tumor in the prostate. Burned-out PCa may be difficult to diagnose and treat due to its rarity.


Asunto(s)
Neoplasias Óseas/diagnóstico , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Adenocarcinoma/patología , Biomarcadores de Tumor , Biopsia , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad
10.
Int J Urol ; 25(5): 507-512, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29651796

RESUMEN

OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography-guided permanent iodine-125 seed brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence-free survival, progression-free survival, cancer-specific survival and overall survival. RESULTS: A total of 484 patients with low-risk (259 patients) or intermediate-risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year actuarial biochemical recurrence-free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence-free survival outcomes in low- (P = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate-specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence-free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression-free survival, cancer-specific survival or overall survival. CONCLUSIONS: In patients with low- or intermediate-risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.


Asunto(s)
Braquiterapia/métodos , Hormonas/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Terapia Neoadyuvante , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/terapia , Anciano , Terapia Combinada , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
11.
J Infect Chemother ; 22(2): 108-11, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26712583

RESUMEN

OBJECTIVES: The aim of this study is to characterize the potential differences between male and female patients with acute pyelonephritis (AP) and to predict the severity of AP based on the length of hospital stay. METHODS: We conducted a retrospective medical chart review of 172 consecutive adult patients who were hospitalized in Tsuyama Central Hospital due to AP from January 2007 through June 2012. We analyzed the length of hospital stay by the proportional hazard model. RESULTS: A total of 172 patients were identified who were admitted to our hospital with a diagnosis of AP. Of them, 62% (106/172) were female. Except for urological malignancy, there was no significant difference between men and women in underlying disease. Out of 26 variables, univariate analysis in male showed that only urolithiasis (OR 1.75, p = 0.0294) was significantly associated with longer hospital stay, while septic shock (OR 3.18, P = 0.003), urological malignancy (OR 2.94, P = 0.002), age over 65 (OR 1.66, p = 0.018) and neurogenic bladder (OR 1.92, p = 0.014) were all associated with longer hospital stay in female patients. CONCLUSIONS: This is the first report to identify the risk factors for prolonged hospital stay for the patients who were admitted with AP in the Japanese population. The risk factors causing prolonged hospital stay were totally different between males and females. Reviewing the medical history based on sex gender might enable a clinician to predict the severity of acute pyelonephritis during the initial evaluation.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Pielonefritis/epidemiología , Pielonefritis/etiología , Anciano , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Choque Séptico
12.
Mol Cancer ; 14: 122, 2015 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-26084402

RESUMEN

BACKGROUND: Docetaxel is the first chemotherapy agent approved for treatment of metastatic castration-resistant prostate cancer (mCRPC). The limited survival benefit associated with the quick emergence of resistance and systemic toxicity diminished its efficacy. JNK-mediated apoptosis is one of the mechanisms of docetaxel activity whereas ERK1/2-c-Myc-CXCR4 signaling is implicated in the development of resistance and induction of migration. The aim of this study was to evaluate the hypothesis that the combination treatment with docetaxel and GLIPR1-ΔTM will synergistically induce greater cell death and inhibit the emergence of resistance and development of metastatic potential in prostate cancer (PCa) cells. METHODS: The synergistic effects of the docetaxel and GLIPR1-ΔTM were evaluated with DNA fragmentation, DAPI staining and MTS using paired t-test and isobologram study. The effects of the drugs on JNK and ERK1/2-c-Myc-CXCR4 signaling were evaluated with Western blot, DNA fragmentation, and MTS assays using the JNK inhibitor SP600125, and CXCR4 siRNA. The results of docetaxel and GLIPR1-ΔTM combination on migration were examined with scratch assay using the CXCR4 inhibitor AMD3100 while our hypothesis was examined in vivo using VCaP orthotopic xenograft model. RESULTS: We found that GLIPR1-ΔΤΜ synergized with docetaxel to induce apoptosis in VCaP and PC-3 PCa cells through induction of JNK signaling and concomitant inhibition of ERK1/2-c-Myc-CXCR4 signaling. We showed that JNK activation mediates the apoptotic effects of the drug combination and that CXCR4 knockdown increases its efficacy. We also found that the addition of GLIPR1-ΔΤΜ to docetaxel decreases the migration of VCaP and PC-3 cells. The combination treatment with docetaxel and GLIPR1-ΔTM inhibited tumor growth and decreased metastatic potential in VCaP xenografts more than single agents did. CONCLUSIONS: Our data suggested that addition of GLIPR1-ΔTM treatment in PCa cells increases the efficacy of docetaxel and may inhibit the emergence of drug resistance; potentially permitting a decrease of docetaxel dose for patients with mCRPC eliminating its systemic toxicities.


Asunto(s)
Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/farmacología , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/farmacología , Neoplasias de la Próstata/patología , Eliminación de Secuencia , Taxoides/farmacología , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Docetaxel , Sinergismo Farmacológico , Activación Enzimática/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Proteínas de la Membrana , Ratones Desnudos , Metástasis de la Neoplasia , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Receptores CXCR4/metabolismo , Factores de Tiempo , Ensayos Antitumor por Modelo de Xenoinjerto
13.
BMC Urol ; 15: 27, 2015 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-25879548

RESUMEN

BACKGROUND: Radical prostatectomy is a standard surgical treatment of clinically localized prostate cancer. Margin status has been found to be an independent predictor of biochemical recurrence (BCR) after open radical prostatectomy in several large series but this is still controversy in Robotic Assisted Radical Prostatectomy (RARP) series. We therefore wanted to investigate the prognostic significance of positive surgical margin (PSM) and other pathological factors on BCR in patients treated with RARP by a single surgeon. METHODS: Prospectively collected data of 439 patients treated with RARP between October 2005 and June 2013 by a single surgeon at a single institution were analyzed. BCR was defined as follow-up PSA level > 0.2 ng/ml on two separate occasions or patients who had to undergo salvage therapy. Kaplan Meier curves and Log Rank test were used to compare the risk of BCR. Univariate and Multivariate Cox Regression analyses were performed to determine the prognostic impact of age, BMI, prostate weight, PSA prior to surgery, pathological T-stage, pathological Gleason sum, PSM and operative period. RESULTS: In this study period, 34 out of 439 had BCR, giving an overall BCR rate of 7.7% for this cohort. Overall 2- and 3-year BCR-free survival rates were 93% and 88%, respectively. Patients with a PSM had a 2-year BCR free survival of 88% compared to 94% in those with negative margins (p < .0001). On the multivariate analysis, PSM as well as pathological Gleason sum > = 8, PSA, pathological stage and operative period were significantly associated with BCR. CONCLUSIONS: In our case series of RARP performed by a single surgeon, PSM as well as pathological Gleason sum, PSA, pathological stage and early operative period for this surgeon were the independent predictors of BCR.


Asunto(s)
Recurrencia Local de Neoplasia/epidemiología , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Anciano , Índice de Masa Corporal , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Pronóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Recurrencia , Factores de Riesgo , Robótica
14.
Int J Cancer ; 134(8): 2003-13, 2014 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-24590455

RESUMEN

GLIPR1 is a p53 target gene known to be downregulated in prostate cancer, and increased endogenous GLIPR1 expression has been associated with increased production of reactive oxygen species, increased apoptosis, decreased c-Myc protein levels and increased cell cycle arrest. Recently, we found that upregulation of GLIPR1 in prostate cancer cells increases mitotic catastrophe through interaction with heat shock cognate protein 70 (Hsc70) and downregulation of Aurora kinase A and TPX2. In this study, we evaluated the mechanisms of recombinant GLIPR1 protein (glioma pathogenesis-related protein 1-transmembrane domain deleted [GLIPR1-ΔTM]) uptake by prostate cancer cells and the efficacy of systemic GLIPR1-ΔTM administration in a prostate cancer xenograft mouse model. GLIPR1-ΔTM was selectively internalized by prostate cancer cells, leading to increased apoptosis through reactive oxygen species production and to decreased c-Myc protein levels. Interestingly, GLIPR1-ΔTM was internalized through clathrin-mediated endocytosis in association with Hsc70. Systemic administration of GLIPR1-ΔTM significantly inhibited VCaP xenograft growth. GLIPR1-ΔTM showed no evidence of toxicity following elimination from mouse models 8 hr after injection. Our results demonstrate that GLIPR1-ΔTM is selectively endocytosed by prostate cancer cells, leading to increased reactive oxygen species production and apoptosis, and that systemic GLIPR1-ΔTM significantly inhibits growth of VCaP xenografts without substantial toxicity.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas de Neoplasias/uso terapéutico , Proteínas del Tejido Nervioso/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/genética , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Clatrina/metabolismo , Endocitosis/efectos de los fármacos , Endocitosis/genética , Endosomas/metabolismo , Humanos , Lisosomas/metabolismo , Masculino , Proteínas de la Membrana , Ratones , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Trasplante de Neoplasias , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Transporte de Proteínas/efectos de los fármacos , Transporte de Proteínas/genética , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Eliminación de Secuencia/genética , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Int J Urol ; 20(8): 812-7, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23294011

RESUMEN

OBJECTIVES: To describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients. METHODS: From January 2004 to April 2011, 466 consecutive Japanese patients underwent permanent iodine-125-seed brachytherapy (median follow up 48 months). International Prostate Symptom Score and Radiation Therapy Oncology Group toxicity data were prospectively collected. Prostate volume, International Prostate Symptom Score before and after brachytherapy, and postimplant analysis were examined for an association with urinary toxicity, defined as Radiation Therapy Oncology Group urinary toxicity of Grade 1 or higher. Logistic regression analysis was used to examine the factors associated with urinary toxicity. RESULTS: The rate of Radiation Therapy Oncology Group urinary toxicity grade 1 or higher at 1, 6, 12, 24, 36 and 48 months was 67%, 40%, 21%, 31%, 27% and 28%, respectively. Grade 2 or higher urinary toxicity was less than 1% at each time-point. International Prostate Symptom Score was highest at 3 months and returned to normal 12 months after brachytherapy. On univariate analysis, patients with a larger prostate size, greater baseline International Prostate Symptom Score, higher prostate V100, higher prostate V150, higher prostate D90 and a greater number of seeds had more acute urinary toxicities at 1 month and 12 months after brachytherapy. On multivariate analysis, significant predictors for urinary toxicity at 1 month and 12 months were a greater baseline International Prostate Symptom Score and prostate V100. CONCLUSIONS: Most urinary symptoms are tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicity after brachytherapy is strongly related to the baseline International Prostate Symptom Score and prostate V100.


Asunto(s)
Braquiterapia/efectos adversos , Neoplasias de la Próstata/radioterapia , Trastornos Urinarios/etiología , Enfermedad Aguda , Adulto , Pueblo Asiatico , Enfermedad Crónica , Estudios de Seguimiento , Humanos , Radioisótopos de Yodo/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas
16.
Urol Case Rep ; 34: 101470, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33145177

RESUMEN

6p21 translocation renal cell carcinoma (RCC) was newly classified in the WHO 2016 classification as a subtype of microphthalmia-associated transcription factor (MIT) family translocation RCC.A 42-year-old man was referred to our hospital with an asymptomatic solid mass in the right kidney identified during routine medical checkup. Computed tomography (CT) revealed a 14-mm buried-type solid mass accompanied by punctate calcification. CT-guided biopsy suggested clear-cell carcinoma. He underwent robotic-assisted partial nephrectomy. Pathological findings revealed 6p21 translocation RCC based on diffuse nuclear immunoreactivity for TFEB and TFEB gene rearrangement in tumor cells by FISH analysis.

17.
Int J Cancer ; 126(7): 1562-9, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-19626590

RESUMEN

We have recently shown that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) exhibits a potent tumor-specific cell-killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad-REIC-induced apoptosis. The aim of the present study was to determine the molecular mechanisms of resistance to Ad-REIC. First, we isolated resistant clones from a human prostate cancer cell line, PC3, after repeated exposure to Ad-REIC. Infection efficiency of the adenovirus vector and expression level of REIC/Dkk-3 in the resistant clones were similar to those in the parental PC3 cells. By screening for alteration in levels and functional status of proteins involved in Ad-REIC-induced apoptosis, we found that BiP/GRP78, an ER-residing chaperone protein, was expressed at higher levels consistently among resistant cells. Expression levels of BiP and rates of apoptosis induced by Ad-REIC were inversely correlated. Down-regulation of BiP with siRNA sensitized the resistant cells to Ad-REIC in vivo as well as in culture. These results indicate that BiP is a major determinant of resistance to Ad-REIC-induced apoptosis. Thus BiP is useful for diagnosis of inherent and acquired resistance of cancers and also as a target molecule to overcome resistance to the gene therapeutic Ad-REIC.


Asunto(s)
Resistencia a Antineoplásicos , Terapia Genética , Proteínas de Choque Térmico/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias de la Próstata/terapia , Proteínas Adaptadoras Transductoras de Señales , Adenoviridae/genética , Animales , Apoptosis , Western Blotting , Proliferación Celular , Células Cultivadas , Senescencia Celular/genética , Quimiocinas , Regulación hacia Abajo , Chaperón BiP del Retículo Endoplásmico , Fibroblastos/metabolismo , Fibroblastos/patología , Proteínas de Choque Térmico/antagonistas & inhibidores , Proteínas de Choque Térmico/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Regiones Promotoras Genéticas , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
19.
J Robot Surg ; 14(2): 255-260, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31119473

RESUMEN

Increasingly, studies have explored health-related quality-of-life (HRQOL) outcomes after robot-assisted radical prostatectomy (RARP). Nevertheless, no study has compared differences between anterior and posterior surgical approaches. The aim of this study is to assess differences of HRQOL following these two surgical approaches. From January 2012 to September 2017, 653 patients underwent RARP at our institution. We included patients who underwent operations by three experienced surgeons with interchangeability of role as console operator, and who could evaluate preoperatively the Expanded Prostate Cancer Index Composite (EPIC) score. Patients treated with neoadjuvant hormonal therapy were excluded. HRQOL was assessed using the EPIC score, and the questionnaire was administered at 6 timepoints: the baseline survey was conducted within 3 months before the surgery, and follow-up surveys were conducted at 2 weeks, 1, 3, 6, and 12 months after surgery. We defined the minimal clinically important difference (MCID) as half the standard deviation of the baseline score for each domain. A total of 201 patients were included in this retrospective study. Of these, 146 patients underwent RARP using an anterior surgical approach and 55 patients underwent a posterior approach. The clinical characteristics had no significant differences except for median prostate volume between the anterior and posterior groups (27 ml vs 29 ml, p = 0.049). There were no significant differences between the two groups in score decline beyond the MCID in any domain at any timepoint. Our study demonstrates no significant differences in HRQOL between anterior and posterior surgical approaches to RARP.


Asunto(s)
Prostatectomía/métodos , Calidad de Vida , Procedimientos Quirúrgicos Robotizados/métodos , Humanos , Estudios Longitudinales , Masculino , Resultado del Tratamiento
20.
Mol Clin Oncol ; 10(6): 605-609, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31031975

RESUMEN

The aim of the present study was to investigate the impact of incidental prostate cancer (IPCa), which was diagnosed by holmium laser enucleation of the prostate (HoLEP), on long-term oncological and functional outcomes. A total of 482 patients who underwent HoLEP for benign prostatic hyperplasia (BPH) between 2008 and 2016 at our institution were retrospectively reviewed. We defined IPCa as prostate cancer (PCa) according to the enucleated tissue of transitional zone. Therefore, 64 patients were excluded for the following reasons: Prostate-specific antigen (PSA) ≥4.0 ng/ml and no prostate biopsy (n=46); and PSA ≥4.0 ng/ml and diagnosed with PCa by prostate biopsy performed during HoLEP (n=18). Notably, 418 patients were included in the study and divided into two groups: The BPH group and the IPCa group. For 5 years, postoperative PSA and functional outcomes were evaluated. Of 418 patients, 25 (6%) were diagnosed with IPCa by HoLEP, 21 patients (84%) had a Gleason score ≤6 and 5 patients (20%) received adjuvant therapy for PCa following HoLEP. No significant differences were observed between groups for preoperative PSA, PSA density, or urinary and sexual function outcomes; however, age at the time of HoLEP significantly differed between groups (71.7 vs. 75.5 years, P=0.026). Long-term (5-year) urinary outcomes demonstrated sustained improvement. Postoperative PSA increased gradually in the IPCa group (3-year, P=0.033; 4-year, P=0.037); International Index of Erectile Function 5 conversely decreased (5-year, P=0.068). According to the present results, if standard PSA screening and prostate biopsy are performed, watchful waiting for IPCa is feasible, and IPCa does not impact on 5-year urinary outcomes.

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