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1.
Support Care Cancer ; 28(12): 5743-5750, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32206969

RESUMEN

PURPOSE: The optimal management of malignant extrinsic ureteral obstruction (MUO) remains unclear. It is necessary to assess the patient prognosis in deciding the adaptation of drainage of renal pelvis. In this study, we investigated the clinical outcomes after ureteral stenting for MUO and the predictive factors for overall survival in order to create a risk-stratification model. METHODS: We retrospectively analyzed the clinical and laboratory data of 93 patients with radiologically significant hydronephrosis associated with MUO who underwent successful stent placement between May 2005 and May 2018. RESULTS: The median survival duration after the initial stent insertion was 266 days. Of the 93 patients, 70 died, and the median interval from the first stent insertion to death was 160 days. Multivariate analysis showed that gastric cancer as the primary disease, poor performance status before stenting, and treatment after stent insertion were significant predictors of survival. According to these three factors, we stratified patients into the following four prognostic groups: no-factor (43 patients), one-factor (23 patients), two-factor (23 patients), and three-factor (4 patients) groups. This classification was effective for predicting survival, and the median survival durations in these groups were 807, 269, 44, and 12 days, respectively (p < 0.001). CONCLUSIONS: Our stratification model of patients with a poor prognosis after ureteral stent placement for MUO may allow urologists and clinicians to identify patients who will benefit from ureteral stenting.


Asunto(s)
Stents/normas , Obstrucción Ureteral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Obstrucción Ureteral/mortalidad
2.
Cancer Immunol Immunother ; 69(4): 663-675, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31980914

RESUMEN

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (µg/µg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.


Asunto(s)
Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Proteínas de la Membrana/inmunología , Neoplasias/inmunología , Proteína Adaptadora de Señalización NOD2/inmunología , Receptor Toll-Like 9/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antineoplásicos/sangre , Anticuerpos Antineoplásicos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Vacunas contra el Cáncer/administración & dosificación , Línea Celular Tumoral , Femenino , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Masculino , Ratones Endogámicos BALB C , Persona de Mediana Edad , Neoplasias/patología , Neoplasias/terapia , Proteína Adaptadora de Señalización NOD2/metabolismo , Receptor Toll-Like 9/metabolismo , Vacunación/métodos
3.
Int J Clin Oncol ; 24(3): 306-312, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30298199

RESUMEN

BACKGROUND: This study investigated the clinical outcomes of stent placement for malignant extrinsic ureteral obstruction (MUO) and predictive factors for stent failure. METHODS: We retrospectively analyzed clinical data for 91 patients with radiologically significant hydronephrosis due to MUO who underwent successful stent placement. In total, 132 ureters were stented for the decompression. Factors related to stent failure were analyzed with a Cox proportional hazards model. RESULTS: Stent failure occurred in 25 ureters in 20 patients. The median interval to failure was 63 days. The multivariate analysis showed that the significant predictors of stent failure were bladder invasion and severe hydronephrosis before the stent insertion. The patients were divided into three groups based on these two factors: low-risk (neither factor; 85 patients), intermediate-risk (one factor; 37), and high-risk (both factors; 10). The median stent failure-free survival rate at 3 months was 94.8% in the low-risk, 71.8% in the intermediate-risk and 55.6% in the high-risk group, respectively. Of the ureters with stent failure, there was successful re-replacement of internal stents in 3 low-risk, 6 intermediate-risk and no high-risk ureters. Replacement by nephrostomy was done in 2 low-risk, 5 intermediate-risk and 7 high-risk ureters. CONCLUSION: The patients considered at low-risk could be managed without stent failure by internal stenting. However, the patients at high-risk may require the consideration of nephrostomy or other alternatives as the initial treatment. Our stratification model may allow better risk stratification for patients with regard to ureteral stenting, helping to identify patients for whom ureteral stenting is indicated.


Asunto(s)
Stents , Obstrucción Ureteral/mortalidad , Obstrucción Ureteral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hidronefrosis/etiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Tasa de Supervivencia , Insuficiencia del Tratamiento , Resultado del Tratamiento , Uréter/cirugía , Obstrucción Ureteral/patología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias del Cuello Uterino/patología
4.
Hinyokika Kiyo ; 63(12): 503-507, 2017 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-29370660

RESUMEN

In this study, we retrospectively reviewed the experiences at our single institute in the treatment of malignant extrinsic ureteral obstruction (MUO) using ureteral stents to investigate the clinical outcomes and the predictive factors of stent failure. In 52 ureters of 38 patients who had radiologically significant hydronephrosis due to MUO, internal ureteral stents (The BARD(R) INLAY(TM) ureteral stent set) were inserted. The median follow-up interval after the initial stent insertion was 124.5 days (4-1,120). Stent failure occurred in 8 ureters (15.4%) of the 7 patients. The median interval from the first stent insertion to stent failure was 88 days (1-468). A Cox regression multivariate analysis showed that the significant predictors of stent failure were bladder invasion. Based on the possibility of stent failure, the adaptation of the internal ureteral stent placement should be considered especially in a patient with MUO combined with bladder invasion.


Asunto(s)
Neoplasias/complicaciones , Stents , Uréter , Obstrucción Ureteral/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Obstrucción Ureteral/etiología
5.
Hinyokika Kiyo ; 62(8): 431-3, 2016 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-27624111

RESUMEN

Emphysematous cystitis (EC) is a rare form of acute complicated urinary tract infection (UTI). We report a case of EC with bladder diverticulum. A 77-year-old man who had a medical history of diabetes mellitus was admitted to our hospital with the chief complaint of macrohematuria and pneumaturia. Based on the findings of an abdominal computed tomography and cystoscopy, the diagnosis of EC and bladder diverticulum was made with its characteristic feature being gas within the bladder wall and lumen and a cystic lesion from the bladder. His condition improved immediately with a combination of bladder drainage and appropriate antibiotics. The cystography revealed a very large diverticulum causing incomplete bladder emptying and stagnation of urine. We considered diabetes mellitus and a large amount of residual urine after urination due to bladder diverticulum and neurogenic bladder as the possible causal factors of EC in this case.


Asunto(s)
Cistitis/complicaciones , Divertículo/diagnóstico por imagen , Divertículo/etiología , Enfisema/complicaciones , Vejiga Urinaria/anomalías , Anciano , Cistitis/diagnóstico por imagen , Cistitis/terapia , Cistoscopía , Divertículo/terapia , Enfisema/diagnóstico por imagen , Enfisema/terapia , Humanos , Masculino , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vejiga Urinaria/diagnóstico por imagen
6.
Nihon Hinyokika Gakkai Zasshi ; 104(5): 657-62, 2013 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-24187853

RESUMEN

PURPOSE: We examined the safety and efficacy of photo-selective vaporization of the prostate (PVP) using a 120-W high-performance system (HPS) for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: We prospectively reviewed the records of 25 patients who had undergone PVP using a 120-W HPS in our institution. Patients were evaluated pre-operatively, and at 2 weeks and 1, 3, and 6 months postoperatively. RESULT: The mean age was 73.6 years, and the mean estimated preoperative prostate volume was 51.5 ml. Laser vaporization was performed successfully in all 25 patients. The operating time was 104 +/- 29 minutes. The mean decrease in hemoglobin was 0.6 g/dl on post-operative day 1. The International Prostate Symptom Score (IPSS), QOL score, maximum flow rate, and residual urine volume were significantly improved 2 weeks after the procedure. There were no serious complications during the peri-operative period, and no patients were transfused. CONCLUSION: PVP using a 120-W HPS was shown to be an effective, safe procedure for patients with BPH and lower urinary tract symptoms.


Asunto(s)
Boratos/uso terapéutico , Terapia por Láser/métodos , Compuestos de Litio/uso terapéutico , Próstata/cirugía , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
7.
Hinyokika Kiyo ; 59(8): 491-5, 2013 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-23995524

RESUMEN

We prospectively reviewed the records of 62 patients who had sought evaluation at our hospital with a chief complaint of male climacteric symptoms. Late-onset hypogonadism (LOH)-related symptoms were evaluated during the initial visit based on the Aging Males' Symptoms (AMS) score, International Index of Erectile Function (IIEF) -5 score, and Center for Epidemiologic Studies Depression Scale (CES-D). Laboratory and endocrinologic testing, including the free testosterone (FT) level, was performed with blood samples collected before 10 : 00 am. The AMS psychological and CES-D scores in patients with a FT >8.5 pg/ml were significantly higher than those in patients with a FT ≦8.5 pg/ml. The study included 32 patients who were diagnosed with LOH (FT ≦8.5 pg/ml) and treated with androgen replacement therapy (ART). The total, somatic, psychological, and sexual scores of the AMS were significantly decreased after the third intramuscular administration of testosterone enanthate; there were no serious complications. Because a significant proportion of depressed patients may be amongst the patients with aging male's symptoms, it is important to consider depression in the exclusion diagnosis during a clinical examination for LOH.


Asunto(s)
Andropausia/fisiología , Adulto , Anciano , Andrógenos/uso terapéutico , Depresión/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Testosterona/sangre
8.
Hinyokika Kiyo ; 59(6): 377-80, 2013 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-23827872

RESUMEN

Here, we report a case of malignant lymphoma (ML) of the prostate. A 77-year-old man was referred to our hospital with the chief complaint of left lumbago. Computed tomography imaging showed a large mass below the bladder, as well as left hydronephrosis resulting from infiltration of the mass. Magnetic resonance imaging (MRI) revealed enlargement and high-intensity of the whole prostate with diffusionweighted image. An enlarged, stony, hard prostate was palpable on digital rectal examination, but the prostate-specific antigen (PSA) level was 4.65 ng/ml. Since the patient developed urinary retention and macrohematuria, transurethral hemostasis and biopsy were performed. Histological findings and immunohistochemical studies revealed diffuse large B-cell non-Hodgkin's lymphoma (DLBCL). MRI is thought to play a critical role in localization diagnosis of Non-Hodgkin's lymphoma (NHL) since NHL demonstrates characteristic signs. Although the frequency of primary ML of the prostate is low, by paying careful attention to the characteristic signs on MRI and examination findings, we should consider a differential diagnosis of ML of the prostate, which is not a typical manifestation of prostatic cancer.


Asunto(s)
Linfoma/patología , Neoplasias de la Próstata/patología , Anciano , Humanos , Imagen por Resonancia Magnética , Masculino
9.
Urol Oncol ; 31(6): 787-95, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21803620

RESUMEN

OBJECTIVES: To investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival. METHODS: Eighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy. RESULTS: The manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression. CONCLUSIONS: This is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neuropéptidos/metabolismo , Fragmentos de Péptidos/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas de Secreción de la Vesícula Seminal/metabolismo , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Estudios de Cohortes , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Modelos de Riesgos Proporcionales , Próstata/metabolismo , Factores de Tiempo
10.
Mol Clin Oncol ; 1(2): 326-330, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24649170

RESUMEN

The aim of this study was to evaluate the frequency of expression of the cancer-testis antigens (CTAs) NY-ESO-1, MAGE-A4 and SAGE, in renal cell carcinoma (RCC) patients compared to that in head and neck cancer (HNC) patients, which represent a positive control with a high incidence of CTA expression, to identify novel target antigens for immunotherapy. We prospectively examined frozen tissue samples collected from surgery or biopsy from 35 RCC and 40 HNC patients. Total RNA was extracted, and real-time reverse transcription-polymerase chain reaction (RT)-PCR was performed to determine the expression of MAGE-A4, NY-ESO-1 and SAGE. MAGE-A4 was not detected in any of the RCC samples, although a low incidence of NY-ESO-1 (5.7%; 2/35) and SAGE (2.9%; 1/35) expression was observed. No samples demonstrated co-expression of the three CTAs. By contrast, a comparatively high incidence of CTA expression was detected in squamous cell carcinoma (SCC) specimens of HNC patients. The actual incidence was 42.5% (17/40) for MAGE-A4, 20% (8/40) for NY-ESO-1 and 15% (6/40) for SAGE. The incidence of co-expression was 7.5% (3/40) for MAGE-A4 and NY-ESO-1, 7.5% (3/40) for MAGE-A4 and SAGE, 7.5% (3/40) for NY-ESO-1 and SAGE, and 2.5% (1/40) for the CTAs. The number of HNC samples positive for MAGE-A4 was significantly higher compared to that of RCC samples. The remaining two antigens, NY-ESO-1 and SAGE, were expressed at high levels in HNC compared to RCC samples. Limited frequency of CTA (NY-ESO-1, MAGE-A4 and SAGE) expression was demonstrated in RCC compared to HNC samples.

11.
Hinyokika Kiyo ; 58(5): 231-5, 2012 May.
Artículo en Japonés | MEDLINE | ID: mdl-22767276

RESUMEN

The patient was a 74-year-old man. Computed tomography (CT) detected a right renal tumor with paraaortic lymph node swelling. Radical nephrectomy and left lymphadenectomy were performed in September 2008. Interferon-alpha (6 million international units three times per week) was administered as adjuvant therapy. Due to the development of side effects, including fatigue, the patient's immunotherapy was discontinued after 6 months. Radiofrequency ablation for pulmonary metastasis was performed 9 months after surgery. A nodular pedunculated tumor was detected on the posterior wall of the urinary bladder by CT, and transurethral resection was performed 18 months after nephrectomy/lymphadenectomy. Since the pathological diagnosis of the bladder tumor was clear cell carcinoma, that tumor was thought to have originated from the renal cell carcinoma. We have summarized 43 cases of bladder metastasis of renal cell carcinoma in Japanese patients, including ours.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Neoplasias de la Vejiga Urinaria/secundario , Anciano , Carcinoma de Células Renales/terapia , Humanos , Escisión del Ganglio Linfático , Masculino , Nefrectomía , Neoplasias de la Vejiga Urinaria/terapia
12.
Jpn J Clin Oncol ; 42(6): 534-40, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22438406

RESUMEN

OBJECTIVE: To evaluate long-term clinical outcomes in cT1c-T3a prostate cancer patients following delayed-combined androgen blockade therapy. METHODS: From January 2001 to December 2004, 92 cT1c-T3a prostate cancer cases were enrolled. Medical castration and anti-androgen treatment were used sequentially as delayed-combined androgen blockade therapy. Time to prostate-specific antigen biochemical failure was estimated, and risk factors for prostate-specific antigen biochemical failure were evaluated. RESULTS: The average patient age was 76.4 years (range, 59-91 years), the median observation period was 52.8 months (range, 26-106.6 months) and the median pre-treatment prostate-specific antigen level was 14 ng/ml (range, 3.68-492 ng/ml). The TNM classification distribution was as follows: T1c, n= 27; T2a, n = 39; T2b, n = 20; and T3a, n = 6. In the multivariate analysis, Gleason's score ≥8 (P < 0.05; hazard ratio, 3.02), prostate-specific antigen nadir >1.4 ng/ml (P = 0.001; hazard ratio, 8.76) and a half-life of the prostate-specific antigen level >1.2 months (P < 0.005; hazard ratio, 6.3) during the initial 6 months of luteinizing hormone-releasing hormone agonist monotherapy were significant independent risk factors for prostate-specific antigen biochemical failure with luteinizing hormone-releasing hormone agonist monotherapy. The high-risk group, which had at least one of these three risk factors, had a shorter time to prostate-specific antigen biochemical failure than the low-risk group, during luteinizing hormone-releasing hormone agonist monotherapy (P < 0.0001). For the total delayed-combined androgen blockade therapy observation period, the free-prostate-specific antigen biochemical failure rate was 88.3% at 5 years. Only a maintenance period following luteinizing hormone-releasing hormone agonist monotherapy (P < 0.005; hazard ratio, 16.8) was revealed to be a significant independent risk factor for prostate-specific antigen biochemical failure with total delayed-combined androgen blockade. CONCLUSIONS: The free-prostate-specific antigen biochemical failure rate of delayed-combined androgen blockade therapy in our study was as valuable as those in other androgen deprivation therapy of previous reports.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Algoritmos , Anilidas/administración & dosificación , Esquema de Medicación , Goserelina/administración & dosificación , Humanos , Estimación de Kaplan-Meier , Leuprolida/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Estadificación de Neoplasias , Nitrilos/administración & dosificación , Oportunidad Relativa , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Compuestos de Tosilo/administración & dosificación , Insuficiencia del Tratamiento , Resultado del Tratamiento
13.
J Cell Biochem ; 112(12): 3604-11, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21809373

RESUMEN

In the tumor microenvironment, carcinoma-associated fibroblasts (CAFs) are considered to play a critical role in the promotion of tumorigenesis. However, the mechanisms that generate CAFs are not well elucidated. To understand how CAFs are generated during primary cancer progression, we investigated the biochemical characteristics of normal human prostate stromal cells (PrSC) co-cultured with human prostate cancer (PCa) cells in vitro. In primary cultures of human PCa-derived stromal cells (PCaSC-8 and PCaSC-9), expression of TNC, ACTA2, EGF, FGF7, and IGF1 mRNA was generally higher than PrSC but gene expression patterns were not uniform between PCaSC-8 and PCaSC-9 cells. Transforming growth factor ß (TGFß) and vascular endothelial growth factor (VEGF) protein levels in both PCaSC-8 and PCaSC-9 cells were generally higher than PrSC but levels of both secreted proteins were not same. When PrSCs were co-cultured with androgen-sensitive LNCaP cells or its sublines, androgen-low-sensitive E9 cells and androgen-insensitive AIDL cells, mRNA expression of IGF1 was significantly increased in all combinations. In contrast, expression of COL1A1, TNC, and ACTA2 mRNA was significantly increased only in LNCaP + PrSC and E9 + PrSC co-cultures. Protein production of VEGF was significantly increased only in LNCaP + PrSC and E9 + PrSC co-cultures. Increase of TGFß protein was observed only in E9 + PrSC co-cultures. These biochemical characteristics of PrSC were partially recapitulated in TGFß-treated PrSC. We have demonstrated that normal fibroblasts co-cultured with cancer cells become activated and exhibit biochemical characteristics of CAFs in a heterogenous manner. Our results suggest that heterogenous induction of CAF-like differentiation might be strongly dependent on biochemical characteristics of adjacent cancer cells.


Asunto(s)
Diferenciación Celular , Próstata/citología , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Técnicas de Cocultivo , Fibroblastos/citología , Perfilación de la Expresión Génica , Humanos , Masculino , Próstata/metabolismo , Neoplasias de la Próstata/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
14.
Cancer Prev Res (Phila) ; 4(1): 87-96, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21205739

RESUMEN

In prostate cancer, tumor-stroma interactions play a critical role in the promotion of tumorigenesis, and thus the prevention of those interactions is a promising target to suppress tumor growth. Several studies demonstrated that alpha(1)-adrenoceptor (α(1)-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G(1) cell-cycle arrest. However, their direct actions on stromal cells surrounding cancer cells have not yet been elucidated. In this study, we investigated the effects of subtype-selective α(1)-AR antagonists (naftopidil, tamsulosin, and silodosin) on prostate tumor growth with a focus on the role of stroma, using commercially available fibroblast cells (PrSC). Tumorigenic studies in vivo showed significant reductions in tumor growth when E9 cells (an androgen low-sensitive LNCaP subline) grafted with PrSC were treated with naftopidil. In in vitro analyses, naftopidil and silodosin showed antiproliferative effects on PCa cells regardless of androgen sensitivity and α(1)-AR subtype expression. In PrSC, a strong growth inhibitory effect was observed with naftopidil but not silodosin. Flow cytometric analysis revealed that naftopidil, but not silodosin, induced G(1) cell-cycle arrest in both PCa cells and PrSC. In naftopidil-treated PrSC, total interleukin-6 protein was significantly reduced with increased suppression of cell proliferation. Silodosin induced weak early apoptosis only in PCa cells. These findings demonstrated that naftopidil strongly suppressed cell proliferation of stromal cells, resulting in decreased tumorigenic soluble factor, suggesting that naftopidil might be effective in preventing stromal support of tumor cells.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Naftalenos/farmacología , Piperazinas/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Células del Estroma/metabolismo , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Humanos , Técnicas para Inmunoenzimas , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Desnudos , Neoplasias de la Próstata/patología , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células del Estroma/patología
15.
Differentiation ; 80(2-3): 82-8, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20638776

RESUMEN

Transforming growth factor-α (TGFα) promotes cell proliferation by binding to the epidermal growth factor receptor (EGFR). TGFα and EGFR overexpression have been reported in various human cancers. However, whether TGFα induces cancer by itself is unknown in urogenital organs. To investigate whether TGFα overexpression induces carcinogenesis in urogenital organs, we analyzed the phenotypes of urogenital organs in male TGFα transgenic (TG) mice of the CD1 strain. Urogenital organs including the kidney, bladder, prostate, seminal vesicles, testes, and epididymis were isolated from 4- to 48-week-old TGFα TG and wild-type (WT) CD1 mice. Prostates were separated into anterior prostate (AP), dorsolateral prostate (DLP), and ventral prostate (VP). Neither tumor formation nor epithelial hyperplasia was observed in the TGFα TG mouse urogenital organs that we have investigated. Histopathologically, in prostate, we found an increased number of p63-positive basal epithelial cells in the TGFα TG mice AP and DLP. There was no morphological change in the stromal component, such as hypercellular stroma or fibrosis. However, bladder weight was greater in TGFα TG mice than that in WT mice, and distended bladders were observed macroscopically in 19 of 20 TGFα TG mice over 20 weeks of age. Ki67 labeling index was increased significantly in the TGFα TG mouse urethral epithelium, whereas neither epithelial hyperplasia nor hypertrophy was observed. In conclusion, our results suggest that TGFα overexpression in mouse urogenital organs alone may not be responsible for tumor formation and epithelial hyperplasia, but is involved in bladder outlet obstruction.


Asunto(s)
Factor de Crecimiento Transformador alfa/genética , Sistema Urogenital/embriología , Animales , Secuencia de Bases , Cartilla de ADN , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Reacción en Cadena de la Polimerasa
16.
Hinyokika Kiyo ; 56(5): 273-5, 2010 May.
Artículo en Japonés | MEDLINE | ID: mdl-20519926

RESUMEN

We report a case of a large vesicourethral stone resulting from a long-term indwelling urethral catheter. A 66-year-old man visited our hospital emergency room on October 24, 2006 with a chief complaint of difficult urination. Although a urethral catheter was inserted temporarily based on the diagnosis of the doctor on duty, the patient did not return to our hospital for follow-up examination. On July 10, 2008, he was wheeled into our hospital with symptoms of general fatigue, urinary retention and post-renal failure due to urethral catheter obstruction. The catheter was undisturbed, and computed tomography revealed a large bladder stone that extended along the lines of the catheter. A cystostomy was established, and after renal function had recovered, the bladder stone was completely removed via laparotomy following the transurethral approach. The stone consisted of magnesium ammonium phosphate and calcium phosphate. It was concluded that the stone was closely related to a urinary tract infection caused by a Proteus strain. We discuss this unusual case, which is characterized by the stone size and the clinical course.


Asunto(s)
Catéteres de Permanencia/efectos adversos , Enfermedades Uretrales/etiología , Cálculos de la Vejiga Urinaria/etiología , Cálculos Urinarios/etiología , Cateterismo Urinario/efectos adversos , Humanos , Enfermedad Iatrogénica , Masculino , Persona de Mediana Edad , Factores de Tiempo
17.
Clin Exp Med ; 10(2): 99-106, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19826760

RESUMEN

Alpha1-adrenoceptor antagonists (alpha1-blockers) are currently used as first-line drugs for the treatment of benign prostatic hyperplasia (BPH). However, cases of BPH are often encountered in which the efficacy of alpha1-blockers decreases and switching to surgical treatment is required. One factor responsible for this resistance includes structural changes in prostatic tissue architecture following repeated oral administration of alpha1-blockers. Forty patients suspected of having prostate cancer, but without evidence of malignancy on prostatic biopsy were divided into two groups: an untreated group (n = 17) and an oral alpha1-blocker-treated group (n = 23). Twenty-one patients exhibiting resistance to oral alpha1-blocker therapy who underwent surgery were assigned into the surgically treated group. Each tissue sample was subjected to Masson's trichrome staining to distinguish collagen fibers from smooth muscle constituting prostatic stroma. The mean collagen fiber share was 62.2 +/- 10.4% in the untreated group, 72.1 +/- 9.1% in the oral alpha1-blocker-treated group, and 72.2 +/- 15.7% in the surgically treated group. Focusing on cases exhibiting high-collagen fiber share (70% or more), the distribution in each of the two alpha1-blocker-treated groups (16 of the 23 cases from the oral alpha1-blocker-treated group and 10 of the 21 cases from the surgically treated group) differed significantly from that in the untreated group (2 of the 17 cases). Our findings suggest that the accumulation of collagen fibers in prostatic stroma could be one of the factors responsible for alpha1-blocker treatment.


Asunto(s)
Antagonistas Adrenérgicos alfa/uso terapéutico , Resistencia a Medicamentos , Próstata/efectos de los fármacos , Próstata/patología , Hiperplasia Prostática/tratamiento farmacológico , Administración Oral , Antagonistas Adrenérgicos alfa/administración & dosificación , Anciano , Anciano de 80 o más Años , Histocitoquímica , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Microscopía , Persona de Mediana Edad , Hiperplasia Prostática/cirugía
18.
Hinyokika Kiyo ; 54(10): 651-6, 2008 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-19048929

RESUMEN

We investigated the safety and efficacy of photoselective vaporization of the prostate (PVP) in 318 men who had lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia with or without oral anticoagulant therapy (OAT). PVP was done using an 80 W potassium titanyl phosphate (KTP) laser under general or spinal anesthesia. We evaluated perioperative parameters, functional outcome (international prostate symptom score, quality of life score, maximum flow rate, postvoid residual urine volume), and adverse events up to 3 months postoperatively. The results in 51 patients under OAT (the group includes 6 men ongoing oral anticoagulants during the procedure) were compared with those obtained in 267 men who underwent PVP for the same indication but who were not under OAT (control). KTP laser vaporization was successfully performed on all patients. There was minimal blood loss, thus none of the patients needed a blood transfusion. No major complications occurred intraoperatively or postoperatively. In patients under OAT, the international prostate symptom score, quality of life score, maximum flow rate and postvoid residual urine volume were significantly improved from preoperative data (p < 0.05), and were comparable with the control. Although postoperative gross hematuria increased with resumption of OAT, PVP using 80 W KTP laser proved to be safe and effective for men who were taking oral anticoagulant medication.


Asunto(s)
Anticoagulantes/uso terapéutico , Terapia por Láser/métodos , Hiperplasia Prostática/cirugía , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del Tratamiento , Urodinámica/fisiología , Volatilización
19.
Int J Urol ; 15(12): 1067-71, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19054171

RESUMEN

OBJECTIVES: We present one year observations on Photoselective Vaporization of the Prostate (PVP) of 101 men with benign prostatic hyperplasia (BPH) to investigate its safety and efficacy. METHODS: 101 patients underwent Photoselective Vaporization of the Prostate (PVP) using 80 W Potassium-titanyl-phosphate (KTP) laser 17 patients were being treated with oral anticoagulant therapy, and anticoagulants were stopped before operation. Baseline characteristics, perioperative data, adverse events and postoperative outcome were evaluated immediate postoperatively, and at 2 weeks and 1, 3, 6 and 12 months postoperatively were recorded. RESULTS: With all 101 patients KTP laser vaporization was performed successfully. There was minimal blood loss and none of patients need blood transfusion. No major complication occurred intraoperatively or postoperatively. At 1, 3, 6, and 12 months mean International Prostate Symptom Score index (IPSS) decreased from 20.3 preoperatively to 8.9, 6.9, 6.2 and 7.2. Mean QQL score decreased from 5.1 to 2.3, 1.7, 1.5 and 1.6. Mean urinary peak flow increased from 7.5 ml per second to 15.6, 16.7 16.7 and 16.7 respectively. Complication was mild, included transient dysuria (8.9%). CONCLUSIONS: Photoselective vaporization of the prostate (PVP) using 80W Potassium-titanyl-phosphate (KTP) laser for benign prostatic hyperplasia (BPH) proved to be an effective and safe procedure for our patients including those treated with oral anticoagulants.


Asunto(s)
Terapia por Láser , Láseres de Estado Sólido/uso terapéutico , Hiperplasia Prostática/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Terapia por Láser/efectos adversos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
20.
Int J Urol ; 13(3): 315-7, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16643637

RESUMEN

We report herein a case of ureteral obstruction associated with pelvic inflammatory disease in a long-term intrauterine contraceptive device (IUD) user. A 62-year-old woman presented with a 2-week history of left flank pain and high fever, but no abdominal pain. She had forgotten the use of an IUD. Retrograde pyelography showed a stricture in the lower third of the left ureter. Magnetic resonance showed swelling of the uterus wall and left parametria, but did not reveal the presence of an IUD. Subtotal hysterectomy, bilateral salpingo-oophorectomy and left nephronureterectomy was performed. The IUD was then found in the uterine cavity. The results of pathological and bacteriological findings for Actinomyces infection were negative. Therefore we diagnosed this case as ureteral obstruction associated with pelvic inflammatory disease. Ureteral obstruction associated with pelvic inflammatory disease in a long-term IUD user is extremely rare.


Asunto(s)
Dispositivos Intrauterinos/efectos adversos , Enfermedad Inflamatoria Pélvica/complicaciones , Obstrucción Ureteral/etiología , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Histerectomía , Imagen por Resonancia Magnética , Persona de Mediana Edad , Nefrectomía , Enfermedad Inflamatoria Pélvica/diagnóstico , Enfermedad Inflamatoria Pélvica/cirugía , Factores de Tiempo , Obstrucción Ureteral/diagnóstico , Obstrucción Ureteral/cirugía , Urografía
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