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OBJECTIVES: This study aimed to elucidate the clinical characteristics and predictors of long-term postoperative urinary incontinence (PUI) after robot-assisted radical prostatectomy (RARP). METHODS: This study included patients who underwent RARP at our institution and were stratified into PUI (≥1 pad/day) and continence (0 pad/day) groups at 60 months after RARP. A propensity score-matched analysis with multiple preoperative urinary status (Expanded Prostate Cancer Index Composite urinary subdomains, total International Prostate Symptom Score (IPSS), and IPSS-quality of life scores) was performed to match preoperative urinary status in these groups. Serial changes in urinary status and treatment satisfaction preoperatively and until 60 months after RARP were compared, and predictors of long-term PUI were assessed using multivariate logistic regression analysis. RESULTS: A total of 228 patients were included in the PUI and continence groups (114 patients each). Although no significant difference in preoperative urinary status was observed between the two groups, the postoperative urinary status significantly worsened overall in the PUI group than in the continence group. Treatment satisfaction was also significantly lower in the PUI group than in the continence group from 12 to 60 months postoperatively. Multivariate logistic regression analysis revealed that age (≥70 years) and biochemical recurrence (BCR) were significant predictors of the long-term PUI group (p < 0.05). CONCLUSIONS: Patients with long-term PUI had poor overall postoperative urinary status and lower treatment satisfaction than the continence group. Considering the age and risk of BCR is important for predicting long-term PUI when performing RARP.
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OBJECTIVE: To assess the association among preoperative total testosterone levels, postoperative sexual function, and prognosis after robot-assisted radical prostatectomy. METHODS: Patients who underwent robot-assisted radical prostatectomy in our institution were included in the study. Based on preoperative total testosterone levels, they were divided into low (<3.0 ng/mL) and high (≥3.0 ng/mL) total testosterone groups. Sexual function was evaluated using the International Index of Erectile Function scores, Expanded Prostate Cancer Index Composite scores, and the potency rate from preoperatively to 12 months after surgery. Oncological outcomes were evaluated based on biochemical recurrence. RESULTS: Out of 233 patients included, no significant difference in sexual function was found between the high (n = 183) and the low (n = 50) total testosterone groups at any point before or after surgery. However, in nerve-sparing cases, preservation in postoperative sexual function was observed only in the high total testosterone group (International Index of Erectile Function scores and Expanded Prostate Cancer Index Composite sexual function scores, at any point after surgery, p < 0.05; potency rate, at 3, 6, and 12 months after surgery; p < 0.05). Additionally, the high total testosterone group showed better biochemical recurrence-free survival than the low total testosterone group (p = 0.008). CONCLUSIONS: In the high total testosterone group, preservation in sexual function was observed after the nerve-sparing procedure, while the biochemical recurrence rate was low. Therefore, patients with high levels of total testosterone may be advised to consider nerve-sparing interventions.
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BACKGROUND/AIM: Recent studies have reported conflicting findings regarding the significance of hydronephrosis (HN) in muscle-invasive bladder cancer (MIBC). The molecular characteristics of MIBC with HN are unclear, therefore, we aimed to address the gaps in previous research and elucidate HN's molecular significance in patients with MIBC. MATERIALS AND METHODS: Clinical, genetic, and imaging information on bladder cancer patients enrolled in The Cancer Genome Atlas were obtained from public databases to analyze the association between the presence of hydronephrosis and genetic alterations and molecular subtyping. A total of 108 patients who underwent total cystectomy for MIBC at the Hiroshima University Hospital were enrolled in the study to verify the association between HN and renal function with patient prognosis. RESULTS: We observed a statistically significant difference in the distribution of molecular subtypes (p=0.0146). The proportion of patients with the luminal papillary subtype was approximately twice as high in patients with HN (48.8%) than in those without HN (25.0%). The mutation frequency of fibroblast growth factor receptor (FGFR) 3 was approximately three-fold higher in patients with HN (20.9%) than in those without HN (7.1%). Multivariate analysis, which considered HN and estimated glomerular filtration rate as confounding factors in our MIBC cohort, revealed that reduced renal function, but not HN, was an independent predictor for overall survival. CONCLUSION: MIBC presenting HN exhibits a high frequency of mutations in the FGFR3 gene. In addition, not HN itself, but reduced renal function due to HN may worsen the prognosis for MIBC.
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Hidronefrosis , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Masculino , Cistectomía , Hidronefrosis/genética , Hidronefrosis/etiología , Mutación , Invasividad Neoplásica , Pronóstico , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
AIM: This study aimed to evaluate the risk classification system using the detailed positive surgical margin (PSM) status to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed 427 patients who underwent RARP between January 2016 and March 2020. We investigated risk factors for BCR using univariate and multivariate Cox proportional hazard regression models. The biochemical recurrence-free survival (BRFS) rate was assessed using the Kaplan-Meier method. RESULTS: The median follow-up period was 43.4 months and 99 patients developed BCR. In the multivariate analysis, maximum PSM length > 5.0 mm and the International Society of Urological Pathology grade group (ISUP GG) at the PSM ≥3 were predictive factors for BCR in patients with a PSM. In the multivariate analysis, these factors were also independent predictive factors in the overall study population, including patients without a PSM. We classified the patients into four groups using these factors and found that the 1-year BRFS rates in the negative surgical margin (NSM) group, low-risk group (PSM and neither factor), intermediate-risk group (either factor), and high-risk group (both factors) were 94.9%, 94.5%, 83.1%, and 52.9%, respectively. The low-risk group showed similar BRFS to the NSM group (p = 0.985), while the high-risk group had significantly worse BRFS than the other groups (p < 0.001). CONCLUSION: Maximum PSM length > 5.0 mm and ISUP GG at the PSM ≥3 were independent predictive factors for BCR after RARP. Risk classification for BCR using these factors is considered to be useful and might help urologists decide on additional treatment after RARP.
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INTRODUCTION: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). METHODS: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and Gene Set Enrichment Analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC. RESULTS: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells, however, it did not influence the proliferation of cells. RNA sequencing and Gene Set Enrichment Analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival. CONCLUSIONS: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment.
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Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.
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OBJECTIVE: Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting. METHODS: A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified. RESULTS: The median age of patients was 74 years, and the median prostate-specific antigen value at the time of submission was 18.6 ng/ml. Fifty-seven (95%) of 60 cases were metastatic castration-resistant prostate cancers, and 3 cases (5%) were non-metastatic. Among all genetic alterations, androgen-receptor alteration was the most frequently detected in 17 cases (28.3%), followed by 15 cases of TP53 (25.0%), 14 cases of CDK12 (23.3%), 10 cases of phosphatase and tensin homolog (16.7%) and 9 cases of ATM (15.0%) mutations. A total of 13 patients (21.7%) received systemic therapy according to the comprehensive genomic profiling testing results. Overall, the survival rate was significantly greater in the group treated through systemic therapy based on comprehensive genomic profiling testing compared with the group without new therapeutic treatment (P = 0.041). CONCLUSIONS: Comprehensive genomic profiling testing is recommended in castration-resistant prostate cancer patients identified as resistant to standard therapy as this can provide a new therapeutic option.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Anciano , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Estudios Retrospectivos , Japón , Antígeno Prostático Específico , GenómicaRESUMEN
INTRODUCTION: The modified 5-item frailty index can be used to evaluate frailty using 5 routinely encountered clinical variables. This study aimed to assess the impact of the modified 5-item frailty index in patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma. PATIENTS AND METHODS: In this multicenter retrospective study, we calculated the modified 5-item frailty index scores of patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma between 2010 and 2022. Patients were categorized into the high (≥2) and low (≤1) modified 5-item frailty index score groups. To assess the prognostic influence of the preoperative modified 5-item frailty index, we conducted Cox proportional regression analyses concerning progression-free, overall, and cancer-specific survival. RESULTS: Of 434 patients, 82, and 352 were classified into the high and low modified 5-item frailty index score groups, respectively. The high modified 5-item frailty index score group had significantly higher rates of severe surgical complications (P = .038) and ≥30 days of hospitalization (P = .049) and significantly worse progression-free (P = .012) and overall survival (P = .002) than the low modified 5-item frailty index score group. The multivariable Cox proportional hazard analysis revealed that a high modified 5-item frailty index score was independently associated with poor progression-free (P = .044), overall (P = .017), and cancer-specific survival (P = .005). CONCLUSION: The modified 5-item frailty index emerged as a significant predictive indicator of severe surgical complications and postoperative survival outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.
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Carcinoma de Células Transicionales , Fragilidad , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Humanos , Nefroureterectomía , Neoplasias de la Vejiga Urinaria/cirugía , Pronóstico , Carcinoma de Células Transicionales/cirugía , Estudios Retrospectivos , Neoplasias Urológicas/patología , Fragilidad/diagnósticoRESUMEN
BACKGROUND/AIM: Bladder cancer with histological variant (HV) has different morphological features from usual urothelial carcinoma (UC). The aim of this study was to evaluate the oncological outcomes of HV in patients with bladder cancer. PATIENTS AND METHODS: We retrospectively evaluated data from 102 patients with UC of the bladder treated with radical cystectomy between 1998 and 2017. Pathological findings including HV were assigned by one dedicated pathologist. Recurrence-free survival (RFS) and cancer-specific survival (CSS) and overall survival (OS) were estimated by Cox regression models. RESULTS: In total, 26 patients (25.5%) had HV, and the most common variant was squamous differentiation, followed by glandular differentiation and a mixed variant consisted of squamous and glandular differentiation. The presence of HV was associated with RFS and CSS (p=0.018, p=0.036, respectively). CONCLUSION: HV has more aggressive tumor biological features compared to those with pure UC. The presence of HV was associated with poor survival.
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Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias Urológicas/patología , Neoplasias Urológicas/cirugía , Cistectomía/métodos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Oncología Médica/métodos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Vejiga Urinaria/patología , Vejiga Urinaria/cirugíaRESUMEN
PURPOSE: Few studies mention the necessity of antimicrobial prophylaxis (AMP) for transurethral resection of bladder tumor (TURBT) and the risk factors for postoperative urinary tract infections (UTIs) after TURBT. To evaluate the necessity of AMP and to detect the risk of UTIs, we examined the perioperative clinical factors. METHODS: 687 patients who underwent TURBT between 2006 and 2017 at Hiroshima Prefectural Hospital were examined retrospectively. We defined the postoperative UTIs as febrile UTIs (≥ 38 °C). The AMP for the TURBT that we used was mostly cephalosporin generation 1. The association between the perioperative clinical/pathological factors and postoperative UTIs was assessed by logistic regression retrospectively. RESULTS: 21 patients (3.1%) suffered from postoperative UTIs, and almost all of them were successfully treated with the immediate administration of antibiotics. Univariate analysis showed that past pelvic radiotherapy (p = 0.024, odds ratio (OR) 6.00), tumor size (≥ 2cm) (p = 0.008, OR 3.38), age (≥ 75 years) (p = 0.036, OR 2.65), preoperative hospital stay (≥ 5 days) (p = 0.017, OR 3.76), asymptomatic pyuria (p = 0.038, OR 2.54) and bacteriuria (p = 0.044, OR 2.97) were all associated with postoperative UTIs. CONCLUSIONS: We demonstrated that AMP was effective for patients who underwent TURBT, and history of pelvic radiotherapy, high age, preoperative hospital stay and a certain tumor size were the risk factors as well as pyuria and bacteriuria of postoperative UTIs.
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Profilaxis Antibiótica , Cistectomía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Neoplasias de la Vejiga Urinaria/cirugía , Infecciones Urinarias/epidemiología , Infecciones Urinarias/prevención & control , Anciano , Anciano de 80 o más Años , Cistectomía/métodos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , UretraRESUMEN
(Objective) The aim of this study is to investigate the treatment outcome of laparoscopic radical prostatectomy (LRP). (Patients and methods) The study cohort consisted of 926 hormone-naïve patients with localized prostate cancer who underwent LRP at the Hiroshima Endourological Association from January 2007 to December 2016. (Results) The mean age was 69.4 years, the mean initial PSA was 9.1 ng/ml, and the mean follow-up period was 40.3 months. The D'Amico Risk Classification was Low: 232 cases, Intermediate: 344 cases, and High: 350 cases. Nerve preservation was performed bilaterally for 138 patients and unilaterally for 181 patients. The mean operative time was 181.0 minutes and the mean estimated blood loss was 360.7 ml. As the number of experienced cases increased, the operative time was significantly shorter and the estimated blood loss was significantly decreased. According to Clavien-Dindo classification, the ratio of perioperative complication degree IIIa or above was 4.0% (37 cases). The pathological results were Gleason score (GS) ≤6: 174 cases, GS7: 514 cases, GS ≥8: 232 cases, pT2≥: 704 cases, pT3a: 172 cases, pT3b: 47 cases, pT4: 3 cases, pN0: 917 cases, and pN1: 9 cases. Positive surgical margins were found in 278 cases (30.0%). The biochemical recurrence-free survival rate at 5 years was 78.1%. In multivariate analysis, age (≥70 yrs), initial PSA (≥10 ng/ml), biopsy GS (GS ≥8), cancer positive core ratio at biopsy (≥30%), pT (pT≥3), pathological GS (GS≥8), positive surgical margin and total number of patients in the facility were predictive factors of postoperative biochemical PSA recurrence. Younger age and nerve preservation were found to be predictive factors for the early recovery of urinary continence after surgery, with 88% regaining urinary continence at 12 months after surgery. (Conclusion) This study revealed the clinical outcome and appropriate candidates for LRP in Japanese patients.
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Laparoscopía/métodos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Factores de Edad , Anciano , Estudios de Seguimiento , Humanos , Japón , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Trousseau's syndrome is known as a thromboembolic disorder due to hypercoagulation accompanied with advanced cancer. A 67-year-old man presented with disequilibrium and back pain, and magnetic resonance imaging of his brain indicated multiple cerebral infarctions at the acute stage. A computed tomography scan showed enlargement of multiple paraaortic lymph nodes. From these findings, we suspected that this patient had Trousseau's syndrome. The patient started anticoagulant treatment involving constant infusion with heparin Na. We also examined the origin of enlarged multiple paraaortic lymph nodes by investigating the tumor markers, which showed that the prostate specific antigen value (PSA) was extremely high. We conducted a prostatic biopsy and the pathological findings showed prostate cancer. The Combined Androgen Blockade (CAB) therapy was effective in reducing PSA value and shrinkage of the paraaortic lymph nodes. After the blood coagulation ability was improved to a normal state, we changed the anticoagulant treatment to subcutaneous injection of heparin Ca. There was no recurrence of cerebral infarction and no regrowth of prostate cancer 6 months after CAB therapy. Trousseau's syndrome is known as a poor prognosis syndrome because there is no effective therapy for the advanced stage of the accompanying cancer. However, CAB therapy is effective for advanced prostate cancer and long-term prognosis is expected. Starting anticoagulant treatment at the acute stage and maintaining anticoagulant treatment at the chronic stage are important in the treatment of Trousseau's syndrome accompanied with prostate cancer.
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Infarto Cerebral/terapia , Neoplasias de la Próstata/terapia , Tromboembolia/terapia , Trombofilia/terapia , Anciano , Antagonistas de Andrógenos/administración & dosificación , Heparina/administración & dosificación , Humanos , Masculino , Síndrome , Resultado del TratamientoRESUMEN
The Notch pathway has been implicated in both oncogenic and tumour-suppressive roles in cancer depending on the tissue type and cellular context. However, until recently, little was known about the pathway in bladder cancer. Studies have revealed that NOTCH1 copy number and expression are decreased in bladder cancer and NOTCH1 activation in bladder cancer cell lines reduces proliferation, suggesting that NOTCH1 acts as a tumour suppressor. Furthermore, in transgenic models, bladder cancer is promoted by bladder-specific inactivation of a component of the γ-secretase complex, which liberates the intracellular domain of neurogenic locus Notch homologue protein (NOTCH) and starts the signalling cascade. By contrast, further work has demonstrated that NOTCH2 acts as an oncogene that promotes cell proliferation and metastasis through epithelial-to-mesenchymal transition, cell cycle progression, and maintenance of stemness. Studies indicating that NOTCH1 and NOTCH2 have opposite effects on the progression of bladder cancer could give rise to potential therapeutic approaches aimed at blocking or restoring the Notch pathway.
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Biomarcadores de Tumor/metabolismo , Carcinoma/metabolismo , Receptor Notch1/metabolismo , Receptor Notch2/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Carcinoma/patología , Proliferación Celular , Transición Epitelial-Mesenquimal , Humanos , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Orthotopic mouse models of urothelial cancer are essential for testing novel therapies and molecular manipulations of cell lines in vivo. These models are either established by orthotopic inoculation of human (xenograft models) or murine tumor cells (syngeneic models) in immunocompromised or immune competent mice. Current techniques rely on inoculation by intravesical instillation or direct injection into the bladder wall. Alternative models include the induction of murine bladder tumors by chemical carcinogens (BBN) or genetic engineering (GEM).
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Modelos Animales de Enfermedad , Neoplasias Urológicas/patología , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica/inducido químicamente , Xenoinjertos , Humanos , Ratones , Ratones Transgénicos , Neoplasias Urológicas/etiologíaRESUMEN
(Purpose) We report five cases of adrenal myelolipoma with surgical treatment, and analyze the patients' background and clinical courses. (Patients and methods) From 2004 to 2017, five patients diagnosed adrenal myelolipoma were underwent surgical treatment at our hospital. We investigate the patients' background and clinical courses retrospectively. (Results) Median age was 53 years old. Four of them were male and one was female. The tumor was located on the right side in four cases and the left side in one case. All cases were incidentally found by abdominal ultrasound or computer tomography (CT) during a medical check or image examination for other disease. Whereas all cases were asymptomatic, they have past history either hypertension, diabetes or obesity. The tumor size at the time of diagnosis was from 28 mm to 80 mm (median 58 mm). All tumors were nonfunctioning, and diagnosed by CT scan preoperatively. The median tumor size at the time of operation was 66 mm. (Conclusion) We report five cases of adrenal myelolipoma treated surgically. The opportunity of encountering this disease has been increasing as the recent improvement of diagnostic imaging such as CT, MRI, and etc. However, there is no widely-accepted treatment algorithm. We should manage them carefully, because spontaneous rupture of adrenal myelolipoma has been reported in some cases.
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PURPOSE: Recent molecular analyses of bladder cancer open the door to significant advances in targeted therapies. NOTCH has been identified as a tumor suppressor in bladder cancer, but prior reports have focused on NOTCH1 Here we hypothesized that NOTCH2 is an oncogene suitable for therapeutic targeting in bladder cancer. EXPERIMENTAL DESIGN: We studied genomic aberrations of NOTCH, compared survival and tumor progression according to NOTCH2 expression levels, and studied NOTCH2 function in vitro and vivo RESULTS: We report a high rate of NOTCH2 copy number gain in bladder cancer. High NOTCH2 expression was identified especially in the basal subtype and in mesenchymal tumors. NOTCH2 activation correlated with adverse disease parameters and worse prognosis by immunohistochemistry. Forced overexpression of the intracellular domain of NOTCH2 (N2ICD) induced cell growth and invasion by cell-cycle progression, maintenance of stemness and epithelial-to-mesenchymal transition (EMT). These effects were abrogated by silencing of CSL, indicating that the effects were mediated through the canonical NOTCH signaling pathway. In an orthotopic xenograft model, forced overexpression of N2ICD increased growth, invasion, and metastasis. To explore the potential for therapeutic targeting of NOTCH2, we first silenced the receptor with shRNA and subsequently treated with a specific inhibitory antibody. Both interventions decreased cell growth, invasion, and metastasis in vitro and in the orthotopic xenograft model. CONCLUSIONS: We have demonstrated that NOTCH2 acts as an oncogene that promotes bladder cancer growth and metastasis through EMT, cell-cycle progression, and maintenance of stemness. Inhibition of NOTCH2 is a rational novel treatment strategy for invasive bladder cancer. Clin Cancer Res; 22(12); 2981-92. ©2016 AACR.
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Transición Epitelial-Mesenquimal/genética , Receptor Notch2/genética , Receptor Notch2/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Activación Enzimática/genética , Dosificación de Gen/genética , Humanos , Metástasis Linfática/genética , Ratones , Invasividad Neoplásica/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Receptor Notch1/biosíntesis , Receptor Notch2/antagonistas & inhibidores , Receptor Notch3/biosíntesis , Transducción de Señal/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We report a case of sarcomatoid carcinoma of the ureter in a 82-year-old woman. She was admitted to our hospital with right hydronephrosis. A computed tomography (CT) and retrograde pyelography (RP) showed a solid tumor at right ureter with right hydronephrosis and 3 cm solid tumor on the right abdominal wall. She underwent laparoscopic nephroureterectomy and excision of abdominal subcutaneous tumor. Pathological diagnosis was urothelial carcinoma with sarcomatoid variant, pT3, grade 3 and abdominal wall metastasis. Other metastasis occured in left kidney and ileum about 1 month after the operation, and then she underwent laparoscopic partial nephrectomy and ileocecal resection. The histopathological diagnosis was sarcomatoid carcinoma with positive staining for granulocyte-colony stimulating factor (G-CSF). The paient died of multiple metastases 5 months after first operation. As far as we know, this is the first report of G-CSF producing infiltrating sarcomatoid carcinoma of the ureter in Japanese paper.
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Factor Estimulante de Colonias de Granulocitos/biosíntesis , Hidronefrosis/etiología , Neoplasias Ureterales/patología , Anciano de 80 o más Años , Resultado Fatal , Femenino , Humanos , Metástasis de la Neoplasia , Nefrectomía , Tomografía Computarizada por Rayos X , Neoplasias Ureterales/complicaciones , Neoplasias Ureterales/metabolismo , Neoplasias Ureterales/cirugíaRESUMEN
Circadian rhythms are controlled by a system of negative and positive genetic feedback loops composed of clock genes. Although many genes have been implicated in these feedback loops, it is unclear whether our current list of clock genes is exhaustive. We have recently identified Chrono as a robustly cycling transcript through genome-wide profiling of BMAL1 binding on the E-box. Here, we explore the role of Chrono in cellular timekeeping. Remarkably, endogenous CHRONO occupancy around E-boxes shows a circadian oscillation antiphasic to BMAL1. Overexpression of Chrono leads to suppression of BMAL1-CLOCK activity in a histone deacetylase (HDAC) -dependent manner. In vivo loss-of-function studies of Chrono including Avp neuron-specific knockout (KO) mice display a longer circadian period of locomotor activity. Chrono KO also alters the expression of core clock genes and impairs the response of the circadian clock to stress. CHRONO forms a complex with the glucocorticoid receptor and mediates glucocorticoid response. Our comprehensive study spotlights a previously unrecognized clock component of an unsuspected negative circadian feedback loop that is independent of another negative regulator, Cry2, and that integrates behavioral stress and epigenetic control for efficient metabolic integration of the clock.
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Factores de Transcripción ARNTL/metabolismo , Relojes Circadianos/fisiología , Péptidos y Proteínas de Señalización del Ritmo Circadiano/metabolismo , Criptocromos/metabolismo , Proteínas Represoras/metabolismo , Células 3T3 , Secuencia de Aminoácidos , Animales , Células COS , Línea Celular , Chlorocebus aethiops , Relojes Circadianos/genética , Ritmo Circadiano/genética , Ritmo Circadiano/fisiología , Péptidos y Proteínas de Señalización del Ritmo Circadiano/biosíntesis , Péptidos y Proteínas de Señalización del Ritmo Circadiano/genética , Criptocromos/genética , Histona Desacetilasas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Datos de Secuencia Molecular , Receptores de Glucocorticoides/metabolismo , Proteínas Represoras/biosíntesis , Proteínas Represoras/genética , Alineación de Secuencia , Transcripción Genética/genéticaRESUMEN
OBJECTIVE: We retrospectively compared the clinical outcomes of Lithoclast assisted lithotripsy (L group) with those of Holmium YAG laser assisted lithotripsy (H group). PATIENTS AND METHODS: We analyzed records for operation time, duration of ureteral stenting, complication and stone-free rates in the L group (388 patients) and the H group (368 patients) for the primary procedure. RESULTS: The stone locations (L group/H group) were U1 in 141/181, U2 in 69/57, and U3 in 178/130. Respective median stone sizes (L group/H group) were: U1,: 10.0/10.0 mm; U2,: 7.0/10.0 mm;, and U3,: 6.0/7.0 mm. Secondary procedures were performed in 79 L group patients and 35 H group patients. The median operation times (L group/H group) were 29.5/25.0 minutes. The median durations of ureteral stenting (L group/H group) were 4.0/4.0 days. The stone-free rates (L group/H group) according to the locations of the stones were 69.3/82.0% in U1, 85.5/87.0% in U2, and 92.0/98.4% in U3. Complications (L group/H group) were ureter perforation in 8/5 cases, pyelonephritis in 7/2 cases, ureteral stricture in 2/6 cases, and stone push up in 27/13 cases. CONCLUSION: The operation time for holmium YAG laser assisted lithotripsy was significantly shorter than that of the Litoclast assisted procedure, and the stone-free rate with holmium YAG laser assisted lithotripsy was better than that with Lithoclast assisted lithotripsy for U1 and U3 stones.