RESUMEN
N-cadherin is a transmembrane glycoprotein expressed by mesenchymal origin cells and is located at the adherens junctions. It regulates also cell motility and contributes to cell signaling. In previous studies, we identified that its anomalous expression in bladder carcinoma was a tumor progression marker. A pharmacological approach to inhibit N-cadherin expression or to block its function could be relevant to prevent disease progression and metastasis development. The morphological exploration of T24 invasive bladder cancer cells by atomic force microscopy (AFM) revealed a spindle-like shape with fibrous structures. By engaging force spectroscopy with AFM tip functionalized with anti-E or anti-N-cadherin antibodies, results showed that T24 cells expressed only N-cadherin as also demonstrated by Western blotting and confocal microscopy. For the first time, we demonstrated by RTqPCR and Western blotting analyses that the peroxisome proliferator-activated receptor ß/δ (PPARß/δ) agonist GW501516 significantly decreased N-cadherin expression in T24 cells. Moreover, high non-cytotoxic doses of GW501516 inhibited confluent T24 cell wound healing closure. By using AFM, a more sensitive nanoanalytical method, we showed that the treatment modified the cellular morphology and diminished N-cadherin cell surface coverage through the decreasing of these adhesion molecule-mediated interaction forces. We observed a greater decrease of N-cadherin upon GW501516 exposure with AFM than that detected with molecular biology techniques. AFM was a complementary tool to biochemical techniques to perform measurements on living cells at the nanometer resolution level. Taken together, our data suggest that GW501516 could be an interesting therapeutic strategy to avoid bladder cancer cell spreading through N-cadherin decrease.
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Antígenos CD/metabolismo , Cadherinas/metabolismo , Transición Epitelial-Mesenquimal , Microscopía de Fuerza Atómica/métodos , PPAR delta/agonistas , PPAR-beta/agonistas , Tiazoles/farmacología , Neoplasias de la Vejiga Urinaria/metabolismo , Antígenos CD/ultraestructura , Cadherinas/ultraestructura , Línea Celular Tumoral , Movimiento Celular , Humanos , Transducción de Señal , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/ultraestructuraRESUMEN
BACKGROUND: Non-muscle invasive bladder cancers (NMIBC: pTa, pT1) are characterised by a high risk of recurrence and/or progression. Identification of prognostic markers is needed to improve both diagnosis and management of the disease. The aim of this study was to analyse the expression of A-FABP (adipocyte-fatty acid binding protein) and to evaluate its prognostic value in bladder cancer with a long term clinical follow-up. METHODS: A-FABP expression was investigated by immunohistochemistry in 236 tumours (114 pTa, 61 pT1, 61 pT2-4). Immunostaining was classified as negative (absent or weak immunostaining and moderate or strong staining on ≤10% of cells) or positive (moderate or strong staining on > 10% of cells). Event-free survival (EFS) and overall survival (OS) were determined with a 87.3 months median follow-up in the overall cohort. Recurrence-free survival (RFS) and progression-free survival (PFS) were established in NMIBC. RESULTS: Loss of A-FABP was associated with higher mean age, high stage/grade, and the presence of metastatic lymph nodes. It was correlated with shorter median EFS (17.5 vs 62.5 months; p = 0.001) and mean OS (76.7 vs 154.2 months; p = 0.009) and with higher risk of progression in the pTa/pT1 subgroup (HR, 0.36; 95% CI, 0.13-0.96; p = 0.041) and importantly in the pTa tumours (HR, 0.34; 95% CI, 0.10-0.97; p = 0.045). CONCLUSION: These results demonstrated that loss of A-FABP expression following a long follow-up was predictive of pTa and pTa/pT1 progression. Immunohistochemistry on diagnostic biopsy is easy to use and could be of value to help clinicians to propose appropriate treatment for these tumours.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/patología , Proteínas de Unión a Ácidos Grasos/biosíntesis , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/mortalidad , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
GW501516 is a selective and high-affinity synthetic agonist of peroxisome proliferator-activated receptor ß/δ (PPARß/δ). This molecule promoted the inhibition of proliferation and apoptosis in few cancer cell lines, but its anticancer action has never been investigated in bladder tumor cells. Thus, this study was undertaken to determine whether GW501516 had antiproliferative and/or apoptotic effects on RT4 and T24 urothelial cancer cells and to explore the molecular mechanisms involved. Our results indicated that, in RT4 cells (derived from a low-grade papillary tumor), GW501516 did not induce cell death. On the other hand, in T24 cells (derived from an undifferentiated high-grade carcinoma), this PPARß/δ agonist induced cytotoxic effects including cell morphological changes, a decrease of cell viability, a G2/M cell cycle arrest, and the cell death as evidenced by the increase of the sub-G1 cell population. Furthermore, GW501516 triggered T24 cell apoptosis in a caspase-dependent manner including both extrinsic and intrinsic apoptotic pathways through Bid cleavage. In addition, the drug led to an increase of the Bax/Bcl-2 ratio, a mitochondrial dysfunction associated with the dissipation of ΔΨm, and the release of cytochrome c from the mitochondria to the cytosol. GW501516 induced also ROS generation which was not responsible for T24 cell death since NAC did not rescue cells upon PPARß/δ agonist exposure. For the first time, our data highlight the capacity of GW501516 to induce apoptosis in invasive bladder cancer cells. This molecule could be relevant as a therapeutic drug for high-grade urothelial cancers.
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Apoptosis/efectos de los fármacos , PPAR delta/agonistas , PPAR-beta/agonistas , Tiazoles/farmacología , Neoplasias de la Vejiga Urinaria/patología , Western Blotting , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Invasividad Neoplásica , Especies Reactivas de Oxígeno/metabolismo , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Health-related quality of life (HRQoL) has been positioned as one of the major endpoints in oncology. Thus, there is a need to validate cancer-site specific survey instruments. This study aimed to perform a transcultural adaptation of the 50-item Expanded Prostate cancer Index Composite (EPIC) questionnaire for HRQoL in prostate cancer patients and to validate the psychometric properties of the French-language version. METHODS: The EPIC questionnaire measures urinary, bowel, sexual and hormonal domains. The first step, corresponding to transcultural adaptation of the original English version of the EPIC was performed according to the back translation technique. The second step, comprising the validation of the psychometric properties of the EPIC questionnaire, was performed in patients under treatment for localized prostate cancer (treatment group) and in patients cured of prostate cancer (cured group). The EORTC QLQ-C30 and QLQ-PR25 prostate cancer module were also completed by patients to assess criterion validity. Two assessments were performed, i.e., before and at the end of treatment for the Treatment group, to assess sensitivity to change; and at 2 weeks' interval in the Cured group to assess test-retest reliability. Psychometric properties were explored according to classical test theory. RESULTS: The first step showed overall good acceptability and understanding of the questionnaire. In the second step, 215 patients were included from January 2012 to June 2014: 125 in the Treatment group, and 90 in the Cured group. All domains exhibited good internal consistency, except the bowel domain (Cronbach's α = 0.61). No floor effect was observed. Test-retest reliability assessed in the cured group was acceptable, expect for bowel function (intraclass coefficient = 0.68). Criterion validity was good for each domain and subscale. Construct validity was not demonstrated for the hormonal and bowel domains. Sensitivity to change was exhibited for 5/8 subscales and 2/4 summary scores for patients who experienced toxicities during treatment. CONCLUSIONS: The French EPIC questionnaire seems to have adequate psychometric properties, comparable to those exhibited by the original English-language version, except for the construct validity, which was not available in original version.
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Comparación Transcultural , Neoplasias de la Próstata/psicología , Calidad de Vida , Encuestas y Cuestionarios , Adulto , Anciano , Francia , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/terapia , Psicometría , Reproducibilidad de los Resultados , Conducta Sexual , TraduccionesRESUMEN
Thiazolidinediones, including rosiglitazone and troglitazone, are insulin-sensitizing drugs and high-affinity ligands for the peroxisome proliferator-activated receptor gamma (PPARgamma). Apart from their antidiabetic activity, these molecules possess antitumor properties. We investigated their potential apoptotic effects on RT4 (derived from a well-differentiated Grade I papillary tumor) and T24 (derived from an undifferentiated Grade III carcinoma) bladder cancer cells. Rosiglitazone induced G2/M or G0/G1 phase cell cycle arrest in RT4 and T24 cells, respectively. Only troglitazone triggered apoptosis via extrinsic and intrinsic pathways in both cell lines. Interestingly, rosiglitazone amplified TRAIL-induced apoptosis in TRAIL-sensitive RT4 cells or let TRAIL-resistant T24 cells to respond to TRAIL. Thiazolidinediones acted through PPARgamma activation-independent mechanisms. The underlying mechanisms involved for the first time in cancer cells the upregulation of soluble and/or membrane-bound TRAIL. This was associated with increased cell surface death receptor 5 expression and c-FLIP and survivin downregulation, mediated in part through proteasome-dependent degradation in troglitazone-promoted cell death. Therefore, the combination of rosiglitazone and TRAIL could be clinically relevant as chemopreventive or therapeutic agents for the treatment of TRAIL-resistant high-grade urothelial cancers.
Asunto(s)
Apoptosis/efectos de los fármacos , PPAR gamma/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Tiazolidinedionas/farmacología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Western Blotting , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Citometría de Flujo , Humanos , Proteínas Inhibidoras de la Apoptosis , Proteínas Asociadas a Microtúbulos/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Survivin , Activación Transcripcional , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
OBJECTIVE: The objective of this study was to analyze the effects of obesity on postoperative complications and patient and graft survival after kidney transplantation. METHODS: We retrospectively included 506 patients who received a kidney transplant in our center during eleven years. Obesity was defined by a body mass index ≥ 30 kg/m2 based on World Health Organization criteria. Using univariate and multivariate analyses, we evaluated the impact of obesity on surgical complications according to the Clavien-Dindo classification up to 30 days after surgery. The impact of obesity on graft and patient survival was assessed using a Cox proportional regression model. RESULTS: Seventy-one patients were obese (14%), and mean follow-up was 63.1 months (59.7-66.5). By multivariable analysis, obesity was associated with delayed graft function (hazard ratio [HR] = 2.60 [1.31-5.02], P = .004). Obesity was not associated with surgical complications, but cardiovascular history was (HR = 1.68 [1.09-2.99], P = .048). By Cox regression analysis, obesity was significantly associated with a higher risk of graft loss (HR = 1.55 [1.06-2.99], P = .042) but not with patient survival (HR = 1.82 [0.88-3.79], P = .106). CONCLUSION: Obesity was associated with delayed graft function and graft loss. However, it was not associated with surgical complications. Kidney transplantation remains the best therapy for obese patients suffering from end-stage renal disease, despite shorter graft survival.
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Supervivencia de Injerto , Trasplante de Riñón/mortalidad , Obesidad/complicaciones , Complicaciones Posoperatorias/epidemiología , Adulto , Funcionamiento Retardado del Injerto/epidemiología , Femenino , Humanos , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate four predictive scores for stone-free rate (SFR) after flexible ureterorenoscopy (f-URS) with holmium-YAG laser fragmentation of renal and ureteral lithiasis. METHODS: We carried out a retrospective analysis of 800 f-URS procedures performed in our institution between January 2009 and December 2016. For each procedure, a single surgeon calculated the following scores: S.T.O.N.E score; Resorlu Unsal Stone Score (RUSS); modified Seoul National University Renal Complexity (S-ReSC) score; and Ito's score. RESULTS: Overall SFR was 74.1%. Univariate analysis demonstrated that stone size (p<0.0001), stone volume (p<0.0001), stone number (p = 0.004), narrow lower pole infundibulopelvic angle (IPA) (p = 0.003) and lower pole location + IPA <45° (p = 0.011) were significantly associated with SFR. All scores differed between the stone-free and non-stone-free groups. Area under the curve of the receiving operator characteristics curve was calculated for each score: 0.617 [95%CI: 0.575-0.660] for the S.T.O.N.E score; 0.644 [95%CI: 0.609-0.680] for the RUSS; 0.651 [95%CI: 0.606-0.697] for the S-ReSC score; and 0.735 [95%CI: 0.692-0.777] for Ito's nomogram. CONCLUSION: All four scores were predictive of SFR after f-URS. Ito's score was the most sensitive. However, the performance of all scores in this analysis was lower than in developmental studies.
Asunto(s)
Cálculos Renales/terapia , Litotripsia por Láser , Cálculos Ureterales/terapia , Ureteroscopía , Adulto , Anciano , Femenino , Humanos , Cálculos Renales/química , Láseres de Estado Sólido/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Cálculos Ureterales/químicaRESUMEN
Superficial pT1 bladder tumors are characterized by a high risk of recurrence and progression in grade and stage. Few studies provided evidence that loss of adipocyte-fatty acid binding protein (A-FABP) expression was associated with bladder cancer progression. A-FABP is a lipid binding protein playing a role in intracellular lipid transport and metabolism, as well as in signal transduction. We reported from bladder tumors that decrease of A-FABP transcript level significantly correlated to tumor stage and to histologic grade (p < 0.05). Namely, in poor prognosis high grade pT1 tumors there was a loss of A-FABP expression compared to good prognosis tumors suggesting that re-expression of A-FABP could be a therapeutic approach in early stage bladder cancer to prevent disease progression. We demonstrated for the first time that this marker is upregulated by Peroxisome Proliferator-Activated Receptor (PPAR) alpha, beta and gamma in T24 cells (derived from an undifferentiated grade III carcinoma) and only by PPARbeta in RT4 cells (derived from a well differentiated grade I papillary tumor). This effect occurred through a PPAR-dependent transcriptional mechanism without modifying mRNA stability and interestingly required de novo protein synthesis. Data as a whole suggest a prognostic significance of A-FABP in bladder cancer outcome and the potential utility of overexpression of this protein by PPAR agonists open up new perspectives in the treatment of bladder cancer. (c) 2008 Wiley-Liss, Inc.
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Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Transicionales/metabolismo , Proteínas de Unión a Ácidos Grasos/biosíntesis , Regulación Neoplásica de la Expresión Génica , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Urotelio/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Proteínas de Unión a Ácidos Grasos/metabolismo , Humanos , Persona de Mediana Edad , Transducción de SeñalRESUMEN
OBJECTIVES: Twist is considered as transcription factor that regulates epithelial mesenchymal transition (EMT) by at least inhibition of E-cadherin expression. EMT is a key event in the tumor invasion process. The purpose of this study is to investigate the expression of Twist but also those of E- and N-cadherin in human primary bladder tumor and to evaluate its prognostic value. As smoking cigarettes is a strong bladder cancer risk factor, we tried to evaluate the impact of the tobacco status on these molecular abnormalities. MATERIALS AND METHODS: To delineate on the oncogenic role for Twist in human bladder cancer, we evaluated the E- and N-cadherin but also Twist expression (n = 70) by immunohistochemistry. We evaluated the prognostic value of these expressions. Moreover, we tried to correlate these protein expressions to the smoking status of the patients. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Of the 70 bladder tumors, 28 (40%) cases were positive for Twist expression, 16 (23%) cases were negative for E-cadherin expression, and 12 (17%) were positive for N-cadherin expression. When categorized into negative vs. positive expression, Twist was associated with the stage (P = 0.001), the grade (P < 0.001), the progression (P = 0.02), and the E-cadherin expression (P = 0.01). Moreover, positive Twist expression clearly predicted poorer PFS (P = 0.02). In the multivariate analysis, both positive Twist expression and loss of E-cadherin expression were independent prognostic factors for PFS (P = 0.046 and P = 0.001, respectively) and only loss of E-cadherin expression for the OS (P < 0.001). We also demonstrated that almost 60% (16/28) of patients with Twist-positive expression were current smokers at the time of the diagnosis, corroborating the fact that smoking modulates the expression of EMT markers including Twist. CONCLUSION: Positive Twist expression may be a useful prognostic marker for patients with bladder cancer. Its expression seems to be correlated to the tobacco status of the patients.
Asunto(s)
Proteínas Nucleares/biosíntesis , Fumar , Proteína 1 Relacionada con Twist/biosíntesis , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Cadherinas/biosíntesis , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica/estadística & datos numéricos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
The present investigation was conducted first to determine whether correlation exists between VEGF-A and -B mRNA levels and clinicopathological parameters and to assess their prognostic value in bladder cancer, then to clarify the expression level and biological significance of VEGF-A isoforms. Total RNA was isolated from 37 specimens of bladder cancer. Northern blot analysis revealed that VEGF-B mRNA was not expressed either in normal urothelium or in bladder cancer and detected three VEGF-A transcripts of 5.2, 4.5 and 1.7 kb in length, respectively. The VEGF-A transcript levels were greater in cancer tissues than in normal urothelium. They were significantly higher in pT2-T4 than in pTa and pT1 urothelial tumors and thus, were correlated to the pathologic stage. Contrary to the 4.5 kb transcript, elevated expression of the 5.2 and 1.7 kb transcripts was correlated with the histologic grade and the presence of carcinoma in situ. Patients with higher VEGF-A mRNA levels had a significantly shorter survival without progression compared to those with lower levels. Three VEGF-A splice variants were detected by southern blotting namely, VEGF121, 165 and 189. The expression intensity of each isoform was evaluated by quantitative real-time RT-PCR in 20 new fresh frozen recent tumors. VEGF121 and VEGF165 were expressed at the similar level. On the contrary, they were significantly more expressed than VEGF189 (p<0.05). The three isoforms were higher expressed in pT2 bladder cancers than in pTa tumors (p<0.05). There was only a significant correlation between the increased expression level of VEGF121 and 165 and the histological grade of the lesion (p<0.05). To conclude, VEGF-A mRNA level is a potential prognostic indicator of progression in bladder cancer as well as the expression level of the different VEGF-A splice variants.
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Biomarcadores de Tumor/genética , Carcinoma in Situ/genética , Carcinoma de Células Transicionales/genética , Neoplasias de la Vejiga Urinaria/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor B de Crecimiento Endotelial Vascular/genética , Empalme Alternativo , Northern Blotting , Southern Blotting , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Carcinoma in Situ/terapia , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/terapia , Línea Celular Tumoral , Supervivencia sin Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Invasividad Neoplásica , Estadificación de Neoplasias , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
INTRODUCTION: The incidence of genitourinary tumors (GUT) in renal transplant recipients (RTR) is higher than in the general population. We previously reported that CD4 lymphocytopenia is associated with a high incidence of skin cancer in RTR. Here, we investigate whether persistent CD4 T cell lymphopenia is associated with GUT occurrence. PATIENTS AND METHODS: A total of 433 patients were included in this study. All patients underwent annually systematic lymphocyte subset (CD3, CD4, CD8, CD19) determination by flow cytometry. RESULTS AND CONCLUSION: During the follow-up period, 13 patients developed GUT: 6 patients a prostate adenocarcinoma (incidence 0.06%/year) and 7 patients a renal cell carcinoma (incidence 0.07%/year). The patients with GUT were older than those without. Both groups did not differ in posttransplant duration, dialysis mode and duration, induction regimen, or acute rejection history. No persistent CD4 lymphopenia was observed in the patients with GUT. Although CD4 T cell lymphopenia is associated with skin cancer in long-term RTR, it did not appear to be a risk factor for GUT. This suggests that other factors encountered in the setting of kidney transplantation (e.g., immunosuppressive drugs, end-stage renal failure, etc.) favor the development of GUT in RTR.
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Linfocitos T CD4-Positivos , Carcinoma de Células Renales/sangre , Neoplasias Renales/sangre , Trasplante de Riñón/efectos adversos , Linfopenia/etiología , Neoplasias de la Próstata/sangre , Subgrupos de Linfocitos T , Neoplasias de la Vejiga Urinaria/sangre , Anciano , Carcinoma de Células Renales/etiología , Femenino , Humanos , Neoplasias Renales/etiología , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/etiología , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/etiologíaRESUMEN
PURPOSE: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion and spreading. In bladder cancer, loss or reduced E-cadherin expression has been associated with poor survival, and aberrant expression of N-cadherin has been associated with the invasive phenotype of bladder carcinoma cells. The purpose of this study was to investigate whether N-cadherin expression was associated with the bladder tumor progression. EXPERIMENTAL DESIGN: E-cadherin and N-cadherin expression was evaluated by immunohistochemistry in 101 tumors (pT1 and pT2-T3) and by reverse transcription-PCR analysis and immunohistochemistry in 28 other fresh frozen tumors (pT(a), pT1, and pT2-T3). RESULTS: N-cadherin expression was absent in normal urothelium, appeared in stage pT1, and increased in pT2-pT3 tumors. In most cases, increased N-cadherin expression in invasive tumors was associated with loss of E-cadherin expression. Progression-free survival and multivariate analyses revealed that N-cadherin expression is an independent prognostic marker for pT1 tumor progression. Analysis of the 28 frozen tumors by immunohistochemistry and reverse transcription-PCR showed a good correlation between protein and gene expression in pT1 and pT2-T3 tumors. Interestingly, in pT(a) tumors, N-cadherin was not immunodetected, whereas mRNA was present in 50% of cases. CONCLUSION: Regulatory defects in the N-cadherin promoter, abnormalities at the translational, or protein processing levels could explain the discrepancies between protein and mRNA expression. Most importantly, this study identified N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clearly, N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated.
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Cadherinas/genética , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Reproducibilidad de los Resultados , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Known activators of the Peroxisome Proliferator-Activated Receptor γ (PPARγ), thiazolidinediones (TZD) induce apoptosis in a variety of cancer cells through dependent and/or independent mechanisms of the receptor. We tested a panel of TZD (Rosiglitazone, Pioglitazone, Ciglitazone) to shed light on their potential therapeutic effects on three cervical cancer cell lines (HeLa, Ca Ski, C-33 A). In these cells, only ciglitazone triggered apoptosis through PPARγ-independent mechanisms and in particular via both extrinsic and intrinsic pathways in Ca Ski cells containing Human PapillomaVirus (HPV) type 16. It also inhibits cervical cancer xenograft development in nude mice. Ciglitazone kills cervical cancer cells by activating death receptor signalling pathway, caspase cascade and BH3 interacting-domain death agonist (Bid) cleavage through the up-regulation of Death Receptor 4 (DR4)/DR5 and soluble and membrane-bound TNF related apoptosis inducing ligand (TRAIL). Importantly, the drug let TRAIL-resistant Ca Ski cells to respond to TRAIL through the downregulation of cellular FLICE-Like Inhibitory Protein (c-FLIP) level. For the first time, we revealed that ciglitazone is able to decrease E6 viral oncoprotein expression known to block TRAIL pathway and this was associated with cell death. Our results highlight the capacity of ciglitazone to restore TRAIL sensitivity and to prevent E6 blocking action to induce apoptosis in cervical cancer cells.
RESUMEN
Loss of intercellular adhesion facilitates tumor invasion. To clarify the relation between altered expression of cell adhesion molecules and progression of T1 superficial bladder tumors, 101 cases (71 T1 tumors, 30 T2/T3 tumors) were examined immunohistochemically for E-cadherin and alpha-, beta-, and gamma-catenins. A highly significant correlation was observed between the decreased expression of all molecules and increased TNM stage (P < .001). Univariate analysis, performed in cases of T1 tumors, revealed association of abnormal E-cadherin with beta-catenin diminution. Survival curves were established with the Kaplan-Meier method and analyzed according to clinical and histopathologic parameters using the log-rank test. Cox multivariate analysis revealed only gamma-catenin as an independent predictor of progression-free survival in patients with stage T1 bladder urothelial tumors. The characterization of T1 tumors that will progress could lead to the identification of patients who might benefit from surgery to avoid vesical muscle invasion and, consequently, metastasis.
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Biomarcadores de Tumor/análisis , Cadherinas/biosíntesis , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Progresión de la Enfermedad , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , alfa Catenina/biosíntesis , beta Catenina/biosíntesis , gamma Catenina/biosíntesis , Anciano , Femenino , Humanos , Masculino , Neoplasias de los Músculos/metabolismo , Neoplasias de los Músculos/secundario , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Urotelio/metabolismo , gamma Catenina/análisisRESUMEN
The authors report the case of a 75-year-old patient who developed Corynebacterium urealyticum encrusted cystitis six months after open prostatectomy, complicated by vesicocutaneous fistula, which required bladder catheterization for several days. Encrustation of the bladder wall induced marked bilateral ureteropyelocaliceal dilatation without renal failure. Medical treatment by antibiotic therapy and oral acidification of the urine allowed regression of the plaques and resolution of the dilatation.
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Infecciones por Corynebacterium/tratamiento farmacológico , Cistitis/tratamiento farmacológico , Cistitis/microbiología , Anciano , Humanos , MasculinoRESUMEN
OBJECTIVE: The objective of this study was to devaluate the risk of renal cancer in patients with atypical renal cysts and to compare radiological data used to establish the Bosniak classification with clinical or histological data. MATERIAL AND METHOD: We performed a retrospective study on 37 patients managed in our establishment for atypical renal cyst between January 1995 and April 2003. The following criteria were analysed: gender, age, clinical examination and circumstances of discovery imaging findings, Bosniak classification, treatment modalities and follow-up data. These criteria were compared in two populations according to the presence or absence of associated renal cancer. RESULTS: In this series, 6 patients presented a stage II cyst. No cancer was demonstrated in this group of cysts. Ten patients presented a stage IIF cyst and 2 cancers were detected in this group (i.e. 20%). Fourteen patients presented a stage III cyst, with a cancer in 4 cases (30%) and 7 patients presented a stage IV cyst with 6 cancers (86%). CONCLUSION: The Bosniak classification is currently the reference classification fr the diagnosis of cystic diseases of the kidney. Although stages I and II (cysts with minor changes not requiring surveillance) and stages III and IV (suspicious malignant cysts which require surgical exploration) raise few diagnostic problems, stage IIF (indeterminate cyst requiring radiological surveillance) may be the source of diagnostic difficulties with a risk of missing an associated renal cancer.
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Enfermedades Renales Quísticas/clasificación , Enfermedades Renales Quísticas/patología , Neoplasias Renales/clasificación , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate the complications, the morbidity and mortality of renal transplantation in patients with a vascular prosthesis inserted either prior to or at the same time as renal transplantation. PATIENTS AND METHOD: Between January 2001 and January 2006, six renal transplantations were performed in patients with arterial vascular prostheses or requiring concomitant insertion of a vascular prosthesis during renal transplantation. The mean age was 58 years [range: 47-69 years]. In each case, we evaluated operative difficulties, complications and postoperative course (morbidity, mortality) and the renal functional result. RESULTS: The mean operating time was 230 minutes [range: 130-380 minutes] with a mean blood loss of 390 ml [175-750 ml]. Three patients required another surgical operation for femoral thrombosis, iliofemoral thrombosis and compressive haematoma. The median length of hospital stay was 21 days [range: 9-78 days]. Graft function was restored immediately in all six patients, and one case of graft loss was observed. The morbidity was higher than that usually observed after renal transplantation. With a mean follow-up of 26 months, the vascular and renal results are satisfactory. CONCLUSION: Renal transplantation in patients with a history of vascular prosthesis or requiring replacement of the vascular prosthesis at the same time as renal transplantation can be performed with satisfactory results but with an increased morbidity. The vascular treatment must be part of a multidisciplinary strategy in the context of transplantation.
Asunto(s)
Prótesis Vascular , Trasplante de Riñón , Anciano , Supervivencia de Injerto , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Vasculares/cirugíaRESUMEN
The authors report the cases of a 41-year-old woman with a large arteriovenous fistula between a branch of the renal artery and the main renal vein in the renal hilum and a peripheral pseudoaneurysm secondary to a knife wound to the kidney. These lesions were successfully treated by embolization. In the light of this case, the authors illustrate the possibility of performing more than one embolization on the same kidney and emphasize the successful embolization of a large, high-flow arteriovenous fistula.
Asunto(s)
Aneurisma Falso/terapia , Fístula Arteriovenosa/terapia , Embolización Terapéutica , Arteria Renal , Venas Renales , Adulto , Aneurisma Falso/complicaciones , Fístula Arteriovenosa/complicaciones , Fístula Arteriovenosa/patología , Femenino , HumanosRESUMEN
OBJECTIVE: To analyze results (stone-free rate [SFR]) and complications after flexible ureterorenoscopy (f-URS) for renal or lumbar ureteral lithiasis in patients with a previous ureteral stenting (US). PATIENTS AND METHODS: We conducted a single-center retrospective study, including all f-URS procedures achieved in our department, between January 2004 and December 2010, for renal or lumbar ureteral urinary lithiasis. In total, 497 procedures were performed: 316 procedures in patients with a ureteral stent placed before the surgery for renal colic, sepsis, or renal failure (group 1) and 181 procedures in patients without US (group 2). Success was defined as a complete SFR at 6-month follow-up. Surgical morbidity was defined using the Clavien-Dindo grading system. RESULTS: Groups 1 and 2 were well balanced in terms of demographic data, number, and size of stones. Ureteral location was significantly higher in group 1 (30.2% vs 16.3%, p = 0.0006). Surgery characteristics were similar in both groups. By univariate analysis, SFR tended to be slightly higher in the group with prior ureteral stenting (72% vs 63%, p = 0.05). SFR for ureteral location was also higher after previous ureteral stenting (81.5% vs 59.4%, p = 0.023). By multivariate analysis, only stone size and number were correlated with f-URS failure. Complication rate was comparable in both groups (10.7% vs 11.8%, p = 0.7). CONCLUSION: Technical aspects of the f-URS procedure were not modified by ureteral stenting. We found that f-URS in patients with ureteral stenting was not associated with a better SFR, except in case of ureteral location in univariate analysis. Ureteral stenting was not independently related to f-URS outcome by multivariate analysis.
Asunto(s)
Cálculos Renales/cirugía , Riñón/cirugía , Stents , Uréter , Cálculos Ureterales/cirugía , Ureteroscopía/métodos , Urolitiasis/complicaciones , Adulto , Anciano , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Análisis Multivariante , Cólico Renal/cirugía , Insuficiencia Renal/cirugía , Estudios Retrospectivos , Sepsis/cirugía , Resultado del TratamientoRESUMEN
The frequency of erectile dysfunction can be increased in certain populations, such as patients with renal failure in whom the incidence of erectile dysfunction is estimated to be between 50% to 70% depending on the stage of renal failure. In this population, even more than in the general population, erectile dysfunction appears to be due to multiple aetiologies, combining organic and psychological disorders. Although renal transplantation is the treatment of choice for end-stage renal failure, it appears to have very variable effects on erectile dysfunction, as it may improve erectile dysfunction in the same way as global quality of life. However, some authors have demonstrated the aggravating role of renal transplantation on quality of erection, or even de novo appearance of erectile dysfunction. Progress in the fields of dialysis and renal transplantation have considerably improved the quality of life of patients with chronic renal failure. However, this improvement of quality of life does not always concern the patient's sex life. The main causes of erectile dysfunction in haemodialysed patients are endocrine disorders, uraemic neuropathy, tissue lesions related to chronic renal failure, and drugs. These factors of erectile dysfunction are partially corrected by transplantation, but other factors can subsequently be involved, such as drugs or vascular causes. The objective of this study is therefore to conduct a review of the literature on erectile dysfunction (epidemiology, pathophysiology, treatment) in patients with end-stage renal failure (dialysis) and after renal transplantation.