RESUMO
BACKGROUND: Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence. METHODS: We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A>G (p.105 Ile>Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate these associations. RESULTS: Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P = 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) = 3.16, 95% confidence interval (95% CI) = 1.41-7.06, P = 0.005) and multivariate models (HR = 3.01, 95% CI = 1.13-8.02, P = 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P = 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR = 3.06, 95% CI = 1.20-7.80, P = 0.019). CONCLUSIONS: Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
Assuntos
Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Estudos de Casos e Controles , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Prostatectomia , Neoplasias da Próstata/cirurgia , Fatores de RiscoAssuntos
Humanos , Masculino , Pessoa de Meia-Idade , Adrenalectomia , Hipertensão , Laparoscopia , FeocromocitomaRESUMO
Introduccion: El Psat es el marcador mas usado en patologias prostaticas: 10-30 por ciento circula como PSA I y 70-90 por ciento complejado (PSAc). Se ha propuesto que el indice PSAI/PSAt podria variar entre patologias benignas y malignas. Objetivo: El objetivo de este estudio fue establecer el mejor punto de corte para PSAI/PSAt en una poblacion con sospecha clinica-analitica de neoplasia prostatica. Material y metodos: a 136 varones con sospecha clinica-analitica de neoplasia prostatica se les realizo tacto rectal (TR) dosajes sericos de PSAt y PSAI, ecografia transrectal y biopsia. Se calculo sensibilidad y especificidad para diferentes puntos de corte PSAI/PSAt usando como metodo patron el resultado de la biopsia. Resultados: Todos los pacientes presentaron TR no sospechoso: en 47 individuos menores 60 años se detecto PSAt entre 2,50-9,99 ng/ml, 85 pacientes presentaron PSAI/PSAt mayor de 25 por ciento. La especificidad dignostica del indice PSAI/PSAt mostro una disminucion progresiva a medida que se aumento el punto de corte manteniendose los niveles de sensibilidad. Conclusiones: en la poblacion estudiada el indice PSAI/PSAt con mejor especificidad diganostica de CaP fue 15 por ciento en lugar del 25 por ciento empleado previamente
Assuntos
Antígeno Prostático EspecíficoRESUMO
Introduccion: El Psat es el marcador mas usado en patologias prostaticas: 10-30 por ciento circula como PSA I y 70-90 por ciento complejado (PSAc). Se ha propuesto que el indice PSAI/PSAt podria variar entre patologias benignas y malignas. Objetivo: El objetivo de este estudio fue establecer el mejor punto de corte para PSAI/PSAt en una poblacion con sospecha clinica-analitica de neoplasia prostatica. Material y metodos: a 136 varones con sospecha clinica-analitica de neoplasia prostatica se les realizo tacto rectal (TR) dosajes sericos de PSAt y PSAI, ecografia transrectal y biopsia. Se calculo sensibilidad y especificidad para diferentes puntos de corte PSAI/PSAt usando como metodo patron el resultado de la biopsia. Resultados: Todos los pacientes presentaron TR no sospechoso: en 47 individuos menores 60 años se detecto PSAt entre 2,50-9,99 ng/ml, 85 pacientes presentaron PSAI/PSAt mayor de 25 por ciento. La especificidad dignostica del indice PSAI/PSAt mostro una disminucion progresiva a medida que se aumento el punto de corte manteniendose los niveles de sensibilidad. Conclusiones: en la poblacion estudiada el indice PSAI/PSAt con mejor especificidad diganostica de CaP fue 15 por ciento en lugar del 25 por ciento empleado previamente(AU)
Assuntos
Antígeno Prostático EspecíficoRESUMO
1. Oxidative stress (OS) is a biological entity indicated as being responsible for several pathologies, including diabetes. Diabetes can also be associated with human cirrhosis. Portal hypertension (PH), a major syndrome in cirrhosis, produces hyperdynamic splanchnic circulation and hyperaemia. The present study was designed to investigate the occurrence of OS in prehepatic PH rat livers following the induction of diabetes. 2. Five groups of rats were used: control, sham operated, chronic diabetes (induced with a single dose of streptozotocin at 60 mg/kg, i.p.), prehepatic PH and chronic diabetic plus prehepatic PH. The occurrence of OS was determined in liver homogenates by measuring hydroperoxide-initiated chemiluminescence and the activity of anti-oxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). 3. Prehepatic PH produced a significant increase in hydroperoxide-initiated chemiluminescence in the liver compared with control and sham-operated rats, whereas the liver in chronic diabetic rats showed no difference. However, chemiluminescence values decreased almost by 50% in the chronic diabetic plus prehepatic PH group. Concomitantly, the activities of the anti-oxidant enzymes in chronic diabetes, prehepatic PH and chronic diabetic plus prehepatic PH groups were decreased (P < 0.05 vs control and sham-operated groups). 4. Livers from the chronic diabetic group did not show any evidence of the occurrence of OS, whereas the prehepatic PH group showed the occurrence of OS. The association of PH and chronic diabetes resulted in a significant decrease in the occurrence of OS, which could be explained by an anti-oxidant response to an OS.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Hipertensão Portal/metabolismo , Estresse Oxidativo/fisiologia , Animais , Catalase/metabolismo , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Hipertensão Portal/complicações , Técnicas In Vitro , Fígado/enzimologia , Medições Luminescentes , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Introducción: La búsqueda de un reservorio urinario continente ortotópico de fácil realización y con una continencia satisfactoria, nos llevó a desarrollar esta variante técnica. Material y métodos: Se presenta la experiencia en 10 enfermos, estudiados en el período 1997-2000, con diagnóstico de Carcinoma Transicional Infiltrante de vejiga a los que se les realizó cistoprostatectomía radical y se confeccionó reservorio urinario con colon derecho e íleon terminal efectuando la anastomosis entre apéndice y uretra en forma término-terminal. Resultados: Las complicaciones postoperatorias fueron mínimas, incluyendo pérdida transitoria de orina peritalla vesical en un enfermo, y absceso de herida quirúrgica en otro. El volumen promedio obtenido fue de 500 cc., con una continencia efectiva principalmente diurna. El seguimiento de los pacientes no muestra progresión de la enfermedad ni alteraciones del árbol urinario superior. Conclusiones: Esta variante técnica resulta una alternativa interesante para la confección de un reservorio urinario seguro y efectivo. Creemos que con el aumento de la casuística estaremos en condiciones de demostrar los beneficios de nuestra variante técnica y compararla con otras técnicas de difusión universal.
Assuntos
Humanos , Neoplasias da Bexiga Urinária , Anastomose Cirúrgica , UretraRESUMO
Introducción: La búsqueda de un reservorio urinario continente ortotópico de fácil realización y con una continencia satisfactoria, nos llevó a desarrollar esta variante técnica. Material y métodos: Se presenta la experiencia en 10 enfermos, estudiados en el período 1997-2000, con diagnóstico de Carcinoma Transicional Infiltrante de vejiga a los que se les realizó cistoprostatectomía radical y se confeccionó reservorio urinario con colon derecho e íleon terminal efectuando la anastomosis entre apéndice y uretra en forma término-terminal. Resultados: Las complicaciones postoperatorias fueron mínimas, incluyendo pérdida transitoria de orina peritalla vesical en un enfermo, y absceso de herida quirúrgica en otro. El volumen promedio obtenido fue de 500 cc., con una continencia efectiva principalmente diurna. El seguimiento de los pacientes no muestra progresión de la enfermedad ni alteraciones del árbol urinario superior. Conclusiones: Esta variante técnica resulta una alternativa interesante para la confección de un reservorio urinario seguro y efectivo. Creemos que con el aumento de la casuística estaremos en condiciones de demostrar los beneficios de nuestra variante técnica y compararla con otras técnicas de difusión universal.(AU)
Assuntos
Humanos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/urina , Neoplasias da Bexiga Urinária/terapia , Anastomose Cirúrgica , Uretra/cirurgiaRESUMO
Prehepatic Portal Hypertension (PH) leads to morphologic changes in the rat Central Nervous System, including alterations of the blood brain barrier (BBB), and astrogliosis and angiogenesis in CA1 and CA4 hyppocampal fields. The present study investigates functional changes in portal hypertensive rats. Wistar Kyoto rats were used (240 g/bw) and allotted in two groups: GI (n = 8) portal hypertensive rats obtained through a regulated stenosis of the portal vein (Groszmann), and GII (n = 6), sham-operated rats. We have analyzed: BBB integrity with the Trypan Blue diffusion method (TB, Reynolds), protein concentration (PC) in Cerebrospinal Fluid (CSF) and plasma (Bradford method), electroencephalographic activity (EEG), cerebral edema expressed as brain water content (gravidimetric test), and behavior: Animex, righting reflex, pain reflex and Rotarod. TB was positive in GI in peripheral vascular areas in hippocampus, PC in CSF (ug/ml)(mean +/- SED) was GI: 40.6 +/- 6.8 and GII: 16.5 +/- 4.2 (p < 0.005), and the plasma levels were (mg/ml): GI: 108.8 +/- 7.6 and GII: 87.4 +/- 2 (NS). The EEG showed a higher power of the delta band in hypertensive rats (GI: 0.551 +/- 0.033 and GII: 0.342 +/- 0.031, p < 0.008), but water content was not different between GI and GII (water%/per/g/tissue) (GI: 79.21 +/- 0.2, GII: 78.95 +/- 0.18). These results, showing functional changes in the BBB and brain activity without behavioral alterations, suggest the development of a subclinic form of hepatic encephalopathy in our model of PH rats.
Assuntos
Barreira Hematoencefálica/fisiologia , Encefalopatia Hepática/fisiopatologia , Hipertensão Portal/fisiopatologia , Animais , Água Corporal , Córtex Cerebral/química , Córtex Cerebral/fisiologia , Proteínas do Líquido Cefalorraquidiano/análise , Masculino , Ratos , Ratos Endogâmicos WKYRESUMO
BACKGROUND/OBJECTIVE: Injection of bacterial lipopolysaccharide (LPS) into male rats activates genes that in turn induce many enzymes that participate in the animals' response to LPS. There is induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in many tissues. This induction could result from combination with cell surface LPS receptors that directly induce both genes, or the nitric oxide (NO) released as a result of iNOS induction could induce COX-2. METHODS: To distinguish between these two possibilities, specific inhibitors of iNOS and COX-2 activity, aminoguanidine (AG) and meloxicam (MLX), respectively, were injected either peripherally or intracerebroventricularly (i.c.v.), and their effect on NO and prostaglandin E (PGE) production induced by LPS in the medial basal hypothalamus (MBH) and anterior pituitary gland (AP) were determined. RESULTS: Peripheral injection of AG blocked iNOS-derived NO production in the AP but not in the MBH. When AG was injected i.c.v., iNOS-derived NO production in the MBH was blocked. MLX injected peripherally blocked COX-2-derived PGE(2) production in the MBH and AP, whereas AG injected peripherally or i.c.v. was ineffective. Since AG was only effective in blocking iNOS-derived NO production in the MBH when injected i.c.v., AG apparently does not effectively cross the blood brain barrier, whereas MLX injected peripherally inhibited PGE production, probably by inhibiting COX-2 activity in both the MBH and AP. AG was ineffective in preventing the increase in PGE derived from COX-2 in either the MBH or AP. CONCLUSION: LPS directly induces both enzymes, iNOS and COX-2, in the hypothalamus and AP.
Assuntos
Dinoprostona/biossíntese , Endotoxemia/complicações , Hipotálamo/enzimologia , Inflamação/enzimologia , Inflamação/etiologia , Óxido Nítrico/biossíntese , Adeno-Hipófise/enzimologia , Animais , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Guanidinas/farmacologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiopatologia , Inflamação/fisiopatologia , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Meloxicam , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Adeno-Hipófise/efeitos dos fármacos , Adeno-Hipófise/fisiopatologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Sprague-Dawley , Tiazinas/farmacologia , Tiazóis/farmacologia , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Prehepatic Portal Hypertension (PH) leads to morphologic changes in the rat Central Nervous System, including alterations of the blood brain barrier (BBB), and astrogliosis and angiogenesis in CA1 and CA4 hyppocampal fields. The present study investigates functional changes in portal hypertensive rats. Wistar Kyoto rats were used (240 g/bw) and allotted in two groups: GI (n = 8) portal hypertensive rats obtained through a regulated stenosis of the portal vein (Groszmann), and GII (n = 6), sham-operated rats. We have analyzed: BBB integrity with the Trypan Blue diffusion method (TB, Reynolds), protein concentration (PC) in Cerebrospinal Fluid (CSF) and plasma (Bradford method), electroencephalographic activity (EEG), cerebral edema expressed as brain water content (gravidimetric test), and behavior: Animex, righting reflex, pain reflex and Rotarod. TB was positive in GI in peripheral vascular areas in hippocampus, PC in CSF (ug/ml)(mean +/- SED) was GI: 40.6 +/- 6.8 and GII: 16.5 +/- 4.2 (p < 0.005), and the plasma levels were (mg/ml): GI: 108.8 +/- 7.6 and GII: 87.4 +/- 2 (NS). The EEG showed a higher power of the delta band in hypertensive rats (GI: 0.551 +/- 0.033 and GII: 0.342 +/- 0.031, p < 0.008), but water content was not different between GI and GII (water
/per/g/tissue) (GI: 79.21 +/- 0.2, GII: 78.95 +/- 0.18). These results, showing functional changes in the BBB and brain activity without behavioral alterations, suggest the development of a subclinic form of hepatic encephalopathy in our model of PH rats.