RESUMO
RESUMEN Los tumores secretores de catecolaminas, feocromocitoma y paraganglioma son entidades poco frecuentes y potencialmente letales si no son diagnosticadas y tratadas a tiempo. El laboratorio cumple un rol fundamental en el diagnóstico y seguimiento de estos tumores a través de la evidencia bioquímica de un exceso de catecolaminas. Sin embargo, muchas veces suele ser dificultoso arribar a un diagnóstico temprano, debido a la baja incidencia de estos tumores y a la dificultad de hallar laboratorios con equipamiento especializado. El marcador bioquímico y las técnicas utilizadas para su medición han ido cambiando con el correr de los años. Tradicionalmente, la medición de catecolaminas en orina era la prueba bioquímica utilizada. Posteriores hallazgos de metabolitos aumentados en la orina de paciente llevaron al uso de ensayos colorimétricos para la detección de ácido vainillin mandélico y metanefrinas como marcadores diagnósticos adicionales de tumor. Las pruebas actuales para el diagnóstico bioquímico muestran una excelente precisión diagnóstica. La medición de metanefrinas libres de plasma utilizando cromatografía líquida de alta resolución con detección electroquímica o de espectrometría de masas en tándem proporciona la máxima precisión para el diagnóstico de estos tumores.
ABSTRACT Catecholamine-secreting neuroendocrine tumors called Pheochromocytoma and Paraganglioma are rare entities, but potentially lethal if diagnosis and treatment are not established early enough. Clinical Laboratory plays an important role in the diagnosis and follow-up of these tumors, through the biochemical evidence of a hyperproduction of catecholamines and its metabolites.
RESUMO
AIM AND BACKGROUND: Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in many important aspects of cell biology that are related to tumorigenesis. There are opposite evidences of the role of EGFR in renal cancer and the outcome of EGFR-targeted therapies, suggesting the complexity of EGFR signaling pathways. In vitro, osteopontin (OPN) and nuclear factor kappa B (NF-κB) are thought to be involved in specific ligand-independent EGFR activation that could have a role in resistance to EGFR mAb therapy. Aim of this study was to analyze the relationship between EGFR and OPN at the protein and mRNA level, as well as their relation to NF-κB in clear cell renal cell carcinoma (CCRCC). MATERIALS AND METHODS: Expression of EGFR, OPN, and p65 NF-κB protein was analyzed using immunohistochemistry and compared mutually in 88 CCRCC samples. Expression of EGFR and OPN mRNAs was analyzed using quantitative Real-time PCR in 22 CCRCC samples and compared mutually and with NF-κB protein expression. RESULTS: Epidermal growth factor receptor mRNA level was higher in CCRCC samples in comparison with normal renal tissue (p = 0.012) and was associated with high OPN mRNA level, and with NF-κB activation (p < 0.001 and p = 0.045, respectively). Immunohistochemical staining showed the inverse association; high EGFR protein expression was related with low OPN and NF-κB protein expression (p < 0.001 and p = 0.047, respectively). CONCLUSION: Epidermal growth factor receptor gene is upregulated in CRCC and associated with OPN gene expression and NF-kB signaling. The inverse relation between OPN and EGFR at the protein level could probably reflect dynamic changes that EGFR undergoes following activation.
Assuntos
Carcinoma de Células Renais/genética , Receptores ErbB/genética , Neoplasias Renais/genética , NF-kappa B/metabolismo , Osteopontina/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , NF-kappa B/genética , Osteopontina/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Regulação para CimaRESUMO
We studied 6123 pregnant women and their 341 newborn (NB), from Santa Fe city, by the following serological tests for chagasic infection: Direct Agglutination with and without 2-mercaptoethanol, Indirect Hemagglutination and Indirect Immunofluorescence test, and by identification of parasites by Fresh drops, Strout and/or by Xenodiagnosis. The prevalence of seropositivity found in pregnant women was of 14.62% with a 73% of migratory history. The parasitological studies yielded 9/341 incidence of transplacentary infection. Clinical examinations were made in the infected newborn (NB). They were treated with Benznidazol or Nifurtimox, and post-treatment evolution was evaluated. We registered connatal infection in twin-brothers. Brothers/sisters (siblings) of infected NB were also studied. Some of them were seropositive and the others seronegative. Results here obtained show that this way of transmission is important, and should be considered even in low endemicity areas. The parasitological assays proved to be decisive for the NB infection diagnosis (Table 1). The serological assays enabled us to follow the non-infected NB up to their negativization. A 6 month follow-up is recommended. It is impossible to define only one clinical outline because both symptomatic and asymptomatic infected NB may be found with gestational age at term and pre-term and when born with a weight above or below 2000 g. We obtained parasitological and serological negativization in all cases. The chagasic pregnant woman does not necessarily transmit the infection to all her descendents. Only 2.64% are infected. It is possible to systematize the diagnosis without extra resources beyond the usual ones.
Assuntos
Doença de Chagas/congênito , Complicações Parasitárias na Gravidez , Animais , Argentina , Doença de Chagas/diagnóstico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Nifurtimox/administração & dosagem , Nitroimidazóis/administração & dosagem , Gravidez , Prevalência , Trypanosoma cruzi/imunologiaRESUMO
We studied 6123 pregnant women and their 341 newborn (NB), from Santa Fe city, by the following serological tests for chagasic infection: Direct Agglutination with and without 2-mercaptoethanol, Indirect Hemagglutination and Indirect Immunofluorescence test, and by identification of parasites by Fresh drops, Strout and/or by Xenodiagnosis. The prevalence of seropositivity found in pregnant women was of 14.62
with a 73
of migratory history. The parasitological studies yielded 9/341 incidence of transplacentary infection. Clinical examinations were made in the infected newborn (NB). They were treated with Benznidazol or Nifurtimox, and post-treatment evolution was evaluated. We registered connatal infection in twin-brothers. Brothers/sisters (siblings) of infected NB were also studied. Some of them were seropositive and the others seronegative. Results here obtained show that this way of transmission is important, and should be considered even in low endemicity areas. The parasitological assays proved to be decisive for the NB infection diagnosis (Table 1). The serological assays enabled us to follow the non-infected NB up to their negativization. A 6 month follow-up is recommended. It is impossible to define only one clinical outline because both symptomatic and asymptomatic infected NB may be found with gestational age at term and pre-term and when born with a weight above or below 2000 g. We obtained parasitological and serological negativization in all cases. The chagasic pregnant woman does not necessarily transmit the infection to all her descendents. Only 2.64
are infected. It is possible to systematize the diagnosis without extra resources beyond the usual ones.
RESUMO
Distintos autores postularon una faccion antigenica especifica para el T. cruzi, que aparentemente fue encontrada en la superficie celular y membrana flagelar del T. cruzi.Nosotros hemos querido semicuantificar esta faccion, puesta de manifiesto por inmunoelectroforesis (arco 5) y relacionarla con nuestro patron serologico. Las distintas reacciones que lo comprenden, utilizan distintas fracciones antigermicas y tienen distintos principios biologicos. De esta manera, parecerian existir una asociacion entre la cantidad de arco 5 y titulos altos en los sueros por reaccion de aglutinacion directa. No sucedio lo mismo con inmunofluorescencia indirecta, ni en hemoaglutinacion pasiva. El estudio permitio observar distintos sistemas antigeno-anticuerpo cuando se enfrentan sueros de infectados chagasicos y extractos solubles de T. cruzi. Estos aparecen cualitativa y cuantitativamente en forma diferente en las placas de inmunoprecipitacion en los estados cronicos e agudos de la infeccion. En sueros de infectados en que el arco 5 no se observa, se postula que podrian existir otros sistemas antigeno-anticuerpos especificos para el T. cruzi. Se hace una evaluacion de la tecnica como posible metodologia diagnostica y su aplicacion mas importante
Assuntos
Antígenos , Trypanosoma cruziRESUMO
Distintos autores postularon una faccion antigenica especifica para el T. cruzi, que aparentemente fue encontrada en la superficie celular y membrana flagelar del T. cruzi.Nosotros hemos querido semicuantificar esta faccion, puesta de manifiesto por inmunoelectroforesis (arco 5) y relacionarla con nuestro patron serologico. Las distintas reacciones que lo comprenden, utilizan distintas fracciones antigermicas y tienen distintos principios biologicos. De esta manera, parecerian existir una asociacion entre la cantidad de arco 5 y titulos altos en los sueros por reaccion de aglutinacion directa. No sucedio lo mismo con inmunofluorescencia indirecta, ni en hemoaglutinacion pasiva. El estudio permitio observar distintos sistemas antigeno-anticuerpo cuando se enfrentan sueros de infectados chagasicos y extractos solubles de T. cruzi. Estos aparecen cualitativa y cuantitativamente en forma diferente en las placas de inmunoprecipitacion en los estados cronicos e agudos de la infeccion. En sueros de infectados en que el arco 5 no se observa, se postula que podrian existir otros sistemas antigeno-anticuerpos especificos para el T. cruzi. Se hace una evaluacion de la tecnica como posible metodologia diagnostica y su aplicacion mas importante