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ABSTRACT Introduction: The advances in thyroid molecular biology studies provide not only insight into thyroid diseases but accurate diagnosis of thyroid cancer. Objective: Design a tutorial on protein molecular modeling of genetic markers for thyroid cancer. Methods: The proteins were selected using the Protein Data Bank sequence and the basic local alignment search tool (BLAST) algorithm. The obtained sequences were aligned with the Clustal W multiple alignment algorithms. For the molecular modeling, three-dimensional structures were generated from this set of constraints with the SWISS-MODEL, which is a fully automated protein structure homology-modeling server, accessible via the ExPASy web server. Results: We demonstrated protein analysis, projection of the molecular structure and protein homology of the following molecular markers of thyroid cancer: receptor tyrosine kinase (RET) proto-oncogene; neurotrophic tyrosine kinase receptor 1 (NTRK1) proto-oncogene; phosphatase and tensin homolog (PTEN); tumor protein p53 (TP53) gene; phosphoinositide 3-kinase/threonine protein kinase (PI3K/AKT); catenin beta 1 (CTNNB1); paired box 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARG); rat sarcoma viral oncogene (RAS); B-raf proto-oncogene, serine/threonine kinase (BRAF); and thyroid-stimulating hormone receptor (TSHR). Conclusion: This study shows the importance of understanding the molecular structure of the markers for thyroid cancer through bioinformatics, and consequently, the development of more effective new molecules as alternative tools for thyroid cancer treatment.
RESUMO Introdução: Os avanços nos estudos de biologia molecular da tireoide não fornecem apenas uma visão sobre as doenças tireoidianas, mas um diagnóstico preciso do câncer de tireoide. Objetivo: Realizar um tutorial sobre modelagem molecular proteica dos marcadores genéticos do câncer de tireoide. Métodos: As proteínas foram selecionadas utilizando sequência do Banco de Dados de Proteínas e algoritmo basic local alignment search tool (BLAST). As sequências obtidas foram alinhadas com os algoritmos de alinhamento múltiplo Clustal W. Para a modelagem molecular, as estruturas tridimensionais foram geradas a partir deste conjunto com o SWISS-MODEL, um servidor de homologia de modelagem de estrutura proteica totalmente automatizado, acessível por meio do servidor web ExPASy. Resultados: Demonstramos a análise das proteínas, a projeção da estrutura molecular e a homologia proteica dos seguintes marcadores moleculares de câncer de tireoide: proto-oncogene receptor tyrosine kinase (RET); proto-oncogene neurotrophic tyrosine kinase receptor 1 (NTRK1); phosphatase and tensin homolog (PTEN); gene tumor protein p53 (TP53); phosphoinositide 3-kinase/threonine protein kinase (PI3K/AKT); catenina beta 1 (CTNNB1); paired box 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARG); rat sarcoma viral oncogene (RAS); B-raf proto-oncogene, serine/threonine kinase (BRAF) e thyroid-stimulating hormone receptor (TSHR). Conclusão: Este estudo mostra a importância do conhecimento da estrutura molecular dos marcadores de câncer da tireoide por meio da bioinformática e, consequentemente, o desenvolvimento de novas moléculas mais eficazes como ferramentas alternativas para o seu tratamento.
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Introducción: los carcinomas de mama representan un grupo heterogéneo de tumores, tanto en su comportamiento clínico como pronóstico. El tratamiento oncológico pre y postoperatorio en pacientes con carcinoma de mama está condicionado por el resultado histopatológico, inmunohistoquímico y la expresión de c-erbB2. La clasificación molecular del cáncer de mama ha definido grupos de riesgo y manejos diferentes. Objetivo: clasificar los carcinomas de mama según su tipo histológico y subtipos intrínsecos, estudiados en el Laboratorio de Patología y Citología (LAPACI) de Medellín en el año 2011. Materiales y métodos: estudiamos 114 pacientes con cáncer de mama diagnosticadas mediante biopsia cortante, quienes fueron evaluadas entre enero 1 y diciembre 31 de 2011. Se realizó una evaluación histopatológica e inmunohistoquímica del tumor para receptores de estrógenos, progesterona, HER2, KI-67 y con estos resultados se clasificaron los tumores en cuatro subtipos moleculares: luminal A y B, triple negativo y HER2 enriched. En la evaluación clínico-patológica se consideraron: edad, tipo histológico y grado de diferenciación. Resultados:la edad media de presentación del cáncer de mama fue de 55 años y el tipo histológico más común fue el ductal. Los carcinomas de mama más frecuentes fueron los de tipo luminal A (38,5 %), luminal B (32,4 %), triple negativos (15,8 %) y HER2 enriched (13,1 %). Los carcinomas de mama de tipo luminal mostraron ser, con mayor frecuencia, tumores bien diferenciados y con bajo índice de proliferación (Ki-67). En tanto, los carcinomas de mama de tipo triple negativo y HER2 enriched correspondían a tumores pobremente diferenciados, que expresaban un alto índice de proliferación celular. En los grupos de menor edad los tumores fueron más indiferenciados, siendo el subtipo HER2 enriched el que con mayor frecuencia afecta a mujeres pre menopáusicas (40 %) y a las menores de 34 años.s. Conclusión: los subtipos luminal A y B son los carcinomas que presentan mejor grado de diferenciación, por el contrario los subtipos triple negativo y HER2 enriched son predominantemente mal diferenciados y con altos índices de proliferación celular, a su vez son los que más afectan a las mujeres premenopáusicas, y el subtipo HER2 enriched es el que más se presenta en mujeres menores de 35 años.
Introduction: Breast carcinomas represent a heterogeneous group of tumors, both in their clinical behavior and prognosis. The pre and post cancer treatment in patients with breast carcinoma was conditioned by the results of histopathological, immunohistochemical hormone receptor and the expression of c-erbB2. The molecular classification of breast cancer defined risk groups and different treatments. Objectives: To classify breast carcinomas in intrinsic subtypes by immunohistochemical markers and analyze the histopathological features according to the degree of differentiation, age and rate of cell proliferation of different subtypes studied in the laboratory of pathology and cytology (LAPACI) of Medellín in 2011. Materials and Methods: We studied 114 patients diagnosed with breast cancer by cutting biopsy, seen between January 1 and December 31 2011 It takes a histopathological and immunohistochemical evaluation of tumor for estrogen, progesterone, HER2, Ki-67 expression and these results are classified in four intrinsic subtypes: Luminal A and B, triple negative and HER2 enriched. In the clinical-pathological evaluation were considered: age, histological type, degree of differentiation. Results: The most common breast carcinomas were luminal A (38,5%), luminal type B (32,4%), triple negative (15,8%) and HER2 enriched (13,1%). Breast carcinomas showed luminal type being more well differentiated tumors frequency and low proliferation index (Ki-67). Meanwhile, breast carcinomas triple negative and HER2 enriched corresponded to poorly differentiated tumors expressing a high rate of cell proliferation. In the younger age groups were more undifferentiated tumors, HER2 enriched subtype being the most frequently affected premenopausal women (40%) and under 34 years.. Conclusion: The mean age at diagnosis of breast cancer was 55 years, and the most common histological type was ductal; The luminal subtypes A and B are the carcinomas that have better degree of differentiation, however the triple negative and HER2 subtypes are predominantly enriched poorly differentiated, and high rates of cell proliferation in turn are most affecting women premenopausal and HER2 enriched subtype is the most commonly occurs in women under 35 years.
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Se describió la introducción de un método molecular para la identificación de los Enterovirus basado en la amplificación, secuenciación y análisis filogenético de la proteína VP1. Se demostró que este método reduce grandemente el tiempo requerido para la identificación de los Enterovirus aislados y resulta de gran utilidad en la caracterización de aislamientos difíciles de tipificar, con el empleo de los reactivos inmunológicos de rutina. Por la rapidez de ejecución de la técnica reviste vital importancia su uso durante epidemias, dada la rápida determinación del agente causal.
The introduction of a mollecular method to identify the Entoviruses based on the amplification, sequencing and phylogenetic analysis of protein VP1 was described. It was proved that this method reduces significantly the time required for the identification of the isolated Entoviruses and that it is very useful in the characterization of isolates which are difficult to typify by the routine immunoloigical reagents. As it is a very fast technqiue, its use is very important during epidemics to determine the causal agent rapidly.