Estado actual y perspectivas de la imagen molecular PET en México.

Positron-emission tomography (PET) is a medical diagnostic technique by means of which functional images are obtained by recording the spatio-temporal biodistribution of specific radiopharmaceuticals targeted at specific molecular objectives, which provides biochemical information at the molecular level. Early in the first decade of this 21st century, the Faculty of Medicine of the National Autonomous University of Mexico acquired the technology to implement this diagnostic technique in Mexico, thus becoming a pioneer in PET applications in the country and in Latin America. Almost two decades after its implementation in Mexico, PET has become an essential tool in medical clinics. This article describes the background, current state and perspectives of PET molecular imaging in Mexico, and the impact it has had on the management of patients with oncological, neurological and heart diseases.

La tomografía por emisión de positrones (PET) es una técnica de diagnóstico médico mediante la cual se obtienen imágenes funcionales a partir de registrar la biodistribución espacio-temporal de radiofármacos específicos dirigidos a blancos moleculares específicos, proveyendo información bioquímica a nivel molecular. A principios de la primera década de este siglo XXI, la Facultad de Medicina de la Universidad Nacional Autónoma de México implementó esta técnica de diagnóstico en México, convirtiéndose en pionera en aplicaciones PET en el país y Latinoamérica. Casi dos décadas después, la PET se ha convertido en una herramienta esencial en la clínica médica. En este artículo se describen los antecedentes, el estado actual, las perspectivas de la imagen molecular PET en México y el impacto que ha tenido en el manejo de pacientes con enfermedades oncológicas, neurológicas y cardiológicas.

Estado actual y perspectivas de la imagen molecular PET en México / Current status and perspectives of PET molecular imaging in Mexico

Resumen La tomografía por emisión de positrones (PET) es una técnica de diagnóstico médico mediante la cual se obtienen imágenes funcionales a partir de registrar la biodistribución espacio-temporal de radiofármacos específicos dirigidos a blancos moleculares específicos, proveyendo información bioquímica a nivel molecular. A principios de la primera década de este siglo XXI, la Facultad de Medicina de la Universidad Nacional Autónoma de México implementó esta técnica de diagnóstico en México, convirtiéndose en pionera en aplicaciones PET en el país y Latinoamérica. Casi dos décadas después, la PET se ha convertido en una herramienta esencial en la clínica médica. En este artículo se describen los antecedentes, el estado actual, las perspectivas de la imagen molecular PET en México y el impacto que ha tenido en el manejo de pacientes con enfermedades oncológicas, neurológicas y cardiológicas.

Abstract Positron-emission tomography (PET) is a medical diagnostic technique by means of which functional images are obtained by recording the spatio-temporal biodistribution of specific radiopharmaceuticals targeted at specific molecular objectives, which provides biochemical information at the molecular level. Early in the first decade of this 21st century, the Faculty of Medicine of the National Autonomous University of Mexico acquired the technology to implement this diagnostic technique in Mexico, thus becoming a pioneer in PET applications in the country and in Latin America. Almost two decades after its implementation in Mexico, PET has become an essential tool in medical clinics. This article describes the background, current state and perspectives of PET molecular imaging in Mexico, and the impact it has had on the management of patients with oncological, neurological and heart diseases.

La epigenética como herramienta diagnóstica y pronóstica en la estenosis pieloureteral / Epigenetics as a diagnostic and prognostic tool for pyeloureteral stenosis

Objetivo: En los últimos años, numerosos estudios se han centrado en la genética del sistema renal. Betchel et al. en 2010, demostraron como la metilación, fenómeno epigenético, estaría implicado en la perpetuación de la fibrosis. En nuestro estudio queremos demostrar si la epigenética tiene relación con la estenosis pieloureteral y en caso de ser así, si podría ser utilizada como material pronóstico y diagnóstico. Material y métodos: Se ha realizado un estudio descriptivo observacional o transversal en el que se analizó la metilación en el ADN extraído de las muestras de unión pieloureteral en pacientes pediátricos obtenidas durante la cirugía entre 1999 y 2015, resultando un total de 20 pacientes. Los datos clínicos-radiológicos se analizaron según correlación y agrupación de los mismos mediante un paquete software filogenético/estadístico denominado PHYLIP de acceso libre gratuito. Los genes seleccionados sobre los que se realizó la PCR específica de metilación (MSP) fueron: p16, RASSF1A, MGMT, Ciclina D-2, HIN-1, E-Cadherina y RASAL-1. Resultados: Los datos clínico-radiológicos analizados filogenéticamente mediante el programa PHYLIP establecieron 7 grupos de pacientes. Los resultados con respecto a la metilación mostraron una proporción considerable de metilación aberrante en la región del promotor de los genes p16 (25%), MGMT (15%), E-Cadherina (25%),HIN-1 (25%) y RASAL-1 (35%). Se analizó la asociación de los grupos clínico-radiológicos con los estados de metilación/no metilación de cada gen. Conclusiones: Se demuestra que la metilación sí tiene un papel en la fibrosis desarrollada en la estenosis pieloureteral destacando dos patrones clínicos de mal pronóstico asociados a dos clusters epigenéticos de metilación. RASAL-1, E-Cadherina, HIN-1 y p16 serían los candidatos para desarrollar estudios futuros sobre sus implicaciones pronósticas en la estenosis pieloureteral

Objective: In the last few years, numerous studies have focused on the genetics of the renal system. Betchel et al in 2010 demonstrated that methylation, as a epigenetic phenomenon, would be involved in the perpetuation of fibrosis. In our study, we want to demonstrate whether epigenetics is related to pyeloureteral stenosis and, if that is the case, if it could be used as prognostic and diagnostic biomarker. Methods: This is a descriptive observational and cross-sectional study that analyzed the methylation in DNA extracted from pyeloureteral junction samples obtained from surgery in pediatric patients in the period from 1999 to 2015, resulting in a total of 20 patients. Clinical data were analyzed using correlation tests and they were grouped with a free access software statistical phylogenetic package called PHYLIP. The selected genes for methylation-specific PCR (MSP) were the following: p16, RASSF1A, MGMT, Cyclin D-2, HIN-1, E-Cadherin and RASAL-1. Results: The clinical-radiological data analyzed phylogenetically by the PHYLIP program established 7 groups of patients. The results of methylation showed a considerable proportion of aberrant methylation in the promotor region of the genes p16 (25%), MGMT (15%), E-Cadherin (25%), HIN-1 (25%) and RASAL-1 (35%). The association of the clinical-radiological groups with methylation/non-methylation states of each gene was also analyzed. Conclusions: This study demonstrates that methylation does have a role in fibrosis developed in pyeloureteral stenosis. Two clinical patterns of poor prognosis associated with two epigenetic methylation cluster. RASAL-1, E-Cadherin, HIN-1 and p16 would be candidates for future studies on their prognostic implications in pyeloureteral stenosis

[Epigenetics as a diagnostic and prognostic tool for pyeloureteral stenosis.] / La epigenética como herramienta diagnóstica y pronóstica en la estenosis pieloureteral.

OBJECTIVE: In the last few years, numerous studies have focused on the genetics of the renal system. Betchel et al in 2010 demonstrated that methylation, as a epigenetic phenomenon, would be involved in the perpetuation of fibrosis. In our study, we want to demonstrate whether epigenetics is related to pyeloureteral stenosis and, if that is the case, if it could be used as prognostic and diagnostic biomarker. METHODS: This is a descriptive observational and cross-sectional study that analyzed the methylation in DNA extracted from pyeloureteral junction samples obtained from surgery in pediatric patients in the period from 1999 to 2015, resulting in a total of 20 patients. Clinical data were analyzed using correlation tests and they were grouped with a free access software statistical phylogenetic package called PHYLIP. The selected genes for methylation-specific PCR (MSP) were the following: p16, RASSF1A, MGMT, Cyclin D-2, HIN-1, E-Cadherin and RASAL-1. RESULTS: The clinical-radiological data analyzed phylogenetically by the PHYLIP program established 7 groups of patients. The results of methylation showed a considerable proportion of aberrant methylation in the promotor region of the genes p16 (25%), MGMT (15%), E-Cadherin (25%), HIN-1 (25%) and RASAL-1 (35%). The association of the clinical-radiological groups with methylation/non-methylation states of each gene was also analyzed. CONCLUSIONS: This study demonstrates that methylation does have a role in fibrosis developed in pyeloureteral stenosis. Two clinical patterns of poor prognosis associated with two epigenetic methylation cluster. RASAL- 1, E-Cadherin, HIN-1 and p16 would be candidates for future studies on their prognostic implications in pyeloureteral stenosis.

OBJETIVO: En los últimos años, numerosos estudios se han centrado en la genética del sistema renal. Betchel et al. en 2010, demostraron como la metilación, fenómeno epigenético, estaría implicado en la perpetuación de la fibrosis. En nuestro estudio queremos demostrar si la epigenética tiene relación con la estenosis pieloureteral y en caso de ser así, si podría ser utilizada como material pronóstico y diagnóstico. MATERIAL Y MÉTODOS: Se ha realizado un estudio descriptivo observacional o transversal en el que se analizó la metilación en el ADN extraído de las muestras de unión pieloureteral en pacientes pediátricos obtenidas durante la cirugía entre 1999 y 2015, resultando un total de 20 pacientes. Los datos clínicos-radiológicos se analizaron según correlación y agrupación de los mismos mediante un paquete software filogenético/estadístico denominado PHYLIP de acceso libre gratuito. Los genes seleccionados sobre los que se realizó la PCR específica de metilación (MSP) fueron: p16, RASSF1A, MGMT, Ciclina D-2, HIN-1, E-Cadherina y RASAL-1. RESULTADOS: Los datos clínico-radiológicos analizados filogenéticamente mediante el programa PHYLIP establecieron 7 grupos de pacientes. Los resultados con respecto a la metilación mostraron una proporción considerable de metilación aberrante en la región del promotor de los genes p16 (25%), MGMT (15%), E-Cadherina (25%),HIN-1 (25%) y RASAL-1 (35%). Se analizó la asociación de los grupos clínico-radiológicos con los estados de metilación/no metilación de cada gen. CONCLUSIONES: Se demuestra que la metilación sí tiene un papel en la fibrosis desarrollada en la estenosis pieloureteral destacando dos patrones clínicos de mal pronóstico asociados a dos clusters epigenéticos de metilación. RASAL-1, E-Cadherina, HIN-1 y p16 serían los candidatos para desarrollar estudios futuros sobre sus implicaciones pronósticas en la estenosis pieloureteral.

How clinical imaging can assess cancer biology.

Human cancers represent complex structures, which display substantial inter- and intratumor heterogeneity in their genetic expression and phenotypic features. However, cancers usually exhibit characteristic structural, physiologic, and molecular features and display specific biological capabilities named hallmarks. Many of these tumor traits are imageable through different imaging techniques. Imaging is able to spatially map key cancer features and tumor heterogeneity improving tumor diagnosis, characterization, and management. This paper aims to summarize the current and emerging applications of imaging in tumor biology assessment.

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer.

Cancer stem cells play an important role in carcinogenesis and resistance to treatment and may lead to metastasis. The isolation of circulating stem cells involves cell sorting based on the presence of cell surface markers. Many surface markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the present study, we determined the expression of different stem cell markers and their variation in expression at different stages of the treatment process. Samples of EDTA blood were collected from metastatic colorectal cancer patients, and circulating cancer stem cells were isolated for the analysis of the expression of stem cell markers using RT-PCR. These findings were correlated with the response to therapy. All statistical analyses were performed using the GraphPad Prism 5.03 software. Significant differences were found in the expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences were found in c-Kit expression. Correlation in the expression levels of most of the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a predictive value for colon cancer behavior. Evaluation of this stem cell gene expression panel may be useful for predicting the response during the process of treatment, and the relative easy access to samples facilitates this method. Moreover the correlation between CD133 and TWIST1 expression may be associated with tumor regrowth and metastatic relapse.

The role of the adenomatous polyposis coli (APC) in oral squamous cell carcinoma.

The main cause of death in oral squamous cell carcinomas (OSCC) is metastasis. Intercellular adhesion is mediated by a family of glycoproteins called cadherins and other molecules like catenins and APC (adenomatous polyposis coli) among other. The WNT (wingless-type) gene family is a group of genes, key signaling pathway for embryonic development and oncogenesis. The goal of this paper is to describe the role of the APC gene, and its derivatives, in the carcinogenicity pathway of WNT-1, identifying its role as a tumor suppressor gene in OSCC, while describing the genetic (loss of heterozygosity and mutations) and epigenetic alterations that modulate its expression and evaluate its relationship with the clinicopathological parameters of this type of tumors. As for APC, its activity as a tumor suppressor gene appears muted on a relatively frequent basis in these tumors, either by LOH, mutations or epigenetic control mechanisms, thus resulting in a low degree of agreement between the results of different studies.