Low-Dose Aspirin Has Antiproliferative and Apoptosis Effects in HPV16 Tumor Cells and Delays Tumor Development and Growth in an Experimental Model.

OBJECTIVES: The purpose of this study was to investigate the effect of aspirin on epithelial HPV16-transformed cells and its antitumor effects, in an experimental HPV16-positive tumor model. DESIGN: The design of the study is experimental (in vitro and in vivo). PARTICIPANTS/MATERIALS, SETTING, AND METHODS: SiHa and BMK-16/myc cells were treated with aspirin and cell proliferation was determined by MTT; Caspase-Glo 3/7 Assay was used to determine apoptosis. The tumor-bearing mice group was treated with 50 mg/gr/day of aspirin (orally) during 30 days and the antitumor effect was determined. RESULTS: Here, we provide evidence that aspirin has a negative effect on proliferation and induces apoptosis in the human (SiHa) and murine (BMK-16/myc) HPV16 cells. Furthermore, aspirin showed inhibition of tumor growth, and in mice treated with aspirin prior to implantation of tumor cells, the tumor growth was delayed. Also, the effect of aspirin increased survival in tumor-bearing mice and in mice pre-treated with aspirin. LIMITATIONS: It is necessary to carry out in vitro and in vivo studies of the molecular mechanisms involved in the effects of aspirin on tumor cells. CONCLUSION: Aspirin showed antiproliferative effects in tumor cells and inhibited tumor progression and could be effective as a chemopreventive agent. Thus, aspirin deserves further exploration for the treatment of cervical cancer and other neoplasms.

Microarray data analysis for differential expression: a tutorial.

DNA microarray is a technology that simultaneously evaluates quantitative measurements for the expression of thousands of genes. DNA microarrays have been used to assess gene expression between groups of cells of different organs or different populations. In order to understand the role and function of the genes, one needs the complete information about their mRNA transcripts and proteins. Unfortunately, exploring the protein functions is very difficult, due to their unique 3-dimentional complicated structure. To overcome this difficulty, one may concentrate on the mRNA molecules produced by the gene expression. In this paper, we describe some of the methods for preprocessing data for gene expression and for pairwise comparison from genomic experiments. Previous studies to assess the efficiency of different methods for pairwise comparisons have found little agreement in the lists of significant genes. Finally, we describe the procedures to control false discovery rates, sample size approach for these experiments, and available software for microarray data analysis. This paper is written for those professionals who are new in microarray data analysis for differential expression and want to have an overview of the specific steps or the different approaches for this sort of analysis.

Correlation trends for bone mineral density in Mexican women: evidence of familiar predisposition.

OBJECTIVE: Genetic factors determine bone mineral density (BMD) and peak bone density between 20 and 30 years of age, as well as bone mineral loss after menopause. BMD is a predictor of fractures due to osteoporosis and the impact of genetic factors on osteoporosis. The variation in BMD for each individual is determined by an underlying genetic structure, common genetic effects, particularly with respect to compact bones as compared to those that are primarily trabecular. This article presents the correlation of BMD by anatomical site among different samples of Mexican grandmothers, mothers and granddaughters of mixed race. MATERIAL AND METHODS: The present analysis was performed of healthy employees and their healthy relatives from three different health and academic institutions: the Instituto Mexicano del Seguro Social and the Instituto Nacional de Salud Pública, both located in Cuernavaca, Morelos, as well as the Universidad Autónoma del Estado de México. We selected family-related female participants in order to obtain pairs of mothers and daughters and, whenever possible, grandmother-mother-daughter groups. We were able to match 591 mother-daughter pairs for analysis. Additionally, we were able to include grandmothers to create grandmother-mother-daughter triads for further analysis. Bone density measurements were performed of the non-dominant proximal femur, the lumbar spine (L1-L4) and the whole body using a dual X-ray absorptiometry (DXA) Lunar DPX NT instrument. RESULTS: This study included 591 granddaughters, 591 mothers and 69 grandmothers; mean ages were 20, 47 and 72 years old, respectively. A close relationship existed with respect to body mass index (BMI) between mothers and grandmothers (27.9 vs. 27.3). The largest proportion of body fat mass was observed in the group of mothers (28.5%), but was also high in grandmothers (25.7%) and granddaughters (21.1%). The percentage of lean body mass was similar among the three family groups. The correlation of BMD between mothers and grandmothers was greatest for subtotal BMD (0.44) and was very high for the hips (0.39). Using predictive models for hip BMD among grandmothers, mothers and grandchildren, we observed that hip BMD of grandmothers is a predictor of BMD in mothers, with a beta of 0.46 (p 0.001, CI95% 0.19-0.73); (R(2): 0.41). A predictor of BMD of the lumbar spine in grandchildren is BMD of the lumbar spine in mothers (beta 0.30 CI95% 0.07-0.53). CONCLUSIONS: The results obtained in this study suggest that daughters whose mothers have a low BMD for their age will tend to develop the same condition. This indicates the importance of monitoring for girls and adolescent females whose mothers have problems related to osteopenia or osteoporosis. It will therefore be necessary to conduct studies to identify the most significant genes and specific anatomical sites among our population for the purpose of establishing the polymorphic variants for high-risk in the Mexican population.

[An overview in genomic medicine and public health]. / Medicina genómica aplicada a la salud pública.

Genomics, as a scientific discipline responsible for genome maps, sequencing and functional analysis of genomes, allows for continually expanding knowledge of the structure and function of genomes. The influence of genomics on medicine generates a new perspective for how we perceive health and disease, knowing the influence of genetic variations on susceptibility to disease. In the area of public health, genetic epidemiology translates genetic knowledge into individual and public actions, evaluating the effect of the distribution of genetic determinants and their interaction with environmental factors involved in the etiology of human diseases. In addition, genomic medicine suggests new diagnostic systems, genetic associations and nutritional disorders, specific responses to diverse drugs, and the design of new drugs for susceptible groups. And yet, the greatest advances in genomic medicine in the field of health are forthcoming.

Correlation trends for bone mineral density in Mexican women: evidence of familiar predisposition: [review] / Tendencias de correlación para la densidad mineral ósea en mujeres mexicanas: pruebas de predisposición familiar: [revisión]

OBJECTIVE: Genetic factors determine bone mineral density (BMD) and peak bone density between 20 and 30 years of age, as well as bone mineral loss after menopause. BMD is a predictor of fractures due to osteoporosis and the impact of genetic factors on osteoporosis. The variation in BMD for each individual is determined by an underlying genetic structure, common genetic effects, particularly with respect to compact bones as compared to those that are primarily trabecular. This article presents the correlation of BMD by anatomical site among different samples of Mexican grandmothers, mothers and granddaughters of mixed race. MATERIAL AND METHODS: The present analysis was performed of healthy employees and their healthy relatives from three different health and academic institutions: the Instituto Mexicano del Seguro Social and the Instituto Nacional de Salud Pública, both located in Cuernavaca, Morelos, as well as the Universidad Autónoma del Estado de México. We selected family-related female participants in order to obtain pairs of mothers and daughters and, whenever possible, grandmother-mother-daughter groups. We were able to match 591 mother-daughter pairs for analysis. Additionally, we were able to include grandmothers to create grandmother-mother-daughter triads for further analysis. Bone density measurements were performed of the non-dominant proximal femur, the lumbar spine (L1-L4) and the whole body using a dual X-ray absorptiometry (DXA) Lunar DPX NT instrument. RESULTS: This study included 591 granddaughters, 591 mothers and 69 grandmothers; mean ages were 20, 47 and 72 years old, respectively. A close relationship existed with respect to body mass index (BMI) between mothers and grandmothers (27.9 vs. 27.3). The largest proportion of body fat mass was observed in the group of mothers (28.5 percent), but was also high in grandmothers (25.7 percent) and granddaughters (21.1 percent). The percentage of lean body mass was similar...

OBJETIVO: Factores genéticos determinan la densidad mineral ósea (DMO) y el pico máximo de masa ósea entre los 20 y 30 años de edad, así como la pérdida de densidad mineral ósea después de la menopausia. La DMO es un predictor de fracturas debido a osteoporosis y el impacto de factores genéticos sobre esta. La variación en DMO para cada individuo es determinada genéticamente, en particular en lo que concierne a huesos compactos en comparación con aquellos que son principalmente trabeculares. Este artículo presenta la correlación de DMO por sitio anatómico entre abuelas, madres y nietas mexicanas. MATERIAL Y MÉTODOS: El presente análisis fue realizado en empleados sanos y sus familiares sanos de tres diferentes instituciones de salud e instituciones académicas: el Instituto Mexicano del Seguro Social, Instituto Nacional de Salud Pública, ambos localizados en Cuernavaca, Morelos, así como la Universidad Autónoma del Estado de México. Seleccionamos a participantes femeninos relacionados para obtener los pares de madres e hijas y siempre que fuera posible a las abuelas. Nos fue posible recolectar 591 pares de madre-hija para el análisis. Además de incluir a abuelas para crear tríadas abuela-madre-hija para el análisis. Las medidas de densidad ósea fueron realizadas del fémur proximal no dominante, espina lumbar (L1-L4) y DMO total mediante el instrumento DPX DXA Lunar NT. RESULTADOS: Este estudio incluyó a 591 nietas, 591 madres y 69 abuelas; la edad promedio fue 20, 47 y 72 años. Hay una relalción entre el índice de masa corporal (BMI) entre madres y abuelas de 27.9 contra 27.3. La proporción mayor de masa grasa de cuerpo fue observada en el grupo de madres (el 28.5 por ciento), pero también se observó alto en abuelas (el 25.7 por ciento) y nietas (el 21.1 por ciento). El porcentaje de masa magra fue similar entre los tres grupos. La correlación mayor de DMO entre madres y abuelas fue para el DMO subtotal (0.44), y para caderas (0.39)...

Medicina genómica aplicada a la salud pública / An overview in genomic medicine and public health

La genómica, visualizada como una disciplina científica encargada del mapeo, secuenciación y análisis de los genomas, ha facilitado la identificación y comprensión de las formas de organización y función de los genes de los organismos, lo cual ha generado un amplio conocimiento de la estructura y la función de los genomas. La influencia de la genómica en la medicina ha creado una nueva visión acerca de la forma de percibir los episodios patológicos y fisiológicos, tras conocer la influencia de las variaciones genéticas sobre la susceptibilidad a la enfermedad. En la salud pública, mediante la epidemiología genética, el conocimiento genético ha promovido acciones individuales y poblacionales para evaluar el efecto de la distribución de los determinantes genéticos y su interacción con factores ambientales en la etiología de las enfermedades humanas. De modo adicional, la medicina genómica propone nuevos sistemas de diagnóstico, relaciones genéticas y alteraciones alimenticias, respuesta específica a diversos medicamentos y diseño de nuevos fármacos para grupos susceptibles. Sin embargo, los grandes avances de la medicina genómica en el campo de la salud aún son sólo promisorios.

Genomics, as a scientific discipline responsible for genome maps, sequencing and functional analysis of genomes, allows for continually expanding knowledge of the structure and function of genomes. The influence of genomics on medicine generates a new perspective for how we perceive health and disease, knowing the influence of genetic variations on susceptibility to disease. In the area of public health, genetic epidemiology translates genetic knowledge into individual and public actions, evaluating the effect of the distribution of genetic determinants and their interaction with environmental factors involved in the etiology of human diseases. In addition, genomic medicine suggests new diagnostic systems, genetic associations and nutritional disorders, specific responses to diverse drugs, and the design of new drugs for susceptible groups. And yet, the greatest advances in genomic medicine in the field of health are forthcoming.

Correlation between IL-10 gene expression and HPV infection in cervical cancer: a mechanism for immune response escape.

The present study was performed to determine IL-10 expression in cervical tissues in Mexican women according to the severity of the malignity and its association with HPV infection. IL-10 expression showed a clear tendency to increase during the different cervical cancer stages: 37% in LGSIL; 62% in HGSIL; and 84% in cancer. However, all the patients that expressed IL-10 were HPV positives; we found an association with HPV 16. These results suggest a clear relationship between IL-10, HPV and the stage of cervical cancer disease; this event could contribute to the immunosuppressive micro-environment in the tumor site.

A tutorial in genetic epidemiology and some considerations in statistical modeling.

A new door has been opened to health professionals since the completion of the map of the human genome was announced in 2003, coinciding with the 50th anniversary of the discovery of the DNA helical structure by Watson and Crick in 1953. The continuous updating of the technology has enabled scientists to simultaneously analyze thousands of variables for genome analysis. These advances have created new opportunities to locate genes, to assess the gene-gene relationship, to measure the gene-environment interaction, to describe gene products, and to evaluate the gene-disease relationship. In epidemiology, new strategies have been developed to determine cause-effect relationship in case-control studies and cohort studies. With the information provided by the Human Genome Project, new epidemiological designs and new statistical methodology have been developed. The addition of molecular biology to traditional epidemiological approaches has given birth to a new discipline known as genetic epidemiology. The objective of this paper is to provide an introduction to concepts needed for assessing the association between genes and specific diseases in population based studies. Firstly, a description of the genetic concepts is presented as a framework for the epidemiological designs and the statistical procedures that have been utilized in genetic epidemiology. Then, a description of the different designs in genetic epidemiology is presented with the most recent publications. Finally, some considerations in the statistical analysis for genetic epidemiology are discussed.