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Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is expressed in most human cell types (example: Epithelial cells, fibroblasts and endothelial), it serves a key role in the control of cell survival, proliferation and motility. The abnormal expression of FAK has been associated with poor prognosis in cancer, including ovarian cancer. However, although FAK isoforms with specific molecular and functional properties have been characterized, there are a limited number of published studies that examine FAK isoforms in ovarian cancer. The aim of the present study was to analyze the expression level of FAK and its isoforms in ovarian cancer. The expression of FAK kinase and focal adhesion targeting (FAT) domains was determined with immunohistochemistry in healthy ovary, and serous and mucinous cystadenoma, borderline tumor and carcinoma samples. Additionally, the expression of FAK and its isoforms were investigated in three ovarian cancer-derived cell lines with western blotting and reverse transcription-semi-quantitative polymerase chain reaction. An increased expression of FAK kinase domain was determined in serous tumor samples and was associated with advancement of the lesion. FAK kinase domain expression was moderate-to-low in mucinous tumor samples. The expression of the FAK FAT domain in tumor samples was reduced, compared with healthy ovary samples; however, the FAT domain was localized to the cellular nucleus. Expression of alternative transcripts FAK°, FAK28,6 and FAK28 was determined in all three cell lines investigated. In conclusion, FAK kinase and FAT domains are differentially expressed among ovarian tumor types. These results indicated the presence of at least two isoforms of FAK (FAK and the putative FAK-related non-kinase) in tumor tissue, which is supported by the cells producing at least three FAK alternative transcripts. These results may support the use of FAK and its isoforms as biomarkers for ovarian cancer.
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lntroduction: The respiratory syncitial virus is one of the most common causes of mortality in children and older adults in the world. Objective: To predict the initial week of outbreaks and to establish the most relevant climate variables using naive Bayes classifiers and receiver operating characteristic curves (ROC). Materials and methods: The initial dates of the outbreaks in children less than five years old for the period 2005-2010 were obtained for Bogotá, Colombia. We selected the climatological variables using a correlation matrix and we constructed 1,020 models using different climatological variables and data from different weeks previous to the initial outbreak. In addition, we selected models using a six-year period (2005-2010), a four-year period (2005-2008), and a two-year period (2009-2010). We obtained the best predictive models and the most relevant climatological variables to predict the outbreak using naive Bayes classifiers and ROC curves. Results: The best models were those using a two-year period (2009-2010) and week 0, with 52% and 60% of effectiveness, respectively. Humidity was the most frequent variable in the best models (62%). Conclusions: We used naive Bayes classifiers to establish the best models to predict correctly the initial week of the outbreak. Our results suggest that the best models used humidity, wind speed and minimum temperature in outbreaks prediction.
Assuntos
Clima , Infecções por Vírus Respiratório Sincicial/epidemiologia , Teorema de Bayes , Colômbia/epidemiologia , Humanos , Umidade , VentoRESUMO
Introducción. El virus sincitial respiratorio es uno de los principales causantes de mortalidad de niños y adultos mayores en el mundo. Objetivo. Predecir las semanas de inicio de los brotes de infección por el virus sincitial respiratorio en Bogotá entre 2005 y 2010, utilizando variables climatológicas como variables de predicción. Materiales y métodos. Se establecieron las fechas de inicio de los brotes en niños menores de cinco años ocurridas entre 2005 y 2010, en Bogotá D.C., Colombia. Se seleccionaron las variables climatológicas utilizando una matriz de correlación y, posteriormente, se construyeron 1.020 modelos resultado de la combinación de las distintas variables climatológicas y las semanas de antelación al inicio del brote. Se seleccionaron los modelos utilizando los datos correspondientes a periodos de seis (2005-2010), cuatro (2005-2008) y dos años (2009-2010). Se determinaron los mejores modelos y las variables climatológicas más relevantes, utilizando clasificadores bayesanos ingenuos y curvas características de operación del receptor ( Receiver Operating Characteristic, ROC). Resultados. Los mejores resultados se obtuvieron con los modelos que utilizaron el periodo de dos años (2009-2010) y la semana 0, con 52 y 60 % de aciertos, respectivamente. La humedad mínima fue la variable que más apareció en los mejores modelos (62 %). Los clasificadores bayesanos ingenuos permitieron establecer cuáles eran los mejores modelos para predecir la semana de inicio del brote. Conclusiones. Los resultados sugieren que los modelos en que se utilizaron la humedad mínima, la velocidad del viento y la temperatura mínima serían los modelos de predicción más eficaces.
lntroduction: The respiratory syncitial virus is one of the most common causes of mortality in children and older adults in the world. Objective: To predict the initial week of outbreaks and to establish the most relevant climate variables using naive Bayes classifiers and receiver operating characteristic curves (ROC). Materials and methods: The initial dates of the outbreaks in children less than five years old for the period 2005-2010 were obtained for Bogotá, Colombia. We selected the climatological variables using a correlation matrix and we constructed 1,020 models using different climatological variables and data from different weeks previous to the initial outbreak. In addition, we selected models using a six-year period (2005-2010), a four-year period (2005-2008), and a two-year period (2009-2010). We obtained the best predictive models and the most relevant climatological variables to predict the outbreak using naive Bayes classifiers and ROC curves. Results: The best models were those using a two-year period (2009-2010) and week 0, with 52% and 60% of effectiveness, respectively. Humidity was the most frequent variable in the best models (62%). Conclusions: We used naive Bayes classifiers to establish the best models to predict correctly the initial week of the outbreak. Our results suggest that the best models used humidity, wind speed and minimum temperature in outbreaks prediction.
Assuntos
Vírus Sinciciais Respiratórios , Teorema de Bayes , Meteorologia , Epidemias , PrevisõesRESUMO
Maintenance of telomere length is one function of human telomerase that is crucial for the survival of cancer cells and cancer progression. Both telomeres and telomerase have been proposed as possible biomarkers of cancer risk and cancer invasiveness; however, their clinical relevance is still under discussion. In order to improve our understanding of the relationship between telomere length and telomerase activity with cancer invasiveness, we studied telomere length as well as telomerase levels, activity, and intracellular localization in breast cancer cell lines with diverse invasive phenotypes. We found an apparently paradoxical coincidence of short telomeres and enhanced telomerase activity in the most invasive breast cancer cell lines. We also observed that hTERT intracellular localization could be correlated with its level of activity. There was no association between human telomerase reverse transcriptase (hTERT) protein expression levels and invasiveness. We propose that simultaneous evaluation of these two biomarkers-telomere length and telomerase activity-could be useful for the assessment of the invasive capacity and aggressiveness of tumor cells from breast cancer patients.
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Biomarcadores Tumorais/metabolismo , Telomerase/metabolismo , Encurtamento do Telômero , Telômero/genética , Animais , Western Blotting , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Células HeLa , Humanos , Células MCF-7 , Metaloproteinases da Matriz/metabolismo , Camundongos , Microscopia de Fluorescência , Células NIH 3T3 , Invasividade Neoplásica , Fenótipo , Reação em Cadeia da Polimerase/métodos , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Breast cancer is a complex multifactorial genetic disease. Among other factors, race and, to an even greater extent, viruses are known to influence the development of this heterogeneous disease. It has been reported that MMTV-like (HMTV) gene sequences with a 90 to 98% homology to mouse mammary tumor virus are found in several populations with a prevalence range of 0 to 74%. In the Mexican population, 4.2% of patients with breast cancer exhibit the presence of HMTV (MMTV-like) sequences. The aim of this study was to evaluate the presence and current prevalence of retroviral HMTV (MMTV-like) sequences in breast cancer in Mexican women. METHODS: We used nested PCR and real-time PCR with a TaqMan probe. As a positive control, we used the C3H MMTV strain inserted into pBR322 plasmid. To confirm that we had identified the HMTV sequences, we sequenced the amplicons and compared these sequences with those of MMTV and HMTV (GenBank AF033807 and AF346816). RESULTS: A total of 12.4% of breast tumors were HMTV-positive, and 15.7% of the unaffected tissue samples from 458 patients were HMTV-positive. A total of 8.3% of the patients had both HMTV-positive tumor and adjacent tissues. The HMTV-positive samples presented 98% similarity to the reported HMTV sequence. CONCLUSIONS: These results confirm that the HMTV sequence is present in breast tumors and non-affected tissues in the Mexican population. HMTV should be considered a prominent causative agent of breast cancer.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Vírus do Tumor Mamário do Camundongo , Infecções por Retroviridae/complicações , Infecções Tumorais por Vírus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/patologia , Estudos Transversais , DNA Viral , Feminino , Produtos do Gene env/genética , Humanos , Glândulas Mamárias Humanas/virologia , Vírus do Tumor Mamário do Camundongo/classificação , Vírus do Tumor Mamário do Camundongo/genética , México/epidemiologia , Camundongos , Pessoa de Meia-Idade , Filogenia , Prevalência , Estudos Prospectivos , Infecções por Retroviridae/virologia , Infecções Tumorais por Vírus/virologiaRESUMO
En México, la microtia presenta una prevalencia de 7.37/10,000 recién nacidos, la cual es más alta que la reportada en otras poblaciones; por ejemplo, en Estados Unidos es de 2-3/10,000 recién nacidos. Se define como la malformación congénita del oído externo caracterizada por un pabellón auricular pequeño y con alteración en su forma. Se observa más frecuentemente de manera unilateral de lado derecho y en varones, y puede presentarse como defecto aislado o asociada con otras alteraciones como atresia y estenosis del conducto auditivo. Representa una de las principales causas de atención en la consulta externa del departamento de genética de instituciones de tercer nivel. Se considera como una malformación mayor con profundas repercusiones en la función auditiva, y que requiere de una atención multidisciplinaria. En una minoría de casos ha sido posible identificar una causa puramente genética o puramente ambiental, ya que en la mayoría la presentación es multifactorial. Debido a la importancia que representa esta alteración para los diferentes servicios de salud en México, es importante que se conozcan sus bases clínicas, moleculares y hereditarias.
Mexico has a prevalence of microtia of 7.37/10,000 (newborns), 3 times higher than the prevalence reported in other populations (USA 2-3/10,000). Microtia is defined as a congenital malformation of the external ear characterized by a small auricular lobe with an abnormal shape. It is more often unilateral and on the right side. Males are more frequently affected than females. It can occur as an isolated defect or can be associated with other abnormalities such as stenosis of the external auditory canal. In three of the main pediatric hospitals in Mexico, microtia is among the most important causes of attendance in the Genetics Department. Microtia-atresia must be considered as a major malformation with important repercussions in hearing function requiring multidisciplinary medical care in order to limit the disability associated and to provide genetic counseling. Its etiology is complex. Only in a minor number of cases it has been possible to identify a main genetic component (as in monogenic presentations) or a main environmental cause (as in fetal alcohol syndrome or pregestational diabetes). In most cases this malformation is multifactorial. Due to the relevance that the frequency of microtia atresia has in different health services in Mexico, it is important that all medical professionals are aware of its clinical, molecular and inherited characteristics.
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The development of new fields of study in genetics, as the -omic sciences (transcriptomics, proteomics, metabolomics), has allowed the study of the regulation and expression of genomes. Therefore, nowadays it is possible to study global alterations--in the whole genome--and their effect at the protein and metabolic levels. Importantly, this new way of studying genetics has opened new areas of knowledge, and new cellular mechanisms that regulate the functioning of biological systems have been elucidated. In the clinical field, in the last years new molecular tools have been implemented. These tools are favorable to a better classification, diagnosis and prognosis of several human diseases. Additionally, in some cases best treatments, which improve the quality of life of patients, have been established. Due to the previous assertion, it is important to review and divulge changes in the study of genetics as a result of the development of the -omic sciences, which is the aim of this review.
El desarrollo de nuevas áreas de estudio dentro de la genética, como las ciencias ómicas (transcriptómica, proteómica, metabolómica), ha permitido estudiar al genoma a diferentes niveles de regulación y expresión. Gracias a esto, actualmente se pueden estudiar las alteraciones génicas de un organismo de forma global ("genoma") y se puede identificar el efecto que tienen estas alteraciones a nivel de proteína y de la producción de metabolitos. De manera importante, esta nueva forma de estudiar la genética ha abierto nuevos campos de conocimiento y ha dilucidado nuevos mecanismos celulares que rigen el funcionamiento de los sistemas biológicos. A nivel clínico, en los últimos años se han implementado nuevas herramientas moleculares que permiten hacer una mejor clasificación, un mejor diagnóstico, así como un pronóstico más acertado de diversas enfermedades. Asimismo, en algunos casos se han establecido mejores tratamientos que favorecen la calidad de vida de los pacientes. Debido a todo lo anterior, es importante revisar y divulgar el cambio que ha tenido el estudio de la genética gracias al desarrollo de las ciencias ómicas, el cual es el objetivo de esta revisión.
Assuntos
Genômica , Medicina/métodos , HumanosRESUMO
BACKGROUND: In Mexico, breast cancer represents the first cause of cancer death in females. At the molecular level, non-coding RNAs and especially microRNAs have played an important role in the origin and development of this neoplasm In the Anglo-Saxon population, diverse genetic variants in microRNA genes and in their targets are associated with the development of this disease. In the Mexican population it is not known if these or other variants exist. Identification of these or new variants in our population is fundamental in order to have a better understanding of cancer development and to help establish a better diagnostic strategy. METHODS: DNA was isolated from mammary tumors, adjacent tissue and peripheral blood of Mexican females with or without cancer. From DNA, five microRNA genes and three of their targets were amplified and sequenced. Genetic variants associated with breast cancer in an Anglo- Saxon population have been previously identified in these sequences. RESULTS: In the samples studied we identified seven single nucleotide polymorphisms (SNPs). Two had not been previously described and were identified only in women with cancer. CONCLUSION: The new variants may be genetic predisposition factors for the development of breast cancer in our population. Further experiments are needed to determine the involvement of these variants in the development, establishment and progression of breast cancer.
Antecedentes: en México, el cáncer de mama es la primera causa de muerte por cáncer en la mujer. A nivel molecular, los RNAs no codificantes y, en particular, los microRNAs, han tomado un papel importante en el origen y crecimiento de esta neoplasia. En población anglosajona se han reportado diversas variantes genéticas en los genes que codifican los microRNAs y en sus blancos, que se asocian con esta enfermedad. En la población mexicana se desconoce la existencia de estas u otras variantes; por eso su identificación en nuestra población es decisiva para comprender mejor la patogénesis del cáncer y contribuir a establecer una mejor estrategia diagnóstica. Objetivo: buscar y analizar variantes genéticas de tipo SNPs en cinco genes que codifican microRNAs y en tres sitios blancos de estos relacionados con predisposición al cáncer de mama, de mujeres mexicanas con o sin esta neoplasia. Material y métodos: estudio retrospectivo y longitudinal en el que se aisló ADN de tumores mamarios, tejido adyacente al tumor y sangre periférica de mujeres mexicanas con o sin cáncer. A partir del ADN se amplificaron y secuenciaron cinco genes de microRNAs y tres sitios blanco de estos en los que se han reportado variantes genéticas asociadas con el cáncer de mama en población anglosajona. Resultados: en las muestras estudiadas se identificaron siete polimorfismos de un solo nucleótido (SNPs). Dos son variantes no descritas que se encontraron sólo en mujeres con cáncer. Conclusión: las nuevas variantes identificadas pueden ser factores de predisposición genética para cáncer de mama en nuestra población. Para conocer cuál es la participación de estas variantes en el desarrollo, establecimiento y progresión del cáncer de mama se necesita experimentar más.
Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , RNA Neoplásico/genética , Idoso , Neoplasias da Mama/epidemiologia , DNA Complementar/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , México/epidemiologia , MicroRNAs/ultraestrutura , Pessoa de Meia-Idade , Conformação de Ácido Nucleico , Estudos Retrospectivos , Análise de Sequência de DNARESUMO
Anti-estrogens such as tamoxifen are widely used in the clinic to treat estrogen receptor-positive breast tumors. Patients with estrogen receptor-positive breast cancer initially respond to treatment with anti-hormonal agents such as tamoxifen, but remissions are often followed by the acquisition of resistance and, ultimately, disease relapse. The development of a rationale for the effective treatment of tamoxifen-resistant breast cancer requires an understanding of the complex signal transduction mechanisms. In the present study, we explored some mechanisms associated with resistance to tamoxifen, such as pharmacologic mechanisms, loss or modification in estrogen receptor expression, alterations in co-regulatory proteins and the regulation of the different signaling pathways that participate in different cellular processes such as survival, proliferation, stress, cell cycle, inhibition of apoptosis regulated by the Bcl-2 family, autophagy, altered expression of microRNA, and signaling pathways that regulate the epithelial-mesenchymal transition in the tumor microenvironment. Delineation of the molecular mechanisms underlying the development of resistance may aid in the development of treatment strategies to enhance response and compromise resistance.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Antagonistas de Estrogênios/uso terapêutico , Tamoxifeno/uso terapêutico , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Antagonistas de Estrogênios/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologiaRESUMO
Mexico has a prevalence of microtia of 7.37/10,000 (newborns), 3 times higher than the prevalence reported in other populations (USA 2-3/10,000). Microtia is defined as a congenital malformation of the external ear characterized by a small auricular lobe with an abnormal shape. It is more often unilateral and on the right side. Males are more frequently affected than females. It can occur as an isolated defect or can be associated with other abnormalities such as stenosis of the external auditory canal. In three of the main pediatric hospitals in Mexico, microtia is among the most important causes of attendance in the Genetics Department. Microtia-atresia must be considered as a major malformation with important repercussions in hearing function requiring multidisciplinary medical care in order to limit the disability associated and to provide genetic counseling. Its etiology is complex. Only in a minor number of cases it has been possible to identify a main genetic component (as in monogenic presentations) or a main environmental cause (as in fetal alcohol syndrome or pregestational diabetes). In most cases this malformation is multifactorial. Due to the relevance that the frequency of microtia atresia has in different health services in Mexico, it is important that all medical professionals are aware of its clinical, molecular and inherited characteristics.
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We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Anormalidades Múltiplas/patologia , Adolescente , Cromossomos Humanos Par 15/genética , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Hibridização in Situ Fluorescente , FenótipoRESUMO
Apoptosis is controlled by the BCL-2 family of proteins, which can be divided into three different subclasses based on the conservation of BCL-2 homology domains. BIK is a founding member of the BH3-only pro-apoptotic protein family. BIK is predominantly localized in the endoplasmic reticulum (ER) and induces apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria. In this study, we determined that suppression of the death gene Bik promotes resistance to tamoxifen (TAM) in MCF-7 breast cancer cells. We utilized small interfering (siRNA) to specifically knockdown BIK in MCF-7 cells and studied their response to tamoxifen. The levels of cell apoptosis, the potential mitochondrial membrane (∆Ψ(m)), and the activation of total caspases were analyzed. Western blot analysis was used to determine the expression of some BCL-2 family proteins. Flow cytometry studies revealed an increase in apoptosis level in MCF-7 cells and a 2-fold increase in relative BIK messenger RNA (mRNA) expression at a concentration of 6.0 µM of TAM. BIK silencing, with a specific RNAi, blocked TAM-induced apoptosis in 45 ± 6.78% of cells. Moreover, it decreased mitochondrial membrane potential (Ψm) and total caspase activity, and exhibited low expression of pro-apoptotic proteins BAX, BAK, PUMA and a high expression of BCl-2 and MCL-1. The above suggests resistance to TAM, regulating the intrinsic pathway and indicate that BIK comprises an important factor in the process of apoptosis, which may exert an influence the ER pathway, which regulates mitochondrial integrity. Collectively, our results show that BIK is a central component of the programmed cell death of TAM-induced MCF-7 breast cancer cells. The silencing of BIK gene will be useful for future studies to establish the mechanisms of regulation of resistance to TAM.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Tamoxifeno/farmacologia , Antineoplásicos Hormonais/farmacologia , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama , Caspases/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Células MCF-7 , Potencial da Membrana Mitocondrial/genética , Proteínas de Membrana/genética , Proteínas Mitocondriais , Interferência de RNA , RNA Interferente PequenoRESUMO
Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not on children. We examined the global protein and microRNA expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF), and RT(2) miRNA PCR Array System. Proteomic studies revealed 49 proteins with changes on the expression. Interactome showed that vimentin, calreticulin, and 14-3-3 epsilon protein are hub proteins in these neoplasms. MicroRNA analyses demonstrated for the first time novel microRNAs involved in the astrocytoma biology. In conclusion, our results show that novel proteins and microRNAs with expression changes on pediatric astrocytoma could serve as biomarkers of tumor progression. BIOLOGICAL SIGNIFICANCE: Astrocytomas are tumors that progress rapidly and that invade surrounding tissues. Although some drugs have been developed to treat these neoplasms, the mortality of patients is still very high. In this study, we describe for the first time, to our knowledge, some proteins and miRNAs associated with the biology of astrocytic tumors that could be postulated as possible diagnostic or prognostic biomarkers. Altogether, our results indicate that large-scale analyses allow making a fairly accurate prediction of different cellular processes altered in astrocytic tumors.
Assuntos
Astrocitoma/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Proteoma/biossíntese , RNA Neoplásico/biossíntese , Adulto , Astrocitoma/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , ProteômicaRESUMO
BACKGROUND: Recently, a direct correlation with telomere length, proliferative potential and telomerase activity has been found in the process of aging in peripheral blood cells. The objective of the study was to evaluate telomere length and proliferative potential in peripheral blood mononuclear cells (PBMCs) after stimulation with Concanavalin A (ConA) of young adults compared with older adults. METHODS: Blood samples were obtained from 20 healthy young males (20-25 years old) (group Y) and 20 males (60-65 years old) (group O). We compared PBMC proliferation before and after stimulation with ConA. DNA was isolated from cells separated before and after culture with ConA for telomeric measurement by real-time polymerase chain reaction. RESULTS: In vitro stimulation of PBMCs from young subjects induced an increase of telomere length as well as a higher replicative capacity of cell proliferation. Samples from older adults showed higher loss of telomeric DNA (p = 0.03) and higher levels of senescent (≤6.2 kb) telomeric DNA (p = 0.02) and displayed a marked decrease of proliferation capacity. Viability cell counts and CFSE tracking in 72-h-old cell cultures indicated that group O PBMCs (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than group Y (p = 0.04). CONCLUSIONS: Our findings confirm that telomere length in older-age adults is shorter than in younger subjects. After stimulation with ConA, cells are not restored to the previous telomere length and undergo replicative senescence. This is in sharp contrast to the response observed in young adults after ConA stimulation where cells increase in telomere length and replicative capacity. The mechanisms involved in this phenomenon are not yet clear and merit further investigation.
Assuntos
Envelhecimento/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Concanavalina A/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Homeostase do Telômero/efeitos dos fármacos , Adulto , Idoso , Envelhecimento/fisiologia , Células Cultivadas , Humanos , Leucócitos Mononucleares/fisiologia , Masculino , Pessoa de Meia-Idade , Homeostase do Telômero/fisiologia , Adulto JovemRESUMO
Congenital heart defects (CHD) are the third leading cause of death in children <1 year of age in Mexico where there is a high prevalence of the 677C â T polymorphism of the MTHFR gene. This is important because the homozygous 677T/T MTHFR gene and deficiency of folic acid (FA) intake have been associated with CHD. Our objective was to analyze the possible association between the genotype 677T/T of the MTHFR gene and supplementation of FA in Mexican women with the presence of complex CHD in their children. We analyzed genotypes of 31 mothers of children with complex CHD (group I) and 62 mothers of healthy children (group II) and investigated FA supplementation during pregnancy in both study groups. Allele frequencies in group I were 41.9 % for C and 58.1 % for T and 22.6 % for genotype frequencies CC, 38.7 % for CT, and 38.7 % for TT. Allele frequencies in group II were 63.7 % for C and 36.3 % for T and 38.7 % for genotype frequencies CC, 50 % for CT and 11.3 % for TT. Both populations are in Hardy-Weinberg equilibrium. Odds ratio for having a child with a complex CHD was 5.9, p = 0.008 (95 % CI 1.67; 20.63) for the TT genotype. FA supplementation at any time during pregnancy was 90.3 and 87.9 % in groups II and I respectively (p > 0.05). Association was found between the maternal genotype (677/TT MTHFR) with the presence of complex CHD in their offspring. No differences in FA supplementation during any stage were found between groups.
Assuntos
Deficiência de Ácido Fólico/genética , Ácido Fólico/genética , Cardiopatias Congênitas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Suplementos Nutricionais , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , México , Mães , Polimorfismo Genético , Gravidez , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
PURPOSE: The purpose of this study is to determine the association between the BIK/NBK gene expression and estrogen receptor alpha expression. MATERIALS AND METHODS: We determined the association of BIK/NBK gene expression by real time quantitative reverse transcription polymerase chain reaction and estrogen receptor alpha expression by immunohistochemistry in samples of breast cancer tissue. RESULTS: We found a statistically significant correlation of BIK/NBK gene expression with the estrogen receptor alpha expression (ρ = 0.751, p = 0.004). For verify differences of BIK/NBK gene expression among ERα+ and ERα- breast cancer tissues, Mann-Whitney U test was performed, obtaining significant differences. CONCLUSIONS: BIK/NBK gene expression may have important clinical implications and provide predictive, prognostic or therapeutic marker in breast cancer patients according to the estrogen receptor alpha expression.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais , Valor Preditivo dos TestesRESUMO
OBJECTIVES: Describing the behaviour of the A H1N1/09 virus related to time, age and gender in patients having suspected infection, medical health care and laboratory diagnosis. METHOD: This was a descriptive and retrospective study of patients diagnosed as having the influenza A H1N1/09 virus between April 2009 and July 2010 by the Bogotá Public Health Laboratory. RESULTS: The first cases of A H1N1/09 virus were confirmed since week 17, 2009; positivity increased gradually, reaching maximum expression between weeks 31-36, 2009 (43 % to 53 %) and decreased during the 37th week. The age groups most affected were 6-15 years (35.4 %) and 16-25 years (28 %) (p=0.0044); the lowest percentages were found in children aged less than 1 year (8.7 %) and people older than 65 years (7.2 %) (Chi 1.98, p=0.119). The gender ratio was similar: female (18.6 %) and male (17.6 %) (Chi 1.82, p=0.1768). CONCLUSIONS: There was a significant increase in influenza A cases during 2009. However, this did not alter the behaviour of the endemic respiratory syncytial virus; on the other hand, the H1N1/09 subtype replaced the seasonal virus circulating amongst the population of Bogotá, similarly affecting men and women, mainly young adults. The highest prevalence of cases occurred between August and September 2009.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colômbia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos Retrospectivos , Estações do Ano , Adulto JovemRESUMO
Objetivo Describir el comportamiento del virus de Influenza A H1N1/09 según variables de tiempo, edad y sexo, en pacientes con sospecha de infección, atención médica y diagnóstico por laboratorio. Método Estudio descriptivo retrospectivo de pacientes diagnosticados con Influenza A H1N1/09 entre abril 2009 y julio de 2010 en el Laboratorio de salud Pública de Bogotá D.C. Resultados Se confirmaron los primeros casos de Influenza A H1N1/09 desde la semana 17 de 2009; a continuación la positividad creció gradualmente, hasta manifestar su máxima expresión entre las semanas 31 a 36 de 2009 (43 por ciento a 53 por ciento), descendiendo a partir de la semana 37. Los grupos de edad más afectados fueron los de 6 a 15 años (35,4 por ciento) y de 16 a 25 años (28 por ciento) (p=0.0044); las proporciones más bajas se hallaron en menores de 1 año (8,7 por ciento) y mayores de 65 años (7,2 por ciento) (Chi 1,98, p=0.119). La proporción por sexo fue similar: femenino (18,6 por ciento) y masculino (17,6 por ciento) (Chi 1,82, p=0.1768). Conclusiones Durante el año 2009, el virus Influenza A presentó un aumento significativo de casos; sin embargo, no modificó el comportamiento endémico del virus Sincitial Respiratorio. Por otra parte, el subtipo H1N1/09 reemplazó casi en su totalidad al virus estacional que tradicionalmente circulaba entre la población Bogotana y afectó en forma similar a hombres y mujeres, principalmente adultos jóvenes. El mayor predominio de casos se presentó entre los meses de agosto y septiembre de 2009.
Objectives Describing the behaviour of the A H1N1/09 virus related to time, age and gender in patients having suspected infection, medical health care and laboratory diagnosis. Method This was a descriptive and retrospective study of patients diagnosed as having the influenza A H1N1/09 virus between April 2009 and July 2010 by the Bogotá Public Health Laboratory. Results The first cases of A H1N1/09 virus were confirmed since week 17, 2009; positivity increased gradually, reaching maximum expression between weeks 31-36, 2009 (43 percent to 53 percent) and decreased during the 37th week. The age groups most affected were 6-15 years (35.4 percent) and 16-25 years (28 percent) (p=0.0044); the lowest percentages were found in children aged less than 1 year (8.7 percent) and people older than 65 years (7.2 percent) (Chi 1.98, p=0.119). The gender ratio was similar: female (18.6 percent) and male (17.6 percent) (Chi 1.82, p=0.1768). Conclusions There was a significant increase in influenza A cases during 2009. However, this did not alter the behaviour of the endemic respiratory syncytial virus; on the other hand, the H1N1/09 subtype replaced the seasonal virus circulating amongst the population of Bogotá, similarly affecting men and women, mainly young adults. The highest prevalence of cases occurred between August and September 2009.
Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Colômbia/epidemiologia , Vigilância da População , Prevalência , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estudos Retrospectivos , Estações do AnoRESUMO
BACKGROUND: Coronary collateral circulation is a stabilizer factor in myocardial ischemia. We attempted to establish a link between collateral circulation, C-reactive protein (CRP), and telomere shortening. PATIENTS AND METHODS: A case-control study was performed in patients with (group A) and without (group B) coronary collaterals using coronariography. The patients were males, CRP levels and telomere length in circulating leucocytes were measured; Student t test and logistic regression were used to analyze the data. RESULTS: The study included 40 patients aged 53.9 ± 7.0 years (20 per group). Group A exhibited lower CRP levels (2.76 ± 3.34 vs 4.04 ± 3.38; P = .004); whereas telomere length was shorter in group B (2.3 ± 6.9 kb vs 6.1 ± 5.9 kb; P < .0001). CONCLUSIONS: Collateral circulation was associated with telomere shortening and elevation of CRP levels.