RESUMO
Breast cancer is a public health problem in Mexico and the world, being the first cause of cancer death in women. Even though scientific advances have allowed the identification of several risk factors, the use of screening and detection techniques, as well as the therapeutic approach, since breast cancer is a heterogeneous entity, it is necessary to carry out studies that increase the knowledge about its epidemiological, clinical, histopathological and molecular characteristics that allow improving the strategies of prevention, diagnosis, treatment and reduction of complications in order to improve the quality of life and the survival of patients.
El cáncer de mama es un problema de salud pública en México y en el mundo, pues se trata de la primera causa de muerte por cáncer en las mujeres. Aun cuando los avances científicos han permitido la identificación de diversos factores de riesgo, el uso de técnicas de tamizaje y detección, así como el abordaje terapéutico, como el cáncer de mama es una entidad heterogénea, es necesaria la realización de estudios que incrementen el conocimiento sobre sus características epidemiológicas, clínicas, histopatológicas y moleculares, los cuales permitan mejorar las estrategias de prevención, diagnóstico, tratamiento y reducción de complicaciones con la finalidad de mejorar la calidad de vida y la supervivencia de las pacientes.
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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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Human islet amyloid peptide (hIAPP1-37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1-37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1-37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1-37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1-37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1-37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A-F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.
Assuntos
Amiloide/química , Diabetes Mellitus/tratamento farmacológico , Descoberta de Drogas , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Terapia de Alvo Molecular , Animais , Sobrevivência Celular/efeitos dos fármacos , Cerebelo/patologia , Curcumina/química , Curcumina/uso terapêutico , Diabetes Mellitus/patologia , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/toxicidade , Polipeptídeo Amiloide das Ilhotas Pancreáticas/ultraestrutura , Cinética , Camundongos , Simulação de Acoplamento Molecular , Agregados Proteicos , Dobramento de Proteína , Multimerização Proteica , Ratos WistarRESUMO
The Instituto Mexicano del Seguro Social (IMSS) through the Coordinación de Investigación en Salud (Health Research Council) has promoted a strong link between the generation of scientific knowledge and the clinical care through the program Redes Institucionales de Investigación (Institutional Research Network Program), whose main aim is to promote and generate collaborative research between clinical, basic, epidemiologic, educational, economic and health services researchers, seeking direct benefits for patients, as well as to generate a positive impact on institutional processes. All of these research lines have focused on high-priority health issues in Mexico. The IMSS internal structure, as well as the sufficient health services coverage, allows the integration of researchers at the three levels of health care into these networks. A few years after their creation, these networks have already generated significant results, and these are currently applied in the institutional regulations in diseases that represent a high burden to health care. Two examples are the National Health Care Program for Patients with Acute Myocardial Infarction "Código Infarto", and the Early Detection Program on Chronic Kidney Disease; another result is the generation of multiple scientific publications, and the promotion of training of human resources in research from the same members of our Research Networks. There is no doubt that the Coordinación de Investigación en Salud advances steadily implementing the translational research, which will keep being fruitful to the benefit of our patients, and of our own institution.
El Instituto Mexicano del Seguro Social (IMSS), a través de la Coordinación de Investigación en Salud, ha promovido el vínculo entre la generación de conocimiento científico y la actividad asistencial mediante el programa de Redes Institucionales de Investigación, cuyo objetivo principal es la promoción y generación de trabajo de investigación colaborativo entre investigadores del área clínica, básica, epidemiológica, educativa y en economía y sistemas de salud, buscando siempre obtener productos que tengan aplicación directa sobre los pacientes y generen un impacto positivo en los procesos institucionales. Todas las líneas de investigación se enfocan en los temas prioritarios de salud de México. La estructura interna del IMSS y la vasta cobertura de servicios que ofrece permiten incluir en estas redes a personal de los tres niveles de atención médica. A pocos años de su creación, estas redes han generado importantes resultados que se aplican en la normativa institucional en enfermedades con alta carga asistencial y económica; por ejemplo, el programa "Código Infarto" y el Programa de Detección Temprana de Enfermedad Renal Crónica; otro resultado son las múltiples publicaciones científicas y la promoción de la formación de recursos humanos en investigación de los mismos integrantes de nuestras redes de investigación. Sin duda, la Coordinación de Investigación en Salud avanza a grandes pasos en la implementación cada vez más sólida de la investigación traslacional, que seguirá dando frutos en beneficio de nuestros pacientes y de la propia institución.
Assuntos
Academias e Institutos/organização & administração , Pesquisa Biomédica/organização & administração , Colaboração Intersetorial , Programas Nacionais de Saúde/organização & administração , Humanos , México , Previdência Social/organização & administraçãoRESUMO
Expression changes for long non-coding RNAs (lncRNAs) have been identified in adult glioblastoma multiforme (GBM) and in a mixture of adult and pediatric astrocytoma. Since adult and pediatric astrocytomas are molecularly different, the mixture of both could mask specific features in each. We determined the global expression patterns of lncRNAs and messenger RNA (mRNAs) in pediatric astrocytoma of different histological grades. Transcript expression changes were determined with an HTA 2.0 array. lncRNA interactions with microRNAs and mRNAs were predicted by using an algorithm and the LncTar tool, respectively. Interactomes were constructed with the HIPPIE database and visualized with the Cytoscape platform. The array showed expression changes in 156 and 207 lncRNAs in tumors (versus the control) and in pediatric GBM (versus low-grade astrocytoma), respectively. Predictions identified lncRNAs that have putative microRNA binding sites, which might suggest that they function as sponges in these tumors. Also, lncRNAs were shown to interact with many mRNAs, such as Pleckstrin homology-like domain, family A, member 1 (PHLDA1) and sulfatase 2 (SULF2). For example, qPCR found long intergenic non-coding RNA regulator of reprogramming (linc-RoR) expression levels upregulated in pediatric GBM when they were compared with control tissues or with low-grade tumors. Meanwhile, PHLDA1 and ELAV-like RNA binding protein 1 (ELAV1) showed expression changes in tumors relative to the control. Our data showed many lncRNAs with expression changes in pediatric astrocytoma, which might be involved in the regulation of different signaling pathways.
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Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Transdução de Sinais/fisiologia , Adolescente , Astrocitoma/genética , Neoplasias Encefálicas/genética , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND AND AIMS: In April 2009, a new strain of influenza A(H1N1) was identified in Mexico and in the U.S. In June 2009, WHO declared this a pandemic. Health care workers constituted a risk group for their close contact with infected individuals. The aim was to estimate seropositivity for A(H1N1)pdm09 in health staff at the Instituto Mexicano del Seguro Social. METHODS: A two-stage cross-sectional study, before and after vaccination in the same workers, was performed on a random sample of health-care workers. A socio-occupational questionnaire was applied and serum antibodies against influenza A(H1N1)pdm09 were determined through neutralization of retroviral pseudotypes; two logistic regression models for both were constructed. RESULTS: The average (median/mean) age of 1378 participants from 13 work centers was 41.7 years and 68.7% (947) were women. Seroprevalence for the first stage was 26.5% (365) (7.4-43%) vs. 20.8% (11) in a control group from the blood bank; for the second stage, the vaccinated group was 33% (215) (18.2-47%) and 27% (196) (11.6-50%) for the unvaccinated group. In regression models, seropositivity was associated with occupational exposure to suspected influenza infected patients, being physicians, and being vaccinated. CONCLUSIONS: Seropositivity against pandemic virus is similar to what was reported, both for vaccinated (2.8-40.9%) and unvaccinated (18.8-64.7%). Low seroprevalence in the vaccinated group indicates that between 67% and 73% were susceptible to infection. Given the relatively low vaccine-induced seropositivity, it is imperative to increase, hygiene and safety for health staff and at-risk populations, and strengthen epidemiological surveillance.
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Anticorpos Antivirais/sangue , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Adulto , Idoso , Bancos de Sangue , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Modelos Logísticos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Exposição Ocupacional , Médicos , Estudos Soroepidemiológicos , Inquéritos e Questionários , Vacinação , Adulto JovemRESUMO
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.
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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
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.
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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
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: Medical research is a fundamental tool to achieve the advancement of science, through the improvement of strategies aimed to protect, promote and restore an individual's and society's health. Three characteristics are required to obtain approval of the research proposal: scientific relevance, technical quality and the accomplishment of ethical issues. OBJECTIVES: The present review aimed at the determination of the specific criteria to perform a critical review of research proposals. METHODS: A research was carried out in the PubMed, Medline, Ovid and Google Scholar databases, using the terms: peer review, research proposals, review and protocols, and reviewers. A total of 3546 related articles were reviewed, without finding a guide to critically assess research proposals. The guides to assess research articles consider that the quality criteria of the study should have been present since the study's conception; many of the issues described to review articles are incorporated in the review of the research proposals. RESULTS: The specific criteria were integrated to allow the reviewer to critically assess research proposals of different areas with scientific basis. CONCLUSIONS: The reviewer of research proposals should be considered as a professional that contributes to the promotion of knowledge advancement through his/her comments, which allow researchers to improve the quality of research proposals.
Antecedentes: la investigación médica es una herramienta fundamental para lograr el avance de la ciencia al mejorar las acciones encaminadas a proteger, promover y restaurar la salud del individuo y de la sociedad en general. Las tres características imprescindibles para que un protocolo de investigación sea autorizado son: relevancia científica, calidad técnica y el cumplimiento de los aspectos éticos. Material y métodos: estudio retrospectivo efectuado con base en la búsqueda específica en Pubmed, Medline, Ovid y Google Scholar con los términos: peer review, research proposals, review and protocols and reviewers. Debido a que no se identificó ningún artículo que refiriera específicamente los criterios para evaluar protocolos de investigación clínica, se hizo un consenso entre los vocales de la Comisión Nacional de Investigación Científica del Instituto Mexicano del Seguro Social, que está integrada por investigadores titulares de la institución, todos pertenecientes al Sistema Nacional de Investigadores. Se discutieron los criterios que debieran componer una revisión adecuada y cuáles debieran ser los rubros que deben incluirse en el análisis. Resultados: se integraron los criterios específicos que le permitirán al revisor de un protocolo de investigación realizar una crítica con bases metodológicas aceptadas por un consenso de investigadores. Conclusiones: un revisor debe ser considerado como un promotor del avance del conocimiento científico que, mediante sus comentarios y su dictamen, permite que los investigadores incrementen la calidad de sus protocolos de investigación.
Assuntos
Pesquisa Biomédica/normas , Projetos de Pesquisa/normas , Comitês Consultivos , Estudos Epidemiológicos , Humanos , Revisão da Pesquisa por Pares , Estudos Retrospectivos , Redação/normasRESUMO
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
BACKGROUND: The C allele of c.-94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). AIM: We evaluated whether the c.-94C>G polymorphism can be a risk factor for HCM in Mexican patients. METHODS: The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. RESULTS: The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. CONCLUSIONS: The C allele of the c.-94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients.
Assuntos
Cardiomiopatia Hipertrófica/genética , Predisposição Genética para Doença , Sarcoglicanas/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Mutação , Fatores de RiscoRESUMO
Cancer is one of the principal problems in health that affect the Mexican population and beneficiaries of the Instituto Mexicano del Seguro Social. Thus in order to understand better these diseases, to utilize better our resources, and to offer a comprehensive medical care, it is necessary to establish a population-based registries within the context of a national program cancer registry, with the objective of having quality information: completeness, validated and with timeliness.
Assuntos
Neoplasias , Sistema de Registros , Criança , Humanos , MéxicoRESUMO
OBJECTIVE: The goals of this population genetics study were to describe mtDNA haplogroups and ABO and Rh blood group systems of 3 Native Mexican populations, to determine their genetic variability, and to compare their haplogroups with those of 13 Native Mexican populations previously reported. MATERIAL AND METHODS: The three communities under analysis were a Tepehua-speaking community from Huehuetla (Hidalgo state), an Otomi-speaking community from San Antonio el Grande (Hidalgo state), and a Zapotec-speaking community from Juchitán (Oaxaca state). Every subject studied in each community had four grandparents who were born in the same community and spoke the same language. The four Amerindian mtDNA haplogroups (A, B, C and D) were studied by restriction analysis and gel electrophoresis. RESULTS: Regarding the blood groups, the O group was the most frequent in the three populations (97.2, 94.7, and 86.2%, respectively), as well as the Rh+ group (100, 100, 84%). The three populations analyzed were in Hardy-Weinberg equilibrium. In respect to the mtDNA haplogroups, A, B, C and D, their percentage was 33.3, 36.1, 13.9 and 5.6 % in Huehuetla; 39.5, 13.2, 39.5 and 2.6 % in San Antonio el Grande, and 55.3, 21.0, 7.9 and 5.2 % in Juchitán. Between 5 and 11% of the haplogroups were of non-Amerindian origin, probably due to admixture with Caucasian and African populations, as has been reported in the past. No statistically-significant differences were found among the three populations studied or between them and 13 previously reported Native Mexican populations.