ABSTRACT
Breast cancer is now the most common malignant tumor in Chinese women. Approximately 70% of breast cancers express estrogen receptor (ER) which plays a critical role in the development of breast cancer. Endocrine therapy has become one of the most effective treatments for ER-positive breast cancer. At present, the endocrine therapy drugs are mainly divided into three categories: selective ER modulators, selective ER down-regulators and aromatase inhibitors. The adjuvant endocrine therapy with these drugs can reduce the risk of breast cancer recurrence by nearly 40%. However, the resistance of tumor cells to endocrine therapy is a major factor limiting the success of breast cancer treatment. The known mechanisms of endocrine therapy resistance include the concentration of estrogen increased in tumor microenvironment, ER gene mutation, up-regulation of multiple molecular signal pathway, and epigenetic mechanisms. Overcoming endocrine therapy resistance is essential for further improving the benefit rate of endocrine therapy. In this review, the progresses of epigenetic mechanisms (including DNA methylation and histone modification) and epigenetic drugs (including DNAmethyltransferases inhibitors and histone deacetylases inhibitors) of endocrine therapy resistance in ER-positive breast cancer are introduced, in order to further understand the mechanism and therapeutics of endocrine therapy resistance in breast cancer.
ABSTRACT
El tabaquismo es la adicción al tabaco provocada principalmente por diversos componentes activos y tóxicos como la nicotina. El consumo de cigarrillo durante la gestación puede provocar desprendimiento de placenta, placenta previa, embarazo ectópico y aborto espontáneo, como también inducir alteraciones en el feto. En la presente revisión de la literatura se recopiló información en bases de datos como Pub-Med, Embase y Google Académico, concerniente a los posibles efectos del tabaquismo materno durante la gestación sobre el desarrollo de la obesidad infantil. Fueron seleccionados 38 artículos escritos en el idioma inglés y español, publicados a partir de año de 1988 hasta el año 2015, que incluyeron metaanálisis, artículos originales, y revisiones de tema. Se encontró que la exposición al humo del tabaco durante la gestación ha sido ampliamente descrita como un factor de riesgo para la manifestación de alteraciones en el desarrollo fetal como retardo del crecimiento intrauterino y bajo peso al nacer. Además, se ha asociado ampliamente con trastornos del desarrollo infantil en etapas avanzadas, como preescolares y escolares, manifestados en un aumento del índice de masa corporal con respecto al percentil adecuado para la edad; incremento de la incidencia de sobrepeso y obesidad en el infante. Se concluye que la exposición al humo del cigarrillo durante la gestación se relaciona con alteraciones en el crecimiento del niño y en el desarrollo de enfermedades prevalentes asociadas a la obesidad.
Most smokers use tobacco regularly because they are addicted to various active and toxic compounds such as nicotine. Cigarette smoking during pregnancy can cause abruption, placenta previa, ectopic pregnancy and spontaneous abortion, as well as induce alterations in the fetus. In this review, information was collected in databases such as PubMed, Embase and Google Scholar, concerning the possible effects of maternal smoking during pregnancy on the development of childhood obesity. Thirty-eigth articles written in English and Spanish published from year 1988 to 2015, which included meta-analysis, original articles and reviews were selected topic. It was found that exposure to cigarette smoke during pregnancy has been widely described as a risk factor for alterations in fetal development such as intrauterine growth retardation and low birth weight. In addition, it has been widely associated with disorders of child development in advanced stages, preschool and school age: increased body mass index regarding the appropriate percentile for age, and increase in childhood overweight and obesity. It is concluded that exposure to cigarette smoke during pregnancy is associated with changes in child growth and development of prevalent diseases associated with obesity.
Subject(s)
Humans , Female , Pregnancy , Obesity/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Smoking/adverse effects , Obesity/etiology , Prenatal Exposure Delayed Effects/etiology , Tobacco Smoke Pollution/adverse effects , Tobacco Use Disorder/complicationsABSTRACT
Abstract Background: Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD. Objective: To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk. Methods: A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs. Results: Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10‑3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2. Conclusion: These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD.
Resumo Fundamento: Interleucina-6 (IL-6) está implicada na patogênese de doença arterial coronariana (DAC), sendo sua expressão associada com redução da metilação de DNA do promotor do seu gene. Entretanto, não há dados sobre metilação do promotor de IL-6 e risco de DAC. Objetivo: Verificar se a metilação do promotor de IL-6 medida no DNA de leucócitos sanguíneos acha-se associada com risco de DAC. Métodos: este estudo arrolou 212 casos com DAC e 218 controles. Metilação em dois sítios de CpG no promotor de IL-6 foi medida por pirosequenciamento de bissulfito, sendo a metilação média de IL-6 calculada pela média das medidas de metilação dos dois CpGs. Resultados: A média do nível de metilação no promotor de IL-6 nos casos de DAC foi significativamente mais baixa do que nos controles (p = 0,023). Análise de regressão logística mostrou associação inversa entre metilação de IL-6 e risco de DAC. As razões de chance (OR) de DAC para indivíduos no segundo e no primeiro (mais baixo) tercis de metilação de IL-6 foram 1,87 (IC 95%: 1,10-3,20) e 2,01 (IC 95%: 1,19-3,38) (ptrend = 0,013), respectivamente, comparadas à de indivíduos no terceiro (mais alto) tercil. As estimativas de risco relacionado à hipometilação de IL-6 tenderam a ser mais fortes para infarto agudo do miocárdio (ptrend = 0,006). Análise com especificidade de posição de CpG mostrou que hipometilação na posição 1 conferiu maior elevação no risco de DAC do que na posição 2. Conclusão: Tais achados sugerem que a hipometilação de DNA do promotor de IL-6 está associada com elevado risco de DAC, especialmente para infarto agudo do miocárdio. Os dois CpGs distintos no promotor de IL-6 podem contribuir de modo diferente para o desenvolvimento de DAC.