Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/ p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-β induced RUNX2/ p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells.

: escritura del protocolo de investigación, documento de alcance y objetivos, búsqueda de la literatura. Juan Sebastián Castillo: orientación metodológica en la aplicación de la metodología ADAPTE y búsqueda de la literatura. Luz Helena Alba y Raúl Murillo: escritura del presente artículo. Todos los autores calificaron la 'evidencia', realizaron la extracción de datos e intervinieron en diferentes fases del proceso de adaptación de la guía nacional, y revisaron el manuscrito. ARTÍCULO ORIGINAL Biomédica 2013;33:186-204 doi: http://dx.doi.org/10.7705/biomedica.v33i2.651 Recomendaciones para la cesación de la adicción al tabaco en Colombia Introducción. El tabaquismo es el principal factor de riesgo para enfermedades crónicas que constituyen la mayor carga en Colombia. Objetivos. Generar recomendaciones de práctica clínica sobre eficacia y seguridad del tratamiento para la cesación de la adicción al tabaco en adultos colombianos. Materiales y métodos. Se hizo una adaptación basada en la metodología ADAPTE. Se buscaron guías de práctica clínica en Medline, EMBASE, CINAHL, LILACS y Cochrane. Se evaluó la cesación a seis meses para consejería breve e intensiva, terapia de reemplazo nicotínico, bupropión, vareniclina, clonidina, nortriptilina, acupuntura, hipnosis, homeopatía y la combinación de tratamientos. Se utilizó el German Instrument for Methodological Guideline Appraisal (DELBI) para evaluar las guías de práctica clínica. Se seleccionaron las guías con puntaje mayor de 60 % en rigor metodológico y aplicabilidad en Colombia. Las preguntas sin evidencia fuerte se llevaron a consenso. Resultados. Se encontraron 925 referencias, se preseleccionaron 17 guías de práctica clínica y se escogieron 5 para adaptación. La consejería breve e intensiva, la terapia de reemplazo nicotínico, el bupropión, la nortriptilina y la vareniclina son eficaces en la cesación de tabaquismo (incrementó 5,1 % a 22,7 %). Los tratamientos alternativos no tienen eficacia demostrada en la cesación. El uso simultáneo de diferentes formas de terapia de reemplazo nicotínico es la única combinación con eficacia demostrada (OR 1,9; IC 95% : 1,3-2,7). Conclusiones. Existen diversas alternativas con eficacia demostrada para dejar de fumar. Los incrementos en las tasas de cesación son variables y la duración del efecto necesita mayor seguimiento. Para aplicar la consejería breve e intensiva en Colombia, se deben usar formatos estándar. Se requieren evaluaciones económicas para valorar el impacto y seleccionar las mejores intervenciones en el contexto colombiano.Palabras clave: tabaco, tabaquismo, nicotina, cese del tabaquismo, cese del uso de tabaco, guías de práctica clínica como asunto doi: http://dx.doi.org/10.7705/biomedica.v33i2.651 Recommendations for smoking cessation in ColombiaIntroduction: Chronic diseases represent the greatest burden of disease in Colombia for which smoking is the major risk factor. Objectives: To provide clinical practice recommendations based upon efficacy and safety of smoking cessation therapies for Colombian ad...

Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra-osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS-FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS-FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS-FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS-FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter. The EWS-FLI1 fusion gene was evaluated in two patients with ES using conventional cytogenetic, fluorescence in situ hybridization and nested PCR assays, which revealed that the aberrant expression of the EWS-FLI1 gene is accompanied by enrichment of H3K4Me3, H3K9ac and H3K27ac at the promoter region.

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Flow cytometry (FCM) was implemented in 2008 at the Pontificia Universidad Javeriana and later at the Hospital Universitario San Ignacio to examine special samples of patients with hematological malignancies and solid tumors other than bone marrow and peripheral blood for diagnosis and monitoring. This study describes the main findings of special sample evaluation over a six-year period. In all, 1070 samples of body fluids from patients with benign and malignant diseases were examined by FCM. These samples were stabilized with TransFix TM and stained with six-color immunophenotyping panels. Samples included cerebrospinal fluid, bronchoalveolar lavage, pleural fluid, pericardial fluid and ascite fluid from patients with acute and chronic leukemia, myelodysplastic syndromes, lymphomas, myeloma, autoimmune diseases, immunodeficiencies and solid tumors, among others. Flow cytometry provided important information for the classification and detection of minimal numbers of tumor cells in leukemia and lymphoma cases. This work represents the first national report describing FCM implementation in special samples for diagnosis and clinical monitoring of patients with malignant and benign pathologies. Consequently, over the last decade, use of commercially available cell stabilization solutions has been recommended. These solutions can preserve PB and cerebrospinal fluid (CSF) samples over time periods greater than one week after collection [4, 8 -9]. This stabilization preserves cellularity and integrity of both cell surface and intracellular antigens [9].

The placenta can be affected by environmental factors, such as exposure to cigarette smoke. This exposure in the fetal context is considered a risk factor for the development of short-term postnatal diseases, such as asthma. Asthma is an inflammatory disease characterized by predominant acquisition of CD4 T lymphocytes (TLs) of the Th2 type. Transcription factors such as GATA binding protein 3 (GATA3) and STAT6 actively participate in the differentiation of virgin TLs towards the Th2 profile, while transcription factors such as STAT1, T-Box transcription factor 21 (T-BET), RUNX1 and RUNX3 participate in their differentiation towards the Th1 profile. The objective of the current study was to evaluate the impact of exposure to cigarette smoke on the gene expression of STAT1, T-BET, GATA3, IL-4, RUNX1 and RUNX3 during the gestation period, and to determine whether the expression levels of these genes are associated with changes in global methylation. STAT1, GATA3, RUNX1 and RUNX3 protein and mRNA expression levels in the placental tissue of women smokers and non-smoking women were determined via immunohistochemistry and quantitative PCR (qPCR) respectively. Additionally, T-BET and IL-4 mRNA expression levels were determined by qPCR. On the other hand, global methylation was determined via ELISA. In the present study, significant increases were observed in RUNX1 transcription factor expression in placentas from women smokers when compared with placentas of non-smoking women. Similarly, significant increases in the expression of GATA3, IL-4 and RUNX3 mRNA were observed. The changes in gene expression were not associated with changes in the global methylation levels. Finally, a higher frequency of low-birth-weight infants were identified in cases of exposure to cigarette smoke during pregnancy when compared with infants not exposed to cigarette smoke during pregnancy. Thus, the data of the present study contributed to the understanding of the genetic and clinical impacts of exposure to cigarette smoke during pregnancy and its importance in maternal and fetal health.

cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. in this process, the cell cycle is arrested at the G0/G1 phase. p16 inK4a protein is a key regulator of this process via its cyclin-dependent kinase inhibitor (cdKi) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by dna methylation and histone acetylation. Sirtuins (SirTs) are nicotinamide dinucleotide (nad + )-dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative Pcr, Western blot, chiP, and sirnas assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non-senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl-transferase SIRT7 knockdown Mrc5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene.

Electronic cigarettes (ECIGs) are electronic devices that heat and vaporize a solution that usually contains a mixture of glycerol, propylene glycol, water, flavors and various concentrations of nicotine. ECIGs have 3 key components: A power source, a cartridge containing an atomizer along with a liquid solution and a mouthpiece. The solution (often known as e-liquid or e-juice) is heated into an aerosol inhaled by the user. Smoking conventional cigarettes is considered a determinant factor in the development of chronic respiratory diseases, cardiovascular diseases, cancers, and reproductive system dysfunctions. Conventional smoking also causes genome damage and alteration of the transcriptome, due to the amounts of noxious substances emitted during the combustion of these products. Recently, cigarette consumers have begun to use ECIGs as a replacement or substitute practice to help them quit smoking. In addition, an increase in the use of ECIGs and similar devices by young individuals has been reported, which is unsurprising due to the unregulated distribution and sale of these products. The present review article describes and discusses the impact and the noxious effects of substances in ECIGs and other nicotine administration systems on DNA structure, gene expression profile, and epigenetic modification, focusing on the respiratory system and embryonic development.