RESUMEN
Oxidative stress generated by cigarette smoking, environmental pollution, or other noxious particles leads to epigenetic changes in the cells of the respiratory tract. They reflect cell adaptation in response to chronic exposure to external factors. Although there is no change in the genetic code, epigenetic changes may be heritable and translated from one generation to another, accumulating abnormalities and rendering cells into entirely different phenotype, causing disease. DNA methylation, post-translation histone modification, ubiquitination, sumoylation and miRNA transcriptional regulation are the major processes that are responsible for the epigenetic control of gene expression. All of them are reversible. They can be regulated by targeting specific enzymes/proteins involved in the process in order to mitigate inflammation. Chronic respiratory diseases have epigenetic signatures that affect gene expression in the lung. Targeting them provides the development of novel diagnostic and therapeutic approaches in respiratory medicine. Nutrigenomics reveals the beneficial effect of natural phytochemicals, affecting key steps in the signaling pathways of chronic respiratory diseases.
Asunto(s)
Asma/tratamiento farmacológico , Epigénesis Genética/efectos de los fármacos , Nutrigenómica , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Asma/genética , Metilación de ADN , Histonas/metabolismo , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/fisiología , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/genética , UbiquitinaciónRESUMEN
Biomarker research in COPD is becoming the most rapidly progressing sphere in respiratory medicine. Although "omics" generate a huge amount of biomarkers, fibrinogen is the only one validated by the European Medicines Agency. Thousands of studies analyzing different biological samples from the respiratory tract, collected in different ways, using various kits and techniques are generating more and more data, rendering biomarkers very confusing rather than having practical value. It seems that in order to be applicable and validated, biomarkers should be analysed in an accurately described cohort of patients, homogeneous in disease severity and activity. As COPD has multiple mechanisms of pathobiology it raises the issue of which is the most appropriate biological sample reflecting each of them. Unified criteria for tissue sampling, validated kits for respiratory tract probes and standardized technologies should be announced. The review presents the biomarkers that are currently validated and raises the problem of standardization.
Asunto(s)
Citocinas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Esputo/metabolismo , Biomarcadores , Volumen Espiratorio Forzado , Humanos , Inflamación/metabolismo , Pulmón/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Tomografía Computarizada por Rayos X , TranscriptomaRESUMEN
BACKGROUND: αB-crystallin (HspB5) is a chaperone whose role as a marker of innate immunity activation as well as its therapeutic potential have recently been investigated in several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain-Barré syndrome. AIM: The aim of this study is to determine the role of αB-crystallin in chronic obstructive pulmonary disease (COPD) pathogenesis and inflammation. MATERIALS: Plasma levels of αB-crystallin were studied in 163 patients: 52 healthy non-COPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-II; 43 COPD smokers in GOLD stages III-IV. Forty-eight patients were diagnosed with acute inflammatory respiratory disease. The plasma levels of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay (Calbiochem), and were confirmed with Western blotting. Tissue expression of the protein was compared in three different groups of patients: COPD smokers, COPD nonsmokers, and in patients with age-related emphysema. RESULTS: The mean level of anti-αB-crystallin antibodies in non-COPD smokers was 0.291 nm. In COPD smokers it was 0.352 nm and, in patients with inflammatory lung diseases, 0.433 nm. There was a statistically significant difference between COPD smokers and healthy non-COPD smokers (P = 0.010). The same could be observed comparing the group of patients with acute inflammation and non-COPD healthy smokers (P = 0.007). There was no statistically significant difference between patients with mild/moderate inflammation and those with severe COPD. Tissue detection of the protein showed that it was significantly overexpressed in COPD smokers in comparison to COPD nonsmokers and was only slightly expressed in patients with age-related emphysema. CONCLUSION: αB-crystallin is increased in patients with inflammatory lung diseases. Though unspecific, it could be used in a panel of markers discerning COPD smokers from healthy nonsmokers. As αB-crystallin is a regulator of innate immunity and a therapeutic anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be explored further.
Asunto(s)
Pulmón/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/sangre , Cadena B de alfa-Cristalina/sangre , Anciano , Autoanticuerpos/sangre , Biomarcadores/sangre , Western Blotting , Bulgaria/epidemiología , Proteína C-Reactiva/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunidad Innata , Inmunohistoquímica , Pulmón/inmunología , Pulmón/fisiopatología , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Neumonía/sangre , Neumonía/inmunología , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Fumar/efectos adversos , Fumar/epidemiología , Regulación hacia Arriba , Cadena B de alfa-Cristalina/inmunologíaRESUMEN
OBJECTIVE: The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor (EGFR) in lung cancer pathogenesis. MATERIALS AND METHODS: We used the highly reliable method of FISH, applied on tissue microarray (TMA), containing 306 lung tumors of different histological types, grades and tumor stage, in order to analyze the correlations between gene copy number changes and tumor phenotype. RESULTS: The frequency of EGFR copy number changes was 22.2%-2.8% amplifications and 19.4% gains. EGFR gains occurred more commonly in the squamous cell cancers (23.5%) than in adenocarcinomas (11.8%). Amplifications of EGFR were found only in the squamous cell cancers. Regarding cancer phenotype, there was a statistically significant correlation between EGFR copy number changes and histological grade (p = 0.001). No statistically significant relation could be observed with the metastatic spread of the tumors (lymphogenic and haematogenic) (p = 0.082 and p = 0.1, respectively). In our study EGFR could not be determined as a prognostic factor of survival (p = 0.6115). CONCLUSION: EGFR copy number changes could supplement the clinical significance of EGFR as a marker related to its pathogenesis and targeted therapy.