RESUMO
Chronic Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation not fully reversible. However, a number of patients with COPD respond to bronchodilator agents. Some studies have shown polymorphisms in the b2-adrenergic (ADRb2) and muscarinic M2 and M3 receptors (CHRM) that may participate in the modulation of the receptor responses. This study was designed to investigate the existence and the role of adrenergic and muscarinic receptor polymorphisms and their functional impact in COPD. Eighty-two patients with COPD and 17 healthy smokers were recruited and screened for ADRb2 (T164I and R175R), for CHRM2 (rs1824024) and for CHRM3 (-513C/A and -492C/T). Among the polymorphisms studied our results was not able to demonstrate statistically significant association between the polymorphisms studied and COPD risk. Contrarily, we identified, in our COPD population, a significant association with the CHRM2 (rs1824024) polymorphism and disease severity, with lower lung function test values, frequent exacerbations, and poor response to anti-cholinergic drugs. These results suggest the potential role of receptor polymorphism assessment to discriminate newly COPD phenotypes. J. Cell. Physiol. 231: 1745-1751, 2016. © 2015 Wiley Periodicals, Inc.
Assuntos
Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Receptor Muscarínico M2/genética , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/uso terapêutico , Estudos de Casos e Controles , Progressão da Doença , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/uso terapêutico , Fenótipo , Reação em Cadeia da Polimerase , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Receptor Muscarínico M2/antagonistas & inibidores , Receptor Muscarínico M3 , Receptores Adrenérgicos beta 2/genética , Receptores Muscarínicos/genética , Testes de Função Respiratória , Fatores de Risco , Análise de Sequência de DNA , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The regulatory role of dopamine (DA) in endocrine, cardiovascular and renal functions has been extensively studied and used for clinical purposes. More recently DA has been indicated as a regulatory molecule for immune cells and malignant cell proliferation. We assessed the expression and the functional role DA, DA receptors, and transporters in primary small cell lung cancer (SCLC). By HPLC DA plasma levels were more elevated in SCLC patients in comparison with NSCLC patients and healthy controls. SCLC cell expressed DA D1- and D2-like receptors and membrane and vesicular transporters at protein and mRNA levels. We also investigated the effects of independent D1- or D2-like receptor stimulation on SCLC cell cultures. DA D1 receptor agonist SKF38393 induced the increase of cAMP levels and DARPP-32 protein expression without affecting SCLC growth rate. Cell treatment with the DA D1 receptor antagonist SCH23390 inhibited SKF38393 effects. In contrast, the DA D2 receptor agonist quinpirole (10 µM) counteracted, in a dose and time dependent way, SCLC cell proliferation, it did not affect cAMP levels and decreased phosphorylated AKT that was induced by DA D2 receptor antagonist sulpiride. However, in only one SCLC line, stimulation of DA D2 receptor failed to inhibit cell proliferation in vitro. This effect was associated to the existence of rs6275 and rs6277 polymorphisms in the D2 gene. These results gave more insight into DA control of lung cancer cell behavior and suggested the existence of different SCLC phenotypes.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Adenilil Ciclases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Dopamina/sangue , Fosfoproteína 32 Regulada por cAMP e Dopamina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismoRESUMO
We report two cases of solitary fibrous tumor of the pleura (SFTP). The first appeared in a young, new mother as a large mass in the upper lobe of the left lung that caused compression of lung parenchyma without significant respiratory symptoms but with polyarticular paraneoplastic syndrome; the other was documented by an occasional chest x-ray in a man affected by chronic obstructive pulmonary disease (COPD) as a small peripheral mass 4 years before and no longer controlled. Both patients underwent surgical resection with quick and full recovery. SFTP is a benign, slow growing neoplasm that is mostly localized. It appears in adult or elderly patients often with few symptoms. The computed tomography (CT) of the chest with contrast medium is important in order to see the shape of the mass and relationships with adjacent structures but only histology can provide the diagnosis. Surgery is the best treatment.