Asunto(s)
Antineoplásicos/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Piperazinas/efectos adversos , Alveolos Pulmonares/patología , Eosinofilia Pulmonar/patología , Fibrosis Pulmonar/patología , Pirimidinas/efectos adversos , Benzamidas , Humanos , Mesilato de Imatinib , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Eosinofilia Pulmonar/etiología , Fibrosis Pulmonar/etiologíaRESUMEN
Hypermethylation of CpG island is a common mechanism by which tumor suppressor genes are inactivated. The tumor suppressor genes p16(INK4a) and p15(INK4b) are important components of the cell cycles. We have studied the feasibility of detecting tumor-associated aberrant p16(INK4a) and p15(INK4b) methylation in non-small cell lung cancer (NSCLC) using methylation-specific PCR. We found a high frequency of hypermethylation of the p16(INK4a) gene in 17 of 45 cases of NSCLC. In this study, there was no difference between the clinicopathological features or overall survival of patients with and without p16(INK4a) methylation. On the other hand, p15(INK4b) promoter hypermethylation is rare (5/45) in lung cancer and occurs in association with p16(INK4a) methylation. The overall survival of patients with p15(INK4b) methylation was markedly shortened in this series. We also analyzed cells in bronchial washings, and p16(INK4a) methylation was detected in 4 of 17 cases of NSCLC. Moreover, 1 of 10 plasma samples from patients with NSCLC was positive for p16(INK4a) methylation. Our results suggest a possible prognostic role of p15(INK4b) methylation in NSCLC, and that the detection of aberrant p16(INK4a) methylation in both bronchial washings and plasma may be useful for cancer diagnosis.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas Portadoras/genética , Proteínas de Ciclo Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Metilación de ADN , Neoplasias Pulmonares/patología , Proteínas Supresoras de Tumor , Adulto , Anciano , Anciano de 80 o más Años , Líquido del Lavado Bronquioalveolar/citología , Carcinoma de Pulmón de Células no Pequeñas/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina , ADN de Neoplasias/sangre , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Regiones Promotoras Genéticas/genética , Análisis de SupervivenciaRESUMEN
A newly approved oral fluoropyrimidine, TS-1, is a dihydropyrimide dehydrogenase (DPD)-inhibiting fluoropyrimidine (DIF) drug. We describe a case of interstitial pneumonia probably caused by TS-1. A peripheral blood lymphocytes stimulating test (DLST) with TS-1 demonstrated a substantial positive reaction. So far only three cases of TS-1-induced interstitial pneumonia have been reported but the relationship between interstitial pneumonia and TS-1 was demonstrated only in this case. Considering that interstitial pneumonia has also been reported with 5-FU, it is necessary in the future to clarify which component of this drug is directly related to interstitial pneumonia.