RESUMO
Platinum-based chemotherapeutic agents induce the formation of crosslinks in DNA, which are accepted as being responsible for the cytotoxicity of these agents. In this study, we used a modification of the alkaline comet assay for detection of the presence of DNA crosslinks in vitro caused by cisplatin, and in peripheral lymphocytes of patients with non-small cell lung carcinoma undergoing chemotherapy with platinum derivatives. The comet technique modified for the detection of DNA crosslinks was calibrated in vitro by treating HeLa cells and human lymphocytes from healthy donors with different concentrations of cisplatin. A cisplatin dose-dependent formation of DNA crosslinks was observed in in vitro measurements using 10-200 µM concentrations of cisplatin. Lymphocytes from cancer patients were also assayed for the formation and repair of DNA crosslinks. Evidence of crosslink formation and repair was observed in peripheral blood lymphocytes of all cancer patients in this study, although some inter-individual differences were observed in the response to chemotherapy and in repair of DNA crosslinks. We propose that monitoring the number of DNA crosslinks in peripheral blood lymphocytes might be a quick and sensitive method for monitoring a patient's sensitivity to this agent. Modification of the method by incubation of analysed cells with styrene oxide before crosslink analysis by comet assay extends the use of the method also to laboratories which have no facilities to use ionizing irradiation for introducing DNA breaks into the cells.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Ensaio Cometa/métodos , Dano ao DNA , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos/efeitos dos fármacos , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Células HeLa , Humanos , Neoplasias Pulmonares/genética , Linfócitos/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor. Clinical trials have shown its efficacy in advanced non-small cell lung cancer (NSCLC). We conducted a large retrospective study based on clinical experience aiming to prove erlotinib's efficacy and safety in patients with advanced-stage squamous cell NSCLC. Totally 375 patients with advanced-stage (IIIB, IV) squamous cell NSCLC were treated with erlotinib. Erlotinib was continued until disease progression or intolerable toxicity. 1 (0.3%) complete response (CR), 28 (7.5%) partial responses (PR) and 198 (52.8%) stable diseases (SD) were achieved. Overall response rate (ORR) and disease control rate (DCR) were 7.8% and 60.5%, respectively. Median progression-free survival (PFS) was 3.0 months and median overall survival (OS) was 7.6 months. PFS of patients with CR/PR, SD and PD were 7.6, 3.9 and 1.0 months, respectively (P<0.001). OS of patients with CR/PR, SD and PD were 13.3, 10.9 and 3.8 months, respectively (P<0.001).The most common adverse effects were rash and diarrhoea. In conclusion ertlotinib is effective and well-tolerated in patients with advanced-stage squamous cell NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , DNA de Neoplasias/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Associations between nasal and bronchial impairment have been repeatedly described in chronic obstructive pulmonary disease (COPD), whereas nasal mucociliary clearance (MCC) in COPD patients is not yet fully understood. We studied nasal MCC parameters in COPD patients and compared them with healthy adults (HA) and with cystic fibrosis (CF) patients with compromised MCC. METHODOLOGY: An observational study of 98 COPD ex-smokers and subjects from control groups evaluated for nasal MCC time (NMCCt) and by digital video microscopy of nasal mucosa recording ciliary beat frequency (CBF) and ciliary beat pattern. RESULTS: The NMCCt was decreased in HA compared to those with COPD and decreased in those with COPD compared to those with CF. CBF in COPD was lower compared to HA. The index of ciliary dyskinesia in COPD patients differed from HA. We detected higher NMCCt and lower nasal CBF in patients with chronic bronchitis phenotype (CB) compared to non-CB patients. CONCLUSIONS: We confirmed the presence of impaired nasal MCC in COPD ex-smokers. These impairments were apparent predominantly in the CB phenotype.