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1.
Physiol Rep ; 6(2)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29368450

RESUMO

Asthma and chronic obstructive pulmonary disease (COPD), chronic airway inflammatory diseases characterized by airflow limitation, have different etiologies and pathophysiologies. Asthma-COPD Overlap (ACO) has recently been used for patients with mixed asthma and COPD. The pathophysiological mechanisms of ACO have not been clearly understood due to the lack of an appropriate murine model. To investigate its pathophysiology, we examined a murine model by allergen challenge in surfactant protein-D (SP-D)-deficient mice that spontaneously developed pulmonary emphysema. SP-D-deficient mice were sensitized and challenged by ovalbumin (OVA). Lungs and bronchoalveolar lavage fluid (BALF) were collected for analysis, and static lung compliance and airway hyperresponsiveness (AHR) were measured 48 h after the last OVA challenge. In SP-D-deficient, naïve, or OVA-challenged mice, the mean linear intercept and static lung compliance were increased compared with wild-type (WT) mice. There was no significant difference in goblet cell hyperplasia and the gene expression of Mucin 5AC (MUC5AC) between SP-D-deficient and WT OVA-challenged mice. In SP-D-deficient OVA-challenged mice, airway hyperresponsiveness was significantly enhanced despite the lower eosinophil count and the concentration of interleukin (IL)-5 and IL-13 in BALF compared with WT OVA-challenged mice at 120 ventilations per minute. When mice were ventilated at a lower ventilation frequency of 100 ventilations per minute, elevated airway hyperresponsiveness in SP-D-deficient OVA-challenged mice was diminished. This model of emphysematous change with allergic airway inflammation raises the possibility that frequency-dependent airway hyperresponsiveness may be involved in the pathophysiology of ACO.


Assuntos
Asma , Modelos Animais de Doenças , Doença Pulmonar Obstrutiva Crônica , Animais , Hipersensibilidade/etiologia , Inflamação/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/imunologia , Ovalbumina/toxicidade , Enfisema Pulmonar , Proteína D Associada a Surfactante Pulmonar/deficiência , Hipersensibilidade Respiratória/etiologia
2.
Lung Cancer ; 99: 41-5, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27565912

RESUMO

OBJECTIVES: We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100mg/m(2)) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR). RESULTS: Forty-one patients were enrolled between September 2013 and April 2015. The ORR was 31.7% (90% confidence interval, 19.3%-44.1%), which met the primary objective of the study. Median progression-free survival was 4.9 months (95% confidence interval, 2.4-7.4 months) and median overall survival was 13.0 (95% confidence interval, 8.0-18.0 months) months. The median number of treatment cycles was four (range, 1-17) over the entire study period, and the median dose intensity was 89.1mg/m(2) per week. Hematologic toxicities of grade 3 or 4 included neutropenia (19.5%) and leukopenia (17.1%), with no cases of febrile neutropenia being observed. Individual nonhematologic toxicities of grade 3 or higher occurred with a frequency of <5%. CONCLUSION: Weekly nab-paclitaxel was associated with acceptable toxicity and a favorable ORR in previously treated patients with advanced NSCLC. Our results justify the undertaking of a phase III trial comparing nab-paclitaxel with docetaxel in this patient population.


Assuntos
Albuminas/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Paclitaxel/administração & dosagem , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Esquema de Medicação , Feminino , Genes erbB-1 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Retratamento , Resultado do Tratamento
3.
Lung Cancer ; 88(3): 349-51, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25837798
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