RESUMO
OBJECTIVES: To determine the lung cancer screening yield and stages in a union-sponsored low-dose computerized tomography scan program for nuclear weapons workers with diverse ages, smoking histories, and occupations. METHODS: We implemented a low-dose computerized tomography program among 7189 nuclear weapons workers in 9 nonmetropolitan US communities during 2000 to 2013. Eligibility criteria included age, smoking, occupation, radiographic asbestos-related fibrosis, and a positive beryllium lymphocyte proliferation test. RESULTS: The proportion with screen-detected lung cancer among smokers aged 50 years or older was 0.83% at baseline and 0.51% on annual scan. Of 80 lung cancers, 59% (n = 47) were stage I, and 10% (n = 8) were stage II. Screening yields of study subpopulations who met the National Lung Screening Trial or the National Comprehensive Cancer Network Group 2 eligibility criteria were similar to those found in the National Lung Screening Trial. CONCLUSIONS: Computerized tomography screening for lung cancer among high-risk workers leads to a favorable yield of early-stage lung cancers. Public Health Implications. Health equity and efficiency dictate that screening high-risk workers for lung cancer should be an important public health priority.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/etiologia , Programas de Rastreamento , Neoplasias Induzidas por Radiação/diagnóstico por imagem , Neoplasias Induzidas por Radiação/etiologia , Armas Nucleares , Doenças Profissionais/diagnóstico por imagem , Exposição Ocupacional/efeitos adversos , Exposição à Radiação , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/epidemiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Doenças Profissionais/patologia , Doses de Radiação , Fatores de Risco , Fumar/epidemiologia , Estados Unidos/epidemiologiaRESUMO
We have identified a 41-residue peptide, bracketing the aggrecanase cleavage site of aggrecan, that serves as a specific substrate for this enzyme family. Biotinylation of the peptide allowed its immobilization onto streptavidin-coated plates. Aggrecanase-mediated hydrolysis resulted in an immobilized product that reveals an N-terminal neoepitope, recognized by the specific antibody BC-3. This assay is highly specific for aggrecanases; MMPs were inactive in this assay. Reduction of the peptide size below 30 amino acids resulted in a significant diminution of activity. Using the immobilized 41-residue peptide as a substrate, we have developed a 96-well microplate-based assay that can be conveniently used for high-throughput screening of samples for aggrecanase activity and for discovery of inhibitors of aggrecanase activity.
