RESUMO
Nicotine in tobacco smoke is considered carcinogenic in several malignancies including lung cancer. The high incidence of lung adenocarcinoma (LAC) in non-smokers, however, remains unexplained. Although LAC has long been less associated with smoking behavior based on previous epidemiological correlation studies, the effect of environmental smoke contributing to low-dose nicotine exposure in non-smoking population could be underestimated. Here we provide experimental evidence of how low-dose nicotine promotes LAC growth in vitro and in vivo. Screening of nicotinic acetylcholine receptor subunits in lung cancer cell lines demonstrated a particularly high expression level of nicotinic acetylcholine receptor subunit α5 (α 5-nAChR) in LAC cell lines. Clinical specimen analysis revealed up-regulation of α 5-nAChR in LAC tumor tissues compared to non-tumor counterparts. In LAC cell lines α 5-nAChR interacts with epidermal growth factor receptor (EGFR), positively regulates EGFR pathway, enhances the expression of epithelial-mesenchymal transition markers, and is essential for low-dose nicotine-induced EGFR phosphorylation. Functionally, low-dose nicotine requires α 5-nAChR to enhance cell migration, invasion, and proliferation. Knockdown of α 5-nAChR inhibits the xenograft tumor growth of LAC. Clinical analysis indicated that high level of tumor α 5-nAChR is correlated with poor survival rates of LAC patients, particularly in those expressing wild-type EGFR. Our data identified α 5-nAChR as an essential mediator for low-dose nicotine-dependent LAC progression possibly through signaling crosstalk with EGFR, supporting the involvement of environmental smoke in tumor progression in LAC patients.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Nicotina/toxicidade , Receptores Nicotínicos/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Fosforilação , Receptores Nicotínicos/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Community health nurses are on the frontline of providing healthcare to multiethnic groups. Managing and providing effective, culture-specific healthcare can increase the health quality of Taiwan's recently immigrant women, a significant component of this country's population. PURPOSE: This study analyzes the cultural sensitivity of community health nurses and related factors. METHODS: A cross-sectional survey was applied in this study. Participants were nurses who work at health centers in Kaohsiung City and Pingtung County. A total of 230 valid questionnaires were completed. Structure questionnaires used in this study included (a) scale of nurses' cultural sensitivity, (b) scale of multicultural sources, (c) scale of multicultural competence training programs, and (d) table of personal characteristics. Statistical software SPSS 14.0 was used for statistical analysis. RESULTS: Survey results show an average score of community health nurse cultural sensitivity of 49.41 (SD = 7.48). The index score was 65.88. Thus, survey participants in this study earned a cultural sensitivity score below the index score. "Interaction confidence" earned the lowest item score. "Multicultural resources," "self-perceived English proficiency," "multicultural competence training programs," and "having friends with different cultural backgrounds" were significant predictor variables of cultural sensitivity and, together, explained 34.9% of total variance. CONCLUSIONS: Study results may be referenced in designing future in-service and cultural care education programs for community health nurses to improve healthcare quality for new immigrants.