| Summary: | 博士 === 中山醫學大學 === 醫學研究所 === 103 === Lung cancer is the leading cause of cancer death in Taiwan. This study investigated the prognostic factors affecting survival of patients with lung cancer in Taiwan. Data were obtained from the National Health Insurance Research Database (NHIRD) published in Taiwan. Clinicopathologic profiles and prognostic factors of 33,919 lung cancer patients were analyzed between 2002 and 2008 in this retrospective review. The impact of the clinicopathologic factors on overall survival was assessed. Nearly two-thirds of the patients were men. The 5-year survival rate was 15.9%, with a median survival of 13.2 months. The clinical staging of the patients included stage I (n=4,254; 12.5%), stage II (n=1,140; 3.4%), stage III (n=10,161; 30.0%), and stage IV (n=18,364; 54.1%). In the multivariate analysis, age >65 years, sex, cell type, histologic grade, and primary tumor location were identified as independent prognostic factors. In additional to tumor-nodes-metastasis (TNM) staging system, patient sex and age, tumor location, cell type, and differentiation were independent prognostic factors. We recommend incorporation of these factors in order to sub-classify lung cancer patients. Benzo[a]pyrene (B[a]P), the most extensively evaluated polycyclic aromatic hydrocarbons (PAHs) has a potent lung carcinogenic activity derived from tobacco smoking and environmental contamination. An approximately 90% correlation between smoking and lung cancer incidence. This study aimed to investigate the molecular mechanisms responsible for B[a]P-induced cell cycle S-phase accumulation in H1355 non-small cell lung cancer (NSCLC) cell . We found that ERK activity inhibitor PD98059 inhibited B[a]P-induced S-phase accumulation in H1355 using BrdU flow cytometry. In addition, using VSV-G pseudotyped lentivirus –shRNA for MAPK1 (ERK2) silence, checkpoint kinase-1 (Chk1)-phosphorylation induced by B[a]P was abolished. These results suggested that ERK activation and downstream mediator Chk1 may contribute to B[a]P-induced S phase accumulation in H1355 cells. We also found that B[a]P did not induce LC3 conversion and lysosome inhibitor chloroquine (CQ) had no effect on B[a]P-induced S-phase accumulation. Furthermore, histone deacetylases (HDAC) inhibitor chidamide reversed the B[a]P-induced S phase accumulation and blocked ERK phosphorylation. This results indicate that B[a]P induces S phase accumulation via ERK-mediated Chk1 activation. Inhibition of ERK-mediated Chk1 phosphorylation and HDAC inhibitor may be potential in lung cancer therapy development.
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