• Tuberculosis and Respiratory Diseases
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• v.75 no.3
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• pp.95-103
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• 2013

Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.155-164
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• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.428-437
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• 2000

Background : Five year survival rate of postoperative stage I non-small cell lung cancer(NSCLC) reaches to 66%. In the remaining one third of patients, however, cancer recurs and the overall survival of NSCLC remains dismal. To evaluate clinical and pathologic characteristics of recurred NSCLC, the patterns and factors for postoperative recurrence in patients with staged I and II NSCLC were studied. Method : A retrospective analysis was performed in 234 patients who underwent radical resection for pathologic stage I and II NSCLC. All patients who were followed up for at least one year were included in this study. Results : 1) There were 177 men and 57 women The median age was 63. The median duration of the follow up period was 732 days (range 365~1,695 days). The overall recurrence rate was 26.5%, and the recurrence occurred $358.8{\pm}239.8$ days after operation. 2) The ages of recurred NSCLC patients were higher ($63.2{\pm}8.8$ years) than those of non-recurred patients ($60.3{\pm}9.8$ years)(p=0.043). The recurrence rate was higher in stage II (46.9%) than in stage I (18.8%) NSCLC p<0.001. The size of primary lung mass was larger in recurred ($5.45{\pm}3.22\;cm$) than that of non-recurred NSCLC ($3.74{\pm}1.75\;cm$, p<0.001). Interestingly, there were no recurrent cases when the resected primary tumor was less than 2cm. 3) Distant recurrence was more frequent than locoregional recurrence (66.1% vs. 33.9%). Distant recurrence rate was higher in females and in cases of adenocarcinoma. Brain metastasis was more frequent in patients with adenocarcinoma than in those with squamous cell carcinoma (p=0.024). Conclusion: The tumor size and stage were two important factors for determining the possibility of a recurrence. Because distant brain metastasis was more frequent in patients with adenocarinoma, a prospective study should be conducted to evaluate the effectiveness of preoperative brain imaging.

• Tuberculosis and Respiratory Diseases
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• v.68 no.1
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• pp.16-21
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• 2010

Background: Lung cancer is usually diagnosed at an advanced stage, resulting in a poor prognosis. The detection of these lesions at an earlier stage would be a clear benefit to patients. However, it is extremely difficult to detect carcinomatous lesions in the bronchial mucosal sites during a routine bronchoscopy. Methods: This study employed a novel optical technique, known as narrowband imaging (NBI), which allows noninvasive visualization of the microvascular structure of an organ's surface using reflected light. Results: Narrow band imaging was performed on 10 patients who were radiologically suspicious or had a high risk of lung cancer. The median age of the patients was 57.5 years (range, 44~81 years), and 80% of the patients were male. All lesions showed a microvascular proliferation pattern (dotted, tortuous and abruptly ending vessel) on the magnified NBI. Two lesions were confirmed histologically to be adenocarcinoma and the remaining lesions were squamous cell carcinomas. Two lesions were confirmed histologically to be a carcinoma in situ. Conclusion: NBI is a promising and potentially powerful tool for identifying carcinomas at an earlier stage or a central lesion during a routine bronchoscopy examination.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.321-329
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• 2006

Background : To evaluate the clinical characteristics of lung cancer patients in Korea, where there is a higher number of smokers than in Western countries. Methods : A retrospective study was performed on 1655 lung cancer patients, who were diagnosed at a university hospital between September 1996 and August 2005. Age, gender, cell types and clinical stage were analysed. Of 941 patients, who responded to a questionnaire at the time of diagnosis, the smoking habits, occupational history, family history of lung cancer in the first-degree relatives, coexisting diseases (diabetes mellitus and cardiovascular disease), body weight loss, ECOG performance status and presenting symptoms, were examined prospectively. In addition, coexisting diseases including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and active pulmonary tuberculosis were evaluated. Results : Of the 1655 patients, the male to females ratio was 3.6. Squamous cell carcinoma was the most common cancer whereas adenocarcinoma was more common in lifetime nonsmokers or women. 19.9% of the patients were non smokers and 80.1% ever smokers. Since 2000, there was an increase in the incidence of adenocarcinoma with a corresponding decrease in the incidence of squamous cell carcinoma. 6.2% of patients were asymptomatic. A coincident diagnosis of chronic obstructive pulmonary disease, cardiovascular disease, diabetes mellitus, active pulmonary tuberculosis, and idiopathic pulmonary fibrosis was made in: 44.1%, 22.2%, 10.7%, 3.9%, and 1.6% of patients, respectively. A positive family history of lung cancer in the first-degree relatives was identified in 4.4% of patients. An occupational history relevant to lung cancer was identified in 12.2% of patients. Conclusion : There is a high proportion of cigarette smokers in Korean lung cancer patients. The most common cell type was squamous cell carcinoma. However, a more detailed, prospective study of the clinical characteristics will be needed to better characterize lung cancer in Korea.

• The Korean Journal of Cytopathology
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• v.6 no.2
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• pp.140-147
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• 1995

In a six-year period (1988. 5-1994. 4), fine needle aspiration cytology(FNAC) of 322 pulmonary lesions from 296 patients were performed at Soonchunhyang University Hospital. Of these 322, malignancy was diagnosed cytologically in 139(43.2%), suspicious malignancy in 7(2.2%), negative in 164(50.8%), and insufficient material in 12(3.8%). Malignant lesions consisted of 54 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 18 cases of small cell carcinoma. They were verified by histologic examination in 70 cases. There were 2(0.6%) false positive cases due to florid bronchoalveolar hyperplasia and atypical bronchial epithelial cells associated with granulomatous lesion. The overall accuracy rate was 90%, the sensitivity 84.3% and the specificity 94.7%.

• Journal of Chest Surgery
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• v.47 no.1
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• pp.51-54
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• 2014

Primary tumors of the lung are uncommon in pediatric patients, particularly bronchioloalveolar carcinoma (BAC). An 11-year-old female suffering from back pain for 1 month was referred to Seoul St. Mary's Hospital for treatment of a pathologic fracture of the lumbar spine. Comprehensive evaluation disclosed numerous pulmonary metastases of rhabdomyosarcoma (stage IV). During chemotherapy, most of the lung lesions regressed, with the exception of two nodules. Wedge resections, intended for diagnosis and cure, yielded a histologic diagnosis of BAC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.551-557
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• 2015

Background: Differentiating morphologic features based on hematoxylin-eosin (HE) staining is the most common method to classify pathological subtypes of non-small-cell lung cancer (NSCLC). However, its accuracy and inter-observer reproducibility in pathological diagnosis of poorly differentiated NSCLC remained to be improved. Materials and Methods: We attempted to explore the role of immunohistochemistry (IHC) staining in diagnosing pulmonary squamous cell carcinoma (SQCC) with poorly differentiated features by HE staining or with elevated serum adenocarcinoma-specific tumor markers (AD-TMs). We also compared the difference of epidermal growth factor receptor (EGFR) mutation rate between patients with confirmed SQCC and those with revised pathological subtype. Logistic regression analyses were used to test the association between different factors and diagnostic accuracy. Results: A total of 132 patients who met the eligible criteria and had adequate specimens for IHC confirmation were included. Pathological revised cases in poor differentiated subgroup, biopsy samples and high-level AD-TMs cases were more than those with high/moderate differentiation, surgical specimens and normal-level AD-TMs. Moreover, biopsy sample was a significant factor decreasing diagnostic accuracy of pathological subtype (OR, 4.037; 95% CI 1.446-11.267, p=0.008). Additionally, EGFR mutation rate was higher in patients with pathological diagnostic changes than those with confirmed SQCC (16.7% vs 4.4%, p=0.157). Conclusions: Diagnosis based on HE staining only might cause pathological misinterpretation in NSCLC patients with poor differentiation or high-level AD-TMs, especially those with biopsy samples. HE staining and IHC should be combined as pathological diagnostic standard. The occurrence of EGFR mutations in pulmonary SQCC might be overestimated.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6159-6164
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• 2013

Background: Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone, caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNA expression levels of proteins and survival of lung cancer cells in Vitro. Materials and Methods: The A549 cell line was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessed and results were compared among study groups. Results: TQ treatment up-regulated Bax and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased the expression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly decreased when compared with the control group (p=0.004). Conclusions: Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.982-987
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• 1998

Background: Surgical resection is the standad therapy for the stage I lung cancer. We analysed the risk facturs of stage I lung cancer patent and tryed to establish more effective and aggressive treatment modality. Materials and methods: A detailed analysis was undertaken to evaluate the surgical results and to define the risk factors associated with the recurrence and the survival time in 146 consecutive patients with stage I lung cancer who were diagnosed, and resected at Yonsei Medical Center from January 1990 to December 1996. Results: There were 115 males and 31 females. Their ages ranged from 27 to 79 years(mean age:58.9$\pm$9.3 years). The histologic types were squamous carcinoma in 72 cases(49.3%) and adenocarcinoma in 45 cases(30.8%). A pulmonary resection and mediastinal lymph node dissection were done in all cases. A lobectomy was performed in 96 cases(65.7%) and a pneumonectomy in 48 cases(32.9%). There were 5 operative mortalities(3.4%) and complications occured in 24 cases(16.5%). The overall 5-year survival was 64.1%, and survival time did not depend on the type of operation or histologic type. Significant predictors of decreased survival were visceral pleural invasion(p=0.0079), T2 lesion(p=0.0462), and tumor size($\geq$5 cm) in adenocarcinoma(p=0.0472). The overall incidence of recurrence was 33.3%(47 cases; local or regional 6.4%, distant 26.9%). Almost all recurrences(44cases) occurred in T2 lesions. The distant organs that failed were the contralateral lung in 13 patients, the brain in 12, the bone in 10, and other organs in 3. Conclusions: even in stage I lung cancer, we suggest that postoperative adjuvant therapy is recommended in patients with poor prognostic factors such as visceral pleural invasion, T2 lesions, and a tumor size($\geq$5 cm) in the adenocarcinoma.