• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.645-652
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• 2006

Objective: Patients with lung cancer have a relative high risk of developing secondary primary lung cancers. This study examined the additional value of autofluorescence bronchoscopy (AFB) for diagnosing synchronous lung cancers and premalignant lesions. Methods: Patients diagnosed with lung cancer from January 2005 to December 2005 were enrolled in this study. The patients underwent a lung cancer evaluation, which included white light bronchoscopy (WLB), followed by AFB. In addition to the primary lesions, any abnormal or suspicious lesions detected during WLB and AFB were biopsied. Results: Seventy-six patients had non-small cell lung cancer (NSCLC) and 23 had small cell lung cancer (SCLC). In addition to the primary lesions, 84 endobronchial biopsies were performed in 46 patients. Five definite synchronous cancerous lesions were detected in three patients with initial unresectable NSCLC and in one with SCLC. The secondary malignant lesions found in two patients were considered metastatic because of the presence of mediastinal nodes or systemic involvement. One patient with an unresectable NSCLC, two with a resectable NSCLC, and one with SCLC had severe dysplasia. The detection rate for cancerous lesions by the clinician was 6.0% (6/99) including AFB compared with 3.0% (3/99) with WLB alone. The prevalence of definite synchronized cancer was 4.0% (4/99) after using AFB compared with 2.0% (2/99) before, and the staging-up effect was 1.0% (1/99) after AFB. Since the majority of patients were diagnosed with advanced disease, the subjects with newly detected cancerous lesions did not have their treatment plans altered, except for one patient with a stage-up IV NSCLC who did not undergo radiotherapy. Conclusions: Additional AFB is effective in detecting early secondary cancerous lesions and is a more precise tool in the staging workup of patients with primary lung cancer than with WLB alone.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.109-113
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• 2007

Background: In non-small cell lung cancer (NSCLC), malignant pleural effusion is a frequently observed com-plication, and is an important negative prognostic factor. Although many studies concerned to diagnosis and treatment of malignant pleural effusion have been performed, prognostic factors of malignant pleural effusion have rarely been investigated. This study was performed to determine the prognostic factors of malignant pleural effusion n non-small cell lung cancer. Material and Method: We evaluated 33 NSCLC patients with malignant effusion treated between January 2002 and December 2003. We analyzed possible factors: gender, age, TNM Stage, fluid analysis (pH, CEA, LDH, glucose, albumin) and treatment modality. Median survival time of each factor was calculated by Kaplan-Meier method and difference of median survival time between groups of factor compared by log-rank test. The Cox proportional hazards regression model was used to confirm the significance of prognostic factor. Results: Of the 33 patients, 23 (69.7%) patients were adenocarcinoma. The median interval of the diagnosis of lung cancer and malignant effusion was 7.3 months ($25^{th}{\sim}75^{th}:\;3.9{\sim}11.8$), and the median survival time was 3.6 months (95% Confidence Interval: $1.14{\sim}5.99$). In the univariate analysis, using the log-rank test, those with an adenocarcinoma showed a relatively longer median survival time than those of a non-adenocarcinoma (4.067 vs. 1.867 months, p=0.067) without statistical significance. In the multivariate analysis, using the Cox regression, those with a non-adenocarcinoma showed a trend of high risk of cancer death than those with an adenocarcinoma without statistical significance (Relative risk; 2.754, 95% Cl: $0.988{\sim}7.672$, p=0.053). Conclusion: We could not find an independent prognostic factor of malignant pleural effusion in NSCLC. As there was a trend of high risk of cancer death according to histology, further study will be needed.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.358-363
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• 2004

Background : Photodynamic therapy (PDT) involves the use of photosensitizing agents for treatment of malignant disease. PDT is approved by the U.S. Food and Drug Administration for the endobronchial microinvasive nonsmall cell lung cancer and for palliation in patients with obstructing tumors. We report our experience and results of PDT in lung cancer. Method : Ten patients with lung cancer who were diagnosed in Chosun university hospital by histologic confirm through bronchoscopy were included between August 2002 and May 2003. The photosensitizer (Photogem$^{(R)}$, Lomonosov institute of Fine Chemical, Russia/dose 2.0 mg/kg body weight) was injected 48 hours prior to the PDT session. For PDT with the photosensitizer (Photogem$^{(R)}$), Diode LASER system (Biolitec Inc., Germany, wavelength; 633nm) were used. PDTs were done at 48-72 hours after photogem injection. Follow up bronchoscopy and chest X-ray or thorax computerized tomography were done for evaluate PDT response. Results : 9 of 10 patients with endobronchial obstruction showed partial remission with bronchus opening after PDT. Direct reaction of the tumor to PDT was similar in despite of its localization. It was as follows; edema, hyperemia, in-situ bleeding, fibrin film occurrence. Any other complications such as sunburns of skin, inflammation within the PDT zone were not occurred by the end of the fourth week. Conclusion : In the advanced endobronchial disease, PDT has been shown to be useful in treating endobronchial tumors that are causing clinically significant dyspnea or are likely to progress and lead to further clinical complications, such as postobstructive pneumonia.

• Journal of Life Science
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• v.25 no.12
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• pp.1439-1444
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• 2015

Steroid receptor coactivators (SRC) are transcriptional coactivators. Among SRCs, SRC-3 is the most studied in relation to different types of tumors. However, the role of SRC-3 in early lung development and lung cancer has not been well studied. The expression profiles of SRC-3 showed that SRC-3 contributed to bronchial and alveolar development in embryonic lung development. SRC-3 was strongly expressed in Clara cells and type II alveolar cells during fetal lung development (E17.5- E18.5), and SRC-3 was expressed in both cell types in the adult lung. TTF-1 was expressed in the lungs of heterozygote SRC-3 mice and Clara cell-specific-CCSP-TAg tumor mice, along with SRC-3 expression. The expression of TTF-1 was localized at transformed Clara cells and multifocal adenocarcinomas in lung cancer mice. However, SRC-3 was not expressed in the multifocal adenocarcinomas, suggesting that SRC-3 might not be involved in the invasiveness of lung cancer. Cotransfection of TTF-1 in Clara cell-specific mtCC cell lines resulted in significant activation of CCSP expression. However, cotransfection of SRC-3 had no significant effects on transient transfection. These in vivo and in vitro results suggest that SRC-3 does not play a significant role in lung tumor progression. In conclusion, SRC-3 is involved in bronchial and alveolar development in fetal and adult lungs, but it does not play an important role in the progression of Clara cell-derived lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.550-558
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• 2001

Background : It has been reported that younger patients with lung cancer have characteristic features that differ from those in older patients. The prognosis for young patients with this disease is controversial. This study aimed to determine the clinicopathological characteristics, the survival rate, and the risk factors associated with the overall survival rate in younger patients with lung cancer. Methods : The records of 120 young(age${\leq}40$) patients with histologically confirmed lung cancer in the Korea Caneer Center Hospital(KCCH) between Jan. 1992 and Dec. 1998 were retrospectively reviewed. Of 5,082 lung cancer patients registered at the KCCH from 1992 to 1998, 120 older(age>40) patients were randomly selected as the controls. Results : More female patients(45.0% vs. 20.0%, p<0.001) and more adenocarcinoma cases(64.2% vs.38.3%, p<0.001) were found in the younger group, when compared to the older patients. In NSCLC, advanced disease(stage IIIB and IV) was more common in the younger patients(90.2%) than in the older patients(62.7%) (p<0.001). The Median survival was 8.6 months in the younger patients and 12.2 months in the older(p=0.003). In a multivariate analysis, only the advanced-stage was an independent negative prognostic factor. Conclusions : Lung cancer in the younger age group presents with a more advanced stage resulting in a poor survival rate, which suggests that lung cancer in this population is more aggressive than in older patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.962-974
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• 1998

Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

• Journal of Chest Surgery
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• v.38 no.4 s.249
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• pp.263-270
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• 2005

In recent years, a combination of two demographic phenomena, an increased number of older people in the population and an increase in the incidence of lung cancer with age, has made it mandatory to develop therapeutic modalities with less toxicity for the treatment of inoperable elderly patients with lung cancer. Therefore, we investigated the correlation between COX-2 expression and cytotoxicity of Nimesulide, a specific COX-2 inhibitor. Material and Method: Immunohistochemical staining of COX-2 was performed. After exposure of Nimesulide, XTT analysis, FACS analysis and Hoechst staining were carried out. Result: COX-2 protein was expressed in non-treated A549 cells strongly, but not in H1299. Cytotoxicity of Nimesulide against A549 cell and H1299 cell were similar and $IC_{50}$ of Nimesulide in both cell lines were $70.9{\mu}M$ in A549 cell line and $56.5{\mu}M$ in H1299 cell line respectively. FACS analysis showed $G_0/G_1$ arrest in both cell lines and the S phase cell fraction was decreased. Morphologic assessment of apoptosis by Hoechst 33258 staining, many apoptotic cells were detected in both cell lines. Conclusion: Selective COX-2 inhibitor, Nimesulide, can inhibit the proliferation of non-small cell lung cancer cell lines in vitro. Inhibitory effect of Nimesulide are induction of apoptosis and $G_0/G_1$ arrest. There is no correlation between COX-2 expression and cytotoxicity of Nimesulide, a specific COX-2 inhibitor. Therefore, highly selective COX-2 inhibitors such as Nimesulide can be expected to lead to even greater efficacy of their use as adjuncts to various anticancer angents and radiation therapy for the treatment of high-risk patients.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.160-170
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• 2006

Background : The aberrant promoter hypermethylation of p16INK4a, as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of $p16^{INK4a}$ promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation. Methods : Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16INK4amethylation was determined using methylation-specific polymerase chain reaction. Results : $p16^{INK4a}$ methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum. Conclusions : There was a higher level of $p16^{INK4a}$ methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that $p16^{INK4a}$ promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.354-362
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• 1994

Objectives and Methods : The presence of aneuploidy or high proliferative activity in cytologic specimens is considered as complementary for the diagnosis of malignancy. To evaluate the diagnostic usefulness of DNA ploidy and cell cycle analysis in lung cancer, we compared the diagnostic yielding rates of DNA ploidy test by brushing specimens using flow cytometry with bronchoscopic forceps biopsy and brushing cytology. Results : Of the seventy-six cases, 55 cases proved to have malignant diseases(squamous cell cancer: 27, adenocarcinoma: 7, large cell cancer: 1, undifferentiated: 4 and small cell cancer: 16). The incidence of aneuploidy in lung cancer patients was 32.7%(18/55), as opposed to no cases in benign disease. And the proportion of high proliferative activity(S+G2M>22%) in lung cancer patients was 42.9%(15/35), but none in benign diseases. In fifty-six of 75 cases(74.7%), cytology of brushing specimens and DNA analysis(either aneuploidy or high proliferative activity vs. diploidy and low proliferative activity) were in concordance. The sensitivity with only brushing cytology was 41.8%(23/55), but with the addition of DNA analysis, it was increased to 56.4%(31/55), without decreasing the specificity(100%). And there was a case whose clue for malignancy was absent except aneuploidy, and he was confirmed to have squamous cell cancer following open thoracotomy. There were no differences in the frequency of aneuploidy or high proliferative activity between histologic subtypes of bronchogenic malignancy. Conclusions : The diagnostic detection rate of lung cancer was improved with the addition of DNA ploidy and cell cycle analysis, and the presence of aneuploidy or high proliferative activity was a relatively specific indicator of malignant disease. It would be useful to test DNA ploidy and cell cycle analysis with brushing specimen for the diagnosis of bronchogenic malignancy particularly in patients whose biopsy specimen could not be obtainable.

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.5-13
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• 2002

Background: DNA repair plays a crucial role in protecting the genome from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to cancer. The human OGG1 (hOGG1) gene encodes DNA glycosylase/apurinic lyase and excise 8-hydroxyguanine, one of the major premutagenic DNA lesions, which is produced by oxygen radical forming agents including smoking. Recently several polymorphisms in the hOGG1 gene were identified, and it is possible that these polymorphism') may affect the DNA repair capacity and thus modulate cancer susceptibility. The relationship between the codon 326 polymorphism (Ser to Cys) in the hOGG1 gene and lung cancer risk was investigated. Materials and Method: The Ser326Cys genotypes were determined using PCR-RFLP analysis in 299 primary lung cancer patients and 186 healthy controls who were frequency (case:control=3:2) matched according to age and sex. Result: The frequencies of the Ser326Cys genotypes (Ser/Ser, Ser/Cys and Cys/Cys) among cases (23.4%, 51.8%, and 24.7%, respectively) were not significantly different from those among the controls (22.6%,52.1% and 25.3%, respectively). When the analyses were stratified according to age, sex, smoking status and packyears of smoking, no significant association between this polymorphism and lung cancer risk was found. Moreover, the Ser326Cys genotype showed no apparent relationship with any of the histological types of lung cancer. Conclusion: These result suggest that the hOGG1 Ser326Cys polymorphism is not a major contributor to individual lung cancer susceptibility in Koreans.