• Tuberculosis and Respiratory Diseases
• /
• v.48 no.6
• /
• pp.909-921
• /
• 2000

Background : Defects in apoptotic signaling pathways play important role in tumor initiation, progression, metastasis and resistance to treatment. Several proteins which may promote tumorigenesis by inhibiting apoptosis were identified. The survivin protein is the member of inhibitor of apoptosis protein(IAPs) family which inhibits apoptosis. Unlike other IAPs, it is expressed in during the fetal period but not in adult differentiated tissues. Many reports have stated that survivin is selectively expressed in many cancer cell lines and cancer tissues. We performed immunohistochemical analysis for survivin expression in non-mall cell lung cancer to get evaluate its clinical implication. Methods : Twenty nine surgically resected lung cancers were examined. Immunohistochemical staining were performed by immuno-peroxidase technique using avidin-biotinylated horseradish pemxidase complex in the formalin-fixed, paraffin-embedded tissue $4{\mu}m$ section. Anti-survivin polyclonal antibody was used for primary antibody and anti-p53 monoclonal antibody was also used to analyze the correlation between survivin and p53 expression. The survivin expression scores were determined by as the sum of the stained area and intensity. Results : Immunohistochemical analysis showed cancer specific expression of survivin in 20 of 29 cases (69.0%). Western blot analysis also showed the selective survivin expression in tumor tissue. There was no correlation between survivin expression and clinicopathological parameters and prognosis. We analyzed the ∞π'elation between survivin expression and p53 expression, but found none. Conclusion: We confirmed the tumor specific expression of survival in non-small cell lung canær. But this expression was not correlated with clinical parameters as well as histology, tumor stage, recurrence, and survival rate. Also it was not statistically correlated with the expression of p53.

• Tuberculosis and Respiratory Diseases
• /
• v.51 no.6
• /
• pp.540-549
• /
• 2001

Background : Usual interstitial pneumonia (UIP) is a progressive fibrous lung disease with occasional fatal outcomes. However, the extent and rate of progression varies markedly from one patient to another. As a result, it is difficult to determine the time of the initial treatment and assess the disease activity and course. Fibroblast foci (FF) is well known to synthesize collagen actively by their myofibroblasts component. However, the prognostic value of the FF have not been evaluated in patients with VIP. Therefore this study was undertaken to determine how the number of fibroblastic foci can reflect the disease activity and progression. Methods: Twenty patients with UIP(M : F=13 : 7), who were diagnosed by a surgical lung biopsy. The number of fibroblastic foci was analyzed in terms of its correlation with the clinical manifostations, pulmonary function test, arterial blood gas analysis, and a bronchoalveolar lavage(BAL). Results : The number of fibroblastic foci did not correlate with the various lung function tests and the other clinical parameters. Interestingly, the percentage of neutrophils in the bronchoalveolar lavage fluid did correlate with the quantity of the normalized Vv of FF(r=0.60, p<0.05). The patients were divided into 2 groups, group I and II, arbitrarily, according to the value of the normalized Vv. The clinical parameters and the PIT results were not different between the two groups. In particular, the survival rate between the two groups according to the Kaplan-Meier analysis were not different. Conclusion : A large number of FF does not imply a bad prognosis in patients with UIP.

• Tuberculosis and Respiratory Diseases
• /
• v.51 no.6
• /
• pp.570-578
• /
• 2001

Background: With cases of chronic obstructive pulmonary disease(COPD), weight loss and low body weight have been found to correlate with increased mortality and poor prognosis. Therefore, nutritional aspects are an important part of the treatment in cases of COPD. In Korea, there is only limited data available for the changes of resting pulmonary function in relation to nutritional status. This study was carried out to investigate the differences of resting pulmonary function in relation to the nutritional status of patients with COPD. Method : 83 stable patients, with moderate to severe COPD, were clinically assessed for their nutritional status and resting pulmonary function. The patients' nutritional status was evaluated by body weight and fat-free mass (FFM), which was assessed by bioelectrical impedance analysis. According to their nutritional status, the 83 patients were divided into two groups, designated as the depleted, and non-depleted, groups. Result : Of the 83 patients, 31% were characterized by body weight loss and depletion of FFM, whereas 28% had either weight loss or depleted FFM. In the depleted group, significantly lower peak expiratory flow rate(p<0.05) and Kco(p<0.01), but significantly higher airway resistance(Raw, p<0.05) were noted. There was no difference for the non-depleted group in forced expiratory volume at one second, residual volume, inspiratory vital capacity, or total lung capacity. Maximal inspiratory pressure($P_{Imax}$) was also significantly lower in the depleted group(p<0.05). Conclusion : We conclude, from our clinical studies, that nutritional depletion is significantly associated with the change in resting pulmonary function for patients with moderate to severe COPD.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.5
• /
• pp.591-598
• /
• 2001

Background : Primary adenoid cystic carcinoma arising in the bronchus is an uncommon disease that is histologically and ultrastructurally identical to the salivary gland tumor of the same name and regarded as a slow growing low-grade malignancy. We examined its clinical characteristics. Method : We collected 13 Korean cases of primary adenoid cystic carcinoma arising in the bronchus including 5 cases of our own and 8 cases from the literature. Result : The patients ages ranged from 20 to 74. Men numbered 9 and women 4. The presenting symptoms were cough, dyspnea, and hemoptysis. The fiberoptic bronchoscopic findings were primarily hypervascular polypoid mass with a smooth surface that obstructed airway totally or near totally. There were three inoperable cases including two cases with distant metastasis to bone or cervical lymph node and one case with mediastinal invasion. The remaining 10 patients underwent surgical resection. Among them, two patients received postoperative radiotherapy. The median survival was 21 months in the 8 surgical and evaluable cases. One patient lived 13 years without recurrence. The prognosis was relatively favorable in operable cases. Conclusion : It was not common for primary adenoid cystic carcinoma arising in the bronchus to have distant metastasis or invasion to the mediastinum on presentation. The prognosis was relatively favorable in operable cases. It would be important to perform flexible bronchoscopy for early diagnosis and to do surgical treatment if possible.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.4
• /
• pp.488-497
• /
• 1999

Background : Identification of the histologic cell type of lung cancer is important because it is related to the treatment modality and prognosis. Currently, many diagnostic methods are used to determine the cell type. We have studied to evaluate the histologic accuracy of each diagnostic methods in lung cancer. Method : 168 cases were analysed retrospectively, who underwent curative thoracotomy for lung cancer in Seoul National University Hospital from January, 1994 to February, 1997. Sputum cytology, percutaneous needle aspiration(PCNA), percutaneous needle biopsy(PCNB), bronchial washing cytology and flexible bronchoscopic biopsy were evaluated respectively. The k coefficient was applied to evaluate the degree of concordance between the histologic diagnosis obtained by each methods and the one derived from thoracotomy. Results : The k value in sputum cytology was 0.86. In the 34 cases with squamous cell carcinoma(SQ), 32 cases were finally diagnosed as having such by thoracotomy. 7 of the 8 cases with adenocarcinoma(AD) turned out to have the same. The k value in PCNA was 0.51. In the 31 cases with SQ, only 14 cases were finally diagnosed as having such. All of the 3 cases with small cell carcinoma(SC) turned out to have the same. The k value in PCNB was 0.77. The diagnosis was correct in 13 of the 16 patients with SQ and in 30 of the 32 cases with AD. The k value in bronchial washing cytology was 1.0. In all of the 29 cases with SQ and all of the 7 cases with AD, the diagnosis was correct. The k value in flexible bronchoscopic biopsy was 0.77. The diagnosis was correct in 51 of the 52 cases with SQ and in 1 of the 2 cases with SC. Conclusion : The concordance rate with the final histologic diagnosis in sputum cytology, PCNB, bronchial washing cytology and flexible bronchoscopic biopsy were excellent ($k{\geq}0.75$), while that in PCNA was fair (k=0.53). Because PCNA showed lower concordance rate than other diagnostic methods, PCNA is recommended to perform with PCNB.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.6
• /
• pp.898-908
• /
• 2000

Background : Eotaxin a CC chemokine specific for eosinophils, is implicated in the pathogenesis of asthma by recruiting eosinophils into the airways. Theophylline has been used for the treatment of asthma and recently was proposed to have an anti-inflammatory action. The aim of this study is to examine whether theophylline may inhibit the eosinophilic airway inflammation by reducing the expression of eotaxin. Methods : The expression of eotaxin mRNA was assessed by Northern analysis in A549 cells 4 h after stimulation with TNF-$\alpha$ or IL-1$\beta$. And then, theophylline was added to A549 cells stimulated with 0.1 ng/mL IL-1$\beta$. Results : Eotaxin mRNA expression rates induced by 0.1, 1, 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 7%, 22%. 28%, respectively. Eotaxin mRNA expression rates induced by 0.01, 0.1, 1, 10 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 10%, 42%, 63%, 72%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 10 ng/mL TNF-$\alpha$ as compared with $\beta$-actin, were 27%, 18%, 8%, respectively. Eotaxin mRNA expression rate after the addition of 0, 0.001, 0.01, 0.1 ${\mu}M$ dexamethasone induced by 0.1 ng/mL IL-1$\beta$ as compared with $\beta$-actin, were 43%, 47%, 12%, 8%, respectively. Eotaxin mRNA expression rates after the addition of 0, 0.001, 0.01, 0.1, 1, 10 mM theophylline induced by 0.1 ng/mL IL-1$\beta$, as compared with $\beta$-actin, were 48%, 40%, 33%, 22%, 16%, 14%, respectively. Conclusion : These results suggest that theophylline may reduce eosinophil infiltration of the airway at least in part by reducing the expression of eotaxin under the conditions of these experiments.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.2
• /
• pp.189-197
• /
• 2000

Background : Tissue inhibitor of metalloproteinase is a natural inhibitor that counteracts pro teolytic enzymes essential to the invasion of cancer cell. Whether or not TIMP-2 gene transfer via adenovirus could inhibit the invasion of lung cancer cell iη vitro was evaluated for the future purpose of gene therapy against lung cancer. Methods : Recombinant adenovirus-TIMP-2(Ad-TIMP-2) was generated by homologous recombination after pACCMV-TIMP-2 and pJM17 were cotransfected into 293 cell by standard calcium phosphate coprecipitate method. Calu-6, one of the most invasive lung cancer cells, was transduced with Ad-TIMP-2 or Ad-$\beta$gal. Anchorage-independent growth and invasiveness were assessed by soft agar clonogenicity assay and invasion assay using two-chamber, well divided by matrigel. Results : Ad-TIMP-2 transduced calu-6 cells produced biologically active TIMP-2 more than 50 times more than parental calu-6. TIMP-2 gene transfer did not suppress the in vitro tumorigenicity. However, two chamber well assay revealed that Ad-TIMP-2 transduction reduced the invasiveness of calu-6 efficiently (12% compared with parental cell) even at low 10moi. Conclusion : Even though TIMP-2 gene transfer did not inhibit in vitro tumorigenicity, it did inhibit invasion of lung cancer cell in vitro. The inhibition of invasion by Ad-TIMP-2 may be a useful strategy for the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.776-784
• /
• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.5
• /
• pp.585-593
• /
• 2000

Background : International consensus guidelines have recently been developed to improve the assessment and management of asthma. One of the major recommendation of these guidelines is that asthma severity should be assessed through the recognition of key symptoms, such as nocturnal waking, medication requirements, and objective measurements of lung function. Differential classification of asthma severity would lead to major differences in both long term pharmacological management and the treatment of severe exacerbation. Methods : This study examined the relationship between the symptom score and measurements of $FEV_1$ and PEF when expressed as a percentage of predicted values in asthmatics (n=107). Results : The correlation of $FEV_1$ % with PEFR% was highly significant (r=0.83, p<0.01). However, there was agreement in terms of the classification of asthma severity in 76.6% of the paired measurements of $FEV_1$ % and PEFR%. Agreement in the classification of asthma severity was also found in 57.1% of the paired analysis of $FEV_1$ % and symptom score. 39% of the patients classified as having moderate asthma on the basis of $FEV_1$ % recording would be considered to have severe asthma if symptom score alone were used. Low baseline $FEV_1$ and high bronchial responsiveness were associated with a low degree of perception of airway obstruction. Conclusion : The relationships between the symptom score, PEFR and $FEV_1$ were generally poor. When assessing asthma severity, age, duration, $PC_{20}$, and baseline $FEV_1$ should be considered.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.785-794
• /
• 1998

Background: Chemical pleurodesis is a widely used method for the control of symptomatic and recurrent malignant pleural effusions. Talc has been accepted to be the most effective sclerosing agent for chemical pleurodesis. This study was undertaken to evaluate the usefulness of talc pleurodesis via video-assisted thoracoscopic surgery (VATS) in treatment of malignant pleural effusions. Methods : A retrospective analysis of the medical records and radiographic findings was performed. The success of the procedure was defined as daily pleural fluid drainage below 100ml within 1 week after pleurodesis and complete expansion of the lung on simple chest radiograph. Recurrence was defined as reaccumulation of pleural fluid on follow-up chest radiographs, and complete response as no fluid accumulation on follow-up chest radiographs. Results: Between October 1994 and August 1996, talc pleurodesis via VATS was performed in 35 patients. Duration of follow-up ranged from 5 days to 828 days(median 79days). The initial success rate of procedure was 88.6%(31 of 35 cases). Complete responses were observed in 92.8% at 30 days, 75.7% at 90 days and 64.9% at 180 days. Postoperative complications were fever (54.3%), subcutaneous emphysema(11.4%), reexpansion pulmonary edema(2.9%) and respiratory failure(5.7%). But procedure related mortality or respiratory failure was not found. Conclusion: Talc pleurodesis via VATS is a safe and effective method for the control of symptomatic malignant pleural effusions.