• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.855-861
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• 1995

Background: Parathyroid hormone-related protein(PTHrp) was first identified as the cause of hypercalcemia in malignancy. Hypercalcemia can be found in malignancy, especially in the epidermoid carcinoma of the lung, even without extensive metastases to the bones. The application of sensitive assays for PTHrp may help in the early diagnosis of lung cancer, in the monitoring of treatment and in the detection of recurrence. Method: Serum PTHrp was measured by radioimmunoassay detecting the N-terminal 1~34 peptide of human PTHrp(PTHrp 1-34) in 63 histologically confirmed lung cancer patients and 22 healthy controls. Result: Serum PTHrp(mean$\pm$S.E.) was $312{\pm}68.9pg/ml$ in 63 lung cancer patients and $158{\pm}38.2pg/ml$ in 22 controls(p>0.05). PTHrp was $356{\pm}103.9pg/ml$ in 34 epidermoid carcinoma patients, $281{\pm}148.7pg/ml$ in 15 adenocarcinoma patients and $316{\pm}140.8pg/ml$ in 9 small cell carcinoma patients. In epidermoid carcinoma patients, PTHrp was $570{\pm}472.3pg/ml$ in stage II(n=3; p<0.05 vs controls), $166{\pm}22.4pg/ml$ in stage IIIa(n=9), $282{\pm}113.3pg/ml$ in stage IIIb(n=12) and $668{\pm}367.9pg/ml$ in stage IV(n=9; p<0.05 vs controls). PTHrp was significantly increased in 8 epidermoid carcinoma patients with bone metastases($1526{\pm}811.2\;pg/ml$; p<0.0005 vs controls). Hypercalcemia was observed in an epidermoid carcinoma patient whose PTHrp value was 244 pg/ml. Conclusion: The serum PTHrp was increased in advanced epidermoid carcinoma patients even without hypercalcemia. The measurement of PTHrp may be not helpful in the early diagnosis of lung cancer. But the lung cancer should be suspected in the marked elevation of PTHrp. It may be of value in detecting patients of advanced diseases with bone metastases or patients who might develop the malignancy associated hypercalcemia.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.216-223
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• 2001

Purpose : We evaluated retrospectively the outcomes of inoperable squamous cell lung cancer patients treated with radiotherapy to find out prognostic factors affecting survival. Materials and methods : Four hundred and eleven patients diagnosed as squamous cell lung cancer between November 1988 and December 1997 were the basis of this analyses. The planned dose to the gross tumor volume was ranged from 30 to 70.2 Gy. Chemotherapy was combined in 72 patients $(17.5\%)$ with the variable schedule and drug combination regimens. Follow-up period ranged from 1 to 113 months with the median of 8 months and survival status was identified in 381 patients $(92.7\%)$. Overall survival rate was calculated using the Kaplan-Meier method. Results : Age ranged from 23 years to 83 years with the median 63 years. The male to female ratio was about 16:1. For all 411 patients, the median overall survival was 8 months and the 1-year survival rate (YSR), 2-YSR, and 5-YSR were $35.6\%,\;12.6\%,\;and\;3.7\%$, respectively. The median and 5-YSR were 29 months and $33.3\%$ for Stage IA, 13 months and $6.3\%$ for Stage IIIA, and 9 months and $3.4\%$ for Stage IIIB, respectively(p=0.00). The median survival by treatment aim was 11 months in radical intent group and 5 months in palliative, respectively (p=0.00). Of 344 patients treated with radical intent, median survival of patients (N=247) who received planned radiotherapy completely was 12 months while that of patients (N=97) who did not was 5 months (p=0.0006). In the analyses of the various prognostic factors affecting to the survival outcomes in 247 patients who completed the planned radiotherapy, tumor location, supraclavicular LAP, SVC syndrome, pleural effusion, total lung atelectasis and hoarseness were statistically significant prognostic factors both in the univariate and multivariate analyses while the addition of chemotherapy was statistically significant only in multivariate analyses. The acute radiation esophagitis requiring analgesics was appeared in 49 patients $(11.9\%)$ and severe radiation esophagitis requiring hospitalization was shown in 2 patients $(0.5\%)$. The radiation pneumonitis requiring steroid medication was shown in 62 patients $(15.1\%)$ and severe pneumonitis requiring hospitalization was occurred in 2 patients $(0.5\%)$. During follow-up, 114 patients $(27.7\%)$ had progression of local disease with 10 months of median time to recur (range : $1\~87\;months$) and 49 patients $(11.9\%)$ had distant failure with 7 months of median value (range : $1\~52\;months$). Second malignancy before or after the diagnosis of lung cancer was appeared in 11 patients Conclusion : The conventional radiotherapy in the patients with locally advanced squamous cell lung cancer has given small survival advantage over supportive care and it is very important to select the patient group who can obtain the maximal benefit and to select the radiotherapy technique that would not compromise the life quality in these patients.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.474-485
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• 2000

Background : Current studies on multimodal strategy for N2 non-small cell lung cancer are being high interest, have drawn much attention. N2 lung cancer, however, is composed of is divided into several sub groups with that have different prognoses. The prognostic factors still remain controversial. Methods : Between January 1990 and June 1999, 180 patients with N2 lung cancer who underwent surgical resection were investigated, excluding 10 of these for surgical mortality. All patients underwent mediastinal lymph node dissection. 20 clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Results : The overall 5-year survival rate was 20.6%. Multivariable analyses among overall patients revealed 3 significant prognostic factors : Age, Histologic type, Vascular invasion. Based on the result, 49 patients with both age more than 60 and pathologic Non-squamous cell showed a 5-year survival of 5.0%, whereas 37 patients with neither of the factors showed a 5-year survival of 56.6%(p<0.001). And 12 patients with both vascular invasion and pathologic Non-squamous cell showed a 5-year survival of 11.9%, whereas 67 patients with neither of the factors showed a 5-year survival of 33.6%(p=0.01). Conclusion : The prognosis of surgically resected N2 disease varies according to the 3 significant prognosis factors. Tumor size may be an additional influencing factor in the prognosis of N2 disease.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.523-532
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• 1999

Background: With the development of the molecular biological methods, studies of the early diagnosis of lung cancer and the detection in the preneoplastic state by using genetic probes in the high risk groups are widely investigated. In lung cancer, squamous cell carcinoma is considered to progress from the normal bronchial mucosa to the preneoplastic state, and finally to the invasive carcinoma. In this study, we investigated the expression of p53 and c-erbB2 in the normal bronchi and the cancer tissues in patients with squamous cell lung cancer to evaluate the possibility of using these immunohistochemical markers as the diagnostic and prognostic parameters of patients with squamous cell lung cancer. Method: The normal and cancerous bronchial tissues of 25 patients with squamous cell carcinoma of the lung, surgically resected from May 1995 to November 1996, were immunohistochemically stained with the monoclonal antibodies to p53(DAKO-p53) and c-erbB2(phamingen 15821A) respectively. We compared the expression status of these markers between the normal bronchial mucosa and the tumor tissue, and also investigated the relationship between the expression status of these markers in tumor tissues and the pathological stage, and the survival time. Results: The pathological stage was as follows; stage I, II were found in 5 patients respectively, stage IIIA was in 8 patients, stage IIIB was in 4 patients, and stage IV was in 3 patients. The expression rate of p53 in the squamous cell lung cancer was 48%, and it was not expressed in the normal bronchial mucosa. The expression status was increased as the pathological stage advanced(p=0.0091 by test of trend). But there were no relationship between the expression of p53 and the median survival time. C-erbB2 did not yield a significantly meaningful result. Conclusion: p53 was not found in the normal bronchial mucosa, but it was expressed in 48% of the tumor tissue. And the expression rate increased as the pathological stage advanced. So it would be helpful to apply the immunochistochemical stain with p53 in the bronchial biopsy specimen in the early diagnosis trial or staging of squamous cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.565-573
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• 1998

Malignant pleural effusions are most commonly associated with lung cancers, however, it also can be resulted from breast cancers, ovarian cancers, stomach cancers and so on. According to the their histologic types, adenocarcinoma have been known as the most common cell type of malignant pleural effusions and squamous cell carcinoma is rare. We herein present incidences, clinical characteristics and survivals of malignant pleural effusions according to their cell types and primary diseases. The objects are 84 malignant pleural effusion patients diagnosed by pleural fluid cytologic examination or pleural biopsy from Jan. 1992 to May. 1997 in Seoul National University Hospital. A retrospective chart review on their histologic types, biochemical parameters and survivals is described. Among 84 patients, 52 were males and the other 32 were females with 1.6:1 of male and female ratio and their mean age was 57.6 years old. Common symptoms of them wele dyspnea, cough, sputum and pleuritic chest pain. The proportions of bloody nature of effusion, lymphocyte dominant pleural effusion, exudative effusions were 66%, 39% and 93%, respectively. They consisted of 54 cases of adenocarcinoma(33 cases of them were lung cancers), and 10 cases of squamous cell carcinoma (8 cases of them were lung cancers), 10 cases of malignant lymphoma, 8 cases of small cell lung cancer and a case of mesothelioma and leukemia. There was no differences in characteristics of effusions, clinical features and survivals between each histologic cell types. Analyzing them according to primary diseases, no difference except longer survivals in malignant pleural effusions from breast cancer than from other cancers was observed. In conclusion, considering the incidences of histologic types of lung cancers during same period (squamous cell carcinoma; 47%, adenocarcinoma; 33%, small cell lung cancer; 12% and large cell carcinoma; 2%), malignant pleural effusions more likely occurred in adenocarcinoma than other cell types of lung cancers and there was no significant difference of clinical characteristics between histologic types.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.463-474
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• 2002

Background : This study was designed to examine how glutathione, one of the nucleophilic sulfur compounds, effects the cisplatin cellular toxicity in the non-small cell lung cancer cell lines and normal lung epithelial cell line. Materials and Methods : Three cultured cell lines, the lung adenocarcinoma cell(NCL-H23), the lung squamous carcinoma cell(SK-MES-1) and the normal lung epithelial cell(L-132) line were exposed to various concentrations of cisplatin with or without glutathione. The relative viability was estimated as a means of measuring the cisplatin cellular toxicity using the MTT method. Results : In NCI-23, the response to cisplatin was sensitive but glutathione markedly increased the relative survival of the tumor cells by removing the antitumor effect of cisplatin. In both SK-MES-1 and L-132, the responses to cisplatin were less sensitive, and the chemoprotective effect of glutathione compared to and equal cisplatin dose was significantly higher in L-132 than in SK-MES-1(p<0.05). Conclusion : The protective effectes of of glutathione on cisplatin-induced cellular toxicity is more significant in normal lung epithelial cells than in squamous carcinoma cells.

• Tuberculosis and Respiratory Diseases
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• v.64 no.1
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• pp.15-21
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• 2008

Background: The melanoma antigen-encoding (MAGE) genes are known to be expressed in various cancer cells, including non-small cell lung cancer (NSCLC), and are silent in all normal tissues except for the testis. In patients with peripheral NSCLC, bronchial washing fluid can be used to detect the MAGE genes, suggesting a diagnosis of lung cancer. In order to evaluate the diagnostic utility of the MAGE test in patients with peripheral NSCLC, bronchial washing fluid was investigated in patients with peripheral pulmonary nodules, which were invisible as detected by bronchoscopy. Methods: Bronchial washing fluid from 37 patients was used for cytological examinations and MAGE gene detection, using RT-nested-PCR of common A1-A6 mRNA. Results were compared to a final diagnosis of patients as confirmed by pathology. Results: Among the 37 subjects, NSCLC was diagnosed in 21 patients, and benign pulmonary diseases were diagnosed in 16 patients. MAGE mRNA was detected in 10 of 21 (47.6%) NSCLC patients, while conventional cytology examinations were positive for MAGE expression in 2 of 21 (9.5%) cases. MAGE expression was observed in 4 of 16 (25%) benign pulmonary disease patients. Conclusion: The MAGE test of bronchial washing fluid can be used as a sensitive predictor of peripheral NSCLC patients.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.178-183
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• 2001

The nephrotic syndrome that occurs in the absence of renal vein thrombosis, amyloidosis, neoplastic infiltration of the kidneys is an unusual but a well recognized paraneoplastic syndrome. The most frequently reported neoplasms associated with nephrotic syndrome are Hodgkin's disease and various carcinomas. The most common renal lesions are membranous glomerulonephritis(MGN) associated with carcinomas and minimal change lesions associated with Hodgkin's disease. Approximately 40% to 45% of patients clinically manifest the MGN symptoms prior to the diagnosis of the tumor, 40% simultaneously with the tumor and the remaining 15% to 20% following the tumor. Therefore, evaluating the underlying malignancy in patients with MGN is important. Here we report a patient with squamous cell lung cancer, which was detected 12 months after a MGN had been diagnosed, with a review of the relevant literature.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.69-84
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• 1997

Background : Although the overall prognosis of patients with lung cancer is poor, highly effective treatment exists for the small subset of patients with early lung cancer(carcinoma in situ/micro- invasive cancer). But very few patients have benefit from them because these lesions are difficult to detect and localize with conventional white-light bronchoscopy. To overcome this problem, a Lung Imaging Fluorescence Endoscopic device(LIFE) was developed to detect and clearly delineate the exact location and extent of premalignant and early lung cancer lesions using differences in tissue autofluorescence. Purpose : The purpose of this study was to determine the difference of sensitivity and specificity in detecting dysplasia and carcinoma between fluorescence imaging and conventional white light bronchoscopy. Material and Methods : 35 patients (16 with abnormal chest X-ray, 2 with positive sputum study, 2 with undiagnosed pleural effusion, 15 with respiratory symptom) have been examined by LIFE imaging system. After a white light bronchoscopy, the patients were submitted to fluorescence bronchoscopy and the findings of both examinations have been classified in 3 categories(class I, II, III). From of all class n and III sites, 79 biopsy specimens have been collected for histologic examination: a comparison between histologic results and white light or fluorescence bronchoscopy has been performed for assessing sensitivity and specificity of the two methods. Results : 1) Total 79 sires in 35 patients were examined. Histology demonstrated 8 normal mucosa, 21 hyperplasia, 23 dysplasia, and 27 microinvasive and invasive carcinoma. 2) The sensitivity of white light or fluorescence bronchoscopy in detecting dysplasia was 60.9% and 82.6%, respectively. 3) The results of this study showed 70.3 % sensitivity for microinvasive or invasive carcinoma with LIFE system, versus 100% sensitivity for white light in 27 cases of carcinoma. The false negative study of LIFE system was 8 cases(3 adenocarcinoma and 5 small cell carcinoma), which were infiltrated in submucosal area and had normal epithelium. Conclusion : To improve the ability 10 diagnose and stage more accurately, fluorescence imaging may become an important adjunct to conventional bronchoscopic examination because of its high detection rate of premalignant and malignant epithelial lesion. But. it has limitation to detect in submucosal infiltrating carcinoma.