• Tuberculosis and Respiratory Diseases
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• v.63 no.3
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• pp.242-250
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• 2007

Background: Abnormal angiogenesis can induce hypoxia within a highly proliferating tumor mass, and these hypoxic conditions can in turn create clinical problems, such as resistance to chemotherapy. However, the mechanism by which hypoxia induces these changes has not yet been determined. Therefore, this study was conducted to determine how hypoxia induces changes in cell viability and extracellular microenvironments in an in vitro culture system using non-small cell lung cancer cells. Methods: The non-small cell lung cancer cell line, A549 was cultured in DMEM or RPMI-1640 media that contained fetal bovine serum. A decrease in the oxygen tension of the media that contained the culture was then induced in a hypoxia microchamber using a $CO_2-N_2$ gas mixture. A gas analysis and an MTT assay were then conducted. Results: (1) The decrease in oxygen tension was checked the anaerobic gas mixture for 30 min and then reoxygenation was induced by adding a 5% $CO_2-room$ air gas mixture to the chamber. (2) Purging with the anaerobic gas mixture was found to decrease the further oxygen tension of cell culture media. (3) The low oxygen tension resulted in a low pH, lactic acidosis and a decreased glucose concentration in the media. (4) The decrease in glucose concentration that was observed as a result of hypoxia was markedly different when different types of media were evaluated. (5) The decrease in oxygen tension inhibited proliferation of A549 cells. Conclusion: These data suggests that tumor hypoxia is associated with acidosis and hypoglycemia, which have been implicated in the development of resistance to chemotherapy and radiotherapy.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.389-396
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• 1994

Background : The two most important purposes of fiberoptic bronchoscopy in lung cancer patients are obtaining tissue diagnosis and staging. The direct sign of lung cancer on FOB includes visible tumor, with smooth or nodular surface, with or without necrosis and infiltration. Variant cell types of lung cancer have their characteristic biological behaviors respectively. For example, squamous cell carcinoma grows slowly, invades locally and has easy necrosis resulting in cavitation, whereas adenocarcinoma shows early metastasis, small cell carcinoma shows rapid growth and higher early metastasis rate. Based on this, it could be hypothesized that each cell type may have characteristic bronchoscopic finding. Method : To answer this question, we reviewed 106 cases which were diagnosed as primary lung cancer and had bronchoscopically visible specific cancerous lesions. Results : The results were as follows. 1) Squamous cell carcinoma accounted for 66 cases(62.2%), adenocarcinoma 15 cases(14.2%), large cell carcinoma 3 cases(2.8%). 2) The endobronchial tumor lesion was arbitrarily classified into 5 types according to gross characteristics. Type A, multilobulating mass with necrosis, accounted for 24.5%, type B, multilobulating mass without necrosis, 25.5%, type C, round beefy mass, 9.4%, type D, infiltration with mucosal irregularity, 6.6%, and type E, infiltration without mucosal irregularity, 34%. 3) The analysis of correlation between endobronchial tumor pattern and specific cell type revealed that squamous cell carcinoma had relation with the morphologic type B and small cell carcinoma had relation with the morphologic type E, but adenocarcinoma had no preponderance in morphologic type. The gross appearance had influence on the diagnostic yields of biopsies and the diagnostic yields of lobulating mass types(type A, B) were higher than those of other types. Conclusion : From the above observations, it could be concluded that squamous cell carcinoma and small cell carcinoma have relations with specific types of bronchoscopic morphology, but not the case in adenocarcinoma.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.359-366
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• 2005

Background : IGFBP-3 inhibits the mitogenic and anti-apoptotic activity of IGF by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from its degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Method : We attempted to ascertain whether A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC), using PCR-restriction fragment length polymorphism (RFLP). Our study included 104 NSCLC patients and 104 age-, gender-, and smoking status-matched control subjects. Result : In the 104 NSCLC subjects, the genotypic frequencies at the -202 site were as follows: AA = 67 (64.4%), AC = 35 (33.7%), and CC = 2 (1.9%). We did detect significant differences in the genotypic distribution between the NSCLC and the control subjects (p<0.05), and the NSCLC risk correlated significantly with AA genotype at the -202 locus (AA>AC>CC). Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.60 (95% CI: 0.89 - 8.60), and the OR associated with AA genotype was 5.89 (95% CI: 1.92 - 21.16). Conclusion : These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.322-332
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• 1998

Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.310-322
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• 2000

Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.333-340
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• 1998

Background: Lung cancer is the leading cause of cancer over the world. P53 alteration is by far the most common genetic defect in lung cancer. The mutation of p53 protein involves the loss of inhibitory function of p53 related tumor suppressor gene and resultant oncogenesis. The analysis of p53 alterations consists of immunohistochemical stain, PCR based assay, or serologic ELISA (enzyme-linked immunosorbent assay). Methods : Serum levels of p53 mutant protein were measured in 69 cases of lung cancer (adenocarcinoma n=29, epidermoid n=16, small cell n=13, large cell n=1, undifferentiated n=1, undetermined n=9) and 42 controls of respiratory disorders using ELISA. Immunohistochemical stain in tissue was performed using monoclonal antibody of p53 in lung cancer subjects. Results: Both serum p53s in nonsmall cell cancer ($0.28{\pm}0.44ng/ml$) and in small cell cancer ($0.20{\pm}0.14ng/ml$) were not different from controls ($0.34{\pm}0.20ng/ml$). Also there was no significant difference in serum p53 according to tumor stages. P53 immunohistochemical stain showed 50% positivity overall in lung cancer. There were no close correlation between serologic level and positivity of immunohistochemical stain. Conclusion: The serologic determination of p53 mutant protein is thought to have no diagnostic role in lung cancer. Immunohistochemical stain in lung cancer specimen shows 50% positivity.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.45-56
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• 1998

Background: Lung cancer continues to increase worldwide. Also, the proportion of female patients incease and adenocarcinoma is the predominant histological type among lung cancer in many western countries. So, we studied these current trends of lung cancer by clinical approach of recent patients from our department Method: We conducted a retrospective analysis on 212 subjects who were diagnosed with lung cancer at the department of chest medicine in National Medical Center between January 1990 and July 1996. The contents of analysis were patient's profile, clinical manifestation, smoking habits, accuracy of diagnostic methods, histological cell type, staging and treatment, etc. Results: The results were as follows. 1) The ratio of male to female was 5.2 : 1. The peak incidence of age was 7th decade(35.4%). 2) Chief complaints were cough, dyspnea and chest pain, etc. The most common duration of symptoms before the first admission was less than 3 months(57.7%). On the other side, duration more than 1 year represented 6.5%. The early diagnosed patients has been increased from the 1980s. 3) Smokers among the total patients were 77.2%. The proportion of smokers in sqamous cell carcinoma, small cell carcinoma and adenocarcinoma were 88.4%, 85.7% and 55.7%, respectively. Smoking history and histological cell type were correlated in squamous and small cell carcinoma. 4) Squamous cell carcinoma is still the predominant histological type (44.8%), but, adenocarcinoma increased more than the previous study(30.7%). The other histological types were small cell carcinoma(17.0%) and large cell carcinoma(3.8%) in order of their proportions. 5) The accuracy of diagnostic methods were as follows: sputum cytology 75.3%, bronchoscopic biopsy 65.7%, lymph node aspiration cytology 95.8%, percutaneous lung aspiration cytology 94.6% and open lung biopsy 100%. The general accuracies of diagnostic methods were improved than previous studies. 6) Performance status scales on admission were relatively good. After diagnosis, chemotherapy and/or radiotherapy were undertaken in 69.3% of the patients, and only 7.5% of the patients were operated. Conclusion: In our study, squamous cell carcinoma is still the predominant histological cell type, but, adenocarcinoma continues to increase. Because adenocarcinoma is less correlated with smoking habits, further evaluation of other carcinogens than smoking is requested. Screening and early diagnosis of lung cancer is important for good performance status scales in spite of advanced stages. But, we think that the prevention, for example, stop smokings is more important as because of no perfect treatment for lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.84-93
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• 2001

Backgrounds : In the absence of distant metastasis, small cell lung cancer (SCLC) patients presenting with supraclavicular lymph node (SCLN) involvement and pleural effusion can benefit from thoracic radiotherapy. But there are some debate as to the prognostic significance of both SCLN involvement and pleural effusion. The purpose of this study was to determine the prognostic significance of SCLN involvement and pleural effusion in SCLC. Methods : Two Hundred and fifteen patients with histologically confirmed small cell lung cancer, who were treated either at the Keimyung university Dongsan hospital and Kyungpook national university hospital from January 1994 to June 1998, were evaluated retrospectively. The patients were classified as having either limited or extensive stage using the Veterans Administration staging system. Results : SCLN was presented in 10.5% of patients(n=21). The median survival was 247 days for patients with SCLN(n=21) and 264 days for patients without(n=194) (p=0.52). After treatment, the median survival was 298 days for patients with SCLN(n=13) and 348 days for patients without(n=115) (p=0.52). SCLN involvement was not correlated with the presence of distant metastases. Median survival was 459 days for patients with a limited stage without SCLN(n=66), 650 days for those with a limited stage with SCLN (n=7) (p=0.96). Pleural effusion was presented in 24.7% of patients(n=52). The median survival was 198 days for patients with pleural effusion(n=52) and 275 days for patients without(n=163) (p<0.05). After treatment, the median survival was 294 days for patients with a pleural effusion(n=25) and 286 days for patients without(n=103) (p=0.39). The presence of pleural effusion was not correlated with that of distant metastases. The median survival was 395 days for patients with a limited stage without a pleural effusion(n=63), 451 days for those with a limited stage with pleural effusion(n=10) (p=0.92). Conclusionsa : In this study, SCLN involvement does not explain the poor survival rate and the relevance to extensive staged disease. Furthermore, the existence of a pleural effusion did not correlated with the presence of distant metastases. However, the presence of a pleural effusion appears to be a minor prognostic factor in our study. Therefore supraclavicular lymph node involvement and the presence of a pleural effusion in SCLC are not poor prognostic factors, which does not justify any amendment to the staging system currently used.

• Journal of Chest Surgery
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• v.29 no.9
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• pp.1031-1035
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• 1996

International Ass ciation for the Study of Lung Cancer(IASLC) recommended the following classification of small cell lung carcinoma(SCLC) : (1) Small cell carcinoma (2) Mixed small cell/large cell carcinoma (3) Combined small cell carcinoma. Combined small cell carcinomas contain a squamous cell carcinoma or adenocarcinoma component. The prognostic significance of these elements is not known, but since the frequency and extent of non-small cell elements are considerably greater in posttherapy and autopsy tissues, it is possible that the non-SCLC elements are more resistant to therapy than the SCLC cells. Metaplasia & dysplasia of the bronchial surface epithelium are frequently observed in the bronchial biopsy specimens that contain small cell carcinoma of the lung. We report a case of combined small cell carcinoma with squamous element associated with microinvasive squamous cell carcinoma of the bronchial surface epithelium in 68 year old male patient, stage was IIIa. The two lesion are not connected n serial sections.

• Tuberculosis and Respiratory Diseases
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• v.59 no.6
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• pp.674-678
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• 2005

A 78-year-old man was admitted to our hospital as a result of dyspepsia with a 2-month duration. Upon admission, the laboratory data showed a marked elevation in amylase activity in both the serum and urine. The pancreas and salivary glands were considered unlikely to have any clinical involvement in the hyperamylasemia. The chest PA revealed a right side pleural effusion, and the chest CT showed a heterogeneous enhancing mass on the subcarinal area. The patient was diagnosed bronchoscopically with a poorly differentiated squamous cell carcinoma. The amylase isoenzyme patterns indicated the salivary types, but lung cancer was strongly suspected to be the source. In most cases, lung cancers with hyperamylasemia have been diagnosed as adenocarcinomas. A squamous cell carcinoma is quite rare. We report an interesting case of squamous cell lung cancer with hyperamylasemia.