• Radiation Oncology Journal
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• v.8 no.1
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• pp.73-77
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• 1990

From January 1981 to December 1989, total 42 patients with atelectasis from lung cancer were treated with radiation therapy at the Department of Therapeutic Radiology in Kyung Hee University Hospital. The reexpansion of atelectasis after radiotherapy of the lung was evaluated retrospectively, utillzing treatment records and follow-up chest radiographs. Of the patients with non-small cell carcinoma of the lung, the response rate was $62\%$ (21/34). Patient with small cell carcinoma showed a $75\%$ (6/8) response rate. There appears to be some evidence of a relationship of total tumor dose versus response of atelectasis; radiation dose over 40 Gy (1337 ret), had a favorable effect on the rate of response compared with that below 40 Gy (1297 ret), $70\%$(21/30) and $50\%$ (6/12), respectively (p<0.01). Total response rate (partial and complete responses) of all patients was $64\%$ (27/42). Franction size was not contributed to the difference of response rates between small fraction ($180\~200$ cGy) and large fraction (300 cGy), $53\%$ (14/22) and $65\%$ (13/20), respectively. The results of this study suggest that radiation therapy has a definite positive role in management of atelectasis caused by lung cancer, especially in inoperable non-small cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.502-510
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• 1992

Background: Neuron specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase which was first found in extracts of brain tissue, and later in a variety of APUD cells and neurons of the diffuse endocrine system. SCLC shares many APUD properties with normal neuroendocrine cells. NSE immunostaining and serum NSE measurement may be a useful marker of neuroendocrine differentiation in lung tumors and diagnosis of small cell carcinoma. Methods: NSE immunohistochemical staining was done and at the same time serum NSE levels were measured in 22 small cell lung cancer and 21 non small cell lung cancer which were confirmed histologically. Results: 1) NSE immunoreactivity was detected in 9 of the 18 (50%) small cell lung cancer, in 5 of the 16 non small cell lung cancer. 2) Whereas the mean value in non-small cell lung cancer group was $11.79{\pm}4.47\;ng/ml$, the mean level of serum NSE in small cell lung cancer increased up to $59.3{\pm}77.8\;ng/ml$. In small cell lung cancer patients, mean value of limited disease group was $20.19{\pm}12.91\;ng/ml$, while mean value of extended disease group was $91.9{\pm}94.2\;ng/ml$ showing statistically significant difference. If serum levels above 20 ng/ml were tentatively defined as positive, 16 of 22 (73%) patients with SCLC had positive serum NSE level, but only one patient with NSCLC did. There was no correlation between serum NSE level and immunoreactivity of NSE. Conclusion: These studies indicate that serum NSE measurement may be a useful marker for the diagnosis and disease extent and NSE immunostaining can be used to demonstrate the neuroendocrine components of lung tumor.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10937-10941
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• 2015

Pathogenesis of lung cancer is a complicated biological process including multiple genetic and epigenetic changes. Since cigarette smoking is confirmed as the most main risk factor of non-small cell lung cancer (NSCLC), the aim of this study was to determine whether tobacco exposure plays a role in gene methylation. Methylation of the RAR-${\beta}$ gene were detected using methylation-specific polymerase chain reaction in DNA from 167 newly diagnosed cases with NSCLC and corresponding 105 controls. A significant statistical association was found in the detection rate of the promoter methylation of RAR-${\beta}$ gene between NSCLC and controls ($x^2$=166.01; p<0.01), and hypermethylation of the RAR-${\beta}$ gene was significantly associated with smoking status (p=0.038, p<0.05). No relationship was found between RAR-${\beta}$ gene methylation and pathologic staging including clinical stage, cell type, gender and drinking (p>0.05), and the methylation of RAR-${\beta}$ gene rate of NSCLC was slightly higher in stages III+IV (80.0%) than in I+II (70.8%). Similar results were obtained for methylation of the RAR-${\beta}$ gene between squamous cell carcinoma (77.9%) and other cell type lung cancer (73.9%). These results showed that the frequency of methylation increased gradually with the development of clinical stage in smoking-associated lung cancer patients, and tobacco smoke may be play a potential role in RAR-${\beta}$ gene methylation in the early pathogenesis and process in lung cancer, particularly squamous cell carcinoma. Aberrant promoter methylation is considered to be a promising marker of previous carcinogen exposure and cancer risk.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.322-331
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• 1995

Introduction: This study was performed to evaluate the diagnostic usefulness of simultaneous determination of 3 tumor markers {serum carcinoembryonic antigen(CEA), squamous cell carcinoma antigen (SCC Ag) and neuron specific enolase(NSE)} in lung cancer patients. Method: In 113 patients with primary lung cancer(70 with squamous cell carcinoma, 30 with adenocarcinoma, 13 with small cell carcinoma) and 103 patients with benign lung diseases, serum CEA and NSE were measured by enzyme immunoassay, and SCC Ag was measured by microparticle enzyme immunoassay. Results: 1) The mean serum levels of 3 tumor markers were significantly higher in lung cancer groups than benign lung disease groups respectively(p=0.001). 2) In squamous cell carcinoma, the SCC Ag was elevated in 67%, in adenocarcinoma CEA was elevated in 77% and in small cell carcinoma NSE was elevated in 77%, but there were no significant differences according to the stage of each cancer cell types. 3) CEA was the most sensitive marker, but nonspecific to cancer types. SCC Ag was less sensitive than other markers, but more specific toward squamous cell carcinoma, and NSE was more specific to primary lung cancer. 4) As the number of positive tumor markers was increased, the relative possibility of lung cancer was also increased. If two markers were positive, it increased to 77%, and if three markers were positive it increased to 90%. Conclusion: The simultaneous measurement of serum CEA, SCC Ag and NSE would provide additional information for the diagnosis of lung cancer.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Journal of Chest Surgery
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• v.31 no.4
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• pp.362-368
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• 1998

The aim of this study was to evaluate a usefulness of serum SCC antigen in diagnosis or evaluation of therapeutic effect of lung cancer by investigation of the differences of SCC antigen concentration in lung mass according to TNM staging, and mass size of lung cancer. And the other aim was to know whether SCC antigen plays a role in infiltrative growth of lung cancer or not, comparing with concentration of epidermal growth factor receptor(EGFr) in tissue which is related with growth and differentiation of tumor cell. The results of this study were as follows. The concentration of SCC antigen in squamous cell carcinoma of lung(69${\pm}$25ng/ml) was higher than in unaffected lung tissue(34${\pm}$7ng /ml).(p＜0.05). The concentration of SCC antigen was higher in squamous cell carcinoma (69${\pm}$25ng/ml) than in adenocarcinoma (35${\pm}$25ng/ml) (p＜0.05), but the concentration of EGFr showed no any significant difference in both histological types. In small sized mass(＜3cm in diameter) the concentration of SCC antigen in central portion of tumor was higher than that of peripheral portion, whereas in large sized mass($\geq$5cm in diameter), the concentration of SCC antigen in peripheral portion of tumor was higher than that of central portion.(p＜0.05). The concentration of EGFr according to tumor size was not significantly different in central and peripheral portion of tumor. The concentration of SCC antigen according to TNM staging of lung cancer was that from central portion was higher in stage I, II, but that from peripheral portion was higher in stage III, IV (p＜0.05). The concentration of EGFr from central portion was higher in higher TNM stage(not significant) but that from peripheral portion shows no significant changes. In conclusion, the concentration of SCC antigen in tissue was higher in squamous cell carcinoma than in unaffected lung tissue or adenocarcinoma, and the concentration of SCC antigen increased according to tumor size or TNM staging like in serum level. so, serum SCC antigen is a useful tumor marker to diagnose or evaluate therapeutic effect of squamous cell carcinoma of lung. But further studies are necessary to confirm the relation of infiltrative growth in lung cancer and concentration of SCC antigen because there was a different pattern of regional tissue concentration of SCC antigen and EGFr

• Journal of Chest Surgery
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• v.50 no.3
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• pp.153-162
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• 2017

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.

• Journal of Chest Surgery
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• v.33 no.4
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• pp.301-305
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• 2000

Background: The surgical indications of stage IV non-small cell lung cancer(NSCLC) are extremely limited with its controversial results. We analyzed the surgical results and survival in selected patients with resectable stage IV NSCLC. Material and Method: We reviewed the medical records of 21 patients who underwent operation for stage IV NSCLC from Jan. 1992 to Sep. 1999. Result: The mean age of patients was 55.6 years(range: 35 to 78). Sixteen were men and 5 were women. Tissue types were squamous cell carcinoma in 10(45.5%), adenocarcinoma in 9(40.9%), large cell carcinoma in 1 and carcinosarcoma in 1. Distant metastatic lesions were ipsilateral other lobe of lung in 18, brain in 2 and adrenal gland in 1. Pneumonectomy was performed in 16 patients, bilobectomy in 3, and lobectomy in 2 who underwent previous operatin for brain metastasis. Mean follow-up duration was 21.2$\pm$17.7 months. During follow-up period, 13 patients died. Three-and 5-year survival of patients were 38.0% and 19.0%, the median survival time was 19.1$\pm$7.8 months. In the group with ipsilateral pulonary metastasis(PM, n=18), 3- and 5-year survival of patients with N0 and N1(n=9) disease were 64.8% and 32.4%, median survival time was 55.3$\pm$27.2 months. Three-year survival of patients with N2(n=9) disease was 11.1%, median survival time was 10.6$\pm$0.3 months. The survival of N0 and N1 disease group was significantly better than that of N2 disease group(p=0.042). Also the disease free survival of N0 and N1 was significantly better than that of N2 disease in overall group(53.3 months vs 12.1 months, p=0.036) and ipsilateral PM group(63.4 months vs 8.8 months, p=0.001). Conclusion: We suggest that surgical treatment is worthful modality in well selected patients with stage IV NHSCLC especially with ipsilateral PM and N0 or N1 disease,. Nevertheless our study indicate questions that will need to be experienced further in larger studies.

• Journal of Chest Surgery
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• v.20 no.3
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• pp.473-482
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• 1987

The records of 65 patients with a confirmed diagnosis of primary lung cancer who underwent surgical therapy at the Department of Thoracic and Cardiovascular Surgery of the Keimyung University Hospital were analyzed during the period of 8 years and 4 months, from August, 1978 to December, 1986. The peak incidence was observed in the 5th decade of life and the mean age was 52.9 years old. Male versus female ratio was 8.3:1 Cough was the most frequent presenting symptom, 76.9% then chest discomfort, hemoptysis and dyspnea followed in order. 44.6% of the patient had 2 months of prediagnostic symptomatic period, 72.3% had 5 months, and the mean was 5.7 months. As for preoperative diagnosis, 62 of total 65 patients revealed the mass lesion on simple chest x-ray, and 56 of 65 patients on bronchoscopic biopsy, 10 of 37 patients on sputum cytology and 15 of 15 patients on computerized tomography of the chest were positive. Of the 65 patients, 35 [53.9%] had squamous cell carcinoma, 18 [27.7%] adenocarcinoma, 3 [4.6%] large cell carcinoma, and 3 [4.6%] small cell carcinoma all which was oat cell carcinoma. 83.1% of the total patient was resectable, and 34 underwent pneumonectomy and 20 lobectomy. Of these 65 operations, 29 was radical resection, 25 palliative, and 11 exploratory thoracotomy. As for clinical stagings, 23 patients were in Stage, I, another 23 in Stage II and 19 in Stage III, while 16 was in stage, I, 14 in stage ll and 35 in stage III in postoperative staging evaluation. In correlation of postoperative TNM classification and radical resection, those patients who had lung cancer of stage I [14/16] and stage II [9/13] had more radical resection. As postoperative complications, one patient had massive bleeding, two empyema, one empyema with bronchopulmonary fistula, and one cardiac herniation. Operative mortality rate was 1.5% [1 patient]. Mean duration between 1st operation and discovering recurrence in 18 patients was 12.7 months.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10171-10174
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• 2015

Background: The purpose of this study was to determine the prognostic significance of the maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients undergoing surgical treatment for non-small cell lung cancer. Materials and Methods: Seventy-eight consecutive patients (58 with adenocarcinomas, 20 with squamous cell carcinomas) treated with potentially curative surgery were retrospectively reviewed. Results: The SUVmax was significantly higher in the patients with recurrent than with non-recurrent adenocarcinoma (p<0.01). However, among the patients with squamous cell carcinoma, there were no differences with or without recurrence (p=0.69). Multivariate analysis indicated that the SUVmax of adenocarcinoma lesions was a significant predictor of disease-free survival (p=0.04). In addition, an SUVmax of 6.19, the cut-off point based on ROC curve analysis of the patients with pathological IB or more advanced stage adenocarcinomas, was found to be a significant predictor of disease-free survival (p<0.01). Conclusions: SUVmax is a useful predictor of disease-free survival in patients with resected adenocarcinoma, but not squamous cell carcinoma. Patients with adenocarcinoma exhibiting an SUVmax above 6.19 are candidates for more intensive adjuvant therapy.