• Analytical Science and Technology
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• v.22 no.6
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• pp.498-503
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• 2009

Lung cancer is the main cancer on the world today, due to the high case fatality. Lung cancer can devide into two major types, such as small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Mutations in the epidermal growth factor receptor (EGFR) have been described in patients with advanced NSCLC. Mutations in the EGFR are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Thus, the detection of EGFR mutation can offer an effective information in clinical decision-making. In this study, We developed very simple, cheep and rapid mutation detection system by chip-based isothermal amplification method. The method described here has shown the advantages of rapid amplification, high sensitivity, and specificity. Also, it will be useful for rapid and reliable clinical diagnosis of EGFR mutation.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.253-264
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• 2002

Background : It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. Methods : We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. Results : In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was $56.43{\pm}9.41$ yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant diffrernce(P<0.05). There was no association between p27 or uteroglobin expression and survival. Conclusion : The expression degree of CDK4 is related to the prognosis. This findings suggests that the measurement of CDK4 may be useful in identifying patient at high risk for disease recurrence and survival.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.441-452
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• 2002

Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.17-28
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• 2008

This review focuses on the clinical use of $^{18}F-FDG$ PET to evaluate solitary pulmonary nodule (SPN) and non-small cell lung cancer (NSCLC). When SPN or mass without calcification is found on chest X-ray or CT, $^{18}F-FDG$ PET is an effective modality to differentiate benign from malignant lesions. For initial staging of NSCLC, $^{18}F-FDG$ PET is useful, and proved to be cost-effective in several countries. $^{18}F-FDG$ is useful for detecting recurrence, restaging and evaluating residual tumor after curative therapy in NSCLC. For therapy response assessment, $^{18}F-FDG$ PET may be effective after chemotherapy or radiation therapy. $^{18}F-FDG$ PET is useful to predict pathological response after neoadjuvant therapy in NSCLC. For radiation therapy planning, $^{18}F-FDG$ PET may be helpful, but requires further investigations. PET/CT is better for evaluating NSCLC than conventional PET.

• Radiation Oncology Journal
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• v.2 no.2
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• pp.213-219
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• 1984

131 Patients of non·small cell lung cancer treated with irradiation at Yonsei Canter Center from Jan. 1971 to Dec. 1980 were retrospectively analysed. Overall 5 year survival rate was $7\%$ in 117 cases, treated with radiotherapy alone and $33\%$ in 14 Cases, treated with surgery & postoperative ratiotherapy. Their median survival was 9.6 months in the former, while 11.1 months in the latter. The patients treated with radical aim achieved $10\%$ in 5 YSR and with palliative aim, $0\%$. Also, survival according to histolocial classification and staging was obtained. Treatment failure was mostly distant failure (40 cases/49 cases), and within 6 months (34cases/49cases).

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.381-392
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• 2004

Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.

• Journal of Chest Surgery
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• v.34 no.12
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• pp.924-929
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• 2001

Backgroun : The long-term survival after operation of patients with lung cancer invading the chest wall is known to be related to regional nodal involvement, completeness of resection and depth of chest wall involvement. In this study results of complete resection are reviewed to determine survival charateristics. Material and Method: Of 680 consecutive patients who were operated on for primary non-small cell carcinoma between 1988 and 1998, we retrospectively reviewed 55 patients(8.0%) who had complete resection for lung cancer invading the chest wall or parietal pleura. Result: Resection of the chest wall was on bloc in 29 patients(47.3％), and extrapleural in 26(52.7％). In the patients undergoing extrapleural resection, the depth of chest wall invasion was confined to the parietal pleura in all patients(100%). In the patients underging en bloc resection, the pathologic depth of invasion was into the parietal pleura alone in 9(31.0%) and into the chest wall in 20(69.0%). The follow-up rate of these patients was 100%. Hospital mortality was 5.4%(n=3). The actuarial 5-year survival rate was 26% for all hospital survivors(n=52). The actuarial 5-year survival rate of patients with T3N0M0 disease(29%) was better than that of T3N2M0 disease(18%), however, there was no significant(p=0.30) difference. The depth of chest wall invasion had no statistically significant effect on survival in our series, neither for patients with involved lymphatic metastasis nor for those without(p=0.99). Conclusion: These observations indicate that the good five year survival in patients with T3 NSCLC invading the chest wall resulted from complete resection. Survival of patients with lung cancer invading the chest wall after complete resection is dependent on the extent of nodal involvement and much less so on the depth of chest wall invasion.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.638-645
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• 2004

Background : Uteroglobin is a protein produced by the normal bronchial epithelium and its expression level is lower in non-small cell lung cancer tissues and cell lines. It mainly functions as an anti-inflammatory, and when it is overexpressed in cancer cells, the neoplastic phenotype is antagonized. cPLA2 and COX-2, which are also associated with inflammation, were reported to be related to cancer. The relationship between cPLA2, COX-2 and uteroglobin is unclear. The relationship between uteroglobin and ERK, which is related to cell growth, is also not unclear. This study investigated the changes in the cPLA2 and COX-2 expression levels and the ERK activities after the overexpression of uteroglobin in non-small cell lung cancer cell lines. Methods : The A549 and NCI-H460 cell lines were infected by adenovirus-null and adenovirusuteroglobin. The cChange in the cPLA2, COX-2 expression level and ERK activity after uteroglobin overexpression was measured by Western blot. The change in MMP activity was measured by zymography. Results : Western blot revealed decreased expression levels of cPLA2, and COX-2, and increased pERK levels in nonsmall cell lung cancer cells after uteroglobin overexpression. Zymography revealed no changes in the MMP-2 activity and lower MMP-9 activity. U0126, which is a specific inhibitor of ERK-activating kinase MEK-1/-2, prevented the decrease in the MMP-9 activity Conclusions : A decrease in cPLA2 expression, COX-2 expression, MMP-9 activity and a increase in ERK activity may be related to the anticancer effects of uteroglobin in nonsmall cell lung cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.76-83
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• 1995

Background: Despite advances in chemotherapy, the treatment of inoperable non-small cell carcinoma of the lung remains poor. According to the recent reports, the response rates of mitomycin, vinblastine, and cisplatin(MVP) chemotherapy are higher than those of other cisplatin based polychemotherapy and MVP chemotherapy can be used as neoadjuvant chemotherapeutic regimen. But the overall response rates of MVP chemotherapy range from 17 to 53 percent, so we studied the effect of MVP chemotherapy in advanced non-small cell lung cancer. Method: We treated forty patients with stage III or IV non-small cell lung cancer with two courses of MVP chemotherapy($8mg/m^2$ of mitomycin on day 1, $6mg/m^2$ of vinblastine on day 2 & day 14, and $100mg/m^2$ of cisplastin on day 1) at 4 weeks interval. Then all patients were evaluated the response of chemotherapy 4 weeks later, and received further chemotherapy, palliative radiotherapy or supportive therapy according to the patient's condition. We also determined the median survival time and prognostic factors. Results: 1) Nine patients(23%) had a partial reponse, 23 patients(57%) had a stable disease, and disease progressed in 8 patients(20%). There were no patients with complete response. 2) The overall median survival time was 36 weeks(range, 9 to 119+ weeks). The median survival time of responder(partial response) and non-responder(stable and progressed) groups were 60 weeks(range, 36 to 82+ weeks) and 31 weeks(range, 9 to 119+ weeks) respectively(p=0.03). 3) The median survival time of the female group was 71 weeks and significantly prolonged in comparision with 35 weeks of the male group(p=0.01). But, the other prognostic factors didn't affect the survival time and response rate. 4) The median survival times of chemotherapy group and chemotherapy with palliative radiotherapy group were not significantly different. Conclusion: MVP combined chemotherapy is unsatisfactory in improving survival in advanced non-small cell lung cancer. Therefore, further studies are needed to find more active new agents and to estabilish the efficacy of the combined treatment with radiotherapy and/or surgery.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.480-489
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• 2005

Background : Dysregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. This study was designed to assess the pattern of expression and the prognostic value of XIAP in radically resected non-small cell lung carcinoma (NSCLC) patients. Method : The expression of XIAP and its relationship with clinicopathologic parameters (patient age, TNM stage, TNM-pT, TNM-pN, histologic type, VEGF expression, microvessel density, PCNA index) and overall survival were analysed with formalin-fixed, paraffin-embedded blocks from eighty cases of NSCLC. In addition, the apoptotic index (AI) was also assessed. Results : In a regard to histologic type, squamous cell carcinoma (SCC) showed XIAP expression in 91.3%(42/46) and adenocarcinoma (AC) in 61.8%(21/34). The difference was significant(p=0.001). There was no correlation between XIAP expression and other parameters. In the group of AC, XIAP expression showed the signifcant correlation with older age group ${\geq}58years$ and VEGF expression(p=0.028, p=0.014, respectively). The AI in the group with or without XIAP expression were $2.5{\pm}4.9%$ and $18.5{\pm}28.9%$, respectively(p=0.001). Both groups just aforementioned showed no significant difference in median survival time (42.5 months, 29.8 months, respectively). Conclusion : This study suggests that the XIAP expression in NSCLCs could have relation to inhibition of apoptosis, and show differential expression according to histologic type. However, its prognostic role during the progression of NSCLC needs to be further defined.