• 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.

• Journal of Chest Surgery
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• v.39 no.1 s.258
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• pp.1-11
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• 2006

Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.327-337
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• 1999

Background: Reactive oxygen species are involved in multi-stage process of carcinogenesis. The moot of cancer cell lines and cancer cells in tumor tissue produce reactive oxygen species and on the other hand, the activities of catalase, Mn- and CuZn-superoxide dismutase in tumor cells are usually low. These persistent oxidative stress in tumor tissue facilitates tumor invasion and metastasis. 12-kDa thioredoxin, which regulates the intracellular redox potential with glutathione and glutaredoxin is involved in cell activation, proliferation, differentiation and redox-mediated apoptosis. It is also purified as 14-kDa and 10-kDa eooinophilic cytotoxic enhancing factor(ECEF) from human histiocytic cell(U937) and 10-kDa ECEF has more than 20 times eosinophilic stimulation activity than 14-kDa ECEF. It has been reported that adult T-cell leukemia, squamous cell carcinoma of uterine cervix, and hepatocellular carcinoma show increased amounts of human thioredoxin and thioredoxin mRNA is increased in lung cancer. In this study, we investigated the expression of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue and the induction of thioredoxin in macrophage cells after treatment of oxidative stress and endotoxin Methods: We measured the amount of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue by immunoblot analysis and the induction of thioredoxin in mouse monocyte-macrophage cells(RAW 264.7) by treatment of 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin Results: On immunoblot analysis, the expression of 12-kDa thioredoxin was increased in lung cancer tissue compared to paired normal lung tissue. but the expression of catalase and CuZn-SOD were decreased in lung cancer tissue compared to paired normal tissue and the expression of glutathione peroxidase in lung cancer was variable. The expression of truncated thioredoxin was also increased in lung cancer. When mouse monocyte-macrophage cells were treated with 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin, the expression of thioredoxin was peaked at 12 hrs and sustained to 48 hrs. Conclusion: In contrast with other conventional antioxidants, the expression of 12-kDa and truncated thioredoxin in lung cancer were increased and it is closely associated with persistent oxidative stress in tumor microenvironment. Considering especially the biological functions of truncated thioredoxin, the increased amount of truncated thioredoxin has significant role in tumor growth through cell proliferation.

• Journal of Chest Surgery
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• v.39 no.5 s.262
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• pp.376-381
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• 2006

Background: The Ki-67 protein is a biomarker associated with cell proliferation and a valuable negative prognostic factor in non-small cell lung cancer. We investigated the Ki-67 protein expression in resected non-small cell lung cancer to evaluate the impact on clinicopathological characteristics and postoperative prognosis. Material and Method: Using monoclonal antibody Ki-67, we immunohistochemically examined 38 surgically resected non-small ceil lung cancers to determine Ki-67 Labeling Index (LI). We analysed the differences of clinicopathological characteristics and postoperative recurrence and survival between High Ki-67 Group $(LI{\ge}20%)$ and Low Ki-67 Group (LI<20%). Result: The Ki-67 LIs were heterogenous and a mean values was $20.0{\pm}20.05%$. There were no significant differences in age, sex, smoking, TNM stage, and vascular invasion between High Ki-67 Group and Low Ki-67 Group. A High Ki-67 Group was significantly associated with squamous cell type, poor differentiation, and lymphatic invasion $(p{\le}0.05)$. High Ki-67 Group showed a trend of lower survival (median 47.2 vs. 90.5 months, p=0.312) and lower disease-free survival (median 18.2 vs. 72.3 months, p=0.327) than Low Ki-67 Group. Conclusion: These results indicate that increased Ki-67 protein expression may be a negative prognostic factor and showed a trend of shortened survival and disease-free survival. To evaluate the pivotal role of Ki-67 protein expression, a long-term follow-up and further study are required.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.118-125
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• 2019

Background: Lung cancer is a leading cause of morbidity and mortality worldwide, and the incidence continues to rise. Although many prognostic factors have been identified, the clinical characteristics and outcomes in Korean lung cancer patients are not well defined. Methods: Of the 23,254 new lung cancer cases registered at the Korea Central Cancer Registry in 2013, total 489 patients from 19 hospitals were abstracted by the Korean Central Cancer Registry. The clinical data retrospectively analyzed, patients were followed up until December 2015. Results: The median age was 69 years (interquartile range, 60-74 years); 65.4% were male and 62.1% were ever-smokers. Cough was the most common initial symptom (33.5%); 13.1% of patients were asymptomatic. While squamous cell carcinoma was the most common subtype in male patients (37.2%), adenocarcinoma was the most frequent histological type in all patients (48.7%) and females (76.3%). The majority of patients received treatment (76.5%), which included surgery, radiation therapy, and chemotherapy. Older age (hazard ratio [HR], 1.037), lower body mass index (HR, 0.904), ever-smoker (HR, 2.003), small cell lung cancer (HR, 1.627), and distant metastasis (HR, 3.990) were independent predictors of mortality. Patients without symptoms (HR, 0.387) and without treatment (HR, 0.364) were associated with a favorable outcome in multivariate Cox analysis. Conclusion: Lung cancer in Korea occurs predominantly in elderly patients, with adenocarcinoma being the most frequent subtype. The prognosis was poorer in ever-smokers and older, malnourished, and untreated patients with advanced lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.525-532
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• 1999

The parathyroid hormone related protein (PTHrP) is the most common causative peptide of humoral hypercalcemia of malignancy. In contrast, the serum level of parathyroid hormone (PTH) is low to undetectable in the majority of patients with malignancy associated hypercalcemia. Few cases exist in which the production and secretion of PTH by malignant nonparathyroid tumors have been authenticated. To our knowledge, there is very rare case in which a nonparathyroid tumor expressed simultaneously both the PTH and PTHrP. We report a case of squamous cell carcinoma of the lung with hypercalcemia which presented with simultaneous elevation of serum PTH and PTHrP. Severe hypercalcemia (serum calcium, 7.5 mEq/L) was found in a 65-year-old man who had a squamous cell carcinoma of the lung without any bony metastasis and detectable parathyroid abnormalities on isotope scintigraphy. The serum level of intact parathyroid hormone (PTH) con centration was markedly elevated as measured in two site radioimmunoreactive PTH assays (intact PTH 150 pg/mL ; normal 9~55). The serum level of a PTHrP was also increased as measured in C-terminal region specific radioimmunoassay (PTHrP 99.1 pmol/L; normal 13.8~55.3). There are no evidences of coincidental primary hyperparathyroidism in parathyroid MIBI scan and other imaging studies including neck ultrasonography and computed tomography. These results suggest that simultaneous elevation of serum PTH and PTHrP in this patient can be caused by production of both PTHrP and PTH in other nonparathyroid lesions such as squamous cell carcinoma.

• The Korea Journal of Herbology
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• v.35 no.6
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• pp.35-41
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• 2020

Objectives : The object of this study was to observe anticancer and immunomodulatory effects of Formosa plum aqueous extracts (PLe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Method : Three different dosages of PLe, 50, 100 and 200 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation. Five groups, each of seven mice per group were used in the present study as follows. Tumor volume and weights, serum interferon (IFN)-γ levels, serum IL-6 were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. Result : Although no meaningful changes on the tumor weights and volumes were observed after treatment of all three different dosages of PLe, decreases of tumor cell volumes in tumor masses were dose-dependently decreased mediated by increases of apoptosis among tumor cells by treatment of PLe 100 and 200 mg/kg as compared with tumor-bearing control. In addition, decreases on the body weight and gains were also demonstrated in tumor-bearing control with increases of serum IL-6 levels. Conclusion : The results obtained in this study suggest that over 50 mg/kg of PLe showed favorable immunomodulatory and anticachexic effects with anticancer effects in 100 and 200 mg/kg of PLe treated groups on the NCI-H520 cell xenograft. However, detail mechanism studies should be conducted in future with the screening of the biological active compounds in this herb.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.551-561
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• 2021

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.98-103
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• 1993

Background: Inactivation of retinoblastoma gene (Rb) has been observed in a variety of human cancers. Loss of heterozygosity (LOH) of Rb which is a common mode of allelic inactivation of Rb, has been known as a frequent genetic event in small cell lung cancer but it has been detected less frequently in non-small cell lung cancer. To define the role of Rb deletion in lung cancer, we investigated the genomic DNAs of 43 non-small cell lung cancers and 1 small cell lung cancer paired with normal lung tissues obtained by thoracotomy. Methods: The genomic DNAs were obtained by the digestion with proteinase K followed by phenol-chloroform extraction method. The genomic DNAs were digested by restriction endonuclease (EcoRI), separated by agarose gel electrophoresis, transferred to nylon membrane by Southern blot transfer and then hybridized with labelled Rb 1 probe which contains. 1.4 kb sized DNA sequence containing N-terminal portion of Rb. Results: In 26 squamous cell lung cancers, 16 cases were informative after EcoRI digestion and LOH of Rb was found in 10 cases (62.5%). In 17 adenocarcinomas of lung, 11 cases were informative and LOH of Rb was found in five cases (45.4%). The analysis of clinical parameters revealed no significant differences between the two groups with or without LOH of Rb in the aspects of age, sex, degree of differentiation, stage and smoking amount. Conclusions: These results suggest that Rb inactivation is also significantly involved in the molecular pathogenesis of non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.700-708
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• 1993

Background: Lung cancer has become one of the most common cancers in Korea. It is important to determine the accurate histologic types and stages because of different therapeutic modlaity, especially in small cell carcinoma. This study was designed to evaluate diagnostic yields according to variable diagnostic methods in lung cancer. Methods: The records of 683 patients with a confirmed diagnosis of primary lung cancer during the period of 7 years, from January, 1986 until December, 1992 at Presbyterian Medical Center were analyzed retrospectively. Results: 1) Age and sex distributions Male: female sex ratio was 5.57:1 and age distributions were 7th decade 41.4%, 6th decade 30.2%, 8th decade 17.0%, 5th decade 7.9%, 4th decade 2.5%, 9th decade 1.3%, and 3rd decade 0.2% in decreasing order. 2) The frequencies according to histologic cell types were squamous cell carcinoma 44.7%, small cell carcinoma 23.9%, adenocarcinoma 22.8%, alveolar cell carcinoma 2.5%, large cell carcinoma 1.2%. mixed forms 1.2%, undifferenciated cell carcinoma 0.6% and malignant fibrous histiocytoma 0.2%(1 case) in decreasing order. 3) The most common locations of lung cancer were in left upper lobe and right lower lobe, and no differences of diagnostic methods according to locations were noted. 4) In central lesions, bronchoscopic examination was very accurate and frequently used diagnostic method, and in peripheral lesions, transthoracic lung biopsy(TTLB) was apparent1y accurate method. 5) The diagnostic yields of bronchoscopic biopsy, bronchial brushing, sputum cytology, transthoracic lung biopsy and transbronchial lung biopsy(TBLB) were 81.3%, 57.5%, 31.1%, 69.6% and 61.6%, respectively. 6) The concordance rates between the histologic diagnosis with bronchial brushing and sputum-cytology were 91.3% and 98.4%, respectively. 7) It was appropriate in lung cancer to repeat sputum cytology 3 to 5 times. Conclusion: Bronchoscopic examination is important to determine the histologic cell types in lung cancer. In addition, we should be interrested in improving diagnostic yields of sputum cytology as an easy method.