• Journal of Life Science
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• v.32 no.4
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• pp.271-278
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• 2022

The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

• Journal of Preventive Medicine and Public Health
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• v.25 no.1 s.37
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• pp.88-100
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• 1992

This study was conducted to assess the effects of implementation of the patient referral system started July 1st, 1989. A comparison on the pattern of outpatient services of the Departments of Internal Medicine, General Surgery, and Pediatrics at the Yeungnam University Hospital was conducted for each one year period before and after implementation of the patient referral system. The pre-implementation period was from July 1, 1988 to June 30, 1989 and the post-implementation period was from July 1, 1989 to June 30, 1990. The information used for this study was obtained from official forms, prepared by the Yeungnam University Hospital, and submitted to the Korean Medical Insurance Cooperatives. After implementation of the patient referral system, the number of outpatient cases in the Department of Internal Medicine decreased 36.1% from 9,669 cases to 6,181 cases a year. Cases in the Department of General Surgery decreased 23.7% from 1,864 cases to 1,422 cases a year. The number of cases in the Department of Pediatrics decreased 36.9% from 3,372 cases to 2,128 cases a year. After implementation of the patient referral system, the average age of cases in the Departments of Internal Medicine and General Surgery was 52.5 and 49.7 years old, respectively. This was a significant increase in comparison with the pre-implementation period. After implementation of patient referral system, the proportion of new outpatients in the Department of Internal Medicine decreased from 24.1% to 14.6%, the Department of General Surgery from 36.0% to 23.4%, and the Department of Pediatrics from 15.5% to 8.3%. The number of visits per case decreased significantly in the Department of Internal Medicine(from 1.74 to 1.61), but there was no significant change in the Departments of General Surgery and Pediatrics. The length of treatment per case increased significantly in all three departments(from 16.1 days to 19.3 days in the Department of Internal Medicine, from 12.0 days to 15.2 days in the Department General Surgery, and 8.9 days to 11.2 days in the Department of Pediatrics). The number of clinical tests per case increased significantly in the Department of Internal Medicine (from 2.2 to 2.5), in the Department of Pediatrics(from 0.8 to 1.1) and increased in the Department of General Surgery(from 6.4 to 6.6). The average medical cost per case decreased from 43,900 Won to 42,500 Won in the Department of Internal Medicine, while the cost increased from 75,900 Won to 78,500 Won in the Department of General Surgery and from 12,700 Won to 13,500 Won in the Department of Pediatrics. In case-mix, the chronic degenerative disease(i. e. hypertension, diabetes mellitus, angina pectoris, malignant neoplasm, and pulmonary tuberculosis) ranked higher and acute infectious diseases and simple cases(i. e. gastritis and duodenitis, haemorrhoids, anal fissure, carbuncle, acute URI, and bronchitis) ranked lower after implementation of the patient referral system compared to before implementation.

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.510-515
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• 2006

Background : Although 17% of Korean adults over the age of 45 years have chronic obstructive pulmonary disease (COPD), there is only limited data on the cause of death in COPD patients in Korea. Therefore, this retrospective study was performed to examine the cause of death in COPD patients at a referral hospital in Korea. Methods : The medical records of 28 deceased patients diagnosed as COPD in Asan Medical Center from January to December 2003 were reviewed patients had died in Asan Medical Center and 16 patients had died outside the hospital. The Korean National Statistical Office confirmed 88 deceased patients out of 1,078 patients diagnosed as COPD in Asan Medical Center in 2003. After excluding those with tuberculous destroyed lung, bronchiectasis, and lung cancer, 28 COPD patients were evaluated. Results : The causes of death were pulmonary disease including pneumonia in 16 patients (57%), cardiac disease in 5 patients (18%), sudden death in 3 patients (11%), and other causes in 4 patients (14%). The cause of death was pulmonary disease in 83% (10 out of 12 patients) and 38% (6 out of 16 patients) of patients who died in Asan Medical Center and outside the center, respectively (P=0.05). The cause of death was pulmonary disease in 43% of patients with $FEV_1$ more than 50 % of the predicted value and in 55% of patients with $FEV_1$ less than 50 % of the predicted value (P=0.89). Conclusion : Pulmonary disease is the leading cause of death in COPD patients in Korea.

• Journal of Chest Surgery
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• v.42 no.1
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• pp.63-71
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• 2009

Background: The treatment of tracheal stenosis includes less invasive bronchoscopic intervention and more invasive segmental resection & anastomosis. Depending on the patient's clinical features, sometimes all these methods are inappropriate. Silicone T-tube stenting has recently been used as an alternative, safe management of tracheal stenosis. We studied the short term and Intermediate term results of using T-tubes in patients with tracheal stenosis, and this tracheal stenosis was caused by various underlying diseases. Material and Method: We retrospectively reviewed 57 patients with tracheal stenosis and who were treated with T-tubes between Jan 1997 and Apr 2007. Based on the patient's medical records and the imaging studies, we evaluated the clinical findings and status of T-tube removal. Result: There was no T-tube related morbidity or mortality in this series. On follow-up, one patient underwent sleeve resection and end-to-end anastomosis. The T-tube could be successfully removed from 13 patients (13/57, 22.8%) without additional interventions. For another four patients, a T-tube was again inserted after removal of the first T-tube due to tracheomalacia or recurrent stenosis. Four patients died of underlying disease and cancer. The patients' gender and previous tracheostomy significantly affected T-tube removal. By contrast, multiple logistic regression analysis identified gender as a predictor of successfully removing a T-tube. Gender (p=0.033) and previous tracheostomy (p=0.036) were the two factors for success or failure of T-tube removal. Conclusion: A T-tube provided reliable patency of a stenotic airway that was caused by any etiology. We have proven that using a T-tube is safe and effective therapy for patients with tracheal stenosis for the short term or the intermediate term.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.362-368
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• 2008

Background: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. Methods: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. Results: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. Conclusion: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.

• Journal of Life Science
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• v.33 no.2
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• pp.158-168
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• 2023

Natural products have been used to mitigate the effects of cancer and infectious diseases, as they feature diverse bioactivities, such as antioxidant, antibacterial, anti-inflammatory, and immunomodulatory effects. Here, we chose 10 natural products that are well-known as pulmonary enhancers and investigated their bactericidal effects on Streptococcus pneumoniae. In the disk diffusion assay, the growth of S. pneumoniae was significantly regulated by G. fructus treatment regardless of extraction method used. We first adopted spraying as a novel delivery method for G. fructus. Interestingly, mice exposed to G. fructus three times a day for 2 weeks were resistant to S. pneumoniae intranasal infection (shown both through body weight loss and survival rates compared to the control group). Moreover, we confirmed that exposure to G. fructus regulated the colonization of the bacteria despite the sustained inflammation in the lung after exposure to S. pneumoniae, indicating that migrated inflammatory immune cells may involve a host defense mechanism against pulmonary infectious diseases. While a similar number of granulocytes (CD11b⁺Ly6C⁺Ly6G⁺), neutrophils (CD11b⁺Ly6C^intLy6G⁺), and monocytes (CD11b⁺Ly6C^intLy6G^-) were found between groups, a significantly increased number of alveolar macrophages (CD11b⁺CD11c^hiF4/80⁺) was detected in BAL fluids of mice pre-exposed to G. fructus at 5 days after S. pneumonia infection. Taken together, our data suggest that this usage of G. fructus can induce protective immunity against bacterial infection, indicating that facial spray may be helpful in enhancing the defense mechanism against pulmonary inflammation and in evaluating the efficacy of natural products as immune enhancers against respiratory diseases.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.882-893
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• 1996

Background : Over one-third of solitary pulmonary nodules are malignant, but most malignant SPNs are in the early stages at diagnosis and can be cured by surgical removal. Therefore, early diagnosis of malignant SPN is essential for the lifesaving of the patient. The incidence of pulmonary tuberculosis in Korea is somewhat higher than those of other countries and a large number of SPNs are found to be tuberculoma. Most primary physicians tend to regard newly detected solitary pulmonary nodule as tuberculoma with only noninvasive imaging such as CT and they prefer clinical observation if the findings suggest benignancy without further invasive procedures. Many kinds of noninvasive procedures for confirmatory diagnosis have been introduced to differentiate malignant SPNs from benign ones, but none of them has been satisfactory. FOG-PET is a unique tool for imaging and quantifying the status of glucose metabolism. On the basis that glucose metabolism is increased in the malignant transfomled cells compared with normal cells, FDG-PET is considered to be the satisfactory noninvasive procedure which can differentiate malignant SPNs from benign SPNs. So we performed FOG-PET in patients with solitary pulmonary nodule and evaluated the diagnostic accuracy in the diagnosis of malignant SPNs. Method : 34 patients with a solitary pulmonary nodule less than 6 cm of irs diameter who visited Samsung Medical Center from Semptember, 1994 to Semptember, 1995 were evaluated prospectively. Simple chest roentgenography, chest computer tomography, FOG-PET scan were performed for all patients. The results of FOG-PET were evaluated comparing with the results of final diagnosis confirmed by sputum study, PCNA, fiberoptic bronchoscopy, or thoracotomy. Results : (I) There was no significant difference in nodule size between malignant (3.1 1.5cm) and benign nodule(2.81.0cm)(p>0.05). (2) Peal SUV(standardized uptake value) of malignant nodules (6.93.7) was significantly higher than peak SUV of benign nodules(2.71.7) and time-activity curves showed continuous increase in malignant nodules. (3) Three false negative cases were found among eighteen malignant nodule by the FDG-PET imaging study and all three cases were nonmucinous bronchioloalveolar carcinoma less than 2 em diameter. (4) FOG-PET imaging resulted in 83% sensitivity, 100% specificity, 100% positive predictive value and 84% negative predictive value. Conclusion: FOG-PET imaging is a new noninvasive diagnostic method of solitary pulmonary nodule thai has a high accuracy of differential diagnosis between malignant and benign nodule. FDG-PET imaging could be used for the differential diagnosis of SPN which is not properly diagnosed with conventional methods before thoracotomy. Considering the high accuracy of FDG-PET imaging, this procedure may play an important role in making the dicision to perform thoracotomy in diffcult cases.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.290-300
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• 1998

Background: CYFRA 21-1 is a tumor marker which measures a fragment of cytokeratin 19 expressed by epithelial cells in bronchus. It is known that cytokeratin 19 is abundant in squamous epithelial cell cancer of the lung. However, if the incidence of elevated serum CYFRA 21-1 level in patients with benign lung diseases or pulmonary tuberculosis with severe parenchymal damage is high the specificity of CYFRA 21-1 could be decreased. The purpose of this study is to investigate the changes of serum CYFRA 21-1 according to the degree of parenchymal damage and the usefulness of CYFRA 21-1 for diagnosing possibly combined lung cancer in patients with pulmonary tuberculosis. Method: We studied the changes of serum CYFRA 21-1 according to the sputum AFB stain, radiologic manifestation and history of treatment in 81 patients with pulmonary tuberculosis, and 20 healthy persons, 25 patients with lung cancer, as a control group. CYFRA 21-1 concentration in serum was quantified by the immunoradiometry assay(Centocor$^{(R)}$). Result: The results were as follow; Serum CYFRA 21-1 level was significantly lower in patients with pulmonary tuberculosis($1.54{\pm}1.19ng/mL$, p<0.01) as compared to patients with lung cancer($12.25{\pm}15.97ng/mL$), and was slightly higher than the level in heathy persons($0.90{\pm}0.49ng/mL$) but there was no significant difference. Serum CYFRA 21-1 level was below the cut-off value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis but it was above the cut-off value in 64 percent of patients with lung cancer. Serum CYFRA 21-1 level was significantly higher in the initial treatment group($1.91{\pm}1.55ng/mL$, p<0.05) as compared to the treatment. failure group ($0.92{\pm}0.30ng/mL$). According to the sputum AFB smear, serum CYFRA 21-1 level in patients with negative result was slightly higher than the level in patients with positive result but there was no significant difference. According to the radiologic manifestation, serum CYFRA 21-1 level was significantly higher in patients with infiltrative lesion ($2.15{\pm}1.63ng/mL$, p<0.01) as compared to patients with destructive lesion ($l.04{\pm}0.54ng/mL$). As the size of cavity or destructive lesion was larger, the level was significantly lower(p<0.05). Conclusion: As serum CYFRA 21-1 level was significantly higher in the initial treatment group and patients with infiltrative lesion, it suppose to be closely related with the degree of parenchymal damage of the lung of the pulmonary tuberculosis. However CYFRA 21-1 could be useful method for diagnosing lung cancer even in patients with pulmonary tuberculosis combined with lung cancer because of the fact that it was below the cutoff value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis.