• Radiation Oncology Journal
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• v.2 no.2
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• pp.203-211
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• 1984

From 1979 to 1982, 80 patients with unresectable non-small-cell lung cancer without metastasis were treated with high-dose radiotherapy to the primary and to regional lymph nodes with or without supraclavicular lymphatics in the Department of Therapeutic Radiology, Seoul National University Hospital. Of these, 56 patients$(70\%)$ were completely evaluable, and 59 patients$(74\%)$ had squamous cell carcinoma, 13a large cell undifferentiated carcinoma and 831 adenocarcinoma. 21 patients$(26\%)$ had Stage II and 59 patients$(74\%)$ had Stage III. The complete and partial response rate in the high-dose$(\approx\;6,000\;rad)$ radiotherapy was $70\%\;with\;19\%$ complete response. 69 patients$(86\%)$ failed in the treatment, by the failure pattern, $64\%$ had local failure alone, $35\%$ had local failure and distant metastasis and $1\%$ had distant metastasis alone. The failure rate in the thorax were $76\%$ in squamous cell carcinoma, $40\%$in adenocarcinoma and $20\%$ in large cell undifferentiated carcinoma Preliminary result shows that actuarial survival at 1, 2 and 3 years were $56\%,\;26\%\;and\;20\%$ in overall patients and $64\%,\;37\%\;and\;21\%\;in\;Stage\;II\;and\;54\%1,\;21\%\;and\;18\%$ in Stage III, respectively. Overall median survival was 14 months; 17 months in Stage II and 13 months in Stage m. 8 patients$(10\%)$ have lived a minimum of 2 years with no evidence of disease. There was no fatal complication confirmed to be induced by radiotherapy, so definitive high-dose radiotherapy was tolerated well without major problems and resulted in good local control and survival.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.150-156
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• 2006

Background: Gefitinib (ZD 1839, Iressa) is a new anticancer agent; more specifically, it is a selective epidermal growth factor receptor tyrosine kinase inhibitor that is, widely used for various solid cancers, including lung cancer. Cutaneous adverse reactions induced by gefitinib have recently been reported; however, not much on this topic has been reported in the Korean literature. Method: We studied cutaneous adverse reactions of gefitinib in 23 patients who suffered with non-small cell lung cancer at Chonnam National University Hwasun Hospital from October 2004 to September 2005. Result: The patients ranged from 23-72 years old, and there were 17 patients with adenocarcinoma, 5 with squamous cell carcinoma and 1 with bronchioloalveolar carcinoma. The most common adverse reaction was acneiform eruptions in 15 patients (65.2%). This reaction appeared within 2 months after medication, and it didn't correlate with the therapeutic response and tumor type. Pruritus was the second most common reaction (39.1%), which was mild and generalized, especially around eyelid area. Xerosis (26.1%), exfoliation on palm and sole (21.7%), and paronychia (21.7%) followed. Hair breakage and intertrigo were rare adverse reactions. Conclusion: Various cutaneous adverse reactions were observed in patients with non-small cell lung carcinoma after gefitinib treatment. The skin complications could be alleviated with dermatologic consultations and treatments, skin complications could be alleviated.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.16-21
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• 2007

Purpose: We evaluated the diagnostic value of $^{18}F-FDG$ PET/CT (PET/CT) in lymph node staging of non-small cell lung cancer (NSCLC) considering calcification and histologic types as well as FDG uptake. Materials and Methods: Fifty-three patients (38 men, 15 women; mean age, 62 years) with NSCLC underwent surgical resection (tumor resection and lymph node dissection) after PET/CT. After surgery, we compared PET/CT results with the biopsy results, and analyzed lymph node metastases, based on histologic types. PET diagnosis of lymph node metastasis was determined by maximum SUV (maxSUV) > 3.0, and PET/CT diagnosis was determined by maxSUV > 3.0 without lymph node calcification. Results: By PET diagnosis, the sensitivity, specificity, and accuracy of overall lymph node staging were 45% (13 of 29), 91% (228 of 252), and 86% (241 of 281). Specificity was 91% in both squamous cell carcinoma and adenocarcinoma, while sensitivity was 71% in squamous cell carcinoma and 36% in adenocarcinoma. When we excluded calcified lymph node with maxSUV > 3.0 from metastasis by PET/CT diagnosis, specificity improved to 98% in squamous cell carcinoma and 97% in adenocarcinoma. The degree of improvement was not dependent on histologic types. Conclusion: PET/CT improved specificity of lymph node staging by reducing false positive lymph node regardless of histologic types of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.55 no.3
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• pp.267-279
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• 2003

Background : The purpose of this study was to analyze the smoking habits in patients with lung cancer and identify any difference of prevalence according to histologic types of lung cancer. Methods : The data were calculated by total amounts of tar and nicotine inhaled during the whole lifetime according to variation of smoking habit. This study was to investigated any difference of prevalence in lung cancer according to smoking habits. The subjects comprised 150 lung cancer cases and 300 hospital control cases that were matched by age and sex. Smoking habits during the whole lifetime were surveyed by standardized questionnaire. Odds ratios were estimated by unconditional logistic regression analysis. Results : There were 104 male and 34 female lung cancer cases. By histologic type, there were 53 cases of squamous cell carcinoma, 67 of adenocarcinoma and 30 of small cell lung carcinoma. The differences between lung cancer cases and controls according to smoking habits were total duration of smoking, total pack years of smoking and number of cigarettes smoked per day during the previous two years. The odds ratio were higher in Kreyberg I, but not in Kreyberg II, for the longer duration of smoking, the greater total pack years of cigarettes consumed, the more cigarettes smoked per day during the previous two years, the longer duration on non-filter smoking, the earlier life cases who began to smoke, and the higher amounts of calculated total tar and nicotine inhaled over the whole lifetime. When we added grade of inhalation to calculation of amounts of tar and nicotine inhaled over the lifetime, the odds ratios of total inhalation amounts of tar and nicotine were as high as those the without them. Conclusions : This study reconfirmed that smoking habits were strongly associated with lung cancer and that there were different associations between smoking habits and histologic types of lung cancer. In particular, calculations of total tar and nicotine amounts inhaled over the whole lifetime were calculated for the first time in trials from lung cancer epidemiologic studies.

• Journal of Radiation Protection and Research
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• v.43 no.2
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• pp.66-74
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• 2018

Background: Tumor response to anticancer therapies can much be influenced by microenvironmental factors. In this study, we determined the effect of these microenvironmental factors on DNA methylation using A549 human lung adenocarcinoma cell line. Materials and Methods: We subjected A549 cells to various conditions mimicking tumor microenvironment including hypoxia, acidosis (sodium lactate), oxidative stress ($H_2O_2$), bystander effect (supernatant from doxorubicin (Dox)-treated or irradiated cells), and immune cell infiltration (supernatant from THP-1 or Jurkat T cells). Genomic DNA was isolated from these cells and analyzed for DNA methylation. Clonogenic cell survival, gene expression, and metabolism were analyzed in cells treated with some of these conditions. Results and Discussion: We found that DNA methylation level was significantly decreased in A549 cells treated with conditioned media from Dox-treated cells or Jurkat T cells, or sodium lactate, indicating an active transcription. To determine whether the decreased DNA methylation affects radiation sensitivity, we exposed cells to these conditions followed by 6 Gy irradiation and found that cell survival was significantly increased by sodium lactate while it was decreased by conditioned media from Dox-treated cells. We further observed that cells treated with conditioned media from Dox-treated cells exhibited significant changes in expression of genes including BAX and FAS (involved in apoptosis), NADPH dehydrogenase (mitochondria), EGFR (cellular survival) and RAD51 (DNA damage repair) while sodium lactate increased cellular metabolism rather than changing the gene expression. Conclusion: Our results suggest that various tumor microenvironmental factors can differentially influence DNA methylation and hence radiosensitivity and gene expression in A549 cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.516-524
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• 1997

Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{\pm}0.3ng/mL$ in controls, $1.0{\pm}0.3ng/mL$ in benign lung disease patients and $0.9{\pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{\pm}6.7ng/mL$ in controls, $14.9{\pm}6.3ng/mL$ in benign lung disease patients, and $22.1{\pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{\pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{\pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{\pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{\pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{\pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{\pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{\pm}0.6ng/mL$ in stage II, $0.7{\pm}0.4ng/mL$ in stage IIIA, $0.7{\pm}0.4ng/mL$ in stage IIIB, and $0.7{\pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{\pm}8.7ng/mL$ in stage II, $18.4{\pm}4.9ng/mL$ in stage IIIA, $25.3{\pm}9.0ng/mL$ in stage IIIB, and $21.5{\pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{\pm}0.4ng/mL$ in T1-3 and $0.7{\pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{\pm}5.6ng/mL$ in T1-3 and $26.1{\pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{\pm}0.4ng/mL$ in M0 and $0.7{\pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{\pm}8.3ng/mL$ in M0 and $21.5{\pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.576-584
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• 2000

Background : With the increase of cigarette consumption by women and the young, the incidence of lung cancer is expected to increase during the next three or four decades in Korea. The purpose of this study was to analyze the smoking habits in patients with lung cancer and to identify the gender differences in terms of their susceptibility to cigarette related carcinogens. Method : This investigation was a hospital-based case control study, which included the data of 178 case subjects (72 females, 106 males) with lung cancer and 218 control subjects (97 females, 121 males) with diseases unrelated to smoking. The information was obtained through a direct personal interview and a questionnaire related to personal smoking history. Results : The relative frequency of the squamous cell carcinoma was substantially higher in males than in females (61.3% in males, and 29.2% in females), while adenocarcinoma including bronchoalveolar cell carcinoma was higher in females(31.9% in females, 18.9% in males). Kreyberg I lung cancer was of relatively higher frequencies in males and smokers, while Kreyberg II lung cancer was higher in females and never smokers. The odds ratios (ORs) at each exposure level were consistently higher in females than males. For all cell types, the risk of lung cancer was increased with the quantity of smoked cigarettes, duration of smoking, and depth of inhalation. Odds ratio was distinctly higher in Kreyberg I lung cancer than in total lung cancer and a steeper gradient of risk with increased smoking was observed in females. Conclusion : The relative risk for lung cancer was consistently higher in females than in males at every level of exposure to cigarette smoke. This is believed to be due to the higher susceptibility of females to tobacco carcinogens, such as gender associated differences of carcinogen activation and/or the elimination of smoking related metabolites.

• Korean Journal of Radiology
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• v.22 no.4
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• pp.652-662
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• 2021

Objective: To investigate the association between CT imaging features and survival outcomes in patients with primary invasive mucinous adenocarcinoma (IMA). Materials and Methods: Preoperative CT image findings were consecutively evaluated in 317 patients with resected IMA from January 2011 to December 2015. The association between CT features and long-term survival were assessed by univariate analysis. The independent prognostic factors were identified by the multivariate Cox regression analyses. The survival comparison of IMA patients was investigated using the Kaplan-Meier method and propensity scores. Furthermore, the prognostic impact of CT features was assessed based on different imaging subtypes, and the results were adjusted using the Bonferroni method. Results: The median follow-up time was 52.8 months; the 5-year disease-free survival (DFS) and overall survival rates of resected IMAs were 68.5% and 77.6%, respectively. The univariate analyses of all IMA patients demonstrated that 15 CT imaging features, in addition to the clinicopathologic characteristics, significantly correlated with the recurrence or death of IMA patients. The multivariable analysis revealed that five of them, including imaging subtype (p = 0.002), spiculation (p < 0.001), tumor density (p = 0.008), air bronchogram (p < 0.001), emphysema (p < 0.001), and location (p = 0.029) were independent prognostic factors. The subgroup analysis demonstrated that pneumonic-type IMA had a significantly worse prognosis than solitary-type IMA. Moreover, for solitary-type IMAs, the most independent CT imaging biomarkers were air bronchogram and emphysema with an adjusted p value less than 0.05; for pneumonic-type IMA, the tumors with mixed consolidation and ground-glass opacity were associated with a longer DFS (adjusted p = 0.012). Conclusion: CT imaging features characteristic of IMA may provide prognostic information and individual risk assessment in addition to the recognized clinical predictors.

• 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.