• Radiation Oncology Journal
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• v.27 no.4
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• pp.210-217
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• 2009

Purpose: To assess the influence of cyclooxygenase-2 (COX-2) expression on the survival of patients with a combination of rectal cancer and lymph node metastasis. Materials and Methods: The study included rectal cancer patients treated by radical surgery and postoperative radiotherapy at the Dong-A university hospital from 1998 to 2004. A retrospective analysis was performed on a subset of patients that also had lymph node metastasis. After excluding eight of 86 patients, due to missing tissue samples in three, malignant melanoma in one, treatment of gastric cancer around one year before diagnosis in one, detection of lung cancer after one year of diagnosis in one, liver metastasis in one, and refusal of radiotherapy after 720 cGy in one, 78 patients were analyzed. The immunohistochemistry for COX-2 was conducted with an autostainer (BenchMark; Ventana, Tucson, AZ, USA). An image analyzer (TissueMine; Bioimagene, Cupertino, CA, USA) was used for analysis after scanning (ScanScope; Aperio, Vista, CA, USA). A survival analysis was performed using the Kaplan Meier method and significance was evaluated using the log rank test. Results: COX-2 was stained positively in 62 patients (79.5%) and negatively in 16 (20.5%). A total of 6 (7.7%), 15 (19.2%), and 41 (52.6%) patients were of grades 1, 2, and 3, respectively for COX-2 expression. No correlation was found between being positive of COX-2 patient characteristics, which include age (<60-year old vs. $\geq$60), sex, operation methods (abdominoperineal resection vs. lower anterior resection), degrees of differentiation, tumor size (<5 cm vs. $\geq$5 cm), T stages, N stages, and stages (IIIa, IIIb, IIIc). The 5-year overall and 5-year disease free survival rates for the entire patient population were 57.0% and 51.6%, respectively. The 5-year overall survival rates for the COX-2 positive and negative patients were 53.0% and 72.9%, respectively (p=0.146). Further, the 5-year disease free survival rates for the COX-2 positive and negative patients were 46.3% and 72.7%, respectively (p=0.118). The 5-year overall survival rates were significantly different (p<0.05) for the degree of differentiation, N stage, and stage, whereas the 5-year disease free survival rates were significant for N stage and stage. Conclusion: Being positive for and the degree of COX-2 expression did not have a significant influence on the survival of rectal cancer patients with lymph node metastasis. However, N stage and stage did significantly influence the rateof survival. Further analysis of a greater sample size is necessary for the verification of the effect of COX-2 expression on the survival of rectal cancer patients with lymph node involvement.

• Tuberculosis and Respiratory Diseases
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• v.57 no.1
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• pp.32-36
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• 2004

Background : The purpose of this study was to evaluate the usefulness of the pleural fluid carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1) tumor markers as complementary tools for the diagnosis of malignant pleural effusions. Patients and Methods : The levels of pleural and serum CEA and CYFRA 21-1 were prospectively assayed in 222 patients with pleural effusions (150 benign effusions, 57 bronchogenic carcinomas and 15 metastatic carcinomas). Results : The levels of pleural fluid CEA and CYFRA 21-1 in the malignant effusions were significantly higher than those in the benign effusions. With a specificity of 95%, the cut off values for the CEA and CYFRA 21-1 in pleural effusions were 5 and 89 ng/ml, respectively. The diagnostic sensitivities of the pleural fluid CEA and CYFRA 21-1 in malignant effusions were 72 and 54%, respectively, whereas using a combination of the two, the sensitivity increased to 87% (p<0.05). Conclusions : These findings suggest that a combination of the pleural fluid CEA and CYFRA 21-1 in pleural effusions can be useful in the diagnosis of malignant pleural effusions.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.2
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• pp.93-104
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• 2023

This study aimed to identify new markers that cause lung adenocarcinoma by analyzing mutation hotspots for the top five genes with high mutation frequency in lung adenocarcinoma in Koreans by next generation sequencing (NGS) analysis. The association between TP53 mutation types and patterns with smoking, a major cause of lung cancer, was examined. The clinicopathological characteristics of lung adenocarcinoma patients with TP53 P72R SNPs were analyzed. In Korean lung adenocarcinoma cases, regardless of the smoking status, the TP53 P72R SNP was the most frequently occurring mutational hotspot, in which the nucleotide base was transversed from C to G, and the amino acid was substituted from proline to arginine at codon 72 of TP53. An analysis of the clinicopathological characteristics of lung adenocarcinoma cases with TP53 P72R SNP revealed no significant correlation with the patient's age, gender, smoking status, and tumor differentiation, but a significant correlation with low stage (P-value =0.026). This study confirmed an increase in TP53 rather than EGFR, which was reported as the most frequent mutations in lung adenocarcinoma in Koreans through NGS. Among them, TP53 P72R SNP is the most frequent regardless of smoking status.

• Journal of Chest Surgery
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• v.43 no.6
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• pp.681-686
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• 2010

Background: A chest computed-tomography has become more prevalent so that it is more common to detect small sized pulmonary nodules that have not been found in previous simple chest x-ray. If those detected nodules are undersized or located in pulmonary parenchyma, it is difficult to accomplish a biopsy since it is vulnerable to explore them either grossly or digitally. Thus, in our hospital, a thoracoscopic pulmonary wedge resection was performed after locating a lesion by means of hook wire with CT-guided. Material and Method: 31 patients (17 males and 14 female patients) from December in 2006 to June in 2010 became our subjects; their 34 pulmonary nodules were subjected to the thoracoscopic pulmonary wedge resection after locating a lesion by means of hook wire with CT-guided. Also we analyzed a possibility of hook wire dislocation, a frequency of conversion to open thoracotomy, time consumed to operation after location of a lesion, operation time, post operation complication, and histological diagnosis of the lesion. Result: 12 of 34 cases were ground glass lesion, whereas 22 cases of them were solitary pulmonary lesion. The median value of the lesion was 8mm in size (range: 3 to 23 mm), while the median value was 12.5 mm in depth (range: 1 to 34 mm). The median value of time consumed from location of the lesion to anesthetic induction was 86.5 minutes (41~473 minutes); furthermore the mean value of operation time was 103 minutes (25~345 minutes). Intrathoracic wire dislocation was found in one case, but a target lesion was successfully excised. Open thoracotomy was performed in four cases due to pleural adhesion. However, there was no case of conversion to open thoracotomy due to failure to detect a target lesion. In histological diagnosis, metastatic cancer were found in 15 cases, which were the most common, primary lung cancer were in 9 cases, non-specific inflammation were in 3 cases, tuberculosis inflammation were in 2 cases, lymph nodes were in 2 cases, active tuberculosis were in 1 case, atypical adenomatous hyperplasia was in 1 case and normal lung parenchymal finding was in 1 case, respectively. Conclusion: In our hospital, in order to accomplish a precise histological diagnosis of ground-glass lesion and pulmonary nodules in lung parenchyma, location of pulmonary nodules were exactly located with hook wire under chest computed-tomography, which was followed by lung biopsy. We concluded that this was an accurate, minimally invasive and valuable method to minimize the complications and increase of cost of medical service provided.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.291-298
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• 2003

Purpose: We report upon a web-based system for Patterns of Care Study (PCS) devised for Korean radiation oncology. This PCS was designed to establish standard tools for clinical quality assurance, to determine basic parameters for radiation oncology processes, to offer a solid system for cooperative clinical studies and a useful standard database for comparisons with other national databases. Materials and Methods: The system consisted of a main server with two back-ups in other locations. The program uses a Linux operating system and a MySQL database. Cancers with high frequencies in radiotherapy departments in Korea from 1998 to 1999 were chosen to have a developmental priority. Results: The web-based clinical PCS .system for radiotherapy in www.pcs.re.kr was developed in early 2003 for cancers of the breast, rectum, esophagus, larynx and lung, and for brain metastasis. The total number of PCS study items exceeded one thousand. Our PCS system features user-friendliness, double entry checking, data security, encryption, hard disc mirroring, double back-up, and statistical analysis. Alphanumeric data can be input as well as image data. In addition, programs were constructed for IRB submission, random sampling of data, and departmental structure. Conclusion: For the first time in the field of PCS, we have developed a web-based system and associated working programs. With this system, we can gather sample data in a short period and thus save, cost, effort and time. Data audits should be peformed to validate input data. We propose that this system should be considered as a standard method for PCS or similar types of data collection systems.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.614-623
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• 2000

Background : Diffuse alveolar hemorrhage (DAH) is rare but often fatal. To determine the clinical manifestations of DAH, its etiology, clinical course and prognosis were studied. Method : A retrospective analysis was performed in 21 patients that were diagnosed as DAH. Diagnosis of DAH was based on the presence of the "classical triad" of hemoptysis, anemia, and rapidly progressive infiltrates on chest X-ray and a finding of bronchoalveolar lavage or lung biopsy. Results : Thirteen patients (61.9%) had collagen vascular diseases (CVDs) as underlying disease and 10 patients had systemic lupus erythematosus. Females were more prevalent in CVD than in non-collagen vascular disease (NCVD). Otherwise, there were no significant differences between the two groups in terms of clinical manifestations. Dyspnea (95.2%), cough (76.2%), hemoptysis (61.9%), and fever (33.0%) were frequent symptoms. The initial creatinine level was higher in CVD than in NCVD ($3.27{\pm}3.15$ mg/dl vs. $1.19{\pm}0.94$ mg/dl, p=0.030). The corresponding drop in hemoglobin level was $2.69{\pm}1.26$ g/dl. Maximal drop in hemoglobin preceded the progression of infiltrates on the chest radiograph by $1.38{\pm}4.22$ days. The mortality rate was higher in the patients with NCVD than in those with CVD (50.0% vs. 23.1%). Conclusion : The DAH can occur not only in patients with CVD but also in those with NCVD. Higher creatinine level CVD in patients is associated with renal involvement in conjunction with DAH. The maximal drop in hemoglobin preceeding the progression of infiltrates on the chest radiograph suggests that the drop in hemoglobin is important for diagnosing DAH.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.229-236
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• 1996

Purpose : To evaluate the changes of differential counts and lymphocyte subsets in cancer patients' leukocyte before and after radiotherapy. Materials and Methods : From Dec. 1994 to Mar 1995, the changes of leukocyte and its subsets in 16 patients who received radiotherapy in the Dept. of Radiation Oncology of Dong-A University Hospital were investigated. Radiation was delivered from 2700 cGy to 6660 cGy with median dose of 5400 cGy. The results of pre- and Post-radiotherapy were analyzed by paired T-test. The results of patients Who received < 50 Gy and $\geq$ 50 Gy were analyzed by Wilcoxon test. Results : Before and after radiotherapy, there was not any significant differences in the counts of leukocyte, granulocyte and monocyte. A remarkable decrease was noted in lymphocyte counts after radiotherapy(p=0.015). T cells, B cells and natural killer cells were also decreased in number after radiotherapy but it was not significant statistically. 1 helper cells and T suppressor cells were also decreased in number(p>0.05). The ratio of T helper/suppressor cell was decreased from 1.52 to 1, 11 and it was significant statistically(p=0.016). The portion of T suppressor cell among all T cells was increased after radiotherapy (p=0.0195). No significant difference was observed in the analysis of leukocyte and its subsets between patients who received < 50 Gy and $\geq$ 50 Gy, Conclusion : Radiotherapy caused remarkable decrease in lymphocyte count and its subsets. Among all lymphocyte subsets, T helper cell might be the most vulnerable to radiation, considering decreased ratio of T helper/suppressor cell count after radiotherapy.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.41-52
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• 2002

Purpose : 3D conformal radiotherapy, the optimum dose delivered to the tumor and provided the risk of normal tissue unless marginal miss, was restricted by organ motion. For tumors in the thorax and abdomen, the planning target volume (PTV) is decided including the margin for movement of tumor volumes during treatment due to patients breathing. We designed the respiratory gating radiotherapy device (RGRD) for using during CT simulation, dose planning and beam delivery at identical breathing period conditions. Using RGRD, reducing the treatment margin for organ (thorax or abdomen) motion due to breathing and improve dose distribution for 3D conformal radiotherapy. Materials and Methods : The internal organ motion data for lung cancer patients were obtained by examining the diaphragm in the supine position to find the position dependency. We made a respiratory gating radiotherapy device (RGRD) that is composed of a strip band, drug sensor, micro switch, and a connected on-off switch in a LINAC control box. During same breathing period by RGRD, spiral CT scan, virtual simulation, and 3D dose planing for lung cancer patients were peformed, without an extended PTV margin for free breathing, and then the dose was delivered at the same positions. We calculated effective volumes and normal tissue complication probabilities (NTCP) using dose volume histograms for normal lung, and analyzed changes in doses associated with selected NTCP levels and tumor control probabilities (TCP) at these new dose levels. The effects of 3D conformal radiotherapy by RGRD were evaluated with DVH (Dose Volume Histogram), TCP, NTCP and dose statistics. Results : The average movement of a diaphragm was 1.5 cm in the supine position when patients breathed freely. Depending on the location of the tumor, the magnitude of the PTV margin needs to be extended from 1 cm to 3 cm, which can greatly increase normal tissue irradiation, and hence, results in increase of the normal tissue complications probabiliy. Simple and precise RGRD is very easy to setup on patients and is sensitive to length variation (+2 mm), it also delivers on-off information to patients and the LINAC machine. We evaluated the treatment plans of patients who had received conformal partial organ lung irradiation for the treatment of thorax malignancies. Using RGRD, the PTV margin by free breathing can be reduced about 2 cm for moving organs by breathing. TCP values are almost the same values $(4\~5\%\;increased)$ for lung cancer regardless of increasing the PTV margin to 2.0 cm but NTCP values are rapidly increased $(50\~70\%\;increased)$ for upon extending PTV margins by 2.0 cm. Conclusion : Internal organ motion due to breathing can be reduced effectively using our simple RGRD. This method can be used in clinical treatments to reduce organ motion induced margin, thereby reducing normal tissue irradiation. Using treatment planning software, the dose to normal tissues was analyzed by comparing dose statistics with and without RGRD. Potential benefits of radiotherapy derived from reduction or elimination of planning target volume (PTV) margins associated with patient breathing through the evaluation of the lung cancer patients treated with 3D conformal radiotherapy.