• Radiation Oncology Journal
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• v.26 no.1
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• pp.17-23
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• 2008

Purpose: The best treatment for advanced esophageal cancer is chemoradiotherapy followed by surgery. In spite of the advance of multimodality therapy, most patients with esophageal cancer are treated with radiation therapy alone. This study reports the outcome of the use of conventional external beam radiotherapy alone for the treatment of esophageal cancer. Materials and Methods: Between January 1998 and December 2005, 30 patients with squamous cell carcinoma of the esophagus were treated with external beam radiotherapy using a total dose exceeding 40 Gy. Radiotherapy was delivered with a total dose of 44-60 Gy(median dose, 57.2 Gy) over $36{\sim}115$ days(median time, 45 days). Thirteen patients(43.3%) had a history of disorders such as diabetes, hypertension, tuberculosis, lye stricture, asthma, cerebral infarct, and cancers. Four patients metachronously had double primary cancers. The most common location of a tumor was the mid-thoracic portion of the esophagus(56.7%). Tumor lengths ranged from 2 cm to 11 cm, with a median length of 6 cm. For AJCC staging, stage III was the most common (63.3%). Five patients had metastases at diagnosis. Results: The median overall survival was 8.3 months. The survival rates at 1-year and 2-years were 33.3% and 18.7%, respectively. The complete response rate $1{\sim}3$ months after radiotherapy was 20%(6/30) and the partial response rate was 70%(21/30). Sixteen patients(53.3%) had an improved symptom of dysphagia. Significant prognostic factors were age, tumor length, stage, degree of dysphagia at the time of diagnosis and tumor response. Cox regression analysis revealed the aim of treatment, clinical tumor response and tumor length as independent prognostic factors for overall survival. Twenty-eight patients had local failure and another four patients had metastases. Three patients were detected with double primary cancers in this analysis. A complication of esophageal stricture was observed in three patients(10%), and radiation pneumonitis occurred in two patients(6.7%). Conclusion: The prognosis of esophageal cancer remains poor, in spite of advances in radiotherapy techniques. Radiotherapy is one of the main treatment modalities for the relief of dysphagia and treatment related complications are minimal. It is expected that the addition of chemotherapy or another systemic modality to radiotherapy will improve tumor control and increase the survival rate in advanced esophageal cancer.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.512-522
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• 1999

Background: Due to the paucity of suitable donor organs for lung allotransplantation, a number of techniques have been developed to improve the lung preservation. Ultrastructural studies of the morphologic changes of the flushing, preservation and reperfusion injury in donor lungs have rarely been reported. Methods: Adult dogs (n=46) were matched as donors and recipients for the single lung transplantation. The donor lungs were preserved after flushing with preservation solution and transplanted after 20-hours of preservation at $10^{\circ}C$. Ultrastructural features of the lung were examined after flushing, preservation and 2 hours after lung transplantation (reperfusion) respectively. Results: Electron microscopy after flushing showed focal alveolar collapse and mild swelling of type I epithelial cells. After preservation both type I epithelial cells and endothelial cells were swollen and destroyed focally. The endothelial cells showed protrusion of tactile-like structures into the lumina, blebs or vacuoles of the cytoplasm After reperfusion the lung tissue showed fibrin material in the alveoli, prominent type I epithelial cell swelling with fragmented cytoplasmic debris and marked endothelial cell swelling with vacuoles or tactile-like projections. The alveolar macrophages showed active phagocytosis. Scanning electron microscopic examination of the pulmonary parenchyma showed focally alveolar collapse and focal consolidation after the preservation and more prominent changes after the reperfusion procedure. The lungs preserved with low potassium dextran glucose solution, with additional prostaglandin $E_1(PGE_1)$ and verapamil(VP) showed relatively well preserved ultrastructures compared with those which were preserved with modified Euro-Collins or University of Wisconsin, and with additional $PGE_1$ and/or VP. Conclusion: The ultrastructural changes associated with flushing were mild in severity, the donor lungs were injured during the preservation, and further damage was occurred during the reperfusion. The reperfusion injury resulted in prominent pulmonary parenchymal alterations with a pattern of acute lung injury.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.251-258
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• 1998

Purpose : This study was performed to analyze the factors affecting local control in malignant tumors of the parotid gland treated with surgery and postoperative radiation. Materials and methods : Twenty-six patients were treated for malignant tumors of the parotid gland from 1986 to 1995 at Department of Therapeutic Radiology, Chonnam University Hospital. Age of the patients ranged from 14 to 72 years (median : 55 years). Histologically 10 patients of mucoepidermoid carcinoma, 7 of squamous cell carcinoma, 4 of acinic cell carcinoma, 4 of adenoid cystic carcinoma and 1 of adenocarcinoma were treated. Total parotidectomy was performd in 15 of 26 patients, superficial in 7, subtotal in 4. Facial nerve was sacrificed in 5 patients. Postoperatively 4 patients had residual disease, 4 had positive resection margin. Radiation was delivered through an ipsilateral wedged pair of photon in 11 patients. High energy electron beam was mixed with photon in 15 patients. Electron beam dose ranged from 900 cGy to 3800 cGy (median 1700 cGy). Total radiation dose ranged from 5000 cGy to 7560 cGy (median : 6020 cGy). Minimum follow-up period was 2 years. Local control and survival rate were calculated using Kaplan-Meier method. Generalized Wilcoxon test and Cox proportional hazard model were used to test factors affecting local control. Results : Five (19$\%$) of 26 patients had local recurrence. Five year local control rate was 77$\%$. Overall five year survival rate was 70$\%$. Sex, age, tumor size, surgical involvement of cervical lymph node, involvement of resection margin, surgical invasion of nerve, and total dose were analyzed as suggested factors affecting local control rate. Among them patients with tumor size less than 4 cm (p=0.002) and negative resection margin (p=0.011) were associated with better local control rates in univariate analysis. Multivariate analysis showed only tumor size factor is associated with local control rate (p=0.022). Conclusion : This study suggested that tumor size is important in local control of malignant tumors of parotid gland.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.347-355
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• 1999

Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.953-961
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• 1998

Background : In recent years, lung cancer has been one of most common cause of death in Korea. Despite many physician's high degree of pessimism about the gains made in treatment, progressive improvement in the survival of lung cancer by treatment has occurred, particulary in the early stages of the disease. However, a lot of patients refuse treatment or give up in the fight against the disease. This study was done to evaluate factors influencing the compliance to therapy and to lead in the establishment of special programs to enhance compliance in patients with lung cancer. Methods: The medical records of 903 patients, whose ECOG(Eastern Cooperative Oncology Group) performance status was 3 or less and whose medical record was relatively satisfactory, among 1141 patients diagnosed with lung cancer between January 1989 and December 1996 were reviewed retrospectively. Compliance was classified into three groups based on the degree of compliance with physicians practice guideline: (a) compliants; (b) patients who initially complied but gave up of themselves midway during the course of treatment; (c) noncompliants who refused the treatment. Results: The overall compliance rate was 63.9%, which was progressively increased from 57.3-61.3% in 1989 and 1990 to 64.2-67.5% in 1995 and 1996. Age, education level and occupation of patients bore statistically significant relationship with the compliance but sex, marital status and smoking history did not. The compliance was significantly higher in patients without symptoms than with, and was also significantly higher in patients with good performance status. The compliance was significantly high in patients with NSCLC(non-small cell lung cancer) compared to SCLC(small cell lung cancer), but after exclusion of stage I and II, among NSCLC, which had higher compliance to surgery there was no significant difference of compliance by histology. The compliance was significantly lower in advanced stage. Conclusion: To enhance the compliance, special care including education programs about therapy including complication and prognosis are necessary, especially for educationally and economically disadvantaged patients.

• Journal of Life Science
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• v.17 no.5 s.85
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• pp.678-686
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• 2007

Human mesenchymal stem cells(hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum(FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. Previously, we have shown that hADSC can be cultured in human serum(HS) during their isolation and expansion, and that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34 cells mobilized from bone marrow in NOD/SCID mice. In this study we determined whether hADSC grown in HS maintain surface markers expression similar with cells grown in FBS during culture expansion and compared gene expression profile by Affymetrix microarray. Flow cytometry analysis showed that HLA-DR, CD117, CD29 and CD44 expression in HS-cultured hADSC during culture expansion were similar with that in FBS-cultured cells. However, the gene expression profile in HS-cultured hADSC was significantly different from that in FBS-cultured cells. Therefore, these data indicated that HS-cultured hADSC should be used in vivo animal study of hADSC transplantation for direct extrapolation of preclinical data into clinical application.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.409-423
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• 1998

Purpose : This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. Materials and Methods : We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III-B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. Results : The overall 1-year, 2-year, and 3-year survival rates were 63$\%$, 29$\%$, and 26$\%$, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23$\%$ and 16$\%$, respectively. The overall 1-year survival rates according to the stage was 100$\%$ for stage I, 80$\%$ for stage II, 61$\%$ for stage III, and 50$\%$ for stage IV. The overall 1-year 2-year, and 3-year survival rates for stage III patients only were 61$\%$, 23$\%$, and 20$\%$, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 10$\%$ and partial response rate was 50$\%$. Thirty patients (43$\%$) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80$\%$) of these 30 Patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58$\%$): local relapse in 6 patients (43$\%$), distant metastasis in 6 patients (43$\%$) and local relapse with distant metastasis in 2 patients (14$\%$). Therefore, 10 patients (23$\%$) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46$\%$) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59$\%$ in radiotherapy alone and 66$\%$ in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51$\%$ in radiotherapy alone and 68$\%$ in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneunonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. Conclusion : The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.75-87
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• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.322-332
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• 1998

Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.69-84
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• 1997

Background : Although the overall prognosis of patients with lung cancer is poor, highly effective treatment exists for the small subset of patients with early lung cancer(carcinoma in situ/micro- invasive cancer). But very few patients have benefit from them because these lesions are difficult to detect and localize with conventional white-light bronchoscopy. To overcome this problem, a Lung Imaging Fluorescence Endoscopic device(LIFE) was developed to detect and clearly delineate the exact location and extent of premalignant and early lung cancer lesions using differences in tissue autofluorescence. Purpose : The purpose of this study was to determine the difference of sensitivity and specificity in detecting dysplasia and carcinoma between fluorescence imaging and conventional white light bronchoscopy. Material and Methods : 35 patients (16 with abnormal chest X-ray, 2 with positive sputum study, 2 with undiagnosed pleural effusion, 15 with respiratory symptom) have been examined by LIFE imaging system. After a white light bronchoscopy, the patients were submitted to fluorescence bronchoscopy and the findings of both examinations have been classified in 3 categories(class I, II, III). From of all class n and III sites, 79 biopsy specimens have been collected for histologic examination: a comparison between histologic results and white light or fluorescence bronchoscopy has been performed for assessing sensitivity and specificity of the two methods. Results : 1) Total 79 sires in 35 patients were examined. Histology demonstrated 8 normal mucosa, 21 hyperplasia, 23 dysplasia, and 27 microinvasive and invasive carcinoma. 2) The sensitivity of white light or fluorescence bronchoscopy in detecting dysplasia was 60.9% and 82.6%, respectively. 3) The results of this study showed 70.3 % sensitivity for microinvasive or invasive carcinoma with LIFE system, versus 100% sensitivity for white light in 27 cases of carcinoma. The false negative study of LIFE system was 8 cases(3 adenocarcinoma and 5 small cell carcinoma), which were infiltrated in submucosal area and had normal epithelium. Conclusion : To improve the ability 10 diagnose and stage more accurately, fluorescence imaging may become an important adjunct to conventional bronchoscopic examination because of its high detection rate of premalignant and malignant epithelial lesion. But. it has limitation to detect in submucosal infiltrating carcinoma.