• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.9-15
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• 2006

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.269-275
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• 2003

Purpose: To evaluate the results of radiation management on recurrence, survival and prognostic factors of patients with nasopharyngeal cancer Materials and Methods: Forty-nine patients, treated for nasopharyngeal cancer by radiotherapy between January 1984 and June 2000, were retrospectively studied. All patients were followed up for at least 2.5 years. Their median age was 52 years (range 17$\~$78). The histological types were 21 squamous cell carcinoma, 25 undifferentiated carcinoma, and 3 adenoid cystic carcinoma. The tumor stages were as follows: T1 in 14 patients, T2 in 24, T3 in 3, and T4 in 8, and N0 in 17 patients, Nl in 15, N2 in 4 and N3 in 13. Stages I, IIa, IIb ,III, IV and IVb were 4, 7, 12, 5, 8, and 13 patients respectively. Radiation doses of 58$\~$70 Gy (median 68.7 Gy) were given to the nasopahryngeal and involved lymphatic areas and of 46 $\~$ 50 Gy to the uninvolved neck areas. Results: The overall 5 and 10-year actuarial and disease free survival rates were 54.53$\%$ and 47$\%$ and 55.7$\%$ and 45.3$\%$, respectively The overall five-year survival rates were 100$\%$ in stage I , 80$\%$ in stage IIa, 59.5$\%$ in stage IIIb, 40$\%$ in stage III, and 42.2$\%$ in stage IV tumors. Twenty-three patients fatted either loco-regionally or distantly. Incidences of local failure, regional failure and distant metastasis for the first failure were 20.4$\%$, 8.2$\%$ and 20.4$\%$, respectively. Local recurrences were 4.3$\%$ in T1, 12.5$\%$ in T2, 0$\%$ in T3, and 62.5$\%$ in T4 lesions. Distant metastasis was seen in 41.2$\%$ of N2-3 lesions. Fifty percent of local recurrence appeared within 2 years of treatment at the primary lesion, whereas 70$\%$ of distant metastasis appeared within 2 years following treatment. Young age, female, early T stage, N0 stage; and poorly differentiated carcinoma were all related with good survival. However only stage showed statistically significance. Conclusionn: Based on the results of this study, radiation therapy to nasopharyngeal cancer showed high local recurrence in T4 and increased metastasis in N2-3 lesions. To improve local failure, further radiation doses, such as stereotactic radiation or IMRT radiation, are necessary especially in T4 lesions. The high incidence of distant metastasis in positive lymph node patients, indicates that combined radiation and effective chemotherapeutic agents with appropriated schedule are necessary.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.251-256
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• 2000

Purpose : To evaluate efficacy and complication of stereotactic radiosurgery using stereotactic body frame. Methods and Materials :From December 1997 to June 1999, 11 patients with primary and metastatic tumors were treated with stereotactic radiosurgery using stereotactic body frame(Precision TherapyTu). Three patients were treated with primary hepatoma and seven with metastatic tumor from liver, lung, breast, trachea and one with arteriovenous malformation on neck. We used vacuum pillow for immobilization and made skin marker on sternum and tibia area with chest marker and leg marker. Diaphragm control was used for reducing movement by respiration. CT-simulation and treatment planning were peformed. Set-up error was checked by CT-Simulator before each treatment. Dose were calculated on the 80$\~$90$\%$ isodose of isocenter dose and given consecutive 3 fractions for total dose of 30 Gy (10 Gy/fraction). Results :Median follow-up was 12 months. One patient (9$\%$) showed complete response and four Patients (36$\%$) showed partial response and others showed stable disease. Planning target volumes (PTV) ranged from 3 to 111 cc (mean 18.4 n). Set-up error was within 5 mm in all directions (X, Y, Z axis). There was no complication in all patients. Conclusion :In Primary and metastatic tumors, stereotactic body frame is very safe, accurate and effective treatment modality.

• 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.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.114-121
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• 2007

Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

• The Journal of Korean Society for Radiation Therapy
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• v.30 no.1_2
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• pp.97-105
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• 2018

Purpose : Proton Therapy using Bragg-peak, because it has distinct characteristics in providing maximum dosage for tumor and minimal dosage for normal tissue, a medical imaging system that can quantify changes in patient position or treatment area is of paramount importance to the treatment of protons. The purpose of this research is to evaluate the usefulness of the algorithm by comparing the image matching through the set-up and in-house code through the existing dips program by producing a Matlab-based in-house registration code to determine the error value between dips and DRR to evaluate the accuracy of the existing treatment. Materials and Methods : Thirteen patients with brain tumors and head and neck cancer who received proton therapy were included in this study and used the DIPS Program System (Version 2.4.3, IBA, Belgium) for image comparison and the Eclipse Proton Planning System (Version 13.7, Varian, USA) for patient treatment planning. For Validation of the Registration method, a test image was artificially rotated and moved to match the existing image, and the initial set up image of DIPS program of existing set up process was image-matched with plan DRR, and the error value was obtained, and the usefulness of the algorithm was evaluated. Results : When the test image was moved 0.5, 1, and 10 cm in the left and right directions, the average error was 0.018 cm. When the test image was rotated counterclockwise by 1 and $10^{\circ}$, the error was $0.0011^{\circ}$. When the initial images of four patients were imaged, the mean error was 0.056, 0.044, and 0.053 cm in the order of x, y, and z, and 0.190 and $0.206^{\circ}$ in the order of rotation and pitch. When the final images of 13 patients were imaged, the mean differences were 0.062, 0.085, and 0.074 cm in the order of x, y, and z, and 0.120 cm as the vector value. Rotation and pitch were 0.171 and $0.174^{\circ}$, respectively. Conclusion : The Matlab-based In-house Registration code produced through this study showed accurate Image matching based on Intensity as well as the simple image as well as anatomical structure. Also, the Set-up error through the DIPS program of the existing treatment method showed a very slight difference, confirming the accuracy of the proton therapy. Future development of additional programs and future Intensity-based Matlab In-house code research will be necessary for future clinical applications.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.91-99
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• 1999

Propose : This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. Materials and Methods : We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70$\%$) patients was male. Histological types were composed of 3 (6$\%$) keratinizing, 30 (64$\%$) nonkeratinizing squamous cell carcinoma and 13 (28$\%$) undifferentiated carcinoma. Histoiogicai type was not known in 1 patient (2$\%$). We restaged according to the staging system of 1997 American Joint Committee on Cancer Forty seven patients were recorded as follows: 71: 11 (23$\%$), T2a; 6 (13$\%$), T2b; 9 (19$\%$), 73; 7 (15$\%$), 74: 14 (30$\%$), and NO; 7 (15$\%$), Nl: 14 (30$\%$), N2; 21 (45%), N3: 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4$\%$), IIA: 2 (4$\%$), IIB; 10 (21$\%$), III; 14 (30$\%$), IVA; 14 (30$\%$) and IVB; 5 (11$\%$). Radiation therapy was done using 6 MV and 10 MV X- ray of linear accelerator. Electron beam was used for the Iymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin +5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free suwival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Results: Local control rate was 81$\%$ in 5 year. Five year survival rate was 60$\%$ (median survival; 100 months). We included age, sex, cranial nerve deflicit, histologic type, stage group, chemotherapy, elapsed days between chemotherapy and radiotherapy, total radiation dose, period of radiotherapy as potential prognostic factors in multivariate analysis. As a result, cranial none deficit (P=0.004) had statistical significance in local control rate. Stage group and total radiation dose were significant prognostic factors in survival (P=0.000, P=0.012), and in disease free survival rates (P=0.003, P=0.008), respectively. Common complications were xerostomia, tooth and ear problems. Hypothyroidism was developed in 2 patients. Conclusion : In our study, cranial none deficit was a significant prognostic factor in local control rate, and stage group and total radiation dose were significant factors in both survival and disease free survival of nasopharyngeal carcinoma. We have concluded that chemotherapy and radiotherapy used in our patients were effective without any serious complication.

• Journal of Chest Surgery
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• v.38 no.2 s.247
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• pp.157-163
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• 2005

Background: Clinical outcomes of esophageal cancer have not been satisfactory in spite of the development of surgical skills and protocols of adjuvant therapy. We analyzed the results of corrective surgical patients for esophageal cancer from January 1992 to July 2002. Material and Method: Among 129 patients with esophageal cancer, this study was performed in 68 patients who received corrective surgery. The ratio of sex was 59 : 9 (male : female) and mean age was $61.07\pm7.36$ years old. Chief complaints of this patients were dysphagia, epigastric pain and weight loss, etc. The locations of esophageal cancer were 4 in upper esophagus, 36 in middle, 20 in lower, 8 in esophagogastric junction. 60 patients had squamous cell cancer and 7 had adenocarcinoma, and 1 had malignant melanoma. Five patients had neoadjuvant chemotherapy. Result: The postoperative stage I, IIA, IIB, III, IV patients were 7, 25, 12, 17 and 7, respectively. The conduit for replacement of esophagus were stomach (62 patients) and colon (6 patients). The neck anastomosis was performed in 28 patients and intrathoracic anastomosis in 40 patients. The technique of anastomosis were hand sewing method (44 patients) and stapling method (24 patients). One of the early complications was anastomosis leakage (3 patients) which had only radiologic leakage that recovered spontaneously. The anastomosis technique had no correlation with postoperative leakage, which stapling method (2 patients) and hand sewing method (1 patient). There were 3 respiratory failures, 6 pneumonia, 1 fulminant hepatitis, 1 bleeding and 1 sepsis. The 2 early postoperative deaths were fulminant hepatitis and sepsis. Among 68 patients, 23 patients had postoperative adjuvant therapy and 55 paitents were followed up. The follow up period was $23.73\pm22.18$ months ($1\~76$ month). There were 5 patients in stage I, 21 in stage 2A, 9 in stage IIB, 15 in stage III and 5 in stage IV. The 1, 3, 5 year survival rates of the patients who could be followed up completely was $58.43\pm6.5\%,\;35.48\pm7.5\%\;and\;18.81\pm7.7\%$, respectively. Statistical analysis showed that long-term survival difference was associated with a stage, T stage, and N stage (p<0.05) but not associated with histology, sex, anastomosis location, tumor location, and pre and postoperative adjuvant therapy. Conclusion: The early diagnosis, aggressive operative resection, and adequate postoperative treatment may have contributed to the observed increase in survival for esophageal cancer patients.