• Radiation Oncology Journal
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• v.16 no.2
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• pp.99-106
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• 1998

Purpose : We conducted clonogenic assay using human cancer cell lines (MKN-45, PC-14, Y-79, HeLa) to investigate a correlation between the parameters of radiosensitivity. Materials and Methods : Human cancer cell lines were irradiated with single doses of 1, 2, 3, 5, 7 and 10Gy for the study of radiosensitivity and subrethal damage repair capacity was assessed with two fractions of 5Gy separated with a time interval of 0, 1, 2, 3, 4, 6 and 24 hours. Surviving fraction was assessed with clonogenic assay using $Sperman-H\"{a}rbor$ method and mathematical analysis of survival curves was done with linear-quadratic (LQ) , multitarget-single hit(MS) model and mean inactivation dose$(\v{D})$. Results : Surviving fractions at 2Gy(SF2) were variable among the cell lines, ranged from 0.174 to 0.85 The SF2 of Y-79 was lowest and that of PC-14 was highest(p<0.05, t-test). LQ model analysis showed that the values of $\alpha$ for Y-79, MKN-45, HeLa and PC-14 were 0.603, 0.356, 0.275 and 0.102 respectively, and those of $\beta$ were 0.005, 0.016, 0.025 and 0.027 respectively. Fitting to MS model showed that the values of Do for Y-79. MKN-45, HeLa and PC-14 were 1.59. 1.84. 1.88 and 2.52 respectively, and those of n were 0.97, 1.46, 1.52 and 1 69 respectively. The $\v{D}s$ calculated by Gauss-Laguerre method were 1.62, 2.37, 2,01 and 3.95 respectively So the SF2 was significantly correlated with $\alpha$, Do and $\v{D}$. Their Pearson correlation coefficiencics were -0.953 and 0,993. 0.999 respectively(p<0.05). Sublethal damage repair was saturated around 4 hours and recovery ratios (RR) at plateau phase ranged from 2 to 3.79. But RR was not correlated with SF2, ${\alpha}$, ${\beta}$, Do, $\v{D}$. Conclusion : The intrinsic radiosensitivity was very different among the tested human cell lines. Y-79 was the most sensitive and PC-l4 was the least sensitive. SF2 was well correlated with ${\alpha}$, Do, and $\v{D}$. RR was high for MKN-45 and HeLa but had nothing to do with radiosensitivity parameters. These basic parameters can be used as baseline data for various in vitro radiobiological experiments.

• Journal of Veterinary Clinics
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• v.26 no.6
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• pp.556-562
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• 2009

Skin tumors and mammary gland tumors have been shown to be the most common neoplasia in most of the strains of dogs. The risk for tumor development increases significantly with age and the prevalence and distribution are various according to individual tumors. The aim of this study is to classify histopathologically the skin and mammary gland tumors for recent two years, 2005 and 2006. A total of 128 skin and 240 mammary gland samples of dogs were selected that were submitted to National Veterinary Research and Quarantine Service and Kangwon National University from January 1, 2005 to December 31, 2006. The excised tissue were fixed in 10 percent neutral buffered formalin and processed routinely to paraffin wax. Sections were cut at $3{\mu}m$, stained with haematoxylin and eosin. The slides were examined based on the morphological criteria of M. H. Goldschmidt and W. Misdorp under a light microscope. The age of the dogs ranged from 1 to 19 years with a median of 8.7 years. The mean age of the skin and mammary gland tumors was 7.4 and 9.3 years. 47 (12.8%) were males and 259 (70.4%) were female with a male to female ratio of 0.18. Yorkshire terrier and maltese were more susceptible breeds, accounting for 44.3% of skin and mammary gland tumors. In skin tumors, epithelial, adnexal, and mesenchymal origin tumors were 18 (14.1%), 53 (41.4%), and 57 cases (44.5%), repectively. Among the epithelial, adenexal, and mesenchymal origin tumors, basal cell tumor (8.6%), sebaceous adenoma (15.6%), and histiocytoma (25.0%) were predominant in the incidence rate, respectively. In case of mammary gland tumors, 201 (83.8%) were benign and 39 (16.3%) were malignant with a benign to malignant ratio of 5.15. The most frequent mammary gland tumor was benign mixed tumor (35.0%) followed by mammary adenoma-complex type (31.7%).

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.233-243
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• 2000

Purpose : First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. Methods and Material : Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months, Twenty-seven patients (84.4$\%$) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional iymphatics with shrinking field technique. Ail patients received radiotherapy under conventional fractionated schedule (once a day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had Induction chemotherapy with cisplatln and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6$\%$): stage II, 10/32 (31.3$\%$); stage III, 8/32 (25$\%$): stage IV, 9/32 (28.1$\%$). Results :The 5-year overall survival rate of the whole series (32 patients) was 51.7$\%$. The overall survival rate at 5-years was 80$\%$ in stage I, 66.7$\%$ in stage II, 42.9$\%$ in stage III, 25$\%$ in stage IV (p=0.0958). The S-year local control rates after radiotherapy were as fellows: stage I, 100$\%$; stage II, 60$\%$ stage III, 62.5$\%$; stage IV, 44.4$\%$ (p=0.233). Overall vocal preservation rates was 65.6$\%$, 100% In stage I, 70% in stage II, 62.5$\%$ In stage III, 44.4$\%$ in stage IV (p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotllerapy, emergent tracheostomy was done. Four patients were died from distant metastsis, . three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor ( p=0.0215), and radiation dose (more or less than 70.2 Gy) was an important factor on survival (p=0.002). Conclusion : The role of radiotherapy treatment of supraglottic carcinoma is to important factor on survival and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supragiottic carcinomas could be successfully treated with either consewative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone is Inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.77-82
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• 2008

Purpose: We evaluated the failure pattern of the celiac axis, gastric lymph node, and treatment outcome in the upper and mid-esophageal region of cancer patients treated by definitive radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, retrospectively. Materials and Methods: The study constituted the evaluation 108 patients with locally advanced esophageal cancer receiving radiotherapy or a combination of radiotherapy and chemotherapy at Chonbuk National University Hospital from January 1986 to December 2006. In total, 82 patients treated by planned radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, were analysed retrospectively. The study population consisted of 78 men and 2 women(mean age of 63.2 years). In addition, 51 patients received radiotherapy alone, whereas 31 patients received a combination of radiation therapy and chemotherapy. The primary cancer sites were located in the upper portion(17 patients), and mid portion(65 patients), respectively. Further, the patients were in various clinical stages including T1N0-1M0(7 patients), T2N0-1M0(18 patients), T3N0-1M0(44 patients) and T4N0-1M0(13 patients). The mean follow up period was 15 months. Results: The various treatment outcomes included complete response(48 patients), partial response(31 patients) and no response(3 patients). The failure patterns of the lymph node were comprised of the regional lymph node(23 patients) and the distance lymph node which included celiac axis and gastric lymph node(13 patients). However, metastasis was not observed in the regional and distant lymph node in 10 patients, whereas 36 patients were not evaluated. Furthermore, of the 13 patients who developed celiac axis and gastric lymph node metastases, 3 were in stage T1N0-1M0 and 10 were in stage T2-4N0-1M0. A complete response appeared in 12 patients, whereas a partial response appeared in 1 patient. The mean survival time of the patients who appeared for regional and distant lymph node metastasis was 14.4 and 7.0 months, respectively. Conclusion: In locally advanced esophageal cancer patients, who were treated by definitive radiotherapy without celiac axis and gastric lymph node irradiation, the distant lymph node metastasis rate was high and the overall survival rate was lower compared to the regional lymph node metastasis. The incidence of regional and distant lymph node metastasis was high in patients who appeared beyond clinical stage T2 and received radiotherapy alone.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.41-52
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• 1996

Purpose : This paper reports a dosimetric study of 88 patients treated with a combination of external radiotherapy and high dose rate ICR for FIGO stage IIB carcinoma of the cervix. The purpose is to investigate the correlation between the radiation doses to the rectum, external radiation dose to the whole pelvis, ICR reference volume, TDF BED and the incidence of late rectal complications, retrospectively. Materials and Methods : From November 1989 through December 1992, 88 patients with stage IIB cervical carcinoma received radical radiotherapy at Department of Radiation Oncology in Yonsei University Hospital. Radiotherapy consisted of 44-54 Gy(median 49 Gy) external beam irradiation plus high dose rate intracavitary brachytherapy with 5 Gy per fraction twice a week to a total dose of 30 Gy on point A. The maximum dose to the rectum by contrast(r, R) and reference rectal dose by ICRU 38(dr, DR) were calculated. The ICR reference volume was calculated by Gamma Dot 3.11 HDR planning system, retrospectively The time-dose factor(TDF) and the biologically effective dose (BED) were calculated. Results : Twenty seven($30.7\%$) of the 88 patients developed late rectal complications:12 patients($13.6\%$) for grade 1, 12 patients($13.6\%$) for grade 2 and 3 patients($3.4\%$) for grade 3. We found a significant correlation between the external whole pelvis irradiation dose and grade 2, 3 rectal complication. The mean dose to the whole pelvis for the group of patients with grade 2, 3 complication was Higher, $4093.3\pm453.1$ cGy, than that for the patients without complication, $3873.8\pm415.6$ (0.05$7163.0\pm838.5$ cGy, than that for the Patients without rectal complication, $0772.7\pm884.0$ (p<0.05). There was no correlation of the rate of grade 2, 3 rectal complication with the iCR rectal doses(r, dr), ICR reference volume, TDF and BED. Conclusion : This investigation has revealed a significant correlation between the dose calculated at the rectal dose by ICRU 38(DR) or the most anterior rectal dose by contrast(R) dose to the whole pelvis and the incidence of grade 2, 3 late rectal complications in patients with stage IIB cervical cancer undergoing external beam radiotherapy and HOR ICR. Thus these rectal reference points doses and whole pelvis dose appear to be useful Prognostic indicators of late rectal complication in high dose rate ICR treatment in cervical carcinoma.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.9-18
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• 1995

Purpose : A retrospective analysis was performed to investigate the proper management of maxillary sinus carcinoma. Materials and Methods : Authors analysed 33 patients of squamous cell carcinoma of maxillary sinus treated at Chonnam University Hospital from January 1986 to December 1992. There were 24 men and 9 women with median age of 55 years. According to AJCC TNM system of 1988, a patient of T2, 10 patients of T3 and 22 patients of T4 were availalbe, respectively. Cervical lymph node metastases was observed in 5 patients(N 1;4/33, N2b; 1/33). Patients were classified as 3 groups according to management method. The first group, named as 'FAR' (16 patients), was consisted or preoperative intra-arterial chemotherapy with 5-fluorouracil(5-FU;mean of total dosage;3078mg) through the superficial temporal artery with concurrent radiation(mean dose delivered:3433cGy, daily 180-200cGy) and vitamin A(50,000 IU daily), and followed by total maxillectomy and postoperative radiation therapy(mean dose;2351cGy). The second group, named as 'SR'(7 patients), was consisted of total maxillectomy followed by postoperative radiation therapy(mean dose 5920 cGy). The third group, named as 'R'(6 patients), was treated with radiation alone(mean dose;7164cGy). Kaplan-Meier product limit method was used for survival analysis and Mantel-Cox test was performed for significance of survival difference between two groups. Results : Local recurrence free survival rate in the end of 2 year was $100\%$, $50\%$ and $0\%$ in FAR, SR and R group, respectively. Disease free survival rate in 2 years was $88.9\%$, $28.0\%$ and $0\%$ in FAR, SR and R group, respectively. Overall survival rate in 2 years was $88.9\%$, $40\%$ and $50\%$ in FAR, SR and R group, respectively. There were statistically significant difference between FAR and SR or FAR and R group in their local recurrence free, disease free and overall survial rates. But difference of each survival rate between SR and R group was not significant. Conclusion : In this study FAR group revealed better results than SR or R group. In the future prospective randomized study is in need.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.208-218
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• 1999

Background: Lung cancer-associated hypercalcemia is one of the most disabling and life-threatening paraneoplastic disorders. Humoral hypercalcemia is responsible for most lung cancer-associated hypercalcemia. Patients with hypercalcemia are usually in the advanced stage with obvious bulky tumor and carry a poor prognosis. Materials and Methods: Total 29 patients satisfied the following criteria: histologically proven primary lung cancer, corrected calcium level ${\geq}$ 10.5 mg/dL, and symptoms which could possibly be attributed to hypercalcemia. In this retrospective study, we evaluated the various clinical aspects of hypercalcemia, in relation to cancer stage, histologic cell type, mass size, bone metastasis, performance status, and other possible characteristics. Results: Total 29 lung cancer patients with hypercalcemia were studied, and most of them had squamous cell carcinoma in their histologic finding. The incidence of hypercalcemia was significantly higher between 50 and 69 years of age, and in the advancement of cancer stage. Although serum calcium level showed positive correlation with mass size, performance status, and bone metastasis, it was not significant statistically. Altered consciousness was significantly more frequent in the patients with higher serum calcium level. There were no differences in effectiveness among therapeutic regimens. Hypercalcemia was more frequently in the later stage of disease than during the initial diagnosis of lung cancer. Most of the patients died within 1 month after development of hypercalcemia. Conclusion: We concluded that hypercalcemia in lung cancer is related to extremely poor prognosis, and may be one of the causes of death and should be treated aggressively to prevent sudden deterioration or death.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.254-264
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• 2004

Purpose: This study was carried out to confirm clinical values and limitations of postoperative radiotherapy for hypopharyngeal carcinoma, to evaluate various prognostic factors which may affect to the treatment results and to use these results as fundamental data for making a new treatment strategy. Methods and Materials:. A retrospective analysis was peformed on 64 previously untreated patients with squamous cell carcinoma of the hypopharynx, seen between 1988 and 1999 at Pusan National University Hospital. Most of patients were treated by laryngopharyngectomy and neck dissection followed by conventional fractionated postoperative radiotherapy on surgical bed and cervical nodal areas. Results: The five-year overall survival rate and cause-specific survival rate were 42.2 percent and 51.6 percent, respectively. Univariate analysis of various clinical and pathologic factors confirmed the overall stage, TN-stage, secondary primary cancers, surgical positive margin, nodal extracapsular extension, total radiation doses as significant prognostic factors of hypopharyngeal carcinomas. But in multivariate analysis, TN-stage, surgical positive margin and extracapsular extesion were only statistically significant. Conclusion: In resectable cases of hypopharyngeal carcinoma, combined surgery and postoperative radio-therapy obtained good treatement results, even though sacrificing the function of larynx and pharynx. But in advanced and unresectable cases, with respect to survivals and qualify of life issues, we were able to confirm some limitations of combined therapy. So we recommend that comparative studies of recent various chemo-radiotherapy methods and advanced radiotherapy techniques with these data should be needed.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.27-34
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• 1992

Cis-Platinum (DDP) was utilized as a radiosensitizer in a pilot study for stage III and IV squamous cell carcinoma between 1984-1987, and DDP 20 $mg/M^2$/day was administered for 4 days at 3 week interval with concurrent radiotherapy. This study consisted of three phases: cytoreduction phase, eradicative treatment phase and adjuvant phase. Total 59 patients were subjected to evaluate a tumor response and its toxicity. During the eradicative phase,27 patients underwent surgery (group I ), 29 patients were treated with radiotherapy only (group II) and 3 patients did not complete the second phase of therapy. At the cytoreduction phase, $95\%$ response rate with complete response (CR) $47.5\%$ and partial response (PR) $47.5\%$ was observed. Complete tumor clearance (CTC) rate following 2nd phase of therapy was $84\%$ (47/56) with 26/27($96\%$) in group I achieved CTC with surgery and 21/29 ($72\%$) patients In group II achieved CTC following 2nd phase. $67\%$ of primary lesions and $70\%$ of nodal diseases in group I showed no tumor in the surgical specimen. $34\%$ of patiets who achieved CTC at 2nd phase developed recurrence and median time to recur was 8 months. Actuarial disease free survival at 4 years was $59\%$ and $51\%$(24/27) of patients who achieved CTC at 2nd phase were alive without any evidence of disease at median follow-up 31 months (range, 10-48 months). There was no significant difference in overall and disease free survival between group I and II between CR and PR group following 1st Phase. Only significant Prognostic factor in this study was the complete tumor clearance following 2nd phase theapy. In general, toxicity was not excessive. Author concludes that this study confirmed the significant radiosensitizing effect of DDP with the acceptable toxicity and warrant the prospective study to determine optimum scheduling for DDP and radiotherapy which maximizes the therapeutic gain.