• Radiation Oncology Journal
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• v.10 no.2
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• pp.193-204
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• 1992

During the period between March 1983 and December 1990, 74 patients with esophageal carcinoma (EG) were treated with radiation therapy (RT) at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Of these, 6 patients were lost to follow-up, and 13 patients were interrupted. So the remaining 55 patients were analyzed, retrospectively. 32 patients were irradiated with curative aim, 12 patients with palliative intent, 10 patients postoperatively, and 1 patient pre- and post-operatively. Among these 55 patients, 28 patients were treated with chemoradiation modality, and 27 patients with RT alone. All patients were followed for a minimum of 20 months or until death. Of 32 patients irradiated by curative aim, 22 patients (69%) showed partial remission (PR), 6 patients (19%) complete remission (CR). Overall mean survival and two-year survival rate were 15.6 months and 22%. With respect to sex, age, pathologic differentiation, tumor location, tumor size, stage, RT aim, RT response, RT dose, use of chemotherapy and functional categories (FC) of dysphagia at initiation of RT and at finishing RT: Tumor size, stage, RT response had great influences on prognosis and FC at finishing RT had a slight influence on prognosis. Especially, the mean survival and 2-year survival rate in patients with postoperative RT were 24.7 months and 63%, which could be compared with 29.1 months and 43% in radically treated patients with CR. And the mean survival duration and 2-year survival rate in patients irradiated with doses more than 60 Gy were 22.4 months and 29%, and 50~60 Gy were 12.2 months and 12%, respectively. However, no significant difference was shown statistically. Among 12 patients treated with palliative intent, 9 patients (75%) had good improvement in dysphagia and the mean duration of palliative response was 10.6 months.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.130-138
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• 2002

Purpose : This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Materials and Methods : Twenty eight patients with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were peformed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uninformed in 3. Radiation therapy was peformed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was peformed on the prognostic factors affecting the survival rate. Results : The survival rate was $76\%,\;46\%,\;33\%,\;33\%$ at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, 1-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uniand multivariate analysis. Un univariate analysis, the T-stage (p=0.078) and radiation dose (p=0.051) were marginally significant, and the treatment response (p=0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. Conclusion : The treatment response and radiation dose are suggested as th은 statistically significant factors affecting the survival rate of muscle invasive bladder cancer. A Further prospective randomized study is needed to confirm these prognostic factors.

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.581-587
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• 2009

Purpose : To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). Methods : To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX ($12g/m^2$), cisplatin ($100mg/m^2$), and doxorubicin ($60mg/m^2$). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels ($mean{\pm}SE$) at 4 h (peak), 24 h, 48 h, and 72 h were $1292.14{\pm}12.83{\mu}m$, $9.29{\pm}3.89{\mu}m$, $1.73{\pm}1.37{\mu}m$, and $0.58{\pm}0.44{\mu}m$, respectively. The peak MTX serum level was $1292.14{\pm}12.83{\mu}m$. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level ($3.4{\mu}m$) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than $1,400{\mu}m$ (P=0.002) and mean 24-h MTX level of less than $3.4{\mu}m$ (P=0.011). Conclusion : The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.57-64
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• 2006

Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.205-210
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• 2001

Purpose : This study tried to evaluate the effectiveness of combined treatment using radiation therapy and concurrent cisplatin as a radiosensitizer in the management of locally advanced head and neck cancer. Materials and methods : From January 1995 to August 1998, 29 evaluable patients with locally advanced head & neck cancels (AJCC stage $II\~IV$) were received curative radiation therapy $(total\;70\~75.6\;Gy/35\~42\;fractions,\;1.8\~2\;Gy/fraction)$ and concurrent cisplatin chemotherapy ($100\;mg/m^2$, D1, D22, D43). The neck dissections were peformed for residual lymphadenopathy. Follow-up ranged from 5 to 55 months (median 24 months). Results : Twenty-one $(72.4\%)$ patients achieved clinical complete responses. The partial response and minimal response rates were $17.2\%\;and\;10.4\%$, respectively. Locoregional failure rate was $27.6\%$, and included 6 patients with local failures, 4 patients with regional failures, and 2 patients with combined local and regional failures. Four of 29 patients $(13.8\%)$ developed distant metastasis. The disease free survival rate at 3 years was $60\%$. Nasopharyngeal primary tumors or complete responders showed significantly higher disease free survival rate. The grade 3 mucositis and nausea/vomiting was noted in $34.5\%$, respectively. Major prolongation of radiation therapy duration was inevitable in three patients. Twenty-one patients $(72.4\%)$ completed 3 courses of cisplatin and 5 patients received 2 courses of cisplatin. Three patients received only one course of cisplatin due to nephrotoxicity and neurotoxicity, and then changed to 5-FU regimen. Conclusions : Concurrent cisplatin-radiation therapy in locally advanced head and neck cancer showed high response rate, reasonable locoregional control, and survival rate. As expected, acute toxicities were increased, but compliance to treatment was acceptable. Assessment of the effect of the combination in this setting requires further accrual and follow-up.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.108-115
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• 2002

Purpose : A retrospective study was undertaken to determine the role of conventional radiotherapy with or without surgery for treating a supraglottic carcinoma in terms of the local control and survival. Materials and Methods : From Jan. 1986 to Oct. 1996, a total of 134 patients were treated for a supraglottic carcinoma by radiotherapy with or without surgery. Of them, 117 patients who had completed the radiotherapy formed the base of this study. The patients were redistributed according to the revised AJCC staging system (1997). The number of patients of stage I, II, III, IVA, IVB were $6\;(5\%),\;16\;(14\%),\;53\;(45\%),\;32\;(27\%),\;10\;(9\%)$, respectively. Eighty patients were treated by radical radiotherapy in the range of $61.2\~79.2\;Gy$ (mean : 69.2 Gy) to the primary tumor and $45.0\~93.6\;Gy$ (mean : 54.0 Gy) to regional lymphatics. All patients with stage I and IVB were treated by radiotherapy alone. Thirty-seven patients underwent surgery plus postoperative radiotherapy in the range of $45.0\~68.4\;Gy$ (mean : 56.1 Gy) to the primary tumor bed and $45.0\~59.4\;Gy$ (mean : 47.2 Gy) to the regional lymphatics. Of them, 33 patients received a total laryngectomy (${\pm}lymph$ node dissection), three had a supraglottic horizontal laryngectomy (${\pm}lymph$ node dissection), and one had a primary excision alone. Results : The 5-year survival rate (5YSR) of all patients was $43\%$. The 5YSRs of the patients with stage I+II, III+IV were $49.9\%,\;41.2\%$, respectively (p=0.27). However, the disease-specific survival rate of the patients with stage I (n=6) was $100\%$. The 5YSRs of patients who underwent surgery plus radiotherapy (S+RT) vs radiotherapy alone (RT) in stage II, III, IVA were $100\%\;vs\;43\%$ (p=0.17), $62\%\;vs\;52\%$ (p=0.32), $58\%\;vs\;6\%$ (p<0.001), respectively. The 5-year actuarial locoregional control rate (5YLCR) of all the patients was $57\%$. The 5YLCR of the patients with stage I, II, III, IVA, IVB was $100\%,\;74\%,\;60\%,\;44\%,\;30\%$, respectively (p=0.008). The 5YLCR of the patients with S+RT vs RT in stage II, III, IVA was $100\%\;vs\;68\%$ (p=0.29), $67\%\;vs\;55\%$ (p=0.23), $81\%\;vs\;20\%$ (p<0.001), respectively. In the radiotherapy alone group, the 5YLCR of the patients with a complete, partial, and minimal response were $76\%,\;20\%,\;0\%$, respectively (p<0.001). In all patients, multivariate analysis showed that the N-stage, surgery or not, and age were significant factors affecting the survival rate and that the N-stage, surgery or not, and the ECOG performance index were significant factors affecting the locoregional control. In the radiotherapy alone group, multivariate analysis showed that the radiation response and N-stage were significant factors affecting the overall survival rate as well as locoregional control. Conclusion : In early stage supraglottic carcinoma, conventional radiotherapy alone is an equally effective modality compared to surgery plus radiotherapy and could preserve the laryngeal function. However, in the advanced stages, radiotherapy combined with concurrent chemotherapy for laryngeal preservation or surgery should be considered. In bulky neck disease, all the possible planned neck dissections after induction chemotherapy or before radiotherapy should be attempted.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• Journal of Life Science
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• v.23 no.9
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• pp.1118-1125
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• 2013

Naringenin, a naturally occurring citrus flavonone, is a potentially valuable candidate for cancer chemotherapy. However, the cellular and molecular mechanisms responsible for its anticancer activity are largely unknown. In the present study, we attempted to elucidate the mechanisms responsible for naringenin-induced apoptosis in human leukemic U937 cells. We found that naringenin markedly inhibited the growth of U937 cells by decreasing cell proliferation and inducing apoptosis, which was associated with the activation of caspases. A pan-caspase inhibitor, z-VAD-fmk, significantly inhibited naringenin-induced U937 cell apoptosis, indicating that caspases are key regulators of apoptosis in response to naringenin in U937 cells. Although the levels of antiapoptotic Bcl-2 and proapoptotic Bax proteins remained unchanged in naringenin-treated U937 cells, Bcl-2 overexpression attenuated naringenin-induced apoptosis. Furthermore, combined treatment with naringenin and HA14-1, a small-molecule Bcl-2 inhibitor, effectively increased the apoptosis through enhancement of XIAP down-regulation, Bid cleavage, and caspase activation, suggesting that the synergistic effect was at least partially mediated through the death receptor-mediated apoptosis pathway.

• Korean Journal of Head & Neck Oncology
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• v.16 no.1
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• pp.33-36
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• 2000

Objectives: Angiocentric T-cell lymphoma of the head and neck is an angiocentric and angiodestructive lymphoreticular proliferative disorder. It has been treated with various treatment modalities, but its prognosis is poor and the treatment modality is controversial. We performed this study to suggest a treatment modality with improved results. Materials and Methods: We studied 40 cases of pathologically confirmed angiocentric T-cell lymphoma from July 1984 to December 1996, 35 cases of which showed complete response after initial treatment. All the patients were divided into two groups according to treatment modality. 15 cases received radiotherapy alone (Group I) and 20 cases received radiotherapy after five cycles of CHOP-Bleo chemotherapy(Group II). We analyzed the subsites of tumor, stage, treatment modality and treatment outcome and causes of failure for each group, and compared the three-year no evidence of disease(NED) between the two groups. Results: The three-year NED of a combined chemoradiotherapy was higher than that of a radiotherapy alone (p=0.0478). The three-year NED according to groups and stage were as follows: Group I=6/15(40.0%), stage IE=5/10(50.0%), stage IIE=1/5(20%), Group II=13/20(65.0%), stage IE=9/13(69.2%), stage IIE=4/7(57.1%). Radiotherapy alone is not well effective for the nasal cavity lymphoma extended to paranasal sinus and the palate. Conclusion: We are unable to provide clear guidelines for treatment, but recommend the initial treatment with oral alkylating agents and steroids followed by radiotherapy for Ann Arbor stage II tumors and stage I of the palate lymphoma and the nasal cavity lymphoma extended to paranasal sinus.

• Journal of Life Science
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• v.24 no.11
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• pp.1244-1251
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• 2014

Platycodon grandiflorum (PG) has been known to possess many biological effects, including anti-inflammatory and anti-allergy activity and anti-obesity and hyperlipidemia effects. However, little research has been conducted regarding its anticancer effects, with the exception of its ability to stimulate apoptosis in skin cells. There has also been no study regarding PG-induced autophagy. The modulation of autophagy is recognized as one of the hallmarks of cancer cells. Depending on the type of cancer and the context, autophagy can suppress or help cancer cells to overcome metabolic stress and the cytotoxicity of chemotherapy. Therefore, the present study was designed to investigate whether or not extracts from PG-induced cell death were connected with autophagy and apoptosis in HCT-116 human colon cancer cells. PG stimulation decreased cell proliferation in a dose- and time-dependent manner and induced apoptosis, which was partially dependent on the activation of caspases. PG treatment also resulted in the formation of autophagic vacuoles simultaneously with regulation of autophagy-related genes. Interestingly, a PG-mediated apoptotic effect was further triggered by pretreatment with the autophagy inhibitors 3-methyladenin and bafilomycin A1. However, cell viability recovered quite well with bafilomycin A1 treatment. These findings show that PG treatment promotes both autophagy and apoptosis and that PG-induced autophagic response might play a role in the autophagic cell death of HCT-116 cells.