• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.70-78
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• 2007

[ $\underline{Purpose}$ ]: This study analyzed the tumor response, overall survival, progression free survival and related prognostic factors in patients with muscle invasive bladder cancer subjected to bladder preserving treatment. $\underline{Materials\;and\;Methods}$: Between August 1995 and June 2004, 37 patients with muscle invasive (transitional cell carcinoma, clinically stage T2-4) bladder cancer were enrolled for the treatment protocol of bladder preservation. There were 33 males and 4 females, and the median age was 67 years (range $38{\sim}86\;years$). Transurethral resection of the bladder (TURB) was performed in 17 patients who underwent complete resection. The median radiation dose administered was 64.8 Gy (range $55.8{\sim}67\;Gy$). The survival rate was calculated by the Kaplan-Meier method. $\underline{Results}$: An evaluation of the response rate was determined by abdomen-pelvic CT and cystoscopy at three months after radiotherapy. A complete response was seen in 17 patients (46%). The survival rate at three years was 54.7%, with 54 months of median survival (range $3{\sim}91$ months). During the study, 17 patients died and 13 patients had died from bladder cancer. The progression free survival rate at three years was 37.2%. There were 24 patients (64.9%) who had disease recurrence: 16 patients (43.2%) had local recurrence, 6 patients (16.2%) had a distant recurrence, and 2 patients (5.4%) had both a local and distant recurrence. The survival rate (p=0.0009) and progression free survival rates (p=0.001) were statistically significant when compared to the response rate after radiotherapy. $\underline{Conclusion}$: The availability of complete TURB and appropriate chemoradiotherapy were important predictors for bladder preservation and survival.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.1-8
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• 1999

Purpose : Experimental studies have implicated the wild type p53 In cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancels. Methods : Immunohistochemical analysis with a mouse monoclonal antibody (DO-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at 51. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multi-variate analysis was peformed that included all clinical variables and status of p53 expression. Results : Thirty-seven (67.2$\%$) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 70$\%$ of laryngeal, 66.7$\%$ of oropharyngeal, 66.7$\%$ of hypopharyngeal cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease (P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. Conclusions : The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.200-206
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• 2009

Purpose: The incidence of upper gastric cancer and especially the diffuse type have increased in western countries. The aim this study was to investigate the chronologic changes of the clinicopathological features and survival rates of Korean upper gastric cancer patients. Materials and Methods: 1,638 gastric cancer patients who underwent gastrectomy were included in this study and they were divided into two groups; the 1990's (1991~1999, n=987) and the early 2000's (2000~2003, n=651). We evaluated the differences of the clinicopathologic features and the factors that affected the survival rates by univariative and multivariative analysis. Results: The older age (>60) patients increased from 42.7% to 50.7% respectively. Being overweight (body mass index$\geq$23) also increased from 31.5% to 43.2%. For the pathology, the incidence of stage Ia gastric cancer increased (29.8% to 44.5%) and the incidence of stage IV gastric cancer decreased (23.5% to 11.8%). Yet there was no difference according to the WHO classification, Lauren's classification and the location of tumor between the groups. The 5 year survival rates increased 67.7% to 83.7%, according to the group. Multivariative analysis showed that the odd ratios of the early 2000s was 0.715 (95% CI; 0.555~0.921) as compared to that of the 1990s. Conclusion: There were no changes of the clinicopathologic features, like the pattern in western countries, although the incidence early gastric cancer, old age patients and overweight patients increased. The survival rate of early 2000s was better that that of the 1990s.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.469-475
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• 1998

Purpose : To determine the role of Pelvic irradiation in stage I or IIA cervical carcinoma with pelvic nodal metastasis after hysterectomy and bilateral pelvic lymphadenectomy. Materials and Methods : This is a retrospective study of 68 cervical carcinoma patients who were found to have pelvic nodal metastasis at hysterectomy and received pelvic irradiation from 1983 to 1996 at Inje University Seoul Paik Hospital. External beam radiation therapy to pelvis was delivered using 4 MeV Linac and intracavitary irradiation was given via vaginal ovoids or cylinders. Five-year survival and disease-free survival were estimated by Kaplan-Meier Method and prognostic factors related to survival were analysed by log-rank test and Cox proportional hazards regression model. Results : Median length of follow-up was 52months. Five-year overall survival and disease-free survival (DFS) were 81.8$\%$ and 81.7$\%$ respectively. Patients with endometrial invasion had a 57.1$\%$ 5-year DFS compared to 87.5$\%$ for those without endometrial invasion (p=0.0074). Multivariate analysis revealed endometrial invasion as an only statistically significant prognostic factor for 5-year DFS. Among total 15 (22$\%$) recurrences. pelvic recurrences occurred in 4 cases and distant metastases occurred in 13 cases. Conclusion : We have been able to confirm previous results demonstrating marked decrease in local recurrence after pelvic irradiation. In view of the high proportion of distant metastasis found in this study, a trial of aggressive adjuvant systemic therapy and irradiation in early stage cervical carcinoma patients with pelvic nodal metastasis, especially with endometrial invasion, appears to be warranted.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.9
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• pp.1249-1256
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• 2016

Black ginseng (BG) obtained by a 9-fold steaming process of Panax ginseng has been reported to have anti-oxidative, anti-obesity, and anti-diabetes effects. The current study evaluated the protective effect of BG by steaming time in an HCl/ethanol-induced acute gastritis model. BG was divided into four samples according to steaming-drying processing (Gin1, Gin3, Gin6, and BG). High performance liquid chromatography analysis, free radical scavenging activity, and total phenol and flavonoid contents were examined in ginseng and four BG samples. Compared with ginseng, BG showed a stronger radical scavenging effect and higher contents of total phenol and flavonoids. To evaluate the anti-gastritic effect of BG, mice were distributed into five groups: normal mice (N), acute gastritic mice with distilled water (CON), acute gastritic mice with 100 mg/kg of ginseng (Gin0), acute gastritic mice with 100 mg/kg of BG (BG), and acute gastritic mice with 10 mg/kg of sucralfate (SC). After 1 hour of pre-treatment with water, extracts (Gin0 and BG), or drug (SC), experimental groups except for N were orally administered 0.5 mL of 150 mM HCl/60% ethanol (v/v) mixture. Blood was collected 1 hour later from the heart, and gastric tissue was harvested. Reactive oxygen species (ROS) levels were measured in serum, and related protein expression was examined by Western blot assay. In HCl/ethanol-induced acute gastritic mice, treatment with ginseng or BG improved mucosal damage in the histological evaluation. The serum ROS level significantly decreased in the BG-treated group compared with the CON group. Furthermore, expression of inflammatory cytokines significantly decreased in the BG-treated group compared with the CON group. Based on these results, antioxidant and anti-gastritic activities of ginseng were enhanced by streaming-drying processing, in part due to an increase in biological active compounds.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.101-109
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• 2017

This study investigated the effect of the dichloromethane fraction form Katsuwonus pelamis heart on anti-inflammatory responses in lipopolysaccharide-stimulated RAW 264.7 cells and mouse models. Ethanol extract was partitioned with dichloromethane, ethyl acetate, butanol, and water. Among the fractions, the dichloromethane fraction showed a significant decrease in nitric oxide (NO) and pro-inflammatory cytokines [interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$] production compared to ethanol extract. The dichloromethane fraction attenuated the expression of inducible nitric oxide synthase and nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65 proteins in a dose-dependent manner. In addition, the expression of phosphorylation of mitogen-activated protein kinases (MAPKs) was also inhibited by the dichloromethane fraction. Moreover, the administration of 10, 50, and 250 mg/kg body weight-dose dependently inhibited the formation of edema by croton-oil and the application of dichloromethane (2 mg/ear) significantly reduced epidermal and dermal thickness and the infiltrated mast cell numbers. Therefore, the dichloromethane fraction exhibited an anti-inflammation effect by inhibiting $NF-{\kappa}B$ and MAPK signaling activation in macrophages.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.237-246
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• 2004

Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.193-198
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• 2002

Purpose : Oligodendrogliomas (ODG) are a rare, slow growing, tumor in the brain, which can be cured by complete surgical resection, but as yet it is not known if postoperative adjuvant radiation therapy (RT) is essential, We analyzed the treatment results of patients with irradiated ODG to investigate the efficacy of RT in terms of survival rates and other influencing prognostic factors. Methods and Materials : Between March 1983 and December 1997, 42 patients with ODG were treated with RT at our hospital. The RT was peformed dally at a dose of $1.8\~2.0\;Gy$, at 5 fractions per week, to a total dose of between 39.6 Gy and 64.8 Gy (mean 53.3 Gy). The ages of the patients ranged between 5 and 62 years, with a median age of 39 years. The mean follow-up period was 63.4 months (8-152 months). The Kaplan-Meier method was used to assess the survival, and 5 year survival rates (5-YSR). Log rank tests and Cox regression analyses were used to define the significance of prognostic factors. Results : The majority of ODG in this study were located in the cerebral hemisphere $(83.3\%)$. ODG are slightly more common in men than women, and commonly occurs in middle age, between the 3rd and 4th decades. It has been recommended that RT is commenced within 4 weeks following surgery (5-YSR; $86\%\;vs.\;49\%;\;p<0.03$). Histologically well differentiated, as opposed to poorly differentiated, tumors were found to have a more favorable prognosis (p<0.02). The actuarial 5-YSR was $65.3\%$ (median survival 90 months). 5-YSR for the various extents of surgical excision, followed by external RT, was superior to that of biopsy only followed by external RT $(69.9\%\;vs.\;25.6\%,\;p<0.01)$. Tumor size and location, overall elapsed irradiation days, age, sex, whole brain irradiation as a course of treatment and chemotherapy, had no influence on the 5-YSR (p>0.05). Conclusion : A local involved field irradiation with conventional fractionation, commencing within 4 weeks following surgical excision of the tumor, was beneficial for the 5-YSR, but a total radiation dose exceeding 60 Gy did not improve the 5-YSR.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.335-344
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• 2001

Purpose : The aim of this study was to clarify the role of VEGF expression as an independent prognostic factor and to identify the patients at high risk for poor prognosis in stage IB cervical cancer. Materials and methods : A total of 118 patients with stage IB cervical cancer who had radical hysterectomy and pelvic lymph node dissection were included in the study. All known high risk factors of the patients were pathologically confirmed from the surgical specimen. Of the 118 patients, n patients were treated with postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded specimens of post-hysterectomy surgical materials. A semiquantitative analysis was made using a scoring system of 0, +, ++, and +++ for increasing intensity of stain. We classified the patients with scores from 0 to ++ as low VEGF expression and the patients with a score of +++ as high VEGF expression. Results : Of the 118 patients, 35 patients $(29.7\%)$ showed high VEGF expression. Strong correlations were found between the high VEGF expression and both deep stromal invasion (p=0.01) and the positive pelvic node (p=0.03). The 5-year overall and disease-free survival rates for all 118 patients were $95.5\%\;and\;93.8\%$. The 5-year overall (p=0.03) and disease-free survival (p<0.001) rates were $98.5\%\;and\;100%$ for low VEGF expression (0, +, and ++) and $85.5\%\;and\;79.7\%$ for high VEGF expression, respectively. Pelvic and distant failures for low versus high VEGF expression were $1.2\%$ versus $17.1\%$, (p=0.001) and $0\%$ versus $14.3\%$ (p<0.001), respectively. In a Cox multivariate analysis of survival, the high VEGF expression (p=0.02) and the bulky mass (p=0.02) were significant prognostic factors for overall survival. The high VEGF expression (p=0.002), and bulky mass (p=0.01) demonstrated as significant prognostic indicators for disease free survival. Conclusion : These results showed that VEGF expression was a highly significant predictor for pelvic and distant failure and the most significant prognostic factor of overall and disease free survival for the patients with stage IB cervix cancer treated with radical surgery. We strongly suggest that the immune-histochemistry for VEGF expression be performed in a routine clinical setting in order to identify the patients at high risk for poor prognosis in early stage cervical cancer. Furthermore, postoperative and/or chemotherapy did not reduce the pelvic failure and distant metastasis. To improve the cure rate for the patients with high VEGF expression in stage IB cervical cancer, antiangiogenic therapy including anti-VEGF Ab may be new treatment option.