• Title/Summary/Keyword: COX-1, COX-2

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Anti-inflammatory Activity of Antimicrobial Peptide Protaetiamycine 2 Derived from the Protaetia brevitarsis seulensis (흰점박이꽃무지 유래 항균 펩타이드 프로테티아마이신 2의 항염증활성)

  • Lee, Joon Ha;Baek, Minhee;Lee, Hwa Jeong;Kim, In-Woo;Kim, Sun Young;Seo, Minchul;Kim, Mi-Ae;Kim, Seong Hyun;Hwang, Jae Sam
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1218-1226
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    • 2019
  • The white-spotted flower chafer Protaetia brevitarsis seulensis is a medicinally beneficial and important edible insect species. We previously performed an in silico analysis of the Protaetia brevitarsis seulensis transcriptome to identify putative antimicrobial peptides and then tested their antimicrobial and hemolytic activities. These peptides had potent antimicrobial activities against bacteria and yeast without inducing hemolysis. In the present study, the cationic antimicrobial peptide, protaetiamycine 2, was selected for further assessment of its anti-inflammatory properties in mouse macrophage Raw264.7 cells. Protaetiamycine 2 treatment of Raw264.7 cells suppressed LPS-induced nitric oxide production and reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2, as determined by real-time PCR and western blotting. The expression of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) was also attenuated through the MAPKs and $NF-{\kappa}B$ signaling. We also confirmed that protaetiamycine 2 bound to bacterial cell membranes by a specific interaction with LPS. Collectively, these data obtained from LPS-induced Raw264.7 cells indicated that protaetiamycine 2 could have both antimicrobial and anti-inflammatory properties.

Evaluation of p53 and Bax Expression as Prognostic Markers in Invasive Cervical Carcinoma Stage IIB Patients Treated with Radiation Therapy (근치적 방사선치료를 시행한 제2기의 자궁경부암 환자에서 p53과 Bax의 발현과 임상적 의의)

  • Choi Sukjin;Kim Hunjung;Song Eunseop;Kim Changyoung;Lee Meejo;Kim Woochul;Loh John J. K.
    • Radiation Oncology Journal
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    • v.23 no.2
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    • pp.98-105
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    • 2005
  • Purpose : The objective of our study was to evaluate the immunohistochemical expression of p53 and bax proteins as prognostic markers in FIGO stage IIb invasive squamous cell carcinoma of the uterine cervix. Materials and Methods : Sixty-five cases of squamous cell carcinoma of the cervix (stage IIb) that were diagnosed from October 1995 to December 2003 were analyzed retrospectively for the bax and p53 expression. These expressions were determined immunohistochemically and they were correlated to the patients' overall survival and disease-free survival. Results : The overall 5-year survival (OS) rate and the disease-free survival (DFS) rate were $65.1\%$ and $62.9\%$, respectively. p53 and bax immunoreactivity was seen in $26.2\%$ and $52.3\%$ of cases, respectively, with variable levels of expression. On the univariate analysis, only p53 positivity correlated with poor survival in DFS (log-rank test p=0.027), but this significance was not maintained on multivariated analysis by Cox's regression. The nine cases with the immunophenotype ps3+/bax- had the poorest survival. Conclusion : Neither p53 nor bax expression are Independent predictors of the prognosis for stage IIb cervical squamous cancers. Evaluation of p53 and bax co-expression may affect the clinical outcome and further investigation is needed.

Expression of Hypoxia-inducible Factor-$1{\alpha}$ in Non-small Cell Lung Cancer: Relationship to Prognosis and Tumor Biomarkers (비소세포 폐암에서 HIF-$1{\alpha}$의 발현: 예후 및 종양표지자와의 관련성)

  • Cho, Sung-Rae;Byun, Joung-Hun;Kim, Jong-In;Lee, Bong-Geun;Chun, Bong-Kwon
    • Journal of Chest Surgery
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    • v.39 no.11 s.268
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    • pp.828-837
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    • 2006
  • Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

The Role of External Irradiation for the Locally Advanced Papillary Thyroid Cancers (국소적으로 진행된 갑상선 유두암에서의 방사선치료의 역할)

  • Kim Tae-Hyun;Yang Dae-Sik;Kim Chul-Yong;Choi Myung-Sun
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.187-194
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    • 1999
  • Purpose : The aim of this study is to look for the possible efficacy of external irradiation for locally advanced papillary thyroid cancers (stage pT4 or Nl ). Methods and Materials : From August 1981 through September 1997, 91 Patients with locally advanced papillary thyroid cancers (stage pT4 or Nl ) have been treated with external irradiation and followed up at our clinic. All of the patients have been treated with surgical resection. After surgery, 23 patients received postoperative external irradiation with or without ablative radioiodine therapy, whereas the other 68 patients were treated with ablative radioiodine therapy alone. Distributions of sex, age, and stage were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence by age, sex, stage, ablative radioiodine therapy and external irradiation on local control were peformed by using Cox's proportional hazard model. Results : Overall survival rates at 7 years were of no significant difference in both groups. There were $98.1\%$ for no RT group and $90\%$ for RT group (p=0.506). 5-year local control rates were significantly different, these were $95.2\%$ for RT group and $67.5\%$ for no RT group (p=0.0408). An analysis of the prognostic factors, age, sex, stage, and RAI were not significant variables, except for the external irradiation. Conclusion : Adjuvant postoperative external irradiation did not affect overall survival, but significantly improved local control in the patients with locally advanced papillary thyroid cancers (stage pT4 or lympy node involvement).

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Protective effects of Gastrodia rhizoma and steamed & fermented Gastrodiae rhizoma with anti-oxidant efficacy and suppression of NFκB signaling pathway on LPS-induced liver injury (LPS로 유발한 간손상 마우스에서 항산화 및 항염증 효능을 통한 천마와 증숙 발효 천마의 간보호 효과)

  • Kim, Hyoung-Jin;Kwon, O Jun;Lee, Ah Reum;Roh, Seong-Soo;Seo, Young-Bae
    • Journal of Applied Biological Chemistry
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    • v.59 no.3
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    • pp.179-188
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    • 2016
  • This study is aimed to evaluate the protective effect of Gastrodiae rhizoma and steamed, dried & fermented Gastrodiae rhizoma on Lipopolysaccharide (LPS)-induced hepatic injury in the mice model. Sample was selected to GR0F0 (not processed gastrodia rhizome) and GR6F4 (fermented with Saccharomyces cerevisiae before steamed and dried 6 times) based on 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid, and High-performance liquid chromatography analysis. Mice were randomly divided into 4 groups - Normal group, vehicle group (LPS treated), GR0F0 group (fed GR0F0 before LPS treated) and GR6F4 group (fed GR6F4 before LPS treated) with 6 mice in each group. GR0F0 group and GR6F4 group were fed each extract 200 mg/kg/day during 8 days. LPS 20 mg/kg injected to the experimental groups as abdominal injection. We measured aspartate aminotransferase, alanine amino-transferase in serum. GR0F0 and GR6F4 showed a significant decrease compared to the vehicle group. As a result of measuring the ROS, GR6F4 group showed a significant reduction in both the serum and liver tissues compared to the vehicle group. GR0F0 group showed a significant reduction only in the liver tissues. Activator protein-1, cyclooxygenase-2, and Inducible nitric oxide synthase were significantly decreased GR0F0 group and GR6F4 group. But tumor necrosis factor alpha only showed a significant reduction in GR6F4 group. GR0F0 and GR6F4 groups against liver damage in mice with LPS. That showed significant effects on anti-oxidant and anti-inflammatory action. The effects of GR6F4 group showed superior results compared to GR0F0 group. Therefore, Steamed, dried & fermented Gastrodia rhizoma was might have a protective effect on liver injury.

Favorable Outcome in Elderly Asian Patients with Metastatic Renal Cell Carcinoma Treated with Everolimus: The Osaka Urologic Oncology Group

  • Inamoto, Teruo;Azuma, Haruhito;Nonomura, Norio;Nakatani, Tatsuya;Matsuda, Tadashi;Nozawa, Masahiro;Ueda, Takeshi;Kinoshita, Hidefumi;Nishimura, Kazuo;Kanayama, Hiro-Omi;Miki, Tsuneharu;Tomita, Yoshihiko;Yoshioka, Toshiaki;Tsujihata, Masao;Uemura, Hirotsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1811-1815
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    • 2014
  • Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.

Radiotherapy Results of Uterine Cervix Cancer Stape IIB : Overall Survival, Prognostic factors, Patterns of Failure and Late Complications (자궁경부암 병기 IIB에서의 방사선 치료 성적: 생존율 및 예후인자, 치료 후 실패양상, 만성 합병증)

  • Kim Eun-Seog;Choi Doo-Ho;Huh Seung-Jae
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.51-61
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    • 1998
  • Purpose : Treatment of choice for uterine cervix cancer stage IIB is radiotherapy. We analyzed survivals, Prognostic factors, patterns of failure and complications. Materials and Methods : This is a retrospective analysis of 167 patients with stage IIB carcinoma of uterine cervix treated with curative external pelvic and high dose rate intracavitary radiotherapy at the Department of Therapeutic Radiology, Soonchunhyang University Hospital from August 1985 to August 1994. All the patients followed up from 3 to 141 months(mean 60 months) and age of patients ranged from 31 to 78 years at presentation(mean : 55 years). Results : Overall complete response rate was $84\%$. The response rate for squamous cell carcimoma and adenocarcinoma were $86\%$ and $60\%$, respectively. Overall 5-years survival rate and disease free survival rate was 62 and $59\%$, respectively Mass size and treatment response were significant Prognostic factors for survival Pathologic type and parametrial involvement were marginally significants Prognostic factors. Local failure was 43 cases, distant metastasis was 14 cases and local failure plus distant metastasis was 3 cases, and most of local failures occurred within 24 months, distant metastasis within 12 months after treatment Twenty eight($16.8\%$) patients developed late rectal and urinary complications There were tendency to increasing severity and frequency according to increased fractional dose and total(rectal and bladder) dose. Conclusions : Survival rate was significantly related to tumor size and radiotherapy response. Tumor size should be considered in the clinical s1aging. To increased survival and local control, clinical trials such as decreasing duration of radiotherapy or addition of chemotherapy is needed. To detect early recurrence, regular follow up after RT is important. Because total rectal and bladder dose affected late complications. meticulous vaginal packing is needed to optimize dose of normal tissues and to decrease late complications.

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The Surgical Treatment of Atrial Fibrillation in Patients Undergoing Simultaneous Open Heart Surgery (심장세동의 수술요법)

  • Kim, Gi-Bong;Lee, Chang-Ha;Son, Dae-Won
    • Journal of Chest Surgery
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    • v.30 no.3
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    • pp.287-292
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    • 1997
  • .Itrial fibrillation is one of the most common cardiac arrhythmias requiring treatment. About 60% of patients with mitral valvular disease have atrial fibrillation and one third of patients with atrial fibrillation may have the past history of thromboembolic events. Between April 1994 and June 1995, 20 patients with organic heart diseases combined with atrial fibrillation underwent open heart surgery including Cox-maze 111 procedure. There were 6 men and 14 women with an average age of 48 years (range, 31 to 66 years). Nineteen patients had valvular heart diseases and 1 ventricular septal defEct (VSD). Mean duration of atrial fibrillation was 36 months (:42 months) (range, 1 to 132 months). T e past medical history of thromboembolic events was positive in 7 patients (35%) and left atrial thrombus was detected in 9 patients (45%). The concomitant procedures were mitral valve replacement (MVR) and aortic valve replacement (AVR) in 5 patients, MVR in 4, MVd and tricuspid annuloplasty(TAP) in 4, mitral valvuloplasty(Mln) in 3, Mln and Tln in 1, MIW and coronary artery bypass surgery in 1, AVR in 1, and patch closure of VSD in 1. Mean aortic cross-clamping time was 175 minutes (range, 116 to 270 minutes). Atrial fibrillation recurred in 16 patients (80%) during the early postoperative period, but, recurrent atrial fibrillation was converted to regular rhythm at postoperative forty-first day in average. There was no early or late death in this series of 20 patients and postoperative complications were inappropriate tachycardia in 5 patients (25%), low cardiac output syndrome in 3 (15%), aggravated hemiplegic in 1, and acute renal failure in 1. Mean follow-up interval of patient was 16.5 months (range, 10.5 to 24 months) and all patients are currently in regular rhythm. Seventeen patients (85%) are in sinus rhythm and 3 (15%) in junctional rhythm. Right atrial contraction was detected in 95% of patients and left atrial contraction in 63% on postoperative transthoracic echocardiogram. The surgical treatment of atrial fibrillation concomitant with open heart surgery is warranted in the recent clinical setting of improved myocardial protection technique, considering the untoward side-effects of atrial fibrillation.

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Protective effect of matcha green tea (Camellia sinensis) extract on high glucose- and oleic acid-induced hepatic inflammatory effect (고당 및 올레산으로 유도된 간세포에서의 염증반응에 대한 말차(Camellia sinensis) 추출물의 보호효과)

  • Kim, Jong Min;Lee, Uk;Kang, Jin Yong;Park, Seon Kyeong;Shin, Eun Jin;Moon, Jong Hyun;Kim, Min Ji;Lee, Hyo Lim;Kim, Gil Han;Jeong, Hye Rin;Park, Hyo Won;Kim, Jong Cheol;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.53 no.3
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    • pp.267-277
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    • 2021
  • To evaluate hepatoprotective effects, the antioxidant capacities of matcha green tea extract (Camellia sinenesis) were compared to those of green leaf tea and the anti-inflammatory activities in HepG2 cells were investigated. Evaluation of the total phenolic and total flavonoid content, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, and inhibitory effect on lipid peroxidation indicated that the aqueous extract of matcha green tea presented significant catechin content and antioxidant capacity compared to those of green leaf tea. In addition, the extract had considerable inhibitory effects on α-glucosidase, α-amylase, and advanced glycation end-products. The matcha green tea extract significantly increased cell viability and reduced reactive oxygen species in H2O2- and high-glucose-treated HepG2 cells. Furthermore, in response to oleic acid-induced HepG2 cell injury, treatment with matcha green tea aqueous extract inhibited lipid accumulation and regulated the expression of inflammatory proteins such as p-JNK, p-Akt, p-GSK-3β, caspase-3, COX-2, iNOS, and TNF-α. Matcha green tea could be used as a functional material to ameliorate hepatic lipid accumulation and inflammation.

Analysis of Prognostic Factors in Glioblastoma Multiforme (다형성 교모세포증 환자의 예후인자 분석)

  • Chang Sei Kyung;Suh Chang Ok;Lee Sang Wook;Keum Ki Chang;Kim Gwi Eon;Kim Woo Cheol
    • Radiation Oncology Journal
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    • v.14 no.3
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    • pp.181-189
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    • 1996
  • Purpose : To find the more effective treatment methods that improving the survival of patients with glioblastoma multiforme(GBM), we analyze the prognostic factors and the outcome of therapy in patients with GBM. Materials and Methods : One hundred twently-one patients with a diagnosis of GBM treated at Severance Hospital between 1973 and 1993 were analyzed for survival with respect to patients characteristics, that is, duration of symptom, age, and Karnofsky performance status, as well as treatment related variables such as extent of surgery and radiotherapy. Results : The median survival time(MST) and 2-year overall survival rate (OSR) of the patients with GBM were 13 months and $20.8\%$, respectively. Duration of symptom, age, Karnofsky performance status(KPS), radiotherapy, and extent of surgical resection were associated with improved survial in a univariate analysis. Patients whose duration of symptom was longer than 3 months, had the 2-year OSR of $47.2\%$(p=0.0082), who were younger than age 50, $32.9\%$(p=0.0003) In patients with a KPS of 80 or higher, the 2-rear OSR was $36.9\%$(p=0.0422). Patients undergoing radiotherapy had the 2-year OSR of $22.9\%$(p=0.0030), and surgical resection of $23.3\%$ (p<0.000). A Cox regression model confirmed a significant correlation of duration of symptom, age, radiotherapy, and extent of surgical resection with survival, excluding KPS(P=0.8823). The 2-year OSR were $22.3\%$ and $19.4\%$, combined with chemotherapy or without, respectively(p=0.6028). The duration of symptom of 3 months or shorter, 50 years of age or older, and undergoing stereotactic biopsy only were considered as risk factors, then patients without any risk factors had the MST of 29 months and 2-year OSR of $53.9\%$ compared to 4 months and $0\%$ for Patients who had all 3 risk factors. Most of all treatment failures occurred in the primary tumor site($80.4\%$). Conclusion : The duration of symptom, age, radiotherapy, and extent of surgical resection were a prognostically significant indeuendent variables. To get a better survival, it seems to be reasonable that the study design which improves the local control rates is warranted.

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