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Inhibitory Effect of Protaetiamycine 6 on Neuroinflammation in LPS-stimulated BV-2 Microglia (LPS에 의해 활성화된 미세아교세포에서 흰점박이꽃무지 유래 항균 펩타이드 Protaetiamycine 6의 신경염증 억제 효과)

  • Lee, Hwa Jeong;Seo, Minchul;Baek, Minhee;Shin, Yong Pyo;Lee, Joon Ha;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.30 no.12
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    • pp.1078-1084
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    • 2020
  • Protaetia brevitarsis seulensis is an insect belonging to the order Coleoptera. This insect is reported to contain large amounts of physiologically active substances useful for liver protective effect and improvements in blood circulation as well as a broad source of edible protein. Antimicrobial peptides (AMPs) are found in a variety of species, from microorganisms to mammals, and play an important role in the innate immune systems of living things. Microglia are the main source of proinflammatory cytokines and nitric oxide (NO) in the central nervous system. Activated microglia secrete large amounts of neuroinflammatory mediators (e.g., TNF-α, NO, and ROS), which are the main cause of neuronal cell death. In the present study, we investigated the inhibitory effect of Protaetiamycine 6 (PKARKLQKLSAYKTTLRN-NH2), an AMP derived from Protaetia brevitarsis seulensis, on LPS-induced neuroinflammation in BV-2 microglia. Protaetiamycine 6 significantly inhibited NO production without cytotoxicity and decreased the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, Protaetiamycine 6 also reduced the production of neuroinflammatory cytokines on activated BV-2 microglia. These results suggest that Protaetiamycine 6 could be a good source of functional substance to prevent neuroinflammation and neurodegenerative diseases.

Anti-inflammatory effect of Sinhyowoldo-san Extract with regard to Pro-inflammatory Mediators in PMA plus A23187-induced Human Mast Cells (인간 비만세포에서 PMA와 A23187에 의해 유도된 전염증 매개체에 대한 신효월도산 추출물의 항염증 효과)

  • Wi, Gyeong;Yang, Da-Wun;Kang, Ok-Hwa;Kim, Sung-Bae;Mun, Su-Hyun;Seo, Yun-Soo;Kang, Da-Hye;Lim, Jae-Soo;Kim, Ma-Ryong;Kwak, Nam-Won;Kong, Ryong;Kwon, Dong-Yeul
    • The Korea Journal of Herbology
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    • v.29 no.6
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    • pp.117-123
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    • 2014
  • Objectives : Sinhyowoldo-san (SHWDS) is said to be a traditional medicine used for shigellosis, abdominal pain, diarrhea. But mechanism of SHWDS mediated-modulation of immune function is not sufficiently understood. To ascertain the molecular mechanisms of SHWDS 70% EtOH extract on pharmacological and biochemical actions in inflammation, we researched the effect of pro-inflammatory mediators in phorbol-12-myristate-13-acetate (PMA)+ A23187-activated human mast cell line (HMC-1). Methods : In the present research, cell viability was measured by MTS assay. pro-inflammatory cytokine production was measured by performing enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR), and western blot analysis to analyze the activation of mitogen-activated protein kinases (MAPKs), nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). The investigation focused on whether SHWDS inhibited the expressions of interleukin-6 (IL-6), interleukin-8 (IL-8), MAPKs and $NF-{\kappa}B$ in PMA+A23187-activated HMC-1 cells. Results : SHWDS has no cytotoxicity at measured concentration (50, 100, and $250{\mu}g/ml$). SHWDS ($250{\mu}g/ml$) inhibits pro-inflammatory cytokine expression in PMA+ A23187-activated HMC-1 cells. Moreover, SHWDS inhibited cyclooxygenase (COX)-2 expression. In activated HMC-1 cells, SHWDS suppressed phosphorylation of extracellular signal-regulated kinase (ERK 1/2) and c-jun N-terminal Kinase (JNK 1/2). Then, SHWDS suppressed activation of nuclear factor $NF-{\kappa}B$ in nuclear, degradation of IkB ${\alpha}$ in cytoplasm. Conclusions : We propose that SHWDS has an anti-inflammatory therapeutic potential, which may result from inhibition of ERK 1/2, JNK 1/2 phosphorylation and $NF-{\kappa}B$ activation, thereby decreasing the expression of pro-inflammatory genes.

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.

Spontaneous Resolution Rate and Predictive Factors of Resolution in Children with Primary Vesicoureteral Reflux (소아에서 일차성 방광요관역류의 자연소실율 및 관련 인자)

  • Kang, Eun-Young;Kim, Min-Sun;Kwon, Keun-Sang;Park, Eun-Hye;Lee, Dae-Yeol
    • Childhood Kidney Diseases
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    • v.11 no.1
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    • pp.74-82
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    • 2007
  • Purpose : To analyze the clinical characteristics, spontaneous resolution rate and predictive factors of resolution in children with primary vesicoureteral reflux(VUR). Methods : Between October 1991 and July 2003, 149 children diagnosed with primary VUR at Chonbuk National University Hospital were reviewed retrospectively. All of the patients were maintained on low-dose antibiotic prophylaxis and underwent radionuclide cystograms at 1 year intervals over 3 years after the initial diagnosis of VUR by voiding cystourethrogram was made. Results : The median time to resolution of VUR was 24 months and the total 3 year-cumulative resolution rate of VUR was 61.7%. The following variables were associated with resolution of VUR according to univariate analysis-; age<1 year, male gender, mild grade of reflux, unilateral reflux, congenital hydronephrosis as clinical presentation at time of diagnosis of VUR, absence of focal defects in the renal scan at diagnosis, absence of recurrent UTI, renal scars and small kidney during follow-up. After adjustment by Cox regression model, five variables remained as independent predictors of VUR resolution; age<1 yew, relative risk 1.77(P<0.05), VUR grade I+II 2.98(P<0.05), absence of renal scars 2.23(P<0.05), and absence of small kidney 5.20(P<0.01) during follow-up. Conclusion : In this study, spontaneous resolution rate of VUR, even high grade reflux, is high in infants during medical management, and it was related to age, reflux grade at diagnosis, absence of renal scars and small kidney during follow-up. Therefore early surgical intervention should be avoided and reserved for the selected groups.

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Division of the N2 Stage According to the Multiplicity of the Involved Nodal Stations May be Necessary in the N2-NSCLC Patients Who are Treated with Postoperative Radiotherapy (비소세포성 폐암으로 수술 후 방사선치료가 시행된 N2병기 환자들에서 다발 부위 종격동 림프절 전이 여부에 따른 N2병기 구분의 임상적 의미)

  • Yoon, Hong-In;Kim, Yong-Bae;Lee, Chang-Geol;Lee, Ik-Jae;Kim, Song-Yih;Kim, Jun-Won;Kim, Joo-Hang;Cho, Byung-Chul;Lee, Jin-Gu;Chung, Kyung-Young
    • 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.

Anti-inflammatory Activity of Antimicrobial Peptide Papiliocin 3 Derived from the Swallowtail Butterfly, Papilio xuthus (호랑나비 유래 항균 펩타이드 파필리오신 3의 항염증 활성)

  • Shin, Yong Pyo;Lee, Joon Ha;Kim, In-Woo;Seo, Minchul;Kim, Mi-Ae;Lee, Hwa Jeong;Baek, Minhee;Kim, Seong Hyun;Hwang, Jae Sam
    • Journal of Life Science
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    • v.30 no.10
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    • pp.886-895
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    • 2020
  • The development of novel peptide antibiotics with potent antimicrobial activity and anti-inflammatory activity is urgently needed. In a previous work, we performed an in-silico analysis of the Papilio xuthus transcriptome to identify putative antimicrobial peptides and identified several candidates. In this study, we investigated the antibacterial and anti-inflammatory activities of papiliocin 3, which was selected bioinformatically based on its physicochemical properties against bacteria and mouse macrophage Raw264.7 cells. Papiliocin 3 showed antibacterial activities against E. coli and S. aureus without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that papiliocin 3 reduced the expression levels of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). In addition, we examined whether papiliocin 3 could inhibit the expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) in LPS-induced Raw264.7 cells. We found that papiliocin 3 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling. We also confirmed that papiliocin 3 binds to bacterial cell membranes via a specific interaction with lipopolysaccharides. Collectively, these findings suggest that papiliocin 3 could be a promising molecule for development as a novel peptide antibiotic.

An Application Effect of Rhythmic Movement Program for the Health Promotion in the Elderly (노인의 건강증진을 위한 율동적 운동프로그램의 적용효과)

  • 이숙자
    • Journal of Korean Academy of Nursing
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    • v.30 no.3
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    • pp.776-790
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    • 2000
  • Every year the number of the elderly increases in Korea thanks to the improvemen of social and economical levels and the development of medicine. However, many problems such as insufficent care and the isolation of the elderly have been commonplace. This trend exists not only because of increased lifespan but also the changing social structure of the nuclear family. Accordingly, inspite of the development of medicine, geriatric diseases including circulatory diseases are increasing in proportion of elderly population, as well as the severity. Therefore, it is important to emphasize that health care programs provide the best possible health care and functional capacities in terms of healthy elderly lifestyles. Especially, the phenomena of aging and geriatric diseases taking place with the elderly naturally are affected by lifestyle and the drastic changes in exercise patterns. This study aims to improve geriatric health by introducing a rhythmic movement program for the elderly to estabilish a health-promoting self-care system and by developing quality of life, perceived health status, their physical and physiological functions and emotional state. The theoretical framework used in this dissertation is derived from the Health-Promoting Self-Care System Model (Simmons, 1990), which integrates the Self-Care Deficit Nursing Theory (Orem, 1985), the interaction model of Client Health Behavior (Cox, 1982) and the Health Promotion Model (Pender, 1987). As a quasi-experimental design, the nonequivalent control group pretest-posttest design is utilized for this study. The subjects of this study consist of 64 people, over 65 years old who live in 2 nursing homes for the aged located in S city , Kyong-gi province and volunteered for this study from July, 12, 1999 to September, 17, 1999. They are divided into two groups:33 in the experimental group and 31 in the control group. The experimental group particpated in the Rhythmic Movement Program at the nursing home, which was comprised of 45 minutes a session, 5 sessions a week during 9 weeks. In order to measure the results of the Rhythmic Movement Program, aspects of perceived health status, balance, flexibility, grip strength, leg strength, heart rate, blood pressure, depression, anxiety and the quality of life were measured before and after participating in the Rhythimic Movement Program for the experimental group after 9 weeks, as well as the control group. The collected data were processed by SPSS PC+ and analyzed by the X2 test, t-test, ANCOVA and the Pearson Correlation Coefficient. The results of this study are as follows: 1. The perceived health status conditions in the experimental group show statistically significant improvement when compared to the control group (F=17.51, p=.000). 2. The physical and physiological functions, that is, balance (F=17.51, p=.000), flexibility (F=8.01, p=.006), grip strength (F=3.21, p=.018) and leg strength (F=25.78, p=.000) in the experimental group are higher than the control group. The vital signs, that is, the number of heart rate (F=.022, p=.884), systolic pressure (F=1.73 p=.193), and diastolic pressure (F=2.74, p=.103) in the experimental group compared to the control group decreased, but doesn't show statistically significant differences. Immune responses (F=5.13, p=.003) showed statistically significant increases in the experimental group when compared to the control group. 3. The emotional state are improved, that is, degree of depression (F=11.56, p=.001) and degree of anxiety (F=9.14, p=.004) in the experimental group showed statistically significant decreases. 4. The quality of life in the experimental group (F=3.03, p=.037) showed statistically significant differences compared to the control group. 5. The observations of the relationships among the perceived health status, emotional state , the quality of life, the relationships between the perceived health status, the degree of depression (r=-.653, p=.000) and the degree of anxiety (r=-.786, p=.000) were in contrary propotions, while the relationships between the perceived health status and the quality of life (r=.234, p=.008) were in direct propotion. In conclusion, the Rhythmic Movement Program used in this study for geriatric nursing care is simple and safe for application to the elderly and shows significant effects by implementing 5 sessions a week for 9 weeks. The Rhythmic Movement Program improves the quality of life, maintains as well as improves the physical and physiological fuctions and emotional state, therefore this program is strongly recommended for positive applications for independant geriatric nursing health care.

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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.

Anti-inflammatory Activities of Antimicrobial Peptide Locustacin Derived from Locusta migratoria in LPS-stimulated RAW264.7 Cells (풀무치 유래 항균 펩타이드 locustacin의 항염증 활성)

  • Choi, Ra-Yeong;Lee, Joon Ha;Seo, Minchul;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.31 no.10
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    • pp.898-904
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    • 2021
  • Locusta migratoria is a widespread locust species in many parts of the world and is considered an alternative source for the production of protein for value-added ingredients. We previously identified putative antimicrobial peptides derived from L. migratoria through an in silico analysis of its transcriptome. However, its anti-inflammatory effect has not been studied. In this study, we investigated the anti-inflammatory activities of the antimicrobial peptide locustacin (KTHILSFFPSFLPLFLKK-NH2) derived from L. migratoria on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Locustacin (50, 100, and 200 ㎍/ml) significantly reduced the production of nitric oxide (NO) in LPS-stimulated macrophages without any cytotoxicity. Locustacin also inhibited the mRNA and protein expression of pro-inflammatory mediators, such as inducible NO synthase and cyclooxygenase-2, in contrast to the presence of LPS alone. Locustacin decreased the release of LPS-induced pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, and their gene expression in a dose-dependent manner. Furthermore, locustacin (100 and/or 200 ㎍/ml) inhibited phosphorylation levels of extracellular signal regulated kinase, p38, and c-Jun N-terminal kinase. Locustacin also suppressed the degradation of inhibitory kappa B alpha, which was considered to be an inhibitor of nuclear factor kappa B (NF-κB). Collectively, these results demonstrate that locustacin can exert anti-inflammatory effects through the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation, activation of NF-κB, and downstream inflammatory mediators in LPS-stimulated macrophage cells.

Postoperstive Chemoradiotherapy in Locally Advanced Rectal Cancer (국소 진행된 직장암에서 수술 후 화학방사선요법)

  • Chai, Gyu-Young;Kang, Ki-Mun;Choi, Sang-Gyeong
    • Radiation Oncology Journal
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    • v.20 no.3
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    • pp.221-227
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    • 2002
  • Purpose : To evaluate the role of postoperative chemoradiotherapy in locally advanced rectal cancer, we retrospectively analyzed the treatment results of patients treated by curative surgical resection and postoperative chemoradiotherapy. Materials and Methods : From April 1989 through December 1998, 119 patients were treated with curative surgery and postoperative chemoradiotherapy for rectal carcinoma in Gyeongsang National University Hospital. Patient age ranged from 32 to 73 years, with a median age of 56 years. Low anterior resection was peformed in 59 patients, and abdominoperineal resection in 60. Forty-three patients were AJCC stage II and 76 were stage III. Radiation was delivered with 6 MV X rays using either AP-PA two fields, AP-PA both lateral four fields, or PA both lateral three fields. Total radiation dose ranged from 40 Gy to 56 Gy. In 73 patients, bolus infusions of 5-FU $(400\;mg/m^2)$ were given during the first and fourth weeks of radiotherapy. After completion of radiotherapy, an additional four to six cycles of 5-FU were given. Oral 5-FU (Furtulone) was given for nine months in 46 patients. Results : Forty $(33.7\%)$ of the 119 patients showed treatment failure. Local failure occurred in 16 $(13.5\%)$ patients, 1 $(2.3\%)$ of 43 stage II patients and 15 $(19.7\%)$ of 76 stage III patients. Distant failure occurred in 31 $(26.1\%)$ patients, among whom 5 $(11.6\%)$ were stage II and 26 $(34.2\%)$ were stage III. Five-year actuarial survival was $56.2\%$ overall, $71.1\%$ in stage II patients and $49.1\%$ in stage III patients (p=0.0008). Five-year disease free survival was $53.3\%$ overall, $68.1\%$ in stage II and $45.8\%$ in stage III (p=0.0006). Multivariate analysis showed that T stage and N stage were significant prognostic factors for five year survival, and that T stage, N stage, and preoperative CEA value were significant prognostic factors for five year disease free survival. Bowel complication occurred in 22 patients, and was treated surgically in 15 $(12.6\%)$, and conservatively in 7 $(5.9\%)$. Conclusion : Postoperative chemoradiotherapy was confirmed to be an effective modality for local control of rectal cancer, but the distant failure rate remained high. More effective modalities should be investigated to lower the distant failure rate.