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Ethanol Extract from Cnidium monnieri (L.) Cusson Induces G1 Cell Cycle Arrest by Regulating Akt/GSK-3β/p53 Signaling Pathways in AGS Gastric Cancer Cells (AGS 위암세포에서 Akt/GSK-3β/p53 신호경로 조절을 통한 벌사상자 에탄올 추출물의 G1 Cell Cycle Arrest 유도 효과)

  • Lim, Eun Gyeong;Kim, Eun Ji;Kim, Bo Min;Kim, Sang-Yong;Ha, Sung Ho;Kim, Young Min
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.417-425
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    • 2017
  • Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-$3{\beta}$, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-$3{\beta}$, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-$3{\beta}$ inhibitor), and Pifithrin-${\alpha}$ (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-$3{\beta}$/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-$3{\beta}$/p53 signaling pathway in AGS gastric cancer cells.

Root-zone Application of Insecticides in Gelatin Capsules for the Control of Rice Insect Pests (살충제(gelatin capsule 입)의 수도근부처리에 의한 수도해충 방제효과)

  • Choi S. Y.;Heu M. H.;Chung K. Y.;Kang Y. S.;Kim H. K.
    • Korean journal of applied entomology
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    • v.14 no.3 s.24
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    • pp.147-153
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    • 1975
  • During 1973 a field experiment was carried out to evaluate effectiveness of the root zone application of insecticides in medical gelatin capsules for control of several rice insect pests and dwarf virus disease. At three days after transplanting the capsules were pushed by hand about 2.5cm into the soil, near roots of Tongil rice plants. At the given day intervals number of leaf-and plant-hoppers on the hills were recorded by direct count, and dead hearts and white heads by stem borers and dwarf virus infected hills were observed in the experiment plots. Finally grain yields were measured. The percentages of dead hearts and white heads in all the plots were too low for evaluating the effectiveness of insecticides against the striped rice borers. Carbofuran of the insecticides tested was relatively effective against green rice leafhopper (Nephotettixcincticeps) and small brown planthopper (Laodelphax striatellus), although small number of insects on the hills were recorded. Relatively small number of white-backed planthopper (Sogatella furcifera) was occured in the BPMC and Diazinon treated plots. BPMC and Carbofuran were highly effective against the brown planthopper (Nilaparvata lugens) to 80 days after treatment. Incidence of dwarf virus disease was least in the plots of Carbofuran treatment. The highest grain yield was recorded in the plots treated with Carbofuran, and it seemed to be related with good protection from the dwarf virus disease and leaf-and plant-hoppers.

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Clinical Evaluation of Surgical Resection of Pulmonary Tuberculosis (폐결핵에 대한 외과적 치험)

  • Park, Seung-Kyu;Shon, Mal-Hyun;Han, Dong-Gi;Ha, Hyun-Chul;Jin, Young-Ho;Song, Sun-Dae
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.4
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    • pp.474-480
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    • 1995
  • Background: In spite of initial intensive and long-term chemotherapy for pulmonary tuberculosis, many problems remain in the treatment of the residual lesion. The role of surgical intervention for pulmonary tuberculosis is getting rid of such residual lesion of pulmonary tuberculosis to support the healing process and to induce bacteriologically negative conversion in the end. Method: We experienced 30 cases of pulmonary resection for pulmonary tuberculosis from Aug. 1994 through Apr. 1995 in National Masan Tuberculosis Hospital. We conducted retrospective study to analyze several variables for the cases. Results: 1) The ratio between male and female was 4:1(male 24, female 6) and the age of peak incidence was in 3rd and 4th decades. 2) Indications for pulmonary resection in the radiographic findings were cavitary lesions of 19 cases(63.3%), destroyed one side of 8 cases(26.7%) and destroyed one lobe of 3 cases(10%). 3) 16 of 20 cases with unilateral lesions and all of 10 cases with bilateral lesions on chest X-ray films showed AFB positive on preoperative sputum smears. 14 cases(87.5%) of unilateral lesions and 9 cases(90%) of bilateral ones were converted into AFB negative postoperatively. Negative conversion rates of pneumonectomy and lobectomy cases were 100% and 85.7%, respectively. 4) Preoperative combined disease was 3 cases(10%) of DM and postoperative complications were 2 cases(6.7%) of dead space and no death. Conclusion: Chemotherapy only has some limitation in treatment of all tuberculosis. So, surgical intervention for pulmonary tuberculosis is an effective method as partner of chemotherapy.

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Apoptotic Effects and Cell Cycle Arrest Effects of Extracts from Cnidium monnieri (L.) Cusson through Regulating Akt/mTOR/GSK-3β Signaling Pathways in HCT116 Colon Cancer Cells (HCT116 대장암세포에서 AKT/mTOR/GSK-3β 신호경로 조절을 통한 벌 사상자 추출물(CME)의 apoptosis 및 cell cycle arrest 효과)

  • Lim, Eun Gyeong;Kim, Guen Tae;Kim, Bo Min;Kim, Eun Ji;Ha, Sung Ho;Kim, Sang-Yong;Kim, Young Min
    • Journal of Life Science
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    • v.26 no.6
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    • pp.663-672
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    • 2016
  • The Cnidium monnieri (L.) Cusson is an annual plant distributed in China and Korea. The fruit of C. monnieri is used as a medicinal herb that is effective for the treatment of carbuncle and pain in female genitalia. However, the anti-cancer effects of CME have not yet been reported. In this study, we assessed the apoptotic effects and cell cycle arrest effects of ethanol extracts from C. monnieri on HCT116 colon cancer cells. The results of an MTT assay and LDH assay demonstrated a decrease in cell viability and the cytotoxic effects of CME. In addition, the number of apoptotic body and the apoptotic rate were increased in a dose-dependent manner through Hoechst 33342 staining and Annexin V-PI double staining. In addition, cell cycle arrest occurred at the G1 phase by CME. Protein kinase B (Akt) plays an important role in cancer cell survival, growth, and division. Akt down-regulates apoptosis-mediated proteins, such as mammalian target of rapamycin (mTOR), p53, and Glycogen Synthase kinase-3β (GSK-3β). CME could regulate the expression levels of p-Akt, p-mTOR, p-GSK-3β, Bcl-2 family members, caspase-3, and PARP. Furthermore, treatment with CME, LY294002 (PI3K/Akt inhibitor), BIO (GSK-3β inhibitor), and Rapamycin (mTOR inhibitor) showed that apoptotic effects occurred through the regulation of the AKT/mTOR/GSK-3β signaling pathway. Our results demonstrated CME could induce apoptosis and cell cycle arrest in HCT116 colon cancer cells.

Antiviral Properties of Probiotic Mixtures against Rotavirus in the Rat (랫드에서 로타바이러스에 대한 유산균혼합물의 항 바이러스활성)

  • Park, Jae Eun;Lee, Do Kyung;Kim, Min Ji;Kim, Kyung Tae;Choi, Kyung Soon;Seo, Jae Goo;Ha, Nam Joo
    • Korean Journal of Microbiology
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    • v.50 no.4
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    • pp.296-301
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    • 2014
  • Rotavirus is a major cause of acute gastroenteritis in young children in developed and developing countries. The use of probiotics for the treatment of gastrointestinal diseases is both safe and easily accessible. In this study, we evaluated the anti-rotaviral activities of probiotic mixtures in a Sprague-Dawley rat. 24 litters with their dams were randomly assigned to four groups; placebo, phosphate buffered saline (PBS), and two probiotic mixture (PRO-1 and PRO-2) groups. All rats were inoculated with rotavirus at dose of 8 log plaque forming units per rat at 5 days old. Animals in the PRO-1 and PRO-2 groups were orally administered probiotic mixtures 1 or 2, respectively, at a dose of 8 log colony forming units daily during 4 days. For control purposes, placebo and PBS groups were orally administered the same amount of placebo (containing maltose and polydextrose) or PBS once daily for 4 days, respectively. Antiviral analysis was performed by real-time quantitative PCR (RT-qPCR) and observing intestinal villi. As a result, weights of small intestines were greater in the PRO-1, PRO-2 groups than in control groups. Villi were short and villous epithelial necrosis was exhibited in control groups, but these morphological changes were not observed in PRO-1, PRO-2 treated rats. RT-qPCR analysis showed that VP7 gene level of rotavirus in fecal samples and small intestinal epithelial cells were lower in the PRO-1 and PRO-2 groups. These findings suggest that probiotic mixtures may be useful probiotics for the treatment of or as alternative therapies for rotaviral gastroenteritis.

Oxidative Stability of Lipids from Eel (Anguilla japonica) Fed Conjugated Linoleic Acid (Conjugated Linoleic Acid급여 뱀장어(Anguilla japonica) 지질의 산화안정성)

  • Choi, Byeong-Dae;Kang, Seok-Joong;Ha, Young-Lae;Kim, So-Young;Lee, Jae-Jun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.1
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    • pp.61-67
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    • 2006
  • The oxidative stability of lipids from eel (Anguilla japonica) fed diets containing different concentrations of conjugated linoleic acid (CLA) was studied. Eels, 3 weeks of age, with an average weight of 160 g, were randomly divided into 5 groups (5 fishes/group) by body weight, and assigned to one of the five CLA-supplemented diets at the following concentrations: 0, 0.5, 1.0, 2.5, and $5.0\%$ CLA. After 8 weeks of feeding, eels were sacrificed and the total lipid contents were extracted. The lipids from each treatment groups were stored at $37^{\circ}C$ for 5 weeks. Changes in the fatty acid profile, lipid class, weight gained, peroxide value (POV) and carbonyl value (COV) of the lipid from each treatment groups were analyzed weekly. The composition of CLA in the lipids of eels fed with 0.5, 1.0, 2.5, and $5.0\%$ CLA-supplemented diets were 0.5, 1.7, 3.3, and $6.2\%$, respectively After 4 weeks of storage, the proportion of polyunsaturated fatty acids (PUFAs) in the lipid of eels fed diets containing 1.0 and $2.5\%$ CLA were 15.3 and $14.8\%$, respectively. Whereas, lipid extracted from eels fed with 0.5 and $5.0\%$ CLA-supplemented diets contain 11.8 and $7.4\%$ PUFAs, respectively. Lipid from the control sample contained $9.0\%$ PUFAs. POV and COV were found to be the lowest in the lipids samples from 1.0 and $2.5\%$ CLA diets. These results indicate that lipids from diets containing 1.0 or $2.5\%$ CLA were more stable against oxidative rancidity relative to other concentrations, suggesting that these are the appropriate CLA concentrations for the production of stable eel lipids.

Effects of Paper Sludge Application on the Chemical Properties of Paddy Soil and Growth of Paddy Rice;IV. Effects of Paper Sludge Application on the Seasonal Variations of Volatie Lower Fatty Acids in Paddy Soil (제지(製紙)슬러지의 시용(施用)이 논 토양(土壤)의 화학성(化學性)과 수도생육(水稻生育)에 미치는 영향(影響);IV. 슬러지시용(施用)이 토양중(土壤中) 휘발성저급지방산변화(揮發性低級脂肪酸變化)에 미치는 영향(影響))

  • Heo, Jong-Soo;Kim, Kwang-Sik;Ha, Ho-Sung
    • Korean Journal of Environmental Agriculture
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    • v.7 no.1
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    • pp.34-42
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    • 1988
  • To investigate the effects of paper sludge on seasonal variations of volatile lower fatty acids in paddy soil, paper sludge was applied to pots at the rate of either 300, 600, 900 or 1,200 kg/l0a which was either preadjusted at a C/N ratio of 30 : 1 or not adjusted. The decomposition rate of paper sludge, the evolution of $CO_2$, and the fractions of volatile lower fatty acids in the soil were determined. The results are summarized as follows: 1. Paper sludge was decomposed to $35{\sim}44%$, and its C/N ratio was $55{\sim}82$, respectively, at 120 days after treatment. 2. The evolution of $CO_2$, in the soil was proportional to the amount of paper sludge added. Significant positive correlations were observed the $CO_2$ evolution was compared with the decomposition rate of paper sludge, and volatile fatty acid contents in soil. 3. Acetic, propionic, butyric, i-butyric, valeric and i-valeric acids were identified in all the soils investigated. The content of the total volatile fatty acids in the soil increased with as the application of paper sludge increased. The formation of the acids was the highest at 25 days after treatment, and thereafter the contents of the acids decreased as time elapsed. 4. The volatile fatty acids in the soil inhibited the growth of paddy rice in early stages. The contents of acetic, propionic and i-valeric acids in the soil negatively, correlated with the uptake of N, $P_2O_5$, $K_2O$, CaO, MgO and $SiO_2$ in the paddy rice at 25 days after transplantation. In addition, the uptake of $P_2O_5$ and CaO in the paddy rice negatively correlated with the content of butyric acid in the soil. 5. The content of total volatile fatty acids positively correlated with the content of $Fe^{++}$ and $Mn^{++}$ in the soil at 25 days after transplantation. A significantly positive correlation was observed between $Fe^{++}$ and acetic acid contents in the soil.

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Development of User Based Recommender System using Social Network for u-Healthcare (사회 네트워크를 이용한 사용자 기반 유헬스케어 서비스 추천 시스템 개발)

  • Kim, Hyea-Kyeong;Choi, Il-Young;Ha, Ki-Mok;Kim, Jae-Kyeong
    • Journal of Intelligence and Information Systems
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    • v.16 no.3
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    • pp.181-199
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    • 2010
  • As rapid progress of population aging and strong interest in health, the demand for new healthcare service is increasing. Until now healthcare service has provided post treatment by face-to-face manner. But according to related researches, proactive treatment is resulted to be more effective for preventing diseases. Particularly, the existing healthcare services have limitations in preventing and managing metabolic syndrome such a lifestyle disease, because the cause of metabolic syndrome is related to life habit. As the advent of ubiquitous technology, patients with the metabolic syndrome can improve life habit such as poor eating habits and physical inactivity without the constraints of time and space through u-healthcare service. Therefore, lots of researches for u-healthcare service focus on providing the personalized healthcare service for preventing and managing metabolic syndrome. For example, Kim et al.(2010) have proposed a healthcare model for providing the customized calories and rates of nutrition factors by analyzing the user's preference in foods. Lee et al.(2010) have suggested the customized diet recommendation service considering the basic information, vital signs, family history of diseases and food preferences to prevent and manage coronary heart disease. And, Kim and Han(2004) have demonstrated that the web-based nutrition counseling has effects on food intake and lipids of patients with hyperlipidemia. However, the existing researches for u-healthcare service focus on providing the predefined one-way u-healthcare service. Thus, users have a tendency to easily lose interest in improving life habit. To solve such a problem of u-healthcare service, this research suggests a u-healthcare recommender system which is based on collaborative filtering principle and social network. This research follows the principle of collaborative filtering, but preserves local networks (consisting of small group of similar neighbors) for target users to recommend context aware healthcare services. Our research is consisted of the following five steps. In the first step, user profile is created using the usage history data for improvement in life habit. And then, a set of users known as neighbors is formed by the degree of similarity between the users, which is calculated by Pearson correlation coefficient. In the second step, the target user obtains service information from his/her neighbors. In the third step, recommendation list of top-N service is generated for the target user. Making the list, we use the multi-filtering based on user's psychological context information and body mass index (BMI) information for the detailed recommendation. In the fourth step, the personal information, which is the history of the usage service, is updated when the target user uses the recommended service. In the final step, a social network is reformed to continually provide qualified recommendation. For example, the neighbors may be excluded from the social network if the target user doesn't like the recommendation list received from them. That is, this step updates each user's neighbors locally, so maintains the updated local neighbors always to give context aware recommendation in real time. The characteristics of our research as follows. First, we develop the u-healthcare recommender system for improving life habit such as poor eating habits and physical inactivity. Second, the proposed recommender system uses autonomous collaboration, which enables users to prevent dropping and not to lose user's interest in improving life habit. Third, the reformation of the social network is automated to maintain the quality of recommendation. Finally, this research has implemented a mobile prototype system using JAVA and Microsoft Access2007 to recommend the prescribed foods and exercises for chronic disease prevention, which are provided by A university medical center. This research intends to prevent diseases such as chronic illnesses and to improve user's lifestyle through providing context aware and personalized food and exercise services with the help of similar users'experience and knowledge. We expect that the user of this system can improve their life habit with the help of handheld mobile smart phone, because it uses autonomous collaboration to arouse interest in healthcare.

Efficiency of Staging Work-Ups in the Evaluation of Carcinoma of the Uterine Cervix (자궁경부암에 있어서 병기결정을 위한 검사의 효용성)

  • Kim, Jae-Sung;Ha, Sung-Whan
    • Radiation Oncology Journal
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    • v.9 no.2
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    • pp.271-276
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    • 1991
  • A series of 510 patients with carcinoma of the uterine cervix given the curative radiation therapy from March 1979 through December 1986 was evaluated to determine the value of intravenous pyelography (IVP), cystoscopy, sigmoidoscopy, and abdomino-pelvic CT as staging work-up prior to treatment. On IVP and cystoscopy, $10.7\%$(49/456) and $5.3\%$(24/452) showed abnormality, respectively, but only $0.7\%$(3/413) did on sigmoidoscopy. As a result of these work-ups prerequisite to FIGO staging, twenty six ($5.1\%$) out of 510 patients were upstaged from the stage determined by the findings of physical examination alone. The proportions of upstaging in each stage were as follows; none in stage IB (35), IIA (89) and IIIA (8), $7.9\%$(20/252) in stage IIB (14 patients to FIGO stage IIIB, 6 patients to FIGO stage IVA), and $4.8\%$(6/126) in stage IIIB (all to FIGO stage IVA). Positive findings of staging work-ups were found only in patients with advanced stages of stage IIB or over determined by physical examination alone but not in those with earlier stages. CT was performed in 337 patients. CT detected pelvic lymph node (LN) enlargement in $25.2\%$ (85/337) and paraaortic LN enlargement in $7.4\%$(25/337). Pelvic LN positivity was well correlated with increasing stage but paraaortic LN positivity was not. In the evaluation of parametrial involvement, CT findings were in accordance with those of physical examination only in $65.6\%$ (442/674). When compared with endoscopic studeies, CT had much lower positive predictive value than negative predicitive value in the evaluation of adjacent organ invasion. The staging work-ups should be individualized by the disease extent of each patient, and then the efficiency of work-uus may be increased without compromising the appropriate FIGO staging and treatment.

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Results of Radiation Therapy in Stage III Uterine Cervical Cancer (병기 III 자궁경부암의 방사선치료 결과)

  • Moon, Chang-Woo;Shin, Byung-Chul;Yum, Ha-Yong;Jeung, Tae-Sig;Yoo, Myung-Jin
    • Radiation Oncology Journal
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    • v.13 no.3
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    • pp.259-266
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    • 1995
  • Purpose : The aim of this study is to analyze the survival rate, treatment failure and complication of radiation therapy alone in stage III uterine cervical cancer. Materials and Methods : From January 1980 through December 1985, 227 patients with stage III uterine cervical cancer treated with radiation therapy at Kosin Medical Center were retrospectively studied. Among 227 patients, 72 patients($317{\%}$) were stage IIIa, and 155 patients($68.3{\%}$) were stage IIIb according to FIGO classification. Age distribution was 32-71 years (median: 62 years). Sixty nine patients($95.8{\%}$) in stage IIIa and 150 patient ($96.8{\%}$) in stage IIIb were squamous cell carcinoma. pelvic lymph node metastasis at initial diagnosis was 8 patients($11.1{\%}$) in stage IIIa and 29 patients($18.7{\%}$) in stage IIIb, Among 72 patients with stage IIIa, 36 patients ($50{\%}$) were treated with external radiation therapy alone by conventional technique (180-200 cGy/fr.) and 36 patients($50{\%}$) were treated with external radiation therapy with intracavitary radiotherapy(ICR) with $Cs^{137}$ sources, and among 155 patients with stage IIIb, 80 patients ($51.6{\%}$) were treated with external radiation therapy alone and 75 patients ($48.4{\%}$) were treated with external radiation therapy with ICR. Total radiation doses of stage IIIa and IIIb were 65-105 Gy(median: 78.5 Gy) and 65-125.5 Gy (median 83.5 Gy). Survival rate was calculated by life-table method. Results : Complete response rates were $58.3{\%}$(42 patients) in stage IIIa and $56.1{\%}$(87 patients) in stage IIIb. Overall 5 year survival rates were $57{\%}$ in stage IIIa and $40{\%}$ in stage IIIb. Five year survival rates by radiation technique in stage IIIa and IIIb were $64{\%},\;40{\%}$ in the group treated in combination of external radiation and ICR, and $50\%,\;40\%$ in the group of external radiation therapy alone(P=NS). Five year survival rates by response of radiation therapy in stage IIIa and IIIb were $90\%,\;66\%$ in responder group and $10\%,\;7\%$ in non-responder group (P<0.001) There were statistically no significant differences of 5 year survival rate by total radiation doses and external radiation doses(40 Gy vs 50 Gy) of whole or true pelvis in stage IIIa and IIIb(P=NS). Treatment failures rates were $40.3\%$(29 patients) in stage IIla and $57.4\%$(89 patients) in stage IIIb. 17 patients ($23.6\%$) in stage IIIa and 46 patients ($29.7\%$) in stage IIIb experienced complications. Total radiation doses more than 85 Gy produced serious complication in both stage IIIa($50\%$) and IIIb($50\%$). Serious complication rates were higher in group received external radiation doses of 50 Gy than 40 Gy to whole or true pelvis in stage IIIa and IIIb. Serious rectal complication developed in rectal doses more than 65 Gy, and serious bladder complication developed in bladder doses more than 75 Gy. Major cause of death was cachexia due to locoregional failure in both stage IIIa($34.7\%$) and IIIb($43.9\%$). Conclusion : From this study, we found that external radiation therapy with ICR was found to have a tendency to be superior to external radiation therapy alone in survival rate, local control rate and complication rate but not different in statistics, and external radiation doses of 50 Gy than 40 Gy to whole or true pelvis produced serious rectal and bladder complications in stage III uterine cervical cancer.

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