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The Results of Hvperfractionated Radiation Therapy Combined with Taxol for Paraaortic Node Recurrence in Cervix Cancer (대동맥주위 림프절에 재발된 자궁경부암에서 Taxol을 병행한 과분할 방사선치료의 결과)

  • Kim, Jun-Sang;Jang, Ji-Young;Kim, Jae-Sung;Kim, Sam-Yong;Cho, Moon-June
    • Radiation Oncology Journal
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    • v.18 no.1
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    • pp.27-31
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    • 2000
  • Purpose : The aim of this study was to investigate treatment results, toxicity and efficacy of hypefractionated radiation therapy combined with paclitaxel for paraaortic node recurrence in cervix cancer. Materials and Methods: Between September 1997 to March 1999, 12 patients with paraaortic node recurrence in cervix cancer who previously received radical or postoperative radiotherapy were treated with hypefractionated radiation therapy combined with paclitaxel. Of these, 2 patients who irradiated less than 30 Gy were excluded, 10 patients were eligible for this study. Median age was 51 years. Initial FIGO stage was 1 stage IBI, 2 stage IIA, 7 stage IIB. For initial treatment, 7 patients received radical radiotherapy and 3 received postoperative radiotherapy. The paraaortic field encompassed the gross recurrent disease with superior margin at T12, and inferior margin was between L5 and S1 with gap for previously pelvic radiation field. The radiation field was initially anterior and posterior opposed field followed by both lateral field. The daily dose was 1.2 Gy, twice daily fractions, and total radiotherapy dose was between 50.4 and 60 Gy(median, 58.8 Gy). Concurrent chemotherapy was done with paclitaxel as a radiosensitizer. Dose range was from 20 mg/m$^{3}$ to 30 mg/m$^{3}$ (median, 25 mg/m$^{3}$), and cycle of chemotherapy was from 3 to 6 (median, 4.5 cycle). Follow-up period ranged from 3 to 21 months. Results : Interval between initial diagnosis and paraaortic node recurrence was range from 2 to 63 months (median, 8 months). The 1 year overall survival rate and median survival were 75$\%$ and 9.5 months, respectively. The 1 year disease free survival rate and median disease free survival were 30$\%$ and 7 months, respectively. At 1 month after treatment, 4 (40$\%$) achieved a complete response and 6 (60$\%$) experienced a partial response and all patients showed response above the partial response. There was distant metastasis in 6 patients and pelvic node recurrence In 2 patients after paraaortic node irradiation. There was 2 patients with grade 3 to 4 leukopenla and 8 patients with grade 1 to 2 nausea/ vomiting which was usually tolerable with antlemetic drug. There was no chronic complication in abdomen and pelvis during follow up period. Conclusion : hypefractionated radiation therapy combined with paclitaxel chemotherapy diosensitizer showed high response rate and few complication rate in paraaortic node recurrence in cervix cancer Therefore, present results suggest that hypefractionated radiation therapy combined with paclitaxel chemotherapy can be used as optimal treatment modality in this patients.

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The Role of Primary Radiotherapy for Squamous Cell Carcinoma of the Suprag1ottic Larynx (성문상부 상피세포암에서의 근치적 방사선치료의 역할)

  • Kim, Won-Taek;Kim, Dong-Won;Kwon, Byung-Hyun;Nam, Ji-Ho;Hur, Won-Joo
    • Radiation Oncology Journal
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    • v.18 no.4
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    • pp.233-243
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    • 2000
  • Purpose : First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. Methods and Material : Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months, Twenty-seven patients (84.4$\%$) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional iymphatics with shrinking field technique. Ail patients received radiotherapy under conventional fractionated schedule (once a day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had Induction chemotherapy with cisplatln and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6$\%$): stage II, 10/32 (31.3$\%$); stage III, 8/32 (25$\%$): stage IV, 9/32 (28.1$\%$). Results :The 5-year overall survival rate of the whole series (32 patients) was 51.7$\%$. The overall survival rate at 5-years was 80$\%$ in stage I, 66.7$\%$ in stage II, 42.9$\%$ in stage III, 25$\%$ in stage IV (p=0.0958). The S-year local control rates after radiotherapy were as fellows: stage I, 100$\%$; stage II, 60$\%$ stage III, 62.5$\%$; stage IV, 44.4$\%$ (p=0.233). Overall vocal preservation rates was 65.6$\%$, 100% In stage I, 70% in stage II, 62.5$\%$ In stage III, 44.4$\%$ in stage IV (p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotllerapy, emergent tracheostomy was done. Four patients were died from distant metastsis, . three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor ( p=0.0215), and radiation dose (more or less than 70.2 Gy) was an important factor on survival (p=0.002). Conclusion : The role of radiotherapy treatment of supraglottic carcinoma is to important factor on survival and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supragiottic carcinomas could be successfully treated with either consewative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone is Inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

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Analysis of Critical Control Points through Field Assessment of Sanitation Management Practices in Foodservice Establishments (현장실사를 통한 급식유헝별 위생관리실태 분석)

  • Kwak Tong-Kyung;Lee Kyung-Mi;Chang Hye-Ja;Kang Yong-Jae;Hong Wan-Soo;Moon Hye-Kyung
    • Korean journal of food and cookery science
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    • v.21 no.3 s.87
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    • pp.290-300
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    • 2005
  • Increased sanitation management of foodservice establishments is required because most of the reported foodborne-disease outbreaks were in the foodservice industry. The purpose of this study was to determine the important control points for good sanitation. In this study, we inspected twenty foodservice establishments in Seoul, Kyunggi, Kyungnam with a self-developed monitoring tool. These foodservice establishments included secondary schools, universities, and industries. Six of them had appointed as the HACCP-certified establishments from the Korea Food and Drug Administration. The inspection was conducted from June to August in 2002. The inspection tool consisted of nine dimensions and sixty-five items. The dimensions were 'personal sanitation', 'supply of raw food', 'food storage', 'handling of raw food and ready-to-eat', 'cleaning and sterilization', 'waste control', 'pest control', and 'control of establishment and equipment' The highest possible score of this inspection tool is 105 points. Statistical data analysis was completed using the SPSS Package(11.0) for descriptive analysis Kruskal-Wallis. The score for the secondary schools (83.6 points) was higher than for the others and number of in compliance item was 50.9 on average. Therefore, we concluded that the secondary schools' sanitation condition was good. The foodservice establishments acquired HACCP certification was 89.7 points, which was significantly higher than that of establishments not applying foodservices in total score. Instituting the HACCP system in a foodservice is very effective for sanitation management. Many out of the compliance observations were found in the dimensions of 'waste control', 'control of establishment and equipment', and 'supply of raw food' 'Clean condition of refrigerator' item was $65\%$ out of the compliance that was the highest percent in this study. 'Notify and observance of heating/reheating temperature' was $45\%$ out of compliance. Items which were over $30\%$ out of compliance were 'sterilization of knifes and chopping boards in cooking', 'education of workers', 'maintain refrigerator temperature blow $5^{\circ}C$', and 'countermeasure of infection workers' In the results, most of the foodservice establishments were poorly managed in temperature control and cross-contamination. The important control points revealed in this study were preventing contamination, cooking temperature compliance, management of raw food and refrigerator. Therefore foodservice establishments should pay attention to education and training about important control points. The systematic sanitation management monitoring tool developed in this study can be effectively applied for conducting self-inspection and improving the sanitary conditions of their own foodservice operations.

Application of Support Vector Regression for Improving the Performance of the Emotion Prediction Model (감정예측모형의 성과개선을 위한 Support Vector Regression 응용)

  • Kim, Seongjin;Ryoo, Eunchung;Jung, Min Kyu;Kim, Jae Kyeong;Ahn, Hyunchul
    • Journal of Intelligence and Information Systems
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    • v.18 no.3
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    • pp.185-202
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    • 2012
  • .Since the value of information has been realized in the information society, the usage and collection of information has become important. A facial expression that contains thousands of information as an artistic painting can be described in thousands of words. Followed by the idea, there has recently been a number of attempts to provide customers and companies with an intelligent service, which enables the perception of human emotions through one's facial expressions. For example, MIT Media Lab, the leading organization in this research area, has developed the human emotion prediction model, and has applied their studies to the commercial business. In the academic area, a number of the conventional methods such as Multiple Regression Analysis (MRA) or Artificial Neural Networks (ANN) have been applied to predict human emotion in prior studies. However, MRA is generally criticized because of its low prediction accuracy. This is inevitable since MRA can only explain the linear relationship between the dependent variables and the independent variable. To mitigate the limitations of MRA, some studies like Jung and Kim (2012) have used ANN as the alternative, and they reported that ANN generated more accurate prediction than the statistical methods like MRA. However, it has also been criticized due to over fitting and the difficulty of the network design (e.g. setting the number of the layers and the number of the nodes in the hidden layers). Under this background, we propose a novel model using Support Vector Regression (SVR) in order to increase the prediction accuracy. SVR is an extensive version of Support Vector Machine (SVM) designated to solve the regression problems. The model produced by SVR only depends on a subset of the training data, because the cost function for building the model ignores any training data that is close (within a threshold ${\varepsilon}$) to the model prediction. Using SVR, we tried to build a model that can measure the level of arousal and valence from the facial features. To validate the usefulness of the proposed model, we collected the data of facial reactions when providing appropriate visual stimulating contents, and extracted the features from the data. Next, the steps of the preprocessing were taken to choose statistically significant variables. In total, 297 cases were used for the experiment. As the comparative models, we also applied MRA and ANN to the same data set. For SVR, we adopted '${\varepsilon}$-insensitive loss function', and 'grid search' technique to find the optimal values of the parameters like C, d, ${\sigma}^2$, and ${\varepsilon}$. In the case of ANN, we adopted a standard three-layer backpropagation network, which has a single hidden layer. The learning rate and momentum rate of ANN were set to 10%, and we used sigmoid function as the transfer function of hidden and output nodes. We performed the experiments repeatedly by varying the number of nodes in the hidden layer to n/2, n, 3n/2, and 2n, where n is the number of the input variables. The stopping condition for ANN was set to 50,000 learning events. And, we used MAE (Mean Absolute Error) as the measure for performance comparison. From the experiment, we found that SVR achieved the highest prediction accuracy for the hold-out data set compared to MRA and ANN. Regardless of the target variables (the level of arousal, or the level of positive / negative valence), SVR showed the best performance for the hold-out data set. ANN also outperformed MRA, however, it showed the considerably lower prediction accuracy than SVR for both target variables. The findings of our research are expected to be useful to the researchers or practitioners who are willing to build the models for recognizing human emotions.

Semiweekly variation of Spring Phytoplankton Community in Relation to the Freshwater Discharges from Keum River Estuarine Weir, Korea (금강하구언 담수방류와 춘계 식물플랑크톤 군집의 단주기 변동)

  • Yih, Won-Ho;Myung, Geum-Og;Yoo, Yeong-Du;Kim, Young-Geel;Jeong, Hae-Jm
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.10 no.3
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    • pp.154-163
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    • 2005
  • Irregular discharges of freshwater through the water gates of the Keum River Estuarine Weir, Korea, whose construction had been completed in 1998 with its water gates being operated as late as August 1994, drastically modified the estuarine environment. Sharp decrease of salinity along with the altered concentrations of inorganic nutrients are accompanied with the irregular discharges of freshwater into the estuary under the influence of regular semi-diurnal tidal effect. Field sampling was carried out on the time of high tide at 2 fixed stations(St.1 near the Estuarine Weir and St.2 off Kunsan Ferry Station) every other day for 4 months from mid-February 2004 to investigate into the semi-weekly variation of spring phytoplankton community in relation to the freshwater discharges from Keum River Estuarine Weir. CV(coefficient of variation) of salinity measurements was roughly 2 times greater in St.1 than that in St.2, reflecting extreme salinity variation in St.1 Among inorganic nutrients, concentrations of N-nutrients($NO_3^-,\;NO_2^-$ and $NH_4^+$) were clearly higher in St.1, to imply the more drastic changes of the nutrient concentrations in St.1. than St.2 following the freshwater discharges. As a component of phytoplankton community, diatoms were among the top dominants in terms of species richness as well as biomass. Solitary centric diatom, Cyclotella meneghiniana, and chain-forming centric diatom, Skeletonema costatum, dominated over the phytoplankton community in order for S-6 weeks each (Succession Interval I and II), and the latter succeeded to the former from the time of <$10^{\circ}C$ of water temperature. Cyanobacterial species, Aphanizomenon Posaquae and Phormidium sp., which might be transported into the estuary along with the discharged freshwater, occupied high portion of total biomass during Succession Interval III(mid-April to late-May). During this period, freshwater species exclusively dominated over the phytoplankton community except the low concentrations of the co-occurring 2 estuarine diatoms, Cyclotella meneghiniana and Skeletonema costatum. During the 4th Succession Interval when the water temperature was over $18^{\circ}C$, the diatom, Guinardia delicatula, was predominant for a week with the highest dominance of $75\%$ in discrete samples. To summarize, during all the Succession Intervals other than Succession Interval III characterized by the extreme variation of salinity under cooler water temperature than $18^{\circ}C$, the diatoms were the most important dominants for species succession in spring. If the scale and frequency of the freshwater discharge could have been adjusted properly even during the Succession Interval III, the dominant species would quite possibly be replaced by other estuarine diatom species rather than the two freshwater cyanobacteria, Aphanizomenon flosaquae and Phormidium sp.. The scheme of field sampling every other day for the present study was concluded to be the minimal requirement in order to adequately explore the phytoplankton succession in such estuarine environment as in Keum River Estuary: which is stressed by the unpredictable and unavoidable discharges of freshwater under the regular semi-diurnal tide.

Studies on Persistence of Pesticides in Soils and Crops under Polyethylene Film Mulching Culture II. Effect of Polyethylene Film mulching on Weed Emergence, Growth and Yield of Red pepper, Peanut and Sesame (폴리에틸렌 멀칭재배(栽培) 시(時) 농약(農藥)의 토양(土壤) 및 작물체중(作物体中) 잔류(殘留)에 관한 연구(硏究) 제(第) 2 보(報) 폴리에틸렌 멀칭이 잡초발생(雜草發生), 고추, 땅콩, 참깨의 생육(生育) 및 수량(收量)에 미치는 영향(影響))

  • Ryang, H.S.;Moon, Y.H.;Kim, N.E.;Lee, J.H.
    • Korean Journal of Weed Science
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    • v.7 no.3
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    • pp.306-315
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    • 1987
  • In the red pepper field under polythylene film mulching(P.E.-mulching) culture, the weed emergence was completely inhibited by black P.E.-mulching. The emergence in clear P.E.-mulching decreased 90% compared to that in non-mulching. Weeding effect was high in the order of pendimethalin, diphenamid, alachlor and napropamide. The effect of herbicides was higher in clear P.E.-mulching than in non-mulching. Plant height and number of branches increased in the order of clear P.E.-, black P.E.-mulching, while the yield between black P.E.- and clear P.E.-mulching was not different. The herbicides had no effect on the growth and yield. In the peanut field, weed emergence was 80% lower in clear P.E.-mulching than in non-mulching. Weeding effect was excellent in the plot applied with alachlor, napropamide and diphenamid. The total number of branches, main stem height and shoot weight were 2.0, 1.7 and 2.4 times greater in clear P.E.-mulching than in non-mulching, respectively. Peanut yield was about 38% higher under clear P.E.-mulching than under non-mulching. The herbicides had no effect on the growth and yield. In the sesame field, rate of weed emergence was 10 times lower in clear P.E.-mulching than in non-mulching. Weeding effect of alachlor, napropamide and diphenamid was higher under clear P.E.-mulching than under non-mulching. Germination percentage of sesame greatly decreased in non-mulching compared with in clear P.E.-mulching. The germination was inhibited by the treatment of herbicides. The inhibition effect was increased in the order of alachlor, napropamide, and diphenamid. The initial crop injury in treatment of herbicides was greater in non-mulching than in clear P.E.-mulching. The crop recovered from the injury and exhibited regrowth in clear P.E.-mulching except the alachlor treatment, but there was no recovery in non-mulching. There was no significant difference yield between herbicide treatment and hand weeding in non-mulching. Also, no significant difference was obseorbed between napropamide and diphenamid treatment and hand weeding in clear P.E.-mulching.

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Studies on the Constituents of Gynostemma pentaphyllum Makino (덩굴차(Gynostemma pentaphylum Makino)의 성분에 관한 연구)

  • Lee, Heon-Ok;Ko, Young-Su
    • Korean journal of food and cookery science
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    • v.6 no.4 s.13
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    • pp.69-83
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    • 1990
  • Gynostemma pentaphyllum Makino is a kind of perennial liana plant belonging to the Cucurbitaceae family. Since it was first discovered and reported to the Japanese academy in 1977, it came to be widely known to China and Southeast Asia areas as well as Japan. In Korea its name began to appear in the first half of 1980's, and it is now being nationwidely cultivated and popularized as tea stuffs. Gynostemma pentaphyllum Makino has remarkably strong propagation power. In addition. since it contains a great quantity of beneficial components, especially saponin it is believed to have excellent medical effects, too. This study was undertaken to examine the value of Gynostemma pentaphyllum Makino as a health-promotint tea, by investigating the components creating the flaver of tea and the saponin ingredient making medical effects as well as by inspecting whether Gynostemma pentaphyllum Makino products show different component arrangements according to their growing districts. As raw materials of the experiment, three kinds of Gynostemma pentaphyllum Makino samples produced in Suwon, Geochang and Uleungdo were taken. To accomplish the formerly stated goals, the contained quantity of the proximate composition, free sugar, reducing sugar, free amino acid, minerals, tannin, caffeine and vitamin C were measured respectively and compared between the samples, while the saponin content was compared with heat extracted from panax ginseng. The results of the experiment are as follows: 1. In the case of the proximate composition, the crude fat content was the highest in the Gymostemma pentaphyllum Makino material from Geochang (1.62%), the second in that from Suwon (1.56%), and the lowest in that from Uleungdo (1.0%). In addition the Geochang: produced sample had the greatest quantity of the crude protein and ash contents: the order of the crude Protein content was the Geochang produced (17.83%), the Suwon-produced (15.87%), and the Uleungdo-produced(12.28%), while that of the ash content was the Geochang-produced (14.80%), the Uleungdo-produced(10.17%), and the Suwon-produced(9.34%). 2. As for the reducing sugar contents, the Suwon-produced scored the highest of the three (3.3%), while the Geochang-produced was 1.3% and the Uleungdo-produced 0.5%. The total content of free sugar was 1.07% (the Suwon-produced), and 0.49% (the Geochang-produced) respectively but the sample from Uleungdo showed almost no free sugar content. The contained quantity of fructose and glucose was the highest among the kinds of free sugar both in the Suwon-produced and in the Geochang-produced. 3. The content of amino acid was the highest in the Suwon-produced(1.41%), the second in the Geochang-produced(1.37%), and the lowest in the Uleungdo-produced(0.53%). In the experiment, sixteen kinds of amino acid were extracted-Asp. Thr. Ser. Glu. Gly. Ala. Val. Het. Ileu. Leu. Tyr. Phe. Lys. His. Arg. Try. All of them except glutamic acid and methionine showed the highest quantity score in the Suwon-produced, while the glutamic acid content was the higest in the Uleungdo-produced and the methionine content in the Geochang-produced. The sequential arrangement of the sixteen contents according to their magnitude ranged from glycine, aspartic acid, and glutamic acid (the highest) to tryptophan, serine and lysine (the lowest). 4. Ten kinds of mineral were detected-Ca, Mn, Cd, K, Na, Pb, Mg, Fe, Zn, Cu. Among them, the content of Cd, Na, Mg, Zn and Fe was the highest in the Geochang-produced and that of K in the Suwon-produced. 5. The Geochang-produced materials contained much a larger quantity of tannin (6.3%) than the Suwon-produced (2.6%). Neither caffeine nor vitamin C was detected in the three kinds of materials. 6. In the case of the saponin content the Geochang-produced showd 2.39%, the Uleungdo-produced 1.77% and the Suwon-produced 1.49% respectively. However, it was found also that the saponin content of Gymostemma pentaphyllum Makino was the same kind as that of panax ginseng.

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Lymph Node Failure Pattern and Treatment Results of Esophageal Cancer Patients Treated with Definitive Radiotherapy (근치목적 방사선치료를 받은 식도암 환자의 림프절 재발양상과 치료성적)

  • Lee, Sun-Young;Kwon, Hyoung-Cheol;Lee, Heui-Hwan;Kim, Jung-Soo;Kim, Soo-Geon
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.77-82
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    • 2008
  • Purpose: We evaluated the failure pattern of the celiac axis, gastric lymph node, and treatment outcome in the upper and mid-esophageal region of cancer patients treated by definitive radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, retrospectively. Materials and Methods: The study constituted the evaluation 108 patients with locally advanced esophageal cancer receiving radiotherapy or a combination of radiotherapy and chemotherapy at Chonbuk National University Hospital from January 1986 to December 2006. In total, 82 patients treated by planned radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, were analysed retrospectively. The study population consisted of 78 men and 2 women(mean age of 63.2 years). In addition, 51 patients received radiotherapy alone, whereas 31 patients received a combination of radiation therapy and chemotherapy. The primary cancer sites were located in the upper portion(17 patients), and mid portion(65 patients), respectively. Further, the patients were in various clinical stages including T1N0-1M0(7 patients), T2N0-1M0(18 patients), T3N0-1M0(44 patients) and T4N0-1M0(13 patients). The mean follow up period was 15 months. Results: The various treatment outcomes included complete response(48 patients), partial response(31 patients) and no response(3 patients). The failure patterns of the lymph node were comprised of the regional lymph node(23 patients) and the distance lymph node which included celiac axis and gastric lymph node(13 patients). However, metastasis was not observed in the regional and distant lymph node in 10 patients, whereas 36 patients were not evaluated. Furthermore, of the 13 patients who developed celiac axis and gastric lymph node metastases, 3 were in stage T1N0-1M0 and 10 were in stage T2-4N0-1M0. A complete response appeared in 12 patients, whereas a partial response appeared in 1 patient. The mean survival time of the patients who appeared for regional and distant lymph node metastasis was 14.4 and 7.0 months, respectively. Conclusion: In locally advanced esophageal cancer patients, who were treated by definitive radiotherapy without celiac axis and gastric lymph node irradiation, the distant lymph node metastasis rate was high and the overall survival rate was lower compared to the regional lymph node metastasis. The incidence of regional and distant lymph node metastasis was high in patients who appeared beyond clinical stage T2 and received radiotherapy alone.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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The 1998, 1999 Patterns of Care Study for Breast Irradiation After Breast-Conserving Surgery in Korea (1998, 1999년도 우리나라에서 시행된 유방보존수술 후 방사선치료 현황 조사)

  • Suh Chang-Ok;Shin Hyun Soo;Cho Jae Ho;Park Won;Ahn Seung Do;Shin Kyung Hwan;Chung Eun Ji;Keum Ki Chang;Ha Sung Whan;Ahn Sung Ja;Kim Woo Cheol;Lee Myung Za;Ahn Ki Jung
    • Radiation Oncology Journal
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    • v.22 no.3
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    • pp.192-199
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    • 2004
  • Purpose: To determine the patterns on evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was peformed. Materials and Methods: A web-based database system for korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998$\~$1999 from 15 hospitals were reviewed. Results: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9$\%$) followed by medullary carcinoma (4.2$\%$) and infiltrating lobular carcinoma (1.5$\%$). Pathologic T stage by AJCC was T1 in 59.7$\%$ of the casses, T2 in 29.5$\%$ of the cases, Tis in 8.8$\%$ of the cases. Axillary lymph node dissection was peformed I\in 91.2$\%$ of the cases and 69.7$\%$ were node negative. AJCC stage was 0 in 8.8$\%$ of the cases, stage I in 44.9$\%$ of the cases, stage IIa in 33.3$\%$ of the cases, and stage IIb in 8.4$\%$ of the cases. Estrogen and progesteron receptors were evaluated in 71.6$\%$, and 70.9$\%$ of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2$\%$, wide excision in 11.5$\%$, quadrantectomy in 23$\%$ and partial mastectomy in 27.5$\%$ of the cases. A pathologically confirmed negative margin was obtained in 90.8$\%$ of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90$\%$ of the planned radiotherapy dose. Radiotherapy volume was breast only In 88$\%$ of the cases, breast+supraclavicular fossa (SCL) in 5$\%$ of the cases, and breast+ SCL+ posterior axillary boost in 4.2%$\%$of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45$\~$59.4 Gy (median 50.4) and boost dose was 8$\~$20 Gy (median 10 Gy). The total radiation dose delivered was 50.4$\~$70.4 Gy (median 60.4 Gy). Conclusion: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.