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The Results of Hyperfractionated Radiotherapy on Locally Advanced Non-Small Cell Lung Cancer (국소적으로 진행된 비소세포 폐암에 대한 과분할 방사선 치료의 성적)

  • Hur, Won-Joo;Lee, Hyung-Sik;Kim, Jeong-Ki;Choi, Young-Min;Lee, Ho-Jun;Youn-Seon-Min;Kim, Jae-seok;Kim, Hyo-Jin;Woo-Jong-Soo;Choi, Pill-Jo;Lee, Ki-Nam
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.275-282
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    • 1998
  • Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

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Concurrent Chemoradiotherapy in Locally Advanced Carcinoma of The Uterine Cervix : A Phase I/II Prospective Study (국소적으로 진행된 자궁경부암의 방사선치료와 복합 항암화학요법의 동시치료 결과)

  • Kang One Chul;Choi Eun Kyung;Chung Weon Kuu;Kim Jong Hoon;Chang Hyesook;Kim Yong Man;Kim Young Tak;Nam Joo Hyun;Mok Jung-Eun;Lee Moo-Song
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.311-323
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    • 1998
  • Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

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Peripheral Neutrophil Count and Respiratory Failure in Preterm Infant (조산아에서 말초혈액 중성구수와 호흡 부전증과의 연관성)

  • Lee, Kum Joo;Yun, Soo Young;Lee, Ran;Hean, Jae Ho;Jung, Ghee Young;Park, Jin Hee;Park, Young Sun
    • Clinical and Experimental Pediatrics
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    • v.45 no.5
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    • pp.596-602
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    • 2002
  • Purpose : The purpose of this study was to analyze the association of peripheral neutrophil count with the development of respiratory failure in preterm infants. Methods : A retrospective study was conducted from January 1993 to December 1999 on 44 preterm infants, who were admitted to the neonatal intensive care unit of St. Francisco hospital. Preterm infants(birth weight 500 to 1,350 gm) who had a complete blood count obtained within 2 hours after delivery. Patients in the lowest of neutrophil count(early neutropenia, < $1.0{\times}10^9/L$) were compared with patients in the remaining group. Results : Low neutrophil count were transient in early neutropenia group. The concentration the circulating neutrophil count rose from $0.85{\pm}0.11{\times}10^9/L$ at average of 2 hours after delivery to $5.3{\pm}2.7{\times}10^9/L$ at 24 hours after delivery in the early neutropenia group and from $3.6{\pm}1.6{\times}10^9/L$ to $5.8{\pm}3.2{\times}10^9/L$ in the non-neutropenia group during the same time period. Compare to the non-neutropenia group, the neutropenia group had a lower birth weight($1,046.50{\pm}180.76gm$ Vs $1,156.70{\pm}124.99gm$), a lower Apgar score(1 min : $3.41{\pm}1.18$ Vs $4.30{\pm}1.46$, 5 min : $5.41{\pm}0.87$ Vs $6.15{\pm}0.95$), and a higher incidence of bronchopulmonary dysplasia(27.27% Vs 7.0%). Patients who had early neutropenia were more likely to require mechanical ventilation, supplemental oxygen and hospital stay. Also, main effect factors for the two groups were birth weight(Odds ratio=5.457, 95% CI=1.551-27.525), initial peripheral blood white cells(odds ratio=8.308, 95% CI=2.054-52.699), and bronchopulmonary dysplasia(odds ratio=0.099, 95% CI=0.017-0.397). Conclusion : A low count of neutrophil in the systemic circulation of premature infants within 2 hours of birth is associated with more severe respiratory distress.

Processing of Water Activity Controlled Fish Meat Paste by Dielectric Heating 1. Formulation and Processing Conditions (내부가열을 이용한 보장성어육(고등어) 연제품의 가공 및 제품개발에 관한 연구 1. 원료${\cdot}$첨가물의 배합 및 가공조건)

  • LEE Kang-Ho;LEE Byeong-Ho;You Byeong-Jin;SUH Jae-Soo;JO Jin-Ho;JEONG In-Hak;JEA Yoi-Guan
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.17 no.5
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    • pp.353-360
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    • 1984
  • As an effort to expand the utilization of mackerel which has been thought disadvantageous to processors due to the defects in bloody dark color of meat, high content of lipid, and low stability of protein, and to develope a new type of product, so called, preservative fish meat paste, the processing method was studied in which dielectric heating was applied by means of cooking, pasteurization, dehydration, and control of water activity. The principle of this method is based on that dielectric heating can initiate a rapid dispersion or displacement of moisture in the meat tissue so that the level of water acivity can be controlled by dehydration with hot air meanwhile the product is cooked, pasteurized, and texturized. And the product is finally heated with electric heaters and vacuum sealed to stabilize water activity and storage stability. In present paper, a formula for preparing the fish meat-stach paste, the conditions of dielectric heating and dehydration, shape and size of the product, and other parameters were tested to optimize the process operation. A formula of the fish meat-starch paste to provide proper textural properties and water activity was $10\%$ starch, $1.5\%$ salt, $3\%$ soybean, $0.6\%$ MSG, $2\%$ sucrose, and $3\%$ sorbitol against the weight of fish meat. A proper shape and size of the product to avoid foaming and case hardening during heating was sliced disc of 8 cm $diameter{\times}0.8$ cm thickness or $10{\times}10$ cm square plate with 1.0 cm thickness. The disc shape was recommended because it resulted more uniform heating, minimum foaming and case hardening. And it was also advantageous that disc was simply provided when the fish meat disc was stuffed in the same, solidified in boiling water for 2 to 3 minutes, and sliced. Condition of dielectric heating was critical to decide the levels of sterility, water activity, and textural property of the product. The temperature at the center of the meat disc slices was raised up to $95^{\circ}C$ in 1.5 minutes so that continuous exposure to microwave caused expanded tissue and hardening ending up with a higher water content. Heating for 5 to 6 minutes was adequate to yield the final water activity of 0.86 to 0.83(35 to $40\%$ moisture). It is important, however, that heating had to be done periodically, for instance, in the manner of 2.0, 1.5, 1.5, and 1.0 minute to give enough time to displace or evaporate moisture from the meat tissue. The product was dehydrated for 2 to 3 minutes by hot air of $60^{\circ}C$, 3 to 5m/sec and finally exposed to electric heaters for 5 to 6 minutes until the surface was roasted deep brown. These conditions of heating and dehydration resulted in a complete reduction of total plate count from an initial count of $5.3{\times}10^6/g$ to less than $3{\times}10^2/g$. General composition of the product was $40.1\%$ moisture, $20.8\%$ protein, $17.4\%$ lipid, $16.2\%$ carbohydrate, and $5.5\%$ ash. Textural properties revealed folding test AA, hardness 42, cohesiveness 0.53, toughness 4.6, and elasticity 0.8.

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The Effect of Two Terpenoids, Ursolic Acid and Oleanolic Acid on Epidermal Permeability Barrier and Simultaneously on Dermal Functions (우솔릭산과 올레아놀산이 피부장벽과 진피에 미치는 영향에 대한 연구)

  • Suk Won, Lim;Sung Won, Jung;Sung Ku, Ahn;Bora, Kim;In Young, Kim;Hee Chang , Ryoo;Seung Hun, Lee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.2
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    • pp.263-278
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    • 2004
  • Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1mg/mL UA or 0.1-1mg/mL ONA after tape stripping, and TEWL (transepidermal water loss) was measured. The recovery rate increased in those UA or ONA treated groups (0.1mg/mL UA and 0.5mg/mL ONA) at 6h more than 20% compared to vehicle treated group (p < 0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/mL per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from 1 week without TEWL alteration (p < 0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA=UA > vehicle). LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA > ONA > vehicle). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via PPAR Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either ONA (10${\mu}$M) or UA (10${\mu}$M) for 24 h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via PPAR Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

Chest CT findings and Clinical features in Mediastinal Tuberculous Lymphadenitis (종격동 결핵성 임파선염의 흉부전산화 단층촬영 소견과 임상 양상에 대한고찰)

  • Lee, Young-Sil;Kim, Kyeong-Ho;Kim, Chang-Sun;Cho, Dong-Ill;Rhu, Nam-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.4
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    • pp.481-491
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    • 1995
  • Background: Recently there has been a trend of an increasing incidence of mediastinal tuberculous lymphadenitis(MTL) in adults. MTL often cause bronchial stenosis or esophago-mediastinal fistula. In spite of effective treatment, it is difficult to cure. Moreover, relapse frequently occurs. Authors analyzed chest CT findings and clinical features of 29 cases with MTL Methods: 29 cases with MTL were retrospectively studied with the clinical and radiologic features from April 1990 to March 1995 Results: 1) A total of 29 cases were studied. 12 cases were male and 17 cases were female. The male to female ratio was 1:1.4 Mean age was 29 years old. The 3rd decade(45%) was the most prevalent age group 2) The most common presenting symptoms and signs were palpable neck masses(62%) followed by cough(59%) and sputum(38%) 3) Except in one case of MTL, all patients had coexisting pulmonary tuberculosis, cervical tuberculous lymphadenitis, endobronchial tuberculosis and tuberculous pleurisy. Among the coexisting tuberculous diseases, Pulmonary tuberculosis was the most common(76%) 4) On simple chest X-ray, mediastinal enlargement was noted in 21 cases(72%), but it was not noted in 8 cases(28%). The most frequently involving site was the paratracheal node in 16 cases(72%). Rt side predominence(73%) was noted 5) Patterns of node appearance on a postcontrast CT scan were classified into 3 types. There were 19 cases(30%) of the Homogenous type, 30 cases(47%) of the Central low density type and 15 cases(23%) of the Peripheral fat obliteration type. The most common type was the central low density type. The most common lymph node size was 1~2 cm(88%) 6) The most frequently involved site was the paratracheal node in 26 cases(89%) by chest CT. Rt side(63%) was predominant 7) 9 cases(43%) had complete therapy and most common treatment duration was 13 - 18 months. 12 cases(57%) had incomplete continuing antituberculous medication and half of the cases had been treated above 19 months. Conclusion: Chest CT findings of MTL showed central low density area and peripheral rim enhancement, so this characteristic findings could differentiate it from other mediastinal diseases and help a diagnosis of tuberculosis. In spite of effective antituberculous medication, it is difficult to cure. Moreover, relapse frequently occurs. Further studies will be needed of the clinical features and the treatment of MTL.

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Study about the clinical features and Pulmonary function Tst of Endobronchial Tuberculosis (기관지결핵의 임상상 및 폐기능검사에 관한 연구)

  • Chung, Hee-Soon;Lee, Jae-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.147-158
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    • 1996
  • Background : Endobronchial tuberculosis(ET) is known to affect frequently young female and serious complication like bronchial stenosis would occur if early diagnosis and treatment for ET is not performed immediately. But ET shows normal chest roentgenogram in about 10% of patients, and is often confused with bronchial asthma because ET presents clinical features like cough, dyspnea, wheezing in history and physical examination. The pulmonary function test(PFT) feature of ET is not well known, but when we consider the fact that ET is pathophysiologically different from bronchial asthma, if there is any feature of PFT in ET, and we know it, PFT will be very helpful for diagnosis and follow up of ET. Methods : We performed both PFT and bronchoscopy in 68 ET patients who visited Boramae hospital, and were confirmed as ET by bronchoscopic biopsy and were followed prospectively from November 1991 to March 1995. After history taking and physical examination, we performed chest roentgenogram, complete blood count, sputum AFB stain and culture, and also performed PFT before anti-tuberculosis chemotherapy. PFT was classified as restrictive, if only PVC was reduced below 80%, and obstructive, if only FEV1 was reduced below 75%. In the case of both FVC and FEV1 were reduced, PFT was classified as restrictive if FEY1/FVC was greater than 75%, and mixed if FEV1/FVC was reduced below 75%. We repeated the PFT and bronchoscopy for 68 ET patients who were proven by biopsy in the first month and sixth month after starting anti-tuberculosis chemotherapy, and studied the feature and change of PFT of the ET and the relation between PFT and the bronchoscopic finding, and obtained following results. Results: 1) Number of male patients was 12, and that of female patient was 56, and mean age was $35.4{\pm}17yr$.(17-74yr). Clinical symptom was in the order of cough(86.8%), dyspnea(63.2%), fever(17.6%) and hemoptysis (10.3%), and the wheezing and stridor were audible among the 40 patients(58.4%) in the physical examination. 2) Hemoglobin level was below 12g/dl among 25 patients (36.8%), and WBC level was above $10,000/mm^3$ among 9 patients(13.2%) and ESR was above 20 among 46 patients (67.6%) and AFB stain and culture were positive among 50 patients(73.5%). 3) The dominant roentgenographic finding of ET was fibronodular feature in 35 patients(51.5%), pneumonic feature in 14 patients (20.6%), collapse in 11 patients(16.2%), mass-like lesion in 3 patients(4.4%), cavitary lesion in 2 patients(2.9%), and normal in 3 patients(4.4%). 4) PFT feature at the time of diagnosis of ET was normal in 16 patients(23.5%), restrictive pattern in 32 patients (47%), obstructive in 4 patients(5.8%), and mixed in 14 patients(23.5%). So restrictive pattern was the dominate feature of ET. 5) The PFT feature was little correlated with the gross finding of bronchoscopy, but the change of PFT during treatment of ET showed relatively good correlation with the change of bronchoscopic finding. 6) FVC(2.30L vs. 2.61L) and FEV1(1.74L vs. 2.06L) increased significantly (p < 0.01), but FEV1/FVC(82% vs. 83%) and PEF(3.45L/sec vs. 3.95L/sec) did not change significantly after 1 month of treatment (p > 0.01), and there was no significant change among all parameters during first and sixth month of treatment(p > 0.01). Conclusion : PFT may be useful in the diagnosis and treatment follow up of ET but further study would be needed to confirm it.

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Prognostic Value of TNM Staging in Small Cell Lung Cancer (소세포폐암의 TNM 병기에 따른 예후)

  • Park, Jae-Yong;Kim, Kwan-Young;Chae, Sang-Cheol;Kim, Jeong-Seok;Kim, Kwon-Yeop;Park, Ki-Su;Cha, Seung-Ik;Kim, Chang-Ho;Kam, Sin;Jung, Tae-Hoon
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.322-332
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    • 1998
  • Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.

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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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Studies on the Directivity of Gokjungkyeong(Kyung Overlapped with Gok) which was specified in Byeokgye-ri, Yangpyeong-gun and the Hwaseo Lee, Hang-ro's Management in Byeokwon Garden (양평 벽계리에 설정된 곡중경(曲中景)의 지향성과 화서(華西) 이항로(李恒老)의 벽원(蘗園) 경영)

  • Jung, Woo-Jin;Rho, Jae-Hyun
    • Journal of the Korean Institute of Traditional Landscape Architecture
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    • v.34 no.3
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    • pp.78-97
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    • 2016
  • The objectives of this study are to examine the context of the establishment of Suhoe Gugok, Byeokgye Gugok Vally, and Nosan Palkyung, which have been established in Seojong-myeon of Yangpyeong-gun, by literature review and site investigations, and to determine the sceneries of Byeokgye scenic site as enjoyed and managed during the period of Hwaseo Lee, Hang-ro(華西 李恒老). The results of the study are as follows. First, Byeokgye Gugok Vally(黃蘗九曲) and Nosan Palkyung(蘆山八景), which have been established after the period of Hwaseo and theorized to have been established around key scenic areas associated with Hwaseo's activities, the analysis results showed that they were collecting sceneries of modern times. The extensive overlap between Byeokgye Gugok Vally and concentrated scenic elements of Suhoe Gugok(水回九曲), and the artificial configuration from the end point of Suhoe Gugok to the beginning point of Nosan Palkyung, reveal the pattern of space conflict and hegemony between Byeokgyes of Suip-ri and Nomun-ri. This is likely to be caused by the conflict between the historicity of the group that enjoyed Byeokgye prior to Hwaso's period and the strong territoriality of the space filled with the image of Hwaseo. Second, Byeokgye Gugok Vally was the secondary spatial system created by selecting the most scenic sites in Suip-ri while expanding the area of Nosan Palkyung. After establishment of Byeokgye Gugok Vally, the spatial identity of the entire Byeokgyecheon area was effectively established. This was a "Hwaseo-oriented" move, including the complete exclusion of the scenic sites from the pre-Hwaseo period such as Cheongseo Gujang and Suhoe Gugok's Letters Carved on the Rock. Consequently, the entire Byeokgyecheon area was reorganized into a cultural scenic site with Heoseo's influence. Third, Fifth, creations of Gugok(九曲) to determine the lineage of the Hwaseo School from Juja(朱子) to Yulgok(栗谷) to Uam(尤庵) to Hwaseo is likely to be an opportunity of birth and external motivation of the establishment of new Gugok Palkyung. In other words, Nosan Palkyung and Byeokgye Gugok Vally are likely to have been created as a reaction to the change of the center of the Hwaseo School to Okgyedong, and with strategic orientation based on the motivation and needs such as creation of the connecting space between Mui Gugok, Gosan Gugok, and Okgye Gugok, and the elevation of Hwaseo's status. Fourth, from the Hwaseo's Li-centric point of view, all revered sites in Beokwon(蘗園) that he managed existed as the spatial creative work to experience the existence of "li" through the objects in the landscape and the boundary of the spirit of emptiness of the aesthetic self. This clearly shows how Byeokgye Gugok Vally or Nosan Palkyung must be defined, and furthermore, appreciated and approached, prior to discussing it as the space associated with Hwaseo. Fifth, Nosan Palkyung was composed of cultural scenic landscapes of Gokjungkyung(曲中景) with eight scenic sites where Hwaseo gave his teachings and spend time around, in the Byeokgye of Nomun-ri area of Byeokgye Gugok Vally. The sceneries is, however, collected by depending on Hwaseo's Letters Carved on the Rock and poetry. Consequently, an inner exuberance of Nosan Palkyung is satisfied beside Byeokgye Gugok Vally, but its conceptual adequacy leaves room for questions.