기존의 치료에 반응하지 않는 다발성 간전이 대장암 환자에서 방사선조사와 병합한 수지상세포 면역치료의 1, 2상 임상시험

최영민(Youngmin Choi),이형식(Hyung-Sik Lee),권혁찬(Hyuk-Chan Kwon),한상영(Sang-Young Han),최종철(Jong-Cheol Choi),정주섭(Ju-Seop Chung),김창원(Chang-Won Kim),김동원(Dong-Won Kim),강치덕(Chi-Duk Kang) 대한방사선종양학회 2008 Radiation Oncology Journal Vol.26 No.2

목 적: 기존치료에 반응하지 않는 다발성 간전이를 동반한 대장암 환자에서 방사선치료와 병합한 수지상세포 면역 치료의 독성과 반응도를 조사하였다. 대상 및 방법: 2004년 5월부터 2006년 11월까지 다발성 간전이가 동반된 대장암 환자들 중에서 항암화학 요법에 반응하지 않은 환자 중 지원자를 대상으로 연구를 시행하였다. 본 임상 시험에 대하여 동아대학교병원과 부산대학교병원의 임상윤리심의위원회의 허가를 획득하였고, 동의서에 서명한 환자들을 임상 시험의 대상으로 등록하였다. 환자의 말초 혈액으로부터 수지상세포를 추출하여 배양하였다. 임상시험 일자에 맞추어서 6×106개의 수지상세포를 바이알(0.5 ml)에 넣어서 디씨백/아이알 주사를 만들었다. 수지상세포 면역치료는 2주 간격으로 간전이암조직에 3회 주사하고, 5주에 내약성 평가를 하였다. 내약성 평가를 통과한 환자에게는 8주에 4번째 수지상세포 면 역치료를 하였다. 병의 악화가 없거나 임상시험에 대한 환자의 동의 철회가 없는 경우에는 5, 6번째 수지상세포면역치료를 각각 12, 16주에 시행하였다. 방사선치료는 수지상세포 면역치료를 주사할 간전이암 부위에 주사하기 전일 및 당일에 4 Gy씩을 조사하였다. 내약성 평가는 3×106개의 수지상세포로부터 시작하여, 12×106개의 수지상세포까지 시행하였다. 내약성 평가의 최대 내성 용량으로 추가 임상시험을 하였다. 수지상세포 면역치료 주사를 맞은 모든 환자들에서 안전성 평가를 하였다. 4회 이상 주사를 맞은 환자들을 대상으로 10주에 치료 반응을 평가하여 유효성을 조사하였다. 결 과: 임상시험에 등록한 24명 중 22명에서 수지상세포 면역치료를 시행하였다. 내성약 평가에는 14명이 등록하여 11명에서 평가를 완료하였다. 시험약과의 관련성이 있을 것으로 생각되는 grade 3 이상의 약물반응으로 인한 이상반응은 없었다. 12×106개의 수지상세포를 내성용량으로 확인하였고, 내성용량인 12×106개 수지상세포 면역치료를 이용하여 8명에서 추가로 시험을 하였다. 치료에 대한 환자들의 내성은 양호하였고, grade 3을 초과하는 치명적인 부작용은 발생되지 않았다. 4회 이상의 수지상세포 면역치료 주사를 받은 환자가 17명이었고, 이 중의15명에서는 종양의 반응도 평가가 이루어졌다. 본 연구의 목적은 안전성 평가이지만, 면역치료의 유효성 평가를 위해, 방사선치료와 수지상세포 면역치료 주사가 시행된 부위 외의 간전이암에서 반응도를 조사 하였다. 면역치료의 반응은 평가가 이루어진 환자들에서 정지성 병변이 4명, 진행성 병변이 11명 이었다. 결 론: 수지상세포 면역치료와 병행한 방사선치료는 이론적으로 국소 및 전신 제어에 상승효과가 있을 것으로 기대할 수 있다. 하지만 기존 치료에 반응하지 않는 매우 진행된 직장암 환자들을 대상으로 한 본 연구에서는 방사선 치료와 병합한 수지상세포 면역치료로 인한 심각한 부작용의 발생은 없었다는 결과와 4예에서의 정지성 병변의 관찰을 보고한다. 수지상세포의 최대 투여 용량, 적절한 투여 방법, 적절한 방사선의 양, 방사선과 수지상 세포의적절한 투여 간격 등에 관한 추가 연구를 통하여, 향후 제 2상, 3상 시험으로서의 진행 여부에 긍정적인 결과를얻을 수 있다고 판단한다. Purpose: To assess the toxicity and tumor response induced by DCVac/IRⓇ dendritic cell (DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of 6×106 DCs were packed into a vial (DCVac/IRⓇ, 0.5 ml) at the convenience of each patient’s schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses (3×106 to 12×106 DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The 12×106 DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The DCVac/IRⓇ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials

치아회분과 석고혼합제재 매식후 Digital Subtraction Radiography에 의한 골량 변화의 평가

김재덕,최의환,김광원,조영곤,김동기 大韓口腔顎顔面 放射線學會 1999 Imaging Science in Dentistry Vol.29 No.2

Purpose : To assess the methods for the clinical evaluation of the longitudinal bone changes after implantation of tooth ash-plaster mixture into the defect area of human jaws. Materials and methods : Tooth ash-plaster mixtures were implanted into the defects of 8 human jaws. 48 intraoral radiograms taken with copper step wedge as reference at soon, 1st, 2nd, 4th, and 6th week after implantation on mixture were used. X-ray raking was standardized by using Rinn XCP device customized directly to the individual dentition with resin bite block. The images inputted by Quick scanner were digitized and analyzed by NIH image program. Cu-equivalent values were measured at the implanted sites from the periodic digital images. Analysis was performed by the bidirectional subtraction with color enhancement and the surface plot of resliced contiguous image. The obtained results by the two methods were compared with Cu-equivalent value changes. Results : The average determination coefficient of Cu-equivalent equations was 0.9988 and the coefficient of variation of measured Cu values ranged from 0.08∼0.10. The coefficient of variation of Cu-equivalent values measured at the areas of the mixture and the bone by the conversion equation ranged from 0.06∼0.09. The analyzed results by the bidirectional subtraction with color enhancement were coincident with the changes of Cu-equivalent values. The surface plot of the resliced contiguous image showed the three dimensional view of the longtudinal bone changes on one image and also coincident with Cu-equivalent value changes after implantation. Conclusion : The bidirectional subtraction with color enhancement and the surface plot of the resliced contiguous image was very effective and reasonable to analyze clinically and qualitatively the longitudinal bone change. These methods are expected to be applicable to the non-destructive test in other fields.(J Korean Oral Maxillofac Radiol 1999;29:423-434)

스포츠심리학의 의미와 역할기대에 관한 현장의 관점

장덕선,이동재 群山大學校 1995 論文集 Vol.22 No.-

본 연구는 한국의 스포츠인들이 정의하는 스포츠 심리학의 역할 기대에 대한 조사를 하기 위해 코치와 선수를 대상으로 개방형 질문지를 사용하여 조사하였다. 스포츠 심리학의 의미는 선수 6개 코치 5개의 범주로 나누어 졌으며, 역할은 선수 9개, 코치 5개 범주로 나누어 분석되었다. 코치나 선수의 스포츠 심리학에 정의는 공통적인 요인이 발견되었음을 알 수 있다. 이들은 스포츠 심리학을 경기력 향상, 긴장과 불안 등 심리적 문제상태를 파악하여 대처할 수 있는 방안을 제시해 주는 학문이라고 대체로 정의하고 있는 것이다. 한국에서의 스포츠인들이 스포츠심리학이 해주기를 바라는 역할에 대한 공통점은 긴장해소와 조절방법, 자신감 강화, 안정과 편안함 등으로 나타났다. 그 외에 선수들은 심리훈련을 할 수 있는 방법을 제시해 주는 것과 심리상태를 파악하는 것, 연구 조사 결과의 현장적용을 해줄 것을 바라고 있으며, 코치들은 경기력을 향상시키는 것이 바로 스포츠 심리학의 역할로 제시하였다. 스포츠 심리학의 필요성은 스포츠 심리학의 중요성, 스포츠 심리학자의 필요성, 심리기술 훈련의 필요성, 경기력의 결정요인으로 정신적/신체적 비중을 살펴본 결과 80% 이상의 지지율을 보여주고 있다. 이러한 결과를 볼 때 선수와 코치는 스포츠 심리학의 현장적용과 스포츠 심리학자가 절실히 요구됨을 알 수 있다.

단일 사례 사격선수의 집중루틴 훈련의 효과

장덕선,김병준,구해모,신동성 한국스포츠심리학회 2004 한국스포츠심리학회지 Vol.15 No.1

본 연구는 소총사수 P의 집중력 훈련에 관한 것이다. P 선수는 만 21세의 남자선수로서 운동경력은 8년이며, 10M 공기소총이 주종목이다. 집중력훈련은 단일사례실험 중 가장 단순한 시계열 설계인 AB 설계를 적용하였다. A단계에서 집중력, 주의력 질문지가 1-2주 간격으로 4회 반복측정 되었으며, B단계는 7월-10월까지 집중력 훈련이 진행되는 기간으로 개별면담과 질문지 측정, 수행평가를 위한 시합기록이 수집되었다. 집중력 질문지는 1개월에 1회 측정되었고, 주의력 검사지는 집중훈련 전과 후에 각각 한차례 시행되었다. 집중 루틴은 선수의 개인적 습관과 장점을 최대한 존중하여 훈련과 최고시합 때 습관적으로 하는 행동과 생각을 포함시켜 상당한 시합 부담 상황에서도 최고시합때의 행동과 생각의 흐름을 유지할 수 있도록 강력한 의미를 가진 행위와 키워드로 구성하였다. 완성된 루틴 프로그램은 4개월 훈련 후 집중력과 주의력, 수행평가를 실시하였다. 훈련결과 루틴 훈련은 집중조절 능력을 향상시켰으며, 주의유형은 긍정적인 형태는 증가하고 부정적 형태는 감소하였다. 수행 기록은 루틴 훈련 과정에서 출전한 5회 시합에서 모두 결선에 진출하므로서 수행향상에도 기여한 것으로 밝혀졌다. This study is about a concentration training of a rifle Marksman, P, The male Marksman P is 21 years old, and has played a rifle for eight years. His major is 10M air rifle. We apply AB design which is the simplest time-series design among single case experiments. In A step, we have applied the questionnaire for examining the ability of concentration and attentiveness for four times at an interval of 1 or 2 weeks. In B step, we developed a programme for improving the concentration training and applied it to the player. During the training in B step, which had continued from July to October, we have collected individual interviews, survey, records of games in order to evaluate achievement. The questionnaire for concentration has been served once a month, and the TAIS has been operated once each time before and after the concentration training. The concentration routine is directed to the way of considering the athlete's personal habit and merit most. Therefore, the concentration routine includes the essential matters of habitual acting and thought in ordinary training and in the final match. The concentration routine is consist of powerful meaningful movement and keyword in order to maintain the stream of movement and thought at the final match even though the Marksman is under the heavy pressure of the game. The practice evaluation has been done by a completed routine programme after the four-month-training. After examining the result of the evaluation, the concentration training improves the ability of controlling concentration. The positive type of TAIS is increased and the negative type is decreased. About the record of achievement, the player had advanced to the final once before the training, on the other hand, advanced to all the five final matches after the training. Consequently, it is discovered that the concentration training contributes to the achievement.

DSC법에 대한 제지슬럿지와 스티렌 공중합체의 열분해속도

설수덕,왕석주,이동호 동아대학교 환경문제연구소 1997 硏究報告 Vol.20 No.2

The kinetics of thermal degradation on blend of the paper sludge and waste styrene copolymer, such as high density polystyrene(HDPA), low density polystyrene (LDPS), poly(styrene-co-acrylonitrile)(SAN), poly(acrylonitrile-butadiene-styrene)(ABS) were anaryzed using the thermal analysis, pyrolysis gas chromatography with the stream of nitrogen gas(30ml/min) and infra-red spectroscopy at isothermal temperature(200, 250, 300, 350℃). 1. The values of apparent activation energy evaluated by DTA method was consistent with eath other very well. 2. The maximum value of heat of decomposition evaluated by DSC method was 80% ABS and 20% paper sludge(11,120cal/g) 3. The thermal degradation of PS/sludge was considered to be carried out by the main chain scission and ABS/sludge, SAN/sludge were to be carried out by the randim chain scission over 300℃. The thermogravimetric trace curve agreed with the theoretical equation.GC

廢황산제일철로부터 Goethite의 산화침전반응에 관한 연구

설수덕,신동옥 동아대학교 환경문제연구소 1997 硏究報告 Vol.20 No.1

The influence of precipitants on the particle formation and growth of geothite by means of aerial oxidative precipitation from aqueous solution of ferrous sulfate with KOH, Ca(OH)₂, NaHCO₃, and H₂O₂ as a precipitants have been studided on the same oxidative precipitation condition. Submicron of needle-like geothite( a-FeOOH) particle was obtained from all kinds of alkaline precipitants KOH, Ca(OH)₂ and NaHCO₃. On the other hand, NaNO₃ and H₂O₂ were didn't not influence on the particle formation and growth. The kinetics of geothite particle formation and growth from aqueous solution of ferrous sulfate with KOH as a precipitant have been studied. The influence of air flow rate, reaction temperature and initial mole ratio, R_(o)=[Fe^(2+)]_(o)/[OH^(-)]_(o), on the kinetics of particle formation and growth are investigated by static pH experiment. The results show that the increase of air flow rate, reaction temperature and initial mole ratio increases the oxidation rate through the particle formation and growth. The activation energy of particle formation and growth is 11.71 KJ/mol and 16.16 KJ/mol and rate equation of particle formation and particle growth can be written as follows: <particle formation> - d[Fe^(2+)]/dt = 1.69×10 ₄ [P_(O₂)]^(0.56) [OH^(-)]^(1.71)exp(- 11.71/RT) <particle growth> - d[Fe^(2+)]/dt = 1.46×10 ₄ [P_(O₂)]^(0.66) [OH^(-)]^(2.19)exp(- 16.16/RT)

배드민턴경기시 심박수 변화에 의한 운동 강도와 에너지 소모

조동진,최덕묵 조선대학교 스포츠과학연구소 1995 스포츠科學硏究 Vol.7 No.-

The purpose of this study is to measure the amount of energy consumption and the degree of exercise strength in badmintion singles. The subjects of this study were 6 badminton players of "D" Chemistry in Incheon. We measured, calculated and reported the degree of exercise strength and the amount of the energy consumption in using the Nomogram of Astrands through the change of heart rate in badminton games and the work ability and VO2 with the change of Heart rate during exercise. The results are as follows: 1. In singles, the degree of absolute exercise strength was 5 minutes and 17 seconds (24.8%) over 171 beats/min., 6 minutes and 1 second (32 %) in 167-170 beats/min., 4 minutes and 25 seconds (20.4%) in 151-160 beats/min., 3 minutes and 20 seconds (15.3%) in 141-150 beats/min., 1 minute and 20 seconds (3.1%) in 131-140 beats/min., 35 seconds (0.9%) in 121-130 beats/min., 28 seconds (1.7%) in 111-120 beats/min., 28 seconds (1.7%) in 101-110 beats/min., and 40 seconds (2.7%) below 100 beats/min.. The average was 131(± 7.4) beats/min.. 2. In singles, the degree of relative exercise strengh was 8 minutes and 38 seconds (45.7%) in 81-90%HRmax., 5 minutes and 5 seconds (27%) in 71-80%HRmax., 3 minutes and 42 seconds (18.3%) in 61-70% HRmax., 1 minute and 30 seconds (5.5%) in 41-50%HRmax.. The average was 76.1 (±5.1%)HRmax.. 3. in singles, the amount of energy consumption of players was 292.8 Kcal. (game time : 18 minutes) 4. Regression on relative exercise intensity between Total Time and Average HR showed Y=150.42+6.707317×10-3 Time (R2 = 0.05, t = 0.48, SEE = 7.55). Regression on relative exercise intensity between Total Time and % Average HR showed Y=71.17+4.593496×10-3 Time (R2 = 0.04, t = 0.40, SEE = 6.16). 5. Regression on VO2 max and Total energy consumption showed Y=10239.63022+598.25266·TEC (R2 = 0.10344, t = 0.76, SEE = 1051.10241). 6. Regression on VO2 max and PWC170 showed Y=23.86302+59.825027·PWC (R2 = 0.10344, t = 0.760, SEE = 105.11024).

α-셀로로오즈와 AN의 Graft공중합체의 열분해 특성

설수덕,이동호 동아대학교 공과대학부설 생산기술연구소 1998 生産技術硏究所硏究論文集 Vol.3 No.2

Thermal decomposition mechanism and kinectics of α-cellulose on Grafting of Acrylonitrile onto partially α-Cellulose were obtained using thermal analysis, pyrolysis gas chromatography and fourier transform-infrared spectrometer method under dynamic and isothermal condition in the stream of nitrogen. 1. the values of activation energy evaluated by Friedman's and Ozawa's method were consistent with each other very well. it was possible to determine the thermal stability of samples from these results. 2. the optimum thermal stabilization in Acrylonitrile-grafted α-cellulose was obtained in composition of 5∼10% AN.

PMMA/TCNQ, PMMA/PCPA blend의 氣體透過와 熱的特性

설수덕,김동건 東亞大學校 大學院 1990 大學院論文集 Vol.15 No.-

The thermal degradation of poly methyl methacrylate (PMMA), tetra cyano quino dimethane (TCNQ), and poly chloro phenyl acetylene (PCPA) mixtures were carried out thermogravimetry and gas permeability in the stream of nitrogen from 25∼500℃, and 70∼13℃ respectively. The value of activation energies of thermal degradation determined by thermogravimetry and gas permeability method were 25∼59 K cal/mol and 3.2∼12.0 K cal/mol, respectively. The values of decomposition activation energies of PMMA/TCNQ=97/3 and PMMA/PCPA=95/5 miture were presented high thermal stabilization. The value of diffusion activation energies were decreased with increaing TCNQ and PCPA.

단일전극을 가진 마이크로 가스센서의 제작 및 특성

송갑득,박영일,이상문,이윤수,최낙진,주병수,서무교,허증수,이덕동 한국센서학회 2002 센서학회지 Vol.11 No.6

센서의 안정도와 감도를 개선시킬 수 있는 단일전극을 가진 열선형 마이크로 가스센서를 제작하였다. 일반적으로, 금속산화물 반도체를 이용한 가스센서는 히터전극과 감지전극의 두 개의 전극을 가지고 있다. 제작된 센서는 히터전극위에 감지물질을 형성하여 단일 전극을 가지는 구조를 가지고 있다. 히터와 감지전극으로 사용되는 Pt는 glass 기판위에 스퍼터링법으로 형성하였으며, SnO_2 감지물질은 제작된 Pt 전극위에 열증착시켜 형성하였다. SnO_2막은 lift-off 공정을 이용해서 패턴을 형성하고 1시간 동안 산소분위기에서 열산화하였다. 제작된 소자의 크기는 1.92x.1 mm^2 이다. CO 가스에 대한 감지특성을 조사한 결과 1,000 ppm에 대해 100 mV의 출력변화를 나타내었으며, 넓은 농도범위(0 ~ 10,000 ppm에서 선형적인 전압출력을 나타내었다. 또한 가스 반응 전과 반응 후의 전압출력을 비교해 볼 때, 1 % 이내의 편차를 나타내는 우수한 회복성을 나타내었다. Micro gas sensor with single electrode was proposed for improving stability and sensitivity, Generally, metal oxide gas sensors have two electrodes for heating and sensing. This fabricated new type sensor have only a single electrode by forming a sensing material onto heating electrode. Pt as a heating and sensing electrode was sputtered on glass and a SnO_2 sensing material was thermally evaporated on Pt electrode. SnO_2 was patterned by lift-off process and then thermally oxidized in O_2 condition for 1 hr., 600 ℃. The size fabricated sensor was 1.9 x 2.1 mm^2. As a result of CO gas sensing characteristics, this sensor showed 100 mV change for 1,000 ppm and linearlity for wide range(0 ~ 10,000 ppm) of gas concentrations. And the sensor shows a good recovery characteristics of 1 % deviation compared to initial resistance.