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Evaluations of Spectral Analysis of in vitro 2D-COSY and 2D-NOESY on Human Brain Metabolites (인체 뇌 대사물질에서의 In vitro 2D-COSY와 2D-NOESY 스펙트럼 분석 평가)

  • Choe, Bo-Young;Woo, Dong-Cheol;Kim, Sang-Young;Choi, Chi-Bong;Lee, Sung-Im;Kim, Eun-Hee;Hong, Kwan-Soo;Jeon, Young-Ho;Cheong, Chae-Joon;Kim, Sang-Soo;Lim, Hyang-Sook
    • Investigative Magnetic Resonance Imaging
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    • v.12 no.1
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    • pp.8-19
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    • 2008
  • Purpose : To investigate the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar nuclear Overhauser effect/enhancement (NOE) interaction through 2D- correlation spectroscopy (COSY) and 2D- NOE spectroscopy (NOESY) techniques. Materials and Methods : All 2D experiments were performed on Bruker Avance 500 (11.8 T) with the zshield gradient triple resonance cryoprobe at 298 K. Human brain metabolites were prepared with 10% $D_2O$. Two-dimensional spectra with 2048 data points contains 320 free induction decay (FID) averaging. Repetition delay was 2 sec. The Top Spin 2.0 software was used for post-processing. Total 7 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), lutamine (Gln), glutamate (Glu), myo-inositol (Ins), and lactate (Lac) were included for major target metabolites. Results : Symmetrical 2D-COSY and 2D-NOESY pectra were successfully acquired: COSY cross peaks were observed in the only 1.0-4.5 ppm, however, NOESY cross peaks were observed in the 1.0-4.5 ppm and 7.9 ppm. From the result of the 2-D COSY data, cross peaks between the methyl protons ($CH_3$(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methylene protons (CH2(3,$H{\alpha}$)) at 2.50ppm and methylene protons ($CH_2$,(3,$H_B$)) at 2.70 ppm were observed in NAA. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. From the result of 2-D NOESY data, cross peaks between the NH proton at 8.00 ppm and methyl protons ($CH_3$) were observed in NAA. Cross peaks between the methyl protons ($CH_3$(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methyl protons (CH3) at 3.03 ppm and methylene protons (CH2) at 3.93 ppm were observed in Cr. Cross peaks between the methylene protons ($CH_2$(3)) at 2.11 ppm and methylene protons ($CH_2$(4)) at 2.35 ppm, and between the methylene protons($CH_2$ (3)) at 2.11 ppm and methine proton (CH(2)) at 3.76 ppm were observed in Glu. Cross peaks between the methylene protons (CH2 (3)) at 2.14 ppm and methine proton (CH(2)) at 3.79 ppm were observed in Gln. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. Conclusion : The present study demonstrated that in vitro 2D-COSY and NOESY represented the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar NOE interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2DCOSY study.

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Comparison of Nutrient Intakes of Korean Elderly People Living in Rural Area Between 24-hour Recall and Food Frequency Method (24시간회상법과 식품섭취빈도조사법을 이용한 농촌지역 노인의 영양소 섭취수준 비교)

  • Cho, Young-Eun;Lee, Soo-Lim;Cho, Eun-Hyun;Lomeda, Ria-Ann L;Kwak, Eun-Hee;Kim, Yang-Ha;Kwun, In-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.6
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    • pp.698-707
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    • 2006
  • Precise and correct assessment of nutrient intake using appropriate dietary intake method is necessary to improve the nutritional status of the target people group. It is more likely so in elderly people since their dietary habits and inadequate nutrient intakes are of special concern even worse in rural areas. Two popular methods of gathering dietary intake are 24-hour recall and food frequency method (or food frequency questionnaire). In the present study, we conducted both 24-hour recall and food frequency method on 120 rural elderly people $(aged\;65{\sim}74\;years)$, 62 male and 58 female. The dietary intakes were analyzed and the correlation of the dietary intake between 24-hour recall and food frequency method to determine the reliability between two methods. Also each nutrient intake was compared to recommended dietary allowance (RDA) or nutrient reference value (NRV) as appropriate. Even correlation did not show significance between the two methods except for dietary fiber intake (0.65 at p<0.01) and energy-yielding nutrients which mostly showed similar results with nutrient intake level. These support the possible reliability between 24-hours record and food frequency method that is also shown on the cases of most mineral and vitamin intakes. Thus, the food frequency method used in this study for the assessment of nutrient intakes of the elderly people would be reliable for the assessment of the nutrient intake along with the 24-hour recall. Also, the present study results suggested that rural female elderly people would be under optimal nutriture status due to the lower food intake measured by 24-hour recall. The optimal food frequency method would be considered to be developed for the precise nutrient assessment.

The Changing Aspects of North Korea's Terror Crimes and Countermeasures : Focused on Power Conflict of High Ranking Officials after Kim Jong-IL Era (북한 테러범죄의 변화양상에 따른 대응방안 -김정일 정권 이후 고위층 권력 갈등을 중심으로)

  • Byoun, Chan-Ho;Kim, Eun-Jung
    • Korean Security Journal
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    • no.39
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    • pp.185-215
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    • 2014
  • Since North Korea has used terror crime as a means of unification under communism against South Korea, South Korea has been much damaged until now. And the occurrence possibility of terror crime by North Korean authority is now higher than any other time. The North Korean terror crimes of Kim Il Sung era had been committed by the dictator's instruction with the object of securing governing fund. However, looking at the terror crimes committed for decades during Kim Jung Il authority, it is revealed that these terror crimes are expressed as a criminal behavior because of the conflict to accomplish the power and economic advantage non powerful groups target. This study focused on the power conflict in various causes of terror crimes by applying George B. Vold(1958)'s theory which explained power conflict between groups became a factor of crime, and found the aspect by ages of terror crime behavior by North Korean authority and responding plan to future North Korean terror crime. North Korean authority high-ranking officials were the Labor Party focusing on Juche Idea for decades in Kim Il Sung time. Afterwards, high-ranking officials were formed focusing on military authorities following Military First Policy at the beginning of Kim Jung Il authority, rapid power change has been done for recent 10 years. To arrange the aspect by times of terror crime following this power change, alienated party executives following the support of positive military first authority by Kim Jung Il after 1995 could not object to forcible terror crime behavior of military authority, and 1st, 2nd Yeongpyeong maritime war which happened this time was propelled by military first authority to show the power of military authority. After 2006, conservative party union enforced censorship and inspection on the trade business and foreign currency-earning of military authority while executing drastic purge. The shooting on Keumkangsan tourists that happened this time was a forcible terror crime by military authority following the pressure of conservative party. After October, 2008, first military reign union executed the launch of Gwanmyungsung No.2 long-range missile, second nuclear test, Daechung marine war, and Cheonanham attacking terror in order to highlight the importance and role of military authority. After September 2010, new reign union went through severe competition between new military authority and new mainstream and new military authority at this time executed highly professionalized terror crime such as cyber/electronic terror unlike past military authority. After July 2012, ICBM test launch, third nuclear test, cyber terror on Cheongwadae homepage of new mainstream association was the intention of Km Jung Eun to display his ability and check and adjust the power of party/military/cabinet/ public security organ, and he can attempt the unexpected terror crime in the future. North Korean terror crime has continued since 1980s when Kim Jung Il's power succession was carried out, and the power aspect by times has rapidly changed since 1994 when Kim Il Sung died and the terror crime became intense following the power combat between high-ranking officials and power conflict for right robbery. Now South Korea should install the specialized department which synthesizes and analyzes the information on North Korean high-ranking officials and reinforce the comprehensive information-collecting system through the protection and management of North Korean defectors and secret agents in order to determine the cause of North Korean terror crime and respond to it. And South Korea should participate positively in the international collaboration related to North Korean terror and make direct efforts to attract the international agreement to build the international cooperation for the response to North Korean terror crime. Also, we should try more to arrange the realistic countermeasure against North Korean cyber/electronic terror which was more diversified with the expertise terror escaping from existing forcible terror through enactment/revision of law related to cyber terror crime, organizing relevant institute and budget, training professional manpower, and technical development.

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Distortion of the Dose Profile in a Three-dimensional Moving Phantom to Simulate Tumor Motion during Image-guided Radiosurgery (방사선수술에서 종양 움직임을 재현시킨 움직이는 팬텀을 이용하여 선량 분포의 왜곡에 대한 연구)

  • Kim, Mi-Sook;Ha, Seong-Hwan;Lee, Dong-Han;Ji, Young-Hoon;Yoo, Seong-Yul;Cho, Chul-Koo;Yang, Kwang-Mo;Yoo, Hyung-Jun;Seo, Young-Seok;Park, Chan-Il;Kim, Il-Han;Ye, Seong-Jun;Park, Jae-Hong;Kim, Kum-Bae
    • Radiation Oncology Journal
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    • v.25 no.4
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    • pp.268-277
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    • 2007
  • Purpose: Respiratory motion is a considerable inhibiting factor for precise treatment with stereotactic radiosurgery using the CyberKnife (CK). In this study, we developed a moving phantom to simulate three-dimensional breathing movement and investigated the distortion of dose profiles between the use of a moving phantom and a static phantom. Materials and Methods: The phantom consisted of four pieces of polyethylene; two sheets of Gafchromic film were inserted for dosimetry. Treatment was planned to deliver 30 Gy to virtual tumors of 20, 30, 40, and 50 mm diameters using 104 beams and a single center mode. A specially designed robot produced three-dimensional motion in the right-left, anterior-posterior, and craniocaudal directions of 5, 10 and 20 mm, respectively. Using the optical density of the films as a function of dose, the dose profiles of both static and moving phantoms were measured. Results: The prescribed isodose to cover the virtual tumors on the static phantom were 80% for 20 mm, 84% for 30 mm, 83% for 40 mm and 80% for 50 mm tumors. However, to compensate for the respiratory motion, the minimum isodose levels to cover the moving target were 70% for the $30{\sim}50$ mm diameter tumors and 60% for a 20 mm tumor. For the 20 mm tumor, the gaps between the isodose curves for the static and moving phantoms were 3.2, 3.3, 3.5 and 1.1 mm for the cranial, caudal, right, and left direction, respectively. In the case of the 30 mm tumor, the gaps were 3.9, 4.2, 2.8, 0 mm, respectively. In the case of the 40 mm tumor, the gaps were 4.0, 4.8, 1.1, and 0 mm, respectively. In the case of the 50 mm diameter tumor, the gaps were 3.9, 3.9, 0 and 0 mm, respectively. Conclusion: For a tumor of a 20 mm diameter, the 80% isodose curve can be planned to cover the tumor; a 60% isodose curve will have to be chosen due to the tumor motion. The gap between these 80% and 60% curves is 5 mm. In tumors with diameters of 30, 40 and 50 mm, the whole tumor will be covered if an isodose curve of about 70% is selected, equivalent of placing a respiratory margin of below 5 mm. It was confirmed that during CK treatment for a moving tumor, the range of distortion produced by motion was less than the range of motion itself.

Effects of Formaldehyde/Urea Molar Ratio on Bonding Strength of Plywood and Properties of Sliver-PB and Strand-PB (F/U 몰비의 변이가 합판의 접착성과 Sliver-PB, Strand-PB의 물성에 미치는 영향)

  • Park, Heon;You, Young-Sam
    • Journal of the Korean Wood Science and Technology
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    • v.27 no.2
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    • pp.38-45
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    • 1999
  • This study was to figure out proper Formaldehyde/Urea molar ratio of UF resin with satisfactory bonding strength of plywood and properties of particleboard. The six kinds of UF resins were manufactured with F/U molar ratio 1.0, 1.2, 1.4, 1.6, 1.8, and 2.0. The boards were made of three kinds of raw materials : Veneer, Sliver-Particle and Strand-Particle. Manufacturing condition of plywood : amount of mixing resin was 150g/$m^2$. The fourty secs/mm simple-pressing schedule in the pressure 10kgf/$m^2$ was applied for 480mm${\times}$700mm board at the temperature of $110^{\circ}C$ in a hot press. Manufacturing condition of particleboard : Target density was 0.65g/$cm^2$. The stepwise 9 minutes- multi-pressing schedule in the maximum pressure 40kgf/$cm^2$, the minimum pressure 15kgf/$cm^2$ was applied for $480mm{\times}634mm{\times}12mm$ board at the temperature of $150^{\circ}C$ in a hot press. The results are as follows : I. In bonding strength, plywood which was made by F/U molar ratio 1.2 showed the highest value. Other molar ratio resin also gave the satisfied value of KS standard, 7.5kgf/$cm^2$. 2. In internal bond strength of particleboard, Sliver-Particleboard(SLPB) and Strand-Particleboard(STPB) varied respectively from 5.9kgf/$cm^2$ to 4.8kgf/$cm^2$, from 6.7kgf/$cm^2$ to 5.4kgf/$cm^2$. SLPB with F/U=1.2 and STPB with F/U=1.6 had higher IB value. Also, both SLPB and STPB showed lower IB value in F/U molar ratio 2.0 and 1.0. 3. SLPB and STPB with six kinds of UF resin respectively satisfied bending strength of KS standard 150 Type(130kgf/$cm^2$) and 200 Type(180kgf/$cm^2$). Bending strength data for both of SLPB and STPB showed little or no loss from F/U=1.8 to F/U=1.2. Also, STPB was approximately two times higher than that of SLPB. Therefore, the raw material's shape had more effect on bending strength than the FlU molar ratio. 4. F/U=1.6 and 1.4 showed the lower thickness swelling in SLPB and STPB. All of STPBs satisfied thickness swelling of KS standard, under 12%.

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Rectal Bleeding and Its Management after Irradiation for Cervix Cancer (자궁경부암 환자에서 방사선치료 후에 발생한 직장출혈과 치료)

  • Chun Mison;Kang Seunghee;Kil Hoon-Jong;Oh Young-Taek;Sohn Jeong-Hye;Jung Hye-Young;Ryu Hee Suk;Lee Kwang-Jae
    • Radiation Oncology Journal
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    • v.20 no.4
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    • pp.343-352
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    • 2002
  • Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.

Air Cavity Effects on the Absorbed Dose for 4-, 6- and 10-MV X-ray Beams : Larynx Model (4-, 6-, 10-MV X-선원에서 공기동이 흡수선량에 미치는 효과 : 후두모형)

  • Kim Chang-Seon;Yang Dae-Sik;Kim Chul-Yong;Choi Myung-Sun
    • Radiation Oncology Journal
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    • v.15 no.4
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    • pp.393-402
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    • 1997
  • Purpose : When an x-ray beam of small field size is irradiated to target area containing an air cavity, such as larynx, the underdosing effect is observed in the region near the interfaces of air and soft tissue. With a larynx model, air cavity embedded in tissue-equivalent material, this study is intonded for examining Parameters, such as beam quality, field size, and cavity size, to affect the dose distribution near the air cavity. Materials and Methods : Three x-rar beams, 4-, 6- and 10-MV, were employed to Perform a measurement using a 2cm $(width){\times}L$ (length in cm, one side of x-ray field used 2cm (height) air cavity in the simulated larynx. A thin window parallel-plate chamber connected to an electrometer was used for a dosimetry system. A ratio of the dose at various distances from the cavity-tissue interface to the dose at the same points in a homogeneous Phantom (ebservedlexpected ratio, O/E) normalized buildup curves, and ratio of distal surface dose to dose at the maximum buildup depth were examined for various field sizes. Measurement for cavity size effect was performed by varying the height (Z) of the air cavity with the width kept constant for several field sizes. Results : No underdosing effect for 4-MV beam for fields larger than $5cm\times5cm$ was found For both 6- and 10-MV beams, the underdosing portion of the larynx at the distal surface was seen to occur for small fields, $4cm\times4cm\;and\;5cm\times5cm$. The underdosed tissue was increased in its volume with beam energy even for similar surface doses. The relative distal surface dose to maximum dose was changed to 0.99 from 0.95, 0.92, and 0.91 for 4-, 6-, and 10-MV, respectively, with increasing field size, $4cm\times4cm\;to\;8cm\times8cm$, For 6- and 10-MV beams, the dose at the surface of the cavity is measured less than the predicted by about two and three percent. respectively. but decrease was found for 4-MV beam for $5cm\times5cm$ field. For the $4cm\timesL\timesZ$ (height in cm). varying depth from 0.0 to 4.8cm, cavity, O/E> 1.0 was observed regardless of the cavity size for any field larger than about $8cm\times8cm$. Conclusion : The magnitude of underdosing depends on beam energy, field size. and cavity size for the larynx model. Based on the result of the study. caution must be used when a small field of a high quality x-ray beam is irradiated to regions including air cavities. and especially the region where the tumor extends to the surface. Low quality beam. such as. 4-MV x-ray, and larger fields can be used preferably to reduce the risk of underdosing, local failure. In the case of high quality beams such as 6- and 10-MV x-rays, however. an additional boost field is recommended to add for the compensation of the underdosing region when a typically used treatment field. $8cm\times8cm$, is employed.

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Comparison of Virtual Wedge versus Physical Wedge Affecting on Dose Distribution of Treated Breast and Adjacent Normal Tissue for Tangential Breast Irradiation (유방암의 방사선치료에서 Virtual Wedge와 Physical Wedge사용에 따른 유방선량 및 주변조직선량의 차이)

  • Kim Yeon-Sil;Kim Sung-Whan;Yoon Sel-Chul;Lee Jung-Seok;Son Seok-Hyun;Choi Ihl-Bong
    • Radiation Oncology Journal
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    • v.22 no.3
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    • pp.225-233
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    • 2004
  • Purpose: The Ideal breast irradiation method should provide an optimal dose distribution In the treated breast volume and a minimum scatter dose to the nearby normal tissue. Physical wedges have been used to Improve the dose distribution In the treated breast, but unfortunately Introduce an Increased scatter dose outside the treatment yield, pavllculariy to the contralateral breast. The typical physical wedge (FW) was compared with 4he virtual wedge (VW) to do)ermine the difference In the dose distribution affecting on the treated breast and the contralateral breast, lung, heart and surrounding perlpheral soft tissue. Methods and Materials: The data collected consisted of a measurement taken with solid water, a Humanoid Alderson Rando phantom and patients. The radiation doses at the ipsllateral breast and skin, contralateral breast and skin, surrounding peripheral soft tissue, and Ipsllateral lung and heart were compared using the physical wedge and virtual wedge and the radiation dose distribution and DVH of the treated breast were compared. The beam-on time of each treatment technique was also compared Furthermore, the doses at treated breast skin, contralateral breast skin and skin 1.5 cm away from 4he field margin were also measured using TLD in 7 patients of tangential breast Irradiation and compared the results with phantom measurements. Results: The virtual wedge showed a decreased peripheral dose than those of a typical physical wedge at 15$^{\circ}$, 30$^{\circ}$, 45$^{\circ}$, and 60$^{\circ}$. According to the TLD measurements with 15$^{\circ}$ and 30$^{\circ}$ virtual wedge, the Irradiation dose decreased by 1.35$\%$ and 2.55$\%$ In the contralateral breast and by 0.87$\%$ and 1.9$\%$ In the skin of the contralateral breast respectively. Furthermore, the Irradiation dose decreased by 2.7$\%$ and 6.0$\%$ in the Ipsllateral lung and by 0.96$\%$ and 2.5$\%$ in the heart. The VW fields had lower peripheral doses than those of the PW fields by 1.8$\%$ and 2.33$\%$. However the skin dose Increased by 2.4$\%$ and 4.58$\%$ In the Ipsliateral breast. VW fields, In general, use less monitor units than PW fields and shoriened beam-on time about half of PW. The DVH analysis showed that each delivery technique results In comparable dose distribution in treated breast. Conclusion: A modest dose reduction to the surrounding normal tissue and uniform target homogeneity were observed using the VW technique compare to the PW beam in tangential breast Irradiation The VW field is dosmetrically superlor to the PW beam and can be an efficient method for minimizing acute, late radiation morbidity and reduce 4he linear accelerator loading bV decreasing the radiation delivery time.

A Phase I/II Trial of $DCVac/IR^{(R)}$ Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases (기존의 치료에 반응하지 않는 다발성 간전이 대장암 환자에서 방사선조사와 병합한 수지상세포 면역치료의 1, 2상 임상시험)

  • Choi, Young-Min;Lee, Hyung-Sik;Kwon, Hyuk-Chan;Han, Sang-Young;Choi, Jong-Cheol;Chung, Ju-Seop;Kim, Chang-Won;Kim, Dong-Won;Kang, Chi-Duk
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.104-112
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    • 2008
  • Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ 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 $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 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($3{\times}10^6\;to\;12{\times}10^6$ 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 $12{\times}10^6$ 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 $DCVac/IR^{(R)}$ 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.

Tumor-suppressor Protein p53 Sensitizes Human Colorectal Carcinoma HCT116 Cells to 17α-estradiol-induced Apoptosis via Augmentation of Bak/Bax Activation (17α-Estradiol에 의한 인체 대장암 세포주 HCT116의 에폽토시스에 수반되는 Bak/Bax의 활성화에 미치는 종양억제단백질 p53의 강화효과)

  • Han, Cho Rong;Lee, Ji Young;Kim, Dongki;Kim, Hyo Young;Kim, Se Jin;Jang, Seokjoon;Kim, Yoon Hee;Jun, Do Youn;Kim, Young Ho
    • Journal of Life Science
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    • v.23 no.10
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    • pp.1230-1238
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    • 2013
  • The regulatory effect of the tumor-suppressor protein p53 on the apoptogenic activity of $17{\alpha}$-estradiol ($17{\alpha}-E_2$) was compared between HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells. When the HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells were treated with $2.5{\sim}10{\mu}M$ $17{\alpha}-E_2$ for 48 h or with $10{\mu}M$for various time periods, cytotoxicity and an apoptotic sub-$G_1$ peak were induced in the HCT116 ($p53^{+/+}$) cells in a dose- and time-dependent manner. However, the HCT116 ($p53^{-/-}$) cells were much less sensitive to the apoptotic effect of $17{\alpha}-E_2$. Although $17{\alpha}-E_2$ induced aberrant mitotic spindle organization and incomplete chromosome congregation at the equatorial plate, $G_2/M$ arrest was induced to a similar extent in both cell types. In addition, $17{\alpha}-E_2$-induced activation of Bak and Bax, ${\Delta}{\Psi}m$ loss, and PARP degradation were more dominant in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells. In accordance with enhancement of p53 phosphorylation (Ser-15) and p53 levels, p21 and Bax levels were elevated in the HCT116 ($p53^{+/+}$) cells treated with $17{\alpha}-E_2$. The HCT116 ($p53^{-/-}$) cells exhibited barely or undetectable levels of p21 and Bax, regardless of $17{\alpha}-E_2$ treatment. On the other hand, although the level of Bcl-2 was slightly lower in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells, it remained relatively constant after the $17{\alpha}-E_2$ treatment. Together, these results show that among the components of the $17{\alpha}-E_2$-induced apoptotic-signaling pathway, which proceeds through mitotic spindle defects causing mitotic arrest, subsequent activation of Bak and Bax and the mitochondria-dependent caspase cascade, leading to PARP degradation, $17{\alpha}-E_2$-induced activation of Bak and Bax is the upstream target of proapoptotic action of p53.