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Pharmacokinetic Study of CKD-602, A New Camptothecin Derivative: Distribution, Metabolism and Excretion (신규 캄토테신계 항암제 CKD-602의 약물동태: 분포, 대사 및 배설)

  • Lee, Ju-Mong;Lee, Jun-Hee;Kim, Joon-Kyum;Shin, Hee-Jong;Lee, Hyung-Ki;Lee, Sang-Joon;Hong, Chung-Il
    • YAKHAK HOEJI
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    • v.42 no.4
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    • pp.437-446
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    • 1998
  • The distribution, metabolism and excretion of CKD-602{20(S)-7-[2-(N-Isopropylamino)ethyl]camptothecin HCI), a new camptothecin derivative, were investigated in rats after a sing le administration of CKD-602. 1. The tissue levels of CKD-602 given to mice by the intravenous route at a dose of 20mg/kg were the highest in intestine, followed in descending order by kidney, liver, stomach,lung, heart, spleen and plasma. The concentrations of CKD-602 after 24hrs decreased to less than 2% of the peak level in most tissues except the skin. The urinary and fecal excretion of CKD-602 were 47.6% and 44.4% of the administered dose, respectively, with 0.7% remaining in the rinse. 2. After administration of CKD-602 at 10mg/kg in rats, metabolism of this compound was examined in plasma, urine, and feces. The plasma samples were collected for 24hr, urinary and fecal samples for 72hr. While any peak of CKD-602 in HPLC chromatograms was not detected from plasma and urine it was detected in feces (peaks, 9.8 min). However, additional peak area was about 0.5% of the peak area of parent CKD-602. Therefore, CKD-602 may be eliminated with the parent form and rarely metabolized in the body. 4. After I.v. administration of CKD-602 at 10mg/kg in rats, urinary and fecal excretions were examined for 72hrs post dose period. 87% of total urinary excretion of CKD-602 was excreted within 8hr after administration, 53%, and 32% of total fecal excreted amounts were determined in 0-24 hr and 24-48hr periods, respectively. The total excretion amounts of CKD-602 into urine and feces were 94% of the administered dose.

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Purification of a Protease Produced by Bacillus subtilis PCA 20-3 Isolated from Korean Traditional Meju (전통 메주로부터 분리한 Bacillus subtilis PCA 20-3 유래 Protease 의 정제)

  • Lim, Seong-Il;Yoo, Jin-Young
    • Korean Journal of Food Science and Technology
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    • v.31 no.6
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    • pp.1635-1641
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    • 1999
  • Bacillus subtilis PCA20-3 was isolated from meju and was found to produce a protease. The strain produced the maximum amount of enzyme in the medium containing soytone (0.2%), soluble starch (2%), $(NH_4)_2SO_4\;(0.1%),\;CaCl_2(0.1%),\;yeast\;extract\;(0.01%),\;K_2HPO_4\;(0.1%),\;and\;KH_2PO_4\;(0.1%)$. Protease was first concentrated by ammonium sulfate (80% saturation, w/v) precipitation of culture supernatant. Then the enzyme was purified by column chromatography using CM Sephadex C-50. The collected proteins were rechromatographed using Sephadex G-100 gel filtration column. The fraction with protease active from Sephadex G-100 gel chromatography was found to be pure when examined by SDS-polyacrylamide gel electrophoresis and YMC-pak reverse phase chromatography. Specific activity, yield and purity were 76 U/mg. 2.7%, and 7.6 fold, respectively. The molecular weight of the enzyme was estimated to be 31.5 kDa by SDS-PAGE. The number of amino acids calculated from molecular weight was evaluated about 321 residues. N-terminal sequence of the enzyme was $Val^1-Pro^2-Tyr^3-Gly^4-Val^5-Ser^6-Gln^7-Gly^8-Lys^9-Ala^{10}$.

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Effects of Different Exercise Training Mode on Exercise Specificity and Transability (트레이닝 형태의 차이가 운동 특이성(exercise specificity)과 전사효과(transability)에 미치는 영향)

  • Kim, Young-Il;Kwak, Yi-Sub
    • Journal of Life Science
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    • v.19 no.7
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    • pp.968-975
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    • 2009
  • The purpose of the present study was to examine effects of different exercise training modes (Aerobic Training, Resistance Training) on exercise specificity and transability. The tested subjects, composed of 10 healthy males without known family history or medical illnesses, were divided into two groups: Aerobic Training Group (ATG; n=5) and Resistance Training Group (RTG; n=5). An aerobic training program, based on maximum oxygen consumption rates taken during standard testing, was conducted in 60 minute sessions 3 times a week, and the Heart Rate Reserve (HRR) at 70% of maximum oxygen consumption rate was measured the using Polar. In the weight training program, based on repetition maximum rate (1-RM) taken during standard testing, the weight at 70% of such rates was measured during 60 minute sessions of 7 categories of exercise (Bench press, Leg press, Squat, Shoulder press, Arm curt Lat pull down, Triceps pull down), conducted 3 times a week. The data collected from this research were calculated to obtain average and differences compared to standards using an SPSS 11.0 statistics package. In conclusion, increase in V0$_{2max}$ and production of NO$_x$ (NO$_2$/NO$_3$), reduction of %fat, MAPwere shown effective in aerobic training and in different exercise tests, and aerobic testing within the aerobic training group (ATG) was shown to be more effective. In contrast, resistance training was shown to be more effective for the reduction of CK and LDH, and even in different tests, the resistance test within the resistance training group (RTG) showed to be more effective. Exercise specificity also significantly increased in both groups (ATG, RTG). but there was no significant difference in transability in both groups (ATG, RTG).

Synthesis of Binuclear Bismacrocyclic Iron(II) Complex by the Aerobic Oxidation of Iron(II) Complex of 1,4,8,11-Tetraazacyclotetradecane

  • Myunghyun Paik Suh;Gee-Yeon Kong;Il-Soon Kim
    • Bulletin of the Korean Chemical Society
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    • v.14 no.4
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    • pp.439-444
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    • 1993
  • The aerobic oxidation of the Fe(II) complex of 1,4,8,11-tetraazacyclotetradecane, [Fe(cyclam)$(CH_3CN)_2](ClO_4)_2$, in MeCN in the presence of a few drops of $HClO_4$ leads to low spin Fe(III) species [Fe(cyclam)$(CH_3CN)_2](ClO_4)_3$. The Fe(III) cyclam complex is further oxidized in the air in the presence of a trace of water to produce the deep green binuclear bismacrocyclic Fe(II) complex $[Fe_2(C_{20}H_{36}N_8)(CH_3CN)_4](ClO_4)_4{\cdot}2CH_3CN$. The Fe(II) ions of the complex are six-coordinated and the bismacrocyclic ligand is extensively unsaturated. $[Fe_2(C_{20}H_{36}N_8)(CH_3CN)_4](ClO_4)_4{\cdot}2CH_3CN$ crystallizes in the monoclinic space group $P2_1/n$ with a= 13.099 (1) ${\AA}$, b= 10.930 (1) ${\AA}$, c= 17.859 (1) ${\AA}$, ${\beta}$= 95.315 $(7)^{\circ}$, and Z= 2. The structure was solved by heavy atom methods and refined anisotropically to R values of R= 0.0633 and $R_w$= 0.0702 for 1819 observed reflections with F > $4{\sigma}$ (F) measured with Mo K${\alpha}$ radiation on a CAD-4 diffractometer. The two macrocyclic units are coupled through the bridgehead carbons of ${\beta}$-diimitie moieties by a double bond. The double bonds in each macrocycle unit are localized. The average bond distances of $Fe(II)-N_{imine}$, $Fe(II)-N_{amine}$, and $Fe(II)-N_{MeCN}$ are 1.890 (5), 2.001 (5), and 1.925 (6) ${\AA}$, respectively. The complex is diamagnetic, containing two low spin Fe(II) ions in the molecule. The complex shows extremely intense charge transfer band in the near infrared at 868 nm with ${\varepsilon}$= 25,000 $M^{-1}cm^{-1}$. The complex shows a one-electron oxidation wave at +0.83 volts and two one-electron reduction waves at -0.43 and-0.72 volts vs. Ag/AgCl reference electrode. The complex reacts with carbon monoxide in $MeNO_2$ to form carbonyl adducts, whose $v_{CO}$ value (2010 $cm^{-1}$) indicates the ${\pi}$-accepting property of the present bismacrocyclic ligand.

Influence of Gd0.1Ce0.9O2-δ Interlayer between La0.6Sr0.4Co0.2Fe0.8O3-δ Cathode and Sc-doped Zirconia Electrolyte on the Electrochemical Performance of Solid Oxide Fuel Cells (La0.6Sr0.4Co0.2Fe0.8O3-δ 공기극과 Sc이 도핑된 지르코니아 전해질 사이에 삽입한 Gd0.1Ce0.9O2-δ 중간층이 고체산화물 연료전지의 전기화학적 성능에 미치는 영향)

  • Lim, Jinhyuk;Jung, Hwa Young;Jung, Hun-Gi;Ji, Ho-Il;Lee, Jong-Ho
    • Ceramist
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    • v.21 no.4
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    • pp.378-387
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    • 2018
  • The optimal fabrication conditions for $Gd_{0.1}Ce_{0.9}O_{2-{\delta}}$(GDC) buffer layer and $La_{0.6}Sr_{0.4}Co_{0.2}Fe_{0.8}O_{3-{\delta}}$ (LSCF) cathode on 1mol% $CeO_2-10mol%\;Sc_2O_3$ stabilized $ZrO_2$ (CeScSZ) electrolyte were investigated for application of IT-SOFCs. GDC buffer layer was used in order to prevent undesired chemical reactions between LSCF and CeScSZ. These experiments were carried out with $5{\times}5cm^2$ anode supported unit cells to investigate the tendencies of electrochemical performance, Microstructure development and interface reaction between LSCF/GDC/CeScSZ along with the variations of GDC buffer layer thickness, sintering temperatures of GDC and LSCF were checked, respectively. Electrochemical performance was analyzed by DC current-voltage measurement and AC impedance spectroscopy. Microstructure and interface reaction were investigated by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Although the interfacial reaction between these materials could not be perfectly inhibited, We found that the cell, in which $6{\mu}m$ GDC interlayer sintered at $1200^{\circ}C$ and LSCF sintered at $1000^{\circ}C$ were applied, showed good interfacial adhesions and effective suppression of Sr, thereby resulting in fairly good performance with power density of $0.71W/cm^2$ at $800^{\circ}C$ and 0.7V.

Measurement uncertainty analysis of radiophotoluminescent glass dosimeter reader system based on GD-352M for estimation of protection quantity

  • Kim, Jae Seok;Park, Byeong Ryong;Yoo, Jaeryong;Ha, Wi-Ho;Jang, Seongjae;Jang, Won Il;Cho, Gyu Seok;Kim, Hyun;Chang, Insu;Kim, Yong Kyun
    • Nuclear Engineering and Technology
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    • v.54 no.2
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    • pp.479-485
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    • 2022
  • At the Korea Institute of Radiological and Medical Sciences, physical human phantoms were developed to evaluate various radiation protection quantities, based on the mesh-type reference computational phantoms of the International Commission on Radiological Protection. The physical human phantoms were fabricated such that a radiophotoluminescent glass dosimeter (RPLGD) with a Tin filter, namely GD-352M, could be inserted into them. A Tin filter is used to eliminate the overestimated signals in low-energy photons below 100 keV. The measurement uncertainty of the RPLGD reader system based on GD-352M should be analyzed for obtaining reliable protection quantities before using it for practical applications. Generally, the measurement uncertainty of RPLGD systems without Tin filters is analyzed for quality assurance of radiotherapy units using a high-energy photon beam. However, in this study, the measurement uncertainty of GD-352M was analyzed for evaluating the protection quantities. The measurement uncertainty factors in the RPLGD include the reference irradiation, regression curve, reproducibility, uniformity, energy dependence, and angular dependence, as described by the International Organization for Standardization (ISO). These factors were calculated using the Guide to the Expression of Uncertainty in Measurement method, applying ISO/ASTM standards 51261(2013), 51707(2015), and SS-ISO 22127(2019). The measurement uncertainties of the RPLGD reader system with a coverage factor of k = 2 were calculated to be 9.26% from 0.005 to 1 Gy and 8.16% from 1 to 10 Gy. A blind test was conducted to validate the RPLGD reader system, which demonstrated that the readout doses included blind doses of 0.1, 1, 2, and 5 Gy. Overall, the En values were considered satisfactory.

Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile In Vitro

  • Daiana V. Lopes Alves;Cesar Claudio-da-Silva;Marcelo C. A. Souza;Rosa T. Pinho;Wellington Seguins da Silva;Periela S. Sousa-Vasconcelos;Radovan Borojevic;Carmen M. Nogueira;Helio dos S. Dutra;Christina M. Takiya;Danielle C. Bonfim;Maria Isabel D. Rossi
    • International Journal of Stem Cells
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    • v.16 no.4
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    • pp.425-437
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    • 2023
  • Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68+/FXIII-A- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α+ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

Decomposition Characteristics of Fungicides(Benomyl) using a Design of Experiment(DOE) in an E-beam Process and Acute Toxicity Assessment (전자빔 공정에서 실험계획법을 이용한 살균제 Benomyl의 제거특성 및 독성평가)

  • Yu, Seung-Ho;Cho, Il-Hyoung;Chang, Soon-Woong;Lee, Si-Jin;Chun, Suk-Young;Kim, Han-Lae
    • Journal of Korean Society of Environmental Engineers
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    • v.30 no.9
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    • pp.955-960
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    • 2008
  • We investigated and estimated at the characteristics of decomposition and mineralization of benomyl using a design of experiment(DOE) based on the general factorial design in an E-beam process, and also the main factors(variables) with benomyl concentration(X$_1$) and E-beam irradiation(X$_2$) which consisted of 5 levels in each factor was set up to estimate the prediction model and the optimization conditions. At frist, the benomyl in all treatment combinations except 17 and 18 trials was almost degraded and the difference in the decomposition of benomyl in the 3 blocks was not significant(p > 0.05, one-way ANOVA). However, the % of benomyl mineralization was 46%(block 1), 36.7%(block 2) and 22%(block 3) and showed the significant difference of the % that between each block(p < 0.05). The linear regression equations of benomyl mineralization in each block were also estimated as followed; block 1(Y$_1$ = 0.024X$_1$ + 34.1(R$^2$ = 0.929)), block 2(Y$_2$ = 0.026X$_2$ + 23.1(R$^2$ = 0.976)) and block 3(Y$_3$ = 0.034X$_3$ + 6.2(R$^2$ = 0.98)). The normality of benomyl mineralization obtained from Anderson-Darling test in all treatment conditions was satisfied(p > 0.05). The results of prediction model and optimization point using the canonical analysis in order to obtain the optimal operation conditions were Y = 39.96 - 9.36X$_1$ + 0.03X$_2$ - 10.67X$_1{^2}$ - 0.001X$_2{^2}$ + 0.011X$_1$X$_2$(R$^2$ = 96.3%, Adjusted R$^2$ = 94.8%) and 57.3% at 0.55 mg/L and 950 Gy, respectively. A Microtox test using V. fischeri showed that the toxicity, expressed as the inhibition(%), was reduced almost completely after an E-beam irradiation, whereas the inhibition(%) for 0.5 mg/L, 1 mg/L and 1.5 mg/L was 10.25%, 20.14% and 26.2% in the initial reactions in the absence of an E-beam illumination.

Effects of Chronic Treatments with 5-HT Uptake Inhibitors on the [$^3H$]Imipraine and [$^3H$]Paroxetine Binding, [$^3H$]5-HT Uptake, and 5-HT Content of the Rabbit Platelet (5-HT 흡수억제성 항우울제들이 가토혈소판의 [$^3H$]Imipramine과 [$^3H$]Paroxetine Binding, [$^3H$]5-HT 흡수, 및 5-HT함량에 미치는 영향)

  • Won, Kyong-Sik;Lee, Min-Soo;Shin, Kyung-Ho;Chun, Boe-Gwun;Kwak, Dong-Il
    • Korean Journal of Biological Psychiatry
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    • v.1 no.1
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    • pp.88-97
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    • 1994
  • Many evidences are compatible with the correlation between the inhibition of [$^3H$] imipramine([$^3H$]IMI) and [$^3H$]paroxetine([$^3H$]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [$^3H$]IMI and [$^3H$]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [$^3H$]IMI and [$^3H$]PAT binding sites. This study was carried to clarify the correlation between the [$^3H$]IMI and [$^3H$]PAT binding parameters and the tissue 5-HT content or/and [$^3H$]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher $B_{max}$ of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [$^3H$]IMI binding $B_{max}$ and $K_d$ of the rabbit platelets were $6.4{\pm}1.2$pmol/mg protein and $10.9{\pm}2.1$nM and those in the [$^3H$]PAT binding were $8.6{\pm}1.1$pmol/mg protein and $1.6{\pm}0.3$nM, respectively. AP slightly increased $B_{max}$ of [$^3H$]IMI binding and both [$^3H$]IMI binding and [$^3H$]PAT binding $K_d$, and i contrast, it slightly decreased $B_{max}$ of [$^3H$]PAT binding. FO Slightly increased $K_d$ of both and [$^3H$]IMI and [$^3H$]PAT binding and slightly decreased $B_{max}$ of [$^3H$]IMI and [$^3H$]PAT binding. SA produced the significant increase of [$^3H$]PAT binding $B_{max}$ and the slight increase of both [$^3H$]IMI and [$^3H$]PAT binding $K_d$ and in contrast, it slightly decreased $B_{max}$ and of [$^3H$]IMI binding. And, the $V_{max}$ and $K_m$ of platelet [$^3H$]5-HT uptake were $24.2{\pm}2.4$pmol/$10^8$ platelets/min and $3.3{\pm}0.3$nM, respectively. The $V_{max}$ was little affected by AP, FO, or SA, but the [$^3H$]5-HT uptake $K_m$ value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [$^3H$]IMI or [$^3H$]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.

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Use of Respiratory Motion Reduction Device (RRD) in Treatment of Hepatoma (간암의 방사선치료 시 호흡운동 감소장치(respiratory motion reduction device, RRD)의 유용성에 관한 연구)

  • Lee Suk;Seong Jinsil;Kim Yong Bae;Cho Kwang Hwan;Kim Joo Ho;Jang Sae Kyung;Kwon Soo Il;Chu Sung Sil;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.19 no.4
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    • pp.319-326
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    • 2001
  • Purpose : Planning target volume (PTV) for tumors in abdomen or thorax includes enough margin for breathing-related movement of tumor volumes during treatment. Depending on the location of the tumor, the magnitude of PTV margin extends from 10 mm to 30 mm, which increases substantial volume of the irradiated normal tissue hence, resulting in increase of normal tissue complication probability (NTCP). We developed a simple and handy method which can reduce PTV margins in patients with liver tumors, respiratory motion reduction device (RRD). Materials and methods : For 10 liver cancer patients, the data of internal organ motion were obtained by examining the diaphragm motion under fluoroscope. It was tested for both supine and prone position. A RRD was made using MeV-Green and Styrofoam panels and then applied to the patients. By analyzing the diaphragm movement from patients with RRD, the magnitude of PTV margin was determined and dose volume histogram (DVH) was computed using AcQ-Plan, a treatment planning software. Dose to normal tissue between patients with RRD and without RRD was analyzed by comparing the fraction of the normal liver receiving to $50\%$ of the isocenter dose. DVH and NTCP for normal liver and adjacent organs were also evaluated. Results : When patients breathed freely, average movement of diaphragm was $12{\pm}1.9\;mm$ in prone position in contrast to $16{\pm}1.9\;mm$ in supine position. In prone position, difference in diaphragm movement with and without RRD was $3{\pm}0.9\;mm$ and 12 mm, respectively, showing that PTV margins could be reduced to as much as 9 mm. With RRD, volume of the irradiated normal liver reduced up to $22.7\%$ in DVH analysis. Conclusion : Internal organ motion due to breathing can be reduced using RRD, which is simple and easy to use in clinical setting. It can reduce the organ motion-related PTV margin, thereby decrease volume of the irradiated normal tissue.

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