Vascular Endothelial Growth Factor Inhibits irradiation-induced Apoptosis in Human Umbilical Vein Endothelial Cells

이송재,김동윤,Lee Song Jae,Kim Dong-Yun Korean Society for Radiation Therapy 2002 大韓放射線治療技術學會誌 Vol.14 No.1

혈관내피세포 성장 인자(Vascular endothelial growth factor, VEGF)는 혈관내피세포 특이하게 성장요인으로 작용하는 물질로 알려져 있다. 전리방사선에 대한 혈관내피세포의 효과는 정상조직에 대한 반응에 있어 아주 중요한 요소일 것으로 생각된다. 본 연구는 방사선 조사에 의해 배양시킨 혈관내피세포에서 apoptosis가 유도되는지, 유도가 된다면 VEGF에 의해 apoptosis가 억제되는지 그리고 apoptosis의 억제가 어떤 경로를 경유하는지를 실험하였다. 혈관내피세포에 방사선를 조사한 결과, 대조군에 비하여 선량이 증가함에 따라 apoptosis가 증가하였다. 같은 조건하에서 VEGF는 농도 의존적으로 apoptosis를 억제하였다. Antiapoptotic factor로서 VEGF가 어떤 신호 과정을 경유하는지를 밝히고자, 혈관내피세포에 방사선을 조사하여 apoptosis를 유도하면서 Flt-1과 Flk-1/KDR receptor를 처리하였다. 그결과 VEGF에 유도된 apoptosis 억제효과가 차단되었다. Phosphatidylinositol 3'-kinase(PI3-kinase) 특정 억제 물질인 Wortmanin과 LY294002를 방사선 조사한 혈관내피에 VEGF와 함께 처리했을 때 VEGF에 의해 유도된 apoptosis를 억제하였다. 이같은 결과는 VEGF가 방사선 조사로 일어나는 세포 치사를 억제하는 중요한 역할을 담당하며, In Vivo의 실험이 더 이루어져야 할 것으로 생각된다. Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we examined the effect of VEGF on radiation induced apoptosis and receptor/second messenger signal transduction pathway for VEGF effect in human umbilical vein endothelial cells (HUVECs). VEGF was found to protect HUVECs against the lethal effects of ionizing radiation by inhibiting the apoptosis induced in these cells by radiation exposure. VEGF (1-30 ng/ml) dose dependently inhibited apoptosis by irradiation. Pre-treatment with Flt-1 and Flk-l/KDR receptor blocked the VEGF-in duced antiapoptotic effect. Phosphatidylinositol 3'-kinase (PI3-kinase) specific inhibitor, Wortman in and LY294002, blocked the VEGF-induced antiapoptotic effect. These data suggest that VEGF may play an important role in survival of HUVECs due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation.

A Study of the Adjustment and Treatment Depending on the Change of Prostate Location Using DIPS in Proton Beam Therapy for Prostate Gland in which a Fiducial Gold Marker was Inserted

박준기,김선영,김태윤,최계숙,염두석,강동윤,최승오,박지연,Park, June-Ki,Kim, Sun-Young,Kim, Tae-Yoon,Choi, Kye-Sook,Yeom, Doo-Suk,Kang, Dong-Yoon,Choi, Seung-O,Park, Ji-Youn Korean Society for Radiation Therapy 2008 대한방사선치료학회지 Vol.20 No.1

Purpose: To monitor the changes of location of prostate gland using DIPS and to examine the adjustment and proton beam therapy depending on the movement of prostate gland in proton beam therapy for prostate gland in which a fiducial gold marker was inserted. Materials and Methods: This study was conducted in ten patients with prostate cancer who received proton beam therapy since April of 2008. To monitor the change of prostate location, three fiducial gold markers were inserted prior to the treatment. To minimize the movement of prostate gland, patients were recommended to urinate prior to the treatment, to intake a certain amount of water and to concomitantly undergo rectal balloon. In these patients, the set-up position was identical to that for a CT-simulation. The PA (posterior-anterior) and lateral images were obtained using both DIPS (digital image positioning system) and a plain radiography, and they were compared between the two imaging modalities. Thus, the changes of the location of fiducial gold marker were assessed based on three coordinates (x, y, z) and then adjusted. This was followed by proton beam therapy. Results: Images which were taken using a plain radiography were compared with those which were taken using DIPS. In ten patients, according to a reference bony marker, the mean changes of the location of fiducial gold marker based on an iso-center were X-axis: $\pm$0.116 cm, Y-axis: $\pm$0.19 cm and Z-axis: $\pm$0.176 cm. These ten patients showed a difference in the changes of location of prostate gland and it ranged between RT: 0.04 cm and RT: 0.24 cm on the X-axis; between Inf: 0.03 cm and Sup: 0.42 cm on the Y-axis; and Post: 0.05 cm and Ant: 0.35 cm on the Z-axis. Conclusion: To minimize the movement of prostate gland, as the pre-treatment prior to the treatment. In all the patients, however, three fiducial gold markers showed a daily variation which were inserted in the prostate gland. Based on the above data, Thus, the requirement of gold marker matching system depending on the daily variation in the proton beam therapy for which more accurate establishment of target was confirmed. It is assumed that an accurate effect of proton beam therapy would be enhanced by adjusting the target-center depending on the location change of prostate gland using DIPS which was used in the current study.

Evaluation of the Usefulness of the Respiratory Guidance System in the Respiratory Gating Radiation Therapy

이영철,김선명,도경민,박근용,김건오,김영범,Lee, Yeong-Cheol,Kim, Sun-Myung,Do, Gyeong-Min,Park, Geun-Yong,Kim, Gun-Oh,Kim, Young-Bum Korean Society for Radiation Therapy 2012 대한방사선치료학회지 Vol.24 No.2

목 적: 호흡동조방사선치료(Respiratory Gating Radiation Therapy, RGRT)에서 호흡의 안정성은 매우 중요한 인자이다. 이러한 호흡의 안정을 위해 본인의 호흡주기를 직접 확인할 수 있도록 시청각시스템을 이용한 호흡유도시스템을 개발하였고 이의 유용성을 평가하고자 하였다. 대상 및 방법: 2011년 6월부터 2012년 4월까지 본원에서 호흡동조방사선치료를 받은 7명의 환자를 대상으로 시청각시스템을 이용하지 않는 자유호흡을 먼저 측정하고 자체개발한 호흡유도시스템을 이용한 호흡을 측정하였다. 시청각시스템을 이용한 호흡연습 후에는 치료실내에서의 자가호흡과 시청각시스템을 이용한 호흡을 각각 측정하였다. 측정된 데이터는 호흡주기, 호흡함수의 면적을 구하여 표준편차를 구하였으며, 이를 분석하여 치료전후의 호흡변화를 알아 보았다. 결 과: 자유호흡과 오디오 유도시스템, 시청각 유도시스템의 표준편차는 PTP (peak to peak)가 각각 0.343, 0.148, 0.078이다. 호흡주기는 각각 0.645, 0.345, 0.171이며, 호흡함수의 면적은 각각 2.591, 1.008, 0.877로 나타났다. 전체 환자의 CT실과 치료실에서의 차이를 평균한 값은 PTP가 0.425, 호흡주기가 1.566, 호흡면적이 3.671로 측정되었다. 호흡유도시스템 적용전후의 표준편자는 PTP가 0.265, 호흡주기가 0.474, 호흡면적이 1.714의 차이를 나타내었다. 자유호흡과 시청각유도시스템 적용전후의 값을 T-검정한 결과에서는 PTP, 주기, 호흡함수면적에서 각각 P-value 0.035, 0.009, 0.010의 값을 나타냈다. 결 론: 호흡동조방사선치료에서 호흡조절은 치료의 성패를 좌우할 만큼 중요한 인자이다. 자유호흡이나 청각에 의존한 호흡주기 획득에 비해 시청각 호흡유도 시스템을 이용한 경우에 보다 안정적인 호흡을 얻을 수 있었다. 특히, 치료실에서도 같은 시스템을 이용하여 호흡을 조절함으로써 호흡주기의 재현성이 뛰어났다. 이러한 시스템은 호흡불안정에 의한 치료시간의 지연을 줄이고 좀 더 정확하고 정밀한 치료가 가능하게 되었다. Purpose: The respiration is one of the most important factors in respiratory gating radiation therapy (RGRT). We have developed an unique respiratory guidance system using an audio-visual system in order to support and stabilize individual patient's respiration and evaluated the usefulness of this system. Materials and Methods: Seven patients received the RGRT at our clinic from June 2011 to April 2012. After breathing exercise with the audio-visual system, we measured their spontaneous respiration and their respiration with the audio-visual system respectively. With the measured data, we yielded standard deviations by the superficial contents of respiratory cycles and functions, and analyzed them to examine changes in their breathing before and after the therapy. Results: The PTP (peak to peak) of the standard deviations of the free breathing, the audio guidance system, and the respiratory guidance system were 0.343, 0.148, and 0.078 respectively. The respiratory cycles were 0.645, 0.345, and 0.171 respectively and the superficial contents of the respiratory functions were 2.591, 1.008, and 0.877 respectively. The average values of the differences in the standard deviations among the whole patients at the CT room and therapy room were 0.425 for the PTP, 1.566 for the respiratory cycles, and 3.671 for the respiratory superficial contents. As for the standard deviations before and after the application of the PTP respiratory guidance system, that of the PTP was 0.265, that of the respiratory cycles was 0.474, and that of the respiratory superficial contents. The results of t-test of the values before and after free breathing and the audio-visual guidance system showed that the P-value of the PTP was 0.035, that of the cycles 0.009, and that of the respiratory superficial contents 0.010. Conclusion: The respiratory control could be one of the most important factors in the RGRT which determines the success or failure of a treatment. We were able to get more stable breathing with the audio-visual respiratory guidance system than free breathing or breathing with auditory guidance alone. In particular, the above system was excellent at the reproduction of respiratory cycles in care units. Such a system enables to reduce time due to unstable breathing and to perform more precise and detailed treatment.

Analysis of inter-fraction and intra-fraction errors during volumetric modulated arc therapy in Pancreas Ca

조영필,서동린,홍택균,강태영,백금문,홍동기,윤인하,김진산,Jo, Young Pil,Seo, Dong Rin,Hong, Taek Kyun,Kang, Tae Yeong,Beck, Geum Mun,Hong, Dong Ki,Yun, In Ha,Kim, Jin San Korean Society for Radiation Therapy 2014 대한방사선치료학회지 Vol.26 No.2

목 적 : 췌장 환자 방사선 치료 중 기점(Fiducial) 대상 내부 및 외부 종양 움직임의 오차를 정량화 하고자 한다. 또한 cone beam computed tomography (CBCT) 를 기반으로 호흡 시 췌장의 움직임 분석하고자 한다. 대상 및 방법 : 용적 세기변조 회전조사 (V-MAT)를 적용, 정위적 방사선 치료를 국소 진행성 췌장암 환자 11명을 대상으로 하였다. CBCT 및 직교 투시이미지를 적용하여 기점(Fiducial Marker)의 Inter, intra-fraction 움직임 변화를 치료 전, 치료 진행 시 분석하였다. 결 과 : 치료 후 프로토콜을 오프라인 교정 프로토콜을 사용하여, CBCT 와 직교투시 간의 평균 오차(범위)는 0.0(-1.7~4.0), 0.3(-0.5~3.0) and 0.0(-4.1~6.6)mm 측방 (LR), 세로 (AP) 및 종 방향 (SI) 이였다. 무작위 Inter-fraction Setup 오차 결과는 -0.1, -2.3 and -1.1 mm: 95% Fiducial포함 마진은 각 9.9, 7.8, 12.5mm로 수식되었다. 결 론 : 위 분석으로 뼈 일치 정렬 후 잔류 불확실성이 있으며, SI 방향에 큰 임의의 움직임은 적합한 여백이 필요하다. 주변 내부 장기를 보호, 내부 장기 문제점을 최소화, 호흡편차를 고려, 치료 시 정기적으로 측정하여야 한다. Purpose : To assess target motion during radiotherapy by quantifying daily setup errors and inter-fractional and intra-fractional movements of pancreatic fiducials. Materials and Methods : Eleven patients were treated via stereotactic body radiotherapy (SBRT) with volumetric modulated arc therapy. Bony setup errors were calculated using cone beam computed tomography (CBCT). Inter-fractional and intrafractional fiducial (seed) motion was determined via cone beam computed tomography (CBCT) projections and orthogonal fluoroscopy. Results : Using an off-line correction protocol, setup errors were 0.0 (-1.7-4.0), 0.3 (-0.5-3.0), and 0.0 (-4.1-6.6) mm for the left-right, anterior-posterior, and superior-inferior directions respectively. Random inter-fractional setup errors in the mean fiducial positions were -0.1, -1.1, and -2.3 mm respectively. Intra-fractional fiducial margins were 9.9, 7.8, and 12.5 mm, respectively. Conclusion : Online inter-fractional and intra-fractional corrections based on daily kV images and CBCT expedites SBRT of pancreatic cancer. Importantly, inter-fractional and intra-fractional motion needs to be measured regularly during treatment of pancreatic cancer to account for variations in patient respiration.

DOSIMETRY OF ASYMMETRIC COLLIMATIORS

전병철,방동완,정갑수,신동봉,박재일,Jeon, Byeong-Chul,Bang, Dong-Wan,Jung, Kap-Soo,Shin, Dong-Bong,Park, Jae-Il Korean Society for Radiation Therapy 1996 大韓放射線治療技術學會誌 Vol.8 No.1

두경부와 유방과의 접합부위인 쇄골상와(Supraclavicular lymph nodes)의 방사선치료(Half-beam techniques)에 있어서 비대칭 콜리메이터(Asymmetric collimators) 역할의 효용성과 접합부위에 균등한 선량(Uniform dose)을 유도하고자 본 측정을 시도하였다. 본 실험은 선형가속기 (Clinac 600C, 2100C, 2100CD)를 이용하였고 에너지는 4Mev와 10Mev를 사용하였다. 에너지별로 최대선량지점(Build-up)과 후방산란선(Back scatter-ray)을 고려하여 필름의 위${\cdot}$아래에 판톰을 위치시키고, ${\pm}0.0mm$, 0.1mm, 0.2mm로 콜리메이터의 간격을 두어 중심부위의 선량을 측정하였다. 측정결과 기계별로 비대칭 콜리메이터의 선량분포가 다름을 알 수 있었다. 즉, 600C에서는 X-jaw를 사용하여 0.0mm로 간격을 주지 않았을 때, 2100C에서는 X-jaw를 사용하여 0.1mm 간격을 주었을 때 가장 이상적인 선량분포를 나타냈고, 2100CD에서는 Y-jaw를 사용하여 0.1mm 간격을 두었을 때 균등한 선량분포를 얻을 수 있었다. 따라서 본 저자들은 다음과 같은 결론을 얻을 수 있었다. 1 . 비대칭 콜리메이터를 사용한, 접합부위의 방사선 치료시에는 정기적인 측정과 기계별 비대칭 콜리메이터의 특성을 파악하는 것이 중요하리라고 사료된다. 2. 접합부위의 방사선 치료시, 비대칭 콜리메이터의 사용은 접합부위에 선량과다(hot spots)와 과소(cold spots)없이 균등한 선량분포를 얻을 수 있어 Half-beam 사용시 임상적으로 유용할 것으로 사료된다. PURPOSE : To investigate the effect of asymmetric jaws for delivering a uniform accurate dose of radiation to the junctions. METHODS & MATERIALS : A linear accelerator with a set of asymmetric jaws(varian 600C, 2100C, 2100CD with 4mev, 10mev, 10mev). Dose disribution was measured at the junctions with films in phantom. Total $10{\times}20cm^2$ with each $10{\times}10cm^2$ in deviation of ${\pm}1mm$ jaws. RESULTS : Film dosimetry showed the accuracy of asymmetric jaws depending on the machine. CONCLUSION : Understanding the mechanical characteristics of the use of half-beam at the junctions, without hot or cold regions.

Analysis of the Dose Distribution of Moving Organ using a Moving Phantom System

김연래,박병문,배용기,강민영,이귀원,방동완,Kim, Yon-Lae,Park, Byung-Moon,Bae, Yong-Ki,Kang, Min-Young,Lee, Gui-Won,Bang, Dong-Wan Korean Society for Radiation Therapy 2006 대한방사선치료학회지 Vol.18 No.2

Purpose: Few researches have been peformed on the dose distribution of the moving organ for radiotherapy so far. In order to simulate the organ motion caused by respiratory function, multipurpose phantom and moving device was used and dosimetric measurements for dose distribution of the moving organs were conducted in this study. The purpose of our study was to evaluate how dose distributions are changed due to respiratory motion. Materials and Methods: A multipurpose phantom and a moving device were developed for the measurement of the dose distribution of the moving organ due to respiratory function. Acryl chosen design of the phantom was considered the most obvious choice for phantom material. For construction of the phantom, we used acryl and cork with density of $1.14g/cm^3,\;0.32g/cm^3$ respectively. Acryl and cork slab in the phantom were used to simulate the normal organ and lung respectively. The moving phantom system was composed of moving device, moving control system, and acryl and cork phantom. Gafchromic film and EDR2 film were used to measure dose ditrbutions. The moving device system may be driven by two directional step motors and able to perform 2 dimensional movements (x, z axis), but only 1 dimensional movement(z axis) was used for this study. Results: Larger penumbra was shown in the cork phantom than in the acryl phantom. The dose profile and isodose curve of Gafchromic EBT film were not uniform since the film has small optical density responding to the dose. As the organ motion was increased, the blurrings in penumbra, flatness, and symmetry were increased. Most of measurements of dose distrbutions, Gafchromic EBT film has poor flatness and symmetry than EDR2 film, but both penumbra distributions were more or less comparable. Conclusion: The Gafchromic EBT film is more useful as it does not need development and more radiation dose could be exposed than EDR2 film without losing film characteristics. But as response of the optical density of Gafchromic EBT film to dose is low, beam profiles have more fluctuation at Gafchromic EBT. If the multipurpose phantom and moving device are used for treatment Q.A, and its corrections are made, treatment quality should be improved for the moving organs.

Evaluation of dose variation at the vertex during Total Skin Electron Beam

Jeon Byeong-Chul,An Seung-Kwon,Lee Sang-Gyu,Kim Joo-Ho,Cho Kwang-Hwan,Cho Jung-Hee,Park Jae-Il Korean Society for Radiation Therapy 2000 大韓放射線治療技術學會誌 Vol.12 No.1

목적 전신피부 전자선 치료시 두정부의 scalp는 항상 사방향으로 입사된다. 본 연구는 두정부에서의 선량균등성을 향상시키기 위한 목적으로 본원에서 자체 제작한 전자선 반사체(electron reflector)를 두정부의 scalp 위치에 놓아 반사되는 전자선을 이용하여 선량변화를 조사하고 전자선 반사체의 효용성을 평가하고자 한다. 대상 및 방법 두정부에서의 선량측정은 6MeV 전자선을 이용한 전리조(ion-chamber)와 열형광선량계(TLD)를 사용하였고, 산란되는 전자선의 영향을 평가하기 위해 자체 제작한 $40{\times}40cm^2$, 1 mm 두께의 전자선 반사체를 팬톰위에 위치시켜 선량을 측정하였다 결과 두정부에서의 표면선량은 전자선 반사체를 사용하지 않았을 때에 $37.8\%$로 나타났으며, 이에 반해 반사체를 사용하였을 때는 $62.2\%$의 선량증가를 나타내었다. 결론 일반적으로 시행되는 전신피부전자선조사는 두정부에서의 under-dose를 확인할 수 있었고, 본원에서 자체 제작한 전자선 반사체 사용시 두정부에서의 선량 균등성이 향상되어 추가적인 치료가 필요치 않을 것으로 생각된다. Purpose : The vertex scalp is always tangentially irradiated during total skin electron beam(TSEB) This study was discuss to the dose distribution at the vertex scalp and to evaluate the use of an electron reflector. positioned above the head as a means of improving the dose uniformity. Methods and Materials Vetex dosimetry was performed using ion-chamber and TLD. Measurements were 6 MeV electron beam obtained by placing an acrylic beam speller in the beam line. Studies were performed to investigate the effect of electron scattering on vertex dose when a lead reflector $40{\times}40cm$ in area, was positioned above the phantom. Results : The surface dose at the vertex, in the without of the reflector was found to be less than $37.8\%$ of the skin dose. Use of the lead reflector increased this value to $62.2\%$ for the 6 MeV beam. Conclusion : The vertex may be significantly under-dosed using standard techniques for total skin electron beam. Use of an electron reflector improves the dose uniformity at the vertex and may reduce or eliminate the need for supplemental irradiation.

Comparison of Volumes between Four-Dimensional Computed Tomography and Cone-Beam Computed Tomography Images using Dynamic Phantom

김성은,원희수,홍주완,장남준,정우현,최병돈,Kim, Seong-Eun,Won, Hui-Su,Hong, Joo-Wan,Chang, Nam-Jun,Jung, Woo-Hyun,Choi, Byeong-Don Korean Society for Radiation Therapy 2016 대한방사선치료학회지 Vol.28 No.2

목 적 : Computerized imaging reference systems 동적팬텀을이용한 cone-beamcomputed tomography(CBCT) 영상과 four-dimensionalcomputed tomography(4DCT) 영상의 체적을 비교분석 하고자 한다. 대상 및 방법 : 동적팬텀 내에 직경 1, 2, 3 cm 노드를 각각 삽입하고, CT simulator와 TruebeamSTx X-ray Imaging system을 이용하여 4DCT 영상과 CBCT 영상을 얻었다. 4DCT 영상은 maximum intensity projection(MIP), minimum intensity projection(MinIP), 그리고 average intensity projection(AVG)영상으로 재구성 하고 노드의 체적은 Eclipse system의 CT ranger tool로 CT number를 설정하여 측정하였다. 결 과 : CBCT를 기준으로 노드1, 2, 3 cm의 체적을 비교하였을 때 4DCT의 MIP는 0.54~2.33, 5.16~8.06, 9.03~20.11 ml, MinIP는 0.00~1.48, 0.00~8.47, 1.42~24.85 ml, AVG는 0.00~1.17, 0.00~2.19, 0.04~3.35 ml의 차이를 보였다. 결 론 : 노드의 체적을 비교한 결과 CBCT 영상은 4DCT의 AVG 영상과 유사한 것으로 확인되었다. Purpose : The aim of this study was to compare the differences between the volumes acquired with four-dimensional computed tomography (4DCT)images with a reconstruction image-filtering algorithm and cone-beam computed tomography (CBCT) images with dynamic phantom. Materials and Methods : The 4DCT images were obtained from the computerized imaging reference systems (CIRS) phantom using a computed tomography (CT) simulator. We analyzed the volumes for maximum intensity projection (MIP), minimum intensity projection (MinIP) and average intensity projection (AVG) of the images obtained with the 4DCT scanner against those acquired from CBCT images with CT ranger tools. Results : Difference in volume for node of 1, 2 and 3 cm between CBCT and 4DCT was 0.54~2.33, 5.16~8.06, 9.03~20.11 ml in MIP, respectively, 0.00~1.48, 0.00~8.47, 1.42~24.85 ml in MinIP, respectively and 0.00~1.17, 0.00~2.19, 0.04~3.35 ml in AVG, respectively. Conclusion : After a comparative analysis of the volumes for each nodal size, it was apparent that the CBCT images were similar to the AVG images acquired using 4DCT.