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Biological Markers as Predictors of Radiosensitivity in Syngeneic Murine Tumors (동계 마우스 종양의 방사선 감수성 예측인자로서의 생물학적 표지자)

  • Chang Sei-Kyung;Kim Sung-Hee;Shin Hyun-Soo;Seong Jin-Sil
    • Radiation Oncology Journal
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    • v.24 no.2
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    • pp.128-137
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    • 2006
  • Purpose: We investigated whether a relationship exists between tumor control dose 50 ($TCD_{50}$) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between $TCD_{50}$, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Materials and Methods: Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used In this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were $8{\sim}12$ weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for $TCD_{50}$, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of $p53,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-X_L,\;Bcl-X_S$, and p34. Correlation analysis was peformed whether the level of RIA were correlated with $TCD_{50}$ or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with $TCD_{50}$, TGD, RIA. Results: The level of RIA showed a significant positive correlation (R=0.922, p=0.026) with TGD, and showed a trend to correlation (R=-0.848), marginally significant correlation with $TCD_{50}$ (p=0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of $p21^{WAF1/CIP1}$ and 34 showed a significant correlation either with $TCD_{50}$ (R=0.893, p=0.041 and R=0.904, p=0.035) or with TGD (R=-0.922, p=0.026 and R=-0.890 p=0.043). The tumors with high constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 were less radiosensitive than those with low expression. Conclusion: Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 can be used as biological markers which predict the radiosensitivity.

Prognostic Factors Influencing the Result of Postoperative Radiotherapy in Endometrial Carcinoma (자궁내막암의 수술 후 방사선치료 결과에 영향을 미치는 예후인자)

  • Ki Yong-Kan;Kwon Byung-Hyun;Kim Won-Taek;Nam Ji-Ho;Yun Man-Su;Lee Hyung-Sik;Kim Dong-Won
    • Radiation Oncology Journal
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    • v.24 no.2
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    • pp.110-115
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    • 2006
  • Purpose: This study was performed to determine the prognostic factors influencing relapse pattern, overall and disease-free survival in patients treated with postoperative radiotherapy for endometrial carcinoma. Materials and Methods: The records of 54 patients with endometrial adenocarcinoma treated postoperative radiotherapy at Pusan National University Hospital between April 1992 and May 2003 were reviewed retrospectively. Median age of the patients was 55 (range $35{\sim}76$). The distribution by surgical FIGO stages were 63.0% for 0Stage I, 14.8% for Stage II, 22.2% for Stage III. All patients received postoperative external radiotherapy up to $41.4{\sim}54Gy$ (median: 50.4 Gy). Additional Intravaginal brachytherapy was app led to 20 patients (37.0% of all). Median follow-up time was 35 months ($5{\sim}115$ months). Significant factors of this study: histologic grade, Iymphovascular space invasion and myometrial invasion depth were scored (GLM score) and analyzed. Survival analysis was peformed using Kaplan-Meier method. The log-rank test was used for univariate analysis and the Cox regression model for multivariate analysis. Results: 5-year overall and disease-free survival rates were 87.7% and 871%, respectively. Prognostic factors related with overall and disease-free survival were histologic grade, Iymphovascular space invasion and myometrial invasion according to the univariate analysis. According to the multivariate analysis, Iymphovascular space invasion was associated with decreased disease-free survival. GLM score was a meaningful factor affecting overall and disease-free survival (p=0.0090, p=0.0073, respectively) and distant recurrence (p=0.0132), which was the sum of points of histologic grade, Iymphovascular space Invasion and myometrial invasion. Total failure rate was 11% with 6 patients. Relapse sites were 2 para-aortic Iymph nodes, 2 lungs, a supraclavicular Iymph node and a vagina. Conclusion: The prognosos in patients with endometrial carcinoma treated by postoperative radiotherapy was closely related with surgical histopathology. If further explorations confirm the system of prognostic factors in endometrial carcinoma, it will help us to predict the progression pattern and to manage.

Superficial Dosimetry for Helical Tomotherapy (토모테라피를 이용한 표면 치료 계획과 선량 분석)

  • Kim, Song-Yih;You, Sei-Hwan;Song, Tae-Soo;Kim, Yong-Nam;Keum, Ki-Chang;Cho, Jae-Ho;Lee, Chang-Geol;Seong, Jin-Sil
    • Radiation Oncology Journal
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    • v.27 no.2
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    • pp.103-110
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    • 2009
  • Purpose: To investigate the feasibility of helical tomotherapy on a wide curved area of the skin, and its accuracy in calculating the absorbed dose in the superficial region. Materials and Methods: Two types of treatment plans were made with the cylinder-shaped 'cheese phantom'. In the first trial, 2 Gy was prescribed to a 1-cm depth from the surface. For the other trial, 2 Gy was prescribed to a 1-cm depth from the external side of the surface by 5 mm. The inner part of the phantom was completely blocked. To measure the surface dose and the depth dose profile, an EDR2 film was inserted into the phantom, while 6 TLD chips were attached to the surface. Results: The film indicated that the surface dose of the former case was 118.7 cGy and the latter case was 130.9 cGy. The TLD chips indicated that the surface dose was higher than these, but it was due to the finite thickness of the TLD chips. In the former case, 95% of the prescribed dose was obtained at a 2.1 mm depth, while the prescribed does was at 2.2 mm in the latter case. The maximum dose was about 110% of the prescribed dose. As the depth became deeper, the dose decreased rapidly. Accordingly, at a 2-cm depth, the dose was 20 % of the prescribed dose. Conclusion: Helical tomotherapy could be a useful application in the treatment of a wide area of the skin with curvature. However, for depths up to 2 mm, the planning system overestimated the superficial dose. For shallower targets, the use of a compensator such as a bolus is required.

Comparison of Wound Healing in Porcine Skin with Continuous-Wave and Pulsed Mode $CO_2$ Laser Incisions (돼지에서 연속형 $CO_2$ 레이저와 펄스형 $CO_2$ 레이저를 이용한 피부절개시 창상치유 평가)

  • Lee, Jae-Yeon;Cho, Sung-Whan;Park, Chang-Sik;Kim, Myung-Cheol
    • Journal of Veterinary Clinics
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    • v.27 no.6
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    • pp.647-651
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    • 2010
  • The advantages of the $CO_2$ laser are offset by the delay in laser wound healing secondary to thermal damage. To minimize the undesirable thermal damage of the $CO_2$ laser, investigators have developed technical advances in the delivery system of the laser energy. This study compared tissue healing of the continuous and the pulsed modes $CO_2$ laser wounds in an animal surgery model. Five healthy Landrace and Yorkshire mixed breeds of both genders were used (45-51 kg, 4-6 months old, three males and two females). A full thickness wound of skin ($2{\times}2{\times}2cm^2$) was made over on the each pig's both sides of dorsal midline at 0, 7, 14, and 18 days. The wounds created at 18, 14, 7 and 0 days were named post-wounding day (PWD) 3, 7, 14 and 21, respectively. In each pig, one wound (left side) was treated pulsed $CO_2$ laser and the other wound (right side) was treated continuous wave $CO_2$ laser. Each wound was closed with two interrupted suture of 3-0 sutures. At 21 days after initial wounding, each wound was taken for histological evaluations. The degrees of reepithelialization were performed more prominently in the pulsed mode group than in the continuous mode group. The degrees of granulation were greater significantly in pulsed mode group than those in the continuous mode on PWD 3 (p < 0.05). The degrees of fibroblasts in the pulsed mode group were greater significantly in comparison to those in the continuous mode group on PWD 7, (p < 0.05). In conclusion, reepithelialization, granulation and fibroblasts in the pulsed mode group were greater markedly in comparison to those in the continuous mode group. It was considered that pulsed mode $CO_2$ laser was more suitable for the skin incision than the continuous mode $CO_2$ laser.

Mouse model system based on apoptosis induction to crypt cells after exposure to ionizing radiation (방사선에 전신 조사된 마우스 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구)

  • Kim, Tae-Hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.571-578
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    • 2001
  • To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and a significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

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Ultrastructrual Change of Myocardium in Open Cardiac Surgery with Cold Blood Cardioplegia (개심술 시 냉혈성 심정지액 사용에 따른 허혈 전후 심근 미세구조의 변화)

  • 김병호;김대현;공준혁;조준용;손윤경;이종태
    • Journal of Chest Surgery
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    • v.36 no.9
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    • pp.638-645
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    • 2003
  • The purposes of this study were to evaluate the effect of myocardial protection with our cold blood cardioplegic solution and to observe the relationship between ultrastructural study and other evaluation methods and its effectiveness. Material and Method: We evaluated the changes of myocardial ultrastructure using semi-quantitative scoring system, CK-MB fraction, SGOT and LDH1/LDH2, and EKG in 18 patients undergoing valvular heart surgery and coronary artery bypass grafting (CABG). Right atrial auricular biopsies were taken before the cardiopulmonary bypass (CPB) and shortly after the end of CPB. Myocardium-related serum enzymes & EKG were checked for 3 days of postoperative period and their postoperative peak enzyme value and observed new Q wave & ST segment elevation in EKG were choosen. Result: There were 8 males and 10 females, and their mean age was 55.6$\pm$13. Eight patients underwent valvular heart surgery and ten coronary artery bypass grafting, The mean CPB time was 119$\pm$29 minutes and the mean aortic cross-clamp (ACC) time was 75.4$\pm$24 minutes. Before the start of CPB, the mean mitochondrial score was 4.28$\pm$0.53 and after the end of CPB, it significantly increased to 2.35$\pm$0.79. There was no evidence of perioperative myocardial infarction in terms of myocardiumrelated serum enzyme value and Q wave and ST change in EKG. There was no significant relationship between pre-CPB and post-CPB mitochondrial score and the mean time of CPB and ACC, and the mean value of postoperative peak CK-MB, SGOT and LDH1/LDH2, but there was relatively positive correlation of CPB time with peak LDH1/LDH2. Conclusion: Despite the apparent satisfactory results in myocardium-related serum enzymes & EKG, with this study using the cold blood cardioplegic solution, there were many changes in myocardial ultrastructures, and more studies are needed to obtain further information.

Construction of the Genomic Expression Library of Bacillus anthracis for the Immunomic Analysis (면역체 분석을 위한 탄저균 유전자 발현 라이브러리의 구축)

  • Park, Moon-Kyoo;Jung, Kyoung-Hwa;Kim, Yeon-Hee;Rhie, Gi-Eun;Chai, Young-Gyu;Yoon, Jang-W.
    • Korean Journal of Microbiology
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    • v.46 no.1
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    • pp.21-26
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    • 2010
  • As the causative agent of Anthrax, Bacillus anthracis causes an acute fatal disease in herbivores such as cattle, sheep, and horses as well as humans. The therapeutics and prevention of anthrax currently available are based on antibiotics and the live attenuated vaccine strains, which may be problematic due to the emergency of antibiotic resistant strains or residual virulence in those vaccine strains. Therefore, it has been required to develop novel therapeutics and vaccines which are safer and applicable to humans. Recently, the development of the multivalent vaccine targeting both spores and vegetative cells of B. anthracis along with anthrax toxin has been reported. In our attempts to screen potential candidates for those multivalent vaccines, the whole genomic expression library of B. anthracis was constructed in this study. To the end, the partial digests of the genomic DNA from B. anthracis (ATCC 14578) with Sau3AI were ligated with the inducible pET30abc expression vectors, resulting in approximately $1{\times}10^5$ clones in E. coli BL21(DE3). The redundancy test by DNA nucleotide sequencing was performed for the randomly selected 111 clones and found 56 (50.5%) B. anthracis genes, 17 (15.3%) vector sequences, and 38 (34.2%) unknown genes with no sequence homology by BLAST. An inducible expression of the recombinant proteins was confirmed by Western blot. Interestingly, some clones could react with the antiserum against B. anthracis. These results imply that the whole genomic library constructed in this study can be applied for analyzing the immunomes of B. anthracis.

Quality Control of Tungsten-188/Rhenium-188 Generator (Tungsten-188/Rhenium-188 발생기의 정도관리)

  • Chang, Young-Soo;Jeong, Jae-Min;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.5
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    • pp.425-432
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    • 1998
  • Purpose: For the purpose of using Re-188 as a therapeutic radionuclide, we performed the quality control of the W-188/Re-188 generator system. Materials and Methods: Several quality control tests of the Re-188 eluate from generator were carried out for about 300 days. After elution of Re-188 with normal saline (20 ml), chromatogram and gamma-ray spectrum of Re-188 eluate were obtained. The presence of aluminum which was derived from the alumina bed of the generator was detected by using aluminum ion indicator kit. Re-188 eluate was allowed to decay for several days, and then W-188 breakthrough in the Re-188 eluate was measured by detecting gamma-ray at 227 keY and 290 keV. The pH and the pyrogenicity of the eluate were checked. The Re-188 bolus was concentrated with ion exchange columns. Results: The radioactivity of Re-188 eluate from the generator was $67.4{\pm}7.0%$ of W-188 during 270 days, and it was highest at third day after previous elution. Radiochemical purity of Re-188 eluate obtained from chromatogram was higher than 99%. Gamma-ray spectrum of Re-188 eluate showed a peak at 155 keV. Aluminum ion and W-188 contamination were not detected. The PH of Re-188 eluate was 3 and the concentration yield was 85%. Conclusion: Our experiments and results on quality control tests of Re-188 eluate from W-188/Re-188 generator may be useful for setting W-188/Re-188 generator in hospitals.

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Control Efficacy of Carboxylic Acid Amide Fungicides against Pepper Phytophthora Blight Causing Phytophthora capsici (고추 역병에 대한 Carboxylic Acid Amide계 살균제의 방제 효과)

  • Shin, Jin-Ho;Kim, Jooh-Young;Kim, Hyeong-Jo;Choi, Young-Ki;Kim, A-Hyeong;Lee, Kyeong-Hee;Rho, Chang-Woo;Kim, Heung-Tae
    • The Korean Journal of Pesticide Science
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    • v.14 no.4
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    • pp.463-472
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    • 2010
  • It was conducted to investigate the control efficacy of carboxylic acid amide (CAA) fungicides, such as benthiavalicarb, iprovalicarb, dimethomorph and mandipropamid, against pepper Phytophthora blight caused by P. capsid in the laboratory and the field. The fungicides inhibited mycelial growth and direct sporangium germination of P. capsid strongly, while there was no activity of all fungicides against zoospore release from sporangium. In greenhouse test, they showed the good protective and curative effect against pepper Phytophthora blight. Benthiavalicarb applied at $100{\mu}g\;mL^{-1}$ 7 days before inoculation prevented pepper Phytophthora blight by 100%, even though the zoosporangiurn suspension of P. capsid adjusted to not only $5{\times}10^3$ zoosporangia $mL^{-1}$ but also $1{\times}10^5$ zoosporangia $mL^{-1}$ was inoculated by soil-drenching. Except for dimethomorph, the other fungicides showed an excellent control activity over 2 years from 2009 to 2010 in the field test. The control value of dimethomorph applied at $250{\mu}g\;mL^{-1}$ was low, 27.2% in 2009, but that of dimethomorph applied even at $125{\mu}g\;mL^{-1}$ was high, 89.5% in 2010. All the fungicides showed good inhibitory effect on the mycelial growth and the direct germination of zoosporangiurn, and controlled pepper Phytophthora blight preventively and curatively, can be used to establish the spray system for control1ing the pepper disease.

Study for the Geochemical Reaction of Ca-feldspar, Amphibole and Olivine with Supercritical $CO_2$ and Brine on the $CO_2$ Sequestration Condition (이산화탄소 지중저장 조건에서 초임계이산화탄소와 염수 반응에 의한 Ca-사장석, 각섬석, 감람석의 지화학적 변화 연구)

  • Kang, Hyun-Min;Park, Min-Ho;Park, Sang-Hee;Lee, Min-Hee;Wang, Soo-Kyun
    • Economic and Environmental Geology
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    • v.44 no.2
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    • pp.123-133
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    • 2011
  • The lab scale experiments to investigate the geochemical reaction among supercritical $CO_2$-mineral-brine which occurs at $CO_2$ sequestration sites were performed. High pressurized cell system (l00 bar and $50^{\circ}C$) was designed to create supercritical $CO_2$ in the cell, simulating the sub-surface $CO_2$ storage site. From the high pressurized cell experiment, the surface changes of Ca-feldspar, amphibole (tremolite) and olivine, resulted from the supercritical $CO_2$-mineral-brine reaction, were observed and the dissolution of minerals into the brine was also investigated. The mineral slabs were polished and three locations on the surface were randomly selected for the image analysis of SPM and the surface roughness value (SRV) of those locations were calculated to quantify the change of mineral surface for 30 days. At a certain time interval, SPM images and SRVs of the same mineral surface were acquired. The secondary minerals precipitated on the mineral surfaces were also analyzed on SEM/EDS after the experiment. From the experiments, the average SRV of Ca-feldspar increased from 2.77 nm to 20.87 nm for 30 days, suggesting that the dissolution of Ca-feldspar occurs in active when the feldspars contact with supercritical $CO_2$ and brine. For the amphibole, the average SRV increased from 2.54 nm to 8.31 nm and for the olivine from 0.77 nm to 11.03 run. For the Ca-feldspar, $Ca^{2+}$, $Na^+$, $Fe^{2+}$, $Si^{4+}$, $K^+$ and $Mg^{2+}$ were dissolved in the highest order and $Si^{4+}$, $Ca^{2+}$, $Fe^{2+}$ and $Mg^{2+}$ for the amphibole. Fe (or Mg) - oxides were precipitated as the secondary minerals on the surfaces of amphibole and olivine after 30 days reaction. Results suggested that $Ca^{2+}$, $Fe^{2+}$ and $Mg^{2+}$ rich minerals would be significantly weathered when it contacts with the supercritical $CO_2$ and brine at $CO_2$ sequestration sites.