• Title/Summary/Keyword: exact methods

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Incase of Same Region Treatment by using a Tomotherapy and a Linear Accelerator Absorbed Dose Evaluation of Normal Tissues and a Tumor (토모테라피와 선형가속기를 이용한 동일 부위의 치료 시 종양 및 정상조직의 흡수선량 평가)

  • Cheon, Geum-Seong;Kim, Chang-Uk;Kim, Hoi-Nam;Heo, Gyeong-Hun;Song, Jin-Ho;Hong, Joo-Yeong;Jeong, Jae-Yong
    • The Journal of Korean Society for Radiation Therapy
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    • v.22 no.2
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    • pp.97-103
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    • 2010
  • Purpose: Treating same region with different modalities there is a limit to evaluate the total absorbed dose of normal tissues. The reason is that it does not support to communication each modalities yet. In this article, it evaluates absorbed dose of the patients who had been treated same region by a tomotherapy and a linear accelerator. Materials and Methods: After reconstructing anatomic structure with a anthropomorphic phantom, administrate 45 Gy to a tumor in linac plan system as well as prescribe 15 Gy in tomotherapy plan system for make an ideal treatment plan. After the plan which made by tomoplan system transfers to the oncentra plan system for reproduce plan under the same condition and realize total treatment plan with summation 45 Gy linac treatment plan. To evaluate the absorbed dose of two different modalities, do a comparative study both a simple summation dose values and integration dose values. Then compare and analyze absorbed dose of normal tissues and a tumor with the patients who had been exposured radiation by above two differents modalities. Results: The result of compared data, in case of minimum dose, there are big different dose values in spleen (12.4%). On the other hand, in case of the maximum dose, it reports big different in a small bowel (10.2%) and a cord (5.8%) in head & neck cancer patients, there presents that oral (20.3%), right lens (7.7%) in minimum dose value. About maximum dose, it represents that spinal (22.5), brain stem (12%), optic chiasm (8.9%), Rt lens (11.5%), mandible (8.1%), pituitary gland (6.2%). In case of Rt abdominal cancer patients, there represents big different minimum dose as Lt kidney (20.3%), stomach (8.1%) about pelvic cancer patients, it reports there are big different in minimum dose as a bladder (15.2%) as well as big different value in maximum dose as a small bowel (5.6%), a bladder (5.5%) in addition, making treatment plan it is able us to get. Conclusion: In case of comparing both simple summation absorbed dose and integration absorbed dose, the minimum dose are represented higher as well as the maximum dose come out lower and the average dose are revealed similar with our expected values data. It is able to evaluate tumor & normal tissue absorbed dose which could had been not realized by treatment plan system. The DVH of interesting region are prescribed lower dose than expected. From now on, it needs to develop the new modality which are able to realize exact dose distribution as well as integration absorbed dose evaluation in same treatment region with different modalities.

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Performance Characteristics of 3D GSO PET/CT Scanner (Philips GEMINI PET/DT) (3차원 GSO PET/CT 스캐너(Philips GEMINI PET/CT의 특성 평가)

  • Kim, Jin-Su;Lee, Jae-Sung;Lee, Byeong-Il;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.4
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    • pp.318-324
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    • 2004
  • Purpose: Philips GEMINI is a newly introduced whole-body GSO PET/CT scanner. In this study, performance of the scanner including spatial resolution, sensitivity, scatter fraction, noise equivalent count ratio (NECR) was measured utilizing NEMA NU2-2001 standard protocol and compared with performance of LSO, BGO crystal scanner. Methods: GEMINI is composed of the Philips ALLEGRO PET and MX8000 D multi-slice CT scanners. The PET scanner has 28 detector segments which have an array of 29 by 22 GSO crystals ($4{\times}6{\times}20$ mm), covering axial FOV of 18 cm. PET data to measure spatial resolution, sensitivity, scatter fraction, and NECR were acquired in 3D mode according to the NEMA NU2 protocols (coincidence window: 8 ns, energy window: $409[\sim}664$ keV). For the measurement of spatial resolution, images were reconstructed with FBP using ramp filter and an iterative reconstruction algorithm, 3D RAMLA. Data for sensitivity measurement were acquired using NEMA sensitivity phantom filled with F-18 solution and surrounded by $1{\sim}5$ aluminum sleeves after we confirmed that dead time loss did not exceed 1%. To measure NECR and scatter fraction, 1110 MBq of F-18 solution was injected into a NEMA scatter phantom with a length of 70 cm and dynamic scan with 20-min frame duration was acquired for 7 half-lives. Oblique sinograms were collapsed into transaxial slices using single slice rebinning method, and true to background (scatter+random) ratio for each slice and frame was estimated. Scatter fraction was determined by averaging the true to background ratio of last 3 frames in which the dead time loss was below 1%. Results: Transverse and axial resolutions at 1cm radius were (1) 5.3 and 6.5 mm (FBP), (2) 5.1 and 5.9 mm (3D RAMLA). Transverse radial, transverse tangential, and axial resolution at 10 cm were (1) 5.7, 5.7, and 7.0 mm (FBP), (2) 5.4, 5.4, and 6.4 mm (3D RAMLA). Attenuation free values of sensitivity were 3,620 counts/sec/MBq at the center of transaxial FOV and 4,324 counts/sec/MBq at 10 cm offset from the center. Scatter fraction was 40.6%, and peak true count rate and NECR were 88.9 kcps @ 12.9 kBq/mL and 34.3 kcps @ 8.84 kBq/mL. These characteristics are better than that of ECAT EXACT PET scanner with BGO crystal. Conclusion: The results of this field test demonstrate high resolution, sensitivity and count rate performance of the 3D PET/CT scanner with GSO crystal. The data provided here will be useful for the comparative study with other 3D PET/CT scanners using BGO or LSO crystals.

The Analysis of Dose in a Rectum by Multipurpose Brachytherapy Phantom (근접방사선치료용 다목적 팬톰을 이용한 직장 내 선량분석)

  • Huh, Hyun-Do;Kim, Seong-Hoon;Cho, Sam-Ju;Lee, Suk;Shin, Dong-Oh;Kwon, Soo-Il;Kim, Hun-Jung;Kim, Woo-Chul;K. Loh John-J.
    • Radiation Oncology Journal
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    • v.23 no.4
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    • pp.223-229
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    • 2005
  • Purpose: In this work we designed and made MPBP(Multi Purpose Brachytherapy Phantom). The MPBP enables one to reproduce the same patient set-up in MPBP as the treatment of the patient and we tried to get an exact analysis of rectal doses in the phantom without need of in-vivo dosimetry. Materials and Methods: Dose measurements were tried at a point of rectum 1, the reference point of rectum, with a diode detector for 4 patients treated with tandem and ovoid for a brachytherapy of a cervix cancer. Total 20 times of rectal dose measurements were made with 5 times a patient. The set-up variation of the diode detector was analyzed. The same patient set-ups were reproduced in self-made MPBP and then rectal doses were measured with TLD. Results: The measurement results of the diode detector showed that the set-up variation of the diode detector was the maximum $11.25{\pm}0.95mm$ in the y-direction for Patient 1 and the maximum $9.90{\pm}4.50mm,\;20.85{\pm}4.50mm,\;and\;19.15{\pm}3.33mm$ in the z-direction for Patient 2, 3, and 4, respectively. Un analyzing the degree of variation in 3 directions the more variation was showed in the z-direction than x- and y-direction except Patient 1. The results of TLD measurements in MPBP showed the relative maximum error of 8.6% and 7.7% at a point of rectum 1 for Patient 1 and 4, respectively and 1.7% and 1.2% for Patient 2 and 3, respectively. The doses measured at R1 and R2 were higher than those calculated except R point of Patient 2. this can be thought to related to the algorithm of dose calculation, whcih corrects for air and water but is guessed not to consider the correction for the scattered rays, but by considering the self-error (${\pm}5%$) TLD has the relative error of values measured and calculated was analyzed to be in a good agreement within 15%. Conclusion: The reproducibility of dose measurements under the same condition as the treatment could be achieved owing to the self-made MPMP and the dose at the point of interest could be analyzed accurately. If a treatment is peformed after achieving dose optimization using the data obtained in the phantom, dose will be able to be minimized to important organs.

Usefulness Evaluation of Artifacts by Bone Cement of Percutaneous Vertebroplasty Performed Patients and CT Correction Method in Spine SPECT/CT Examinations (척추 뼈 SPECT/CT검사에서 경피적 척추성형술 시행 환자의 골 시멘트로 인한 인공물과 CT보정방법의 유용성 평가)

  • Kim, Ji-Hyeon;Park, Hoon-Hee;Lee, Juyoung;Nam-Kung, Sik;Son, Hyeon-Soo;Park, Sang-Ryoon
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.49-61
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    • 2014
  • Purpose: With the aging of the population, the attack rate of osteoporotic vertebral compression fracture is in the increasing trend, and percutaneous vertebroplasty (PVP) is the most commonly performed standardized treatment. Although there is a research report of the excellence of usefulness of the SPECT/CT examination in terns of the exact diagnosis before and after the procedure, the bone cement material used in the procedure influences the image quality by forming an artifact in the CT image. Therefore, the objective of the research lies on evaluating the effect the bone cement gives to a SPECT/CT image. Materials and Methods: The images were acquired by inserting a model cement to each cylinder, after setting the background (3.6 kBq/mL), hot cylinder (29.6 kBq/mL) and cold cylinder (water) to the NEMA-1994 phantom. It was reconstructed with Astonish (Iterative: 4 Subset: 16), and non attenuation correction (NAC), attenuation correction (AC+SC-) and attenuation and scatter correction (AC+SC+) were used for the CT correction method. The mean count by each correction method and the count change ratio by the existence of the cement material were compared and the contrast recovery coefficient (CRC) was obtained. Additionally, the bone/soft tissue ratio (B/S ratio) was obtained after measuring the mean count of the 4 places including the soft tissue(spine erector muscle) after dividing the vertebral body into fracture region, normal region and cement by selecting the 20 patients those have performed PVP from the 107 patients diagnosed of compression fracture. Results: The mean count by the existence of a cement material showed the rate of increase of 12.4%, 6.5%, 1.5% at the hot cylinder of the phantom by NAC, AC+SC- and AC+SC+ when cement existed, 75.2%, 85.4%, 102.9% at the cold cylinder, 13.6%, 18.2%, 9.1% at the background, 33.1%, 41.4%, 63.5% at the fracture region of the clinical image, 53.1%, 61.6%, 67.7% at the normal region and 10.0%, 4.7%, 3.6% at the soft tissue. Meanwhile, a relative count reduction could be verified at the cement adjacent part at the inside of the cylinder, and the phantom image on the lesion and the count increase ratio of the clinical image showed a contrary phase. CRC implying the contrast ratio and B/S ratio was improved in the order of NAC, AC+SC-, AC+SC+, and was constant without a big change in the cold cylinder of the phantom. AC+SC- for the quantitative count, and AC+SC+ for the contrast ratio was analyzed to be the highest. Conclusion: It is considered to be useful in a clinical diagnosis if the application of AC+SC+ that improves the contrast ratio is combined, as it increases the noise count of the soft tissue and the scatter region as well along with the effect of the bone cement in contrast to the fact that the use of AC+SC- in the spine SPECT/CT examination of a PVP performed patient drastically increases the image count and enables a high density of image of the lesion(fracture).

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Evaluation of Radiation Exposure to Nurse on Nuclear Medicine Examination by Use Radioisotope (방사성 동위원소를 이용한 핵의학과 검사에서 병동 간호사의 방사선 피폭선량 평가)

  • Jeong, Jae Hoon;Lee, Chung Wun;You, Yeon Wook;Seo, Yeong Deok;Choi, Ho Yong;Kim, Yun Cheol;Kim, Yong Geun;Won, Woo Jae
    • The Korean Journal of Nuclear Medicine Technology
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    • v.21 no.1
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    • pp.44-49
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    • 2017
  • Purpose Radiation exposure management has been strictly regulated for the radiation workers, but there are only a few studies on potential risk of radiation exposure to non-radiation workers, especially nurses in a general ward. The present study aimed to estimate the exact total exposure of the nurse in a general ward by close contact with the patient undergoing nuclear medicine examinations. Materials and Methods Radiation exposure rate was determined by using thermoluminescent dosimeter (TLD) and optical simulated luminescence (OSL) in 14 nurses in a general ward from October 2015 to June 2016. External radiation rate was measured immediately after injection and examination at skin surface, and 50 cm and 1 m distance from 50 patients (PET/CT 20 pts; Bone scan 20 pts; Myocardial SPECT 10 pts). After measurement, effective half-life, and total radiation exposure expected in nurses were calculated. Then, expected total exposure was compared with total exposures actually measured in nurses by TLD and OSL. Results Mean and maximum amount of radiation exposure of 14 nurses in a general ward were 0.01 and 0.02 mSv, respectively in each measuring period. External radiation rate after injection at skin surface, 0.5 m and 1 m distance from patients was as following; $376.0{\pm}25.2$, $88.1{\pm}8.2$ and $29.0{\pm}5.8{\mu}Sv/hr$, respectively in PET/CT; $206.7{\pm}56.6$, $23.1{\pm}4.4$ and $10.1{\pm}1.4{\mu}Sv/hr$, respectively in bone scan; $22.5{\pm}2.6$, $2.4{\pm}0.7$ and $0.9{\pm}0.2{\mu}Sv/hr$, respectively in myocardial SPECT. After examination, external radiation rate at skin surface, 0.5 m and 1 m distance from patients was decreased as following; $165.3{\pm}22.1$, $38.7{\pm}5.9$ and $12.4{\pm}2.5{\mu}Sv/hr$, respectively in PET/CT; $32.1{\pm}8.7$, $6.2{\pm}1.1$, $2.8{\pm}0.6$, respectively in bone scan; $14.0{\pm}1.2$, $2.1{\pm}0.3$, $0.8{\pm}0.2{\mu}Sv/hr$, respectively in myocardial SPECT. Based upon the results, an effective half-life was calculated, and at 30 minutes after examination the time to reach normal dose limit in 'Nuclear Safety Act' was calculated conservatively without considering a half-life. In oder of distance (at skin surface, 0.5 m and 1 m distance from patients), it was 7.9, 34.1 and 106.8 hr, respectively in PET/CT; 40.4, 199.5 and 451.1 hr, respectively in bone scan, 62.5, 519.3 and 1313.6 hr, respectively in myocardial SPECT. Conclusion Radiation exposure rate may differ slightly depending on the work process and the environment in a general ward. Exposure rate was measured at step in the general examination procedure and it made our results more reliable. Our results clearly showed that total amount of radiation exposure caused by residual radioactive isotope in the patient body was neglectable, even comparing with the natural radiation exposure. In conclusion, nurses in a general ward were much less exposed than the normal dose limit, and the effects of exposure by contacting patients undergoing nuclear medicine examination was ignorable.

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The Benefit of KT-2000 Knee Ligament Arthrometer in Diagnosis of Anterior Cruciate Ligament Injury (슬관절 전방 십자 인대 파열의 진단에 있어서 KT-2000 기기의 유용성)

  • Park, Jai-Hyung;Kim, Hyoung-Soo;Jung, Kwang-Gyu;Yoo, Jeong-Hyun
    • Journal of the Korean Arthroscopy Society
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    • v.8 no.2
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    • pp.82-88
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    • 2004
  • Purpose: In this study, we intended to ascertain the benefit of KT-2000 Knee arthrometer(KT-2000) in the diagnosis of ACL(Anterior cruciate ligament) injury by comparing the anterior displacement of normal knee with that of ACL deficient knee. Materials and Methods: We designated two examiners to measure the anterior displacement of the knee joint of 30 healthy individuals, using KT-2000, at 30$^{\circ}$ flexion setting of muscle full relaxation, contraction, 25$^{\circ}$ internal rotation and 25$^{\circ}$ external rotation and analyzed these results according to the variables and measured the preoperative anterior displacement of the ACL injured knee in the 30 patients who have gone through an arthroscopic ACL reconstruction later. Results: The results of examiner 1 are 6.5${\pm}$1.5 mm, 2.5${\pm}$0.9 mm, 4.8${\pm}$1.2 mm, 6.4${\pm}$1.3 mm in right knee and 5.6${\pm}$1.3 mm, 2.1${\pm}$0.8 mm, 4.5${\pm}$1.2 mm, 5.2${\pm}$1.3 mm in left knee, in order of muscle full relaxation, contraction, 25$^{\circ}$ internal rotation and 25$^{\circ}$ external rotation. The results of examiner 2 are 6.9${\pm}$1.2mm, 2.9${\pm}$1.1mm, 5.6${\pm}$1.6mm, 6.9${\pm}$1.5mm in right, 5.5${\pm}$1.7 mm,1.9${\pm}$0.9 mm, 5.1${\pm}$1.9 mm, 5.7${\pm}$1.6 mm in left knee, The side to side difference of examiner 1 in the setting of muscle relaxation is 0.9${\pm}$1.0 mm. The anterior displaement of ACL injured knee is average 11${\pm}$2.93 mm and difference of average 6.5${\pm}$2.31 mm form that of normal. In comparison between the right and left knees of healthy individuals, the both results of two examiners showed the statistical difference in the setting of muscle full relaxation but, the results showed the side to side difference below 2 mm in 25case(83%), 21case(70%) respectively and above 3 mm in just 1 case. In the comparison between the normal and ACL injured knees, the results show the statistical difference of the side to side difference in the setting of muscle relaxation(p<0.05). Conclusion: The KT-2000 result is affected by relaxation of muscles around knee, flexion angle of knee joint, rotation of tibia, the strength of displacing force, time of the test and physical factors as height and weight. However, the Accuracy of diagnosis of ACL injury by KT-2000 will increase if the examiner is skillful and the tests are made on the exact position of knee joint.

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Pipetting Stability and Improvement Test of the Robotic Liquid Handling System Depending on Types of Liquid (용액에 따른 자동분주기의 분주능력 평가와 분주력 향상 실험)

  • Back, Hyangmi;Kim, Youngsan;Yun, Sunhee;Heo, Uisung;Kim, Hosin;Ryu, Hyeonggi;Lee, Guiwon
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.2
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    • pp.62-68
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    • 2016
  • Purpose In a cyclosporine experiment using a robotic liquid handing system has found a deviation of its standard curve and low reproducibility of patients's results. The difference of the test is that methanol is mixed with samples and the extractions are used for the test. Therefore, we assumed that the abnormal test results came from using methanol and conducted this test. In a manual of a robotic liquid handling system mentions that we can choose several setting parameters depending on the viscosity of the liquids being used, the size of the sampling tips and the motor speeds that you elect to use but there's no exact order. This study was undertaken to confirm pipetting ability depending on types of liquids and investigate proper setting parameters for the optimum dispensing ability. Materials and Methods 4types of liquids(water, serum, methanol, PEG 6000(25%)) and $TSH^{125}I$ tracer(515 kBq) are used to confirm pipetting ability. 29 specimens for Cyclosporine test are used to compare results. Prepare 8 plastic tubes for each of the liquids and with multi pipette $400{\mu}l$ of each liquid is dispensed to 8 tubes and $100{\mu}l$ of $TSH^{125}I$ tracer are dispensed to all of the tubes. From the prepared samples, $100{\mu}l$ of liquids are dispensed using a robotic liquid handing system, counted and calculated its CV(%) depending on types of liquids. And then by adjusting several setting parameters(air gap, dispense time, delay time) the change of the CV(%)are calcutated and finds optimum setting parameters. 29 specimens are tested with 3 methods. The first(A) is manual method and the second(B) is used robotic liquid handling system with existing parameters. The third(C) is used robotic liquid handling system with adjusted parameters. Pipetting ability depending on types of liquids is assessed with CV(%). On the basis of (A), patients's test results are compared (A)and(B), (A)and(C) and they are assessed with %RE(%Relative error) and %Diff(%Difference). Results The CV(%) of the CPM depending on liquid types were water 0.88, serum 0.95, methanol 10.22 and PEG 0.68. As expected dispensing of methanol using a liquid handling system was the problem and others were good. The methanol's dispensing were conducted by adjusting several setting parameters. When transport air gap 0 was adjusted to 2 and 5, CV(%) were 20.16, 12.54 and when system air gap 0 was adjusted to 2 and 5, CV(%) were 8.94, 1.36. When adjusted to system air gap 2, transport air gap 2 was 12.96 and adjusted to system air gap 5, Transport air gap 5 was 1.33. When dispense speed was adjusted 300 to 100, CV(%) was 13.32 and when dispense delay was adjusted 200 to 100 was 13.55. When compared (B) to (A), the result increased 99.44% and %RE was 93.59%. When compared (C-system air gap was adjusted 0 to 5) to (A), the result increased 6.75% and %RE was 5.10%. Conclusion Adjusting speed and delay time of aspiration and dispense was meaningless but changing system air gap was effective. By adjusting several parameters proper value was found and it affected the practical result of the experiment. To optimize the system active efforts are needed through the test and in case of dispensing new types of liquids proper test is required to check the liquid is suitable for using the equipment.

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Analysis of p53 and Retinoblasoma(Rb) Gene Polymorphisms in Relation to Lung Cancer in Koreans (한국인 폐암 환자에 대한 p53 및 Rb유전자의 다형성 분석)

  • Lee, Kyung-Sang;Sohn, Jang-Won;Yang, Suck-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo;Lee, Jung-Hee;Lee, Chun-Geun;Cho, Youl-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.534-546
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    • 1997
  • Background : The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But, so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. Methods : In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis. The two intragenic polymorphisms of the p53 gene(exon 4/ AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain reaction- restriction fragment length polymorphisms(PCR-RFLPs). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. Results : There were no significant differences in the genotype distributions of the p53 gene between lung cancer patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AccII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known to be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p = 0.0297) or adenocarcinomas(p = 0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were also noted between the high dose smokers and low dose smokers including non-smokers(p = 0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio = 0.46, 95% C.I. = 0.25-0.86, p = 0.0124). The combined genotype distribution of the exon 4 AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/Pro and r2/r2(odds ratio = 1.97,95% C.I. = 0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio = 0.54, 95% C.I. = 0.25-1.14). Conclusion : The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koeans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed.

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The Effect of Interferon-γ on Bleomycin Induced Pulmonary Fibrosis in the Rat (Interferon-γ 투여가 쥐에서의 Bleomycin 유도 폐 섬유화에 미치는 영향)

  • Yoon, Hyoung Kyu;Kim, Yong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.1
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    • pp.51-66
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    • 2004
  • Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.