• Archives of Pharmacal Research
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• 제29권11호
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• pp.1018-1023
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• 2006

Chemoresistance remains the major obstacle to successful therapy of cancer. In order to understand the mechanism of multidrug resistance (MDR) that is frequently observed in lung cancer patients, here we studied the contribution of MDR-related proteins by establishing lung cancer cell lines with acquired resistance against etoposide. We found that human H460 lung cancer cells responded to etoposide more sensitively than A549 cells. Among MDR-related proteins, the expression of p-glycoprotein (Pgp) and lung resistance protein (LRP) were much higher in A549 cells compared with that in H460 cells. When we established H460-R1 and -R2 cell lines by progressive exposure of H460 cells to increasing doses of etoposide, the response against etopbside as well as doxorubicin was greatly reduced in R1 and R2 cells, suggesting MDR induction. Induction of MDR was not accompanied by a decrease in the intracellular accumulation of etoposide and the expression of MDR-related proteins that function as drug efflux pumps such as Pgp and MRP1 was not changed. We found that the acquired resistance paralleled an increased expression of LRP in H460 cells. Taken together, our data suggest the implicative role of LRP in mediating MDR in lung cancer.

• 한국환경보건학회지
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• 제31권4호
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• pp.254-259
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• 2005

Permethrin, a synthetic pyrethroid insecticide, has been widely used to protect domestic animals and the public health, as well as in agriculture against a variety of pests, which provides potential for environmental exposure. Permethrin is classified as possible human carcinogen and endocrine disrupting chemical by many international authorities. However, its developmental effects have been rarely studied. This study investigated the effects of permethrin during embryo-genesis. Developmental toxicity of permethrin was evaluated using short-term in vitro battery system. Gestation day 9.5 rat embryos (organogenesis) were cultured with permethrin (0.1,0.4 and 0.8 mg/ml) for 48 hours using whole embryo culture system. All the treatments exhibited significant decreases in the total morphological score. Permethrin induced significant growth retardation and the developmental abnormality at doses of 0.4 and 0.8 mg/ml. Moreover, the DNA and protein contents of embryos decreased in dose-dependent manner. These observations suggest that permethrin contributes to toxicity on embryonic developments in rats.

• Nuclear Engineering and Technology
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• 제50권5호
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• pp.745-750
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• 2018

New exercise technology such as the virtual reality (VR)-based exercise system is required to meet soaring demand for target participants in exercises and to alleviate the difficulties in personnel mobilization through an alternative approach to the exercise system. In a previous study, event tree methodologies were introduced in setting up an exercise scenario of a VR-based radiological exercise system. In the scenario, the locations at which major events occur are rephrased as nodes, routes as paths, and public response actions as protective actions or contents of an exercise at individual locations. In the study, a model for estimating effective doses to the participants is proposed to evaluate the exercise system, using the effective dose rates at particular times and locations derived from a computer program. The effective dose received by a student when she/he follows a successful route is about a half of the dose received when she/he does not follow the exercise guide directions. In addition, elapsed time to finish an exercise when following a successful route is less than one-third of the time spent to finish an exercise when following the guide's directions.

• 방사선산업학회지
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• 제5권1호
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• pp.1-5
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• 2011

Since proteomics can be employed to compare changes in the expression levels of many proteins under particular genetic and environmental conditions, using mass spectrometry to establish radiation stimulon, we performed two-dimensional gel electrophoresis and identified E. coli proteins whose expressions are affected by high dose of ionizing radiation. After exposure to 3 kGy, it was found that 6 proteins involved in carbon and energy metabolism were reduced. Although 4 of 7 protein spots showing a significant increase in expression level were neither identified nor classified, uridine phosphorylase (Udp), superoxide dismutase (SodB), and thioredoxin-dependent thiol peroxidase (Bcp) were proven to be up-regulated after irradiation. This suggests that E. coli subjected to high doses of radiation (3 kGy) may operate a defense system that is able to detoxify reactive oxygen species and stimulate the salvage pathway of nucleotide synthesis to replenish damaged DNA.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.1-14
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• 2019

Resveratrol was first isolated in 1939 by Takaoka from Veratrum grandiflorum O. Loes. Following this discovery, sporadic descriptive reports appeared in the literature. However, spurred by our seminal paper published nearly 60 years later, resveratrol became a household word and the subject of extensive investigation. Now, in addition to appearing in over 20,000 research papers, resveratrol has inspired monographs, conferences, symposia, patents, chemical derivatives, etc. In addition, dietary supplements are marketed under various tradenames. Once resveratrol was brought to the limelight, early research tended to focus on pharmacological activities related to the cardiovascular system, inflammation, and cancer but, over the years, the horizon greatly expanded. Around 130 human clinical trials have been (or are being) conducted with varying results. This may be due to factors such as disparate doses (ca. 5 to 5,000 mg/day) and variable experimental settings. Further, molecular targets are numerous and a dominant mechanism is elusive or nonexistent. In this context, the compound is overtly promiscuous. Nonetheless, since the safety profile is pristine, and use as a dietary supplement is prevalent, these features are not viewed as detrimental. Given the ongoing history of resveratrol, it is reasonable to advocate for additional development and further clinical investigation. Topical preparations seem especially promising, as do conditions that can respond to anti-inflammatory action and/or direct exposure, such as colon cancer prevention. Although the ultimate fate of resveratrol remains an open question, thus far, the compound has inspired innovative scientific concepts and enhanced public awareness of preventative health care.

• 핵의학기술
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• 제16권1호
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• pp.50-56
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• 2012

일시 출입자로 분류된 핵의학과 출입 환경미화원은 주기적으로 타과와 업무순환을 하고, 또한 작업 시간과 환경 등의 변화가 많기 때문에 관리하기에 어려운 점이 있으며 따라서 이들의 분류를 명확히 할 필요가 있다. 이에 본 논문에서는 핵의학과에서 근무하는 환경미화원의 피폭 상황을 분석하여 일시 출입자로 분류된 조건의 타당성에 대하여 검토해 보고 작업 환경의 변화 및 근무 시간의 조절이 필요한가를 알아보았다. 우선 먼저 PET실과 혈액 검사실에서 근무하는 환경미화원과 감마 카메라실에서 근무하는 환경 미화원 2명을 대상으로 한 달간 근무 시간 중에 OSL을 각각 착용시켜 개인 피폭 선량을 측정하였다. 둘째로 survey meter를 이용하여 두 명의 환경미화원의 작업 환경, 근무 형태에 따라 시간대 별로 핵의학과 내 14개 구역을 선정, 총 10회 공간 선량률을 측정한 결과 이들의 피폭 선량은 연간 1mSv를 초과하지 않았으며, survey meter를 이용하여 조사한 결과 또한 연간 1 mSv를 초과하지 않을 것으로 추정되지만 그 수치가 1 mSv에 근접하였다. 따라서 일시 출입자로써의 분류를 좀 더 명확히 하기 위해서는 PET 안정실과 같은 피폭이 상대적으로 많은 구역에서의 노출 확률을 줄이기 위하여 이들에게 방사선 관리 구역내 교육을 실시하고, 또한 근무시간 및 근무 형태를 적절히 변경한다면 이들의 피폭 선량은 확연히 줄어들 것으로 사료된다.

• 대한디지털의료영상학회논문지
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• 제14권2호
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• pp.23-31
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• 2012

There are AEC mode and fix mode to exposure when the whole spine antero-posterior radiography is done by using DR equipment. This study compared the utility of fix mode to AEC mode, by evaluating organ dose and effective dose and by examining the quality of radiographic image. GE DEFINIUM 8000 and ART-200X Rando Phantom manufactured by Flukebiometical were used for this study. The Rando phantom was set in front of wall detector of X-rays equipment. AEC mode was set at 80kVp and Fix mode was set at 80kVp, 25mAs, 32mAs, 40mAs, and 50mAs. Whole spine AP image were aquired by combining C, T-L and L-S spine images obtained through 3 exposures. When obtaining C, T-L and L-S spine images, were checked for Air kerma (mGy) value calculated by UNFORS Xi meter attached at the phantom surface of center of radiation field. The effective and organ doses were compared by PCXMC program (PC-Based Monte Carlo Program). The quality of obtained radiographic image was evaluated visually by 3 radiologists using resolution chart. When the effective doses was calculated based on tissue weighting factor of ICRP-103, 1.278mSv was measured by AEC mode, and Fix mode measured 0.405mSv at 25mAs, 0.518mSv at 32mAs, 0.649mSv at 40mAs, and 0.810mSv at 50mAS. In addition, the organ dose measured with esposure at 25mAs by Fix mode was almost equivalent to the organ dose by AEC mode, at the esophagus, thyroid, oral mucosa, salivaly glands located at the cervical spine part, while the organ dose by Fix mode was in general lower than the organ dose by AEC mode at the other organs. When Fix mode at 32mAs, 40mAs, and 50mAs was compared to AEC mode for organ dose in 26 organs, AEC mode had higher measurement in 21 organs but not for than brain, trachea, thyroid, oral mucosa, and salivaly glands which are located at the cervical spine part. The image quality evaluated by resolution test chart was much higher with AEC mode than the quality with Fix mode at all exposure conditions. However, while the image quality of cervical spine exposured at 50mAs by Fix mode was lower than the quality of AEC mode, thoraco-lumbar spine and lumbo-sacral spine were calculated and the quality was similar to AEC mode. Scoliosis occurs mainly at thoraco-lumbar and lumbo-sacral spine, not at cervical spine. Compared to AEC mode, Using the appropriate protocol (80kVp, 50mAs) of fix mode for whole spine AP radiography was thought to be useful because the image quality of the thoraco-lumar and lumbo-sacral spine was similar on AEC mode, Also organ and effective doses can be decreased with Fix mode. Therefore, It is considered that fix mode can be used properly with AEC mode for whole spine AP radiography when considering patient's body posture.

• Asian Pacific Journal of Cancer Prevention
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• 제17권6호
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• pp.2979-2982
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• 2016

Background: High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. Materials and Methods: Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. Results: We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (p < 0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two tailed Fisher exact test). In other words, the beam radiation to rectum and rectosigmoid that also reached the ovaries reduced the risk of ovarian cancer by 44%. In addition, there was a significant inverse relationship between ovarian cancer in white women and radon background radiation (r = - 0.465. p = 0.002) and total background radiation (r = -0.456, p = 0.002). Because increasing age and obesity are risk factors for ovarian cancer, multivariate linear regression was performed. The inverse relationship between ovarian cancer incidence and radon background was significant (${\beta}=-0.463$, p = 0.002) but unrelated to age (${\beta}=-0.080$, p = 0.570) or obesity (${\beta}=-0.180$, p = 0.208). Conclusions: The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권2호
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• pp.129-134
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• 2001

Since NNK is one of the most abundant tobacco-specific alkaloids and a strong carcinogenic nitrosamine, it has been used for evaluating a potential of carcinogenicity in the animal models. The present study has attempted to examine the potential of carcinogenicity of NNK in human epithelial cells, from which the cell type the most of cancers including oral cancer and nasal cavity cancer are originated. The cellular model used for the study is a human keratinocyte cell system immortalized by Ad12-SV40 hybrid virus. The cellular system has successfully been used for the carcinogenicity studies because of its limitless life span, epithelial morphology and nontumorigenicity. When cells were treated with a variety of NNK concentrations, levels of saturation density and soft agar colony formation were increased in a dose-dependent fashion. Colonies of large cell aggregates were above 5 at the higher doses. The results indicate that exposure of human cells with NNK induced loss of contact inhibition and increases of anchorage independence and cellular adhesion, which are typical characteristics of the neoplatically transformed cells. When cells were exposed with 100uM NNK for 2hr, mRNA levels of IL-1 and PAI-2 were increased in a dose-dependent manner, but expression of TGF- 1 was not affected. While expression of growth regulatory factors were altered with a short-term exposure, there was no alteration of these factors in the NNK-transformed cells. However, mRNA levels of fibronectin were increased both in the short-term treatment and in the transformation. The results suggest that altered expression of extracellular matrix such as fibronectin following short-term exposure might be fixed in the genome and these altered properties be continuously transfered throughout the cell division. Western blot analysis showed a translocation of PKC- from cytosolic fraction to the particulate fraction, indicating a possible role of NNK in the signal transduction pathway. The present study provided an evidence that NNK in the smoking may be associated with epithelial origin cancer such as oral and nasal cavity cancers. In addition, this study suggested that altered expression of extracellular matrix and PKC may play an important role in the carcinogenic mechanism of NNK.

• Journal of Radiation Protection and Research
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• 제39권3호
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• pp.150-158
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• 2014

각 의료기관 내 방사선 관련 종사자나 방사선 치료환자들은 진단 및 치료 시 필연적으로 의료상 피폭을 수반하게 된다. 국제방사선방호위원회(ICRP) 권고나 국제원자력기구(IAEA)의 기준에 따라 기준선량 제약치를 적용 및 권고 받고 있지만 1차 피폭대상자인 종사자나 환자들의 피폭최적관리를 위해서는 잠재적인 피폭대상자들에게 기존의 피폭관리 시스템보다 직접적이고 가용성이 높은 측정 및 분석 방법이 필요하다. 따라서 본 연구에서는 기존에 구비된 휴대용 단말과 연동하여 원거리에서 실시간으로 방사선 모니터링이 가능한 시스템을 개발하였다. 모니터링 시스템은 검출부, 영상부, 통신부 세 부분으로 구성되었다. 검출부는 시스템의 소형화를 위해 실리콘 광증배소자(silicon photomultiplier) 기반 섬광검출기를 설계하였으며, 영상부는 무선 CCD (charge-coupled device)카메라 모듈을 사용하여 검출부와 함께 Bluetooth 통신모듈을 통해 휴대용 단말로 측정된 방사선 정보와 영상이 전송된다. 제작된 시스템은 성능 평가를 위해 진단용 X-ray 발생장치와 $^{137}Cs$, $^{22}Na$, $^{60}Co$, $^{204}Tl$, $^{90}Sr$ 선원을 사용하였다. 측정결과를 통해 개발된 시스템은 gamma, beta, X-ray에 대해서 검출 반응성을 확인하였고, 방사선 세기에 따른 응답 선형성과 MCNPX 전산코드를 이용한 측정 거리에 따른 시스템의 검출 정확도 평가 시 3% 내외의 오차범위를 확인하였다. 본 연구의 결과는 방사선 검출 시스템 구성의 비용절감 효과와 개인피폭정도관리에 기여할 것으로 기대한다.