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Genetic Toxicity Test of o-Nitrotoluene by Ames, Micronucleus, Comet Assays and Microarray Analysis
Lee, Eun-Mi,Lee, So-Youn,Lee, Woo-Sun,Kang, Jin-Seok,Han, Eui-Sik,Go, Seo-Youn,Sheen, Yhun-Yong,Kim, Seung-Hee,Park, Sue-Nie The Korean Society of Toxicogenomics and Toxicopro 2007 Molecular & cellular toxicology Vol.3 No.2
o-Nitrotoluene is used to synthesize artificial dyes and raw materials of urethane resin. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of onitrotoluene. TA1535 and TA98 cells were treated with o-nitrotoluene to test its toxicity by basic genetic toxicity test. Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to o-nitrotoluene was analyzed using Affymatrix genechip. The result of Ames test was that o-nitrotoluene treatment did not increase the mutations both in base substitution strain TA1535 and in frame shift TA98. o-Nitrotoluene has not increased micronuclei in CHO cells. But onitrotoluene increased DNA damage in L5178Y cell. Two-hundred two genes were initially selected as differentially expressed genes in response to o-nitrotoluene by microarray analysis and forty four genes among them were over 2 times of log fold changed. These forty four genes could be candidate biomarkers of genetic toxic action of o-nitrotoluene related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to the DNA damage will be useful to understand the detailed mechanism of action of o-nitrotoluene.
( Woo Sun Lee ),( Jee Eun Kim ),( Joo Hwan Kim ),( Kyung Hye Koo ),( Seul Lee ),( Yhun Yong Sheen ),( Young Na Yum ),( Dong Sup Kim ),( Sue Nie Park ) 한국동물실험대체법학회 2009 한국동물실험대체법학회 학술대회집 Vol.2009 No.1
Genotoxicity tests are not only to identify compounds with genotoxic damage but also to be used for the interpretation of carcinogenicity studies. Recently ICH genotoxicity test guideline is on the process of changing from 1997 version to new one(ICH S2(R1) step3, 2008) to improve the evaluation power of genotoxicity test system specifically suggesting to consider the mode of action of chemicals for evaluation. Considering in vivo target site of carcinogen, we tried to perform genotoxicity tests and systems approaches to predict or categorize both lung and liver cancer related chemicals. We performed conventional genotoxicity battery tests together with several new or alternative test methods including comet assay and micronucleus assay. In addition, we employed genomics, proteomics and ras-, E7-transgenic systems to understand the mode of action of chemicals. These studies have been carried out by intra-and extra mural projects including international bodies such as OECD/IPCS and national regulatory US_FDA/NCTR and Japan(JaCVAM). I will be presenting what we have carried out. Understanding mutagenic mode of action using toxicogenomics approaches and genotoxicity testing in in vitro and in vivo study may provide more information useful for the risk assessment based on discrimination between genotoxicity and nongenotoxicity in carcinogens. (These researches were supported by grants (국제협565, 561 & 나노독541) to S. Park and a grant(응용연510) to Y. Sheen from Korea Food & Drug Administration in 2008.
Emphysema as a Risk Factor for the Outcome of Surgical Resection of Lung Cancer
Lee, Sung Ah,Sun, Joo Sung,Park, Joo Hun,Park, Kyung Joo,Lee, Sung Soo,Choi, Ho,Sheen, Seung Soo,Chung, Woo Young,Lee, Keu Sung,Park, Kwang Joo,Hwang, Sung Chul The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.8
<P>It is unclear whether emphysema, regardless of airflow limitation, is a predictive factor associated with survival after lung cancer resection. Therefore, we investigated whether emphysema was a risk factor associated with the outcome after resection for lung cancer. This study enrolled 237 patients with non small cell lung cancer with stage I or II who had surgical removal. Patient outcome was analyzed based on emphysema. Emphysema was found in 43.4% of all patients. Patients with emphysema were predominantly men and smokers, and had a lower body mass index than the patients without emphysema. The patients without emphysema (n=133) survived longer (mean 51.2±3.0 vs. 40.6±3.1 months, <I>P</I>=0.042) than those with emphysema (n=104). The univariate analysis showed a younger age, higher FEV<SUB>1</SUB>/FVC, higher body mass index, cancer stage I, and a lower emphysema score were significant predictors of better survival. The multivariate analysis revealed a younger age, higher body mass index, and cancer stage I were independent parameters associated with better survival, however, emphysema was not. This study suggests that unfavorable outcomes after surgical resection of lung cancer should not be attributed to emphysema itself.</P>
Lee, Woo-Sun,Kim, Hyun-Joo,Lee, Eun-Mi,Kim, Joo-Hwan,Suh, Soo-Kyung,Kwon, Kyung-Jin,Sheen, Yhun-Yong,Kim, Seung-Hee,Park, Sue-N. The Korean Society of Toxicogenomics and Toxicopro 2007 Molecular & cellular toxicology Vol.3 No.2
8-Hydroxyquinoline is used as antibacterial agent and antioxidant based on its function inducing the chelation of ferrous ion present in host resulting in production of chelated complex. This complex being transported to cell membrane of bacteria and fungi exerts antibacterial and antifungal action. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of 8-hydroxyquinoline. TA1535 and TA98 cells were treated with 8-hydroxyquinoline to test its toxicity by basic genetic toxicity test, Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to 8-hydroxyquinoline were analyzed using Affymatrix genechip. The result of Ames test was that 8-hydroxyquinoline treatment increased the mutations in base substitution strain TA1535 and likewise, 8-hydroxyquinoline also increased mutations in frame shift TA98. 8-Hydroxyquinoline increased micronuclei in CHO cells and DNA damage in L5178Y. 8-Hdroxyquinoline resulted in positive response in all three tests showing its ability to induce not only mutation but also DNA damage. 783 Genes were initially selected as differentially expressed genes in response to 8-hydroxyquinoline by microarray analysis and 34 genes among them were over 4 times of log fold changed. These 34 genes could be candidate biomarkers of genetic toxic action of 8-hydroxyquinoline related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to their biological function will be useful to understand the detailed mode of action of 8-hydroxyquinoline.
이정찬 ( Jung Chan Lee ),박정진 ( Jeong Jin Park ),신동혁 ( Dong Hyuk Sheen ),최영미 ( Young Mi Choi ),박남규 ( Nam Gyu Park ),김우규 ( Woo Kyu Kim ),이윤종 ( Yun Jong Lee ),이은봉 ( Eun Bong Lee ),송영욱 ( Yeong Wook Song ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.2
Objective: To determine the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of knee osteoarthritis (OA). Methods: In this randomized, placebo-controlled, double-blind trial, 51 patients with knee OA, diagnosed according to the criteria of the American College of Rheumatology, were treated with PEMF or placebo. Eleven patients failed to attend after screening and were excluded from analysis. Treatment consisted of 3 half-hour periods of exposure per week over 6 weeks in a specially designed cylindrical device that emits low-frequency pulsed electromagnetic fields (25 gauss, 12 Hz). The primary outcome measure was reduction in pain on movement using a 10 cm visual analog scale. Secondary outcome measures included joint swelling and tenderness, the Lequesne index, and overall evaluations of improvement by the patient and examining physician. Evaluations were made at baseline, 3 week and 6 week during treatment and 4 weeks after finishing treatment. Results: There were no significant differences between PEMF and placebo groups in respect of any outcome measures after treatment. Range of motion and knee swelling tended to be improved in the PEMF group. There were no clinically relevant adverse effects attributable to PEMF treatment. Conclusion: These results suggest that the PEMF treatment has no clinically significant benefits in patients with knee OA resistant to conventional treatment. The larger studies are needed to confirm the efficacy of PEMF therapy in knee OA.
Lee, Hongpyo,Nam, Yoonho,Gho, Sung-Min,Han, Dongyeob,Kim, Eung Yeop,Lee, Sheen-Woo,Kim, Dong-Hyun Korean Society of Magnetic Resonance in Medicine 2018 Investigative Magnetic Resonance Imaging Vol.22 No.4
Purpose: The objective of this study was to obtain improved susceptibility weighted images (SWI) of the cervical spinal cord using respiratory-induced artifact compensation. Materials and Methods: The artifact from $B_0$ fluctuations by respiration could be compensated using a double navigator echo approach. The two navigators were inserted in an SWI sequence before and after the image readouts. The $B_0$ fluctuation was measured by each navigator echoes, and the inverse of the fluctuation was applied to eliminate the artifact from fluctuation. The degree of compensation was quantified using a quality index (QI) term for compensated imaging using each navigator. Also, the effect of compensation was analyzed according to the position of the spinal cord using QI values. Results: Compensation using navigator echo gave the improved visualization of SWI in cervical spinal cord compared to non-compensated images. Before compensation, images were influenced by artificial noise from motion in both the superior (QI = 0.031) and inferior (QI = 0.043) regions. In most parts of the superior regions, the second navigator resulted in better quality (QI = 0.024, P < 0.01) compared to the first navigator, but in the inferior regions the first navigator showed better quality (QI = 0.033, P < 0.01) after correction. Conclusion: Motion compensation using a double navigator method can increase the improvement of the SWI in the cervical spinal cord. The proposed method makes SWI a useful tool for the diagnosis of spinal cord injury by reducing respiratory-induced artifact.
Managing injection-induced seismic risks
Lee, Kang-Kun,Ellsworth, William L.,Giardini, Domenico,Townend, John,Ge, Shemin,Shimamoto, Toshihiko,Yeo, In-Wook,Kang, Tae-Seob,Rhie, Junkee,Sheen, Dong-Hoon,Chang, Chandong,Woo, Jeong-Ung,Langenbruc American Association for the Advancement of Scienc 2019 Science Vol.364 No.6442
<P>Heat transported from deep within Earth's crust can be used to generate electricity or provide direct heating by circulating fluid through permeable fracture networks in hot rock. Because naturally permeable systems are rare, enhanced geothermal system (EGS) technology stimulates the creation of permeable pathways in otherwise impermeable rock by means of the injection of water under high pressure, creating new fractures and causing preexisting fractures to open. But several EGS projects have encountered problems of induced seismicity, particularly the moment magnitude (<I>M</I><SUB>w</SUB>) 5.5 earthquake in 2017 that occurred near an EGS drill site in Pohang, Republic of Korea (South Korea). Here we explore the implications of, and derive lessons from, the Pohang experience. The Pohang earthquake provides unequivocal evidence that EGS stimulation can trigger large earthquakes that rupture beyond the stimulated volume and disproves the hypothesis that the maximum earthquake magnitude is governed by the volume of injected fluids. Because that hypothesis tacitly underpins hazard-based methods used for managing induced seismicity, those methods must be revised and based on considerations of risk.</P>
Melphalan Modulates the Expression of E7 Specific Biomarkers in E7-Tg Mice
SHEEN, YHUN YHONG,KIM, EUN JIN,KIM, HEE JONG,LEE, SO JUNG,KANG, JEONG WOO,LEE, DONG HUN,CHOI, HEE SOOK,KIM, JIN MAN,YANG, YOUNG,PARK, SUE NIE,YOON, DO YOUNG 梨花女子大學校 藥學硏究所 2011 藥學硏究論文集 Vol.- No.21
HPV oncoproteins are selectively retained and expressed in HPV infected carcinoma cells. The E7 oncoprotein interacts with the tumour suppressor Rb, and leads to the progression of oncogenesis. In a previous study, E7 biomarkers were identified in E7 Tg mice. In this study, in order to investigate whether a genotoxic carcinogen would modulate carcinogenesis in the E7-Tg mice, an anticancer drug, melphalan, was intraperitoneally injected into E7-Tg mice for eight weeks at two-day intervals and then genes and proteins were analysed using Omics approaches and RT-qPCR. RT-qPCR was performed to confirm whether E7 biomarkers would be modulated by melphalan treatment in E7-Tg mice, revealing that up-regulated E7 markers such as cyclin B1, CD166, and actin alpha1 were down-regulated, whereas expression of down-regulated E7 markers such as vimentin was restored by melphalan treatment. These results suggest that melphalan inhibits carcinogenesis via modulating E7-specific genes and proteins expressed in the lung tissues of E7 Tg mice.