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      • Characterizing a rice mutant showing early senescence phenotype.

        Kang-Ie Lee,Backki Kim,Yoye Yu,Jaebok Cho,Joohyun Lee,Hee-Jong Koh 한국육종학회 2012 한국육종학회 심포지엄 Vol.2012 No.07

        In plant, senescence is associated with various aspects of the final stage of leaf development, nutrient relocation from leaves to reproducing seeds and stress resistance, and yield which is the most important trait in crops. Thus, the increase of knowledge on the regulatory processes of plant senescence will allow us to manipulate senescence for agronomic benefit in the future. of genetic studies have been conducted with mutants, where most of studies were focused on the delayed senescence mutants which are associated with positive factors on senescence by treating EMS to Koshikari, we induced a mutant showing early senescence phenotype, which possibly enable us to identify a negative factor of senescence. The appearance of the mutant is identical before booting stage and then the mutant showed senescence phenotype rignt before booting stage whereas Koshikari have health green leaves. The clumn length of the mutant is 98cm and the panicle length is 23cm as same as those of Koshikari. The chlorophyl contents of the mutant leaves, measured by SPAD, decreased during senescence. The soluble protein contents in the mutant leaves also decreased but no differences in the constitution reolved 1D-SDS-PAGE was detected. However, an additional shotgun proteomic approach to detect the differences of the protein constitutions during the senescence in the mutant leaves will be conducted.

      • Thematic Poster : TP-46 ; Promoter Methylation of MIR137 and Its Clinical Significance in Surgically Resected Lung Cancer

        ( Nah Yeon Kang ),( Su Yeon Choi ),( Young Kyoon Kim ),( Ie Ryung Yoo ),( Dae Hee Han ),( Dong Soo Lee ),( Yeon Sil Kim ),( Sook Hee Hong ),( Jin Hyoung Kang ),( Kyo Young Lee ),( Jae Gil Park ),( Soo 대한결핵 및 호흡기학회 2014 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.118 No.-

        Background: Recent studies suggest that miR-137 functions as tumor suppressor in various tumors including colorectal cancer, glioblastoma multiforme, oral cancer, and squamous cell carcinoma of the head and neck. The silencing of miR-137 could be related with its abnormal promoter hypermethylation. The purpose of this study was to investigate the significance of MIR137 promoter methylation in lung cancer. Methods: Lung cancer cell lines were treated with DNA methyltransferase inhibitor (5’-Aza) and/or HDAC inhibitor (Trichostatin A) whether miR-137 could be reactivated. From paired tumor and adjacent non-tumor lung tissues (n=50), real-time RT-PCR for miR-137 expression and cyclin dependent kinase 6 (CDK6), quantitative methylation specific PCR for methylation analysis, and bisulfite modified DNA sequencing for validation were used for the study. Results: miR-137 was reactivated by treatment with 5’-Aza and/or Trichostatin A in lung cancer cell lines. miR-137 was significantly downregulated and CDK6 was significantly upregulated in lung tumor tissues compared with adjacent non-tumor tissues. Quantitative methylation specific PCR showed increased MIR137 promoter methylation in lung tumor tissues compared with adjacent non-tumor tissues, which was further validated with bisulfite sequencing. Conclusions: These results suggest that miR-137 has a role of tumor suppressor and its expression is regulated by promoter methylation. The decreased expression of miR-137 combined with increased expression of CDK6 could be associated with lung cancer carcinogenesis.

      • Poster Session : PS 1586 ; Lung Cancer : Promoter Methylation of MIR137 and Its Clinical Signifi cance in Surgically Resected Lung Cancer

        ( Na Hyeon Kang ),( Su Yeon Choi ),( Young Kyoon Kim ),( Ie Ryung Yoo ),( Dae Hee Han ),( Dong Soo Lee ),( Yeon Sil Kim ),( Sook Hee Hong ),( Jin Hyoung Kang ),( Kyo Young Lee ),( Jae Gil Park ),( Soo 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Background: Recent studies suggest that miR-137 functions as tumor suppressor in various tumors including colorectal cancer, glioblastoma multiforme, oral cancer, and squamous cell carcinoma of the head and neck. The silencing of miR-137 could be related with its abnormal promoter hypermethylation. The purpose of this study was toinvestigate the signifi cance of MIR137 promoter methylation in lung cancer. Methods: Lung cancer cell lines were treated with DNA methyltransferase inhibitor (5`-Aza) and/or HDAC inhibitor (Trichostatin A) whether miR-137 could be reactivated. From paired tumor and adjacent non-tumor lung tissues (n=50), real-time RT-PCR for miR-137 expression and cyclin dependent kinase 6 (CDK6), quantitative methylation specifi c PCR for methylation analysis, and bisulfi te modifi ed DNA sequencing for validation were used for the study. Results: miR-137 was reactivated by treatment with 5`-Aza and/or Trichostatin A in lung cancer cell lines. miR-137 was signifi cantly downregulated and CDK6 was significantlyupregulated in lung tumor tissues compared with adjacent non-tumor tissues. Quantitative methylation specifi c PCR showed increased MIR137 promoter methylation in lung tumor tissues compared with adjacent non-tumor tissues, which was further validated with bisulfi te sequencing. Conclusions: These results suggest that miR-137 has a role of tumor suppressor and its expression is regulated by promoter methylation. The decreased expression of miR- 137 combined with increased expression of CDK6 could be associated with lung cancer carcinogenesis.

      • Detection of copy number variations using array-based comparative genomic hybridization analysis in rice responding to different types of ionizing radiations

        Sun-Hee Kim,Jung Eun Hwang,Kang-Ie Lee,Jin-Baek Kim,Sang Hoon Kim,Bo-Keun Ha,Joon-Woo Ahn,Si-Yong Kang,Dong Sub Kim 한국육종학회 2013 한국육종학회 심포지엄 Vol.2013 No.07

        Copy number variations (CNVs) are considered major sources of genetic variation, and CNVs may influence phenotypic variation and gene expression. To detect CNVs, rice seeds were exposed with 100~400 Gy of gamma-ray (GA, 60Co), cosmic-ray (CR) by Russia ISS, and 30 and 40 Gy of ion beam (IB, 220 Mev carbon ion). After the exposed rice seeds were cultured in 1/2 MS medium for 14 days, they were used for array-based Comparative genomic hybridization (CGH) analysis using Agilent’s RICE CGH array. As a results, the highest number of CNVs (Gain 808 and Loss 24,080) were detected in the CR treatment, whereas GA100 (100 Gy of GA) was identified the least CNVs. Compared individual chromosome, the chromosome 8 and 11 were identified the highest CNVs, the chromosome 3 had the least CNVs. Most of identified CNVs existed in the range of 10~500kb. In particular, the same CNV locations among different types of ionizing radiation were observed in chromosome 12, and these CNVs contained the commonly 5 amplified genes, containing retrotransposon protein, NADH-ubiquinone oxidoreductase chain 3, heavy metal transport/detoxification protein domain containing protein, and 2 unknown proteins. Other studies were reported that Ty1 (Long Terminal Repeat-retrotransposon family 1) transcription and retrotransposition were induced by different environmental stresses such as ionizing radiation, UV-light exposure, DNA damage and nutrient starvation in Saccharomyces cerevisiae. Our results also show that retrotransposon protein (LOC_Os12g34016) was specifically amplified by different types of ionizing radiation.

      • Analysis of transcriptome change in high level of VitE accumulating rice mutant induced by in vitro mutagenesis

        Jung Eun Hwang,Sun-Hee Kim,Kang-ie Lee,Sun-Goo Hwang,Jin-Baek Kim,Sang Hoon Kim,Bo-Keun Ha,Si-Yong Kang,Dong Sub Kim 한국육종학회 2013 한국육종학회 심포지엄 Vol.2013 No.07

        VitE (tocotrienols and tocopherols) are micronutrients with antioxidant properties synthesized by photosynthetic bacteria and plants that play important roles in animal and human nutrition. A new mutant line, T1001-1, was isolated from in vitro mutagenized population by ionizing radiation and shown to have increased VitE contents. The total VitE content was 26% increased in the T1001-1 mutant seeds compare with cv. Dongan (wild-type). In addition, we showed that the mutant confers retarded seedling growth during the early seedling growth stage in rice. To study the molecular mechanism of VitE biosynthesis, we used the rice microarray to identify genes that are upor down-regulated in T1001-1 mutant. In addition, we identified differentially regulated pathway using MapMan analysis, which provides deep insight into changes in transcript and metabolites. Our results enhanced the transcription of genes involved in starch and lipid metabolism in T1001-1 mutant. To identify the molecular mechanisms of the events involving transcription factors in tocopherol accumulation, we compared the expression patterns of transcription factors. The AP2-EREBP, WRKY, C2H2 transcription factor were up-regulated, whereas the MYB family was down-regulated in T1001-1 mutant. Our results demonstrate change of important transcript in high level of VitE accumulating rice mutant.

      • SCIEKCI등재

        Efficacy of Initial Treatment with Clevudine in Naive Patients with Chronic Hepatitis B

        ( Hyeon Woong Yang ),( Byung Seok Lee ),( Tae Hee Lee ),( Heon Young Lee ),( Kwan Woo Nam ),( Young Woo Kang ),( Hee Bok Chae ),( Seok Hyun Kim ),( Seok Bae Kim ),( Hyang Ie Lee ),( An Na Kim ),( Il H 대한내과학회 2010 The Korean Journal of Internal Medicine Vol.25 No.4

        Background/Aims: Clevudine, a pyrimidine nucleoside analogue, has potent antiviral effects in patients with chronic viral hepatitis B (CHB). We report the efficacy of initial treatment with clevudine in naive patients with CHB living in Daejeon and Chungcheong Province, South Korea. Methods: One hundred five adults with CHB were administered 30 mg of clevudine per day for an average of 51 weeks. We evaluated viral markers and liver biochemistry retrospectively every 3 months. Results: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatitis B virus (HBV) DNA before the treatment were 184 ± 188 IU/L, 150 ± 138 IU/L, and 7.1 ± 1.2 log copies/mL, respectively. Undetectable rates (< 60 IU/mL) of DNA were 36.2%, 68.9%, 83.6%, 76.2%, and 75.8% at 12, 24, 36, 48, and 60 weeks, respectively. Seroconversion rates were 9.1%, 13.6%, 24.6%, 26.5%, and 26.1% and ALT normalization rates were 64.5%, 78.1%, 87.9%, 90.0% at 12, 24, 36, and 48 weeks, respectively. Six patients (5.7%) had a viral breakthrough. Conclusions: Clevudine is a useful drug in the initial treatment of patients with CHB, with a potent antiviral effect and low incidence of viral breakthrough. (Korean J Intern Med 2010;25:372-376)

      • SCOPUSKCI등재

        연구논문 : 대전과 충청남북도에 거주하는 만성 C형간염 환자에서 페그인터페론 알파 2a와 2b의 초치료 효과 비교

        김정일 ( Jeong Il Kim ),김석현 ( Seok Hyun Kim ),이병석 ( Byung Seok Lee ),이헌영 ( Heon Young Lee ),이태희 ( Tae Hee Lee ),강영우 ( Young Woo Kang ),이향이 ( Hyang Ie Lee ),김안나 ( An Na Kim ),남순우 ( Soon Woo Nam ),박병출 ( By 대한간학회 2008 Clinical and Molecular Hepatology(대한간학회지) Vol.14 No.4

        목적: 페그인터페론 알파 2a와 알파 2b는 만성 C형간염의 표준치료제로 사용되고 있으나 두 약제의 치료반응을 비교한 연구는 거의 없는 실정이다. 본 연구는 만성 C형간염의 초치료로서 리바비린과의 병합요법 시 페그인터페론 2a와 2b의 치료 효과와 부작용을 비교해 보고자 하였다. 대상과 방법: 2004년 1월부터 2007년 7월까지 대전과 충청남북도에 위치한 7개의 대학병원에서 만성 C형간염 또는 이로 인한 대상성 간경변증으로 진단받고 페그인터페론과 리바비린 병합요법을 시행한 환자 97명의 의무기록을 후향적으로 분석하였다. 페그인터페론 알파 2a군이 48명, 2b군이 49명이었으며, HCV 유전자형 1형에 감염된 환자에 대해서는 페그인터페론 알파 2a (180 ?g/주) 또는 알파 2b (1.5 ?g/kg/주) 및 리바비린(1,000~1,200 mg/일)을 48주간, 비1형 환자에 대해서는 위와 동일한 용량의 페그인터페론과 리바비린(800 mg/일)을 24주간 투여하였다. 결과: 전체 환자에서 페그인터페론 알파 2a와 2b의 조기 바이러스반응(89.6% vs. 89.7%), 치료 종료 바이러스반응(79.2% vs. 79.5%) 및 지속바이러스반응(72.9% vs. 73.5%)은 두 약제 간에 유의한 차이가 없었다. 또한 HCV 유전자형에 따라 각 바이러스반응을 분석하였을 때도 유전자 1형과 비1형 모두에서 두 약제 간에 유의한 차이를 발견할 수 없었다. 총 97명 중에 치료를 조기 중단한 환자는 10명(10.3%)이었고, 페그인터페론 알파 2a와 2b가 각각 7명(14.6%), 3명(6.1%)이었으나 유의한 차이는 없었다. 부작용으로는 독감양 증상이 가장 흔하였으며, 부작용의 종류별 발생빈도는 두 약제간에 유의한 차이가 없었다. 결론: 만성 C형간염 환자의 초치료로서 리바비린과의 병합치료 시 페그인터페론 알파 2a와 2b 간에 치료효과와 부작용 발생빈도에 있어 유의한 차이가 없었다. Backgrounds/Aims: Peginterferon alpha-2a or -2b is the standard treatment regimen in chronic hepatitis C. However, there have been few comparative studies of the efficacies of these two types of peginterferon. We evaluated their efficacies in combination with ribavirin as a initial treatment for chronic hepatitis C. Methods: Ninety-seven patients were treated with peginterferon alpha-2a (180 ?g/week, n=48) or peginterferon alpha-2b(1.5 ?g/kg/week, n=49) plus ribavirin (800 mg/day for 24 weeks in genotype non-1 or 1,000-1,200 mg/day for 48 weeks in genotype 1). Virologic responses including the early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and adverse effects were analyzed retrospectively. Results: The virologic response rates did not differ significantly between peginterferon alpha-2a and -2b: 89.6% and 89.7% for EVR, 79.2% and 79.5% for ETR, 72.9% and 73.5% for SVR, respectively. Analysis of the virologic responses according to genotype also revealed no significant differences in SVR between peg-interferon alpha-2a and -2b (59.3% vs. 59.7% for genotype 1 and 90.5% vs. 83.3% for genotype non-1, respectively), or in adverse effects including flu-like symptom, rash, itching, neutropenia, and thrombocytopenia. Conclusions: We found no significant differences in therapeutic efficacies and adverse effects between the alpha-2a and -2b types of peginterferon as the initial treatment regimen in naive chronic hepatitis C patients. (Korean J Hepatol 2008;14:493-502)

      • SCISCIESCOPUS

        The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer.

        Lee, Dong-Soo,Kim, Yeon-Sil,Jung, So-Lyoung,Lee, Kyo-Young,Kang, Jin-Hyoung,Park, Sarah,Kim, Young-Kyoon,Yoo, Ie-Ryung,Choi, Byung-Ock,Jang, Hong-Seok,Yoon, Sei-Chul Saikon Pub. Co 2012 TUMOR BIOLOGY Vol.33 No.4

        <P>Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p < 0.0001). The area under the receiver operating curve of serum CEA for the prediction of brain metastasis was 0.724 (p = 0.0001). The present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.</P>

      • Long-term outcome and toxicity of hypofractionated stereotactic body radiotherapy as a boost treatment for head and neck cancer: the importance of boost volume assessment

        Lee, Dong Soo,Kim, Yeon Sil,Cheon, Jae Seok,Song, Jin Ho,Son, Seok Hyun,Jang, Ji Sun,Kang, Young Nam,Kang, Jing Hyoung,Jung, So Lyoung,Yoo, Ie Ryung,Jang, Hong Seok BioMed Central 2012 Radiation oncology Vol.7 No.-

        <P><B>Background</B></P><P>The aim of this study was to report the long-term clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) as a boost treatment for head and neck cancer.</P><P><B>Materials and methods</B></P><P>Between March 2004 and July 2007, 26 patients with locally advanced, medically inoperable head and neck cancer or gross residual tumors in close proximity to critical structures following head and neck surgery were treated with SBRT as a boost treatment. All patients were initially treated with standard external beam radiotherapy (EBRT). SBRT boost was prescribed to the median 80% isodose line with a median dose of 21 (range 10–25) Gy in 2–5 (median, 5) fractions.</P><P><B>Results</B></P><P>The median follow-up after SBRT was 56 (range 27.6 − 80.2) months. The distribution of treatment sites in 26 patients was as follows: the nasopharynx, including the base of the skull in 10 (38.5%); nasal cavity or paranasal sinus in 8 (30.8%); periorbit in 4 (15.4%); tongue in 3 (11.5%); and oropharyngeal wall in 1 (3.8%). The median EBRT dose before SBRT was 50.4 Gy (range 39.6 − 70.2). The major response rate was 100% with 21 (80.8%) complete responses (CR). Severe (grade ≥ 3) late toxicities developed in 9 (34.6%) patients, and SBRT boost volume was a significant parameter predicting severe late complication.</P><P><B>Conclusions</B></P><P>The present study demonstrates that a modern SBRT boost is a highly efficient tool for local tumor control. However, we observed a high frequency of serious late complications. More optimized dose fractionation schedule and patient selection are required to achieve excellent local control without significant late morbidities in head and neck boost treatment.</P>

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