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      • An eQTL variant for LKB1 gene and the clinical outcomes of chemotherapy in non-small cell lung cancer

        서혜원,( Deuk Kju Jung ),( Hyo-gyoung Kang ),( Shin Yup Lee ),( Jin Eun Choi ),( Mi Jeong Hong ),( Sook Kyung Do ),( Jang Hyuck Lee ),( Seung Soo Yoo ),( Jaehee Lee ),( Seung Ick Cha ),( Chang Ho Kim ),( 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.0

        Background: We conducted this study to identify regulatory variants in cancer-related pathway genes which can predict clinical outcomes of chemotherapy in advanced NSCLC, using a comprehensive list of regulatory SNPs prioritized by RegulomeDB. Methods: A total of 509 potentially functional SNPs in cancer-related pathway genes were evaluated. The SNPs were analyzed in a discovery set (n=198), and an independent validation set (n=181). The associations of the SNPs with chemotherapy response and overall survival (OS) were analyzed. Results: In the discovery set, 95 SNPs were significantly associated with clinical outcomes. Among the 95 SNPs, only rs10414193A>G in the intronic region of ARID3A, an eQTL for LKB1, was consistently associated with chemotherapy response and OS in the validation set. In combined analysis, the rs10414193A>G was significantly associated with worse response to chemotherapy (adjusted odds ratio=0.63, 95% CI=0.47-0.85, P=0.002), and with worse OS (adjusted hazard ratio=1.25, 95% CI=1.08-1.45, P=0.004). Luciferase assay showed a significantly higher LKB1 promoter activity associated with rs10414193G allele compared with rs10414193A allele (P=0.0009). Conclusions: Our results suggest that rs10414193A>G may be useful for the prediction of clinical outcomes of chemotherapy in advanced NSCLC.

      • Functional polymorphisms in PD-L1 gene and clinical outcomes of patients with non-small cell lung cancer treated with first-line paclitaxel-cisplatin chemotherapy

        ( So Yeon Lee ),( Deuk Kju Jung ),( Jin Eun Choi ),( Sun Ha Choi ),( Minjung Kim ),( Hyewon Seo ),( Yong Dae Lee ),( Seung Soo Yoo ),( Shin Yup Lee ),( Jaehee Lee ),( Seung Ick Cha ),( Chang Ho Kim ) 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.0

        Purpose: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxel-cisplatinchemotherapy. Experimental Design: A total of 379 patients with advanced stage NSCLC were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. Results: Among the 12 SNPs investigated, PD-L1 rs2297136T>C and rs4143815C>G were significantly associated with clinical outcomes after chemotherapy. The rs2297136T>C was significantly associated with both better chemotherapy response and better OS (adjusted odds ratio [aOR] = 1.82, 95% CI = 1.19-2.77, P = 0.006; adjusted hazard ratio [aHR] = 0.76, 95% CI = 0.61-0.94, P = 0.01), and the rs4143815C>G had a significantly better response to chemotherapy (aOR = 1.42, 95% CI = 1.05-1.93, P = 0.02) under additive model for the variant alleles. Consistent with the individual genotype analyses, rs2297136C-rs4143815G haplotype harboring variant alleles at both loci was significantly associated with better chemotherapy response and OS compared with combined other haplotypes (aOR = 1.92, 95% CI = 1.27-2.91, P = 0.002; aHR = 0.76, 95% CI = 0.61-0.94, P = 0.01, respectively). Conclusions: PD-L1 rs2297136T>C and rs4143815C>G polymorphisms may be useful for the prediction of clinical outcome of 1st line paclitaxel-cisplatin chemotherapy in NSCLC.

      • Pri-let-7a-2 rs1143770C>T Associated with Prognosis of Surgically Resected Non-Small Cell Lung Cancer

        ( Yong Dae Lee ),( Kyung Min Shin ),( Deuk Kju Jung ),( Won Kee Lee ),( Hyewon Seo ),( So Yeon Lee ),( Seung Soo Yoo ),( Shin Yup Lee ),( Seung Ick Cha ),( Jaehee Lee ),( Chang Ho Kim ),( Yangki Seok 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.0

        Background: Evidence indicates that the let-7 microRNA (miRNA) may be a prognostic factor in lung cancer. Genetic variation in miRNA precursors could influence the processing and expression of miRNAs, which could affect the prognosis of lung cancer. We aimed to investigate the impact of single nucleotide polymorphisms (SNPs) of pri-let-7 on the prognosis of non-small cell lung cancer (NSCLC). Methods: Seven hundred sixty-one patients with surgically resected NSCLC were included. The four SNPs (pri-let-7a-2 rs1143770 and rs629367, pri-let-7a-1 rs10739971, and pri-let-7f-2 rs17276588) were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were evaluated. Results: Of the four SNPs analyzed, the rs1143770C>T was identified to be significantly associated with OS and DFS. The rs1143770 CT or TT genotype exhibited a significantly better OS and DFS compared with the rs1143770 CC genotype (adjusted hazard ratio for OS = 0.67, 95% confidence interval = 0.49―0.91, P = 0.01 and adjusted hazard ratio for DFS = 0.74, 95% confidence interval = 0.58―0.95, P = 0.02). Conclusions: This observation indicates that the pri-let-7a-2 rs1143770C>T may have a prognostic impact on surgically resected NSCLC.

      • KCI등재

        Body Weight is Inversely Associated with Anti-SARS-CoV-2 Antibody Levels after BNT162b2 mRNA Vaccination in Young and Middle Aged Adults

        Nam Su Youn,Jeon Seong Woo,Jung Deuk Kju,Heo Sung-Jae 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.3

        Background This study aimed to determine factors affecting serum levels of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies 2 months after coronavirus disease 2019 (COVID-19) vaccination in young and middle aged healthy adults. Materials and Methods Healthcare workers who have no history of SARS-CoV-2 infection, were enrolled at 2 months after second shot of BNT162b2 mRNA COVID-19 vaccine. Antibody immunoglobulin G against the spike protein subunit of SARS-CoV-2 was semi-quantitatively measured using 4 commercial enzyme-linked immunosorbent assay kits. Factors affecting anti-SARS-CoV-2 antibodies levels were investigated. Results Fifty-one persons (22 - 54 years, male sex; 19.6%) were enrolled and all participants acquired anti-SARS-CoV-2 antibodies in four diagnostic kits. Anti-SARS-CoV-2 antibodies were strongly correlated between diagnostic kits; SG Medical and Genscript (r = 0.942), SG Medical and HB Healthcare (r = 0.903), and HB Healthcare and Genscript (r = 0.868). We investigated factors affecting antibody level using SG medical kit. The median inhibition was 93.1%, and 84.0% of participants showed >90.0% inhibition. Systemic adverse event severity had no association with the anti-SARS-CoV-2 antibodies level. Antibody level was inversely correlated with weight (-0.312, P = 0.027), body mass index (BMI) (r = -0.303, P = 0.032), and body surface area (r = -0.285, P = 0.044). In multivariate analysis, the upper 50% of anti-SARS-CoV-2 antibodies (≥93.1%) was inversely associated with weight (odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.04 - 0.83 in weight ≥55kg) and BMI (OR: 0.12; 95% CI: 0.03 - 0.61 in BMI ≥22 kg/m2). Conclusion Anti-SARS-CoV-2 antibody was inversely correlated with weight and BMI, which may be used as a marker to predict immune response of BNT162b2 mRNA vaccination in young and middle aged adults. Trial Registration ClinicalTrials.gov Identifier: NCT05083026 Background This study aimed to determine factors affecting serum levels of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies 2 months after coronavirus disease 2019 (COVID-19) vaccination in young and middle aged healthy adults. Materials and Methods Healthcare workers who have no history of SARS-CoV-2 infection, were enrolled at 2 months after second shot of BNT162b2 mRNA COVID-19 vaccine. Antibody immunoglobulin G against the spike protein subunit of SARS-CoV-2 was semi-quantitatively measured using 4 commercial enzyme-linked immunosorbent assay kits. Factors affecting anti-SARS-CoV-2 antibodies levels were investigated. Results Fifty-one persons (22 - 54 years, male sex; 19.6%) were enrolled and all participants acquired anti-SARS-CoV-2 antibodies in four diagnostic kits. Anti-SARS-CoV-2 antibodies were strongly correlated between diagnostic kits; SG Medical and Genscript (r = 0.942), SG Medical and HB Healthcare (r = 0.903), and HB Healthcare and Genscript (r = 0.868). We investigated factors affecting antibody level using SG medical kit. The median inhibition was 93.1%, and 84.0% of participants showed >90.0% inhibition. Systemic adverse event severity had no association with the anti-SARS-CoV-2 antibodies level. Antibody level was inversely correlated with weight (-0.312, P = 0.027), body mass index (BMI) (r = -0.303, P = 0.032), and body surface area (r = -0.285, P = 0.044). In multivariate analysis, the upper 50% of anti-SARS-CoV-2 antibodies (≥93.1%) was inversely associated with weight (odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.04 - 0.83 in weight ≥55kg) and BMI (OR: 0.12; 95% CI: 0.03 - 0.61 in BMI ≥22 kg/m2). Conclusion Anti-SARS-CoV-2 antibody was inversely correlated with weight and BMI, which may be used as a marker to predict immune response of BNT162b2 mRNA vaccination in young and middle aged adults. Trial Registration ClinicalTrials.gov Identifier: NCT05083026

      • KCI등재

        Telomerase Activity and the Risk of Lung Cancer

        Jeon, Hyo-Sung,Choi, Jin Eun,Jung, Deuk Kju,Choi, Yi Young,Kang, Hyo Gyoung,Lee, Won-Kee,Yoo, Seung Soo,Lim, Jeong-Ok,Park, Jae Yong The Korean Academy of Medical Sciences 2012 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.27 No.2

        <P>Telomerase play a key role in the maintenance of telomere length and chromosome integrity. We have evaluated the association between telomerase activity and the risk of lung cancer in peripheral blood. Telomerase activity in peripheral blood mononuclear cells was measured by a PCR-designed telomeric repeat amplification protocol in 63 lung cancer patients and 190 healthy controls that were matched for age, gender, and smoking status. Telomerase activity was significantly lower in the lung cancer patients than in controls (mean ± standard deviation; 1.32 ± 1.65 vs 2.60 ± 3.09, <I>P</I> < 1 × 10<SUP>-4</SUP>). When telomerase activity was categorized into quartiles based on telomerase activity in the controls, the risk of lung cancer increased as telomerase activity reduced (<I>P</I><SUB>trend</SUB> = 1 × 10<SUP>-4</SUP>). Moreover, when the subjects were categorized based on the median value of telomerase activity, subjects with low telomerase activity were at a significantly increased risk of lung cancer compared to subjects with high telomerase activity (adjusted odds ratio = 3.05, 95% confidence interval = 1.60-5.82, <I>P</I> = 7 × 10<SUP>-4</SUP>). These findings suggest that telomerase activity may affect telomere maintenance, thereby contributing to susceptibility to lung cancer.</P>

      • SCISCIESCOPUS

        Polymorphisms in cancer-related pathway genes and lung cancer

        Lee, Shin Yup,Kang, Hyo-Gyoung,Choi, Jin Eun,Jung, Deuk Kju,Lee, Won Kee,Lee, Hyun Chul,Lee, So Yeon,Yoo, Seung Soo,Lee, Jaehee,Seok, Yangki,Lee, Eung Bae,Cha, Seung Ick,Cho, Sukki,Kim, Chang Ho,Lee, European Respiratory Society 2016 The European respiratory journal Vol.48 No.4

        <P>We evaluated the associations between potentially functional variants in a comprehensive list of cancer-related genes and lung cancer in a Korean population.</P><P>A total of 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes involved in carcinogenesis were evaluated using an Affymetrix custom-made GeneChip in 610 nonsmall cell lung cancer patients and 610 healthy controls. A replication study was conducted in an independent set of 490 cases and 486 controls. 68 SNPs were significantly associated with lung cancer in the discovery set and tested for replication.</P><P>Among the 68 SNPs, three SNPs (corepressor interacting with RBPJ 1 (<I>CIR1</I>) rs13009079T>C, ribonucleotide reductase M1 (<I>RRM1</I>) rs1465952T>C and solute carrier family 38, member 4 (<I>SLC38A4</I>) rs2429467C>T) consistantly showed significant associations with lung cancer in the replication study. In combined analysis, adjusted odds ratio for <I>CIR1</I> rs13009079T>C, <I>RRM1</I> rs1465952T>C and <I>SLC38A4</I> rs2429467C>T were 0.69, 0.71 and 0.73, respectively (p=4×10<SUP>−5</SUP>, 0.01 and 0.001, respectively) under the dominant model. The relative mRNA expression level of <I>CIR1</I> was significantly associated with rs13009079T>C genotypes in normal lung tissues (ptrend=0.03).</P><P>These results suggest that the three SNPs, particularly <I>CIR1</I> rs13009079T>C, may play a role in the pathogenesis of lung cancer.</P>

      • Polymorphisms in the Caspase Genes and the Risk of Lung Cancer

        Lee, Shin Yup,Choi, Yi Young,Choi, Jin Eun,Kim, Min Jung,Kim, Jong-Sik,Jung, Deuk Kju,Kang, Hyo-Gyoung,Jeon, Hyo-Sung,Lee, Won Kee,Jin, Guang,Cha, Seung Ick,Kim, Chang Ho,Jung, Tae Hoon,Park, Jae Yong Elsevier 2010 JOURNAL OF THORACIC ONCOLOGY Vol.5 No.8

        <P>INTRODUCTION:: Caspases (CASPs) are important regulators and executioners in apoptosis pathway and play a crucial role in the development and progression of cancer. On the basis of the interactions of CASPs in the apoptotic pathway, we evaluated the association between 11 polymorphisms of CASP3, 6, 7, 8, 9, and 10 genes and the risk of lung cancer. METHODS:: The genotypes were determined in 720 patients with lung cancer and 720 healthy controls frequency matched for age and gender. RESULTS:: In individual polymorphism analysis, the CASP7 rs2227310C>G and CASP9 rs4645981C>T were associated with 1.40-fold and 1.28-fold increased risk of lung cancer under recessive and dominant models for the variant allele of each polymorphism, respectively. In the case of the CASP3 77G>A, subjects with the GG genotype were at a 1.19-fold increased risk of lung cancer compared with those with at least one variant allele. When the three polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of risk genotypes increased (ptrend <0.001). Subjects with two and three risk genotypes carried a significantly increased risk of lung cancer compared with those with zero risk genotype (adjusted odds ratio = 1.56, 95% confidence interval = 1.14-2.13, p = 0.005 and adjusted odds ratio = 2.54, 95% confidence interval = 1.28-5.02, p = 0.008, respectively). CONCLUSIONS:: These results suggest that a combined analysis of these three CASP gene polymorphisms might better predict the risk of lung cancer than analysis of a single polymorphism.</P>

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