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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>
Lee, Won Kee,Lee, Shin Yup,Choi, Jin Eun,Seok, Yangki,Lee, Eung Bae,Lee, Hyun Cheol,Kang, Hyo‐,Gyoung,Yoo, Seung Soo,Lee, Myung Hoon,Cho, Sukki,Jheon, Sanghoon,Kim, Young Chul,Oh, In Jae,Na, Koo John WileySons Australia, Ltd 2017 Thoracic cancer Vol.8 No.3
<P><B>Background</B></P><P>This multicenter study was performed to develop a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non‐small cell lung cancer (NSCLC) patients.</P><P><B>Methods</B></P><P>A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression.</P><P><B>Results</B></P><P>Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis‐prediction model, we categorized patients into low, intermediate, and high‐risk groups, which had greater accuracy in predictive ability (log‐rank statistics = 54.66) than the conventional tumor node metastasis staging (log‐rank statistics = 39.56). Next, we generated a prognosis‐prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high‐risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy.</P><P><B>Conclusions</B></P><P>This prognosis‐prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.</P>
TSC2 genetic variant and prognosis in non‐small cell lung cancer after curative surgery
Lee, Yong Hoon,Do, Sook Kyung,Lee, Shin Yup,Kang, Hyo‐,Gyoung,Choi, Jin Eun,Hong, Mi Jeong,Lee, Jang Hyuck,Lee, Eung Bae,Jeong, Ji Yun,Shin, Kyung Min,Lee, Won Kee,Seok, Yangki,Cho, Sukki,Yoo, S Wiley-Blackwells 2019 Thoracic Cancer Vol.10 No.2
<P>This study was conducted to investigate the associations between polymorphisms of genes involved in the LKB1 pathway and the prognosis of patients with non‐small cell lung cancer (NSCLC) after surgical resection. Twenty‐three single nucleotide polymorphisms (SNPs) in the LKB1 pathway were investigated in 782 patients with NSCLC who underwent curative surgery. The association of SNPs with overall survival (OS) and disease‐free survival (DFS) were analyzed. Among the 23 SNPs investigated, <I>TSC2</I> rs30259G > A was associated with significantly worse OS and DFS (adjusted hazard ratio for OS 1.88, 95% confidence interval 1.21–2.91, <I>P</I> = 0.005; adjusted hazard ratio for DFS 1.65, 95% confidence interval 1.15–2.38, <I>P</I> = 0.01, under codominant models, respectively). Subgroup analysis showed that SNPs were significantly associated with survival outcomes in squamous cell carcinoma, ever‐smokers, and stage I, but not in adenocarcinoma, never‐smokers, and stage II–IIIA. The results suggest that <I>TSC2</I> rs30259G > A may be useful to predict prognosis in patients with NSCLC, especially squamous cell carcinoma, after curative surgery.</P>
Younghwa Lee,Sukki Yoon,Youngwoo Lee,Marla B. Royne 글로벌지식마케팅경영학회 2016 Global Marketing Conference Vol.2016 No.7
We study liberals and conservatives in the United States and Korea to see how they respond to charity advertising that appeals to either equality or proportionality. The findings robustly demonstrate that in both countries, liberals respond more favorably to equality appeals, but conservatives respond more favorably to proportionality appeals. Study 1, conducted in the United States, finds that liberals find equality appeals more effective, but conservatives find proportionality appeals more effective. Study 2, conducted in Korea, shows that liberals (conservatives) estimate that they are more (less) likely to receive rewards for donating when charity advertising uses equality rather than proportionality appeals.
Yoo, Seung Soo,Hong, Mi Jeong,Choi, Jin Eun,Lee, Jang Hyuck,Baek, Sun Ah,Lee, Won Kee,Lee, So Yeon,Lee, Shin Yup,Lee, Jaehee,Cha, Seung Ick,Kim, Chang Ho,Cho, Sukki,Park, Jae Yong The Korean Academy of Medical Sciences 2016 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.31 No.3
<P>Recently, genetic variants in the WNT signaling pathway have been reported to affect the survival outcome of Caucasian patients with early stage non-small cell lung cancer (NSCLC). We therefore attempted to determine whether these same WNT signaling pathway gene variants had similar impacts on the survival outcome of NSCLC patients in a Korean population. A total of 761 patients with stages I–IIIA NSCLC were enrolled in this study. Eight variants of WNT pathway genes were genotyped and their association with overall survival and disease-free survival were analyzed. None of the eight variants were significantly associated with overall survival or disease-free survival. There were no differences in survival outcome after stratifying the subjects according to age, gender, smoking status, and histological type. These results suggest that genetic variants in the WNT signaling pathway may not affect the survival outcome of NSCLC in a Korean population.</P>
Hong, Mi Jeong,Yoo, Seung Soo,Choi, Jin Eun,Kang, Hyo‐,Gyoung,Do, Sook Kyung,Lee, Jang Hyuck,Lee, Won Kee,Lee, Jaehee,Lee, Shin Yup,Cha, Seung Ick,Kim, Chang Ho,Lee, Eung Bae,Cho, Sukki,Jheon, S John Wiley and Sons Inc. 2018 Cancer Science Vol.109 No.12
<P>RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non‐small‐cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival (<I>P </I><<I> </I>0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease‐free survival under a dominant model (<I>P </I>=<I> </I>2 × 10<SUP>−5</SUP> and <I>P </I>=<I> </I>0.001, respectively). rs2257609 is located in the <I>SLC5A10</I> intron, but RegulomeDB predicted that this variant affected <I>DRG2</I>, not <I>SLC5A10</I> expression. The expression level of <I>SLC5A10</I> was not different with the rs2257609 genotype. However, <I>DRG2</I> expression was different according to the rs2257609 genotype (<I>P</I><SUB>trend</SUB><SUP> </SUP>= 0.03) and was significantly higher in tumor than in non‐malignant lung tissues (<I>P </I>=<I> </I>1 × 10<SUP>−5</SUP>). Luciferase assay also showed higher promoter activity of <I>DRG2</I> in samples with the rs2257609 T allele (<I>P </I><<I> </I>0.0001). rs2257609 C>T affected <I>DRG2</I> expression and, thus, influenced the prognosis of early‐stage non‐small‐cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014‐04‐210‐003).</P>
<i>TP53</i> Mutations in Korean Patients with Non-small Cell Lung Cancer
Lee, Eung Bae,Jin, Guang,Lee, Shin Yup,Park, Ji Young,Kim, Min Jung,Choi, Jin Eun,Jeon, Hyo Sung,Cha, Seung Ick,Cho, Sukki,Kim, Chang Ho,Park, Tae-In,Jung, Tae Hoon,Son, Ji-Woong,Park, Jae Yong The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.5
<P>Although <I>TP53</I> mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, <I>TP53</I> mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. <I>TP53</I> mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, <I>P</I><0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, <I>P</I>=0.01). Our study provides clinical and molecular characteristics of <I>TP53</I> mutations in Korean patients with NSCLCs.</P>
Lee Woochan,Lee Seyoon,Yoon Jung-Ki,Lee Dakyung,Kim Yuri,Han Yeon Bi,Kim Rokhyun,Moon Sungjin,Park Young Jun,Park Kyunghyuk,Cha Bukyoung,Choi Jaeyong,Kim Juhyun,Ha Na-young,Kim Kwhanmien,Cho Sukki,Cho 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
We present an in-depth single-cell atlas of in vitro multiculture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single-cell profiling identified new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single-cell datasets of human lung tissues, we discovered immune-primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.
Sukki Kang,석차옥,Juyong Lee,Myeong Sup Lee 대한화학회 2008 Bulletin of the Korean Chemical Society Vol.29 No.2
FLOWERING LOCUS T (FT) and TERMINAL FLOWER 1 (TFL1) in Arabidopsis are homologous proteins that perform opposite functions: FT is an activator of flowering, and TFL1 is a repressor. It was shown before that change of a single amino acid (His88) of TFL1 to the corresponding amino acid (Tyr) of FT is enough to convert the floral repressor to an activator. However, structural basis of the functional conversion has not been understood. In our molecular dynamics simulations on modified TFL1 proteins, a hydrogen bond present in native TFL1 between the His88 residue and a residue (Asp144) in a neighboring external loop became broken by change of His88 to Tyr. This breakage induced conformational change of the external loop whose structure was previously reported to be another key functional determinant. These findings reveal that the two important factors determining the functional specificities of the floral regulators, the key amino acid (His88) and the external loop, are correlated, and the key amino acid determines the functional specificity indirectly by affecting the conformation of the external loop.