The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma

PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G→A or C→T) rather than a transversion mutation (G→T or G→C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.ope

Distinct clinical features and outcomes in never-smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement.

BACKGROUND: The objectives of this study were to determine the proportions of major oncogenic alterations and to examine survival in genotype-specific subsets of never-smokers with nonsmall cell lung cancer (NSCLC). METHODS: The authors concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes and investigated anaplastic lymphoma kinase (ALK) gene rearrangements in samples from 229 never-smokers with NSCLC. ALK rearrangements were identified by fluorescent in situ hybridization and were confirmed by immunohistochemistry. Mutations in EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct sequencing. RESULTS: Of 229 tumors, the frequency of EGFR mutations, ALK rearrangements, KRAS mutations, and no mutations (wild type [WT]) in any of the 3 genes (WT/WT/WT) was 48%, 8.3%, 3.5%, and 40.2%, respectively. All genetic alterations were mutually exclusive. The median progression-free survival after treatment with EGFR tyrosine kinase inhibitors (TKIs) was 12.8 months, 6.3 months, 2.1 months, and 1.6 months in patients with EGFR mutations, the WT/WT/WT genotype, KRAS mutations, and ALK rearrangements, respectively. In a Cox regression model, the adjusted hazard ratio for the risk of disease progression after treatment with EGFR TKIs was 0.59 (95% confidence interval [CI], 0.40-0.87; P = .008) for patients with EGFR mutations, 4.58 (95% CI, 2.07-10.15; P < .001) for patients with ALK rearrangements, and 4.23 (95% CI, 1.65-10.8; P = .003) for patients with KRAS mutations. Overall survival also differed significantly among genotypes. CONCLUSIONS: To the authors' knowledge, this was the largest comprehensive and concurrent analysis to date of 3 major oncogenic alterations in a cohort of East Asian never-smokers with NSCLC. Because survival outcomes differed among genotypes, and drugs that target specific alterations currently are available, genetic profiling to identify genotype-specific subsets can lead to successful treatment with appropriate kinase inhibitors. Copyright © 2011 American Cancer Society.ope

(A)Study on Plato`s dialectic

학위논문(박사)--서울대학교 대학원 :교육학과,2006.Docto

Understanding Research Competence at Graduate Level:Different Conceptions from Graduate Students, Graduates,and Professors

이 연구는 대학원 수준에서 연구역량에 대한 인식과 연구역량이 발휘되는 양상을 파악하는 것을 그 목적으로하였다. 이를 위하여 서울 소재의 연구중심대학 중의 하나인 A대학교 교육학과 대학원의 석·박사과정 재학생에 대한 표적집단면접과 동 대학원을 졸업한 연구원 및 교수 총 31명을 대상으로 한 개별면담을 통하여 교육연구자가 갖추어야 할 역량에 대한 인식과 연구 수행 경험 사례를 수집하고 분석하였다. 연구 결과, 연구역량의 구성요소는 집단에 따라 다른 것으로 나타났으나, 글쓰기와 의사소통능력은 세 집단에서 모두 중요한 요소인것으로 밝혀졌다. 아울러 연구자로서의 발달단계에 따라 연구역량를 이해하는 방식과 중요하다고 인식하는 구성요소가 다른 것으로 나타났다. 이상의 결과를 토대로 대학원 교육에서 연구역량을 개발할 수 있는 방안을 제시하였다. 이 연구는 새로운 지식을 창출할 수 있는 역량을 가진 인재 양성을 목적으로 하는 대학원 교육에서 요구되는 구체적인 역량요소를 제시하고, 나아가 연구역량 요소들이 실제 연구 활동에서 가지는 의미와 기능을 드러냄 으로써 연구역량 개발 방향에 시사점을 제공하였다는 점에서 의의가 있다. This study was conducted to investigate the ways graduate students, researchers, and professors characterize research competences in the context of graduate education. This study tried to provide a detailed description of actual demands, difficulties, or even accomplishments researchers experienced during the course of education research. In order to answer the research questions, four graduates of the department and seven professors from the department of education of a research-oriented university in Korea were individually interviewed, and focus group interviews with students in the graduate program were executed twice. Unlike the existing component-based approach, this study adopted an interpretative and context-based approach to understanding research competence. Findings suggest that the meaning of education research competence differs according to the developmental stages. Rather than a specific set of attributes of research competence, context and the meaning of education research played key role in research competence. Based on these analyses, practical and theoretical implications in understanding and developing research competence were suggested