EGFR polymorphism as a predictor of clinical outcome in advanced lung cancer patients treated with EGFR-TKI

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. MATERIALS AND METHODs: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. RESULTS: SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. CONCLUSION: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.ope

한국인 제1형 신경섬유종(NF1) 환자의 돌연변이 분석

Dept. of Medical Science/석사[한글] 제 1형 신경섬유종은 가장 흔한 유전성 질환 중의 하나로 NF1 유전자의 돌연변이에 의해 유발되며 상염색체 우성으로 유전되는 질환이다. 약 3,000명당 한명꼴로 나타나며 신경성 섬유종, 커피색반점, axillary freckling, lisch nodule등의 증상을 동반하고, 한 가족 안에서도 임상적 증상이 매우 다양하게 나타난다고 알려져있다. NF1은 17q11.2 에 위치한, 350kb 크기의 유전자로 60개의 엑손으로 구성되어있으며, 11-13kb의 mRNA로 전사된 후 2,818개의 아미노산으로 이루어진 neurofibromin을 합성한다. neurofibromin은 ras-specific GTPase activating protein(GAPs)과 기능과 구조가 매우 유사한 GAP-related domain(GRD, 360 a.a)을 가지고 있으며, 이는 ras의 활성조절을 저하시키는 역할을 한다. 제 1형 신경섬유종의 30～50％가 NF1 유전자의 자연발생적인 돌연변이에 의해 나타나며 어떠한 유전질환 보다도 높은 돌연변이 발생 빈도를 보인다( ～1×104/gamete/generation). 그로인해 유전자가 규명된지 14년이 지났지만 돌연변이 위치에 대한 정보는 매우 한정적이다. 그 밖에도 유전자의 크기가 매우 크다는 점, homologous pseudogene의 존재 (10), 특정 위치가 아닌 매우 다양한 위치에서 돌연변이가 발생하는 특징으로 인해 돌연변이의 위치를 찾아내는데 어려움을 겪고 있다. 본 연구에서는 PCR, DHPLC, direct sequencing 방법을 통하여 36명의 NF1환자의 유전자 돌연변이를 분석한 결과 31명에게서 발병 원인 유전자를 찾아낼 수 있었다(86%). 분석결과 하나의 indel, 세종류의 insertion, 일곱종류의 deletion, 열여섯종류의 nonsense/miss sense mutations, 두종류의 splicing error, 열여섯 종류의 polymorphsim이 발견되었으며, 그 중 스물한종류의 돌연변이는 보고되지 않은 새로운 것이었다. [영문]Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorder with an incidence of 1 : 3,500 which is caused by mutations in the NF1 gene. NF1 is characterized particularly by caf？-au-lait spots and fibromatous tumors of the skin. The NF1 gene is located on the chromosome 17q11.2 and spans approximately 350 kb of genomic DNA. It consist of 60 exons which translates into neurofibromin.Screening of mutations in NF1 gene is complicated because of the large size of the gene, the presence of pseudogenes, the great variety of possible lesions, and the lack of significant mutational clustering.We screened for mutations in 36 patients who are clinically diagnosed as neurofibromatosis type 1. The whole coding sequences and all splice sites were examined for mutations using DHPLC followed by direct sequencing of PCR products. Disruptive mutations were identified in 31 individuals with an overall mutation detection rate of 86%. The mutations included one indel (nt.4079), three insertions (nt.1233, 4159, 4630), seven deletions (nt.953, 1017, 1418, 1541, 2679, 2816, 3525), sixteen missense / nonsense mutations (192, 384, 386, 465, 467, 489, 616, 1403, 1619, 2157, 2197, 2237, 2426, 2429, 2483, 2496 codon) and two splicing error (IVS 25, 34). Sixteen unclassified polymorphisms were also detected. Twenty one (72.4%) of the identified disruptive mutations are novel. Eight mutations have been previously reported. It appeared that mutational spectrum of NF1 gene in patients is heterogeneous as previously shown in other populations. By using strategies for mutation screening in NF1 gene used in this study can easily be applied for clinical purpose.ope

Japans Quest for East Asian Community and China : Idea and Reality

동아시아공동체 구상은 21세기 일본 외교의 변형을 표상한다. 이 글은 일본의 동아시아공동체 구상의 정책적 내용을 동아시아의 귀환과 중국의 부상이라는 조건 속에서 검토하고 동아시아의 진화와 지역질서의 변환에 갖는 함의를 찾는다. 특히 지역주의 프로젝트가 내포한 탈국제정치적 성격이 동아시아 전통국제질서와 밀접히 연결되어 있다는 점에 주목하고, 일본의 동아시아공동체 정책을 동아시아 시공간의 구조와 장기지속의 패턴 속에서 검토한다. 이를 통해 넓게는 동아시아 지역주의의 특수성을 성찰하고 좁게는 일본 지역주의 정책의 이중성을 규명한다.Japans quest for East Asian Community represents a metamorphosis of Japanese deplomacy in 21st century. This paper reviews political contents of Japanese regional community idea in the context of the return of East Asia and the rise of China, and seeks to find its implications for the evolution of East Asia and the transformation of regional order. Paying attention to the fact that the post-international political features of the East Asian regionalism are deeply rooted in the traditional regional order, this article sends Japans regional community policy back to the structure and longlasting patterns of East Asian time-space. In doing so, it reflects the particularity of East Asian regionalism and investigates the double face of Japanese regional policy

Cloning of glucosyltransferase from ixeris dentata form. albiflora Hara

Thesis(master`s)--서울대학교 대학원 :농생명공학부,2006.Maste

한국 주식시장에서의 유동성과 투자주체별 주문패턴에 대한 연구

학위논문(석사)--서울대학교 대학원 :경영학과 경영학전공,2000.Maste

유리섬유탄소섬유계를 이용한 이종 및 경사형 복합재료에 관한 연구

학위논문(석사)--서울대학교 대학원 :공업화학과,1998.Maste

Re-evaluation of Force Transfer Mechanism of Welded Steel Moment Connections

용접 철골 모멘트접합부는 일반적으로 평면유지의 가정을 전제한 초등휨이론에 의해 설계되어 왔다. 그러나 1994년 노스리지 지진 이후 보-기둥 접ㅈ합부의 설계에 초등휨이론으르 적용하는 것은 타당치 않음이 몇몇 연구자에 의해 제기된 바가 있다. 본 연구에서는 필자의 최근 해석 및 실험연구를 주 근거로 하여 다양한 형식의 접합부의 응력전달 메커니즘을 재평가하고 거의 모든 용접 모멘트접합부의 설계에 초등휨이론을 적용하는 것이 부적절함을 보이고자 하였다. 보의 웨브, 수평헌지의 웨브, 리브 등과 같은 수직 플레이트 접합요소는 모두 스트럿 작용에 의해 응력을 전달하는 유사성이 있음을 해석적, 실험적으로 확인하였다. 또한 최근 가장 큰 주목을 받고 있는 고연성 RBS 접합부의 전단력 응력전달 메커니즘은 PN형식 접합부의 그것과 크게 다르지 않음을 확인하였다. 아울러 접합부 설계에 유용하게 활용될 수 있는 단순화된 해석적 응력전달 모형을 소개하였다.; Employing the classical beam theory for the design of welded steel moment connections has been brought into question by several researchers since the 1994 Northridge earthquake. In this study, the load transfer mechanism in various welded steel moment connections is comprehensively reviewed mainly based on recent studies conducted by the writer. Available analytical and experimental results showed that the load path in almost all the welded steel moment connections is completely different from that as predicted by the classical beam theory. Vertical plates near the connection such as the beam web, the web of the straight haunch, and the rib act as a strut rather than following the classical beam theory. The shear force transfer in the RBS connection is essentially the same as that in PN type connection. Some simplified analytical models that can be used as the basis of a practical design procedure are also presented.본 연구를 위한 2003년도 서울대학교 신임교수 연구정착금 지원에 감사드립니다

Electronic and optoelectronic nanodevice arrays using semiconductor nanostructures

DoctorSemiconductor nanostructures, such as nanorods, nanowires, nanotubes, nanowalls, and so forth, have attracted much attention as vital components for fabricating various electronic and optoelectronic devices due to their several potential advantages over semiconductor thin films. The excellent material characteristics of single-crystalline nanostructures, such as high carrier mobility, high radiative recombination rate, and long minority carrier life time, have enabled the fabrication of high-performance electronic and optoelectronic devices. In addition, the ability to fabricate composition-modulated heterostructures with a high-quality interface made it possible to fabricate sophisticated nanoscale electronic and optoelectronic devices. For practical applications, however, several critical issues still remain, including reliable and precise characterization of physical properties of individual nanostructures and integration of functional nanodevices in a controlled manner.The electrical properties of individual nanostructures, such as carrier concentration and mobility, were measured typically by field-effect transport measurements. However, they are strongly influenced by surface and interface states, also cannot be used for the heavily-doped nanostructures. Meanwhile, temperature-dependent thermoelectric power measurements allowed us to determine the carrier concentration of highly-doped ZnO nanorods and GaN nanowires, even when the conventional field-effect estimation is not possible.In addition, electronic device applications using a single ZnO nanorod and its coaxial heterostructure have been investigated. In the top-gate geometry, first, the device characteristics of ZnO nanorod field-effect transistors (FETs) were significantly enhanced due to geometrical enhancement of gate capacitance. In addition, ZnO/Mg0.2Zn0.8O coaxial nanorod heterostructure FETs exhibited the excellent electrical characteristics with much higher mobility and smaller subthreshold swing values, compared with bare ZnO nanorod FETs. Such enhancement in device performances was mainly attributable to both in-situ surface passivation and carrier confinement effects through the heteroepitaxial growth of a lattice-matched Mg0.2Zn0.8O shell layer with a wider band gap than ZnO nanorods. Furthermore, the modulation doping with a site-specific doping profile not only enabled the control of electrical conductivity in both ZnO nanorod and ZnO/Mg0.2Zn0.8O coaxial nanorod heterostructure, but also showed great promise in fabricating high-mobility electrical devices.For more practical applications, vertical nanostructures grown on various substrates, including ZnO nanowall networks and GaN/ZnO coaxial nanorod heterostructures, were used to fabricate electronic and light-emitting devices. Selective-area growth of ZnO nanowall networks on the insulating AlN/Si substrate enabled the fabrication of network electrical devices with the controlled electrical characteristics, which were useful for high-sensitive gas sensing. In addition, on selectively-grown ZnO nanowall networks on the patterned graphene films, high-quality GaN microscale film arrays were fabricated by lateral overgrowth, which enabled the fabrication of transferable GaN light-emitting diodes (LEDs) on arbitrary substrates. Meanwhile, high-quality GaN/ZnO coaxial nanorod heterostructures grown randomly on large graphene films were used to fabricate flexible inorganic nanostructure LEDs. The nanostructure LEDs were transferred onto flexible plastic substrates, which operated reliably in a flexible form without significant degradation of the LED performance.Considerable advances in nanodevice fabrication have been achieved using position-controlled coaxial nanomaterial heterostructure arrays. Nanoarchitecture LED microarrays were fabricated on many different substrates, including sapphire, Si, and graphene substrates using position-controlled GaN/In1-xGaxN/GaN/ZnO coaxial nanotube heterostructure arrays. The nanoarchitecture LED microarrays emitted strong visible light originated from individual nanoarchitectures. The position-controlled coaxial nanoarchitecture arrays provide the significant opportunities for the fabrication of high-efficiency LEDs and integrated optoelectronic devices. More generally, they may be employed in the fabrication of many other optoelectronic devices, including laser diodes and solar cells