31 research outputs found

    구강편평세포암종에서 DNA hypermethylation에 의한 glutathione peroxidase 3 발현의 임상병리학적 의의

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    Dept. of Dentistry/박사Reactive oxygen species (ROS) have been shown to be involved in tumor initiation and progression via structural changes in cancer-related genes. Glutathione peroxidase 3 (GPX3), a member of the glutathione peroxidase family, is a major scavenger of ROS produced by normal metabolism or after oxidative damage to host cells. A possible tumor suppressor function of GPX3 and its downregulation caused by promotor hypermethylation have been investigated in various cancers. In this study, we investigated the association between methylation status and GPX3 expression in oral squamous cell carcinoma (OSCC) and further investigated the clinicopathological significance of GPX3 expression in patients with OSCC who underwent long-term follow-up. Promoter hypermethylation of GPX3 was frequently detected in both OSCC cell lines (100%) and tissue samples (75%). In contrast, only 33.3% of normal oral mucosa samples showed hypermethylation of GPX3. In OSCC cell lines, GPX3 expression was restored after 5-aza-2’-deoxycytidine treatment at both the mRNA and protein levels. GPX3 protein expression was significantly decreased in OSCC tissues (56.1%) compared to normal oral mucosa (100%). In patients with OSCC, GPX3 downregulation was significantly associated with histological grade (P=0.005), lymph node metastasis (P=0.001), vascular invasion (P=0.016), and poor prognosis (P=0.007). We concluded that promoter hypermethylation-induced GPX3 downregulation is significantly related to poor prognostic indicators and decreased overall survival in OSCC, and these findings provide further evidence for GPX3 as a novel diagnostic and prognostic biomarker in patients with OSCC. 활성산소는 암유전자의 구조적 변화를 일으켜 암의 발생과 진행에 관련이 되어있다. glutathione peroxidase 3(GPX3)는 glutathione family중 하나이며 활성산소를 제거하는 주요 항 산화 효소이다. 다양한 암에서 promoter hypermethylation에 의한 GPX3의downregulation GPX3의 tumor suppressor로서의 가능성에 관한 많은 연구들이 있었다. 본 연구의 목적은 구강편평세포암종에서 methylation정도와 GPX3발현에 관한 상관관계를 보고, 구강편평세포암종 환자에서 GPX3발현정도가 임상병리학적 예후에 미치는 영향을 보고자 하였다. GPX3 promoter hypermethylation은 구강편평세포암종 세포주와 조직에서 모두 높은 빈도(100%, 75%)로 관찰되었으나 정상 구강 점막조직에서는 낮은 빈도(33.3%)로 관찰되었다. 구강편평세포암종 세포주에서 demethylation agent인 5-Aza처리 후 GPX3 발현이 복원되었고, GPX3 downregulation과 methylation은 연관성을 가지고 있음을 확인하였다. 모든 정상 구강점막조직에서 GPX3 protein발현이 관찰되었다. 반면에 구강편평세포암종 조직에서는 정상 구강점막조직에 비하여GPX3 protein발현이 통계학적으로 유의한 감소를 보였다. 구강편평세포암종 환자 군에서 GPX3 발현은 세포 분화도, 림프절 전이, 혈관침습 및 누적 생존률에서 각각 통계학적 유의성을 보였다. 결론적으로 promoter hypermethylation에 의한GPX3 downregulation은 구강편평세포암종 환자의 진단 및 예후를 보는 생체표지자로의 의미가 있다고 할 수 있겠다.ope

    신경건축학 : 뇌에게 행복의 공간에 대해 묻다

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    왜 한국에 있는 모든 학교 교실들은 다 똑같이 생겼을까? 사각형으로 생긴 교실의 맨 앞엔 커다란 칠판이 붙어 있고, 그 뒤로 책상들과 의자들이 차례로 줄지어 늘어서 있다. 뒷벽엔 영락없이 시간표와 학습 자료가 붙어 있고, 출입문이 앞뒤로 두 개씩 나 있다. 이렇게 생긴 교실에서 학생들이 공부하면 집중이 잘되고 학습 효율이 높아지는 걸까? 똑같이 생긴 교실에서 12년 동안 공부하는 학생들은 과연 행복할까? 뱀처럼 구불구불하게 생긴 교실에서 학생들이 대여섯 명씩 둘러앉아 공부하면 수업 효율은 과연 어떻게 될까? 선생님이 교실 한가운데서 가르치고 칠판 색깔이 분홍색이라면 학생들이 집중을 더 잘 할 수 있지 않을까? 지난 20세기까지만 해도 과학자들은 이런 질문을 제기할 생각조차 하지 못했다. 건축 분야에서 이런 식의 질문은 매우 중요한 이슈지만, 그 해답은 뇌를 연구하는 신경과학자들이 찾아야 하기 때문이었다. 인간의 사고과정에 대한 관찰이 불가능한 건축가들에게 이런 질문은 부질없는 짓이었고, 건축에 대한 이해가 부족한 신경과학자들은 이런 질문이 얼마나 중요한지 몰랐다. 공간과 건축은 그 안에서 생활하는 사람을 위한 것이지만, 건축가들은 그저 자신의 예술가적 직관과 영감으로, 그리고 오랜 경험과 관행으로 지금까지 설계를 하고 디자인을 해왔다. 이 글은 신경건축학 분야의 태동과 신경 건축학에 대해 간략하게 소개하고자 한다

    플루오로 알킬기를 측쇄로 가지는 빗살형 고분자와 시나모일기 또는 올리고(에틸렌 글라이콜)기를 측쇄로 가지는 자극응답성 고분자의 합성, 분석 및 응용

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    학위논문 (박사)-- 서울대학교 대학원 : 화학생물공학부, 2012. 8. 이종찬.본 연구에서는 플루오로 알킬기를 측쇄로 가지는 빗살형 고분자와 시나모일기 또는 올리고(에틸렌 글라이콜)기를 측쇄로 가지는 자극 응답성 고분자를 합성하고 분석하였으며 낮은 표면 에너지 고분자, 자가 복원성 고분자, 고분자 유도 용액 등과 같은 응용 분야로의 적용 가능성에 대해서 모색하였다. 빗살형 불소 고분자는 고유의 낮은 표면에너지 때문에 전자재료, 접착 방지 코팅, 그리고 의약 재료 등과 같은 다양한 분야에서 응용 되고 있으며 다양한 방법으로 불소 고분자를 합성하려는 노력이 이루어지고 있다. 또한 자극 응답성 고분자는 주변의 화학적, 물리적 자극에 반응하여 고분자 구조나 성질을 변화시키는 특성을 가지고 구조 변화, 이온 혹은 분자 전달, 젖음성 변화, 그리고 접촉 성질 변화 등과 같은 다양한 현상을 보이게 된다. 이러한 고분자는 약물 전달이나 진단, 조직 공학, 자가 복원성 고분자와 같은 시스템에서 적용을 시도 되고 있다. 먼저 본 연구에서는 측쇄에 플루오로 알킬기를 가지는 폴리옥시에틸렌계 고분자를 합성하여 플루오로 알킬기의 함유량에 따른 표면 구조 변화를 확인하였다. 또한 이러한 표면 구조의 변화가 표면 에너지에 미치는 영향을 살펴보고 그 상관 관계를 도출하고자 하였다. 다양한 플루오로 알킬기 함유량을 가지는 고분자 중 플루오로 알킬기가 58 % 이상 함유 된 빗살형 고분자들이 열에 의해 어닐링 되었을 때 매우 낮은 표면 에너지를 가지는 것이 확인 되었으며 이때 고분자 표면에서의 파라크리스탈 구조의 배열이 매우 좋아지는 것을 확인할 수 있었다. 두번째, 초소수성과 방오, 항균 성질을 가지는 은-플루오로 알킬 복합체에 대해서 연구하였다. 은 염과 퍼플루오로티올의 간단한 반응을 통해 형성된 이 복합체는 그 반응 비율이 1:2 이상일 때 계층적인 마이크로/나노 사이즈의 와이어 형태로 구조가 만들어 졌으며, 이러한 복합체는 초소수성과 함께 박테리아에 대한 방오 성질을 가지는 것을 확인하였다. 또한 UV 조사를 통해 와이어 구조 표면위에 은 나노 입자를 형성 시킬 수 있었으며 항균 성질 또한 구현해 낼 수 있었다. 세번째, 빛에 반응하여 표면 강도가 달라지는 메타아크릴레이트계 고분자 필름을 형성하여 복원성을 가지는 필름으로의 응용 가능성에 대한 연구를 진행하였다. 빛에 응답하는 시나모일기를 측쇄에 가지고 가역적인 가교 반응을 통해 표면 강도를 조절 할 수 있게 디자인 된 고분자는 유리전이온도를 조절함으로써 적당한 온도에서 상처가 나도 복원이 가능하도록 하였다. UV 조사를 통해 상처난 필름의 강도를 낮추고, 적절한 열을 가해 상처를 복원, 마무리로 다시 UV를 조사하여 가교 시킴으로서 고유의 강도로 복원하는 시스템을 고안하여 성공적으로 복원이 가능한 필름을 구현할 수 있었다. 마지막으로 측쇄에 올리고(에틸렌 글라이콜)기를 포함하여 LCST 성질을 보이는 고분자를 합성하고 이온성기를 측쇄로 가지는 고분자와 공중합을 통해 정삼투 시스템의 유도 용액으로 사용 가능한 고분자를 합성하였다. 열에 반응하는 고분자와 이온성을 가지고 높은 삼투압을 유발할 수 있는 고분자의 공중합을 통해 적절한 삼투압과 LCST 수치를 가지는 고분자가 성공적으로 합성되었으며 그 중 올리고(에틸렌 글라이콜)기와 이온성기의 비율이 8:2 를 가지는 고분자가 정삼투압 유도 용질 분야에서 새로운 고분자 유도 용질로 사용되기에 적합할 것으로 판단 되었다.This study presents the synthesis, characterization, and applications of comb-like fluorinated polymers and stimuli-responsive polymers. Through control over the polymer side chain structures, I investigate the various polymer properties and attempt to apply the polymers to the many applications such as antifouling, antibacterial, healing, and water purification. Comb-like fluoropolymers have many applications in areas such as microelectronics, anti-adhesive coatings, and medical materials on account of their low surface energy values. Because of this, there was much effort to synthesize polymers with fluorinated alkyl segments in the side chains. On the other hand, stimuli-reponsive polymers can adapt to surrounding environments, change the molecular formation, regulate transport of ions and molecules, change wettability and adhesion of different species on external stimuli or convert chemical and biochemical signals into optical, electrical, thermal and mechanical signals, and vice versa. These materials are playing an incresasingly important part in a diverse range of applications, such as drug delivery, diagnostics, tissue engineering, healable materials and smart optical systems. Firstly, a series of comb-like fluorinated poly(oxyethylene)s having different content of fluoroalkyl side group were prepared to examine the effect of the surface structure variation on the surface properties. When the thin films of the polymers having ≥58 mol % of fluoroalkyl side groups were annealed, surface energy decreases and surface stability against polar liquids improved. This surface property behavior was found to be correlated with changes of the paracrystalline structure orientation and scattering unit numbers after the annealing process very well. However the average tilt angle and d-spacing of the fluoroalkyl side group and the paracrystalline ordering of the thin films did not changes, if any, after the annealing process. Near edge X-ray absorption fine structure (NEXAFS) spectroscopy and grazing incidence X-ray diffraction (GIXD) were used to determine the surface structure and contact angle measurement were conducted to measure the surface properties. Secondly, silver-perfluorodecanethiolate complexes having superhydrophobic, antifouling, antibacterial properties were prepared by a reaction of silver nitrate with perfluorodecanethiol. When the silver nitrate to perfluorodecanethiol molar ratio was 1/2, silver-perfluorodecanethiolate complexes having hierarchical micro-/nano-sized wire shapes were obtained, and they showed superhydrophobic and antifouling properties. After UV irradiation, silver nanoparticles were generated on the wires, and exhibited antibacterial properties. Thirdly, a series of polymethacrylate films having different glass transition temperatures (Tg) was synthesized and demonstrated to form healable films with different surface hardnesses. A photo-responsive cinnamoyl side group was used both as a crosslinker to control the surface hardness and as a plasticizer to vary the Tg. Two contrasting factors, chain mobility for healing and surface hardness for mechanical properties, were evaluated with heating and UV irradiation to establish the suitable polymer films and healing condition. We achieved the overall healing process with the polymethacrylate film containing a photocrosslinkable cinnamoyl side group. This study presents the practical basis for healable polymer approaches and provides the considerable candidates. Finally, we report on a novel thermo-responsive copolymer with ionic group which could be used as a draw solute for forward osmosis (FO) process. 2-(2-Methoxyethoxy)ethyl methacrylate (MEO2MA), characterized by a thermo-responsive group with LCST behavior for the recycling process, was copolymerized with 2-(methacryloyloxy)ethyl trimethylammonium chloride (MTAC), which have ionic group in a capable of demonstrating the high osmotic pressure. By controlling the composition of two monomer, both high osmotic pressure and proper LCST point could be obtained. The copolymers prepared with suitable composition of MEO2MA:MTAC have the considerable potential for use as a novel draw solute for FO process.TABLE OF CONTENTS Abstract ii List of Figures vii List of Tables x Chapter 1 Introduction 1.1. Motivation 2 1.2. Fluorinated polymers having low surface energy 4 1.3. Healable materials 5 1.4. Polymer draw solute for forward osmosis system 6 1.5. References 11 Chapter 2 Molecular Structure and Surface Properties of Comb-Like Fluorinated Poly(oxyethylene)s Having Different Content of Fluoroalkyl Side Group 2.1. Introduction 15 2.2. Experimental 18 2.3. Results and Discussion 23 2.4. Conclusions 37 2.5. References 51 Chapter 3 Silver-Perfluorodecanethiolate Complexes Having Superhydrophobic, Antifouling, Antibacterial Properties. 3.1. Introduction 57 3.2. Experimental 59 3.3. Results and Discussion 62 3.4. Conclusions 70 3.5. References 76 Chapter 4 Healable Polymethacrylate Films Having Photocrosslinkable Cinnamoyl Side Group 4.1. Introduction 81 4.2. Experimental 84 4.3. Results and Discussion 88 4.4. Conclusions 98 4.5. References 107 Chapter 5 Thermo-Responsive Copolymers with Ionic Group as Novel Draw Solutes for Forward Osmosis Processes 5.1. Introduction 111 5.2. Experimental 113 5.3. Results and Discussion 116 5.4. Conclusions 121 5.5. References 127 Abstract in Korean 129Docto

    Radical Prostatectomy: Respective Roles and Comparisons of Robotic and Open Surgeries

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    Over the years, several surgical modifications have been incorporated into radical prostatectomy in order to improve the surgical outcome. Despite the rapid dissemination of robot-assisted laparoscopic prostatectomy (RALP) through the urologic community, comparative studies on the practicality of RALP compared to open radical prostatectomy (OP) are lacking. Thus, it remains difficult to draw any conclusions regarding cancer control and postoperative morbidity. This review will introduce the evolution of surgical technique and the current status of RALP in relation to OP in the management of localized prostate cancer focusing on the perioperative, oncological and functional outcomes. Based on the review of literatures, perioperative outcomes, such as blood loss, transfusion rates, hospitalization duration and complication rates, all favored RALP. The positive surgical margin rates of RALP were similar to those of OP with regard to the oncological outcomes. With regard to the functional outcomes, OP and RALP also showed similar continence and potency rates. However, refinements in technique employed during RALP have improved the early return of continence postoperatively. Although OP remains the gold standard treatment in localized prostate cancer, robotic surgery and continued technical advancements will ultimately improve patient outcomes. However, further prospective randomized comparative clinical trials with a long-term follow-up utilizing validated questionnaire are needed to prove the superiority of either surgical approach in terms of functional and oncological outcomes. In addition, RALP technique will need a substantial decrease in the cost of the robotic system to achieve wider global acceptance and applicationope

    Prognostic Significance of the Tumor Volume and Tumor Percentage for Localized Prostate Cancer

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    PURPOSE: Tumor volume has been thought to be an important predictive factor for significant prostate cancer. We assessed the impact of the tumor volume(TV) and the tumor percentage(TP) of radical prostatectomy specimens on the pathological variables and the oncological outcome. MARERIALS AND METHODS: The tumor percentage and tumor volume were calculated for 525 cases by a single pathologist who determined the volume based on the surface area of the slides involved by tumor of the prostate. Univariate and multivariate logistic regression analyses were used to characterize the association of TP categories(20%) and TV(7.5cc) with the clinicopathological variables. Biochemical recurrence(BCR) was estimated using Kaplan-Meier analysis and Cox's hazard regression model. RESULTS: The mean prostate cancer volume was 6.5+/-8.5cc(median: 3.8, range: 0.04-73.8) and the mean percent tumor composition was 0.17+/-0.19 (median: 0.1, range: 0.01-0.95). A higher tumor volume and a higher tumor percentage were associated with extra-capsular extension(ECE), a positive surgical margin(PSM), a higher pT stage and a higher prostate-specific antigen(PSA) Gleason score(all p<0.05). In addition, TP was the independent predictor of ECE(adjusted odds ratio(OR): 22.66, 95% confidence interval(CI): 1.801-285.079, p=0.016), but the tumor volume was not associated with ECE on the multivariate logistic analyses. On the Kaplan-Meier analysis, but not on the Cox-hazard analyses, the TP did demonstrate a significant association with biochemical recurrence(p=0.035), yet the TV did not reach statistical significance(p=0.190). CONCLUSIONS: Our data indicates that the tumor percentage had a significant effect on the BCR on the Kaplan-Meier analysis. The tumor percentage rather than the tumor volume might be more useful to predict the prognosis of prostate cancer

    Pathologic Outcome of Unilateral Low Risk Prostate Cancers on Multicore Prostate Biopsy after Radical Prostatectomy

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    PURPOSE: To investigate clinicopathologic characteristics of unilateral, low risk prostate cancers detected via multi(>or=12)-core prostate biopsy. MATERIALS AND METHODS: One hundred four patients who underwent radical retropubic prostatectomy(RRP) for unilateral, low risk prostate cancer (clinical stage or=12)-core prostate biopsy were enrolled. In this retrospective study, we reviewed the patients' preoperative and pathologic data to assess potential predictors of pT2c or greater disease at the time of RRP, as well as characteristics of such disease. RESULTS: Of the 104 subjects, only 34(32.7%) were pathologically-proven to have unilateral disease, while the others showed pathologically-bilateral or worse disease from analysis of the RRP specimens. Subjects pathologically found to have uni- and bi-lateral disease showed no significant differences regarding age, prostate-specific antigen(PSA), free-to-total PSA ratio, prostate volume, clinical stage, number of positive cores, biopsy Gleason score, number of total biopsy sites, and highest percentage of tumor at any biopsy site. Multivariate logistic regression analysis revealed no significant preoperative predictors of pT2c or greater disease at RRP. CONCLUSIONS: Most patients with unilateral, low risk prostate cancer detected on multi(>or=12)-core prostate biopsy actually had pathologically- worse disease. For clinically-localized prostate cancer, a more accurate method to identify appropriate candidates for unilateral or focal ablative therapy should be developed

    Prognostic Significance of Multifocal Tumor in Radical Prostatectomy

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    Purpose: We investigate the impact of tumor multifocality on the biochemical recurrence rate after radical prostatectomy. Materials and Methods: Data was collected from 525 patients who underwent radical prostatectomy for clinically localized prostate cancer from 2003 to 2007. We evaluated the potential associations of multifocality with various clinical and pathologic factors. The ability to predict extra-capsular extension (ECE) was tested by logistic regression models, whereas biochemical recurrence (BCR) was assessed via Kaplan-Meier analyses and Cox-hazard regression models. The BCR was defined as a level of serum prostate-specific antigen (PSA) of 0.2ng/ml or greater on consecutive evaluations. Results: Multifocality was observed to be significantly associated with the presence of a high grade Gleason pattern (p=0.014), the pT stage (p< 0.001), ECE (p=0.005) and a positive surgical margin (PSM) (p=0.019). Moreover, it was the independent predictor of ECE on multivariate logistic regression analyses (p=0.039). However, although multifocality had a significant influence on biochemical recurrence on the Kaplan-Meier analyses (log rank test, p=0.019), only the PSA level and the Gleason score were significant predictors of BCR on the multivariated Cox-hazard analyses. Conclusions: Although multifocality was associated with adverse pathologic features, it had no significant effect on biochemical recurrence on the multivariated cox-hazard analyses

    (An) orthotopic nude mouse model of tongue carcinoma

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    치의학과/석사[한글] 일반적으로 구강암의 80-90%는 편평세포암종 (squamous cell carcinoma) 으로 좋지 못한 예후를 보인다. 혀에 암종이 발생하면 임파절 전이가 양측성으로 이루어 질 수 있고, 혈관분포가 풍부한 근육조직으로 이루어져 있기 때문에 암세포의 침투 및 성장 속도가 빠르며 경부 임파절 전이가 잘 된다. 따라서 동물실험 모델을 개발하기도 어렵지만, 개발하여도 종양 유발 후에 식이 섭취의 어려움을 초래하여 실험 동물들이 빨리 사망하기 때문에 적절한 후속의 연구를 진행하는데 많은 어려움이 있다. 이에 저자는 YD-10Bmod 세포주를 세포수 별로 누드마우스의 혀에 이종이식 하여 구강설암의 발생 정도를 관찰하여 구강설암 연구에 적절한 동물실험 모델을 개발하고자 하여 다음과 같은 결과를 얻었다. 1. 누드마우스의 혀에 YD-10Bmod 세포주를 5x10⁴cells/mouse로 이종이식한 실험군에서는 종양 중심부 괴사를 동반한 침윤성 종양성장이 실험 5주차에서 부터 관찰되었다. 2. 누드마우스의 혀에 YD-10Bmod 세포주를 5x10?cells/mouse로 이종이식한 실험군에서는 실험 4주차부터 종양 중심부 괴사를 동반한 침윤성 종양 성장이 관찰되었다. 3. 누드마우스의 혀에 YD-10Bmod 세포주를 5x10?cells/mouse로 이종이식한 실험군 에서는 실험 3주차부터 종양세포의 급격한 증식을 보였고, 5주차에서는 종양의 크기가 급속히 성장하여 실험동물이 사망 하였다. 이상의 결과로 YD-10Bmod 세포주를 누드마우스의 혀에 이종이식하여 형성된 종양은 인체의 혀에서 발생된 설암과 유사하게 주위조직으로의 침윤과 종양중심부 괴사의 소견을 보였다. 그리고 이종이식한 세포 수에 따라 종양의 크기나 종양중심부 괴사가 되는 시기가 다른 것으로 보아, 향후 이종이식하는 YD-10Bmod 세포주의 세포수를 5x10⁴cells/mouse 이하로 더 적게 이종이식 하면 누드마우스의 생존기간을 더 연장할 수 있을 것으로 사료되었다. 따라서 효과적인 항암제의 개발을 위한 연구모델로도 유용하게 이용할 수 있을 수 있으며, 설암의 경부 임파절전이 양상까지도 관찰이 가능한 실험동물 모델을 확립할 수 있을 것으로 기대된다. [영문] Squamous cell carcinoma, which is 80-90% of oral cancers, generally shows poor prognosis. Development of carcinoma on oral tongue may cause bilateral cervical lymph node metastasis, rapid invasion and growth of the cancer cells due to rich blood supply in muscle tissues. It is not only difficult to develop an animal experimental model, but also to proceed follow-up research after the development of such model as the induction of cancer lead to difficulty in taking nutrition for the experimental animals that often causes early death. In this study, author have transplanted YD-10Bmod cells into nude mouse oral tongues with different cells number and observed the development aspect of oral tongue cancers. The results are as follows. 1. In group where 5x104 cells/mouse of the YD-10Bmod cells had been transplanted into each nude mouse oral tongue, invasive cancer growth with central necrosis was observed from the 5th week of the experiment. 2. In group where 5x105 cells/mouse of the YD-10Bmod cells had been transplanted into each nude mouse oral tongue, invasive cancer growth with central necrosis was observed from the 4th week of the experiment. 3. In group where 5x106 cells/mouse of the YD-10Bmod cells had been transplanted into each nude mouse oral tongue, cancer presented sudden proliferation from the 3rd week of the experiment, and rapid growth of the tumor mass lead to death of the nude mouse on the 5th week of the experiment. The cancer developed from orthotopic transplantation of YD-10Bmod cells into nude mouse oral tongue show invasiveness and central necrosis of the tumor, similar to the cancers developed human oral tongue cancer. The difference in tumor size and the time of central necrosis development depending on the number of transplanted tumor cells shows the feasibility of extending the survival period of the nude mouse by limiting the transplanted tumor cells to 5x104 cells/mouse or under per nude mouse. Therefore, this nude mouse model could be used effectively in developing effective chemotheray agent and establishing an animal experimental model that can be used to study the mechanism of cervical lymph node metastasis of the oral tongue cancer.ope

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