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系統識別號 U0026-0812200911263352
論文名稱(中文) 殘留應力產生彎曲之微雙層結構及其在微光學之應用
論文名稱(英文) Stress-Induced Bending of Micromachined Bilayer Structures and Their Micro-Optics Applications
校院名稱 成功大學
系所名稱(中) 工程科學系碩博士班
系所名稱(英) Department of Engineering Science
學年度 93
學期 2
出版年 94
研究生(中文) 郭如男
學號 n9891112
學位類別 博士
語文別 英文
口試日期 2005-05-12
論文頁數 106頁
口試委員 指導教授-潘文峰
召集委員-李國賓
口試委員-李輝煌
口試委員-陳顯禎
口試委員-吳建中
口試委員-林哲信
關鍵字(中) 殘留應力
微懸臂樑結構
光學微機電
微光學
關鍵字(英) residual stress
micromachined cantilever structure
optical MEMS
micro-optics
學科別分類
中文摘要   微雙層材料之懸臂樑結構已經被廣泛地使用在微機電系統之研究。它可以作為很有用的元件以利於各種不同的應用(例如:光學微機電系統)。其中利用兩層不同薄膜組成之雙層材料懸臂樑結構經常被使用,當犧牲層被蝕刻完及鬆脫結構後,上層材料(通常為金屬)會呈現殘留應力現象使結構產生彎曲變形。本研究首先使用有限元素法模擬如此的彎曲變形並且和理論及實驗結果做對照。本文對於殘留應力彎曲之微雙層材料懸臂樑結構的形狀效應首先做一有系統的研究。

  本研究亦成功地發展出許多微光學元件,包括光開關、光柵、凹面鏡及掃瞄鏡片等等。我們亦提出利用殘留應力彎曲之懸臂樑所做出的一高效能光交換器。此光交換器使用一扭轉軸及彎曲之蹺蹺板結構,基本上有較低的驅動電壓並且可提供多個切換功能,此外它的次毫秒切換時間及光插入損失(0.65dB)已被驗證。如此精細的元件使得它可理想地建構高密度的光交換器於一個晶片上以作為光通訊方面的應用。

  最後,本研究整合發展出的微光學元件設計微型化系統於光學應用上,幾個微光學系統已被驗證包括:(1)使用三維鏡面及光柵之新型微光學干涉儀系統,(2)利用殘留應力彎曲凹面鏡之微光學聚焦系統,和(3)利用三色混光波導元件及微掃瞄鏡片之投影顯示器。結果顯示這些微光學元件可成功地整合成系統,最後冀望本研究對光學微機電領域能有所貢獻。
英文摘要  Micromachined cantilevers are a common component in many MEMS (Micro-Electro-Mechanical-Systems) and MOEMS (Micro-Opto-Electro-Mechanical Systems) applications. One of the most frequently employed cantilevers has a bilayer structure composed of two different thin-film layers (i.e. a base layer and an additional layer). The sacrificial-layer etching and drying processes involved in the fabrication of bilayer cantilevers induce residual stresses in the additional layer (generally metal). These stresses cause the cantilever to become activated and to curl up. This study establishes a finite element model to analyze this deformation. The accuracy of this model is verified through experimental and theoretical analysis. Having established a theoretical model, this study performs a systematic investigation into the influences of the geometrical shape of the bilayer structure and the area of coating deposition on the stress-induced bending of micromachined bilayer structures.

 This study successfully develops several micro-optics components using the stress-induced cantilevers, including an optical switch, a grating mirror, a concave mirror, and a scanner. A high performance optical crossconnect device which operates by exploiting the stress-induced bending of a micromachined bilayer cantilever is also presented. The use of a curved polysilicon seesaw structure and a torsional beam lowers the electrostatic operating voltage of the optical switch substantially and provides a multi-switching function. Furthermore, the device demonstrates a sub-millisecond switching time and a low optical insertion loss (0.65 dB). The compact nature of the optical multi-switch element renders it an ideal candidate for the construction of optical crossconnects (OXCs) with a large number of ports on a chip for optical communication applications.

 Finally, the micro-optic MEMS components developed in this study are integrated to construct miniature systems suitable for optical applications. Several micro-systems are demonstrated, including: (1) a novel micro-optic interferometer system incorporating three-dimensional micromirrors and microgratings, (2) a three-dimensional optical focusing system based on the stress-induced bending of a concave micromirror, and (3) a projection display technique utilizing three-color-mixing waveguides and micro scanning devices. The results confirm the feasibility of the developed micro-optic systems and represent a significant contribution toward the further development of optical MEMS applications.
論文目次 English Abstract …………………………………………I
Chinese Abstract ……………………………………… III
Acknowledgements ………………………………………… V
Table of Contents ………………………………………VI
List of Tables ………………………………………… IX
List of Figures …………………………………………X
Nomenclature …………………………………………XIV

Chapter 1:
INTRODUCTION
1.1 Background-MEMS and Its Optical Applications…………………1
1.2 Motivation and objectives………………………………3
1.3 Thesis organization…………………………………3

Chapter 2:
SHAPE EFFECT OF METAL FILMS ON STRESS-INDUCED BENDING OF MICROMACHINED BILAYER CANTILEVER
2.1 Introduction………………………………………6
2.2 Theory……………………………………………7
2.3 Design and fabrication…………………………………9
2.4 Finite element analysis…………………………………11
2.5 Results and discussion…………………………………12

Chapter 3:
A HIGH PERFORMANCE STRESS-INDUCED MICROMACHINED OPTICAL SWITCH WITH A MULTI-SWITCHING FUNCTION USING A SEESAW STRUCTURE
3.1 Introduction………………………………………17
3.2 Design and fabrication…………………………………18
3.3 Double-switch design….…………………………………21
3.4 Results and discussion…………………………………22

Chapter 4:
SURFACE-MICROMACHINED OPTICAL INTERFEROMETRY SYSTEM UTILIZING THREE-DIMENSIONAL MICROMIRRORS AND MICROGRATINGS
4.1 Introduction………………………………………24
4.2 Design and fabrication…………………………………26
4.3 Results and discussion…………………………………28

Chapter 5:
THREE-DIMENSIONAL OPTICAL FOCUSING SYSTEMS UTILIZING STRESS-INDUCED BENDING OF CONCAVE MICROMIRRORS
5.1 Introduction………………………………………30
5.2 Design and fabrication…………………………………32
5.3 Finite element analysis…………………………………34
5.4 Results and discussion…………………………………34

Chapter 6:
PROJECTION DISPLAY TECHNIQUE UTILIZING THREE-COLOR-MIXING WAVEGUIDES AND MICRO SCANNING DEVICES
6.1 Introduction………………………………………37
6.2 Design and fabrication…………………………………38
6.3 Results and discussion…………………………………39

Chapter 7:
CONCLUSIONS
7.1 Overview of dissertation………………………………41
7.2 Future works………………………………………43

REFERENCES 44
TABLES 52
FIGURES 52
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系統識別號 U0026-0812200911311507
論文名稱(中文) 應用壓阻微懸臂結構表面應力機制於CMOS製程生化感測器之研究
論文名稱(英文) Development of Surface Stress-Based Piezoresistive Microcantilever Biosensor by CMOS Process
校院名稱 成功大學
系所名稱(中) 航空太空工程學系碩博士班
系所名稱(英) Department of Aeronautics & Astronautics
學年度 93
學期 2
出版年 94
研究生(中文) 殷宗義
學號 p4890115
學位類別 博士
語文別 英文
口試日期 2005-06-25
論文頁數 133頁
口試委員 口試委員-馮榮豐
口試委員-蔡明蒔
口試委員-楊文彬
口試委員-江達雲
指導教授-楊世銘
口試委員-胡潛濱
召集委員-高騏
口試委員-陳國聲
口試委員-許耿禎
關鍵字(中) 生化感測器
表面應力
壓阻微懸臂結構
關鍵字(英) piezoresistive microcantilever
surface stress
biosensors
學科別分類
中文摘要   由於微尺度懸臂結構具有高自然振頻,高表面能與低熱容量等機械物理特性,已被應用於新型生化感測器之設計與製作。當待測之生化檢體附著於微懸臂結構表面時,分子與微結構間所產生之表面應力變化將引發微結構形變,而形變可直接由包埋之壓阻層讀取。然而由於壓阻層之熱效應,且生化反應產生之表面應力為一雙軸向應力負載;因此微懸臂結構之力學行為對壓阻層之訊號量測是生化感測器之重要關鍵。

  本文提出一個二維力學模型以分析微懸臂結構於表面應力與熱效應負載之下之力學行為。分析結果顯示表面應力之雙軸效應對此壓阻微懸臂結構之性能影響極大,且壓阻層之熱效應將嚴重影響表面應力之量測。因此,本文提出一種條狀式分子吸附層之設計以及一種微型雙懸臂結構之新型設計以解決此熱效應並有效提升感測器之表面應力量測靈敏度。本文也提出整合於此感測器晶片之橋式電路分析輔以訊號處理,用以消除電路偏壓讀值以及溫度漂移所產生之雜訊。

  同時為整合此壓阻微懸臂結構與微流體系統於單一感測晶片,本文首次提出一相容於半導體標準CMOS 製程之生化感測器晶片設計與製作。感測器晶片之微結構釋放與微流道封裝可利用簡易之後製程來達成。經由晶片實際的量測,證實微懸臂結構顯著之熱效應與條狀式分子吸附層設計之效能。以硫醇 (thiol) 修飾之單股DNA (ssDNA) 為例實際應用此生化感測器晶片之線上量測,結果顯示單股DNA 引發之等效表面應力變化為0.15 N/m,晶片之表面應力量測靈敏度為3.5 10-5 m/N,優於現存文獻之研究成果。本文提出之壓組式微懸臂結構與整合感測器晶片之分析、設計與製造將可提供此生化感測器一個嶄新的研究方向。
英文摘要   Many new biosensors design based on microcantilever have been proposed by using the fast and sensitive response of micromechanical detection. Microcantilever with embedded piezoresistor has been proposed recently to measure the surface stress change induced by bioanalytes. However, such biosensors are vulnerable to the thermal effect from piezoresistor and the biaxial effect of surface stress from biochemical reaction. Improved microcantilever design for better performance is desirable.

  This study proposes a two-dimensional mechanics model to analyze the piezoresistive effect of the four-layer microcantilever under surface stress and thermal loading. Analyses show that the biaxial effect of surface stress is crucial and the thermal effect from the piezoresistor is lethal to surface stress measurement. A stripe pattern design on the immobilized layer is proposed to improve the surface stress sensitivity while minimizing the thermal effect. In addition, an innovative double-microcantilever design is also developed to isolate the thermal effect. In sensor operation, however, different layer composition of active and reference microcantilever leads to an offset voltage and the associated temperature drift. An integrated bridge circuit design in biosensor chip is also proposed to provide signal conditioning for improving sensor performance. A biosensor chip with integrated piezoresistive microcantilever and microchannel is fabricated by complementary metal-oxide-semiconductor (CMOS) compatible process. The immobilized layer on microcantilever and seal of microchannel can be accomplished by lift-off technique and polydimethylsiloxane (PDMS) channel cover in post-processing. An on-chip biosening of thiol-modified ssDNA is conducted to validate the sensor performance. Measurement result shows the induced surface stress from the immobilized ssDNA is approximately 0.15 N/m, and the surface stress sensitivity of the biosensor is calculated as m/N. Design, analysis and experimental verification demonstrate that the microcantilever with embedded piezoresistor and signal conditioning circuit is preferable to biosensor applications.
論文目次 ABSTRACT i
CONTENTS iii
LIST OF TABLES vi
LIST OF FIGURES vii
NOMENCLATURE xii

CHAPTER I INTRODUCTION 1
1.1 Motivation 1
1.2 Literature Review 4
1.2.1 Microcantilever in biosensors 4
1.2.2 Formation of surface stress 6
1.2.3 Readout 7
1.3 Scope of Work and Outlines 8

CHAPTER II MODELING OF PIEZORESISTIVE MICROCANTILEVER UNDER SURFACE STRESS AND THERMAL LOADING 14
2.1 Introduction 14
2.2 Surface Stress in Microcantilever 14
2.3 Thermal Effect in Microcantilever 19
2.4 Design of Microcantilever 23
2.5 Summary 25

CHAPTER III DOUBLE-MICROCANTILEVER DESIGN FOR SURFACE STRESS MEASUREMENT 38
3.1 Introduction 38
3.2 Double-Microcantilever Design 38
3.3 Summary 43

CHAPTER IV BRIDGE CIRCUIT DESIGN IN BIOSENSOR CHIP 53
4.1 Introduction 53
4.2 Bridge Circuit Design 54
4.3 Offset Voltage in Bridge Circuit 56
4.4 Effect of Temperature Drift 58
4.5 Summary 61

CHAPTER V FABRICATION OF BIOSENSOR CHIP 71
5.1 Introduction 71
5.2 MEMS by CMOS Process 71
5.3 Four-layer Microcantilever in Biosensor Chip 73
5.3.1 Biosensor chip design 73
5.3.2 Fabrication of biosensor chip 75
5.3.3 Post-processing and fabrication results 82
5.4 Double-microcantilever in Biosensor Chip 84
5.5 Summary 85

CHAPTER VI MEASUREMENT OF BIOANALYTES IN BIOSENSOR CHIP 102
6.1 Introduction 102
6.2 Thermo-Electrical Property of Piezoresistive Microcantilever 102
6.3 On-Chip Measurement of Bioanalytes 103
6.3.1 Package of biosensor chip and instrumentation 103
6.3.2 Thiol-modified DNA 104
6.3.3 Performance of biosensor chip 106
6.4 Summary 109

CHAPTER VII SUMMARY AND CONCLUSIONS 120

REFERENCES 124
PUBLICATION LIST 132
VITA 133
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系統識別號 U0026-0812200911372466
論文名稱(中文) 真菌幾丁聚醣降低癌症化療藥物副作用 之效果評估及其機制之探討
論文名稱(英文) Study on the Prevention Effects of Chitosan in Cancer Chemotherapy – Induced Adverse Effects and Related Mechanisms
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 93
學期 2
出版年 94
研究生(中文) 許棠閔
學號 S7692109
學位類別 碩士
語文別 中文
口試日期 2005-07-06
論文頁數 77頁
口試委員 口試委員-蘇哲俊
指導教授-王應然
召集委員-何元順
口試委員-侯自詮
關鍵字(中) 副作用
5-氟尿嘧啶
幾丁聚醣
癌症化學治療
關鍵字(英) 5-Fluorouracil
side effects
Chitosan
Cancer Chemotherapy
學科別分類
中文摘要   癌症化學治療通常被用來對付無法用手術去除的癌細胞,不過在接受癌症化學治療的過程中,會對病人產生不良的副作用,影響病人健康。真菌幾丁聚醣(Chitosan)為真菌類細胞壁中的主要成分。研究發現幾丁聚醣具有許多生物活性作用,如增進免疫功能、保護腸胃道及抑制腫瘤細胞生長等。本研究的目的在探討真菌幾丁聚醣對於癌症化學治療所產生的副作用是否有改善的效果,且不影響癌症化療藥物的抗癌效果,並探討其相關的機制。首先利用動物實驗模式,以骨髓毒性、胃腸毒性、免疫功能作為副作用指標,來評估真菌幾丁聚醣對於癌症化學治療藥物(5-氟尿嘧啶,5-FU) 所引發的副作用是否有改善的效果。小鼠實驗中單獨以5-FU給藥及5-FU合併真菌幾丁聚醣方式給藥,藉由測定腫瘤體積與重量、骨髓中CD 19細胞百分比、血液中白血球與淋巴球數量、小腸蔗糖酶活性、腹瀉發生率、微核試驗及彗星分析來評估抗癌效果、副作用發生情形和相關機轉的探討。研究結果顯示,5-FU合併真菌幾丁聚醣給藥並不影響5-FU抑制癌細胞生長的效果。真菌幾丁聚醣減輕了由5-FU所造成骨髓中CD 19百分比及血液中白血球與淋巴球細胞數量的下降情形。5-FU合併真菌幾丁聚醣可以降低小腸黏膜受到損害及延緩小鼠腹瀉的發生率。在微核測驗與彗星分析結果中顯示出5-FU合併真菌幾丁聚醣減少了5-FU對於正常細胞染色體與DNA的傷害。由實驗結果推論,真菌幾丁聚醣可能經由降低5-FU對於正常細胞之DNA傷害,而改善了5-FU所誘發骨髓毒性、免疫毒性與腸胃毒性之副作用。
英文摘要  Cancer chemotherapy is used to treat tumor cells that can not be removed by surgery. In the process of treatment, however, cancer chemotherapy often induces side effects and reduces health of cancer patients. Chitosan is the main component of the fungi’s cell wall. Chitosan has several biological activities such as immuno-enhancing ability, protection mucosa damage in gastrointestinal track and anti-tumor activity. The purpose of this study was to investigate whether Chitosan could improve the side effects induced by chemotherapeutic agent without loss its anti-tumor ability and their related mechanisms. The study examined the anti-tumor activity and side effects (meylotoxicity, immunotoxicity and gastrointestinal toxicity) of combined treatment of chemotherapeutic drug 5-Fluorouracil (5-FU) and Chitosan in vivo. We measured the weight and volume of tumor, percentage of CD19 in bone marrow, leukocyte number, lymphocyte number, sucrase activity, incidence of diarrhea, micronucleated polychromatic erythrocytes (MNPCE) frequency and Comet assay in mice treated with 5-FU plus Chitosan or 5-FU alone to evaluate the effects of Chitosan on the 5-FU-induced anti-tumor activity and side effects. The results showed that 5-FU plus Chitosan inhibited the tumor growth as well as 5-FU alone. Chitosan improved the reduction of leukocyte number, lymphocyte number and CD19 percentage of bone marrow induced by 5-FU. 5-FU combined with Chitosan reduced the injury of the small intestinal mucosa and delayed the onset of diarrhea in mice. 5-FU combined with Chitosan also decreased MNPCE frequency and DNA damage caused by 5-FU in bone marrow cells. The results demonstrate that Chitosan may improve adverse effects induced by 5-FU through reduction DNA damage of normal cell.
論文目次 中文摘要 1
Abstract 2
第一章、緒論 7
第二章、文獻回顧 8
第一節、癌症化學治療 8
第二節、5-氟尿嘧啶簡介 9
第三節、幾丁質與幾丁聚醣簡介 10
第四節、CD3-T淋巴球與CD19-B淋巴球 11
第五節、微核試驗 12
第六節、彗星分析(Comet assay) 13
第七節、癌症化學治療與腹瀉 13
第三章、研究目的 15
第四章、研究架構 16
第一節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之抑癌能力 16
第二節、Pilot study -小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情況 17
第三節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情況 18
第四節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之腹瀉發生率 19
第五節、小鼠實驗模式評估真菌幾丁聚醣降低5-FU藥物副作用機制之探討 20
第五章、研究材料與方法 21
第一節、研究材料 21
第二節、研究方法 23
第三節、統計分析 36
第六章、實驗結果 37
第一節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之抑癌能力 37
第二節、Pilot study -小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情形 37
第三節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情形 39
第四節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之腹瀉發生率 41
第五節、小鼠實驗模式評估真菌幾丁聚醣降低5-FU藥物副作用機制之探討 41
第七章、討論 43
第八章、結論 47
第九章、參考文獻 48
附 錄 57
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系統識別號 U0026-0812200911373384
論文名稱(中文) 尤金.奧尼爾的《鯨油》與《瓊斯皇帝》: 權力、慾望與資本主義
論文名稱(英文) Eugene O’Neill’s Ile and The Emperor Jones: Power, Desires and Capitalism
校院名稱 成功大學
系所名稱(中) 外國語文學系在職專班
系所名稱(英) Department of Foreign Languages & Literature (on the job class)
學年度 93
學期 2
出版年 94
研究生(中文) 薛虹雲
學號 k2789113
學位類別 碩士
語文別 英文
口試日期 2005-06-28
論文頁數 75頁
口試委員 指導教授-閻振瀛
口試委員-石光生
口試委員-范瑞芬
關鍵字(中) 美國寫實主義
美國夢
資本主義
慾望
權力
關鍵字(英) American Realism
American Dream
capitalism
desires
power
學科別分類
中文摘要   美國在資本主義的自由經濟模式下,形成了以發財與致富為最終目標的「美國夢」。然而,追求財富須以正當的方式為之,而非唯利是圖,不擇手段,無所不用其極;否則,就如聖經馬太福音第十六章第二十六節提到 “人若賺得了全世界,賠上自己的生命,又有什麼益處呢?” 尤金.奧尼爾藉著《鯨油》與《瓊斯皇帝》二劇來闡述其對資本主義下的經濟制度作批判,劇中的主角為了追求個人的財富與名利,前者是不達目的絕不終止,罔顧親情的呼喚;後者則極盡詐騙之能事,運用從白人社會所習得的詐術,奴役與他相同的族類,為的只是滿足一己之私慾,兩者終究付出了無法挽回的代價。
  本論文共有四章,第一章為緒論,簡述美國戲劇的發展,並以尤金.奧尼爾的《鯨油》與《瓊斯皇帝》二劇為主幹,切入論文之主題─權力、慾望與資本主義三者之間的關係。第二、三章,則分別就《鯨油》與《瓊斯皇帝》二劇的情節內容來探討權力、慾望與資本主義於劇中的呈現。在結論部分,本人以台灣實業界鉅子許文龍先生為例,說明一個企業家在資本主義經濟模式下,其應具備追求財富的態度,表示個人一些粗淺的看法。
英文摘要   In the United States, under the exaltation of capitalism, people try to pursue their wealth is no other than to fulfill the so-called merican Dream’. However, the making of profits should be within the proper limits. The making of profits without taking into good onsideration of the measures used to make them is not allowed. Biblical dictum in Matt. 16.26, “For what is a man profited, if he shall gain the whole world, and lose his own soul?” Eugene O’Neill criticized the value of capitalism through Ile and The Emperor Jones. The protagonists in both plays voraciously seek for their materialistic goals. The former didn’t stop his pursuing without attaining the goal, regardless of his wife’s earnest request for turning homeward;the latter then gave no limits to victimize the natives with the exploitive habits that he had learned from the white men. What they sought was to satisfy their personal desires and power. Finally they both paid for the unredeemable fate.
  In the introductory chapter, I give a general review about Eugene O’Neill and American theatre, and, also, I give a theme study about power, desires and capitalism. In Chapters Two and Three, Ile and The Emperor Jones are respectively studied according to the subjects such as power, desires and capitalism. In the concluding chapter, I take the Taiwan business tycoon Wen-long Hsu as an example to pronounce my personal comments about a businessman’s attitude toward profits.
論文目次 Table of Contents

Chapter One:
Introduction--------------------------------------------------------------1

Chapter Two: Ile----------------------------------------------------------------------29

Chapter Three:
The Emperor Jones--------------------------------------------------------------------39

Chapter Four: Conclusion---------------------------------------------------------------58

Abbreviations------------------------------------------------------------67

Illustrations------------------------------------------------------------68

Bibliography-------------------------------------------------------------69
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系統識別號 U0026-0812200911394855
論文名稱(中文) Morusin抑制NF-kB路徑導致癌細胞凋亡
論文名稱(英文) Morusin induces NF-kB-mediated apoptosis in cancer cells
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 93
學期 2
出版年 94
研究生(中文) 吳鳳翎
學號 s4692403
學位類別 碩士
語文別 中文
口試日期 2005-07-22
論文頁數 93頁
口試委員 口試委員-蘇純立
指導教授-翁舷誌
口試委員-李政昌
口試委員-林忠男
關鍵字(中) 癌症
桑白皮
細胞凋亡
關鍵字(英) morusin
apoptosis
NF-kB
cancer
學科別分類
中文摘要   在台灣地區人類十大死因之中,惡性腫瘤始終高居第一位。因此,在一般被認為溫和的中草藥裡,尋找適合的癌症治療藥物,並希望能進一步探究其是否具備癌症預防的效果。在中草藥桑白皮中,經粗萃取而得化合物之一,Morusin,發現對於腫瘤細胞的生長有抑制的情形,在先前的研究已知Morusin可以抑制大腸直腸癌細胞HT-29,主要是透過粒線體膜電位喪失,並且使得Caspase 活性增加,產生細胞凋亡的情形。經由MTT assay證實,morusin也可造成肝癌細胞Hep 3B細胞凋亡,其六天的IC50為7.14uM,在其他癌症細胞也會有抑制情形。更深入探討morusin造成癌症細胞產生apoptosis的其他因子。首先,在與癌症有密切關係的轉錄因子,NF-kB方面,發現NF-kB入核的情形被morusin抑制,在功能方面也發現,NF-kB與DNA結合的能力也被morusin抑制,在此可以推測morusin主要是藉由降低轉錄因子NF-kB的表現,而使得原本不斷生長的癌症細胞,其增生能力受到抑制。而NF-kB路徑上游的受許多因子調控,在與細胞增生與生存相關的路徑,Akt路徑,發現在這條路徑上的相關的調控分子,也受到影響。因此可以證明morusin對癌症細胞的影響,主要是令其與增生相關PI3K-Akt路徑受到抑制,而使NF-kB下游調控許多與生存相關的基因與蛋白質也受到抑制。另外,在Hep 3B細胞中,也發現,morusin誘使其產生細胞凋亡情形;在細胞週期的分析中,發現sub-G1期DNA量增加,與apoptotic body產生,主要是經由caspase 9的表現量增加,使得caspase activated DNase(DFF40)在細胞核裡表現量增加,進而切割細胞的DNA。所以,本研究中證實morusin對大腸直腸癌細胞造成抑制情形,是經由Akt,而在肝癌細胞中也可誘發其細胞凋亡的產生,藉由本實驗可以發現morusin作為癌症治療藥物的潛力,並希望在將來能夠更進一步研究其預防癌症的能力與在臨床上應用的可能。
英文摘要  Colorectal and hepatocellular carcinoma cause leading malignant death worldwide. Since the ways to treat cancer are still limited, Chinese herbal medicine became a choice to expand. The crude extracts of M. australis (Moraceae) are remedy used to treat disease in Taiwan. The specific goal of the present study is to determine the anti-tumor mechanism of morusin, isolated from M. australis, in human colorectal and hepatocellular carcinoma cell lines. Previous experimental results revealed that morusin inhibited the growth of human colorectal cancer HT-29 cells by the activation of caspases and loss of mitochondria membrane potential. The present study further demonstrated that NF-kB and its DNA biding activity were decreased after morusin treatment in HT-29 cells. Decrease in phosphorylation of PDK1, Akt, IKK, IkBandBad, the upstream regulators of NF-kB, was also observed. In hepatocellular carcinoma Hep 3B cells, increase of sub-G1 and nuclear condensation were induced by morusin. The IC50 of morusin in Hep 3B cells was 7.1uM which is far lower than 29.8uM in peripheral blood mononuclear cells (PBMC). Activation of caspase 9, decrease in DFF-45, increase of nuclear DFF-40, and suppression in NF-kB level and its DNA biding activity were also observed in Hep 3B cells. These findings suggest that morusin induce apoptosis of cancer cells through the inhibition of NF-kB by downregulation of Akt signaling pathway. The apoptotic mechanism induced by morusin provide a new field in cancer therapy.
論文目次 中文摘要……………………………………………………1
英文摘要……………………………………………………2
緒論…………………………………………………………3
實驗材料……………………………………………………17
實驗方法……………………………………………………22
結果…………………………………………………………34
討論…………………………………………………………40
參考文獻……………………………………………………51
附圖表………………………………………………………76
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李時珍.本草綱目.木部.桑.1596
趙健麟(民93)Morusin經由細胞凋亡抑制大腸直腸癌細胞生長之作用機轉。國立成功大學微生物及免疫學研究所論文。中華民國。台南

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系統識別號 U0026-0812200911405284
論文名稱(中文) 以蛋白質體分析方法尋找膀胱癌病人尿液中蛋白質生物指標
論文名稱(英文) Proteomic analysis of urinary proteins from bladder cancer patients for biomarker discovery
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 93
學期 2
出版年 94
研究生(中文) 劉家瑗
學號 S7692407
學位類別 碩士
語文別 中文
口試日期 2005-07-27
論文頁數 85頁
口試委員 召集委員-游一龍
指導教授-廖寶琦
口試委員-郭浩然
口試委員-郭余民
關鍵字(中) 膀胱癌
蛋白質體學
尿液蛋白質
高效能液相層析串聯式質譜儀
關鍵字(英) biomarker
urinary protein
bladder cancer
proteomic
LC-MS/MS
學科別分類
中文摘要   膀胱癌,為常見泌尿系統癌症的一種,尤為生殖泌尿腫瘤中次常見的死因。而台灣南部的烏腳病流行區則有特別高的膀胱癌發生率。傳統上用以診斷膀胱癌的方法具侵入性且花費昂貴,因此,找出診斷膀胱癌的新方法是迫切需要的。本研究的目的是利用蛋白質體學分析方法建立膀胱癌病人尿液中的蛋白質分布圖譜。選取來自台灣西南地區的膀胱癌病人、烏腳病流行區的膀胱癌病人以及對照組共三組配對成實驗組進行尿液中蛋白質體內容的分析。人體的體液如尿液,具有複雜的基質;其中可能包含各種無機鹽類、緩衝液及蛋白質,而這些成分可能對樣本在質譜的分析上造成干擾甚或失敗。雖然蛋白質體二維膠電泳技術已發展多年,但於研究過程中發現,其對於尿液蛋白質體的鑑定工作上仍有限制。因此,本研究所使用的方法是將尿液淨化後以奈米高效能液相層析電噴灑串聯式質譜儀來分析尿液中蛋白質體。此分析方法的建立工作將有利於往後以蛋白質體資料庫鑑定膀胱癌病人蛋白質體之不同表現,進一步甚可尋找膀胱癌的蛋白質生物指標。
英文摘要  Bladder cancer, one of the common urologic cancers, represents the second most common cause of death among genitourinary tumors. The higher bladder cancer incidence rates have been observed in the endemic area of black foot disease (BFD) in southern Taiwan. The traditional bladder cancer diagnose methods are both invasive and expensive, thus developing new approaches for the diagnosis of bladder cancer are in urgent need. The aim of this study is utilized proteomic approach to establish urinary protein patterns. In this study, the result details protein profiles in urine from control, BFD bladder cancer, and non-BFD bladder cancer patients. Biofluids, such as urine, from very complex matrixes often contain large kinds of inorganic salt, buffers, and proteins. However, the presence of contaminants virtually ensures the failure of subsequent analysis of the sample by mass spectrometry. Although impressive improvements in 2DE technologies have occurred in recent years, identification of urine proteins is still challenging. In this experiment, it tends to complete a study for a urine sample cleanup strategy and identification by using nano-HPLC-ESI-MS/MS spectrometry. These proteins are valuable for mass identification of differentially expressed proteins involved in proteomics database and screening biomarker to further study in human bladder cancer. The significance for creating a strategy of urinary proteome analyze for new bladder cancer marker proteins discover, and for their simultaneous display and analysis in patients suffering from bladder disorders has been examined.
論文目次 中文摘要…………………………………………………………………………I
英文摘要…………………………………………………………………………II
謝誌………………………………………………………………………………III
主目錄……………………………………………………………………………V
表目錄……………………………………………………………………………VII
圖目錄……………………………………………………………………………VIII
中英文對照表……………………………………………………………………IX
英文縮寫對照表…………………………………………………………………X

第一章 緒論
第一節 研究動機…………………………………………………………1
第二節 研究目的…………………………………………………………1
第二章 文獻探討
第一節 膀胱癌……………………………………………………………2
第二節 蛋白質體學………………………………………………………10
第三節 尿液蛋白質體分析………………………………………………15
第三章 研究材料與方法
第一節 研究架構…………………………………………………………22
第二節 尿液樣品採取……………………………………………………23
第三節 樣品前處理………………………………………………………24
第四節 蛋白質二維膠體電泳分析………………………………………27
第五節 高效能液相層析質譜儀分析……………………………………35

第四章 結果與討論
第一節 蛋白質二維膠體電泳分析結果…………………………………42
第二節 高效能液相層析串聯質譜儀分析結果…………………………53
第五章 結論
第一節 結論………………………………………………………………64

參考文獻…………………………………………………………………………66
附錄一 重複分析樣品的三次分析base peak層析圖………………………74
附錄二 解凍/冷凍樣品的三次分析base peak層析圖…………………….75
附錄三 樣品的三次分析base peak層析圖…………………………………76
附錄四 健康尿液中蛋白質體……………………………………………….78
附錄五 烏腳病流行區膀胱癌特異蛋白胺基酸序列……………………….82
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系統識別號 U0026-0812200911411123
論文名稱(中文) 探討紫杉醇誘導人類口腔癌症細胞株細胞凋亡之機制
論文名稱(英文) The Mechanism of Paclitaxel-induced apoptosis in human oral cancer cell lines
校院名稱 成功大學
系所名稱(中) 細胞生物及解剖學研究所
系所名稱(英) Institute of Cell Biology and Anatomy
學年度 93
學期 2
出版年 94
研究生(中文) 林志壕
學號 t9692106
學位類別 碩士
語文別 英文
口試日期 2005-06-28
論文頁數 67頁
口試委員 口試委員-劉明毅
指導教授-蕭振仁
指導教授-黃步敏
關鍵字(中) 紫杉醇
口腔癌症細胞株
細胞凋亡
關鍵字(英) Oral cancer cell lines
Apoptosis
Paclitaxel
學科別分類
中文摘要   細胞凋亡在多細胞生物的體內平衡扮演了重要的角色,而且硫胱氨酸蛋白脢(caspase)、Bcl-2家族蛋白酶和絲裂原活化蛋白激酶 (mitogen-activated protein kinase, MAPK)都有參與調控細胞的機制。目前有很多種抗癌藥物可以引起癌症細胞進行細胞凋亡中,如:紫杉醇 (paclitaxel)。紫杉醇是一種抗微小管的藥劑,可以抑制正常細胞分裂週期的進行而達到治療癌症的效果。口腔癌在台灣的發生率有逐年提高的現象,並且紫杉醇已經被用來治療頭頸部癌症。然而紫杉醇誘導頭頸部癌症細胞凋亡的機制仍然不清楚,了解抗癌藥物誘導細胞凋亡的機制對於臨床上的用藥是很重要的。因此,在我們要研究紫杉醇是如何誘導口腔癌症細胞株 (HSC-3, OEC-M1和OC3) 進行細胞凋亡。值得特別關注的是OEC-M1和OC3為台灣本土性的口腔癌細胞株。我們發現紫杉醇 (50和500 nM)處理這三株口腔癌症細胞株48小時後,可以引起口腔癌細胞株型態上的改變,並可以降低細胞的存活率。除此之外,紫杉醇可引起三株口腔癌細胞株去氧核醣核酸的斷裂。OEC-M1及OC3的細胞分裂週期有明顯的停留在G2/M週期,而且三株口腔癌症細胞株的subG1週期都是呈現增加的現象,指出紫杉醇引起口腔癌症細胞死亡是透過細胞凋亡機制。在OEC-M1以及OC3口腔癌症細胞株中,我們發現有硫胱氨酸蛋白脢 (caspase-3, -6, -7, -8和-9) 的活化,而且有看到poly (ADP-ribose) polymerases (PARP)失去活性。除此之外,絲裂原活化蛋白激酶家族中的JNK和Bcl-2都有被磷酸化的現象。另外我們使用硫胱氨酸蛋白脢的抑制劑 (Z-VAD) 去抑制口腔癌症細胞株 (OEC-M1和OC3) 細胞凋亡,結果發現口腔癌症細胞株的存活率可以增加,但是卻無法使細胞死亡的情形回復到百分之百。總結之,紫杉醇可以誘導口腔癌症細胞株進行細胞凋亡,並且硫胱氨酸蛋白脢、Bcl-2蛋白酶以及JNK有參與在其中。
英文摘要   Cell suicide or apoptosis plays an important role in the maintenance of cellular homeostasis in multicellular organisms, and the caspase cascades, Bcl-2 family proteins and mitogen-activated protein kinases (MAPKs) are involved in apoptosis. In cancer cell lines, apoptosis can be induced by many kinds of therapy-related inducer, such as paclitaxel (Taxol), a microtubule-stabilizing agent, suppressing several kinds of tumors by arresting cell-cycle progression. In Taiwan, the incidence of oral cancer increases in recent years, and paclitaxel has been successfully used for treatment of head and neck cancers. However the detail mechanism is still not sufficient. Understanding the molecular mechanisms of a chemotherapeutic agent on cancer cells is indispensable for clinical applications. Hence, we investigated the effect and mechanism of paclitaxel on oral cancer cell lines (HSC-3, OEC-M1, and OC3). It should be noted that, OEC-M1 and OC3 cells are indigenous oral cancer cell lines in Taiwan. We observed that 50 nM and 500 nM paclitaxel could cause morphological changes and significantly decreased cell viability after 48 hours treatment in all three cell lines. Additionally, paclitaxel induced the DNA fragmentation of these cell lines, in which OEC-M1 and OC3 cells significantly arrested at G2/M phase. In addition, the amount of subG1 increased among three cell lines, which indicated that paclitaxel triggered cell death through apoptosis. In OEC-M1 and OC3 cells, the activation of the caspases-3, -6, -7, -8, -9 and the cleavage of poly ADP-ribose polymerase (PARP) were detected. Moreover, the JNK and Bcl-2 were phosphorylated in OEC-M1 and OC3 cell lines. In caspase general inhibitor experiment, the general inhibitor (Z-VAD-FRM) could increase the cell viability, but could not prevent all cell death. In summary, paclitaxel could induce oral cancer cell lines apoptosis through caspase and MAPKs cascades in OEC-M1 and OC3 cells.
論文目次 TABLE OF CONTENTS
ABSTRACT
Chinese……………………………………………………………..i
English……………………………………………………………..ii
INTRODUCTION……………………………………………………..1
MATERIALS AND METHODS……………………………………8
Chemicals………………………………………………………….8
Cells and cell culture………………………………………………9
Morphology study…………………………………………………9
MTT assay………………………………………………………..10
Flow cytometry analysis………………………………………….10
Immunoblot analysis……………………………………………...11
Caspase inhibitors treatment……………………………………...12
Statistics…………………………………………………………..12
RESULTS
Effects of paclitaxel on morphological changes in human
oral cancer cell lines……………………….……………………..13
Effects of paclitaxel on cell viability in human oral cancer
cell lines………………………………….……………………….13
Effects of paclitaxel on cell cycle progression in human oral
Cancer cell lines………………………………………………......14
The percentage of paclitaxel-induced subG1 and G2/M phases
of cell cycle progression in human oral cancer cell lines……...…15
Effects of paclitaxel on caspases-8 and -9 protein expression
in human oral cancer cell lines…………………………………...16
Effects of paclitaxel on effector caspase proteins expression
in human oral cancer cell lines………………………………...…17
Effects of paclitaxel on PARP protein cleavage in human
oral cancer cell lines……………………………………………...18
The effects of paclitaxel on the activation of MAPK pathway
in human oral cancer cell lines…………………………………...19
The effects of paclitaxel on the expression of p-Bcl-2 paclitaxel in
human oral cancer cell lines……………………………………...20
The effects of general caspase inhibitor (z-VAD-fmk)
in paclitaxel-induced cell death in human oral cancer cell lines....21
DISCUSSION………………………………………………………...23
REFERENCES……………………………………………………….29
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系統識別號 U0026-0812200911425021
論文名稱(中文) 缺氧誘導因子-1alpha調控CD151之探討
論文名稱(英文) Regulation of CD151 (plate-endothelial tetraspanin antigen 3, PETA-3) by hypoxia inducible factor-1alpha
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 93
學期 2
出版年 94
研究生(中文) 蔡秀真
學號 s3692107
學位類別 碩士
語文別 中文
口試日期 2005-07-19
論文頁數 79頁
口試委員 召集委員-湯銘哲
口試委員-劉校生
指導教授-蔡少正
關鍵字(中) 缺氧
大腸直腸癌
缺氧誘導因子-1alpha
CD151
關鍵字(英) HIF-1alpha
hypoxia
PETA-3
CD151
colon cancer
學科別分類
中文摘要   缺氧(hypoxia)的定義指細胞或組織處在低於正常氧氣分壓的狀態下。當細胞遭遇到缺氧時,會造成許多細胞功能的改變,而促使細胞能適應這樣的環境,其中這樣的機制大部分可透過缺氧誘導因子-1alpha來調控。當缺乏氧氣時,細胞內的缺氧誘導因子-1alpha會與缺氧誘導因子-1beta結合形成二聚體,並結合到受其調控基因的DNA缺氧反應序列上,進而調控下游基因的表現。在臨床的研究報導指出,缺氧會造成腫瘤組織對於癌症治療上具有抵抗性,並且在許多的癌症中均發現缺氧誘導因子-1alpha過量表現的情形。先前我們實驗室利用生物資訊的方式,分析文獻中已被報導證實受到缺氧誘導因子-1alpha調控基因的HRE及其周圍序列,進而建構一個較長序列HRE模型,將人類及小鼠所有基因的啟動子區域與此模型做比對,結果得到許多可能受到缺氧調控的基因,CD151為其中之一可能受到缺氧調控的基因,並且這樣的想法在目前的文獻中尚未被探討。CD151是一個穿越細胞膜的蛋白(屬於tetraspanin superfamily的成員之一),過去研究指出CD151在許多的細胞中均有表現(大部分於上皮細胞、內皮細胞及血小板等),而CD151在細胞中所扮演的角色被認為與細胞的附著和細胞移動的能力相關,並且被認為參與在許多癌症侵襲轉移的過程中。首先,我們由臨床的檢體中發現CD151於同一大腸直腸癌病人腫瘤組織中的表現量明顯低於正常組織,由於觀察到這樣的現象,因此在接下來的研究我想探討缺氧是否會影響CD151基因的表現?藉由給予大腸直腸癌細胞株化學性模擬缺氧處理後,CD151不論是在mRNA或是在蛋白質的表現量均有明顯的減少,並且這樣的處理也會造成CD151啟動子的活性下降。綜合以上結果,我們證實了缺氧會經由缺氧誘導因子-1alpha來調控CD151基因的表現,而這樣的現象使我們推測缺氧會造成腫瘤細胞CD151表現量減少,使得細胞附著在細胞外基質的能力變弱,因而增加腫瘤細胞的移動能力,進而促進大腸直腸癌的侵襲轉移的過程。
英文摘要  Hypoxia stress has been shown to involve in several biological processes such as angiogenesis and tumorigenesis. The most rapidly growing region of solid tumors undergoe low oxygen tension because of an imbalance in oxygen supply and consumption and this process called hypoxia. Hypoxia inducible factor-1alpha(HIF-1alpha) is a transcription factor that regulates expression of hypoxia response genes. Previously we had constructed a conserved hypoxia response element (HRE) model by bioinformatics methods. By using this model to screen human, mouse, and rat promoter sequences, thousands of the genes containing HREs have been identified. In this study, a novel candidate gene, CD151, is selected for further characterization. CD151 is a member of the tetraspanin superfamily and broadly expressed by a variety of cell types, notably epithelial cells, endothelial cells, muscle cells, Schwann cells, megakaryocytes, and platelets. This molecule is noted for its strong molecular associations with integrins. In vitro functional studies have pointed to a role for CD151 in cell-cell adhesion, cell migration, platelet aggregation, and angiogenesis. It has also been implicated that HIF-1alpha is elevated in colon cancer cells. Given the bioinformatic prediction that the promoter region of CD151 contains functional HRE, it is likely that expression of CD151 in colon cancer cells might be regulated due to elevation of HIF-1alpha. Thus, we aim to determine effects of hypoxia on CD151 expression and its pathophysiological roles on cancer development and progression. We find that expression of CD151 in tumor tissues is lower than that in normal tissue in colon cancer patients. In vitro study demonstrated CD151 protein and mRNA levels are decreased after desferrioxamine mimic chemical hypoxic treatment in colon cancer cell line SW480 and SW620. Promter activity assay further demonstrated that hypoxia treatment inhibits reporter system carrying the HRE of human CD151 promoter. The hypoxia-induced decrease in CD151 expression can be reversed by transfection of dominant negative form HIF-1alpha. Results from this study should provide novel information in elucidating effect of hypoxia on one of the prognostic marker, CD151, in patients with colon cancer.
論文目次 中文摘要..................................................1
Abstract.................................................. 3
誌謝...................................................... 5

目錄...................................................... 6
圖錄...................................................... 9
緒論...................................................... 11
實驗材料與方法............................................ 21
(I)材料:
臨床大腸直腸癌人體檢體之取得........................... 21
使用之細胞株及細胞培養方法............................. 22
(II)實驗方法:
A. 缺氧處理細胞........................................ 23
B. 細胞total RNA 之純化................................ 23
C. 反轉錄聚合酶連鎖反應
(Reverse transcription polymerase chain reaction; RT-PCR)...............................................

24
D. 製備小量質體DNA (Minipreparation of plasmid DNA).... 25
E. 製備大量質體DNA (Midipreparation of plasmid DNA).... 26
F. 免疫組織染色 (Immunohistochemistry)................. 27
G. 蛋白質濃度分析 (Lowry assay)........................ 29
H. 蛋白質電泳與西方轉漬法 (Western blotting)........... 30
I. 細胞轉殖 (Transient transfection)................... 31
J. 螢光酵素檢測 (Luciferase assay)..................... 33
K. 統計分析 (Statistical analysis)..................... 34
結果 .................................................... 35
A. C151於大腸直腸癌病人腫瘤組織的表現量低於正常組織.... 35
B. CD151於大腸直腸癌病人腫瘤組織及與距離腫瘤不同方向
(靠近胃及遠離胃)的正常組織中表現量...................
35
C. CD151於大腸直腸癌病人腫瘤組織及與距離腫瘤不同距離的正常組織中表現量.......................................
36
D. 大腸直腸癌病人臨床分期與CD151蛋白表現量的關係...... 36
E. 利用免疫組織染色觀察大腸直腸癌組織中CD151蛋白的表現.....................................................
37
F. 缺氧誘導因子-1蛋白於大腸直腸癌病人正常組織及腫瘤組織的表現的情形.........................................
37
G. DFO處理大腸直腸癌細胞株SW480及SW620促使CD151 mRNA表現量下降.............................................
38
H. DFO處理大腸直腸癌細胞株SW480及SW620促使CD151 蛋白質表現量下降...........................................
39
I. DFO處理可透過缺氧誘導因子-1促使細胞中CD151蛋白質的表現量減少.............................................
39
J. 利用生物資訊方式分析CD151驅動子所具有的HRE序列..... 40
K. 化學模擬缺氧處理後促使缺氧誘導因子-1蛋白質在細胞核中聚積的情形增加.......................................
40
討論 .................................................... 59
參考文獻 ................................................ 67
附錄: ...................................................
(一)溶液的配製 ........................................ 72
A.細胞培養相關溶液............................. 72
B.蛋白質分析相關溶液........................... 74
C. 細胞萃取相關溶液............................ 74
D. 質體製備相關溶液............................ 75
(二)使用藥品廠牌一覽表 .............................. 77
圖錄
圖一‧ CD151蛋白質於大腸直腸癌病人正常大腸組織及腫瘤組織中的現........................................
42
圖二‧ CD151蛋白質於大腸直腸癌病人靠近肛門處或是接近胃的正常大腸組織與腫瘤組織中的表現量..............
43
圖三‧ CD151蛋白質於大腸直腸癌病人腫瘤組織與距離腫瘤不同遠近的正常大腸組織中的表現量..................
44
圖四‧ 大腸直腸癌病人臨床分期與CD151蛋白質於腫瘤組織或距離腫瘤不同遠近的正常大腸組織中表現量之相關性..............................................

45
圖五‧ 免疫組織染色觀察CD151於人類胎盤中的表現........ 46
圖六‧ 免疫組織染色觀察CD151蛋白質於腫瘤組織及靠近胃或是接近肛門處的正常大腸組織與中的表現量..........
47
圖七‧ 免疫組織染色觀察CD151蛋白質於大腸直腸癌病人腫瘤組織與離腫瘤不同遠近的正常大腸組織中的表現量....
48
圖八‧ 缺氧誘導因子-1蛋白質於大腸直腸癌病人正常大腸組織及腫瘤組織中的表現............................
49
圖九‧ 大腸直腸癌細胞經DFO處理對於細胞核中缺氧誘導因子-1蛋白質表現的影響(聚積的現象)...............
50
圖十‧ 大腸直腸癌細胞株COLO 320DM經DFO處理後CD151 mRNA 的表現量........................................
51
圖十一‧ 大腸直腸癌細胞株SW480及SW620分別經DFO處理後CD151 mRNA 的表現量.............................
52
圖十二‧ 大腸直腸癌細胞株SW480及SW620分別經DMOG處理後CD151 mRNA 的表現量.............................
53
圖十三‧ 大腸直腸癌細胞株SW480經DFO處理後CD151 蛋白質的表現情形........................................
54

圖十四‧ 大腸直腸癌細胞株SW620經DFO處理後CD151 蛋白質的表現情形........................................
55
圖十五‧ 大腸直腸癌細胞株SW480經轉殖dominate negative缺氧誘導因子-1質體後給予DFO處理CD151蛋白質的表現..............................................

56
圖十六‧ CD151驅動子結構及所具有可能缺氧誘導因子-1結合的HRE序列.........................................
57
圖十七‧ 利用25個鹼基的CD151 HRE序列來分析DFO對於CD151啟動子活性的影響................................
58
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