Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 牙醫專業學院
  4. 口腔生物科學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36925
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor吳漢忠(Han-Chung Wu 吳漢忠)
dc.contributor.authorPo-Chin Changen
dc.contributor.author張博欽zh_TW
dc.date.accessioned2021-06-13T08:23:03Z-
dc.date.available2005-09-01
dc.date.copyright2005-08-02
dc.date.issued2005
dc.date.submitted2005-07-19
dc.identifier.citationAn, P., Lei, H., Zhang, J., Song, S., He, L., Jin, G., Liu, X., Wu, J., Meng, L., Liu, M., and Shou, C. (2004). Suppression of tumor growth and metastasis by a VEGFR-1 antagonizing peptide identified from a phage display library. Int J Cancer 111, 165-173.
Arap, W., Kolonin, M. G., Trepel, M., Lahdenranta, J., Cardo-Vila, M., Giordano, R. J., Mintz, P. J., Ardelt, P. U., Yao, V. J., Vidal, C. I., et al. (2002). Steps toward mapping the human vasculature by phage display. Nat Med 8, 121-127.
Arap, W., Pasqualini, R., and Ruoslahti, E. (1998). Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279, 377-380.
Bergers, G., and Benjamin, L. E. (2003). Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3, 401-410.
Bindra, R. S., and Glazer, P. M. (2005). Genetic instability and the tumor microenvironment: towards the concept of microenvironment-induced mutagenesis. Mutat Res 569, 75-85.
Borsum, T., Hagen, I., Henriksen, T., and Carlander, B. (1982). Alterations in the protein composition and surface structure of human endothelial cells during growth in primary culture. Atherosclerosis 44, 367-378.
Breivik, J. (2005). The evolutionary origin of genetic instability in cancer development. Semin Cancer Biol 15, 51-60.
Burg, M. A., Pasqualini, R., Arap, W., Ruoslahti, E., and Stallcup, W. B. (1999). NG2 proteoglycan-binding peptides target tumor neovasculature. Cancer Res 59, 2869-2874.
Carmeliet, P. (2000). Mechanisms of angiogenesis and arteriogenesis. Nat Med 6, 389-395.
Carmeliet, P., and Jain, R. K. (2000). Angiogenesis in cancer and other diseases. Nature 407, 249-257.
Chavakis, E., and Dimmeler, S. (2002). Regulation of endothelial cell survival and apoptosis during angiogenesis. Arterioscler Thromb Vasc Biol 22, 887-893.
de Bono, D. P., and Green, C. (1984). The adhesion of different cell types to cultured vascular endothelium: effects of culture density and age. Br J Exp Pathol 65, 145-154.
Feron, O. (2004). Targeting the tumor vascular compartment to improve conventional cancer therapy. Trends Pharmacol Sci 25, 536-542.
Feron, O., Krasnici, S., Werner, A., Eichhorn, M. E., Schmitt-Sody, M., Pahernik, S. A., Sauer, B., Schulze, B., Teifel, M., Michaelis, U., et al. (2004). Targeting the tumor vascular compartment to improve conventional cancer therapy effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels. Trends Pharmacol Sci 25, 536-542.
Folkman, J. (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med 285, 1182-1186.
Folkman, J. (2002). Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29, 15-18.
Folkman, J. (2004). Endogenous angiogenesis inhibitors. Apmis 112, 496-507.
Gasparini, G., Longo, R., Fanelli, M., and Teicher, B. A. (2005). Combination of antiangiogenic therapy with other anticancer therapies: results, challenges, and open questions. J Clin Oncol 23, 1295-1311.
Geiger, J. H., and Cnudde, S. E. (2004). What the structure of angiostatin may tell us about its mechanism of action. J Thromb Haemost 2, 23-34.
Giordano, R. J., Cardo-Vila, M., Lahdenranta, J., Pasqualini, R., and Arap, W. (2001). Biopanning and rapid analysis of selective interactive ligands. Nat Med 7, 1249-1253.
Hanahan, D., and Folkman, J. (1996). Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86, 353-364.
Hanahan, D., and Weinberg, R. A. (2000). The hallmarks of cancer. Cell 100, 57-70.
Hetian, L., Ping, A., Shumei, S., Xiaoying, L., Luowen, H., Jian, W., Lin, M., Meisheng, L., Junshan, Y., and Chengchao, S. (2002). A novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to its kinase domain receptor. J Biol Chem 277, 43137-43142.
Jemal, A., Murray, T., Ward, E., Samuels, A., Tiwari, R. C., Ghafoor, A., Feuer, E. J., and Thun, M. J. (2005). Cancer statistics, 2005. CA Cancer J Clin 55, 10-30.
Kang, H. T., Bang, W. K., and Yu, Y. G. (2004). Identification and characterization of a novel angiostatin-binding protein by the display cloning method. J Biochem Mol Biol 37, 159-166.
Kerbel, R. S., and Kamen, B. A. (2004). The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 4, 423-436.
Kuo, S. Y., Lin, C. T., and Wu, H. C. (2004). Identification of oral cancer-targeted peptides by in vivo phage display and development of ligand-targeted therapy for oral cancer., In The Nineteenth Joint Annual Conference of Biomedical Sciences. (Taipei, R. O. C.).
Lasky, L. A. (1992). Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science 258, 964-969.
Lee, T. Y., Wu, H. C., Tseng, Y. L., and Lin, C. T. (2004). A novel peptide specifically binding to nasopharyngeal carcinoma for targeted drug delivery. Cancer Res 64, 8002-8008.
Maruta, F., Parker, A. L., Fisher, K. D., Murray, P. G., Kerr, D. J., and Seymour, L. W. (2003). Use of a phage display library to identify oligopeptides binding to the lumenal surface of polarized endothelium by ex vivo perfusion of human umbilical veins. J Drug Target 11, 53-59.
Moser, T. L., Stack, M. S., Asplin, I., Enghild, J. J., Hojrup, P., Everitt, L., Hubchak, S., Schnaper, H. W., and Pizzo, S. V. (1999). Angiostatin binds ATP synthase on the surface of human endothelial cells. Proc Natl Acad Sci U S A 96, 2811-2816.
Mutuberria, R., Satijn, S., Huijbers, A., Van Der Linden, E., Lichtenbeld, H., Chames, P., Arends, J. W., and Hoogenboom, H. R. (2004). Isolation of human antibodies to tumor-associated endothelial cell markers by in vitro human endothelial cell selection with phage display libraries. J Immunol Methods 287, 31-47.
O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, E. H., and Folkman, J. (1994). Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79, 315-328.
Oku, N., Asai, T., Watanabe, K., Kuromi, K., Nagatsuka, M., Kurohane, K., Kikkawa, H., Ogino, K., Tanaka, M., Ishikawa, D., et al. (2002). Anti-neovascular therapy using novel peptides homing to angiogenic vessels. Oncogene 21, 2662-2669.
Pasqualini, R., Koivunen, E., Kain, R., Lahdenranta, J., Sakamoto, M., Stryhn, A., Ashmun, R. A., Shapiro, L. H., Arap, W., and Ruoslahti, E. (2000). Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res 60, 722-727.
Pasqualini, R., Koivunen, E., and Ruoslahti, E. (1997). Alpha v integrins as receptors for tumor targeting by circulating ligands. Nat Biotechnol 15, 542-546.
Pasqualini, R., and Ruoslahti, E. (1996). Organ targeting in vivo using phage display peptide libraries. Nature 380, 364-366.
Rajotte, D., Arap, W., Hagedorn, M., Koivunen, E., Pasqualini, R., and Ruoslahti, E. (1998). Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. J Clin Invest 102, 430-437.
Ruoslahti, E. (2004). Vascular zip codes in angiogenesis and metastasis. Biochem Soc Trans 32, 397-402.
Scott, J. K., and Smith, G. P. (1990). Searching for peptide ligands with an epitope library. Science 249, 386-390.
Sim, B. K., MacDonald, N. J., and Gubish, E. R. (2000). Angiostatin and endostatin: endogenous inhibitors of tumor growth. Cancer Metastasis Rev 19, 181-190.
Tam, J. P., and Zavala, F. (1989). Multiple antigen peptide. A novel approach to increase detection sensitivity of synthetic peptides in solid-phase immunoassays. J Immunol Methods 124, 53-61.
Tan, C., Cruet-Hennequart, S., Troussard, A., Fazli, L., Costello, P., Sutton, K., Wheeler, J., Gleave, M., Sanghera, J., and Dedhar, S. (2004). Regulation of tumor angiogenesis by integrin-linked kinase (ILK). Cancer Cell 5, 79-90.
Tarui, T., Miles, L. A., and Takada, Y. (2001). Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial cells. J Biol Chem 276, 39562-39568.
Troyanovsky, B., Levchenko, T., Mansson, G., Matvijenko, O., and Holmgren, L. (2001). Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol 152, 1247-1254.
Vlodavsky, I., Johnson, L. K., Greenburg, G., and Gospodarowicz, D. (1979). Vascular endothelial cells maintained in the absence of fibroblast growth factor undergo structural and functional alterations that are incompatible with their in vivo differentiated properties. J Cell Biol 83, 468-486.
Wu, H. C., Huang, Y. L., Chao, T. T., Jan, J. T., Huang, J. L., Chiang, H. Y., King, C. C., and Shaio, M. F. (2001). Identification of B-cell epitope of dengue virus type 1 and its application in diagnosis of patients. J Clin Microbiol 39, 977-982.
Yen, Y. T., Lin, C. T., and Wu, H. C. (2003). Generation and functional study of monoclonal antibodies against angiostatin., In The Eighteenth Joint Annual Conference of Biomedical Sciences. (Taipei, R. O. C.).
Zurita, A. J., Arap, W., and Pasqualini, R. (2003). Mapping tumor vascular diversity by screening phage display libraries. J Control Release 91, 183-186.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36925-
dc.description.abstract惡性腫瘤已成為世界及國人重要死因之一。在腫瘤傳統治療上,由於腫瘤細胞的基因不穩定性(genetic instability)高,容易產生抗藥性(drug resistant)的形成。腫瘤生長和轉移仰賴血管生成作用(angiogenesis)的觀念提出後,加上血管內皮細胞的基因變化遠比腫瘤細胞的變化小,使得血管內皮細胞成為重要的癌症治療標的,而血管生成作用的抑制也成為熱門的研究。在本研究中,我們利用噬菌體顯現法(phage display)找尋腫瘤血管內皮細胞的特有結合配位標記。血管靜止蛋白(angiostatin)是內生性的腫瘤血管生成抑制蛋白,具專一性和腫瘤血管內皮細胞結合的能力。利用噬菌體顯現胜肽庫,我們從四個對抗血管靜止蛋白功能性的單株抗體上找到了B細胞抗原決定位。運用這些B-細胞抗原決定位所合成的胜肽配體將有助於尋找出血管靜止蛋白上的功能性區域及發展抗血管生成治療(anti-angiogenesis therapy)。我們也利用噬菌體顯現法和血管內皮生長因子(VEGF)活化處理的人類臍靜脈內皮細胞(HUVEC)作用,可以尋找和增生內皮細胞結合的專一性胜肽序列。我們找出了數個可以和增生內皮細胞具較高結合性的胜肽,其中部份胜肽序列已見於其他發表文章,部份尚未發表仍屬新穎,由此可證明此方法的可行性。在活體動物實驗,我們也證明PCH118 噬菌體株可以專一性的標定到口腔癌細胞的異體移植腫瘤組織。本研究所找尋到具有專一性和活化人類臍靜脈內皮細胞結合的胜肽,未來可以運用於增生人類臍靜脈內皮細胞抗原的純化及確認,並可以發展標的性治療。zh_TW
dc.description.abstractMalignant tumor has become the most important cause of death around the world and in our country. Drug resistance formation due to high genetic instability of tumor cells were reported in conventional tumor therapies. Tumor progress and metastases depend on angiogenesis imply tumor vascular endothelial cells is a potent target of cancer therapy. Endothelial cells are stable in genetic mutations and inhibition of angiogenesis becomes hot research area. In this study, phage display was used to identify tumor vascular endothelial cells specific binding ligands. Angiostatin is a potent endogenous inhibitor of angiogenesis that specific bind to tumor vessels. Using phage-displayed peptide library, we have identified B-cell epitopes from several functional MAbs against angiostatin. These peptide ligands will be useful to identify the functional domain of angiostatin and develop anti-angiogenesis therapy. To identify peptide ligands specific binding to proliferated endothelial cells, phage display biopanning using VEGF stimulated HUVEC was performed. We have identified several peptide ligands with higher capability to bind stimulated-HUVEC. Some motifs of these peptide ligands have been published and some peptide ligands are novel. In vivo homing test showed that phage clone PCH118 targeting specifically to tumor tissue vasculature of oral cancer xenograft. Stimulated HUVEC-binding ligands identify in this study will be valuable to identify proliferated endothelial cell markers as well as develop targeted therapy.en
dc.description.provenanceMade available in DSpace on 2021-06-13T08:23:03Z (GMT). No. of bitstreams: 1
ntu-94-R92450007-1.pdf: 1260119 bytes, checksum: 1c2a8b3fb358f8ed7091dbd63964768a (MD5)
Previous issue date: 2005
en
dc.description.tableofcontents中文摘要 2
Abstract 3
Introduction 5
Materials and Methods 12
Results 17
Discussion 24
References 30
Figures and Tables 35
dc.language.isoen
dc.subject血管內皮細胞標記zh_TW
dc.subject噬菌體顯現法zh_TW
dc.subject抗血管新生zh_TW
dc.subject標的性治療zh_TW
dc.subjecttargeting therapyen
dc.subjectvascular endothelial cell markeren
dc.subjectphage displayen
dc.subjectanti-angiogenesisen
dc.title利用噬菌體顯現法識別活化內皮細胞的結合配體zh_TW
dc.titleIdentification of Stimulated Endothelial Cell-Binding Ligands Using In Vitro Phage Displayen
dc.typeThesis
dc.date.schoolyear93-2
dc.description.degree碩士
dc.contributor.oralexamcommittee郭彥彬,林欽塘
dc.subject.keyword噬菌體顯現法,抗血管新生,標的性治療,血管內皮細胞標記,zh_TW
dc.subject.keywordphage display,anti-angiogenesis,targeting therapy,vascular endothelial cell marker,en
dc.relation.page56
dc.rights.note有償授權
dc.date.accepted2005-07-19
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept口腔生物科學研究所zh_TW
顯示於系所單位:口腔生物科學研究所

文件中的檔案:
檔案 大小格式 
ntu-94-1.pdf
  未授權公開取用
1.23 MBAdobe PDF
顯示文件簡單紀錄


系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved