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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃佩欣(Pei-Hsin Huang) | |
| dc.contributor.author | Hsing-Fang Lo | en |
| dc.contributor.author | 羅杏芳 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:18:25Z | - |
| dc.date.available | 2016-10-07 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-11 | |
| dc.identifier.citation | 1.Negishi, M., I. Oinuma, and H. Katoh, Plexins: axon guidance and signal transduction. Cell Mol Life Sci, 2005. 62(12): p. 1363-71.
2.Parikh, A.A., et al., Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol, 2004. 164(6): p. 2139-51. 3.Takahashi, T., et al., Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell, 1999. 99(1): p. 59-69. 4. Rohm, B., et al., Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal semaphorin 3A. Mech Dev, 2000. 93(1-2): p. 95-104. 5.Gaur, P., et al., Role of class 3 semaphorins and their receptors in tumor growth and angiogenesis. Clin Cancer Res, 2009. 15(22): p. 6763-70. 6.Roodink, I., et al., Semaphorin 3E expression correlates inversely with Plexin D1 during tumor progression. Am J Pathol, 2008. 173(6): p. 1873-81. 7.Roodink, I., et al., Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies. BMC Cancer, 2009. 9: p. 297. 8.Nasarre, P., et al., Semaphorin SEMA3F and VEGF have opposing effects on cell attachment and spreading. Neoplasia, 2003. 5(1): p. 83-92. 9.Serini, G., et al., Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature, 2003. 424(6947): p. 391-7. 10.Banu, N., et al., Semaphorin 3C regulates endothelial cell function by increasing integrin activity. FASEB J, 2006. 20(12): p. 2150-2. 11.Kigel, B., et al., Successful inhibition of tumor development by specific class-3 semaphorins is associated with expression of appropriate semaphorin receptors by tumor cells. PLoS One, 2008. 3(9): p. e3287. 12.Dhanabal, M., et al., Recombinant semaphorin 6A-1 ectodomain inhibits in vivo growth factor and tumor cell line-induced angiogenesis. Cancer Biol Ther, 2005. 4(6): p. 659-68. 13.Chung, L., et al., Semaphorin signaling facilitates cleft formation in the developing salivary gland. Development, 2007. 134(16): p. 2935-45. 14.Casazza, A., et al., Sema3E-Plexin D1 signaling drives human cancer cell invasiveness and metastatic spreading in mice. J Clin Invest, 2010. 120(8): p. 2684-98. 15.Takahashi, T. and S.M. Strittmatter, Plexina1 autoinhibition by the plexin sema domain. Neuron, 2001. 29(2): p. 429-39. 16.Janssen, B.J., et al., Structural basis of semaphorin-plexin signalling. Nature, 2010. 467(7319): p. 1118-22. 17.Mauti, O., et al., Expression patterns of plexins and neuropilins are consistent with cooperative and separate functions during neural development. BMC Dev Biol, 2006. 6: p. 32. 18.Renaud, J., et al., Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells. Nat Neurosci, 2008. 11(4): p. 440-9. 19. Roodink, I., et al., Plexin D1 expression is induced on tumor vasculature and tumor cells: a novel target for diagnosis and therapy? Cancer Res, 2005. 65(18): p. 8317-23. 20. Ochiumi, T., et al., Neuropilin-1 is involved in regulation of apoptosis and migration of human colon cancer. Int J Oncol, 2006.29(1): p.105-116. 21. Kruger, RP., J. Aurandt, and Kun-Liang Guan, Semaphorins command cells to move. Nat Rev Mol Cell Biol, 2005. 6(10): p. 789-800. 22. Appleton, BA., et al., Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding. EMBO J, 2007. 26(23): p.4902-4912. 23. Klostermann, A., et al., The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like protein (EVL) via a novel carboxyl-terminal zyxin-like domain. J Biol Chem, 2000. 275(50): p. 39647-53. 24. Geretti, E. and M. Klagsbrun, Neuropilis: novel targets for anti-angiogenesis therapies. Cell Adh Migr, 2007. 1(2): p.56-61. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37051 | - |
| dc.description.abstract | Semaphorin 3A (Sema3A) 為Semaphorins 家族中的一個成員，是一種分泌蛋白，其生物作用包括指引軸突逐退的線索 (axonal repulsive guidance cue) 與正常或腫瘤細胞的附著、 游移等有關。過去研究已知穿膜蛋白Plexins和Neuropilins共同組成受體蛋白複合體 (receptor protein complex)，來傳導Sema3A在細胞內的訊號。但不同種類的Plexins是否可形成受體蛋白複合體，則尚未被報導。
本文論文皆在探討 (一) Plexin A2和Plexin D1是否會形成蛋白複合體來傳遞Sema3A的生物效應；以及 (二) Plexin A2和Plexin D1是否會共同或各別表現在特定的組織腫瘤中？若其然，則與腫瘤生成或病人病程有否統計上的關聯。針對探討主旨一，採用之實驗方法包括 1.利用西方墨點法及免疫沉澱法來偵測Plexin A2 和Plexin D1是否會形成蛋白複合體。方法2.利用免疫螢光法來觀察Plexin A2和 Plexin D1是否會在同一細胞的相同位置中表現 (co-localized)。方法3.為了更進一步確認Plexin A2和Plexin D1之間是否會直接形成蛋白複合體，於是設計了一連串的融合蛋白：將Plexin A2轉形到帶有螢光蛋白ECFP的ECFP-N1的載體中；將Plexin D1轉形到帶有螢光蛋白EYFP 的 EYFP-N1的載體中，利用螢光共振能量轉移的方法來研究Plexin A2和Plexin D1之間的關係。針對研究主旨二，為了得知Plexin A2和Plexin D1是否會共同或各別表現在特定的組織腫瘤中，採用本實驗室已架構的腫瘤tissue array，以免疫組織化學 (immunohistochemistry) 的方法，先初步篩選Plexin A2和Plexin D1會在哪些腫瘤組織中表現，再進一步擷取更多病人的檢體及組織切片，進行免疫組織化學染色，以生物統計方法來觀察Plexin A2和Plexin D1與腫瘤的生成或病人的存活率是否有關聯性。 | zh_TW |
| dc.description.abstract | Semaphorin 3A, as one member of Semaphorin superfamily, is a secreted protein. Sema3A, functions as negative mediator of axonal guidance and is involved in the attachment and migration of cells during embryonic development and tumor formation /progression. The transmembrane protein Plexins and Neuropilins can form receptor protein complexes to transduce the signalings of Sema3A in cells whether different kinds of Plexins can compose receptor protein complex remains unknown.
The specific aim of my study is to explore whether Plexin A2 and Plexin D1 can form protein complexes to transduce Sema3A signaling (specific aim-1).Moreover, we explore whether Plexin A2 and Plexin D1 were co-expressed or differentially expressed in certain types of tumor (specific aim-2).For specific aim-1, we used Western blotting, immunoprecipitation, and FRET to detect whether Plexin A2 and Plexin D1 can form protein complexes. For specific aim-2, we used the tumor tissue array paired with normal tissue to screen the expression of Plexin A2 and Plexin D1 by immunohistochemistry. For those tissue-types of tumor, more cases were collected for immunohistochemistry and statistical analysis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:18:25Z (GMT). No. of bitstreams: 1 ntu-100-R97444007-1.pdf: 3411208 bytes, checksum: 062a3c45def3c4c772e831df810e2630 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 目錄 …………………………………………………………1
圖目錄 ……………………………………………………………...2 表目錄 ………………………………………………………….…..3 縮寫表 …………………………………………………………..….4 中文摘要 ………………………………………………………….…..5 英文摘要 ………………………………………………………….…..6 前言 ………………………………………………………….…..7 材料與方法 ……………………………………………………….….12 結果 ……………………………………………………….….16 討論 …………………………………………………….…….24 參考書目 …………………………………………………………..55 附圖 ……………………………………………………………..58 圖目錄 圖一、Plexin A2 和 Plexin D1 不同片段大小的質體建構示意圖.27 圖二、以免疫沉澱法去偵測融合蛋白……………………………...28 圖三、表現融合蛋白的COS-b細胞免疫螢光染色………………..29 圖四、Plexin D1及Plexin A2在COS-b細胞中之螢光表現.……..30 圖五、Plexin A2及Plexin D1螢光共振能量轉移…………………31 圖六、螢光共振能量轉移法之實驗組……………………………...32 圖七、螢光共振能量轉移法之控制組………………………….......33 圖八、Plexin A2 在tissue array中免疫染色的結果……………….34 圖九、Plexin D1 在tissue array中免疫染色的結果……………….35 圖十、Plexin A2在大腸癌中組織免疫染色的表現情形…………..36 圖十一、Plexin D1在大腸癌中組織免疫染色的表現情形………..37 圖十二、NRP1在大腸癌中組織免疫染色的表現情形……………38 圖十三、Sema6A 在大腸癌中組織免疫染色的表現情形………...39 圖十四、Sema3A在大腸癌中組織免疫染色的表現情形…………40 圖十五、Sema3C在大腸癌中組織免疫染色的表現情形….………41 圖十六、Plexin A2和Sema6A Kaplan-Meier存活曲線分析……42 表目錄 表一、實驗相關之引子序列 ………………………………………...43 表二、Plexin A2之腫瘤tissue array初步分析結果 ………………..44 表三、Plexin D1之腫瘤tissue array初步分析結果 ………………..45 表四、螢光共振能量轉移法Efficiency的結果 …………..……….46 表五、蛋白在腫瘤及正常組織中表現程度的相關性分析………......47 表六、各蛋白間表現程度的相關性分析……………………….........49 表七、影響大腸癌病人死亡因素的分布 ………………………......52 表八、影響大腸癌病人死亡因素的單變數Logistic regression分析53 表九、影響大腸癌病人死亡因素的多變數Logistic regression分析53 表 十、影響大腸癌病人死亡因素的單變數存活分析………………..54 表十一、影響大腸癌病人死亡因素的多變數存活分析 .……………54 | |
| dc.language.iso | zh-TW | |
| dc.subject | 受體蛋白複合體 | zh_TW |
| dc.subject | Plexin D1 | en |
| dc.subject | Plexin A2 | en |
| dc.subject | receptor protein complex | en |
| dc.subject | Semaphorins | en |
| dc.title | 探討Plexin A2 和 Plexin D1之間的關聯性 | zh_TW |
| dc.title | The interaction of Plexin A2 and Plexin D1 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林中梧(Chung-Wu Lin),廖怡華(Yi-Hua Liao) | |
| dc.subject.keyword | 受體蛋白複合體, | zh_TW |
| dc.subject.keyword | receptor protein complex,Semaphorins,Plexin A2,Plexin D1, | en |
| dc.relation.page | 59 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
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