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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 翁啟惠(Chi-Huey Wong) | |
dc.contributor.author | Hsin-Yu Lee | en |
dc.contributor.author | 李信佑 | zh_TW |
dc.date.accessioned | 2021-06-15T04:11:06Z | - |
dc.date.available | 2013-02-04 | |
dc.date.copyright | 2010-02-04 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-01-27 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45257 | - |
dc.description.abstract | 大部分癌症細胞表面會表現多量的特定醣抗原,Globo H (Fucα1→2Galβ1→ 3GalNAcβ1→ 3Galα1→4Galβ1→ 4Glc)六碳醣是其中一種,它高度表現在乳癌、前列腺癌、卵巢癌、胰腺癌、大腸直腸癌及肺癌之細胞表面。Danishefsky的研究發現Globo H接上KLH蛋白當作疫苗可以產上抗體專一性的針對癌細胞,另外Schultz證明將蛋白質之某一個酪氨酸(Tyr)置換成對硝基苯丙氨酸(pNO2Phe)產生高表現量的抗體,且此抗體亦可針對未突變的蛋白。因此本篇的目標是結合Globo H及pNO2Phe為特別的醣抗原,接上牛血清白蛋白(BSA)當作抗癌疫苗(GHN-BSA),和Globo H直接接上牛血清蛋白結合的抗癌疫苗(GH-BSA)作比較,預期GHN-BSA可以產生高表現量抗體辨認Globo H醣抗原。由動物實驗的結果顯示GHN-BSA產生高表現量的抗體,可惜此沒有辨認Globo H醣抗原,而是辨認pNO2Phe,而由GH-BSA可以產生專一性辨認Globo H的抗體。我們推論因對硝基苯是強烈的免疫抗原,而設計之疫苗上Globo H及pNO2Phe在GHN-BSA占有相同的比例,導致結果不如預期,假如修改其之間的比例或許可以產生高表現的抗體專一性辨認Globo H醣抗原,下一代的GHN-BSA疫苗使用不同的連結方式來提升Globo H和pNO2Phe的比例至5.14/1.36,且動物實驗正要進行,希望可以得到預期的效果。 | zh_TW |
dc.description.abstract | Most of the cancer cells expressed large amounts of carbohydrate antigens on the cell surface. For example, an antigenic hexasaccharide, Globo H (Fucα1→2Galβ1→ 3GalNAcβ1 → 3Galα1→4Galβ1→4Glc), is overexpressed in surfaces of many human cancers, including breast, prostate, ovary, pancreas, colon and lung cancers. It was previously demonstrated that BSA-conjugated Globo H(GH-BSA) adjuvanted with α-GalCer can induce Globo H-specific antibodies. Another study led by Schultz showed that the incorporation of a p-nitrophenylalanine onto TNF can induce a potent antibody response in mice. Herein, we further linked Globo H to p-nitrophenyl group and the resulting unit was conjugated to BSA (GHN-BSA) and explored its immune-eliciting ability as a cancer vaccine. Animal experiments showed that antibodies induced by GHN-BSA vaccine recognized the p-nitrophenyl group but not Globo H carbohydrate antigen. On the other hand, antibodies induced by GH-BSA vaccine recognize Globo H and analogues. We hypothesized that since the p-nitrophenyl group is a strong immunogen and Globo H is a weak one, the same proportion of Globo H to pNO2Phe in the vaccine candidate GHN-BSA would lead to much more antibodies for pNO2Phe. Hence, a new generation of GHN-BSA vaccine with ratio of Globo H over pNO2Phe is 3.78 was synthesized and immunization experiments are ongoing. We wished that raising the ratio of Globo H over pNO2Phe may be able to enhance antibodies specifically to recognize Globo H antigen. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T04:11:06Z (GMT). No. of bitstreams: 1 ntu-99-R96223214-1.pdf: 4500386 bytes, checksum: c15239e4bd39ce1b1039e6d6d9b3706a (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | Abstract ii
中文摘要 iii Chapter1 Introduction 1 1.1 Tumor associated carbohydrate antigens 1 1.2 Synthesis of Globo H 3 1.3 Carbohydrate-based vaccines 6 1.4 Synthesis of glycoconjugate using homobifunctional p-nitrophenyl ester 11 1.5 p-nitrophenyl group is a strong immunogen 12 1.6 Application of glycolipid as immunological adjuvants 14 1.7 Application of glycan microarray 16 Chapter 2 Results and Discussions 19 2.1 Chemical synthesis of Globo H and derivatives 19 2.1.1 Synthesis of Lactose Building Block (9) 21 2.1.2 Synthesis of Galactose Building Block (8) 22 2.1.3 Synthesis of GalNAc Building Block (7) 23 2.1.4 Synthesis of Galactose Building Block (6) 24 2.1.5 Synthesis of Fucose Building Block (3) 25 2.1.6 Synthesis of Disaccharide (4) and Trisaccharide (5) building blocks 26 2.1.7 One-Pot synthesis and Deprotection of Globo H (1) 28 2.2 Chemical synthesis of GHN (49) 30 2.3 Generation and characterization of Globo H glycolconjugate 31 2.4 Mouse immunization 33 2.5 Glycan microarray 34 2.6. Chemical synthesis of L1, L2 and L3 36 2.7 Glycan microarray (part 2) 37 2.8 Chemical synthesis of N-BSA-GH (67) 40 Chapter3 conclusion 42 Chapter 4 Materials and Methods 43 Chapter 5 Reference 71 Appendix Selected NMR and MASS spectra 76 | |
dc.language.iso | en | |
dc.title | Globo-H 結合對硝基苯作為抗癌症疫苗的研究 | zh_TW |
dc.title | Study of anti cancer vaccine by using Globo H combined with p-nitrophenyl group | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-1 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 吳宗益(Chung-Yi Wu) | |
dc.contributor.oralexamcommittee | 張子文(Tse Wen, Chang) | |
dc.subject.keyword | 乳癌,疫苗,醣脂質,佐劑,醣抗原, | zh_TW |
dc.subject.keyword | breast cancer,vaccine,glycolipid,adjuvants,Globo H, | en |
dc.relation.page | 115 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2010-01-27 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 化學研究所 | zh_TW |
顯示於系所單位: | 化學系 |
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