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DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 黃敏銓(Min-Chuan Huang) | |
dc.contributor.author | Hao-Yun Huang | en |
dc.contributor.author | 黃浩雲 | zh_TW |
dc.date.accessioned | 2021-06-08T01:15:53Z | - |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-13 | |
dc.identifier.citation | 1. K. W. Gillison ML, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D., Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 3, 709-720 (2000).
2. G. S. DeRienzo DP, Fraire AE., Carcinoma of the larynx. Changing incidence in women. Arch Otolaryngol Head Neck Surg. 6, 681-684 (1991). 3. B. L. e. Heffner DK, Disease of the trachea. Surgical Pathology of the Head and Neck 2nd ed, 602-631 (2001). 4. P. M. a. P. B. M.S. Cattaruzza, Epidemiology of Laryngeal Cancer Oral Oncol, Eur J Cancer 32, 293-305 (1996). 5. I. WIEST, Expression of Different Carbohydrate Tumour Markers and Galectins 1 and 3 in Normal Squamous and Malignant Epithelia of the Upper Aaerodigestive Tract. ANTICANCER RESEARCH 32, 2023-2030 (2012). 6. J.A. Woolgara, S.N. Rogersb, D. Loweb, J.S. Brownb, E.D. Vaughanb, Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread. Oral oncology 39, 130-137 (2003). 7. S. A. Ferlito A1, Silver CE, Rinaldo A, Mondin V., Incidence and sites of distant metastases from head and neck cancer. Journal for oto-rhino-laryngology and its related specialties 63, 202-207 (2001). 8. P. M. Coutinho, E. Deleury, G. J. Davies, B. Henrissat, An Evolving Hierarchical Family Classification for Glycosyltransferases. Journal of Molecular Biology 328, 307-317 (2003)10.1016/s0022-2836(03)00307-3). 9. S. Hakomori, Glycosylation defining cancer malignancy: new wine in an old bottle. Proceedings of the National Academy of Sciences of the United States of America 99, 10231-10233 (2002); published online EpubAug 6 (10.1073/pnas.172380699). 10. K. W. Moremen, M. Tiemeyer, A. V. Nairn, Vertebrate protein glycosylation: diversity, synthesis and function. Nature reviews. Molecular cell biology 13, 448-462 (2012); published online EpubJul (10.1038/nrm3383). 11. R. G. Spiro, Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 12, 43R-56R (2002). 12. M. A. Patricie Burda, The dolichol pathway of N-linked glycosylation. BBA, (1999). 13. Q. Sun, L. Zhao, Q. Song, Z. Wang, X. Qiu, W. Zhang, M. Zhao, G. Zhao, W. Liu, H. Liu, Y. Li, X. Liu, Hybrid- and complex-type N-glycans are not essential for Newcastle disease virus infection and fusion of host cells. Glycobiology 22, 369-378 (2012); published online EpubMar (10.1093/glycob/cwr146). 14. E. P. Bennett, U. Mandel, H. Clausen, T. A. Gerken, T. A. Fritz, L. A. Tabak, Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family. Glycobiology 22, 736-756 (2012). 15. Y. J. K. a. A. Varki, Perspectives on the significance of altered glycosylation of glycoproteins in cancer. Glycoconjugate journal 14, 569-576 (1997). 16. S. F. Slovin, G. Ragupathi, C. Musselli, C. Fernandez, M. Diani, D. Verbel, S. Danishefsky, P. Livingston, H. I. Scher, Thomsen-Friedenreich (TF) antigen as a target for prostate cancer vaccine: clinical trial results with TF cluster (c)-KLH plus QS21 conjugate vaccine in patients with biochemically relapsed prostate cancer. Cancer immunology, immunotherapy : CII 54, 694-702 (2005). 17. T. Ju, R. P. Aryal, M. R. Kudelka, Y. Wang, R. D. Cummings, The Cosmc connection to the Tn antigen in cancer. Cancer biomarkers : section A of Disease markers 14, 63-81 (2014). 18. B. J. a. G. F. Springer, Conformation of Blood-Group and Virus Receptor Glycoproteins from Red Cells and Secretions. science 162, 365-367 (1968). 19. G. F. Springer, T and Tn, General Carcinoma Autoantigens. science 224, 1198-1206 (1984). 20. T. Ju, V. I. Otto, R. D. Cummings, The Tn antigen-structural simplicity and biological complexity. Angewandte Chemie 50, 1770-1791 (2011). 21. Monique Clement, Jezabel Rocher, Gervaise Loirand and Jacques Le Pendu, Expression of sialyl-Tn epitopes on β1 integrin alters epithelial cell phenotype, proliferation and haptotaxis. Journal of Cell Science, 5059-5069. 22. M. GEORG F. SPRINGER, 't CLIVE R. TAYLOR, MD, DPHIL,+ DONALD R. HOWARD, MD,§ HERTA TEGTMEYER, MT,' PARIMAL R. DESAI, PHD,' SATYA M. MURTHY, PHD,' BARBARA FELDER, MT,* AND EDWARD F. SCANLON, MD' Tn, A Carcinoma-Associated Antigen, Reacts With Anti-Tn of Normal Human Sera Cancer 55, 561-569 (1985). 23. Z. X.-W. W. Qiang, Thomsen-Friedenreich-related antigen and tumors. Acad J Sec Mil Med Univ 24, 899-901 (2003). 24. M. S. Yi Cao, Expression of Thomsen-Friedenreich- Related Antigens in Primary and Metastatic Colorectal Carcinomas. Cancer 76, 1700-1708 (1995). 25. Y. Cao, A. Merling, U. Karsten, S. Goletz, M. Punzel, R. Kraft, G. Butschak, R. Schwartz-Albiez, Expression of CD175 (Tn), CD175s (sialosyl-Tn) and CD176 (Thomsen-Friedenreich antigen) on malignant human hematopoietic cells. International journal of cancer. Journal international du cancer 123, 89-99 (2008). 26. T. Saku, H. Okabe, Differential lectin-bindings in normal and precancerous epithelium and squamous cell carcinoma of the oral mucosa. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 18, 438-445 (1989). 27. T. Ju, G. S. Lanneau, T. Gautam, Y. Wang, B. Xia, S. R. Stowell, M. T. Willard, W. Wang, J. Y. Xia, R. E. Zuna, Z. Laszik, D. M. Benbrook, M. H. Hanigan, R. D. Cummings, Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc. Cancer research 68, 1636-1646 (2008); published online EpubMar 15. 28. R. Kleene, M. Schachner, Glycans and neural cell interactions. Nature reviews. Neuroscience 5, 195-208 (2004); published online EpubMar (10.1038/nrn1349). 29. M. SOPHIE DELORGE, SVEN SAUSSEZ, MD, PATRICIA PELC, MD, BENOIT DEVROEDE, MD, HADELIN MARCHANT, MD, MARIA BURCHERT, PhD, FU-YUE ZENG, PhD, ANDRE DANGUY, PhD, ISABELLE SALMON, MD, PhD, HANS-JOACHIM GABIUS, PhD, ROBERT KISS, PhD, and SERGIO HASSID, MD, PhD,, Correlation of Galectin-3/Galectin-3-Binding Sites with low Differentiation Status in Head and Neck Squamous Cell Carcinomas. Otolaryngology -- Head and Neck Surgery 122, 834-841 (2000). 30. N. I. MASAKO YOKOTA , KATSUHIKO HATAKE ,KATSUNARI YANE , HIROSHI MIYAHARA and TAKASHI MATSUNAGA, Aberrant glycosylation based on the neo-expression of poly-N-acetyllactosamine structures in squamous cell carcinomas of the head and neck. Histochemical Journal 29, 555-562 (1997). 31. B. M., Is the invasive front of an oral carcinoma the most important area for prognostication? oral dis 4, 70-77 (1998). 32. Olga V. Glinskii*, Sudha Sud‡, Valeri V. Mossine§,Thomas P. Mawhinney§, Douglas C. Anthony¶,#,Gennadi V. Glinsky**, Kenneth J. Pienta‡,2and Vladislav V. Glinsky+,¶,2, Inhibition of Prostate Cancer Bone Metastasis by Synthetic TF Antigen Mimic/Galectin-3 Inhibitor Lactulose-L-Leucine. Neoplasia 14, 65-73 (2012). 33. G. M. Imai J, Naito Z, Asano G., Immunohistochemical expression of T, Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma. Anticancer Res. 21, 1327-1334 (2001). 34. J. M. Curry, M. Tuluc, D. Whitaker-Menezes, J. A. Ames, A. Anantharaman, A. Butera, B. Leiby, D. M. Cognetti, F. Sotgia, M. P. Lisanti, U. E. Martinez-Outschoorn, Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer. Cell cycle 12, 1371-1384 (2013). 35. M. Mohammad Ghazizadeh, PhD, Hideomi Ogawa, MD, Yoshihiro Sasaki, BSc, Tsutomu Araki, MD, Kaoru Aihara, MD, Mucin Carbohydrate Antigens (T, Tn, and Sialyl-Tn) in Human Ovarian Carcinomas: Relationship With Histopathology and Prognosis Human Pathology, 960-966 (1997). 36. S. T. Toma V1, Vogt P, Komminoth P, Heitz PU, Roth J., Differentiation-related expression of the Thomsen-Friedenreich glycotope in developing human lung and in lung carcinoma: lack of association with malignancy. Cancer. 85, 2151-2159 (1999). 37. T. C. Barr N1, Young T, Springer GF., Are pancarcinoma T and Tn differentiation antigens? Cancer. 64, 834-841 ( 1989). 38. R. Mi, L. Song, Y. Wang, X. Ding, J. Zeng, S. Lehoux, R. P. Aryal, J. Wang, V. K. Crew, I. van Die, A. B. Chapman, R. D. Cummings, T. Ju, Epigenetic silencing of the chaperone Cosmc in human leukocytes expressing tn antigen. The Journal of biological chemistry 287, 41523-41533 (2012). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18629 | - |
dc.description.abstract | 細胞中蛋白質主要的兩種醣化修飾是N-linked glycoproteins 及 O-linked glycoprotein。Tn 抗原和T 抗原是O型糖化中修飾的前兩個醣基團。在許多癌症病人組織中,醣類抗原的表現會出現異常,導致組織中Tn 抗原和T 抗原的大量表現,發生的原因至今仍不明確。本次實驗取台大醫院的175個病人檢體,以凝集素針對Tn 抗原與T 抗原進行免疫組織染色,觀察在頭頸部鱗狀上皮癌切片中Tn 抗原與T 抗原的表現強度。以VVA偵測Tn表現量,結果顯示,相較於非腫瘤組織,71%的腫瘤組織,有較高的Tn 抗原表現量;以PNA偵測T表現量,結果顯示,相較於非腫瘤組織,69%的腫瘤組織,有較高的T 抗原表現量。之後統計抗原表現強度與各種病理診斷因子的臨床相關性。結果顯示,T 抗原在組織中表現量與淋巴血管浸潤(lymphovascular invasion,LVI)、淋巴結被膜外擴散(Extracapsular spread,ECS)、N stage及癌症分期(clinical stage)呈顯著相關(P<0.05)。腫瘤學上認為LVI、ECS、N stage是發生淋巴及遠端轉移的重要指標。目前對於上皮癌中T 抗原的表現在病理學上的影響仍不明確,未來仍需更多研究闡明T抗原的表現在頭頸部鱗狀上皮癌中對於轉移和癌症進程所扮演的角色。 | zh_TW |
dc.description.abstract | N-linked glycoproteins and O-linked glycoproteins are two main glycoproteins in human cells. Tn and T antigens are the first two glycan units on O-linked glycan chain. Aberrant glycosylation is commonly found in tumors. Many studies have reported an increased Tn and T antigen expression is associated with tumor cell malignancy. However, the underlying mechanism resulting in altered Tn and T antigen expression in tumor malignancies are still poorly understood. In this study, we investigated the expression of the Tn and T antigens in 175 head and neck squamous cell carcinoma patients by immunohistochemistry staining with Vicia villosa agglutinin (VVA) lectin, specific for Tn antigen; and peanut agglutinin (PNA) lectin, specific for T antigen recognition. Our results indicate 71% of the patients display higher Tn antigen expression levels in the tumors compared with the corresponding non-tumor tissues; and 69% of the patients exhibit higher T antigen expression levels in the tumors compared with the corresponding non-tumor tissues. Furthermore, we examined whether Tn and T antigen expression levels correlate with HNSCC clinical pathophysiology. Patients identified with low T antigen expression levels were associated with lymphovascular invasion (LVI), extracapsular spread (ECS), and advanced N stage (P<0.05). LVI, ECS, and N stage are associated with metastasis to lymph nodes or distant sites and high risk of clinical progression. Currently, the implication of aberrant glycosylation and altered Tn and T antigen expressions in cancer malignancies remain unclear. Further studies on the regulation and functional significance of Tn and T antigen occurrence are still required in the understanding of HNSCC progression and metastasis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:15:53Z (GMT). No. of bitstreams: 1 ntu-103-R00424027-1.pdf: 2836640 bytes, checksum: 66fee24960980afc7a2065459b63ded0 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 目 錄
誌謝…………………………………………………………………………………………1 中文摘要……………………………………………………………………………2 英文摘要………………………………………………………………………………3 一、前言………………………………………………………………………………5 1.1 研究動機………………………………………………………………6 1.2 頭頸部鱗狀上皮細胞癌……………………………………………………6 1.3 蛋白質醣化……………………………………………………7 1.4 N-glycosylation………………………………………………………7 1.5 O-glycosylation……………………………………………………8 1.6 癌症與醣化的關係……………………………………………………8 1.7 Tn抗原和T抗原……………………………………………………9 1.8 Tn 抗原……………………………………………………………9 1.9 T 抗原……………………………………………………………9 1.10 O型醣化修飾的步驟……………………………………………………10 1.11凝集素PNA、VVA……………………………………………………10 二、實驗與材料……………………………………………………………………………11 2. 1檢體………………………………………………………………………12 2.2 切片…………………………………………………………………………12 2.3 免疫染色…………………………………………………………………12 2.4 分數統計與資料分析………………………………………………………13 2.5 資料統計分析……………………………………………………………13 2.6 抗原表現位置………………………………………………………………14 三、結果……………………………………………………………………………… 15 3.1 以凝集素VVA進行免疫組織染色,偵測病人成對檢體中Tn抗原的表現量…………………………………………………………………………………16 3.2 以凝集素VVA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中Tn抗原的表現量…………………………………………………………………………………16 3.3 以凝集素PNA進行免疫組織染色,偵測病人成對檢體中T抗原的表現量…………………………………………………………………………………16 3.4 以凝集素PNA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中T抗原的表現量……………………………………………………………………………………17 3.5 以凝集素VVA進行免疫組織染色,偵測病人Tn抗原在腫瘤檢體中的表現情形………………………………………………………………………………………17 3.6 以凝集素PNA進行免疫組織染色,偵測病人T抗原在腫瘤檢體中的表現情形…………………………………………………………………………………………17 3.7 以凝集素VVA做免疫染色,偵測癌細胞中Tn抗原在胞內的分布情況……………………………………………………………………………………18 3.8 以凝集素PNA做免疫染色,偵測癌細胞中T抗原在胞內的分布情況…………………………………………………………………………………18 3.9 VVA及PNA染色區域病理型態…………………………………………18 3.10 Tn antigen表現量和臨床資料的相關性………………………………19 3.11 T antigen表現量和臨床資料的相關性……………………………………19 3.12 術後病人存活統計……………………………………………………………19 3.13 Tn antigen與病人術後存活率…………………………………………20 3.14 T antigen與病人術後存活率……………………………………………20 四、討論……………………………………………………………………………………… 21 4.1 Tn 抗原的細胞表現位置……………………………………………………22 4.2 T抗原的細胞表現位置……………………………………………………22 4.3 T抗原表現的組織特異性……………………………………………………23 4.4 T 抗原與臨床因子的相關性………………………………………………23 4.5術後存活率………………………………………………………………………24 4.6 總結…………………………………………………………………………………25 4.7未來研究:O型糖化修飾蛋白所扮演的角色……………………………………25 五、參考文獻………………………………………………………………………………… 26 六、實驗結果與圖表………………………………………………………………………………31 圖一、O型醣化修飾的步驟…………………………………………………………32 圖二、以凝集素VVA進行免疫組織染色,偵測病人成對檢體中Tn抗原的表現量……………………………………………………………………………………………34 圖三、以凝集素VVA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中Tn抗原的表現量……………………………………………………………………………………35 圖四、以凝集素PNA進行免疫組織染色,偵測病人成對檢體中T抗原的表現量…………………………………………………………………………………………37 圖五、以凝集素PNA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中T抗原的表現量………………………………………………………………………………………38 圖六、以凝集素VVA進行免疫組織染色,偵測病人Tn抗原在腫瘤檢體中的表現情形………………………………………………………………………………………40 圖七、以凝集素PNA進行免疫組織染色,偵測病人T抗原在腫瘤檢體中的表現情形……………………………………………………………………………………41 圖八、以凝集素VVA做免疫染色,偵測癌細胞中Tn抗原在胞內的分布情況……………………………………………………………………………………………42 圖九、以凝集素PNA做免疫染色,偵測癌細胞中T抗原在胞內的分布情況 ……………………………………………………………………………………………43 圖十、VVA及PNA染色區域病理型態…………………………………………………44 圖十一、Tn antigen表現量和臨床資料的相關性……………………………45 圖十二、T antigen表現量和臨床資料的相關性……………………………46 圖十三、Tn antigen與病人術後存活率…………………………………47 圖十四、T antigen與病人術後存活率……………………………………48 圖十五、T antigen表現量對分化程度高低之相關性…………………………49 表一、使用於免疫組織染色的凝集素濃度與呈色時間…………………………50 表二、術後病人存活統計………………………………………………………51 | |
dc.language.iso | zh-TW | |
dc.title | 在頭頸部鱗狀上皮癌中 T 和 Tn 抗原表現與癌病相關性 | zh_TW |
dc.title | Expression of T and Tn antigen in head and neck squamous cell
carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃約翰,張修豪,陳啟豪,何宛玲 | |
dc.subject.keyword | O 型醣化修飾,頭頸部鱗狀上皮癌,Tn 抗原,T 抗原, | zh_TW |
dc.subject.keyword | O-glycans,Squamous cell carcinoma of head and neck,Tn antigen,T antigen, | en |
dc.relation.page | 51 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2014-08-13 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
顯示於系所單位: | 解剖學暨細胞生物學科所 |
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