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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張智芬 | |
| dc.contributor.author | Chih-Chuan Wang | en |
| dc.contributor.author | 王致權 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:20:04Z | - |
| dc.date.available | 2011-09-11 | |
| dc.date.copyright | 2008-09-11 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-24 | |
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Science 283, 689-692. 25. Schwartz, E. L., Wan, E., Wang, F., and Baptiste, N. (1998). Regulation of expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in human colon carcinoma cells. Cancer Res. 58, 1551-1557. 26. Stubbe, J. (1990). Ribonucleotide reductase: amazing and confusing. J.Biol.Chem. 265, 5329-5332. 27. Sumizawa, T., Furukawa, T., Haraguchi, M, Yoshimura, A., Takeyasu, A., Ishikawa, M., Yamada, Y., and Akiyama, S. (1993). Thymidine phosphoryalse activity associated with platelet-derived endothelial cell growth factor. J.Biochem. 114, 9-13. 28. Takahashi, Y., Bucana, C. D., Liu, Wenbiao., Yoneda, J., Kitadai, Y., Cleary, K. R., Ellis, and L. M. (1996). Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells. J. Natl. Cancer Inst. 88, 1146-1151. 29. Takao, S., Akiyama, S., Nakajo, A., Yoh, H., Kitazono, M., Natsugoe, S., Miyadera, K., Fukushima, M., Yamada, Y., and Aikou, T. (2000). Suppression of metastasis by thymidine phosphorylase inhibitor. Cancer Res. 60, 5345-5348. 30. Takebayashi, Y., Yamada, K., Maruyama, I., Fujii, R., Akiyama, S., and Aikou, T. (1995). The expression of thymidine phosphorylase and thrombomodulin in human colorectal carcinomas. Cancer Letters 92, 1-7. 31. Takebayashi, Y., Yamada, K., Miyadera, K., Sumizawa, T., Furukawa, T., Kinoshita, F., Aoki, D., Okumura, H., Akiyama, S., and Aikou, T. (1996). The activity and expression of thymidine phosphorylase in human solid tumours. Eu. J. Cancer 32,1227-1232. 32. Tanaka, Y., Kobayashi, H., Suzuki, M., Kanayama, N., Suzuki, M., and Terao, T. (2002). Thymidine phosphorylase expression in tumor infiltrating macrophages may be correlated with poor prognosis in uterine endometrial cancer. Human Pathol. 33, 1105-1113. 33. Valentino, M. L., Marti, R., Tadesse, S., Lopez, L. C., Manes, J. L., Lyzak, J. Hahn, A., Carelli, V., and Hirano, M. (2007). Thymidine and deoxyuridinr accumulate in tissues of pantients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Letters 581, 3410-3414. 34. Yao, Y., Kubota, T., Sato, K., Takeuchi, H., Kitai, R., and Matsukawa, S. (2005). Interferons upregulate thymidine phosphorylase expression via JAK-STAT-dependent transcriptional activation and mRNA stabilization in human glioblastoma cells. J. Neuro-Oncology 72, 217-223. 35. Zhu, G. H., Lenzi, M., and Schwartz, E. L. (2002). The Sp1 transcription factor contributes to the tumor necrosis factor-induced expression of angiogenic factor thymidine phosphorylase in human colon carcinoma cells. Oncogene 21, 8477-8485. 36. Zhu, G. H., and Schwartz, E. L. (2003). Expression of the angiogenic factor thymidine phosphorylase in THP-1 monocytes: induction by autocrine tumor necrosis factor-α and inhibition by aspirin. Mol. Pharcol. 64, 1251-1258. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37147 | - |
| dc.description.abstract | 胸腺嘧啶磷解酶(thymidine phosphorylase，TP)催化thymidine的磷解反應，此一反應為一可逆反應。除了參與核苷酸的代謝外，亦與血管的新生(angiogenesis)有關， TP降解Thymidine所產生的2-deoxy-ribose可以促進內皮細胞(endothelial cell)的方向性移動(directional migration)，而達到促進血管新生的功能。
TP在腫瘤細胞以及腫瘤相關巨嗜細胞(tumor-associated macrophage)中有較高的表現量，並且在腫瘤發展的過程中扮演重要的角色，藉由促進血管新生以及抑制細胞凋亡(anti-apoposis)來促進腫瘤的生長和轉移。TP在大部份正常的組織細胞中的表現量皆不高，唯獨在單核球(monocyte)、骨髓細胞(myeloid cell)以及樹突細胞(dendritic cell)等少數型態的細胞中有較高的表現量。 在本篇論文當中，我針對TP在單核性白血病(monocytic leukemia)細胞株THP-1中所可能扮演的生理功能進行探討。結果顯示，TP knockdown會造成THP-1細胞生長較為緩慢並且會有細胞死亡的現象，TP為THP-1的生長(proliferation)和存活(survival)所必須的。然而，於培養液中分別加入thymidine、2-deoxy-ribose以及thymine，並無法回復TP knockdown所造成的細胞死亡，顯示TP可能並非藉由參與dTTP以及Thymidine的代謝，而是其他的方式來促進THP-1細胞的生長與存活。 | zh_TW |
| dc.description.abstract | Thymidine phosphorylase (TP) catalyses the reversible phospholysis of thymidine. In addition to its role in nucleotide metabolism, TP is also an angiogenic factor. Its catabolic product, 2-deoxy-ribose produced by phospholysis of thymidine, induces directional migration of endothelial cells in vitro and angiogenesis in vivo.
It has been shown that the expression of TP is elevated in solid tumor and tumor-associated macrophage. TP may promote tumor progression by inducing angiogenesis and inhibiting aopotosis of tumor cells. The expression level of TP in most normal tissues is very low. But only in monocytes, myeloid and dendritic cells, TP is highly expressed. In this study, I investigated the role of TP in monocytic leukemia cell line ,THP-1. By silencing of TP expression, we found that TP knockdown induces growth retardation and cell death, indicating that TP is necessary for the proliferation and survival of THP-1 cells. However, the cell death induced by TP knockdown was not reversed by either thymidine , 2-deoxy-ribose, or thymine, suggesting its survival role other than its metabolic functions in dTTP synthesis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:20:04Z (GMT). No. of bitstreams: 1 ntu-97-R95442018-1.pdf: 1852385 bytes, checksum: 30373f25d6d0ce2e9653eaa7d7ea0a97 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 目 錄
口試委員會審定書…………………………… I 誌謝 ……………………………………………II 中文摘要 …………………………………… III 英文摘要 ………………………………………IV 序論 …………………………………………… 1 實驗方法 ……………………………………… 8 實驗結果 ………………………………………15 討論 ……………………………………………20 圖表 ……………………………………………24 參考文獻 ………………………………………37 | |
| dc.language.iso | zh-TW | |
| dc.subject | 單核性白血球 | zh_TW |
| dc.subject | 胸腺嘧啶磷解酶 | zh_TW |
| dc.subject | 單核性白血病 | zh_TW |
| dc.subject | THP-1 | zh_TW |
| dc.subject | U937 | zh_TW |
| dc.subject | thymidine phosphorylase | en |
| dc.subject | U937 | en |
| dc.subject | THP-1 | en |
| dc.subject | monocytic leukemia | en |
| dc.subject | monocyte | en |
| dc.title | 胸腺嘧啶磷解酶於THP-1細胞存活所扮演的角色 | zh_TW |
| dc.title | The Contribution of Thymidine Phosphorylase in THP-1 Cell Survival. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張明富,張玉生,李明學 | |
| dc.subject.keyword | 胸腺嘧啶磷解酶,單核性白血球,單核性白血病,THP-1,U937, | zh_TW |
| dc.subject.keyword | thymidine phosphorylase,monocyte,monocytic leukemia,THP-1,U937, | en |
| dc.relation.page | 43 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-24 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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