請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36601
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳進庭(Chin-Tin Chen) | |
dc.contributor.author | Hong-Tsun Back | en |
dc.contributor.author | 白康俊 | zh_TW |
dc.date.accessioned | 2021-06-13T08:07:20Z | - |
dc.date.available | 2005-08-02 | |
dc.date.copyright | 2005-08-02 | |
dc.date.issued | 2005 | |
dc.date.submitted | 2005-07-21 | |
dc.identifier.citation | Anne E. P. and David R. C. (1998) Inhibition of human telomerase by 2'-O-methyl-RNA. Proc Natl Acad Sci USA 95, p. 11549
Baumann P. and Cech T. R. (2001) POT1, the putative telomere end-binding protein in fission yeast and humans. Science 292, p. 1171 Blackburn E. H. (2000) Telomere states and cell fates. Nature 408, p. 53 Boklan J., Nanjangud G., MacKenzie K. L., May C., Sadelain M., Moore M. A. (2002)Limited proliferation and telomere dysfunction following telomerase inhibition in immortal murine fibroblasts. Cancer Res. 62, p. 2104 Brown J. P., Wei W. and Sedivy, J. M. (1997) Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277, p. 831 Chang, C.-C.; Wu, J.-Y.; Chien, C.-W.; Wu, W.-S.; Liu, H.; Kang, C.-C.; Yu, L.-J.; Chang, T.-C.(2003)A Fluorescent Carbazole Derivative: High Sensitivity for Quadruplex DNA. Anal. Chem. 75, p. 6177 Chang, C.-C.; Kuo, I.-C.; Ling, I.-F.; Chen, C.-T.; Chen, H.-C.; Lou, P.-J.; Lin, J.-J.; Chang, T.-C.(2004)Detection of Quadruplex DNA Structures in Human Telomeres by a Fluorescent Carbazole Derivative. Anal. Chem. 76, p. 4490 Chung et al. (2003) Identification of a quinoxaline derivative that is a potent telomerase inhibitor leading to cellular senescence of human cancer cells. Biochem. J. 373, p. 523 Damm K., Hemmann U., Garin-Chesa P. (2001)A highly selective telomerase inhibitor limiting human cancer cell proliferation. EMBO J. 20, p. 6958 de Lange T., Shiue L., Myers R. M.(1990)Structure and variability of human chromosome ends. Mol Cell Biol 10, p. 518 Elayadi A. N., Demieville A., Wancewicz E. V., Monia B. P., Corey D. R. (2001) Inhibition of telomerase by 2'-O-(2-methoxyethyl) RNA oligomers: effect of length, phosphorothioate substitution and time inside cells. Nucleic Acids Res. 29, p.1683 Elzbieta Izbicka et al. (1999) Effects of cationic porphyrins as G-Quadruplex interactive agents in human tumor cells. Cancer Research 59, p. 639 Eunice S. Wang, Kaida Wu, Allison C. Chin, Selina Chen-Kiang, Krisztina Pongracz, Sergei Gryaznov, and Malcolm A. S. Moore (2004) Telomerase inhibitior in vitro and in vivo studies in multiple myeloma and lymphoma. Blood, 103, p.258 Gasser S. M. (2000) A sense of the end. Science 288, p. 1377 Gellert M., et al., (1962) Helix formation by guanylic acid. PNAS 48, p. 2013 Gottesman M. M., Fojo T., Bates S. E. (2002) Multidurg resistance in cancer: role of ATP-dependent transporters. Nature Reviews Cancer 2, p. 48 Grand C.L., Han H, Munoz R.M., et al. (2002)The cationic porphyrin TMPyP4 down-regulates c-MYC and human telomerase reverse transcriptase expression and inhibits tumor growth in vivo. Mol Cancer Ther. 1, p. 565 Granger M. P., et al., (2002) Telomerase in cancer and aging. Crit. Rev. Oncol. Hematol. 41, p. 29 Greider C. W. & Blackburn E. H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, p. 405 Greider C. W., Blackburn E. H.(1989)A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 337, p. 331 Greider C. W. (1996) Telomere length regulation. Annu. Rev. Biochem. 65, p. 337 Griffith J. D. et al. (1999)Mammalian telomeres end in a large duplex loop. Cell 97, p. 503 Hahn W. C. et al. (1999) Inhibition of telomerase limits the growth of human cancer cells. Nat Med 5, p. 1164 Hamilton S. E. et al. (1997) Identification of determinants for inhibitor binding within the RNA active site of human telomerase using PNA scanning. Biochemistry 36, p. 11873 Hanaha D. and Weinberg R.A. (2000) The hallmarks of cancer. Cell 100, p. 57 Harley C. B., Futcher A. B. and Greider C. W. (1990) Telomeres shorten during aging of human fibroblasts. Nature, 345, p. 458 Hayflick L., Moorhead P. S. (1961)The serial cultivation of human diploid cell strains. Exp Cell Res 25, p. 585 Hayflick L.(1976)The cell biology of human aging. N Engl J Med 295, p. 1302 Hastie N. D., Dempster M., Dunlop M. G., et al.(1990)Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, p. 866 Herbert B., Pitts A. E., Baker S. I., et al. (1999)Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Natl Acad Sci U S A. 96, p. 14276 Herbert B. S., Pongracz K., Shay J. W., Gryaznov S. M., Shea-Herbert B. (2002)Oligonucleotide N3' P5' phosphoramidates as efficient telomerase inhibitors. Oncogene. 21, p. 638 Huffman K. E., Levene S. D., Tesmer V. M., Shay J. W., Wright W. E. (2000) Telomere shortening is proportional to the size of the G-rich telomeric 3'-overhang. J. Biol. Chem. 275, p. 19719 Izbicka E., Wheelhouse R. T., Raymond E., et al. (1999)Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells. Cancer Res. 59, p. 639 Kim J. H., Kim J. H., Lee G. E., Kim S. W., Kwon I., Gowan S. M., Heald R., Malcolm F. G., Kelland L. R.(2001) Potent Inhibition of Telomerase by Small-Molecule Pentacyclic Acridines Capable of Interacting with G-Quadruplexes Molecular Pharmacology 60, p. 981 Kim M. Y., et al. (2003) The different biological effect of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intermolecular G-quadruplex structure. Cancer research 63, p. 3247 Kim N. W., Piatyszek M. A., Prowse K. R., Harley C. B., West M. D., Ho P. L. C., Coviello G. M., Wright W. E., Weinrich S. L., Shay J. W. (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266, p. 2011 Kondo Y., Koga S., Komata T., Kondo S. (2000) Treatment of prostate cancer in vitro and in vivo with 2-5A-anti-telomerase RNA component. Oncogene 19, p. 2205 McEachern, M. J. et al.(2000)Telomerase and their control. Ann. Rev. Genet. 34, p. 331 McElligott R., Wellinger R. J. (1997) The terminal DNA structure of mammalian chromosomes. EMBO J. 16, p. 3705 Morin G. B.(1989)The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 59, p. 521 Nakajima A., Tauchi T., Sashida G., Sumi M., Abe K., Yamamoto K., Ohyashiki J. H., Ohyashiki K. (2003) Telomerase inhibition enhances apoptosis in human acute leukemia cells: possibility of antitelomerase therapy. Leukemia 17, p. 560 Pascolo E. et al. (2002) Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate. J. Biol. Chem. 277, p. 15566 Pitts A. E., Corey, D. R. (1998) Inhibition of human telomerase by 2'-O-methyl-RNA. Proc. Natl Acad. Sci. USA 95, p. 11549 Read M. et al. (2001) Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors. Proc. Natl Acad. Sci. USA 98, p. 4844 Kerbel R. S. (2001) Clinical Trials of Antiangiogenic Drugs: Opportunities, Problems, and Assessment of Initial Results. Journal of Clinical Oncology 19, p. 45 Gowan S. M., Harrison J. R., Patterson L., Valenti M., Read M. A., Neidle S., Kelland L. R. (2002) A G-Quadruplex-Interactive Potent Small-Molecule Inhibitor of Telomerase Exhibiting in Vitro and in Vivo Antitumor Activity. Mol Pharmacol, 61, p. 1154 Shay J. W., Bacchetti S. (1997) A survey of telomerase activity in human cancer. Eur. J. Cancer. 33, p. 787 Shay J. W., Wright W. E. Werbin H. (1991) Defining the molecular mechanisms of human cell immortalization. Biochim. Biophys. Acta 1072, p. 1 Stansel R. M., de Lange T., Griffith J. D.(2001)T-loop assembly in vitro involves binding of TRF2 near the 3' telomeric overhang. EMBO J. 20, p. 5532 Tetsuzo T., et al. (2003)Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT 095), against human leukemia cells involvement of ATM dependent DNA damage response pathway. Oncogene 22, p. 5338 van Steensel B. and de Lange T (1997) Control of telomere length by the human telomeric protein TRF1. Nature 385, p. 740 van Steensel B., Smogorzewska A. and de Lange T (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92, p. 401 Wright W. E., Pereira-Smith O. M., Shay J. W. (1989) Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts. Mol. Cell. Biol. 9, p. 3088 Zahler A. M., Williamson J. R., Cech T. R., Prescott D. M. (1991) Inhibition of telomerase by G-quartet DNA structures. Nature 350, p. 718 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36601 | - |
dc.description.abstract | 大部分的癌細胞依靠端粒酶(telomerase)來維持DNA端粒(telomere)的長度,而端粒長度的維持對於增生中的細胞是一個必要的條件。一般的體細胞當中並不會偵測到端粒酶的活性,所以抑制端粒酶的作用是一種治療癌症可以考慮的方法。BMVC【3,6-bis(1-methyl-4-vinylpyridium)carbazole 】設計可以與富含鳥糞嘌呤(Guanine rich)的四股結構(G-quadruplex)結合,尤其是人類的端粒序列5’-(TTAGGG)n-3’。本實驗目的在探討BMVC對細胞造成的毒性,以及立即性或後續的生物效應變化。實驗發現: (1)根據TRAP assay,隨著BMVC濃度的增加,端粒酶活性被抑制的情形也逐漸增強。(2) 經過BMVC處理的癌細胞端粒有縮短的現象。(3)MTT assay顯示,BMVC可以選擇性的傷害癌細胞且不會對正常細胞產生毒性。(4)目前研究發現BMVC是進入細胞核中而引起相關的生物效應變化。(5)在細胞的生長能力上,經BMVC處理的癌細胞生長速度有明顯的減慢。 | zh_TW |
dc.description.abstract | Compare to normal somatic cells, more than 85% of cancer cells have higher telomerase activity to maintain their length of telomere. Therefore, inhibiting the function of telomerase is a considerable way to interfere cancer proliferation. BMVC was designed for interacting with G-quadruplex, a DNA four strand structure that is abounded with Guanine nucleotides, especially the sequence of human telomere [5’-(TTAGGG)n-3’]. Based on acute cytotoxicity assay, BMVC has higher cytotoxicity on cancer cells, which 50% lethal dose is about 10 μM. According to telomeric repeat amplification protocol assay, BMVC is a potent telomerase inhibitor with 50% inhibition concentration at 0.25 μM. Under confocal microscopy observation, BMVC enter the nucleus which might further affect cellular function. Cell culture and animal study show that proliferation ability of cancer cells may inhibited under nonacute cytotoxic concentration of BMVC treatment. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T08:07:20Z (GMT). No. of bitstreams: 1 ntu-94-R92450009-1.pdf: 1782188 bytes, checksum: 58ea332d314f0900e75a70c5ec59ab5c (MD5) Previous issue date: 2005 | en |
dc.description.tableofcontents | 縮寫表……………………………………………………….2
英文摘要…………………………………………………….3 中文摘要…………………………………………………….4 序論………………………………………………………….5 研究目的…………………………………………………...12 實驗材料…………………………………………………...13 實驗方法…………………………………………………...15 結果……………………………………………………...…25 第一部份…………………………………………………...25 第二部份……………………………………………...……27 第三部份………………………………………………..….30 第四部份……………………………………………..…….32 第五部份…………………………………………..……….35 討論……………………………………………..………….37 圖表……………………………………………………...…42 附圖………………………………………………………...69 參考文獻…………………………………………………...78 | |
dc.language.iso | zh-TW | |
dc.title | 會結合鳥糞嘌呤四股結構之特殊化合物BMVC所引起之相關抑癌效應探討 | zh_TW |
dc.title | The anti-cancer effect of BMVC, a G-quadruplex binding compound | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 洪瑞隆(Ruey-Long Hong),林淑萍(Shwu-Bin Lin),張大釗(Ta-Chau Chang) | |
dc.subject.keyword | 鳥糞嘌呤四股結構, | zh_TW |
dc.subject.keyword | G-quadruplex binding compound, | en |
dc.relation.page | 84 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2005-07-21 | |
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 目前未授權公開取用 | 1.74 MB | Adobe PDF |
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。