請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18976完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃筱鈞 | |
| dc.contributor.author | Bo-Han Lian | en |
| dc.contributor.author | 連柏翰 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:41:18Z | - |
| dc.date.copyright | 2016-08-25 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-18 | |
| dc.identifier.citation | 1. Pao, W., & Chmielecki, J. (2010). Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nature Reviews Cancer Nat Rev Cancer, 10(11), 760-774. doi:10.1038/nrc2947
2. Jackson, J. R., Patrick, D. R., Dar, M. M., & Huang, P. S. (2007). Targeted anti-mitotic therapies: Can we improve on tubulin agents? Nature Reviews Cancer Nat Rev Cancer, 7(2), 107-117. doi:10.1038/nrc2049 3. Holohan, C., Schaeybroeck, S. V., Longley, D. B., & Johnston, P. G. (2013). Cancer drug resistance: An evolving paradigm. Nature Reviews Cancer Nat Rev Cancer, 13(10), 714-726. doi:10.1038/nrc3599 4. Mcgrogan, B. T., Gilmartin, B., Carney, D. N., & Mccann, A. (2008). Taxanes, microtubules and chemoresistant breast cancer. Biochimica Et Biophysica Acta (BBA) - Reviews on Cancer, 1785(2), 96-132. doi:10.1016/j.bbcan.2007.10.004 5. Sprinzak, D., & Elowitz, M. B. (2005). Reconstruction of genetic circuits. Nature, 438(7067), 443-448. doi:10.1038/nature04335 6. Eldar, A., & Elowitz, M. B. (2010). Functional roles for noise in genetic circuits. Nature, 467(7312), 167-173. doi:10.1038/nature09326 7. Weiss, R. (2013). Synthetic Biology: From Parts to Modules to Therapeutic Systems. Biophysical Journal, 104(2). doi:10.1016/j.bpj.2012.11.2952 8. Khalil, A. S., & Collins, J. J. (2010). Synthetic biology: Applications come of age. Nat Rev Genet Nature Reviews Genetics, 11(5), 367-379. doi:10.1038/nrg2775 9. Kramer, B. P., Fischer, C., & Fussenegger, M. (2004). BioLogic gates enable logical transcription control in mammalian cells. Biotechnol. Bioeng. Biotechnology and Bioengineering, 87(4), 478-484. 10. Lienert, F., Lohmueller, J. J., Garg, A., & Silver, P. A. (2014). Synthetic biology in mammalian cells: Next generation research tools and therapeutics. Nature Reviews Molecular Cell Biology Nat Rev Mol Cell Biol, 15(2), 95-107. doi:10.1038/nrm3738 11. Gross, G., Waks, T., & Eshhar, Z. (1989). Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proceedings of the National Academy of Sciences, 86(24), 10024-10028. doi:10.1073/pnas.86.24.10024 12. Brentjens, R. J., Riviere, I., Park, J. H., Davila, M. L., Wang, X., Stefanski, J., . . . Sadelain, M. (2011). Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood, 118(18), 4817-4828. doi:10.1182/blood-2011-04-348540 13. Lanitis, E., Poussin, M., Klattenhoff, A. W., Song, D., Sandaltzopoulos, R., June, C. H., & Powell, D. J. (2013). Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo. Cancer Immunology Research, 1(1), 43-53. doi:10.1158/2326-6066.cir-13-0008 14. Nissim, L., & Bar-Ziv, R. H. (2010). A tunable dual-promoter integrator for targeting of cancer cells. Mol Syst Biol Molecular Systems Biology, 6. doi:10.1038/msb.2010.99 15. Xie, Z., Wroblewska, L., Prochazka, L., Weiss, R., & Benenson, Y. (2011). Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells. Science, 333(6047), 1307-1311. doi:10.1126/science.1205527 16. Alon, U. (2007). Network motifs: Theory and experimental approaches. Nat Rev Genet Nature Reviews Genetics, 8(6), 450-461. doi:10.1038/nrg2102 17. Evans, T., Rosenthal, E. T., Youngblom, J., Distel, D., & Hunt, T. (1983). Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell, 33(2), 389-396. doi:10.1016/0092-8674(83)90420-8 18. Maity, A. (1995). Cell Cycle-dependent Regulation of the Cyclin B1 Promoter. Journal of Biological Chemistry, 270(47), 28419-28424. doi:10.1074/jbc.270.47.28419 19. Katula, K., & Cogswell, J. (1997). Cyclin-dependent kinase activation and S-phase induction of the cyclin B1 gene are linked through the CCAAT elements. Cell Growth & Differentiation, 8(7), 811-820. 20. Brown, B. D., Gentner, B., Cantore, A., Colleoni, S., Amendola, M., Zingale, A., . . . Naldini, L. (2007). Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol Nature Biotechnology, 25(12), 1457-1467. doi:10.1038/nbt1372 21. Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., . . . Tuschl, T. (2007). A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing. Cell, 129(7), 1401-1414. doi:10.1016/j.cell.2007.04.040 22. Ramkissoon, S. H., Mainwaring, L. A., Ogasawara, Y., Keyvanfar, K., Mccoy, J. P., Sloand, E. M., . . . Young, N. S. (2006). Hematopoietic-specific microRNA expression in human cells. Leukemia Research, 30(5), 643-647. doi:10.1016/j.leukres.2005.09.001 23. Kasashima, K., Nakamura, Y., & Kozu, T. (2004). Altered expression profiles of microRNAs during TPA-induced differentiation of HL-60 cells. Biochemical and Biophysical Research Communications, 322(2), 403-410. doi:10.1016/j.bbrc.2004.07.130 24. He, L., & Hannon, G. J. (2004). MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet Nature Reviews Genetics, 5(7), 522-531. doi:10.1038/nrg1379 25. Gossen, M., & Bujard, H. (1992). Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proceedings of the National Academy of Sciences, 89(12), 5547-5551. doi:10.1073/pnas.89.12.5547 26. Gossen, M., Freundlieb, S., Bender, G., Muller, G., Hillen, W., & Bujard, H. (1995). Transcriptional activation by tetracyclines in mammalian cells. Science, 268(5218), 1766-1769. doi:10.1126/science.7792603 27. Loew, R., Heinz, N., Hampf, M., Bujard, H., & Gossen, M. (2010). Improved Tet-responsive promoters with minimized background expression. BMC Biotechnology BMC Biotechnol, 10(1), 81. doi:10.1186/1472-6750-10-81 28. Fu, N. Y., Sukumaran, S. K., Kerk, S. Y., & Yu, V. C. (2009). Baxβ: A Constitutively Active Human Bax Isoform that Is under Tight Regulatory Control by the Proteasomal Degradation Mechanism. Molecular Cell, 33(1), 15-29. doi:10.1016/j.molcel.2008.11.025 29. Cotter, T. G. (2009). Apoptosis and cancer: The genesis of a research field. Nature Reviews Cancer Nat Rev Cancer, 9(7), 501-507. doi:10.1038/nrc2663 30. Lowe, S. L., Rubinchik, S., Honda, T., Mcdonnell, T. J., Dong, J., & Norris, J. S. (2001). Prostate-specific expression of Bax delivered by an adenoviral vector induces apoptosis in LNCaP prostate cancer cells. Gene Therapy Gene Ther, 8(18), 1363-1371. doi:10.1038/sj.gt.3301531 31. Hanahan, D., & Weinberg, R. (2011). Hallmarks of Cancer: The Next Generation. Cell, 144(5), 646-674. doi:10.1016/j.cell.2011.02.013 32. Whitfield, M. L., George, L. K., Grant, G. D., & Perou, C. M. (2006). Common markers of proliferation. Nature Reviews Cancer Nat Rev Cancer, 6(2), 99-106. doi:10.1038/nrc1802 33. Markusic, D. (2005). Comparison of single regulated lentiviral vectors with rtTA expression driven by an autoregulatory loop or a constitutive promoter. Nucleic Acids Research, 33(6). doi:10.1093/nar/gni062 34. Moullan, N., Mouchiroud, L., Wang, X., Ryu, D., Williams, E., Mottis, A., . . . Auwerx, J. (2015). Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research. Cell Reports, 10(10), 1681-1691. doi:10.1016/j.celrep.2015.02.034 35. Urlinger, S., Baron, U., Thellmann, M., Hasan, M. T., Bujard, H., & Hillen, W. (2000). Exploring the sequence space for tetracycline-dependent transcriptional activators: Novel mutations yield expanded range and sensitivity. Proceedings of the National Academy of Sciences, 97(14), 7963-7968. doi:10.1073/pnas.130192197 36. Tenev, T., Marani, M., Mcneish, I., & Lemoine, N. R. (2001). Pro-caspase-3 overexpression sensitises ovarian cancer cells to proteasome inhibitors. Cell Death Differ Cell Death and Differentiation, 8(3), 256-264. doi:10.1038/sj.cdd.4400808 37. Friedrich, K., Wieder, T., Haefen, C. V., Radetzki, S., Jänicke, R., Schulze-Osthoff, K., . . . Daniel, P. T. (2001). Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance. Oncogene, 20(22), 2749-2760. doi:10.1038/sj.onc.1204342 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18976 | - |
| dc.description.abstract | 化學治療是一種常規的癌症療法，傳統的化學治療藥物對分裂中的細胞具有細胞毒性，透過干擾有絲分裂而達成目的，但其缺乏特定標的並時常產生副作用及治療失敗。骨髓抑制(myelosuppression)是抗分裂化學治療的副作用之一，由骨髓內分裂中的造血幹細胞受到破壞所引起；當骨髓抑制嚴重時，可能會導致嗜中性球低下(neutropenia)並時常伴隨著感染，這將會威脅病患的性命。使用基因治療成為克服此副作用的替代方案：我們使用合成生物學的方式，建立了一個對增生中的腫瘤細胞有細胞毒性並對造血幹細胞無害的合成基因線路；此線路以核糖核酸干擾(RNA interference, RNAi)和四環素控制的表現系統(tetracycline-controllable expression system)為基礎，能偵測到來自個別細胞中細胞週期素B1啟動子(cyclin B1 promoter)和miR-142微型核醣核酸結合位點(microRNA binding site，MBS)的訊息並做出反應。所有本線路使用的元件都以螢光蛋白做為報導基因確認其性能，之後串聯至具有優化後的反饋/前饋迴圈的邏輯匣層內。我們展示了一個合成的邏輯基因線路，在體外實驗中標定並殺死增生中的腫瘤細胞。本研究提供了一個有潛力的策略作為癌症基因治療之用。 | zh_TW |
| dc.description.abstract | Chemotherapy is a conventional treatment for cancer. Traditional chemotherapeutic agents are cytotoxic to dividing cells by means of interfering with mitosis but without specific targeting and often cause side effects and frequent failures. Myelosuppression due to destruction of dividing hematopoietic stem cells (HSCs) in bone marrow is one of the side effects for anti-mitotic chemotherapy. When myelosuppression is severe, it may lead to neutropenia and often company with infections that will threaten patient’s life. An alternative way to overcome this side effect is using gene therapy. With a “synthetic biology” approach, we construct a synthetic genetic circuit that cytotoxic to proliferating tumor cells and spare hematopoietic stem cells. The circuit based on RNA interference (RNAi) and tetracycline-controllable expression system is able to detect and respond to cellular information from cyclin B1 promoter and miR-142 microRNA binding site (MBS) in individual cells. All units of circuit were validated its performance by using fluorescence protein as reporter and then cascaded into layers of logic gates with optimizing feedback/feed-forward loops. Here we present a synthetic logic genetic circuit targeting and killing proliferating tumor cells in vitro. This study provides a potential strategy for cancer gene therapy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:41:18Z (GMT). No. of bitstreams: 1 ntu-105-R03B43007-1.pdf: 4759014 bytes, checksum: 4241086a4c37abfb1d15b3f79a43f1db (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 謝 誌 i
中文摘要 ii Abstract iii Table of Contents iv List of Figures vi Chapter 1 Introduction 1 1.1 Cancer treatment 1 1.2 Synthetic biology approach 2 1.3 Synthetic biology for therapeutic applications 3 1.4 Research purpose 4 1.5 Feedback/feed-forward loops 4 1.6 The sensor units in device 5 1.7 Tetracycline-inducible expression systems 6 1.8 Human BAX-β protein 7 1.9 Specific aims 7 Chapter 2 Materials and Methods 9 2.1 Recombinant DNA construction 9 2.1.1 Bacterial strain and vectors 9 2.1.2 Oligonucleotide sequences for construction 9 2.1.3 Reagents and enzymes 11 2.1.4 Plasmid construction 12 2.2 Cell lines and cell culture 14 2.3 Deliver plasmid DNA into mammalian cells 15 2.3.1 Liposome-mediated transfection 15 2.3.2 Electroporation 16 2.4 Drugs treatment and cell synchronization 17 2.5 Fluorescence microscopy and time-lapse imaging 17 2.6 Flow cytometry 18 2.7 Data analysis and statistics 18 Chapter 3 Results 19 3.1 Construction and characterization of cyclin B1 promoter 19 3.2 Construction and characterization of 4X miR-142 MBS 21 3.3 Construction and characterization of positive auto-regulatory (PAR) feedback loop based on the Tet-On 3G system 22 3.4 Control expression of hBAX-β by the Tet-On 3G system 23 Chapter 4 Discussion 25 Chapter 5 Conclusion and Future Perspectives 28 Reference 30 | |
| dc.language.iso | en | |
| dc.subject | 基因治療 | zh_TW |
| dc.subject | 核糖核酸干擾 | zh_TW |
| dc.subject | 合成生物學 | zh_TW |
| dc.subject | 癌症 | zh_TW |
| dc.subject | 抗分裂 | zh_TW |
| dc.subject | cancer | en |
| dc.subject | RNA interference | en |
| dc.subject | synthetic biology | en |
| dc.subject | gene therapy | en |
| dc.subject | anti-mitotic | en |
| dc.title | 以合成的邏輯匣串聯應用至區別化抗分裂之癌症治療 | zh_TW |
| dc.title | A Cascade of Synthetic Logic Gates for Differentiated Anti-mitotic Cancer Therapy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 朱家瑩,周信宏 | |
| dc.subject.keyword | 癌症,抗分裂,基因治療,合成生物學,核糖核酸干擾, | zh_TW |
| dc.subject.keyword | cancer,anti-mitotic,gene therapy,synthetic biology,RNA interference, | en |
| dc.relation.page | 63 | |
| dc.identifier.doi | 10.6342/NTU201603254 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2016-08-20 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-105-1.pdf 未授權公開取用 | 4.65 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。