請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80408完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃國皓(Kuo-How Huang) | |
| dc.contributor.author | Fu-Shun Hsu | en |
| dc.contributor.author | 許富順 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:06:02Z | - |
| dc.date.available | 2022-01-18 | |
| dc.date.available | 2022-11-24T03:06:02Z | - |
| dc.date.copyright | 2022-01-18 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-01-10 | |
| dc.identifier.citation | 1. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 2012, 62(1):10-29. 2. Ploeg M, Aben KK, Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol 2009, 27(3):289-293. 3. Latini DM, Lerner SP, Wade SW, Lee DW, Quale DZ: Bladder cancer detection, treatment and outcomes: opportunities and challenges. Urology 2010, 75(2):334-339. 4. http://tcr.cph.ntu.edu.tw/main.php?Page=A5 TCRW. 5. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T: Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer 2005, 5(9):744-749. 6. Shah JB, McConkey DJ, Dinney CP: New strategies in muscle-invasive bladder cancer: on the road to personalized medicine. Clin Cancer Res 2011, 17(9):2608-2612. 7. Hsu FS, Wu JT, Lin JY, Yang SP, Kuo KL, Lin WC, Shi CS, Chow PM, Liao SM, Pan CI et al: Histone Deacetylase Inhibitor, Trichostatin A, Synergistically Enhances Paclitaxel-Induced Cytotoxicity in Urothelial Carcinoma Cells by Suppressing the ERK Pathway. Int J Mol Sci 2019, 20(5). 8. Lin WC, Hsu FS, Kuo KL, Liu SH, Shun CT, Shi CS, Chang HC, Tsai YC, Lin MC, Wu JT et al: Trichostatin A, a histone deacetylase inhibitor, induces synergistic cytotoxicity with chemotherapy via suppression of Raf/MEK/ERK pathway in urothelial carcinoma. J Mol Med (Berl) 2018, 96(12):1307-1318. 9. Harker WG, Meyers FJ, Freiha FS, Palmer JM, Shortliffe LD, Hannigan JF, McWhirter KM, Torti FM: Cisplatin, methotrexate, and vinblastine (CMV): an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study. JClinOncol 1985, 3(11):1463-1470. 10. Sternberg CN, Yagoda A, Scher HI, Watson RC, Geller N, Herr HW, Morse MJ, Sogani PC, Vaughan ED, Bander N et al: Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. Cancer 1989, 64(12):2448-2458. 11. von der MH, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM et al: Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. JClinOncol 2000, 18(17):3068-3077. 12. Xu WS, Parmigiani RB, Marks PA: Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007, 26(37):5541-5552. 13. Bolden JE, Peart MJ, Johnstone RW: Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006, 5(9):769-784. 14. Romero D: HDAC inhibitors tested in phase III trial. Nat Rev Clin Oncol 2019, 16(8):465. 15. McClure JJ, Li X, Chou CJ: Advances and Challenges of HDAC Inhibitors in Cancer Therapeutics. Adv Cancer Res 2018, 138:183-211. 16. He S, Dong G, Li Y, Wu S, Wang W, Sheng C: Potent Dual BET/HDAC Inhibitors for Efficient Treatment of Pancreatic Cancer. Angew Chem Int Ed Engl 2020, 59(8):3028-3032. 17. Suraweera A, O'Byrne KJ, Richard DJ: Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi. Front Oncol 2018, 8:92. 18. Giordano TJ: The cancer genome atlas research network: a sight to behold. Endocr Pathol 2014, 25(4):362-365. 19. Poyet C, Jentsch B, Hermanns T, Schweckendiek D, Seifert HH, Schmidtpeter M, Sulser T, Moch H, Wild PJ, Kristiansen G: Expression of histone deacetylases 1, 2 and 3 in urothelial bladder cancer. BMC Clin Pathol 2014, 14(1):10. 20. Buckley MT, Yoon J, Yee H, Chiriboga L, Liebes L, Ara G, Qian X, Bajorin DF, Sun TT, Wu XR et al: The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo. J Transl Med 2007, 5:49. 21. Vallo S, Xi W, Hudak L, Juengel E, Tsaur I, Wiesner C, Haferkamp A, Blaheta RA: HDAC inhibition delays cell cycle progression of human bladder cancer cells in vitro. Anticancer Drugs 2011, 22(10):1002-1009. 22. Qu W, Kang YD, Zhou MS, Fu LL, Hua ZH, Wang LM: Experimental study on inhibitory effects of histone deacetylase inhibitor MS-275 and TSA on bladder cancer cells. Urologic oncology 2010, 28(6):648-654. 23. Ozawa A, Tanji N, Kikugawa T, Sasaki T, Yanagihara Y, Miura N, Yokoyama M: Inhibition of bladder tumour growth by histone deacetylase inhibitor. BJU international 2010, 105(8):1181-1186. 24. Li DR, Zhang H, Peek E, Wang S, Du L, Li G, Chin AI: Synergy of Histone-Deacetylase Inhibitor AR-42 with Cisplatin in Bladder Cancer. The Journal of urology 2015, 194(2):547-555. 25. Yoon CY, Park MJ, Lee JS, Lee SC, Oh JJ, Park H, Chung CW, Abdullajanov MM, Jeong SJ, Hong SK et al: The histone deacetylase inhibitor trichostatin A synergistically resensitizes a cisplatin resistant human bladder cancer cell line. J Urol 2011, 185(3):1102-1111. 26. Yeh BW, Li WM, Li CC, Kang WY, Huang CN, Hour TC, Liu ZM, Wu WJ, Huang HS: Histone deacetylase inhibitor trichostatin A resensitizes gemcitabine resistant urothelial carcinoma cells via suppression of TG-interacting factor. Toxicol Appl Pharmacol 2016, 290:98-106. 27. Abrams SL, Steelman LS, Shelton JG, Wong EW, Chappell WH, Basecke J, Stivala F, Donia M, Nicoletti F, Libra M et al: The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy. Cell Cycle 2010, 9(9):1781-1791. 28. McCubrey JA, Steelman LS, Abrams SL, Chappell WH, Russo S, Ove R, Milella M, Tafuri A, Lunghi P, Bonati A et al: Emerging MEK inhibitors. Expert Opin Emerg Drugs 2010, 15(2):203-223. 29. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, Cervello M, Libra M, Candido S, Malaponte G et al: Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance. Oncotarget 2012, 3(10):1068-1111. 30. Schwartz AL, Ciechanover A: Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu Rev Pharmacol Toxicol 2009, 49:73-96. 31. Amerik AY, Hochstrasser M: Mechanism and function of deubiquitinating enzymes. Biochim Biophys Acta 2004, 1695(1-3):189-207. 32. Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK, Bernards R: A genomic and functional inventory of deubiquitinating enzymes. Cell 2005, 123(5):773-786. 33. Sun T, Liu Z, Yang Q: The role of ubiquitination and deubiquitination in cancer metabolism. Mol Cancer 2020, 19(1):146. 34. Deng L, Meng T, Chen L, Wei W, Wang P: The role of ubiquitination in tumorigenesis and targeted drug discovery. Signal Transduct Target Ther 2020, 5(1):11. 35. Hsu FS, Lin WC, Kuo KL, Chiu YL, Hsu CH, Liao SM, Dong JR, Liu SH, Chang SC, Yang SP et al: PR-619, a General Inhibitor of Deubiquitylating Enzymes, Diminishes Cisplatin Resistance in Urothelial Carcinoma Cells through the Suppression of c-Myc: An In Vitro and In Vivo Study. Int J Mol Sci 2021, 22(21). 36. Dasari S, Tchounwou PB: Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014, 740:364-378. 37. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G: Molecular mechanisms of cisplatin resistance. Oncogene 2012, 31(15):1869-1883. 38. Stordal B, Davey M: Understanding cisplatin resistance using cellular models. IUBMB Life 2007, 59(11):696-699. 39. Stordal B, Pavlakis N, Davey R: A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship. Cancer Treat Rev 2007, 33(8):688-703. 40. Chen SH, Chang JY: New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment. Int J Mol Sci 2019, 20(17). 41. Madden SK, de Araujo AD, Gerhardt M, Fairlie DP, Mason JM: Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc. Mol Cancer 2021, 20(1):3. 42. Miller DM, Thomas SD, Islam A, Muench D, Sedoris K: c-Myc and cancer metabolism. Clin Cancer Res 2012, 18(20):5546-5553. 43. Gabay M, Li Y, Felsher DW: MYC activation is a hallmark of cancer initiation and maintenance. Cold Spring Harb Perspect Med 2014, 4(6). 44. Tanguturi P, Kim KS, Ramakrishna S: The role of deubiquitinating enzymes in cancer drug resistance. Cancer Chemother Pharmacol 2020, 85(4):627-639. 45. Tian X, Isamiddinova NS, Peroutka RJ, Goldenberg SJ, Mattern MR, Nicholson B, Leach C: Characterization of selective ubiquitin and ubiquitin-like protease inhibitors using a fluorescence-based multiplex assay format. Assay Drug Dev Technol 2011, 9(2):165-173. 46. Mullally JE, Moos PJ, Edes K, Fitzpatrick FA: Cyclopentenone prostaglandins of the J series inhibit the ubiquitin isopeptidase activity of the proteasome pathway. J Biol Chem 2001, 276(32):30366-30373. 47. Wang L, Li M, Sha B, Hu X, Sun Y, Zhu M, Xu Y, Li P, Wang Y, Guo Y et al: Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma. Cell Prolif 2021, 54(1):e12919. 48. Yu HJ, Tsai TC, Hsieh TS, Chiu TY: Characterization of a newly established human bladder carcinoma cell line, NTUB1. J Formos Med Assoc 1992, 91(6):608-613. 49. Huang KH, Kuo KL, Chen SC, Weng TI, Chuang YT, Tsai YC, Pu YS, Chiang CK, Liu SH: Down-regulation of glucose-regulated protein (GRP) 78 potentiates cytotoxic effect of celecoxib in human urothelial carcinoma cells. PLoS One 2012, 7(3):e33615. 50. Kuo KL, Lin WC, Ho IL, Chang HC, Lee PY, Chung YT, Hsieh JT, Pu YS, Shi CS, Huang KH: 2-methoxyestradiol induces mitotic arrest, apoptosis, and synergistic cytotoxicity with arsenic trioxide in human urothelial carcinoma cells. PLoS One 2013, 8(8):e68703. 51. Ho IL, Kuo KL, Liu SH, Chang HC, Hsieh JT, Wu JT, Chiang CK, Lin WC, Tsai YC, Chou CT et al: MLN4924 Synergistically Enhances Cisplatin-induced Cytotoxicity via JNK and Bcl-xL Pathways in Human Urothelial Carcinoma. Sci Rep 2015, 5:16948. 52. Chou TC, Talalay P: Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984, 22:27-55. 53. Sridhar SS, Hedley D, Siu LL: Raf kinase as a target for anticancer therapeutics. Molecular cancer therapeutics 2005, 4(4):677-685. 54. Kuo KL, Liu SH, Lin WC, Hsu FS, Chow PM, Chang YW, Yang SP, Shi CS, Hsu CH, Liao SM et al: Trifluoperazine, an Antipsychotic Drug, Effectively Reduces Drug Resistance in Cisplatin-Resistant Urothelial Carcinoma Cells via Suppressing Bcl-xL: An In Vitro and In Vivo Study. Int J Mol Sci 2019, 20(13). 55. Xu P, Xiao H, Yang Q, Hu R, Jiang L, Bi R, Jiang X, Wang L, Mei J, Ding F et al: The USP21/YY1/SNHG16 axis contributes to tumor proliferation, migration, and invasion of non-small-cell lung cancer. Exp Mol Med 2020, 52(1):41-55. 56. Zhou P, Song T, Sun C, He N, Cheng Q, Xiao X, Ran J, Liu M, Xie S: USP21 upregulation in cholangiocarcinoma promotes cell proliferation and migration in a deubiquitinase-dependent manner. Asia Pac J Clin Oncol 2020. 57. Lei H, Shan H, Wu Y: Targeting deubiquitinating enzymes in cancer stem cells. Cancer Cell Int 2017, 17:101. 58. Chen Y, Zhou B, Chen D: USP21 promotes cell proliferation and metastasis through suppressing EZH2 ubiquitination in bladder carcinoma. Onco Targets Ther 2017, 10:681-689. 59. Poondla N, Chandrasekaran AP, Kim KS, Ramakrishna S: Deubiquitinating enzymes as cancer biomarkers: new therapeutic opportunities? BMB Rep 2019, 52(3):181-189. 60. Ma YS, Wang XF, Zhang YJ, Luo P, Long HD, Li L, Yang HQ, Xie RT, Jia CY, Lu GX et al: Inhibition of USP14 Deubiquitinating Activity as a Potential Therapy for Tumors with p53 Deficiency. Mol Ther Oncolytics 2020, 16:147-157. 61. Melo-Cardenas J, Zhang Y, Zhang DD, Fang D: Ubiquitin-specific peptidase 22 functions and its involvement in disease. Oncotarget 2016, 7(28):44848-44856. 62. Kuo KL, Lin WC, Liu SH, Hsu FS, Kuo Y, Liao SM, Yang SP, Wang ZH, Hsu CH, Huang KH: THZ1, a covalent CDK7 inhibitor, enhances gemcitabine-induced cytotoxicity via suppression of Bcl-2 in urothelial carcinoma. Am J Cancer Res 2021, 11(1):171-180. 63. Huang HS, Su HY, Li PH, Chiang PH, Huang CH, Chen CH, Hsieh MC: Prognostic impact of tumor infiltrating lymphocytes on patients with metastatic urothelial carcinoma receiving platinum based chemotherapy. Sci Rep 2018, 8(1):7485. 64. Sonpavde G, Pond GR, Choueiri TK, Mullane S, Niegisch G, Albers P, Necchi A, Di Lorenzo G, Buonerba C, Rozzi A et al: Single-agent Taxane Versus Taxane-containing Combination Chemotherapy as Salvage Therapy for Advanced Urothelial Carcinoma. Eur Urol 2016, 69(4):634-641. 65. Terakawa T, Miyake H, Yokoyama N, Miyazaki A, Tanaka H, Inoue T, Fujisawa M: Clinical outcome of paclitaxel and carboplatin as second-line chemotherapy for advanced urothelial carcinoma resistant to first-line therapy with gemcitabine and cisplatin. Urol Int 2014, 92(2):180-185. 66. Brousell SC, Fantony JJ, Van Noord MG, Harrison MR, Inman BA: Vinflunine for the treatment of advanced or metastatic transitional cell carcinoma of the urothelial tract: an evidence-based review of safety, efficacy, and place in therapy. Core Evid 2018, 13:1-12. 67. Hsu F-S, Su C-H, Huang K-H: A comprehensive review of US FDA-approved immune checkpoint inhibitors in urothelial carcinoma. Journal of immunology research 2017, 2017. 68. Oing C, Rink M, Oechsle K, Seidel C, von Amsberg G, Bokemeyer C: Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond-A Comprehensive Review of the Current Literature. J Urol 2016, 195(2):254-263. 69. De Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Gil T, Marreaud S, Daugaard G, Skoneczna I et al: Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 2012, 30(2):191-199. 70. Yeh BW, Li WM, Li CC, Kang WY, Huang CN, Hour TC, Liu ZM, Wu WJ, Huang HS: Histone deacetylase inhibitor trichostatin A resensitizes gemcitabine resistant urothelial carcinoma cells via suppression of TG-interacting factor. Toxicol Appl Pharmacol 2016, 290:98-106. 71. Dowdy SC, Jiang S, Zhou XC, Hou X, Jin F, Podratz KC, Jiang SW: Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells. Mol Cancer Ther 2006, 5(11):2767-2776. 72. McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A et al: Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochimica et biophysica acta 2007, 1773(8):1263-1284. 73. Jebar AH, Hurst CD, Tomlinson DC, Johnston C, Taylor CF, Knowles MA: FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene 2005, 24(33):5218-5225. 74. Todi SV, Paulson HL: Balancing act: deubiquitinating enzymes in the nervous system. Trends Neurosci 2011, 34(7):370-382. 75. Altun M, Kramer HB, Willems LI, McDermott JL, Leach CA, Goldenberg SJ, Kumar KG, Konietzny R, Fischer R, Kogan E et al: Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol 2011, 18(11):1401-1412. 76. Kuo KL, Liu SH, Lin WC, Chow PM, Chang YW, Yang SP, Shi CS, Hsu CH, Liao SM, Chang HC et al: The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study. Cells 2019, 8(10). 77. Chen H, Liu H, Qing G: Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther 2018, 3:5. 78. Polischouk AG, Holgersson A, Zong D, Stenerlow B, Karlsson HL, Moller L, Viktorsson K, Lewensohn R: The antipsychotic drug trifluoperazine inhibits DNA repair and sensitizes non small cell lung carcinoma cells to DNA double-strand break induced cell death. Mol Cancer Ther 2007, 6(8):2303-2309. 79. Zhu Y, Zhang C, Gu C, Li Q, Wu N: Function of Deubiquitinating Enzyme USP14 as Oncogene in Different Types of Cancer. Cell Physiol Biochem 2016, 38(3):993-1002. 80. Li Y, Seto E: HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harbor perspectives in medicine 2016, 6(10):a026831. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80408 | - |
| dc.description.abstract | "尿路上皮癌（Urothelial carcinoma, UC）在全世界癌症發生率排名前十位，在台灣發生率也有上升的趨勢。接受根除性手術後，仍有 20-50% 的患者會復發和轉移。當患者出現轉移腫瘤時，五年存活率將不到20%。目前的一線化學治療藥物（包括cisplatin和gemcitabine），總體反應率只有約為 50-60%。雖然已開發出用於晚期和轉移性 UC 的二線化療藥物與免疫治療，然而大部分患者的腫瘤仍持續出現抗藥性，最終治療失敗而造成死亡。因此，尋找新的治療方法來克服UC的抗藥性刻不容緩的。 在本研究第一與第二部分中，我們目標在研究組織蛋白去乙醯酶（Histone deacetylase；HDAC）抑制劑: 曲古抑菌素-A （Trichostatin A， TSA） ，在UC的上抗腫瘤效果，並探討TSA能否增加化療藥物對UC的毒殺作用，進一步去釐清其機轉。我們使用了三種膀胱尿路上皮癌細胞株（NTUB1，T24和BFTC-905）以及一種發生於腎臟的上泌尿道尿路上皮癌細胞株（BFTC-909）。實驗證實，TSA 與第一線化療藥物：cisplatin、gemcitabine、doxorubicin和第二線化療藥物 paclitaxel等四種化療藥物合併使用後，皆在UC細胞毒殺作用中產生了顯著的協同作用（Combination index < 1）；TSA並同時抑制了化療藥物所活化的MAPK/ERK抗藥機轉。而此細胞實驗結果，也在腫瘤異體移植的動物實驗中獲得了相同驗證。此外我們也發現，在臨床上對化療反應不佳的病人之UC檢體上，MAPK/ERK磷酸化表現量明顯高於對化療反應良好的UC病人檢體。前兩部分研究的結果證實：TSA與化療藥物合併使用下，經由抑制MAPK/ERK 磷酸化的抗藥機轉，進而增強化療藥物毒殺UC的效用。 在第三部分中，我們探討了去泛素化酶（deubiquitinating enzymes, DUB）抑製劑: PR-619，在cisplatin-resistant UC 中的抗腫瘤作用。首先，在免疫組織化學染色的結果顯示，USP14 和 USP21在化療無效的UC病人檢體中有高度表現，說明了DUB可能與腫瘤抗藥性有正相關，並有潛力成為克服化學抗藥性的新標靶。我們建立了一株對cisplatin具有抗藥性的UC細胞株T24/R。我們發現，PR-619和cisplatin併用時，增強了對T24/R的細胞毒殺作用和凋亡。此外，我們也證明了PR-619可經由抑制c-Myc致癌基因，逆轉UC抗藥性細胞株的抗藥性，進而明顯增強cisplatin對抗藥性UC地毒殺效果。這些結果也在腫瘤異種移植的動物實驗中，獲得相同結果。 總結以上的研究，我們證實了組織蛋白去乙醯酶抑製劑和去泛素化酶抑製劑，除了單獨使用下能有效毒殺UC細胞之外，在兩者個別合併化療藥物使用下，也顯著增強了化療藥物毒殺UC的效果，並抑制了腫瘤細胞抗藥性機轉的產生。這些成果釐清了藥物機轉之外，也提供了克服 UC 抗藥性的新治療策略，具有相當高的臨床應用價值。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:06:02Z (GMT). No. of bitstreams: 1 U0001-0801202218101100.pdf: 88417926 bytes, checksum: 9d03a656b9547cd287c09f4cda80347d (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | "致謝....................................................................................................................... 1 中文摘要....................................................................................................................... 3 Abstract ................................................................................................................... 5 Abbreviations................................................................................................................ 8 Introduction................................................................................................................. 9 Materials and Methods ............................................................................................... 17 Results ........................................................................................................................ 23 Ⅰ. Trichostatin A, a Histone Deacetylase inhibitor, Induces Synergistic Cytotoxicity with Chemotherapy via Suppression of Raf/MEK/ERK Pathway in Urothelial Carcinoma .............................................................................................................. 23 Ⅱ. Trichostatin A synergistically enhances paclitaxel-induced cytotoxicity in urothelial carcinoma cells by suppressing the ERK pathway…...............................................27 ⅡI. PR-619, a General Inhibitor of Deubiquitylating Enzymes, Diminishes Cisplatin Resistance in Urothelial Carcinoma Cells through the Suppression of c-Myc: An In Vitro and In Vivo Study…...................................................................................... 30 Discussion................................................................................................................... 34 Summary..................................................................................................................... 41 Perspectives................................................................................................................. 42 Figures and Tables....................................................................................................... 44 References................................................................................................................... 82" | |
| dc.language.iso | en | |
| dc.subject | 去泛素化酶 | zh_TW |
| dc.subject | 尿路上皮癌 | zh_TW |
| dc.subject | 化學抗藥性 | zh_TW |
| dc.subject | 克莫抗癌 | zh_TW |
| dc.subject | 組織蛋白去乙醯酶 | zh_TW |
| dc.subject | histone deacetylase | en |
| dc.subject | MAPK pathway | en |
| dc.subject | deubiquitinating enzyme | en |
| dc.subject | Urothelial carcinoma | en |
| dc.subject | chemoresistance | en |
| dc.subject | cisplatin | en |
| dc.subject | paclitaxel | en |
| dc.title | 尋找克服尿路上皮癌化學治療抗藥性的治療策略──探討組織蛋白去乙醯酶抑制劑及去泛素化酶抑制劑治療之機轉 | zh_TW |
| dc.title | Explore new treatment strategies for overcoming the chemoresistance of urothelial carcinoma ── Using histone deacetylase inhibitor and deubiquitinating enzymes inhibitor as new treatment targets | en |
| dc.date.schoolyear | 110-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.author-orcid | 0000-0002-4586-7308 | |
| dc.contributor.coadvisor | 林家齊(Chia-Chi Lin) | |
| dc.contributor.oralexamcommittee | 劉興華(Tsai-Chuan Ma),黃凱文(Jo-Jung Yu),廖俊厚(Ching-Lung Tsai),杜元博 | |
| dc.subject.keyword | 尿路上皮癌,化學抗藥性,克莫抗癌,組織蛋白去乙醯酶,去泛素化酶, | zh_TW |
| dc.subject.keyword | Urothelial carcinoma,chemoresistance,cisplatin,paclitaxel,histone deacetylase,deubiquitinating enzyme,MAPK pathway, | en |
| dc.relation.page | 90 | |
| dc.identifier.doi | 10.6342/NTU202200029 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-01-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-0801202218101100.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 86.35 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。