請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65615
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳信銘 | |
dc.contributor.author | Jyun-Sian Wu | en |
dc.contributor.author | 吳俊賢 | zh_TW |
dc.date.accessioned | 2021-06-16T23:54:04Z | - |
dc.date.available | 2025-03-12 | |
dc.date.copyright | 2020-03-12 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2020-02-17 | |
dc.identifier.citation | 1.中華民國衛生福利部. 民國105年死因統計結果分析. 2017.
2.口腔癌工作群編撰小組, T. 口腔癌臨床診療指引; 財團法人國家衛生研究院 (NHRI) 癌症研究所 台灣癌症臨床研究合作組織 (TCOG): 2011. 3.Montero, P.H.; Patel, S.G. Cancer of the oral cavity. Surg Oncol Clin N Am 2015, 24, 491-508. 4.Moeckelmann, N.; Ebrahimi, A.; Dirven, R.; Liu, J.; Low, T.-H.; Gupta, R.; Ashford, B.; Ch’ng, S.; Palme, C.E.; Clark, J.R. Analysis and Comparison of the 8th Edition American Joint Committee on Cancer (AJCC) Nodal Staging System in Cutaneous and Oral Squamous Cell Cancer of the Head and Neck. Ann. Surg. Oncol. 2018, 25, 1730-1736. 5.Subramaniam N, T.K., Anand A, Balasubramanian D, Iyer S. Implementing American Joint Committee on Cancer 8th edition for head-and-neck cancer in India: Context, feasibility, and practicality. Indian J Cancer 2018, 55, 4-8. 6.Edge, S.B.; Compton, C.C. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010, 17, 1471-1474. 7. Kao, S.Y.; Lim, E. An overview of detection and screening of oral cancer in Taiwan. Chin J Dent Res 2015, 18, 7-12. 8. Baskar, R.; Lee, K.A.; Yeo, R.; Yeoh, K.W. Cancer and radiation therapy: current advances and future directions. Int J Med Sci 2012, 9, 193-199. 9. Amable, L. Cisplatin resistance and opportunities for precision medicine. Pharmacol Res 2016, 106, 27-36. 10. Alexis, F. Nano-polypharmacy to treat tumors: coencapsulation of drug combinations using nanoparticle technology. Mol Ther 2014, 22, 1239-1240. 11. Cheng, Y.; Zhao, P.; Wu, S.; Yang, T.; Chen, Y.; Zhang, X.; He, C.; Zheng, C.; Li, K.; Ma, X., et al. Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma. Int J Pharm 2018, 545, 261-273. 12. Guo, S.; Lin, C.M.; Xu, Z.; Miao, L.; Wang, Y.; Huang, L. Co-delivery of cisplatin and rapamycin for enhanced anticancer therapy through synergistic effects and microenvironment modulation. ACS Nano 2014, 8, 4996-5009. 13. Zununi Vahed, S.; Salehi, R.; Davaran, S.; Sharifi, S. Liposome-based drug co-delivery systems in cancer cells. Mater Sci Eng C Mater Biol Appl 2017, 71, 1327-1341. 14. Guo, S.; Miao, L.; Wang, Y.; Huang, L. Unmodified drug used as a material to construct nanoparticles: delivery of cisplatin for enhanced anti-cancer therapy. J Control Release 2014, 174, 137-142. 15. Malik, M.A.; Wani, M.Y.; Hashim, M.A. Microemulsion method: A novel route to synthesize organic and inorganic nanomaterials. Arabian Journal of Chemistry 2012, 5, 397-417. 16. Liu, Y.; Chen, G.; Liu, H.; Li, Z.; Yang, Q.; Gu, X.; Du, Z.; Zhang, G.; Wang, J. Integrated bioinformatics analysis of miRNA expression in Ewing sarcoma and potential regulatory effects of miR-21 via targeting ALCAM/CD166. Artif Cells Nanomed Biotechnol 2019, 47, 2114-2122. 17. Thomson, D.W.; Dinger, M.E. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet 2016, 17, 272-283. 18. Kampen, K.R.; Fancello, L.; Girardi, T.; Rinaldi, G.; Planque, M.; Sulima, S.O.; Loayza-Puch, F.; Verbelen, B.; Vereecke, S.; Verbeeck, J., et al. Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells. Nat Commun 2019, 10, 2542. 19. Lu, D.; Thum, T. RNA-based diagnostic and therapeutic strategies for cardiovascular disease. Nat Rev Cardiol 2019, 16, 661-674. 20. Vecchio, E.; Golino, G.; Pisano, A.; Albano, F.; Falcone, C.; Ceglia, S.; Iaccino, E.; Mimmi, S.; Fiume, G.; Giurato, G., et al. IBTK contributes to B-cell lymphomagenesis in E mu-myc transgenic mice conferring resistance to apoptosis. Cell Death Dis. 2019, 10, 14. 21. Li, J.; Yang, Y.; Huang, L. Calcium phosphate nanoparticles with an asymmetric lipid bilayer coating for siRNA delivery to the tumor. J Control Release 2012, 158, 108-114. 22. McDonald, E.R., 3rd; de Weck, A.; Schlabach, M.R.; Billy, E.; Mavrakis, K.J.; Hoffman, G.R.; Belur, D.; Castelletti, D.; Frias, E.; Gampa, K., et al. Project dRIVE: a compendium of cancer dependencies and synthetic lethal relationships uncovered by large-scale, deep RNAi screening. Cell 2017, 170, 577-592 e510. 23. Chen, W.H.; Lecaros, R.L.; Tseng, Y.C.; Huang, L.; Hsu, Y.C. Nanoparticle delivery of HIF1alpha siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer. Cancer Lett 2015, 359, 65-74. 24. Inglehart, R.C.; Scanlon, C.S.; D'Silva, N.J. Reviewing and reconsidering invasion assays in head and neck cancer. Oral Oncol 2014, 50, 1137-1143. 25. Lam, L.; Logan, R.M.; Luke, C. Epidemiological analysis of tongue cancer in South Australia for the 24-year period, 1977-2001. Aust Dent J 2006, 51, 16-22. 26. Society, A.C. About Oral Cavity and Oropharyngeal. 2016. 27. D'Souza, G.; Kreimer, A.R.; Viscidi, R.; Pawlita, M.; Fakhry, C.; Koch, W.M.; Westra, W.H.; Gillison, M.L. Case–control study of human papillomavirus and oropharyngeal cancer. New England Journal of Medicine 2007, 356, 1944-1956. 28. Chaturvedi, A.K.; Engels, E.A.; Anderson, W.F.; Gillison, M.L. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol 2008, 26, 612-619. 29. Leemans, C.R.; Braakhuis, B.J.; Brakenhoff, R.H. The molecular biology of head and neck cancer. Nat Rev Cancer 2011, 11, 9-22. 30. Chien, H.T.; Young, C.K.; Chen, T.P.; Liao, C.T.; Wang, H.M.; Cheng, S.D.; Huang, S.F. Alcohol-metabolizing enzymes' gene polymorphisms and susceptibility to multiple Head and Neck Cancers. Cancer Prev Res (Phila) 2019, 12, 247-254. 31. Gandini, S.; Botteri, E.; Iodice, S.; Boniol, M.; Lowenfels, A.B.; Maisonneuve, P.; Boyle, P. Tobacco smoking and cancer: a meta-analysis. Int J Cancer 2008, 122, 155-164. 32. Ames, B.N.; Gold, L.S. Endogenous mutagens and the causes of aging and cancer. Mutat Res 1991, 250, 3-16. 33. Lee, D.J.; Lee, H.M.; Kim, J.H.; Park, I.S.; Rho, Y.S. Heavy alcohol drinking downregulates ALDH2 gene expression but heavy smoking up-regulates SOD2 gene expression in head and neck squamous cell carcinoma. World J Surg Oncol 2017, 15, 163. 34. ORGANIZATION, W.H.; CANCER, I.A.F.R.O. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum 2004, 85, 1-334. 35. Jeng, J.H.; Hahn, L.J.; Lin, B.R.; Hsieh, C.C.; Chan, C.P.; Chang, M.C. Effects of areca nut, inflorescence piper betle extracts and arecoline on cytotoxicity, total and unscheduled DNA synthesis in cultured gingival keratinocytes. J Oral Pathol Med 1999, 28, 64-71. 36. Chang, M.C.; Wu, H.L.; Lee, J.J.; Lee, P.H.; Chang, H.H.; Hahn, L.J.; Lin, B.R.; Chen, Y.J.; Jeng, J.H. The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation. J Biol Chem 2004, 279, 50676-50683. 37. Chang, L.Y.; Wan, H.C.; Lai, Y.L.; Kuo, Y.F.; Liu, T.Y.; Chen, Y.T.; Hung, S.L. Areca nut extracts increased expression of inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8, in peripheral blood mononuclear cells. J. Periodont. Res. 2009, 44, 175-183. 38. Chinenov, Y.; Kerppola, T.K. Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene 2001, 20, 2438-2452. 39. Angel, P.; Karin, M. The role of jun, fos and the ap-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta 1991, 1072, 129-157. 40. Nagesh, R.; Kumar, K.M.K.; Kumar, M.N.; Patil, R.H.; Sharma, S.C. Stress activated p38 MAPK regulates cell cycle via AP-1 factors in areca extract exposed human lung epithelial cells. Cytotechnology 2019, 71, 507-520. 41. Li, Y.C.; Chang, J.T.; Chiu, C.; Lu, Y.C.; Li, Y.L.; Chiang, C.H.; You, G.R.; Lee, L.Y.; Cheng, A.J. Areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells. Mol. Carcinog. 2016, 55, 1012-1023. 42. Rivera, C. Essentials of oral cancer. Int J Clin Exp Pathol 2015, 8, 11884-11894. 43. Argiris, A.; Karamouzis, M.V.; Raben, D.; Ferris, R.L. Head and neck cancer. The Lancet 2008, 371, 1695-1709. 44. Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell 2000, 100, 57-70. 45. Messadi, D.V. Diagnostic aids for detection of oral precancerous conditions. Int J Oral Sci 2013, 5, 59-65. 46. McCaul, J.A.; Gordon, K.E.; Clark, L.J.; Parkinson, E.K. Telomerase inhibition and the future management of head-and-neck cancer. Lancet Oncol. 2002, 3, 280-288. 47. Mao, L.; Lee, J.S.; Fan, Y.H.; Ro, J.Y.; Batsakis, J.G.; Lippman, S.; Hittelman, W.; Hong, W.K. Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment. Nat. Med. 1996, 2, 682-685. 48. 三軍總醫院. 正子斷層造影中心 -正子斷層造影中心. Availabe online: https://wwwv.tsgh.ndmctsgh.edu.tw/unit/10015/24210 (accessed on 49. Gonzalez, P.S.; O'Prey, J.; Cardaci, S.; Barthet, V.J.A.; Sakamaki, J.I.; Beaumatin, F.; Roseweir, A.; Gay, D.M.; Mackay, G.; Malviya, G., et al. Mannose impairs tumour growth and enhances chemotherapy. Nature 2018, 563, 719-723. 50. Ang, K.K.; Harris, J.; Wheeler, R.; Weber, R.; Rosenthal, D.I.; Nguyen-Tan, P.F.; Westra, W.H.; Chung, C.H.; Jordan, R.C.; Lu, C., et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010, 363, 24-35. 51. Network, T.N.C.C. NCCN Clinical practice guidelines in oncology; The National Comprehensive Cancer Network: 2001. 52. Liao, C.T.; Chang, J.T.C.; Wang, H.M.; Ng, S.H.; Hsueh, C.; Lee, L.Y.; Lin, C.H.; Chen, I.H.; Huang, S.F.; Cheng, A.J., et al. Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann. Surg. Oncol. 2008, 15, 915-922. 53. Fire, A.; Xu, S.; Montgomery, M.K.; Kostas, S.A.; Driver, S.E.; Mello, C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998, 391, 806-811. 54. Lam, J.K.W.; Chow, M.Y.T.; Zhang, Y.; Leung, S.W.S. siRNA Versus miRNA as Therapeutics for Gene Silencing. Mol. Ther.-Nucl. Acids 2015, 4, 20. 55. Uprichard, S.L. The therapeutic potential of RNA interference. FEBS Lett 2005, 579, 5996-6007. 56. Setten, R.L.; Rossi, J.J.; Han, S.P. The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov 2019, 18, 421-446. 57. Majumdar, R.; Rajasekaran, K.; Cary, J.W. RNA Interference (RNAi) as a Potential Tool for Control of Mycotoxin Contamination in Crop Plants: Concepts and Considerations. Front Plant Sci 2017, 8, 200. 58. Elbashir, S.M.; Lendeckel, W.; Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 2001, 15, 188-200. 59. Gonzalez, F.J.; Xie, C.; Jiang, C. The role of hypoxia-inducible factors in metabolic diseases. Nat Rev Endocrinol 2018, 15, 21-32. 60. Schreiber, T.; Quinting, T.; Dittmer, U.; Fandrey, J.; Sutter, K. Hypoxia-inducible factor 1alpha is Essential for Macrophage-mediated Erythroblast Proliferation in Acute Friend Retrovirus Infection. Sci Rep 2017, 7, 17236. 61. Peng, G.; Liu, Y. Hypoxia-inducible factors in cancer stem cells and inflammation. Trends in Pharmacological Sciences 2015, 36, 374-383. 62. Haase, V.H. HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism. Hemodial Int 2017, 21 Suppl 1, S110-S124. 63. Lisy, K.; Peet, D.J. Turn me on: regulating HIF transcriptional activity. Cell Death Differ. 2008, 15, 642-649. 64. Thirlwell, C.; Schulz, L.; Dibra, H.; Beck, S. Suffocating cancer: hypoxia-associated epimutations as targets for cancer therapy. Clin Epigenetics 2011, 3, 9. 65. Maes, C.; Carmeliet, G.; Schipani, E. Hypoxia-driven pathways in bone development, regeneration and disease. Nat Rev Rheumatol 2012, 8, 358-366. 66. Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003, 3, 721-732. 67. Suzuki, H.; Tomida, A.; Tsuruo, T. Dephosphorylated hypoxia-inducible factor 1 alpha as a mediator of p53-dependent apoptosis during hypoxia. Oncogene 2001, 20, 5779-5788. 68. LaGory, E.L.; Giaccia, A.J. The ever-expanding role of HIF in tumour and stromal biology. Nat Cell Biol 2016, 18, 356-365. 69. Liu, J.; Zhang, C.; Zhao, Y.; Yue, X.; Wu, H.; Huang, S.; Chen, J.; Tomsky, K.; Xie, H.; Khella, C.A., et al. Parkin targets HIF-1alpha for ubiquitination and degradation to inhibit breast tumor progression. Nat Commun 2017, 8, 1823. 70. Rankin, E.B.; Giaccia, A.J. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ 2008, 15, 678-685. 71. Ravi, R.; Mookerjee, B.; Bhujwalla, Z.M.; Sutter, C.H.; Artemov, D.; Zeng, Q.; Dillehay, L.E.; Madan, A.; Semenza, G.L.; Bedi, A. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 2000, 14, 34-44. 72. Li, M.; Xie, H.; Liu, Y.; Xia, C.; Cun, X.; Long, Y.; Chen, X.; Deng, M.; Guo, R.; Zhang, Z., et al. Knockdown of hypoxia-inducible factor-1 alpha by tumor targeted delivery of CRISPR/Cas9 system suppressed the metastasis of pancreatic cancer. J Control Release 2019, 304, 204-215. 73. Byeon, H.K.; Ku, M.; Yang, J. Beyond EGFR inhibition: multilateral combat strategies to stop the progression of head and neck cancer. Exp Mol Med 2019, 51, 8. 74. Tebbutt, N.; Pedersen, M.W.; Johns, T.G. Targeting the ERBB family in cancer: couples therapy. Nat Rev Cancer 2013, 13, 663-673. 75. Lv, Q.; Meng, Z.; Yu, Y.; Jiang, F.; Guan, D.; Liang, C.; Zhou, J.; Lu, A.; Zhang, G. Molecular mechanisms and translational therapies for human epidermal receptor 2 positive breast cancer. Int J Mol Sci 2016, 17. 76. Laisney, J. Characterisation and regulation of the Egfr/Egfr ligand system in fish models for melanoma. 2010. 77. Kalyankrishna, S.; Grandis, J.R. Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol 2006, 24, 2666-2672. 78. Alsahafi, E.; Begg, K.; Amelio, I.; Raulf, N.; Lucarelli, P.; Sauter, T.; Tavassoli, M. Clinical update on head and neck cancer: molecular biology and ongoing challenges. Cell Death Dis 2019, 10, 540. 79. An, Z.; Aksoy, O.; Zheng, T.; Fan, Q.W.; Weiss, W.A. Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies. Oncogene 2018, 37, 1561-1575. 80. Dannenberg, A.J.; Lippman, S.M.; Mann, J.R.; Subbaramaiah, K.; DuBois, R.N. Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention. J Clin Oncol 2005, 23, 254-266. 81. Burotto, M.; Chiou, V.L.; Lee, J.M.; Kohn, E.C. The MAPK pathway across different malignancies: a new perspective. Cancer 2014, 120, 3446-3456. 82. Yang, S.H.; Sharrocks, A.D.; Whitmarsh, A.J. MAP kinase signalling cascades and transcriptional regulation. Gene 2013, 513, 1-13. 83. Johnson, G.L.; Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002, 298, 1911-1912. 84. Peng, Q.; Deng, Z.; Pan, H.; Gu, L.; Liu, O.; Tang, Z. Mitogen-activated protein kinase signaling pathway in oral cancer. Oncol Lett 2018, 15, 1379-1388. 85. Samatar, A.A.; Poulikakos, P.I. Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov 2014, 13, 928-942. 86. Kunz, J.; Henriquez, R.; Schneider, U.; Deuter-Reinhard, M.; Movva, N.R.; Hall, M.N. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 1993, 73, 585-596. 87. Sabers, C.J.; Martin, M.M.; Brunn, G.J.; Williams, J.M.; Dumont, F.J.; Wiederrecht, G.; Abraham, R.T. Isolation of a protein target of the fkbp12-rapamycin complex in mammalian-cells. J. Biol. Chem. 1995, 270, 815-822. 88. Laplante, M.; Sabatini, D.M. mTOR signaling in growth control and disease. Cell 2012, 149, 274-293. 89. Mendoza, M.C.; Er, E.E.; Blenis, J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci 2011, 36, 320-328. 90. Porta, C.; Paglino, C.; Mosca, A. Targeting PI3K/Akt/mTOR Signaling in Cancer. Front Oncol 2014, 4, 64. 91. Yu, M.; Chen, Y.; Zeng, H.; Zheng, Y.; Fu, G.; Zhu, W.; Broeckel, U.; Aggarwal, P.; Turner, A.; Neale, G., et al. PLCgamma-dependent mTOR signalling controls IL-7-mediated early B cell development. Nat Commun 2017, 8, 1457. 92. Mackay, H.J.; Twelves, C.J. Targeting the protein kinase C family: are we there yet? Nat Rev Cancer 2007, 7, 554-562. 93. Diagnostics. BCR Signaling Pathway - Creative Diagnostics. Availabe online: https://www.creative-diagnostics.com/bcr-signaling-pathway.htm (accessed on 94. Su, Y.; Yu, Y.; Liu, C.; Zhang, Y.; Liu, C.; Ge, M.; Li, L.; Lan, M.; Wang, T.; Li, M., et al. Fate decision of satellite cell differentiation and self-renewal by miR-31-IL34 axis. Cell Death Differ 2019, 10.1038/s41418-019-0390-x. 95. Kisseleva, T.; Bhattacharya, S.; Braunstein, J.; Schindler, C.W. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 2002, 285, 1-24. 96. Buchert, M.; Burns, C.J.; Ernst, M. Targeting JAK kinase in solid tumors: emerging opportunities and challenges. Oncogene 2016, 35, 939-951. 97. Shih, C.H.; Chang, Y.J.; Huang, W.C.; Jang, T.H.; Kung, H.J.; Wang, W.C.; Yang, M.H.; Lin, M.C.; Huang, S.F.; Chou, S.W., et al. EZH2-mediated upregulation of ROS1 oncogene promotes oral cancer metastasis. Oncogene 2017, 36, 6542-6554. 98. Sithanandam, G.; Anderson, L.M. The ERBB3 receptor in cancer and cancer gene therapy. Cancer Gene Ther 2008, 15, 413-448. 99. Mendelsohn, J.; Baselga, J. The EGF receptor family as targets for cancer therapy. Oncogene 2000, 19, 6550-6565. 100. Nyati, M.K.; Morgan, M.A.; Feng, F.Y.; Lawrence, T.S. Integration of EGFR inhibitors with adiochemotherapy. Nat Rev Cancer 2006, 6, 876-885. 101. Bernier, J.; Bentzen, S.M.; Vermorken, J.B. Molecular therapy in head and neck oncology. Nat Rev Clin Oncol 2009, 6, 266-277. 102. Bangham, A.D.; Horne, R.W. Negative staining of phospholipids + their structural modification by-surface active agents as observed in electron microscope. J. Mol. Biol. 1964, 8, 660-668. 103. Gerlowski, L.E.; Jain, R.K. Microvascular permeability of normal and neoplastic tissues. Microvasc. Res. 1986, 31, 288-305. 104. Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 1986, 46, 6387-6392. 105. Gref, R.; Minamitake, Y.; Peracchia, M.T.; Trubetskoy, V.; Torchilin, V.; Langer, R. Biodegradable long-circulating polymeric nanospheres. Science 1994, 263, 1600-1603. 106. Shi, J.; Kantoff, P.W.; Wooster, R.; Farokhzad, O.C. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 2017, 17, 20-37. 107. Bulbake, U.; Doppalapudi, S.; Kommineni, N.; Khan, W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics 2017, 9. 108. Mehnert, W.; Mader, K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev 2001, 47, 165-196. 109. Jain, R.K.; Stylianopoulos, T. Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 2010, 7, 653-664. 110. Tong, R.; Chiang, H.H.; Kohane, D.S. Photoswitchable nanoparticles for in vivo cancer chemotherapy. Proc Natl Acad Sci U S A 2013, 110, 19048-19053. 111. Wong, C.; Stylianopoulos, T.; Cui, J.; Martin, J.; Chauhan, V.P.; Jiang, W.; Popovic, Z.; Jain, R.K.; Bawendi, M.G.; Fukumura, D. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc Natl Acad Sci U S A 2011, 108, 2426-2431. 112. Perrault, S.D.; Walkey, C.; Jennings, T.; Fischer, H.C.; Chan, W.C.W. Mediating Tumor Targeting Efficiency of Nanoparticles Through Design. Nano Letters 2009, 9, 1909-1915. 113. Babu, A.; Templeton, A.K.; Munshi, A.; Ramesh, R. Nanoparticle-based drug delivery for therapy of lung cancer: progress and challenges. Journal of Nanomaterials 2013, 2013, 1-11. 114. Kalepu, S.; Manthina, M.; Padavala, V. Oral lipid-based drug delivery systems – an overview. Acta Pharmaceutica Sinica B 2013, 3, 361-372. 115. Mei, L.; Zhang, Z.; Zhao, L.; Huang, L.; Yang, X.L.; Tang, J.; Feng, S.S. Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Adv Drug Deliv Rev 2013, 65, 880-890. 116. Severino, P.; Andreani, T.; Macedo, A.S.; Fangueiro, J.F.; Santana, M.H.; Silva, A.M.; Souto, E.B. Current state-of-art and new trends on lipid nanoparticles (SLN and NLC) for oral drug delivery. J Drug Deliv 2012, 2012, 750891. 117. Ferrati, S.; Nicolov, E.; Bansal, S.; Hosali, S.; Landis, M.; Grattoni, A. Docetaxel/2-hydroxypropyl beta -cyclodextrin inclusion complex increases docetaxel solubility and release from a nanochannel drug delivery system. Curr. Drug Targets 2015, 16, 1645-1649. 118. Alemi, A.; Zavar Reza, J.; Haghiralsadat, F.; Zarei Jaliani, H.; Haghi Karamallah, M.; Hosseini, S.A.; Haghi Karamallah, S. Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy. J Nanobiotechnology 2018, 16, 28. 119. Knop, K.; Hoogenboom, R.; Fischer, D.; Schubert, U.S. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed Engl 2010, 49, 6288-6308. 120. Damodaran, V.; Fee, C. Protein PEGylation: An overview of chemistry and process considerations. European Pharmaceutical Review 2010, 15, 18-26. 121. Allen, T.M.; Hansen, C.; Rutledge, J. Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. Biochim Biophys Acta 1989, 981, 27-35. 122. Nakamura, K.; Yamashita, K.; Itoh, Y.; Yoshino, K.; Nozawa, S.; Kasukawa, H. Comparative studies of polyethylene glycol-modified liposomes prepared using different PEG-modification methods. Biochim Biophys Acta 2012, 1818, 2801-2807. 123. Alexis, F.; Pridgen, E.; Molnar, L.K.; Farokhzad, O.C. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 2008, 5, 505-515. 124. Harris, J.; Martin, N.; Modi, M. PEGylation: a novel process for modifying pharmacokinetics. Clinical pharmacokinetics 2001, 40, 539-551. 125. Hadjesfandiari, N.; Parambath, A. Stealth coatings for nanoparticles. In Engineering of Biomaterials for Drug Delivery Systems, 2018; pp. 345-361. 126. Kawabata, K.; Takakura, Y.; Hashida, M. The fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake. Pharm Res 1995, 12, 825-830. 127. Shen, X.; Corey, D.R. Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs. Nucleic Acids Res 2018, 46, 1584-1600. 128. Zhao, Y.; Huang, L. Lipid nanoparticles for gene delivery. Adv Genet 2014, 88, 13-36. 129. Yao, Y.; Wang, T.; Liu, Y.; Zhang, N. Co-delivery of sorafenib and VEGF-siRNA via pH-sensitive liposomes for the synergistic treatment of hepatocellular carcinoma. Artif Cells Nanomed Biotechnol 2019, 47, 1374-1383. 130. Li, S.D.; Huang, L. Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. J Control Release 2010, 145, 178-181. 131. Subhan, M.A.; Torchilin, V.P. Efficient nanocarriers of siRNA therapeutics for cancer treatment. Transl Res 2019, 10.1016/j.trsl.2019.07.006. 132. Szadvari, I.; Krizanova, O.; Babula, P. Athymic nude mice as an experimental model for cancer treatment. Physiol Res 2016, 65, S441-s453. 133. Bryant, C.D. The blessings and curses of C57BL/6 substrains in mouse genetic studies. Ann N Y Acad Sci 2011, 1245, 31-33. 134. Booth, D.G.; Takagi, M.; Sanchez-Pulido, L.; Petfalski, E.; Vargiu, G.; Samejima, K.; Imamoto, N.; Ponting, C.P.; Tollervey, D.; Earnshaw, W.C., et al. Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery. Elife 2014, 3, e01641. 135. McArthur, K.; Kile, B.T. Apoptotic caspases: multiple or mistaken identities? Trends Cell Biol 2018, 28, 475-493. 136. Lertkiatmongkol, P.; Liao, D.; Mei, H.; Hu, Y.; Newman, P.J. Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31). Curr Opin Hematol 2016, 23, 253-259. 137. Yuan, Y.; Hilliard, G.; Ferguson, T.; Millhorn, D.E. Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. J Biol Chem 2003, 278, 15911-15916. 138. Bhattacharjee, S. DLS and zeta potential - What they are and what they are not? J Control Release 2016, 235, 337-351. 139. Patel, V.R.; Agrawal, Y.K. Nanosuspension: An approach to enhance solubility of drugs. J Adv Pharm Technol Res 2011, 2, 81-87. 140. Frohlich, E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine 2012, 7, 5577-5591. 141. Moroz, E.; Carlin, S.; Dyomina, K.; Burke, S.; Thaler, H.T.; Blasberg, R.; Serganova, I. Real-time imaging of HIF-1alpha stabilization and degradation. PLoS One 2009, 4, e5077. 142. Eskandani, M.; Abdolalizadeh, J.; Hamishehkar, H.; Nazemiyeh, H.; Barar, J. Galbanic acid inhibits HIF-1alpha expression via EGFR/HIF-1alpha pathway in cancer cells. Fitoterapia 2015, 101, 1-11. 143. Poon, E.; Harris, A.L.; Ashcroft, M. Targeting the hypoxia-inducible factor (HIF) pathway in cancer. Expert Rev Mol Med 2009, 11, e26. 144. 葉佳憲. 創新標靶奈米傳輸EGFR靜默RNA技術結合新穎光動力療法於頭頸癌治療; 中原大學生物科技研究所碩士論文: 2016. 145. Lu, Y.; Li, X.; Lu, H.; Fan, Z. 1, 9-Pyrazoloanthrones downregulate HIF-1α and sensitize cancer cells to cetuximab-mediated anti-EGFR therapy. PloS one 2010, 5, e15823-e15823. 146. Wang, G.; Li, Y.; Yang, Z.; Xu, W.; Yang, Y.; Tan, X. ROS mediated EGFR/MEK/ERK/HIF-1α loop regulates glucose metabolism in pancreatic cancer. Biochemical and Biophysical Research Communications 2018, 500, 873-878. 147. Rot, S.; Taubert, H.; Bache, M.; Greither, T.; Würl, P.; Holzhausen, H.-J.; Eckert, A.W.; Vordermark, D.; Kappler, M. Low HIF-1α and low EGFR mRNA expression significantly associate with poor survival in soft tissue sarcoma patients; the proteins react differently. International journal of molecular sciences 2018, 19, 3842. 148. Jin, Q.; Zhou, J.; Xu, X.; Huang, F.; Xu, W. Hypoxia-inducible factor-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib. Oncology letters 2019, 17, 4034-4043. 149. Lu, H.; Liang, K.; Lu, Y.; Fan, Z. The anti-EGFR antibody cetuximab sensitizes human head and neck squamous cell carcinoma cells to radiation in part through inhibiting radiation-induced upregulation of HIF-1α. Cancer letters 2012, 322, 78-85. 150. Aghazadeh, S.; Yazdanparast, R. Activation of STAT3/HIF-1α/Hes-1 axis promotes trastuzumab resistance in HER2-overexpressing breast cancer cells via down-regulation of PTEN. Biochimica et Biophysica Acta (BBA) - General Subjects 2017, 1861, 1970-1980. 151. Neelapu, S.S.; Locke, F.L.; Bartlett, N.L.; Lekakis, L.J.; Miklos, D.B.; Jacobson, C.A.; Braunschweig, I.; Oluwole, O.O.; Siddiqi, T.; Lin, Y., et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-cell lymphoma. New England Journal of Medicine 2017, 377, 2531-2544. 152. Shah, N.N.; Fry, T.J. Mechanisms of resistance to CAR T cell therapy. Nature Reviews Clinical Oncology 2019, 16, 372-385. 153. Mullard, A. Pioneering antisense drug heads into pivotal trials for Huntington disease. Nature Reviews Drug Discovery 2019, 18, 161-163. 154. Liu, X.; Wang, P.; Zhang, C.; Ma, Z. Epidermal growth factor receptor (EGFR): A rising star in the era of precision medicine of lung cancer. Oncotarget 2017, 8, 50209-50220. 155. Baumeister, J.; Chatain, N.; Hubrich, A.; Maie, T.; Costa, I.G.; Denecke, B.; Han, L.; Kustermann, C.; Sontag, S.; Sere, K., et al. Hypoxia-inducible factor 1 (HIF-1) is a new therapeutic target in JAK2V617F-positive myeloproliferative neoplasms. Leukemia 2019, 10.1038/s41375-019-0629-z. 156. Lin, Y.W.; Huang, S.T.; Wu, J.C.; Chu, T.H.; Huang, S.C.; Lee, C.C.; Tai, M.H. Novel HDGF/HIF-1alpha/VEGF axis in oral cancer impacts disease prognosis. BMC Cancer 2019, 19, 1083. 157. Tamura, R.; Tanaka, T.; Akasaki, Y.; Murayama, Y.; Yoshida, K.; Sasaki, H. The role of vascular endothelial growth factor in the hypoxic and immunosuppressive tumor microenvironment: perspectives for therapeutic implications. Med Oncol 2019, 37, 2. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65615 | - |
dc.description.abstract | 癌症是台灣人排行第一的死亡原因,占總死亡人數27.7%,平均每天約有130人死於癌症。其中台灣口腔癌的發生率是世界第一,主要原因與飲食文化中有嚼食檳榔的行為有關。本研究使用新型微脂體磷酸鈣技術Lipid calcium phosphate (LCP),組合Hypoxia-inducible factors-1α (HIF-1α) 與Epidermal growth factor receptor (EGFR) 的small interfering RNA (siRNA) 利用DOPA (1,2-dioleoyl-sn-glycero-3-phosphate, sodium salt)、DOTAP (1,2-dioleoyl-3-trimethylammonium-propane, chloride salt)、DSPE–PEG-2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000], ammonium salt) 等化合物包覆成為奈米大小之微脂體粒子。LCP HIF-1α & EGFR siRNA微脂體的平均粒徑約在38.6 ± 7.4 nm,膜電荷為50.2 ± 0.8 mV。以體外細胞實驗驗證siRNA序列可以有效抑制60% HIF-1α蛋白質表現和抑制81% EGFR蛋白質表現。
體內動物實驗使用異種移植SAS口腔癌細胞之裸鼠的動物模型,用BALB/cAnN.Cg-Foxn1nu/CrlNarl品系的裸鼠在其皮下移植SAS口腔癌細胞,並等待其腫瘤成長是180-201 mm3的口腔癌腫瘤隨機分配5組實驗,分別為正向控制組 (PBS)、負向控制組 (LCP Control siRNA)、HIF-1α siRNA對照組 (LCP HIF-1α siRNA)、EGFR siRNA對照組 (LCP EGFR siRNA) 和HIF-1α & EGFR siRNA組合治療組 (LCP HIF-1α & EGFR siRNA),在第 0、1、2、5、6 和7天注射LCP藥物,其間隔為每24小時一次。每天持續觀察生理狀況,並每日量測腫瘤體積大小和體重,在第13天結束實驗犧牲動物。第13天的結果,PBS組腫瘤體積為500 mm3;LCP Control siRNA組腫瘤體積為542 mm3;LCP HIF-1α siRNA組腫瘤體積為526 mm3;LCP EGFR siRNA組腫瘤體積為532 mm3;LCP HIF-1α & EGFR siRNA組腫瘤體積為379 mm3。受到LCP藥物治療後,LCP HIF-1α & EGFR siRNA組比較PBS組減少121 mm3的腫瘤體積 (P<0.05)。LCP HIF-1α & EGFR siRNA組比較LCP Control siRNA組、LCP HIF-1α siRNA組與LCP EGFR siRNA組的腫瘤體積都有達到顯著的抑制 (P<0.01)。 蘇木精-伊紅染色 (hematoxylin and eosin stain, H&E stain) 觀察動物肝、腎和腫瘤切片,LCP藥物對動物的肝腎組織是沒有毒性,腫瘤切片觀察LCP HIF-1α & EGFR siRNA組有較多凋亡細胞的產生,用Mitotic Figure方法分析確認LCP HIF-1α & EGFR siRNA治療可以減少細胞有絲分裂的發生。LCP HIF-1α & EGFR siRNA在免疫組織染色中與PBS組相比Ki-67細胞增生因子和CD31血管新生因子的表現都有顯著減少,Caspase 3細胞凋亡因子的表現也比PBS組高出71%,代表LCP HIF-1α & EGFR siRNA可以抑制細胞增生,使癌細胞凋亡,並阻止腫瘤繼續生長。免疫組織染色HIF-1α和EGFR的切片染色分析證實LCP包覆HIF-1α與EGFR siRNA可以抑制HIF-1α和EGFR蛋白質表現的效果 (P<0.001)。血液生化分析分析15項與肝、腎和心肌有關的生化因子,數據顯示使用LCP HIF-1α & EGFR siRNA治療的動物,沒有出現與肝、腎和心肌功能相關的毒性產生。總體而言,LCP組合HIF-1α siRNA和EGFR siRNA可以比單獨使用HIF-1α siRNA或EGFR siRNA能更有效的抑制SAS口腔癌腫瘤的生長,並能抑制腫瘤中蛋白質的表現,且不會對動物有毒性產生副作用發生。 | zh_TW |
dc.description.abstract | Cancer is most of the people cause of death in Taiwanese, accounting for 27.7% of deaths. About one day have 130 people die from cancer. The incidence of oral cancer in Taiwan is the highest in the world. The main reason is related to the behavior of chewing areca. Lipid calcium phosphate (LCP) compose of DOPA (1,2-dioleoyl-sn-glycero-3-phosphate, sodium salt)、DOTAP (1,2-dioleoyl-3-trimethylammonium-propane, chloride salt)、DSPE–PEG-2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000], ammonium salt). The LCP technology encapsulated of hypoxia-inducible factors-1α (HIF-1α) and epidermal growth factor receptor (EGFR) small interfering RNA (siRNA). LCP HIF-1α & EGFR siRNA liposome average size was 38.6 ± 7.4 nm, zeta potential was 50.2 ± 0.8 mV. In vitro cell experiments confirmed that siRNA sequences can effectively inhibit the expression of 60% HIF-1α protein and inhibit the expression of 81% EGFR protein.
In vivo animal study used xenograft SAS oral cancer cell animal model. The animal used BALB/cAnN.Cg-Foxn1nu/CrlNarl mice. Inject the SAS oral cancer cell under the mice back skin, and waited tumor growth to 180-201 mm3. The animal group had PBS group, LCP Control siRNA group, LCP HIF-1α siRNA group, LCP EGFR siRNA group and LCP HIF-1α & EGFR siRNA. LCP drugs were injected on days 0, 1, 2, 5, 6 and 7 at intervals of 24 hours. The physiological condition was continuously observed every day, and the tumor volume and body weight were measured daily, and the animals were sacrificed on the 13th day. The day 13th result, PBS group tumor volume was 500 mm3;LCP Control siRNA group tumor volume was 542 mm3;LCP HIF-1α siRNA group tumor volume was 526 mm3;LCP EGFR siRNA group tumor volume was 532 mm3;LCP HIF-1α & EGFR siRNA group tumor volume was 379 mm3。After being treated with LCP drug, LCP HIF-1α & EGFR siRNA group tumor volume was smaller than PBS group 121 mm3 (P<0.05). LCP HIF-1α & EGFR siRNA group tumor volume compares to LCP Control siRNA group, LCP HIF-1α siRNA group and LCP EGFR siRNA group tumor volume had been inhibited (P<0.01). H&E stain (hematoxylin and eosin stain) slice about the animal liver and kidney was showing no toxicity of LCP drug. The tumor H&E stain slice LCP HIF-1α & EGFR siRNA group had apoptosis more than other groups. Mitotic figure data show LCP HIF-1α & EGFR siRNA can reduce mitosis. The expression of Ki-67 and CD31 was significantly decreased in LCP HIF-1α & EGFR siRNA groups compared with PBS group. The LCP HIF-1α & EGFR siRNA group expression of caspase 3 was higher than the PBS groups. The LCP HIF-1α & EGFR siRNA can inhibit cell proliferation, causes apoptosis, and prevents tumor growth. IHC staining of HIF-1α and EGFR protein analysis confirmed that LCP encapsulated HIF-1α and EGFR siRNA could inhibit the expression of HIF-1α and EGFR proteins (P<0.001). Biochemical analysis analyzed 15 biochemical factors related to liver, kidney and heart muscle. The data showed that animals treated with LCP HIF-1α & EGFR siRNA did not develop toxicity associated with liver, kidney and heart. Overall, LCP combined with HIF-1α siRNA and EGFR siRNA can inhibit the growth of SAS oral cancer tumors more effectively than HIF-1α siRNA or EGFR siRNA alone, and can inhibit the expression of proteins in tumors, and not to animals. LCP will not cause side effects. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:54:04Z (GMT). No. of bitstreams: 1 ntu-108-R06450008-1.pdf: 5618230 bytes, checksum: 0abc1b1b9846b3681feb61c30da20613 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員會審定書………………………………………………………………………i
中文摘要…………………………………………………………………………………ii 英文摘要……………………………………………………………………………iiii 致謝………………………………………………………………………………...…...vi 目錄……………………………………………………………………………...……..vii 圖目錄………………………………………………………………………………......xi 表目錄…………………………………………………………………………...…….xiii 第一章 研究介紹………………………………...……………………………………..1 1-1 研究背景…………………………………………………………………………1 1-2 研究動機及目的…………………………………………………………………7 第二章 實驗設計規劃流程…………………………………………………………….9 2-1 動物實驗流程設計………………………………………………………………9 2-2 LCP毒理實驗設計流程………………………………………………………...11 第三章 文獻探討……………………………………………………………………...12 3-1 口腔癌生成機制………………………………………………………………..12 3-2 口腔癌的生長………………………………………………………………......14 3-3 口腔癌的治療…………………………………………………………………..18 3-4 Small interference RAN介紹與機制…………………………………………....19 3-5 缺氧誘導因子(Hypoxia-inducible factors, HIFs) 介紹與機制………………..21 3-6 表皮生長因子受器 (Epidermal growth factor receptor, EGFR) 介紹與機制.24 3-7 奈米藥物 (Nanomedicine)……………………………………………………..30 第四章 材料與方法……………………………………………………………..…….36 4-1 口腔癌細胞株介紹……………………………………………………………..36 4-2動物模型介紹……………………………………………………………….......36 4-3 微脂體磷酸鈣 (Lipid calcium phosphate, LCP) 包覆藥物傳遞……………...37 4-4 siRNA序列………………………………………………………………………39 4-5 siRNA轉染細胞株實驗………………………………………………………....39 4-6 西方點墨法 (Western Blot)……………………………………………………40 4-6-1 蛋白質萃取………………………………………………………………...40 4-6-2 BCA protein assay…………………………………………………………..40 4-6-3 蛋白質電泳………………………………………………………………...41 4-6-4 西方點墨法………………………………………………………………...42 4-6-5 專一性抗體檢測…………………………………………………………...42 4-7 動物實驗………………………………………………………………..............43 4-8 血液生化分析………………………………………………………………......44 4-9 組織包埋與化學染色切片分析………………………………………………..45 4-11 免疫組織染色分析……………………………………………………………46 4-12微血管密度評估 (Microvessel density, MVD) ……………………….47 4-13 細胞存活率分析 (MTT assay) ……………………………………………….47 4-14 實驗統計資料分析……………………………………………………………48 第五章 實驗結果………………………..…..………………………………………...49 5-1 CoCl2細胞毒殺劑量與誘發HIF-1α蛋白質表現免疫分析……………...49 5-1-1 CoCl2細胞毒殺劑量…………………………………………..................49 5-1-2 CoCl2誘發HIF-1α蛋白質表現免疫分析……………………….…….......50 5-2 siRNA於SAS口腔癌細胞的細胞毒殺劑量測試……………………………...51 5-3 siRNA轉染SAS口腔癌細胞蛋白質西方點墨法分析實驗…………………..52 5-4 LCP微脂體包覆藥物粒徑與表面膜電位測定分析結果……………………..54 5-4-1 LCP微脂體包覆Control siRNA粒徑與表面膜電位測定分析結果………54 5-4-2 LCP微脂體包覆HIF-1α siRNA粒徑與表面膜電位測定分析結果.....55 5-4-3 LCP微脂體包覆EGFR siRNA粒徑與表面膜電位測定分析結果……56 5-4-4 LCP微脂體包覆HIF-1α & EGFR siRNA粒徑與表面膜電位測定分析結果…57 5-5 異種移植SAS口腔癌細胞之裸鼠腫瘤體積……………………………..…....58 5-6 異種移植SAS口腔癌細胞之裸鼠體重………………………….…...........60 5-7 異種移植SAS口腔癌細胞之裸鼠之肝、腎和腫瘤病理染色切片……61 5-8 異種移植SAS口腔癌細胞之裸鼠腫瘤免疫組織染色切片…………………63 5-8-1異種移植SAS口腔癌細胞之裸鼠腫瘤Ki-67免疫組織染色切片……......63 5-8-2異種移植SAS口腔癌細胞之裸鼠腫瘤Caspase 3免疫組織染色切片.....65 5-8-3異種移植SAS口腔癌細胞之裸鼠腫瘤CD31免疫組織染色切片...67 5-8-4異種移植SAS口腔癌細胞之裸鼠腫瘤HIF-1α免疫組織染色切片…69 5-8-5異種移植SAS口腔癌細胞之裸鼠腫瘤EGFR免疫組織染色切片………71 5-9 臨床血液生化分析……………………………………..…………………..........73 5-9-1 肝功能指數分析…………………………………………..………….........73 5-9-2 腎功能指數分析………………………………………………..…….........74 5-9-3 肝腎功能指數分析……………………………………………..…….........76 5-9-4 心肌功能指數分析…………………………………..…………………….78 第六章 結果討論……………………………………… ….......…………..………….79 6-1 LCP微脂體包覆藥物粒徑與表面膜電位測定分析結果……………….79 6-2 CoCl2細胞毒殺劑量與誘發HIF-1α蛋白質表現免疫分析………….80 6-3 siRNA於SAS口腔癌細胞的細胞毒殺劑量測試…………………….80 6-4 siRNA轉染SAS口腔癌細胞蛋白質西方點墨法分析實驗……………….81 6-5 異種移植SAS口腔癌細胞之裸鼠腫瘤體積…………………....82 6-6 異種移植SAS口腔癌細胞之裸鼠體重…………...…………..………….....83 6-7 異種移植SAS口腔癌細胞之裸鼠之肝、腎和腫瘤病理染色切片………83 6-8 異種移植SAS口腔癌細胞之裸鼠腫瘤免疫組織染色切片………….…….84 6-9 臨床血液生化分析………………………………………….………........…….84 第七章 結論……....…………..…………………....…………..………..……….……86 參考資料.……………………..……………....……………………………………87 | |
dc.language.iso | zh-TW | |
dc.title | 新穎微脂體 Lipid calcium phosphate組合siRNA下調HIF-1α與EGFR癌化基因治療之口腔癌研究 | zh_TW |
dc.title | Novel liposomal Lipid calcium phosphate combined with siRNA for knockdown of HIF-1α and EGFR genes in oral cancer treatment | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-1 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 許毅芝 | |
dc.contributor.oralexamcommittee | 江俊斌 | |
dc.subject.keyword | 口腔癌,脂質磷酸鈣,DOPA,缺氧誘導因子-1α,上皮生長因子受體,微小干擾RNA, | zh_TW |
dc.subject.keyword | Oral cancer,Lipid calcium phosphate,DOPA,Hypoxia-inducible factor-1α,Epidermal growth factor receptor,Small interference RAN, | en |
dc.relation.page | 99 | |
dc.identifier.doi | 10.6342/NTU202000476 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-02-17 | |
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-108-1.pdf 目前未授權公開取用 | 5.49 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。