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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 郭彥彬 | zh_TW |
| dc.contributor.advisor | Mark Yen-Ping Kuo | en |
| dc.contributor.author | 呂怡潔 | zh_TW |
| dc.contributor.author | Yi-Jie Lu | en |
| dc.date.accessioned | 2024-02-20T16:23:41Z | - |
| dc.date.available | 2024-02-21 | - |
| dc.date.copyright | 2024-02-20 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-11-30 | - |
| dc.identifier.citation | 1. Parkin, D. M., Pisani, P., & Ferlay, J. (1990). Estimates of the worldwide incidence of 25 major cancers in 1990. International Journal of Cancer, 80(6), 827–841.
2. Wong, Y. K., Tsai, W. C., Lin, J. C., et al. (2006). Socio-demographic factors in the prognosis of oral cancer patients. Oral Oncology, 42(9), 893-906. 3. Carvalho, A. L., Nishimoto, I. N., Califano, J.A., et al. (2005). Trends in incidence and prognosis for head and neck cancer in the United States: A site-specific analysis of the SEER database. International Journal of Cancer, 114(5), 806-816. 4. Ramadas, K., Sankaranarayanan, R., Jacob, B. J., et al. (2003). Interim results from a cluster randomized controlled oral cancer screening trial in Kerala, India. Oral Oncology, 39(6), 580-588. 5. Jané-Salas, E., Chimenos-Küstner, E., López-López, J., et al. (2003). Importance of diet in the prevention of oral cancer. Med Oral, 8(4), 260-268. 6. Young, I. S. (2000). National health research institute forum: epidemiological studies on areca quid and oral cancer. Taipei, Taiwan: National Health Research Institute. 7. Lin, W. J., Jiang, R. S., Wu, S. H., et al. (2011). Smoking, alcohol, and betel quid and oral cancer: A prospective cohort study. Journal of Oncology, 2011, 525976. 8. Lu, C. T., Yen, Y. Y., Ho, C. S., et al. (1996). A case-control study of oral cancer in Changhua County, Taiwan. Journal of Oral Pathology & Medicine, 25, 245-248. 9. Liu, Y., Li, Y., Fu, Y., et al. (2017). Quantitative prediction of oral cancer risk in patients with oral leukoplakia. Oncotarget, 8(28), 46057-46064. 10. van der Waal, I. (2014). Oral potentially malignant disorders: Is malignant transformation predictable and preventable? Medicina Oral Patologia Oral y Cirugia Bucal, 19(4), e386-90. 11. Cervigne, N. K., Machado, J., Goswami, R.S., et al. (2014). Recurrent genomic alterations in sequential progressive leukoplakia and oral cancer: Drivers of oral tumorigenesis? Human Molecular Genetics, 23(10), 2618-28. 12. Lee, J. J., Hung, H. C., Cheng, S. J., et al. (2006). Carcinoma and dysplasia in oral leukoplakias in Taiwan: Prevalence and risk factors. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, 101(4), 472 13. Chau, L., Thng, S., Goh, B., et al. (2017). Topical agents for oral cancer chemoprevention: A systematic review of the literature. Oral Oncology, 67, 153-159. 14. Wong, T., & Wiesenfeld, D. (2018). Oral Cancer. Australian Dental Journal, 63(Suppl 1), S91-S99. 15. Kim, S. R., Lee, E. Y., Kim, D. J., et al. (2020). Quercetin inhibits cell survival and metastatic ability via the EMT-mediated pathway in oral squamous cell carcinoma. Molecules, 25(3). 16. Chau, L., Thng, S., Goh, B., et al. (2017). Topical agents for oral cancer chemoprevention: A systematic review of the literature. Oral Oncology, 67, 153-159. 17. Omura, K. (2014). Current status of oral cancer treatment strategies: Surgical treatments for oral squamous cell carcinoma. International Journal of Clinical Oncology, 19(3), 423-430. 18. Montero, P. H., & Patel, S. G. (2015). Cancer of the oral cavity. Surgical Oncology Clinics of North America, 24(3), 491-508. 19. Kumar, M., Nanavati, R., Modi, T. G., et al. (2016). Oral cancer: Etiology and risk factors: A review. Journal of Cancer Research and Therapeutics, 12(2), 458-463. 20. Lin, Y. H., Yen, M. C., Lin, Y. W., et al. (2020). Anti-p53 autoantibody detection in automatic glass capillary immunoassay platform for screening of oral cavity squamous cell carcinoma. Sensors (Basel), 20(4). 21. Han, S., Xuan, Y., Liu, S., et al. (2020). Co-expression of HIF-1 and TLR3 is associated with poor prognosis in oral squamous cell carcinoma. International Journal of Clinical and Experimental Pathology, 13(1), 65-72. 22. Warnakulasuriya, S. (2010). Living with oral cancer: Epidemiology with particular reference to prevalence and lifestyle changes that influence survival. Oral Oncology, 46(6), 407-410. 23. Rooban, T., Joshua, E., Rooban, A., et al. (2005). Health hazards of chewing arecanut and products containing arecanut. Calicut Medical Journal, 3, e3. 24. Bhisey, R. A., Boucher, B. J., Chen, T. H., et al. (2004). IARC working group on the evaluation of carcinogenic risk to humans: Betelquid and Arecanut chewing and some Arecanut-derived nitrosamines. Lyon: IARC Press. 25. Wazir, S. S., Arora, P., Kapoor, S., et al. (2017). Prevalence of areca nut chewing habit among high school children of Parsa district of Nepal. Journal of Oral Biology and Craniofacial Research, 7(3), 161-166. 26. Nagesh, R., Kiran Kumar, K. M., Naveen Kumar, M., et al. (2017). Aqueous areca nut extract induces oxidative stress in human lung epithelial A549 cells: Probable role of p21 in inducing cell death. Gene Reports, 6, 103-111. 27. Shah, G., Chaturvedi, P., & Vaishampayan, S. (2012). Arecanut as an emerging etiology of oral cancers in India. Indian Journal of Medical and Paediatric Oncology, 33(2), 71-79. 28. Garg, A., Chaturvedi, P., Gupta, P. C. (2014). A review of the systemic adverse effects of areca nut or betel nut. Indian Journal of Medical and Paediatric Oncology, 35(1), 3-9. 29. IARC. (2004). Betel-quid and areca-nut chewing and some areca-nut-derived nitrosamines. In IARC (Ed.), IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Summary of Data Reported and Evaluation, Vol. 85 (pp. 1-14). Lyon, France: IARC Press. 30. Ji, W.-T., Chen, H.-R., Lin, Y.-H., et al. (2014). Monocyte chemotactic protein 1 (MCP-1) modulates pro-survival signaling to promote progression of head and neck squamous cell carcinoma. PLoS One, 9(2), e88952. 31. Nair, U. J., Obe, G., Friesen, M., Goldberg, M. T., et al. (1992). Role of Lime in the Generation of Reactive Oxygen Species from Betel-Quid Ingredients. Environmental Health Perspectives, 98, 203-205. 32. Hsieh, Y. P., Chen, H. M., Li, Y. C., et al. (2018). Arecoline activates latent transforming growth factor β1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate. Journal of the Formosan Medical Association, 117(6), 527-534. 33. Prabhu, R. V., Prabhu, V., Chatra, L., et al. (2014). Areca nut and its role in oral submucous fibrosis. Journal of Clinical and Experimental Dentistry, 6(5), e569-e575. 34. Hosein, M., Mohiuddin, S., Fatima, N. (2015). Association between grading of oral submucous fibrosis with frequency and consumption of areca nut and its derivatives in a wide age group: A multi-centric cross-sectional study from Karachi, Pakistan. Journal of Cancer Prevention, 20(3), 216-222. 35. Utsunomiya, H., Tilakaratne, W. M., Oshiro, K., et al. (2005). Extracellular matrix remodeling in oral submucous fibrosis: Its stage-specific modes revealed by immunohistochemistry and in situ hybridization. Journal of Oral Pathology & Medicine, 34(8), 498-507. 36. Tilakaratne, W. M., Klinikowski, M. F., Saku, T., et al. (2006). Oral submucous fibrosis: Review on etiology and pathogenesis. Oral Oncology, 42(6), 561-568. 37. Arakeri, G., Brennan, P. A. (2013). Oral submucous fibrosis: An overview of the etiology, pathogenesis, classification, and principles of management. British Journal of Oral and Maxillofacial Surgery, 51(7), 587-593. 38. Lee, S. S., Tsai, C. H., Yu, C. C., et al. (2013). Snail expression mediates tumor progression in areca quid chewing-associated oral squamous cell carcinoma via reactive oxygen species. PLoS One, 8(7), e67985. 39. Radisky, D. C., Levy, D. D., Littlepage, L. E., et al. (2005). Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature, 436(7047), 123-127. 40. Wang, T. Y., Chen, B. F., Yang, Y. C., et al. (2016). Acquisition cancer stemness, mesenchymal transdifferentiation, and chemoresistance properties by chronic exposure of oral epithelial cells to arecoline. Oncotarget, 7(51), 84072-84081. 41. Peiris-Pagès, M., Martinez-Outschoorn, U. E., Pestell, R. G., et al. (2016). Cancer stem cell metabolism. Breast Cancer Research, 18(1), 55. 42. Delaney, K., Kasprzycka, P., Ciemerych, M. A., et al. (2017). The role of TGF-β1 during skeletal muscle regeneration. Cell Biology International, 41(7), 706-715. 43. Xie, F., Xu, M., Lu, J., et al. (2018). TGF-β signaling in cancer metastasis. Acta Biochimica et Biophysica Sinica (Shanghai), 50(1), 121-132. 44. Derynck, R., Zhang, Y. E. (2003). Smad-dependent and Smad-independent pathways in TGF-beta family signaling. Nature, 425(6958), 577-584. 45. Zhang, Y. E. (2017). Non-Smad signaling pathways of the TGF-β family. Cold Spring Harbor Perspectives in Biology, 9(2). 46. Gatza, C. E., Oh, S. Y., Blobe, G. C. , et al. (2011). Type III TGF-beta receptor enhances colon cancer cell migration and anchorage-independent growth. Neoplasia, 13(8), 758-770. 47. Gonzalez-Santiago, A. E., Vargas-Roig, L. M., Cuello-Carrion, F. D. , et al. (2011). TGF-beta1 serum concentration as a complementary diagnostic biomarker of lung cancer: establishment of a cut-point value. Journal of Clinical Laboratory Analysis, 25(4), 238-243. 48. Xu, J., Lamouille, S., Derynck, R. (2009). TGF-beta-induced epithelial to mesenchymal transition. Cell Research, 19(2), 156-172. 49. Karcher, J., Stumm, G., Wilke, M. (1999). Cytokine expression of transforming growth factor-beta2 and interleukin-10 in squamous cell carcinomas of the head and neck. Comparison of tissue expression and serum levels. HNO, 47(10), 879-884. 50. Yang, L., Pang, Y., Moses, H. L. (2010). TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends in Immunology, 31(6), 220-227. 51. Wen, B., Xu, L. Y., Li, E. M. (2020). LOXL2 in cancer: regulation, downstream effectors and novel roles. Biochimica et Biophysica Acta Reviews on Cancer, 1874, 188435. 52. Ye, M., Song, Y., Pan, S. (2020). Evolving roles of lysyl oxidase family in tumorigenesis and cancer therapy. Pharmacology & Therapeutics, 215, 107633. 53. Li, T., Wu, C., Gao, L., et al. (2018). Lysyl oxidase family members in urological tumorigenesis and fibrosis. Oncotarget, 9(28), 20156-20164. 54. Rosenbloom, J., Ren, S., Macarak, E. (2016). New frontiers in fibrotic disease therapies: The focus of the Joan and Joel Rosenbloom Center for Fibrotic Diseases at Thomas Jefferson University. Matrix Biology, 51, 14-25. 55. Barker, H. E., Cox, T. R., Erler, J. T. (2012). The rationale for targeting the LOX family in cancer. Nature Reviews Cancer, 12, 540-552. 56. Levental, K. R., Yu, H., Kass, L., et al. (2009). Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell, 139, 891-906. 57. Moon, H. J., Finney, J., Ronnebaum, T., Mure, M. (2014). Human lysyl oxidase-like 2. Bioorganic Chemistry, 57, 231-241. 58. Barker, H. E., Chang, J., Cox, T. R., Lang, et al. (2011). LOXL2-mediated matrix remodeling in metastasis and mammary gland involution. Cancer Research, 71(5), 1561-1572. 59. Weidenfeld, K., Schif-Zuck, S., Abu-Tayeh, H., et al. (2016). Dormant tumor cells expressing LOXL2 acquire a stem-like phenotype mediating their transition to proliferative growth. Oncotarget, 7, 71362. 60. Liu, Y., Zhang, Y. B., Liu, T. K., et al. (2013). Lineage-specific expansion of IFIT gene family: An insight. 61. Schoggins, J. W., Wilson, S. J., Panis, M., Murphy, et al. (2011). A diverse range of gene products are effecto 62. Daugherty, M. D., Schaller, A. M., Geballe, A. P., et al. (2016). Evolution-guided functional analyses reveal diverse antiviral specificities encoded by ifit1 genes in mammals. Elife, 5, e14228. 63. Diamond, M. S., Farzan, M. (2013). The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nature Reviews Immunology, 13(1), 46-57. 64. Yang, Y. Y., Zhou, Y., Hou, J., et al. (2017). Hepatic IFIT3 predicts interferon-alpha therapeutic response in patients of hepatocellular carcinoma. Hepatology, 66(1), 152-166. 65. Zhao, Y., Altendorf-Hofmann, A., Pozios, I., et al. (2017). Elevated interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) is a poor prognostic marker in pancreatic ductal adenocarcinoma. Journal of Cancer Research and Clinical Oncology, 143(6), 1061-1068. 66. Yang, J. L., Qu, X. J., Hayes, V. M., , et al. (2007). Erlotinib (OSI-774)-induced inhibition of transitional cell carcinoma of bladder cell line growth is enhanced by interferon-alpha. BJU International, 99, 1539-1545. 67. Yang, J. L., Qu, X. J., Russell, P. J., et al. (2005). Interferon-alpha promotes the anti-proliferative effect of Erlotinib (OSI-774) on human colon cancer cell lines. Cancer Letters, 225, 61-74. 68. Bruzzese, F., Di Gennaro, E., Avallone, et al. (2006). Synergistic antitumor activity of epidermal growth factor receptor tyrosine kinase inhibitor gefitinib and IFN-alpha in head and neck cancer cells in vitro and in vivo. Clinical Cancer Research, 12, 617-625. 69. Cheon, H., Borden, E. C., Stark, G. R. (2014). Interferons and their stimulated genes in the tumor microenvironment. Seminars in Oncology, 41, 156-173. 70. Danish, H. H., Goyal, S., Taunk, N. K., et al. (2013). Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) as a prognostic marker for local control in T1-2 N0 breast cancer treated with breast-conserving surgery and radiation therapy (BCS+RT). Breast Journal, 19, 231-239. 71. Yang, Y., Zhou, Y., Hou, J., et al. (2017). Hepatic IFIT3 predicts interferon-alpha therapeutic response in patients of hepatocellular carcinoma. Hepatology, 66, 152-166. 72. Pidugu, V. K., Pidugu, H. B., Wu, M. M., et al. (2019). Emerging Functions of Human IFIT Proteins in Cancer. Frontiers in Molecular Biosciences, 6, 148. 73. Li, H., Yang, L. L., Wu, C. C., et al. (2020). Expression and Prognostic Value of IFIT1 and IFITM3 in Head and Neck Squamous Cell Carcinoma. American Journal of Clinical Pathology, 153(5), 618-629. 74. Pidugu, V. K., Wu, M. M., Yen, A. H., et al. (2019). IFIT1 and IFIT3 promote oral squamous cell carcinoma metastasis and contribute to the anti-tumor effect of gefitinib via enhancing p-EGFR recycling. Oncogene, 38(17), 3232-3247. 75. Thiery, J. P., Sleeman, J. P. (2006). Complex networks orchestrate epithelial-mesenchymal transitions. Nature Reviews Molecular Cell Biology, 7(2), 131-142. 76. Thiery, J. P., Acloque, H., Huang, R. Y.,et al. (2009). Epithelial-mesenchymal transitions in development and disease. Cell, 139(5), 871-890. 77. Lamouille, S., Xu, J., Derynck, R. (2014). Molecular mechanisms of epithelial-mesenchymal transition. Nature Reviews Molecular Cell Biology, 15(3), 178-196. 78. Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin. Br Foreign Med Chir Rev, 1861, 27(53), 52-65. 79. Kreso, A., Dick, J. E. (2014). Evolution of the cancer stem cell model. Cell Stem Cell, 14(3), 275-291. 80. Brooks, M. D., Burness, M. L., Wicha, M. S. (2015). Therapeutic implications of cellular heterogeneity and plasticity in breast cancer. Cell Stem Cell, 17(3), 260-271. 81. Peiris-Pagès, M., Martinez-Outschoorn, U. E., Pestell, R. G., et al. (2016). Cancer stem cell metabolism. Breast Cancer Research, 18(1), 55. 82. Hu, J., Mirshahidi, S., Simental, A., et al. (2019). Cancer stem cell self-renewal as a therapeutic target in human oral cancer. Oncogene, 38(27), 5440-5456. 83. Mittal, V. (2018). Epithelial mesenchymal transition in tumor metastasis. Annual Review of Pathology, 13, 395-412. 84. Zhu, L. F., Hu, Y., Yang, C. C., et al. (2012). Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells. Laboratory Investigation, 92, 744-752. 85. Pidugu, V. K., Wu, M. M., Yen, A. H., et al. (2019). IFIT1 and IFIT3 promote oral squamous cell carcinoma metastasis and contribute to the anti-tumor effect of gefitinib via enhancing p-EGFR recycling. Oncogene, 38, 3232-3247. 86. Bharti, A., Urs, A. B., Kumar, P. (2021). Significance of HIF-1α Expression and LOXL-2 Localization in Progression of Oral Squamous Cell Carcinoma. Asian Pacific Journal of Cancer Prevention, 22, 341. 87. Zou, H., Wen, B., Li, R. L., et al. (2020). Lysyl oxidase-like 2 promotes esophageal squamous cell carcinoma cell migration independent of catalytic activity. International Journal of Biochemistry & Cell Biology, 125, 105795. 88. Almacellas-Rabaiget, O., Monaco, P., Huertas-Martinez, J., et al. (2020). LOXL2 promotes oncogenic progression in alveolar rhabdomyosarcoma independently of its catalytic activity. Cancer Letters, 474, 1-14. 89. Peinado, H., Del Carmen Iglesias-de la Cruz, M., Olmeda, D., et al. (2005). A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. The EMBO Journal, 24, 3446-3458. 90. Borden, E. C., Williams, B. R. (2011). Interferon-stimulated genes and their protein products: what and how? Journal of Interferon & Cytokine Research, 31(1), 1-4. 91. Madshus, I. H., Stang, E. (2009). Internalization and intracellular sorting of the EGF receptor: a model for understanding the mechanisms of receptor trafficking. Journal of Cell Science, 122, 3433-3439. 92. Tian, Y., Lin, J., Tian, Y., et al. (2018). Efficacy and safety of anti-EGFR agents administered concurrently with standard therapies for patients with head and neck squamous cell carcinoma: A systematic review and meta-analysis of randomized controlled trials. International Journal of Cancer, 142, 2198-2206. 93. Yamaoka, T., Ohba, M., Ohmori, T. (2017). Molecular-targeted therapies for epidermal growth factor receptor and its resistance mechanisms. International Journal of Molecular Sciences, 18, 2420. 94. Chang, J., Nicolau, M. M., Cox, T. R., et al. (2013). LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling. Breast Cancer Research, 15, 1-18. 95. Jiao, J. W., Zhan, X. H., Wang, J. J., et al. (2022). LOXL2-dependent deacetylation of aldolase A induces metabolic reprogramming and tumor progression. Redox biology, 57, 102496. 96. Peng, L., Ran, Y. L., Hu, H., et al. (2009). Secreted LOXL2 is a novel therapeutic target that promotes gastric cancer metastasis via the Src/FAK pathway. Carcinogenesis, 30(10), 1660–1669. 97. Vermorken, J. B., Trigo, J., Hitt, R., et al. (2007). Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 25(16), 2171–2177. 98. Huang, S. F., Chien, H. T., Cheng, S. D. , et al. (2017). EGFR copy number alterations in primary tumors, metastatic lymph nodes, and recurrent and multiple primary tumors in oral cavity squamous cell carcinoma. BMC cancer, 17(1), 592. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91652 | - |
| dc.description.abstract | 根據衛生福利部110年統計，口腔癌居臺灣男性十大癌症中發生年齡最年輕的。也是死亡年增率最高的癌症。儘管不斷有新的治療方法，由於癌細胞發展出轉移能力及治療抗性。口腔癌病人的五年存活率只有45-50 %。離胺基氧化酶樣蛋白2 (lysyl oxidase-like 2; LOXL2)是LOX家族的一種胺基氧化酶。最近研究發現細胞內LOXL2可誘導上皮細胞間質轉化(EMT)及幹細胞特性，可使癌細胞具侵襲與轉移作用。其作用機轉隨不同細胞而不同。但LOXL2蛋白表現與口腔癌癌化過程，機轉及癌幹細胞的關係， 先前尚未有學者發表。本研究先將LOXL2 cDNA的質體送入內生性LOXL2蛋白表現量低的人類口腔癌細胞株TW2.6 和下咽FaDu細胞株。結果顯示，TW2.6及FaDu高表現LOXL2蛋白(TW2.6/LOXL2，FaDu/LOXL2)時，會造成癌細胞生長速度加快，移動及侵襲的能力增強。並可誘導上皮-間葉細胞轉化轉錄因子Snail1，Slug，Twist1 及間質型標記蛋白 N-cadherin 和 Vimentin增加，上皮型標記蛋白E-cadherin減少。亦可誘導誘導TW2.6及 FaDu細胞產生癌幹細胞的特性，例如增加形成癌症聚球體(sphere)的能力，增加幹細胞特性蛋白CD133， CD44，Klf4 ，OCT4， SOX2 和 Nanog 的表現。以siLOXL2 RNA剔除SAS癌症細胞聚球體中LOXL2表現，可以抑制形成癌症聚球體的能力，使聚球體細胞減少。並抑制SAS聚球體幹細胞特性蛋白的表現。免疫缺陷SCID鼠異種移植(xenograft)研究發現，TW2.6/LOXL2比TW2.6及較易形成腫瘤，形成的腫瘤也比較大。使用基因表現微陣列晶片比較高表現LOXL2 的TW2.6及FaDu細胞株與對照組細胞株的基因表現差異，找到下游分子為IFIT1 (Interferon-induced protein with tetratricopeptide repeats 1) 及IFIT3。以IFIT1 及IFIT3 shRNA 分別刪除TW2.6-LOXL2的IFIT1 及IFIT3表現，可抑制 LOXL2誘導的EMT 標記蛋白和幹細胞標記蛋白表現。 口腔鱗狀細胞癌檢體中LOXL2蛋白的表現量與IFIT1 及IFIT3蛋白的表現量呈正相關。值得注意的是，當LOXL2過度表現增加了TW2.6 和FaDu細胞中p-EGFR Y1068 的表現。以EGPR抑制劑Gefitinib藥物，處理TW2.6/LOXL2 和FaDu/LOXL2細胞，相較於TW2.6/Vector 和FaDu/Vector細胞，對於藥物有較敏感的反應。在動物實驗中，也發現Gefitinib對TW2.6/LOXL2的抗腫瘤作用比TW2.6/Vector高 4 倍。LOXL2過度表現增加增強了吉非替尼的腫瘤抑制作用。 LOXL2過度表現可作辨識患者對於EGFR標靶治療的效用。 | zh_TW |
| dc.description.abstract | Despite substantial progress in the detecting and treating head and neck squamous cell carcinoma (HNSCC), the ongoing challenges in overcoming recurrence or metastasis warrant new strategies to improve overall patient survival. Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has recently been identified as an important regulator of tumor progression and metastasis. However, the mechanisms by which LOXL2 affects head and neck cancer are not thoroughly understood. This study found LOXL2-overexpressing buccal SCC TW2.6 cells exhibited enhanced proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC)-phenotypes and significantly increased tumor initiating frequency in SCID mice. LOXL2 increased the levels of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), IFIT3 and phospho-EGFR-Y1086 in LOXL2-overexpressing TW2.6 and hypopharyngeal SCC FaDu cells. IFIT1 and IFIT3 are key downstream components of LOXL2 action in migration, invasion, EMT, and CSC-phenotypes in TW2.6 and FaDu cells. Furthermore, a significant positive correlation between LOXL2 expression and IFIT1 and IFIT3 overexpression in human oral SCC tissues was observed. In addition, LOXL2-overexpressing TW2.6 and FaDu cells were 3.3- to 3.6-fold more susceptible to the EGFR inhibitor gefitinib than were their respective controls. The anti-tumor effect of gefitinib on orthotopic TW2.6/LOXL2 xenograft tumor was 4-fold higher than that on controls. Our results indicate that LOXL2 may be used as a marker to identify patients most likely to respond to EGFR-targeted therapy. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-02-20T16:23:41Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-02-20T16:23:41Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract v 目錄 vi 圖與表目錄 ix 第一章、研究背景與文獻回顧 1 1.1 口腔癌和其健康問題 (Health issue of Oral cancer) 1 1.2 檳榔鹼 (Arecoline) 2 1.3 Transforming growth factor-β1 (TGF-β1) 3 1.4 賴氨酰氧化酶樣蛋白 2（lysyl oxidase-like protein-2, LOXL2） 4 1.5 Interferon-induced protein with tetratricopeptide repeats 6 1.6 上皮間質轉化和癌幹細胞 （Epithelial-Mesenchymal Transition, EMT and Cancer Stem Cell, CSC） 7 1.7吉非替尼（Gefitinib） 8 第二章、研究動機與目的 9 第三章、實驗材料與方法 10 3.1 實驗材料 10 3.2 實驗方法 13 3.2.1 患者與組織 （Patients and tissues） 13 3.2.2 切片染色 （Immunostaining） 13 3.2.3 細胞繼代與培養（Cell culture） 14 3.2.4 蛋白質萃取和BCA蛋白質定量（Protein extraction and BCA quantification） 14 3.2.5 西方墨點法（Western Blot） 15 3.2.6 細胞增生速率測試和存活率試驗 （Cell proliferation and viability） 16 3.2.7 遷移性和侵襲性試驗（Migration and Invasion） 16 3.2.8 聚球體形成試驗 （Sphere forming） 17 3.2.9 基因過表現和剔除 (Overexpression and knockdown gene) 17 3.2.10 動物實驗（Animal studies） 18 3.2.11 微陣列分析（Microarray assay） 18 3.2.12 統計分析 （Statistical analysis） 19 第四章、實驗結果 20 4.1 LOXL2 過表現和剔除之OSCC細胞株生長能力之改變 20 4.2 LOXL2過表現誘導HNSCC細胞的移動及侵襲能力和EMT markers蛋白表現 20 4.3 TW2.6/LOXL2、FaDu/LOXL2 之移動及侵襲能力和EMT markers蛋白表現與其離胺基氧化酶活性無關 21 4.4 LOXL2 透過Snail路徑增強HNSCC細胞的形成聚球體之能力和癌幹細胞特性蛋白表現但與其離胺基氧化酶活性無關 22 4.5 LOXL2 過表現增加了 OSCC腫瘤的大小、腫瘤起始頻率 tumor-initiating frequency (TIF)和EMT、Cancer stemness相關表現 23 4.6 IFIT1和IFIT3介導的HNSCC細胞的移動及侵襲能力、EMT markers和癌幹細胞特性蛋白表現 24 4.7 OSCC中IFIT1和IFIT3的表現與LOXL2表現呈正相關 24 4.8 LOXL2過IFIT1和IFIT3增加EGFR的表現量及gefitinib對HNSCC的抗腫瘤效果 25 第五章、討論與結論 27 圖與表 30 參考文獻 75 附錄 86 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 口腔鱗狀細胞癌 | zh_TW |
| dc.subject | 離胺基氧化酶樣蛋白2 | zh_TW |
| dc.subject | 上皮細胞間質轉化 | zh_TW |
| dc.subject | 癌幹細胞 | zh_TW |
| dc.subject | 表皮生長因子受體 | zh_TW |
| dc.subject | IFIT1 | zh_TW |
| dc.subject | IFIT3 | zh_TW |
| dc.subject | Gefitinib | zh_TW |
| dc.subject | interferon-induced protein with tetratricopeptide repeats 3 | en |
| dc.subject | Lysyl oxidase-like 2 | en |
| dc.subject | cancer stem cells | en |
| dc.subject | interferon-induced protein with tetratricopeptide repeats 1 | en |
| dc.subject | gefitinib. | en |
| dc.title | LOXL2通過IFIT1和IFIT3促進頭頸癌癌幹細胞特性並增強吉非替尼的抗腫瘤作用 | zh_TW |
| dc.title | LOXL2 promotes stemness and enhances anti-tumor effects of gefitinib in head and neck cancer via IFIT1 and IFIT3 | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-1 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.coadvisor | 鄭世榮 | zh_TW |
| dc.contributor.coadvisor | Shih-Jung Cheng | en |
| dc.contributor.oralexamcommittee | 周涵怡;張國威;張育超 | zh_TW |
| dc.contributor.oralexamcommittee | Han-Yi Chou;Kuo-Wei Chang;Yu-Chao Chang | en |
| dc.subject.keyword | 口腔鱗狀細胞癌,離胺基氧化酶樣蛋白2,上皮細胞間質轉化,癌幹細胞,表皮生長因子受體,IFIT1,IFIT3,Gefitinib, | zh_TW |
| dc.subject.keyword | Lysyl oxidase-like 2,cancer stem cells,interferon-induced protein with tetratricopeptide repeats 1,interferon-induced protein with tetratricopeptide repeats 3,gefitinib., | en |
| dc.relation.page | 86 | - |
| dc.identifier.doi | 10.6342/NTU202304389 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-11-30 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 口腔生物科學研究所 | - |
| Appears in Collections: | 口腔生物科學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-112-1.pdf Restricted Access | 55.63 MB | Adobe PDF |
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