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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 郭彥彬(Mark Yen-Ping Kuo) | |
dc.contributor.author | Chia-Ting Huang | en |
dc.contributor.author | 黃家鼎 | zh_TW |
dc.date.accessioned | 2021-06-08T05:23:49Z | - |
dc.date.copyright | 2005-08-02 | |
dc.date.issued | 2005 | |
dc.date.submitted | 2005-07-25 | |
dc.identifier.citation | Al Moustafa, A. E., Alaoui-Jamali, M. A., Batist, G., Hernandez-Perez, M., Serruya, C., Alpert, L., Black, M. J., Sladek, R., and Foulkes, W. D. (2002). Identification of genes associated with head and neck carcinogenesis by cDNA microarray comparison between matched primary normal epithelial and squamous carcinoma cells. Oncogene 21, 2634-2640.
Alevizos, I., Mahadevappa, M., Zhang, X., Ohyama, H., Kohno, Y., Posner, M., Gallagher, G. T., Varvares, M., Cohen, D., Kim, D., et al. (2001). Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysis. Oncogene 20, 6196-6204. Almadori, G., Paludetti, G., Cerullo, M., Ottaviani, F., and D'Alatri, L. (1990). Marijuana smoking as a possible cause of tongue carcinoma in young patients. J Laryngol Otol 104, 896-899. Alonso, L., and Fuchs, E. (2003). Stem cells of the skin epithelium. Proc Natl Acad Sci U S A 100 Suppl 1, 11830-11835. Ang, K. K., Berkey, B. A., Tu, X., Zhang, H. Z., Katz, R., Hammond, E. H., Fu, K. K., and Milas, L. (2002). Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62, 7350-7356. Barrandon, Y., Morgan, J. R., Mulligan, R. C., and Green, H. (1989). Restoration of growth potential in paraclones of human keratinocytes by a viral oncogene. Proc Natl Acad Sci U S A 86, 4102-4106. Bedi, G. C., Westra, W. H., Gabrielson, E., Koch, W., and Sidransky, D. (1996). Multiple head and neck tumors: evidence for a common clonal origin. Cancer Res 56, 2484-2487. Berg, J. W., Schottenfeld, D., and Ritter, F. (1970). Incidence of multiple primary cancers. III. Cancers of the respiratory and upper digestive system as multiple primary cancers. J Natl Cancer Inst 44, 263-274. Bova, R. J., Quinn, D. I., Nankervis, J. S., Cole, I. E., Sheridan, B. F., Jensen, M. J., Morgan, G. J., Hughes, C. J., and Sutherland, R. L. (1999). Cyclin D1 and p16INK4A expression predict reduced survival in carcinoma of the anterior tongue. Clin Cancer Res 5, 2810-2819. Braakhuis, B. J., Tabor, M. P., Kummer, J. A., Leemans, C. R., and Brakenhoff, R. H. (2003). A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 63, 1727-1730. Burns, J. E., Baird, M. C., Clark, L. J., Burns, P. A., Edington, K., Chapman, C., Mitchell, R., Robertson, G., Soutar, D., and Parkinson, E. K. (1993). Gene mutations and increased levels of p53 protein in human squamous cell carcinomas and their cell lines. Br J Cancer 67, 1274-1284. Chow, V., Yuen, A. P., Lam, K. Y., Tsao, G. S., Ho, W. K., and Wei, W. I. (2001). A comparative study of the clinicopathological significance of E-cadherin and catenins (alpha, beta, gamma) expression in the surgical management of oral tongue carcinoma. J Cancer Res Clin Oncol 127, 59-63. Coto, H., and Thomas, E. (1981). Snuff dipping and oral cancer. N Engl J Med 305, 230-231. Delilbasi, C. B., Okura, M., Iida, S., and Kogo, M. (2004). Investigation of CXCR4 in squamous cell carcinoma of the tongue. Oral Oncol 40, 154-157. Edington, K. G., Loughran, O. P., Berry, I. J., and Parkinson, E. K. (1995). Cellular immortality: a late event in the progression of human squamous cell carcinoma of the head and neck associated with p53 alteration and a high frequency of allele loss. Mol Carcinog 13, 254-265. Estilo, C. L., P, O. C., Ngai, I., Patel, S. G., Reddy, P. G., Dao, S., Shaha, A. R., Kraus, D. H., Boyle, J. O., Wong, R. J., et al. (2003). The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the oral tongue. Clin Cancer Res 9, 2300-2306. Ficarra, G. (1989). [Human papilloma virus and pathology of the oral cavity]. Dent Cadmos 57, 82-86, 89-90, 93. Fu, K. K., Pajak, T. F., Trotti, A., Jones, C. U., Spencer, S. A., Phillips, T. L., Garden, A. S., Ridge, J. A., Cooper, J. S., and Ang, K. K. (2000). A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48, 7-16. Gallo, O., Santucci, M., and Franchi, A. (1997). Cumulative prognostic value of p16/CDKN2 and p53 oncoprotein expression in premalignant laryngeal lesions. J Natl Cancer Inst 89, 1161-1163. Geisler, S. A., Olshan, A. F., Weissler, M. C., Cai, J., Funkhouser, W. K., Smith, J., and Vick, K. (2002). p16 and p53 Protein expression as prognostic indicators of survival and disease recurrence from head and neck cancer. Clin Cancer Res 8, 3445-3453. Gonzalez-Moles, M. A., Bravo, M., Ruiz-Avila, I., Esteban, F., Rodriguez-Archilla, A., Gonzalez-Moles, S., and Arias, B. (2003). Adhesion molecule CD44 as a prognostic factor in tongue cancer. Anticancer Res 23, 5197-5202. Hashibe, M., Ford, D. E., and Zhang, Z. F. (2002). Marijuana smoking and head and neck cancer. J Clin Pharmacol 42, 103S-107S. Herbig, U., Jobling, W. A., Chen, B. P., Chen, D. J., and Sedivy, J. M. (2004). Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14, 501-513. Holt, S. E., Wright, W. E., and Shay, J. W. (1996). Regulation of telomerase activity in immortal cell lines. Mol Cell Biol 16, 2932-2939. Hong, W. K., Endicott, J., Itri, L. M., Doos, W., Batsakis, J. G., Bell, R., Fofonoff, S., Byers, R., Atkinson, E. N., Vaughan, C., and et al. (1986). 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med 315, 1501-1505. Hong, W. K., Lippman, S. M., Itri, L. M., Karp, D. D., Lee, J. S., Byers, R. M., Schantz, S. P., Kramer, A. M., Lotan, R., Peters, L. J., and et al. (1990). Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323, 795-801. Hong, W. K., and Sporn, M. B. (1997). Recent advances in chemoprevention of cancer. Science 278, 1073-1077. Horiot, J. C., Bontemps, P., van den Bogaert, W., Le Fur, R., van den Weijngaert, D., Bolla, M., Bernier, J., Lusinchi, A., Stuschke, M., Lopez-Torrecilla, J., et al. (1997). Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Radiother Oncol 44, 111-121. Hunter, K. D., Parkinson, E. K., and Harrison, P. R. (2005). Profiling early head and neck cancer. Nat Rev Cancer 5, 127-135. Jacob, B. J., Straif, K., Thomas, G., Ramadas, K., Mathew, B., Zhang, Z. F., Sankaranarayanan, R., and Hashibe, M. (2004). Betel quid without tobacco as a risk factor for oral precancers. Oral Oncol 40, 697-704. Jayant, K., and Deo, M. G. (1986). Oral cancer and cultural practices in relation to betel quid and tobacco chewing and smoking. Cancer Detect Prev 9, 207-213. Katayama, A., Bandoh, N., Kishibe, K., Takahara, M., Ogino, T., Nonaka, S., and Harabuchi, Y. (2004). Expressions of matrix metalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumor metastases and prognosis. Clin Cancer Res 10, 634-640. Kawakami, K., Kawakami, M., Joshi, B. H., and Puri, R. K. (2001). Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal model of human head and neck cancer. Cancer Res 61, 6194-6200. Kim, E. S., Kies, M., and Herbst, R. S. (2002). Novel therapeutics for head and neck cancer. Curr Opin Oncol 14, 334-342. Knecht, R., Elez, R., Oechler, M., Solbach, C., von Ilberg, C., and Strebhardt, K. (1999). Prognostic significance of polo-like kinase (PLK) expression in squamous cell carcinomas of the head and neck. Cancer Res 59, 2794-2797. Kobayashi, H., Sagara, J., Kurita, H., Morifuji, M., Ohishi, M., Kurashina, K., and Taniguchi, S. (2004). Clinical significance of cellular distribution of moesin in patients with oral squamous cell carcinoma. Clin Cancer Res 10, 572-580. Kosunen, A., Ropponen, K., Kellokoski, J., Pukkila, M., Virtaniemi, J., Valtonen, H., Kumpulainen, E., Johansson, R., Tammi, R., Tammi, M., et al. (2004). Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma. Oral Oncol 40, 257-263. Kresty, L. A., Mallery, S. R., Knobloch, T. J., Song, H., Lloyd, M., Casto, B. C., and Weghorst, C. M. (2002). Alterations of p16(INK4a) and p14(ARF) in patients with severe oral epithelial dysplasia. Cancer Res 62, 5295-5300. Lee, J. I., Soria, J. C., Hassan, K., Liu, D., Tang, X., El-Naggar, A., Hong, W. K., and Mao, L. (2001). Loss of Fhit expression is a predictor of poor outcome in tongue cancer. Cancer Res 61, 837-841. Lee, T. Y., Wu, H. C., Tseng, Y. L., and Lin, C. T. (2004). A novel peptide specifically binding to nasopharyngeal carcinoma for targeted drug delivery. Cancer Res 64, 8002-8008. Leethanakul, C., Patel, V., Gillespie, J., Pallente, M., Ensley, J. F., Koontongkaew, S., Liotta, L. A., Emmert-Buck, M., and Gutkind, J. S. (2000a). Distinct pattern of expression of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays. Oncogene 19, 3220-3224. Leethanakul, C., Patel, V., Gillespie, J., Shillitoe, E., Kellman, R. M., Ensley, J. F., Limwongse, V., Emmert-Buck, M. R., Krizman, D. B., and Gutkind, J. S. (2000b). Gene expression profiles in squamous cell carcinomas of the oral cavity: use of laser capture microdissection for the construction and analysis of stage-specific cDNA libraries. Oral Oncol 36, 474-483. Liao, C. T., Tung-Chieh Chang, J., Wang, H. M., Chen, I. H., Lin, C. Y., Chen, T. M., Hsieh, L. L., and Cheng, A. J. (2004). Telomerase as an independent prognostic factor in head and neck squamous cell carcinoma. Head Neck 26, 504-512. Licciardello, J. T., Spitz, M. R., and Hong, W. K. (1989). Multiple primary cancer in patients with cancer of the head and neck: second cancer of the head and neck, esophagus, and lung. Int J Radiat Oncol Biol Phys 17, 467-476. Lindeberg, H., Fey, S. J., Ottosen, P. D., and Mose Larsen, P. (1988). Human papilloma virus (HPV) and carcinomas of the head and neck. Clin Otolaryngol 13, 447-454. Lindsey, J., McGill, N. I., Lindsey, L. A., Green, D. K., and Cooke, H. J. (1991). In vivo loss of telomeric repeats with age in humans. Mutat Res 256, 45-48. Lo Muzio, L., Pannone, G., Staibano, S., Mignogna, M. D., Rubini, C., Mariggio, M. A., Procaccini, M., Ferrari, F., De Rosa, G., and Altieri, D. C. (2003). Survivin expression in oral squamous cell carcinoma. Br J Cancer 89, 2244-2248. Lu, C. T., Lan, S. J., Hsieh, C. C., Yang, M. J., Ko, Y. C., Tsai, C. C., and Yen, Y. Y. (1993). Prevalence and characteristics of areca nut chewers among junior high school students in Changhua county, Taiwan. Community Dent Oral Epidemiol 21, 370-373. Macfarlane, G. J., Zheng, T., Marshall, J. R., Boffetta, P., Niu, S., Brasure, J., Merletti, F., and Boyle, P. (1995). Alcohol, tobacco, diet and the risk of oral cancer: a pooled analysis of three case-control studies. Eur J Cancer B Oral Oncol 31B, 181-187. MacLennan, R., Paissat, D., Ring, A., and Thomas, S. (1985). Possible aetiology of oral cancer in Papua New Guinea. P N G Med J 28, 3-8. Mao, L., El-Naggar, A. K., Fan, Y. H., Lee, J. S., Lippman, S. M., Kayser, S., Lotan, R., and Hong, W. K. (1996). Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues. Cancer Res 56, 5600-5604. Mao, L., Hong, W. K., and Papadimitrakopoulou, V. A. (2004). Focus on head and neck cancer. Cancer Cell 5, 311-316. Mashberg, A. (1977). Erythroplasia vs. leukoplasia in the diagnosis of early asymptomatic oral squamous carcinoma. N Engl J Med 297, 109-110. McGregor, F., Muntoni, A., Fleming, J., Brown, J., Felix, D. H., MacDonald, D. G., Parkinson, E. K., and Harrison, P. R. (2002). Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine. Cancer Res 62, 4757-4766. McGregor, F., Wagner, E., Felix, D., Soutar, D., Parkinson, K., and Harrison, P. R. (1997). Inappropriate retinoic acid receptor-beta expression in oral dysplasias: correlation with acquisition of the immortal phenotype. Cancer Res 57, 3886-3889. Moriyama-Kita, M., Endo, Y., Yonemura, Y., Heizmann, C. W., Schafer, B. W., Sasaki, T., and Yamamoto, E. (2004). Correlation of S100A4 expression with invasion and metastasis in oral squamous cell carcinoma. Oral Oncol 40, 496-500. Nathan, C. A., Sanders, K., Abreo, F. W., Nassar, R., and Glass, J. (2000). Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic implications. Cancer Res 60, 3599-3604. Ogi, K., Toyota, M., Ohe-Toyota, M., Tanaka, N., Noguchi, M., Sonoda, T., Kohama, G., and Tokino, T. (2002). Aberrant methylation of multiple genes and clinicopathological features in oral squamous cell carcinoma. Clin Cancer Res 8, 3164-3171. Owens, D. M., and Watt, F. M. (2003). Contribution of stem cells and differentiated cells to epidermal tumours. Nat Rev Cancer 3, 444-451. Partridge, M., Pateromichelakis, S., Phillips, E., Emilion, G. G., A'Hern, R. P., and Langdon, J. D. (2000). A case-control study confirms that microsatellite assay can identify patients at risk of developing oral squamous cell carcinoma within a field of cancerization. Cancer Res 60, 3893-3898. Pasqualini, R., and Ruoslahti, E. (1996). Organ targeting in vivo using phage display peptide libraries. Nature 380, 364-366. Pignon, J. P., Bourhis, J., Domenge, C., and Designe, L. (2000). Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355, 949-955. Reichart, P. A. (1995). Oral cancer and precancer related to betel and miang chewing in Thailand: a review. J Oral Pathol Med 24, 241-243. Reichart, P. A., Philipsen, H. P., Mohr, U., Geerlings, H., and Srisuwan, S. (1988). Miang chewing in northern Thai villagers. Trop Geogr Med 40, 39-44. Reichart, P. A., Schmidtberg, W., and Scheifele, C. (1997). Khmer dental and medical students' knowledge about the betel quid chewing habit in Cambodia. Eur J Dent Educ 1, 129-132. Rheinwald, J. G., Hahn, W. C., Ramsey, M. R., Wu, J. Y., Guo, Z., Tsao, H., De Luca, M., Catricala, C., and O'Toole, K. M. (2002). A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status. Mol Cell Biol 22, 5157-5172. Romanov, S. R., Kozakiewicz, B. K., Holst, C. R., Stampfer, M. R., Haupt, L. M., and Tlsty, T. D. (2001). Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes. Nature 409, 633-637. Rosenblatt, K. A., Daling, J. R., Chen, C., Sherman, K. J., and Schwartz, S. M. (2004). Marijuana use and risk of oral squamous cell carcinoma. Cancer Res 64, 4049-4054. Rosin, M. P., Cheng, X., Poh, C., Lam, W. L., Huang, Y., Lovas, J., Berean, K., Epstein, J. B., Priddy, R., Le, N. D., and Zhang, L. (2000). Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res 6, 357-362. Shintani, S., Li, C., Ishikawa, T., Mihara, M., Nakashiro, K., and Hamakawa, H. (2004). Expression of vascular endothelial growth factor A, B, C, and D in oral squamous cell carcinoma. Oral Oncol 40, 13-20. Slaughter, D. P., Southwick, H. W., and Smejkal, W. (1953). Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6, 963-968. Smith, G. P. (1985). Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228, 1315-1317. Sudbo, J., Kildal, W., Risberg, B., Koppang, H. S., Danielsen, H. E., and Reith, A. (2001). DNA content as a prognostic marker in patients with oral leukoplakia. N Engl J Med 344, 1270-1278. Summers, R. M., Williams, S. A., and Curzon, M. E. (1994). The use of tobacco and betel quid ('pan') among Bangladeshi women in West Yorkshire. Community Dent Health 11, 12-16. Sundstrom, B., Mornstad, H., and Axell, T. (1982). Oral carcinomas associated with snuff dipping. Some clinical and histological characteristics of 23 tumours in Swedish males. J Oral Pathol 11, 245-251. Szentirmay, Z., Szanto, I., Balint, I., Polus, K., Remenar, E., Tamas, L., Szentkuti, G., Melegh, Z., Nagy, P., and Kasler, M. (2002). [Causal association between human papilloma virus infection and head and neck and esophageal squamous cell carcinoma]. Magy Onkol 46, 35-41. Tabor, M. P., Brakenhoff, R. H., Ruijter-Schippers, H. J., Van Der Wal, J. E., Snow, G. B., Leemans, C. R., and Braakhuis, B. J. (2002). Multiple head and neck tumors frequently originate from a single preneoplastic lesion. Am J Pathol 161, 1051-1060. Tabor, M. P., Brakenhoff, R. H., van Houten, V. M., Kummer, J. A., Snel, M. H., Snijders, P. J., Snow, G. B., Leemans, C. R., and Braakhuis, B. J. (2001). Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7, 1523-1532. Uehara, M., Sano, K., Ikeda, H., Sekine, J., Irie, A., Yokota, T., Tobita, T., Ohba, S., and Inokuchi, T. (2004). Expression of vascular endothelial growth factor and prognosis of oral squamous cell carcinoma. Oral Oncol 40, 321-325. Ulanovski, D., Stern, Y., Roizman, P., Shpitzer, T., Popovtzer, A., and Feinmesser, R. (2004). Expression of EGFR and Cerb-B2 as prognostic factors in cancer of the tongue. Oral Oncol 40, 532-537. VanWyk, C. W. (1997). Oral submucous fibrosis. The South African experience. Indian J Dent Res 8, 39-45. Wada, S., Yue, L., and Furuta, I. (2004). Prognostic significance of p34cdc2 expression in tongue squamous cell carcinoma. Oral Oncol 40, 164-169. Walker, D. M., Boey, G., and McDonald, L. A. (2003). The pathology of oral cancer. Pathology 35, 376-383. Weber, R. G., Scheer, M., Born, I. A., Joos, S., Cobbers, J. M., Hofele, C., Reifenberger, G., Zoller, J. E., and Lichter, P. (1998). Recurrent chromosomal imbalances detected in biopsy material from oral premalignant and malignant lesions by combined tissue microdissection, universal DNA amplification, and comparative genomic hybridization. Am J Pathol 153, 295-303. Wykoff, C. C., Beasley, N. J., Watson, P. H., Turner, K. J., Pastorek, J., Sibtain, A., Wilson, G. D., Turley, H., Talks, K. L., Maxwell, P. H., et al. (2000). Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 60, 7075-7083. Yoskovitch, A., Hier, M. P., Okrainec, A., Black, M. J., and Rochon, L. (2001). Skin metastases in squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg 124, 248-252. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24378 | - |
dc.description.abstract | 流行病學研究指出,台灣及東南亞地區的口腔癌發生大多與檳榔嚼食習慣有高度相關性。根據衛生署民國九十三年癌症登記報告指出,口腔癌在臺灣男性十大癌症中死亡率與發生率皆位居第四位。儘管近年在診斷及治療之科技上有不少進步,但整體來說,口腔癌病人之五年存活率並未有明顯改變。最近發現結合化學治療和放射線治療或可增加存活率。但這些治療方式無法選擇性對癌細胞做專一的治療,都有嚴重的副作用。專一性的標的療法或許可以解決此一問題。
先前研究指出,利用噬菌體顯現法技術可以篩選出與腫瘤細胞專一性結合的標的胜肽。本研究利用此方法對台灣口腔癌細胞株TW2.6進行篩選找出8種可以和TW2.6結合之噬菌體株。用此方法所找到噬菌體株,具有與口腔癌細胞及專一性結合的能力,同時也可以和在異體移殖的口腔癌腫瘤細胞有專一性的結合。 與口腔癌組織結合的能力分別高於普通組織約12.18到222.46倍。控制組的噬菌體株,則不具有與腫瘤組織專一性結合的能力。當我們將所篩選到的噬菌體株與其相對應的胜肽去做競爭性抑制,發現噬菌體株與口腔癌組織結合的能力可以被合成胜肽明顯抑制。些噬菌體株中以C39噬菌體與腫瘤組織專一性結合能力為最強,同時也能和台灣口腔上皮變異細胞株TW1.5做專一性結合。我們進一步將C39對應的胜肽連結微脂體包裹doxorubicin抗癌藥物(C39-peptide-Lipo-Dox)和單一只有此抗癌藥(Lipo-Dox)來進行抗癌療效比較。結果發現以C39-peptide-Lipo-Dox治療的SCID鼠效果最佳,腫瘤成長部分大小僅為原來的5.51倍。此外相較於Lipo-Dox治療的SCID鼠體重下降22.6%,C39-peptide-Lipo-Dox治療的SCID鼠體重沒有明顯的減少,顯示C39-peptide-Lipo-Dox藥物所引起的副作用受到良好的控制。因此C39標的胜肽不但能提高腫瘤治療效果及專一性,也能減輕藥物的毒性,可提供未來一個口腔癌新穎的治療方式。 | zh_TW |
dc.description.abstract | In Taiwan, oral cancer is the fourth leading cause of cancer death in male. Approximately 80% of all oral cancer deaths are associated with the areca quid chewing habit. Despite significant improvements in diagnosis, local management, and chemotherapy of head and neck cancer, there is no significant increase in long-term survival rates over the past 30 years. To improve the survival rate, we identify several 12-mer peptides specifically binding to a Taiwanese oral squamous cell carcinoma (OSCC) TW2.6 with a phage displayed random peptide library. The selected phage clones and synthetic phage-derived peptides specifically bound to the cell surfaces of TW2.6 cells and a Taiwanese oral dysplasia cell line TW1.5, but not normal oral keratinocyes. In SCID mice bearing OSCC xenografts, the selected phage clones specifically bound to the tumor mass and the effects was inhibited by competition with phage-derived peptides. Among all the selected phage clones, C39-phage showed the highest targeting ability in tumor mass with 27.78-fold increase in concentration compared to control phage. Furthermore, C39-peptide-linked liposomes that carried doxorubicin (C39-peptide-Lipo-Dox) not only suppressed tumor growth better than Lipo-Dox but also showed no significant body weight change. These results indicate that the novel peptides specifically binding to OSCC cells and a good candidate for targeted drug delivery to OSCC solid tumors. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:23:49Z (GMT). No. of bitstreams: 1 ntu-94-R92450010-1.pdf: 413462 bytes, checksum: 432b3c55913a360411123416235bfb5e (MD5) Previous issue date: 2005 | en |
dc.description.tableofcontents | INDEX
Chapter 1 8 INTRODUCTION 8 Oral squamous cell carcinoma 8 The risk factors of oral cancer 9 Field cancerization 10 Molecular basis of HNSCC tumorgenesis 11 Origin of HNSCCs 13 Identified the different aetiologies and prognoses for HNSCCs 14 Chemoprevention for HNSCCs 15 Current treatment and new drugs development of HNSCC 16 Phage display 17 Chapter 2 18 MATERIALS AND METHODS 18 Cell lines and cell culture 18 Phage-display biopanning procedures 19 Idetification of phage clones by ELISA 19 DNA sequencing and computer analysis 20 Plaque assay 20 Peptide synthesis 21 Animal model for study of targeted oral therapy 21 Immunochistochemical staning of phage binding in xenograft tumor mass22 In vitro peptide competitive inhibition of TW2.6 cell-selected phage 23 Conjugation of peptides to PEG-DSPE 24 Preparation of Doxorubicin 24 Aminal model for targeting study 24 Cell viability (MTT) assay 25 Chapter 3 27 Chapter 4 40 RESULTS 40 Screening of oral cancer cell-binding phages and identification of their binding motif 40 Plaque assay of OSCC cell with different selected clones 41 Verification of the target binding activity of displayed peptides derived from selected phage clones 41 Animal model for targeting study of selected phages 42 Animal model for study of C39-peptide targeted therapy 43 Chapter 5 45 DISCUSSION 45 Chapter 6 51 REFERENCE 51 | |
dc.language.iso | en | |
dc.title | 利用腫瘤標的性胜肽作為台灣地區口腔癌治療之研究 | zh_TW |
dc.title | Identification of novel peptides targeting to oral squamous cell carcinoma in Taiwan | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 吳漢忠(Han-Chung Wu) | |
dc.contributor.oralexamcommittee | 郭明良 | |
dc.subject.keyword | 噬菌體顯現法,口腔癌,胜肽, | zh_TW |
dc.subject.keyword | phage display,oral cancer,peptide, | en |
dc.relation.page | 58 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2005-07-25 | |
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 |
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