請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10745
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 詹東榮(Tong-Rong Jan) | |
dc.contributor.author | Chia-Chi Wang | en |
dc.contributor.author | 王家琪 | zh_TW |
dc.date.accessioned | 2021-05-20T21:55:05Z | - |
dc.date.available | 2015-06-07 | |
dc.date.available | 2021-05-20T21:55:05Z | - |
dc.date.copyright | 2010-07-27 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-07-27 | |
dc.identifier.citation | Adhvaryu, S.G., Dave, B.J., Trivedi, A.H., 1991. Cytogenetic surveillance of tobacco-areca nut (mava) chewers, including patients with oral cancers and premalignant conditions. Mutat Res 261, 41-49.
Agarwal, A., Rani, M., Saha, G.K., Valarmathi, T.M., Bahadur, S., Mohanti, B.K., Das, S.N., 2003. Disregulated expression of the Th2 cytokine gene in patients with intraoral squamous cell carcinoma. Immunol Invest 32, 17-30. Ahmed, S., Rahman, A., Hull, S., 1997. Use of betel quid and cigarettes among Bangladeshi patients in an inner-city practice: prevalence and knowledge of health effects. Br J Gen Pract 47, 431-434. Akiyama, H., Sato, Y., Watanabe, T., Nagaoka, M.H., Yoshioka, Y., Shoji, T., Kanda, T., Yamada, K., Totsuka, M., Teshima, R., Sawada, J., Goda, Y., Maitani, T., 2005. Dietary unripe apple polyphenol inhibits the development of food allergies in murine models. FEBS Lett 579, 4485-4491. Bagchi, M., Balmoori, J., Bagchi, D., Stohs, S.J., Chakrabarti, J., Das, D.K., 2002. Role of reactive oxygen species in the development of cytotoxicity with various forms of chewing tobacco and pan masala. Toxicology 179, 247-255. Balaram, P., Pillai, M.R., Abraham, T., 1987. Immunology of premalignant and malignant conditions of the oral cavity. II. Circulating immune complexes. J Oral Pathol 16, 389-391. Balaram, P., Pillai, M.R., Abraham, T., Nalinakumari, K.R., Meenattoor, G., Kannan, S., Hareendran, N.K., Nair, M.K., 1992. Interferon and interleukin-2 induced spontaneous cell-mediated cytotoxicity: a preliminary evaluation. J Cancer Res Clin Oncol 118, 408-410. Baniyash, M., 2004. TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol 4, 675-687. Barker, J.N., Mitra, R.S., Griffiths, C.E., Dixit, V.M., Nickoloff, B.J., 1991. Keratinocytes as initiators of inflammation. Lancet 337, 211-214. Billiau, A., Matthys, P., 2009. Interferon-gamma: a historical perspective. Cytokine Growth Factor Rev 20, 97-113. Bingisser, R.M., Tilbrook, P.A., Holt, P.G., Kees, U.R., 1998. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 160, 5729-5734. Boehm, U., Klamp, T., Groot, M., Howard, J.C., 1997. Cellular responses to interferon-gamma. Annu Rev Immunol 15, 749-795. Boise, L.H., Minn, A.J., Thompson, C.B., 1995. Receptors that regulate T-cell susceptibility to apoptotic cell death. Ann N Y Acad Sci 766, 70-80. Bromley, S.K., Burack, W.R., Johnson, K.G., Somersalo, K., Sims, T.N., Sumen, C., Davis, M.M., Shaw, A.S., Allen, P.M., Dustin, M.L., 2001. The immunological synapse. Annu Rev Immunol 19, 375-396. Bronte, V., Serafini, P., De Santo, C., Marigo, I., Tosello, V., Mazzoni, A., Segal, D.M., Staib, C., Lowel, M., Sutter, G., Colombo, M.P., Zanovello, P., 2003. IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J Immunol 170, 270-278. Bronte, V., Zanovello, P., 2005. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 5, 641-654. Bunt, S.K., Clements, V.K., Hanson, E.M., Sinha, P., Ostrand-Rosenberg, S., 2009. Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 85, 996-1004. Bunt, S.K., Yang, L., Sinha, P., Clements, V.K., Leips, J., Ostrand-Rosenberg, S., 2007. Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 67, 10019-10026. Caddeo, C., Teskac, K., Sinico, C., Kristl, J., 2008. Effect of resveratrol incorporated in liposomes on proliferation and UV-B protection of cells. Int J Pharm 363, 183-191. Canniff, J.P., Harvey, W., 1981. The aetiology of oral submucous fibrosis: the stimulation of collagen synthesis by extracts of areca nut. Int J Oral Surg 10, 163-167. Canniff, J.P., Harvey, W., Harris, M., 1986. Oral submucous fibrosis: its pathogenesis and management. Br Dent J 160, 429-434. Capuano, G., Rigamonti, N., Grioni, M., Freschi, M., Bellone, M., 2009. Modulators of arginine metabolism support cancer immunosurveillance. BMC Immunol 10, 1. Chang, L.Y., Wan, H.C., Lai, Y.L., Kuo, Y.F., Liu, T.Y., Chen, Y.T., Hung, S.L., 2009. Areca nut extracts increased expression of inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-8, in peripheral blood mononuclear cells. J Periodontal Res 44, 175-183. Chang, L.Y., Wan, H.C., Lai, Y.L., Liu, T.Y., Hung, S.L., 2006. Enhancing effects of areca nut extracts on the production of interleukin-6 and interleukin-8 by peripheral blood mononuclear cells. J Periodontol 77, 1969-1977. Chang, M.C., Chiang, C.P., Lin, C.L., Lee, J.J., Hahn, L.J., Jeng, J.H., 2005. Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit. Oral Oncol 41, 757-775. Chang, M.C., Ho, Y.S., Lee, J.J., Kok, S.H., Hahn, L.J., Jeng, J.H., 2002. Prevention of the areca nut extract-induced unscheduled DNA synthesis of gingival keratinocytes by vitamin C and thiol compounds. Oral Oncol 38, 258-265. Chang, M.C., Ho, Y.S., Lee, P.H., Chan, C.P., Lee, J.J., Hahn, L.J., Wang, Y.J., Jeng, J.H., 2001a. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. Carcinogenesis 22, 1527-1535. 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., 2004. 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, 279, 50676-50683. Chang, Y.C., Hu, C.C., Lii, C.K., Tai, K.W., Yang, S.H., Chou, M.Y., 2001b. Cytotoxicity and arecoline mechanisms in human gingival fibroblasts in vitro. Clin Oral Investig 5, 51-56. Chen, C.C., Huang, J.F., Tsai, C.C., 1995. In vitro production of interleukin-6 by human gingival, normal buccal mucosa, and oral submucous fibrosis fibroblasts treated with betel-nut alkaloids. Gaoxiong Yi Xue Ke Xue Za Zhi 11, 604-614. Chen, C.L., Chi, C.W., Liu, T.Y., 2002. Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo. J Toxicol Environ Health A 65, 327-336. Cheynier, V., 2005. Polyphenols in foods are more complex than often thought. Am J Clin Nutr 81, 223S-229S. Chiang, C.P., Chang, M.C., Lee, J.J., Chang, J.Y., Lee, P.H., Hahn, L.J., Jeng, J.H., 2004. Hamsters chewing betel quid or areca nut directly show a decrease in body weight and survival rates with concomitant epithelial hyperplasia of cheek pouch. Oral Oncol 40, 720-727. Chiang, C.P., Hsieh, R.P., Chen, T.H., Chang, Y.F., Liu, B.Y., Wang, J.T., Sun, A., Kuo, M.Y., 2002a. High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis. J Oral Pathol Med 31, 402-409. Chiang, C.P., Wu, H.Y., Liu, B.Y., Wang, J.T., Kuo, M.Y., 2002b. Quantitative analysis of immunocompetent cells in oral submucous fibrosis in Taiwan. Oral Oncol 38, 56-63. Chou, C.Y., Cheng, S.Y., Liu, J.H., Cheng, W.C., Kang, I.M., Tseng, Y.H., Shih, C.M., Chen, W., 2009. Association between betel-nut chewing and chronic kidney disease in men. Public Health Nutr 12, 723-727. Chung, W.G., Miranda, C.L., Stevens, J.F., Maier, C.S., 2009. Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species. Food Chem Toxicol 47, 827-836. Cohen, J.J., Duke, R.C., Fadok, V.A., Sellins, K.S., 1992. Apoptosis and programmed cell death in immunity. Annu Rev Immunol 10, 267-293. Corraliza, I.M., Campo, M.L., Soler, G., Modolell, M., 1994. Determination of arginase activity in macrophages: a micromethod. J Immunol Methods 174, 231-235. Cos, P., Hermans, N., Calomme, M., Maes, L., De Bruyne, T., Pieters, L., Vlietinck, A.J., Vanden Berghe, D., 2003. Comparative study of eight well-known polyphenolic antioxidants. J Pharm Pharmacol 55, 1291-1297. Coughlin, C.M., Salhany, K.E., Gee, M.S., LaTemple, D.C., Kotenko, S., Ma, X., Gri, G., Wysocka, M., Kim, J.E., Liu, L., Liao, F., Farber, J.M., Pestka, S., Trinchieri, G., Lee, W.M., 1998. Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9, 25-34. D'Archivio, M., Filesi, C., Di Benedetto, R., Gargiulo, R., Giovannini, C., Masella, R., 2007. Polyphenols, dietary sources and bioavailability. Ann Ist Super Sanita 43, 348-361. Dammer, R., Wurm, E.M., Niederdellmann, H., Fleischmann, H., Knuchel, R., 1997. [Immunocytochemical venous blood studies in patients with manifest oral cavity carcinomas, oral precancerous conditions, benign tumors and in chronic alcoholic patients]. Mund Kiefer Gesichtschir 1, 95-103. Daniele, R.P., Holian, S.K., 1976. A potassium ionophore (valinomycin) inhibits lymphocyte proliferation by its effects on the cell membrane. Proc Natl Acad Sci U S A 73, 3599-3602. Dasgupta, R., Saha, I., Pal, S., Bhattacharyya, A., Sa, G., Nag, T.C., Das, T., Maiti, B.R., 2006. Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice. Toxicology 227, 94-104. Diaz-Montero, C.M., Salem, M.L., Nishimura, M.I., Garrett-Mayer, E., Cole, D.J., Montero, A.J., 2009. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58, 49-59. Dighe, A.S., Richards, E., Old, L.J., Schreiber, R.D., 1994. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1, 447-456. Doherty, P.C., 1993. Cell-mediated cytotoxicity. Cell 75, 607-612. Dolcetti, L., Marigo, I., Mantelli, B., Peranzoni, E., Zanovello, P., Bronte, V., 2008. Myeloid-derived suppressor cell role in tumor-related inflammation. Cancer Lett 267, 216-225. Dong, C., Flavell, R.A., 2001. Th1 and Th2 cells. Curr Opin Hematol 8, 47-51. Erlejman, A.G., Jaggers, G., Fraga, C.G., Oteiza, P.I., 2008. TNF-alpha-induced NF-kappaB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. Arch Biochem Biophys 476, 186-195. Fesus, L., 1992. Apoptosis. Immunol Today 13, A16-17. Gabrilovich, D.I., Nagaraj, S., 2009. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9, 162-174. Gallina, G., Dolcetti, L., Serafini, P., De Santo, C., Marigo, I., Colombo, M.P., Basso, G., Brombacher, F., Borrello, I., Zanovello, P., Bicciato, S., Bronte, V., 2006. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest 116, 2777-2790. Gastman, B.R., Atarshi, Y., Reichert, T.E., Saito, T., Balkir, L., Rabinowich, H., Whiteside, T.L., 1999. Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes. Cancer Res 59, 5356-5364. Greifenberg, V., Ribechini, E., Rossner, S., Lutz, M.B., 2009. Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur J Immunol 39, 2865-2876. Gu, L., House, S.E., Wu, X., Ou, B., Prior, R.L., 2006. Procyanidin and catechin contents and antioxidant capacity of cocoa and chocolate products. J Agric Food Chem 54, 4057-4061. Gupta, P.C., Warnakulasuriya, S., 2002. Global epidemiology of areca nut usage. Addict Biol 7, 77-83. Hadi, S.M., Bhat, S.H., Azmi, A.S., Hanif, S., Shamim, U., Ullah, M.F., 2007. Oxidative breakage of cellular DNA by plant polyphenols: a putative mechanism for anticancer properties. Semin Cancer Biol 17, 370-376. Haque, M.F., Harris, M., Meghji, S., Barrett, A.W., 1998. Immunolocalization of cytokines and growth factors in oral submucous fibrosis. Cytokine 10, 713-719. Haque, M.F., Harris, M., Meghji, S., Speight, P.M., 1997. An immunohistochemical study of oral submucous fibrosis. J Oral Pathol Med 26, 75-82. Haque, M.F., Meghji, S., Khitab, U., Harris, M., 2000. Oral submucous fibrosis patients have altered levels of cytokine production. J Oral Pathol Med 29, 123-128. Haque, M.F., Meghji, S., Nazir, R., Harris, M., 2001. Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis. J Oral Pathol Med 30, 12-21. Heath, W.R., Carbone, F.R., 2001. Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol 19, 47-64. Heimdal, J.H., Aarstad, H.J., Klementsen, B., Olofsson, J., 1998. Disease stage related in vitro responsiveness of peripheral blood T-lymphocytes in patients with head and neck carcinoma. Acta Otolaryngol 118, 887-891. Hildeman, D.A., Mitchell, T., Kappler, J., Marrack, P., 2003. T cell apoptosis and reactive oxygen species. J Clin Invest 111, 575-581. Ho, W.H., Lee, Y.Y., Chang, L.Y., Chen, Y.T., Liu, T.Y., Hung, S.L., 2010. Effects of areca nut extract on the apoptosis pathways in human neutrophils. J Periodontal Res 45,412-420. Holtzman, M.J., Green, J.M., Jayaraman, S., Arch, R.H., 2000. Regulation of T cell apoptosis. Apoptosis 5, 459-471. Hsu, H.J., Chang, K.L., Yang, Y.H., Shieh, T.Y., 2001. The effects of arecoline on the release of cytokines using cultured peripheral blood mononuclear cells from patients with oral mucous diseases. Kaohsiung J Med Sci 17, 175-182. Huang, B., Pan, P.Y., Li, Q., Sato, A.I., Levy, D.E., Bromberg, J., Divino, C.M., Chen, S.H., 2006. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66, 1123-1131. Huang, P.L., Chi, C.W., Liu, T.Y., 2010. Effects of Areca catechu L. containing procyanidins on cyclooxygenase-2 expression in vitro and in vivo. Food Chem Toxicol 48, 306-313. Huang, P.L., Chi, C.W., Liu, T.Y., 2010. Effects of Areca catechu L. containing procyanidins on cyclooxygenase-2 expression in vitro and in vivo. Food Chem Toxicol 48, 306-313. Hung, S.L., Cheng, Y.Y., Peng, J.L., Chang, L.Y., Liu, T.Y., Chen, Y.T., 2005. Inhibitory effects of areca nut extracts on phagocytosis of Actinobacillus actinomycetemcomitans ATCC 33384 by neutrophils. J Periodontol 76, 373-379. Hung, S.L., Lee, Y.Y., Liu, T.Y., Peng, J.L., Cheng, Y.Y., Chen, Y.T., 2006. Modulation of phagocytosis, chemotaxis, and adhesion of neutrophils by areca nut extracts. J Periodontol 77, 579-585. IARC, 2004. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum 85, 1-334. Ikeda, H., Old, L.J., Schreiber, R.D., 2002. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev 13, 95-109. Jeng, J.H., Chang, M.C., Hahn, L.J., 2001. Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol 37, 477-492. Jeng, J.H., Hahn, L.J., Lin, B.R., Hsieh, C.C., Chan, C.P., Chang, M.C., 1999. 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 28, 64-71. Jeng, J.H., Ho, Y.S., Chan, C.P., Wang, Y.J., Hahn, L.J., Lei, D., Hsu, C.C., Chang, M.C., 2000. Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes. Carcinogenesis 21, 1365-1370. Jeng, J.H., Kuo, M.L., Hahn, L.J., Kuo, M.Y., 1994. Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro. J Dent Res 73, 1043-1049. Jeng, J.H., Lan, W.H., Hahn, L.J., Hsieh, C.C., Kuo, M.Y., 1996. Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro. J Oral Pathol Med 25, 371-375. Jeng, J.H., Wang, Y.J., Chiang, B.L., Lee, P.H., Chan, C.P., Ho, Y.S., Wang, T.M., Lee, J.J., Hahn, L.J., Chang, M.C., 2003. Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-alpha production of oral epithelial cells by areca nut extract and arecoline. Carcinogenesis 24, 1301-1315. Kaminski, N.E., Koh, W.S., Yang, K.H., Lee, M., Kessler, F.K., 1994. Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism. Biochem Pharmacol 48, 1899-1908. Kanda, T., Akiyama, H., Yanagida, A., Tanabe, M., Goda, Y., Toyoda, M., Teshima, R., Saito, Y., 1998. Inhibitory effects of apple polyphenol on induced histamine release from RBL-2H3 cells and rat mast cells. Biosci Biotechnol Biochem 62, 1284-1289. Kenny, T.P., Keen, C.L., Schmitz, H.H., Gershwin, M.E., 2007. Immune effects of cocoa procyanidin oligomers on peripheral blood mononuclear cells. Exp Biol Med (Maywood) 232, 293-300. Kikuchi, K., Kusama, K., Sano, M., Nakanishi, Y., Ishige, T., Ohni, S., Oinuma, T., Nemoto, N., 2006. Vascular endothelial growth factor and dendritic cells in human squamous cell carcinoma of the oral cavity. Anticancer Res 26, 1833-1848. Kim, H.M., Oh, G.T., Hong, D.H., Hyun, B.H., Cha, Y.N., Yoo, B.S., Han, S.B., 1996. Facilitation of apoptosis by autologous serum and related immunosuppression in the splenocyte culture. Immunopharmacology 34, 39-50. Knudson, C.M., Brown, N.M., 2008. Mitochondria potential, bax 'activation,' and programmed cell death. Methods Mol Biol 414, 95-108. Ko, Y.C., Chiang, T.A., Chang, S.J., Hsieh, S.F., 1992. Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors. J Oral Pathol Med 21, 261-264. Ko, Y.C., Huang, Y.L., Lee, C.H., Chen, M.J., Lin, L.M., Tsai, C.C., 1995. Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 24, 450-453. Korangy, F., Hochst, B., Manns, M.P., Greten, T.F., 2010. Immune responses in hepatocellular carcinoma. Dig Dis 28, 150-154. Kumpawat, K., Deb, S., Ray, S., Chatterjee, A., 2003. Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells. Mutat Res 538, 1-12. Laad, A., Kode, J., Chavan, S., Rao, R., Fakih, A.R., Chiplunkar, S., 1996. Limiting dilution analysis of proliferating and cytotoxic lymphocytes in the peripheral blood and tumours of oral cancer patients. Eur J Cancer B Oral Oncol 32B, 337-342. Lai, K.C., Lee, T.C., 2006. Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts. Mutat Res 599, 66-75. Lambert, J.D., Hong, J., Yang, G.Y., Liao, J., Yang, C.S., 2005. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am J Clin Nutr 81, 284S-291S. Lee, J.H., Chang, S.H., Park, Y.S., Her, E., Lee, H.Y., Park, J.W., Han, J.W., Kim, Y.M., Choi, W.S., 2004. In-vitro and in-vivo anti-allergic actions of Arecae semen. J Pharm Pharmacol 56, 927-933. Lee, P.H., Chang, M.C., Chang, W.H., Wang, T.M., Wang, Y.J., Hahn, L.J., Ho, Y.S., Lin, C.Y., Jeng, J.H., 2006. Prolonged exposure to arecoline arrested human KB epithelial cell growth: regulatory mechanisms of cell cycle and apoptosis. Toxicology 220, 81-89. Lee, S.S., Yang, S.F., Tsai, C.H., Chou, M.C., Chou, M.Y., Chang, Y.C., 2008. Upregulation of heme oxygenase-1 expression in areca-quid-chewing-associated oral squamous cell carcinoma. J Formos Med Assoc 107, 355-363. Lee, Y.C., Park, M.H., Baek, N.H., 1991. Effect of gamma-interferon on fibroblast proliferation and collagen synthesis after glaucoma filtering surgery in white rabbits. Korean J Ophthalmol 5, 59-67. Lin, M.H., Chou, F.P., Huang, H.P., Hsu, J.D., Chou, M.Y., Wang, C.J., 2003. The tumor promoting effect of lime-piper betel quid in JB6 cells. Food Chem Toxicol 41, 1463-1471. Lin, S.C., Lu, S.Y., Lee, S.Y., Lin, C.Y., Chen, C.H., Chang, K.W., 2005. Areca (betel) nut extract activates mitogen-activated protein kinases and NF-kappaB in oral keratinocytes. Int J Cancer 116, 526-535. Lin, W.Y., Chiu, T.Y., Lee, L.T., Lin, C.C., Huang, C.Y., Huang, K.C., 2008. Betel nut chewing is associated with increased risk of cardiovascular disease and all-cause mortality in Taiwanese men. Am J Clin Nutr 87, 1204-1211. Lin, W.Y., Pi-Sunyer, F.X., Liu, C.S., Li, T.C., Li, C.I., Huang, C.Y., Lin, C.C., 2009. Betel nut chewing is strongly associated with general and central obesity in Chinese male middle-aged adults. Obesity (Silver Spring) 17, 1247-1254. Liu, T.Y., Chen, C.L., Chi, C.W., 1996. Oxidative damage to DNA induced by areca nut extract. Mutat Res 367, 25-31. Lizarraga, D., Lozano, C., Briede, J.J., van Delft, J.H., Tourino, S., Centelles, J.J., Torres, J.L., Cascante, M., 2007. The importance of polymerization and galloylation for the antiproliferative properties of procyanidin-rich natural extracts. FEBS J 274, 4802-4811. Lotito, S.B., Actis-Goretta, L., Renart, M.L., Caligiuri, M., Rein, D., Schmitz, H.H., Steinberg, F.M., Keen, C.L., Fraga, C.G., 2000. Influence of oligomer chain length on the antioxidant activity of procyanidins. Biochem Biophys Res Commun 276, 945-951. Lozano, C., Julia, L., Jimenez, A., Tourino, S., Centelles, J.J., Cascante, M., Torres, J.L., 2006. Electron-transfer capacity of catechin derivatives and influence on the cell cycle and apoptosis in HT29 cells. FEBS J 273, 2475-2486. Mach, B., Steimle, V., Martinez-Soria, E., Reith, W., 1996. Regulation of MHC class II genes: lessons from a disease. Annu Rev Immunol 14, 301-331. Malmberg, K.J., Arulampalam, V., Ichihara, F., Petersson, M., Seki, K., Andersson, T., Lenkei, R., Masucci, G., Pettersson, S., Kiessling, R., 2001. Inhibition of activated/memory (CD45RO(+)) T cells by oxidative stress associated with block of NF-kappaB activation. J Immunol 167, 2595-2601. Mao, T.K., Van de Water, J., Keen, C.L., Schmitz, H.H., Gershwin, M.E., 2002. Effect of cocoa flavanols and their related oligomers on the secretion of interleukin-5 in peripheral blood mononuclear cells. J Med Food 5, 17-22. Marigo, I., Dolcetti, L., Serafini, P., Zanovello, P., Bronte, V., 2008. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 222, 162-179. Marnett, L.J., 2000. Oxyradicals and DNA damage. Carcinogenesis 21, 361-370. Mathew, A.G., Govindarajan, V.S., 1964. Polyphenolic substances of arecanut. II. Changes during maturation and ripening. Phytochemistry 3, 657-665. Miura, T., Chiba, M., Kasai, K., Nozaka, H., Nakamura, T., Shoji, T., Kanda, T., Ohtake, Y., Sato, T., 2008. Apple procyanidins induce tumor cell apoptosis through mitochondrial pathway activation of caspase-3. Carcinogenesis 29, 585-593. Miyake, M., Ide, K., Sasaki, K., Matsukura, Y., Shijima, K., Fujiwara, D., 2008. Oral administration of highly oligomeric procyanidins of Jatoba reduces the severity of collagen-induced arthritis. Biosci Biotechnol Biochem 72, 1781-1788. Miyake, M., Sasaki, K., Ide, K., Matsukura, Y., Shijima, K., Fujiwara, D., 2006. Highly oligomeric procyanidins ameliorate experimental autoimmune encephalomyelitis via suppression of Th1 immunity. J Immunol 176, 5797-5804. Mohamad, N., Gutierrez, A., Nunez, M., Cocca, C., Martin, G., Cricco, G., Medina, V., Rivera, E., Bergoc, R., 2005. Mitochondrial apoptotic pathways. Biocell 29, 149-161. Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65, 55-63. Mougiakakos, D., Choudhury, A., Lladser, A., Kiessling, R., Johansson, C.C., in 2010 Regulatory T cells in cancer. Adv Cancer Res 107, 57-117. Murali, P.S., Somasundaram, R., Rao, R.S., Fakih, A.R., Gangal, S.G., 1989. Interleukin-2 mediated regulation of mitogen-activated T cell reactivity from different lymphoid sources in patients with squamous cell carcinoma of the oral cavity. J Oral Pathol Med 18, 327-332. Nagaraj, S., Gupta, K., Pisarev, V., Kinarsky, L., Sherman, S., Kang, L., Herber, D.L., Schneck, J., Gabrilovich, D.I., 2007. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 13, 828-835. Nair, U., Bartsch, H., Nair, J., 2004. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms. Mutagenesis 19, 251-262. Nair, U.J., Floyd, R.A., Nair, J., Bussachini, V., Friesen, M., Bartsch, H., 1987. Formation of reactive oxygen species and of 8-hydroxydeoxyguanosine in DNA in vitro with betel quid ingredients. Chem Biol Interact 63, 157-169. Nair, U.J., Friesen, M., Richard, I., MacLennan, R., Thomas, S., Bartsch, H., 1990. Effect of lime composition on the formation of reactive oxygen species from areca nut extract in vitro. Carcinogenesis 11, 2145-2148. Nair, U.J., Nair, J., Friesen, M.D., Bartsch, H., Ohshima, H., 1995. Ortho- and meta-tyrosine formation from phenylalanine in human saliva as a marker of hydroxyl radical generation during betel quid chewing. Carcinogenesis 16, 1195-1198. Neuwirt, H., Arias, M.C., Puhr, M., Hobisch, A., Culig, Z., 2008. Oligomeric proanthocyanidin complexes (OPC) exert anti-proliferative and pro-apoptotic effects on prostate cancer cells. Prostate 68, 1647-1654. Nguyen, K.D., Hoang, A.T., Lee, D.A., 1994. Transcriptional control of human Tenon's capsule fibroblast collagen synthesis in vitro by gamma-interferon. Invest Ophthalmol Vis Sci 35, 3064-3070. Nonaka, G., Hsu, F.L., Nishioka, I., 1981. Structures of dimeric, trimeric, and tetrameric procyanidins from Areca catechu L. J Chem Soc Chem Commun, 781-783. O'Connor, B.P., Gleeson, M.W., Noelle, R.J., Erickson, L.D., 2003. The rise and fall of long-lived humoral immunity: terminal differentiation of plasma cells in health and disease. Immunol Rev 194, 61-76. O'Donnell, R.K., Mick, R., Feldman, M., Hino, S., Wang, Y., Brose, M.S., Muschel, R.J., 2007. Distribution of dendritic cell subtypes in primary oral squamous cell carcinoma is inconsistent with a functional response. Cancer Lett 255, 145-152. Ochoa, A.C., Zea, A.H., Hernandez, C., Rodriguez, P.C., 2007. Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13, 721s-726s. Opferman, J.T., Korsmeyer, S.J., 2003. Apoptosis in the development and maintenance of the immune system. Nat Immunol 4, 410-415. Ostrand-Rosenberg, S., Sinha, P., 2009. Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182, 4499-4506. Pak, A.S., Wright, M.A., Matthews, J.P., Collins, S.L., Petruzzelli, G.J., Young, M.R., 1995. Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res 1, 95-103. Panigrahi, G.B., Rao, A.R., 1982. Chromosome-breaking ability of arecoline, a major betel-nut alkaloid, in mouse bone-marrow cells in vivo. Mutat Res 103, 197-204. Panigrahi, G.B., Rao, A.R., 1984. Induction of in vivo sister chromatid exchanges by arecaidine, a betel nut alkaloid, in mouse bone-marrow cells. Cancer Lett 23, 189-192. Panigrahi, G.B., Rao, A.R., 1986. Study of the genotoxicity of the total aqueous extract of betel nut and its tannin. Carcinogenesis 7, 37-39. Park, Y.C., Rimbach, G., Saliou, C., Valacchi, G., Packer, L., 2000. Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-alpha secretion, and NF-kappaB-dependent gene expression in RAW 264.7 macrophages. FEBS Lett 465, 93-97. Pierini, R., Kroon, P.A., Guyot, S., Ivory, K., Johnson, I.T., Belshaw, N.J., 2008. Procyanidin effects on oesophageal adenocarcinoma cells strongly depend on flavan-3-ol degree of polymerization. Mol Nutr Food Res 52, 1399-1407. Pillai, M.R., Balaram, P., Abraham, T., Nair, M.K., 1987. Lymphocyte populations in premalignant lesions and cancer of the oral cavity. Neoplasma 34, 469-479. Pillai, M.R., Balaram, P., Kannan, S., Sudha, L., Nalinakumari, K.R., Hareendran, N.K., Nair, M.K., 1990. Interferon activation of latent natural killer cells and alteration in kinetics of target cell lysis: clinical implications for oral precancerous lesions. Oral Surg Oral Med Oral Pathol 70, 458-461. Prior, R.L., Gu, L., 2005. Occurrence and biological significance of proanthocyanidins in the American diet. Phytochemistry 66, 2264-2280. Rahman, I., Biswas, S.K., Kirkham, P.A., 2006. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol 72, 1439-1452. Rajendran, R., Sugathan, C.K., Remani, P., Ankathil, R., Vijayakumar, T., 1986. Cell mediated and humoral immune responses in oral submucous fibrosis. Cancer 58, 2628-2631. Ramiro-Puig, E., Perez-Cano, F.J., Ramirez-Santana, C., Castellote, C., Izquierdo-Pulido, M., Permanyer, J., Franch, A., Castell, M., 2007. Spleen lymphocyte function modulated by a cocoa-enriched diet. Clin Exp Immunol 149, 535-542. Ranadive, K.J., Gothoskar, S.V., Rao, A.R., Tezabwalla, B.U., Ambaye, R.Y., 1976. Experimental studies on betel nut and tobacco carcinogenicity. Int J Cancer 17, 469-476. Ranadive, K.J., Ranadive, S.N., Shivapurkar, N.M., Gothoskar, S.V., 1979. Betel quid chewing and oral cancer: experimental studies on hamsters. Int J Cancer 24, 835-843. Reichert, T.E., Strauss, L., Wagner, E.M., Gooding, W., Whiteside, T.L., 2002. Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin Cancer Res 8, 3137-3145. Rice, S.Q., Crane, I.J., Scully, C., Prime, S.S., 1992. Production of a suppressor of lymphocyte proliferation by two human oral carcinoma cell lines. Scand J Immunol 36, 443-452. Rodriguez, P.C., Quiceno, D.G., Ochoa, A.C., 2007. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 109, 1568-1573. Rodriguez, P.C., Quiceno, D.G., Zabaleta, J., Ortiz, B., Zea, A.H., Piazuelo, M.B., Delgado, A., Correa, P., Brayer, J., Sotomayor, E.M., Antonia, S., Ochoa, J.B., Ochoa, A.C., 2004. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64, 5839-5849. Rossner, S., Voigtlander, C., Wiethe, C., Hanig, J., Seifarth, C., Lutz, M.B., 2005. Myeloid dendritic cell precursors generated from bone marrow suppress T cell responses via cell contact and nitric oxide production in vitro. Eur J Immunol 35, 3533-3544. Schroder, K., Hertzog, P.J., Ravasi, T., Hume, D.A., 2004. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75, 163-189. Selvan, R.S., Selvakumaran, M., Rao, A.R., 1991. Influence of arecoline on immune system: II. Suppression of thymus-dependent immune responses and parameter of non-specific resistance after short-term exposure. Immunopharmacol Immunotoxicol 13, 281-309. Serafini, P., Carbley, R., Noonan, K.A., Tan, G., Bronte, V., Borrello, I., 2004. High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 64, 6337-6343. Shankaran, V., Ikeda, H., Bruce, A.T., White, J.M., Swanson, P.E., Old, L.J., Schreiber, R.D., 2001. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107-1111. Shao, Z.H., Becker, L.B., Vanden Hoek, T.L., Schumacker, P.T., Li, C.Q., Zhao, D., Wojcik, K., Anderson, T., Qin, Y., Dey, L., Yuan, C.S., 2003. Grape seed proanthocyanidin extract attenuates oxidant injur | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10745 | - |
dc.description.abstract | 流行病學研究顯示嚼食檳榔會提高罹患口腔黏膜下纖維化症及口腔癌的機率,且實驗證據指出病人免疫系統的惡化與嚼食檳榔所導致的口腔疾病病程的發展有重要的相關性。研究發現檳榔子萃取物能直接引起嗜中性球細胞及多種口腔細胞的死亡且增加細胞的氧化性傷害。由於T淋巴球細胞已被證實為主要浸潤於口腔癌前病變組織或口腔腫瘤的重要免疫細胞,因此推測此大量浸潤的T淋巴球可能會受到檳榔成分的直接作用而導致其媒介的免疫功能受到影響。本論文主要研究檳榔子萃取物對於T淋巴球活性及功能的影響,並進一步探討活性氧化物(ROS)於檳榔子萃取物的免疫調節作用所扮演的角色。此外更進一步研究檳榔子萃取物在活體動物中的免疫調節作用。實驗結果顯示檳榔子萃取物對於脾臟細胞具有明顯的毒性且會抑制介白素-2(interleukin-2)及干擾素-γ(interferon-γ)的分泌,而對於介白素-4的抑制作用則不明顯。上述檳榔子萃取物的抑制作用可以被抗氧化劑N-乙醯半胱胺酸(N-acetyl-L-cysteine以下簡稱NAC)部分且有效的回復。檳榔子萃取物會增加T淋巴球ROS的增加及降低細胞內穀胱甘肽 (glutathione以下簡稱GSH)的含量,顯示檳榔子萃取物可藉由增加細胞內產生ROS來抑制T淋巴球的活化及第一型T幫手淋巴球細胞激素的製造。
檳榔子萃取物明顯地增加脾臟細胞的凋亡、促進粒線體膜電位的去極化、釋放粒線體內cytochrome c、活化細胞內caspase-9 及增加凋亡細胞的ROS。除了粒線體膜電位的去極化完全無法被NAC所預防,NAC對於檳榔子萃取物所引起的上述作用都具有部分但顯著的回復效果。此研究結果指出檳榔子萃取物對於脾臟細胞的毒性作用與活化粒線體凋亡途徑有關,同時會導致細胞內ROS的增加。由於檳榔子萃取物含有豐富的多酚類,進一步研究檳榔子萃取物中的多酚類是否可以引起脾臟細胞的凋亡,結果發現多酚類含量較多的檳榔子萃取物(PANE)同樣具有導致脾臟細胞凋亡的效果,且進一步比較萃取物中不同聚合程度的前花青素(procyanidins),發現聚合程度大於五的pentamers即開始會引起脾臟細胞的凋亡,隨著前花青素聚合程度愈高引起細胞凋亡的程度也愈明顯。此外PANE也會導致細胞內GSH的下降,顯示細胞內氧化性傷害的增加,且細胞內GSH下降的程度也與前花青素聚合程度成正相關。此部分研究顯示檳榔子萃取物中高聚合程度的前花青素可能會導致細胞抗氧化物GSH的下降而引起細胞的凋亡。 活體動物的試驗中發現,腹腔注射檳榔子萃取物及PANE會導致脾臟的腫脹及增加一群CD11b+的骨髓衍生性細胞,此群細胞具有小鼠骨髓衍生性抑制性細胞(MDSC)的重要細胞表面標誌: CD11b及Gr-1。CD11b+Gr-1+ 的細胞族群在給予檳榔子萃取物的小鼠脾臟及血液中的比率有顯著的增加。進一步分析該群細胞的功能發現其抑制性細胞激素介白素-10(IL-10)的分泌量、第一型精胺酸酶(arginase-I)酵素的活性及表現第一型精胺酸酶及誘導型一氧化氮合成酶(inducible nitric oxide synthase;iNOS)基因的能力都有顯著地增加,顯示此群細胞具有骨髓衍生抑制性細胞(myeloid-derived suppressor cell;MDSC)典型的功能特性。 綜合本論文的研究結果,發現檳榔子萃取物具有直接調節細胞媒介免疫反應的作用,包含降低T淋巴球細胞激素的分泌、導致脾臟細胞的凋亡及增加骨髓衍生抑制性細胞的數量。而檳榔子萃取物中的前花青素於上述的免疫調節作用中扮演重要的角色。本論文結果有助於了解檳榔子的成分如何調節免疫細胞及導致細胞媒介免疫反應惡化的可能機制。 | zh_TW |
dc.description.abstract | Areca quid chewing is a major risk factor associated with oral submucous fibrosis and oral cancer. Experimental evidence indicates that immune deterioration is closely associated with the pathophysiology of areca-associated oral diseases. In addition, the induction of oxidative stress and cell death has been shown to play a role in the cytotoxic and genotoxic effects induced by areca nut extracts (ANE) in oral cells and neutrophils. As T lymphocytes are one of the major immunocompetent cells present in the lesions of both OSF and oral cancer patients, it is hypothesized that T cell–mediated immune responses may be altered by ANE. The present studies investigated the immunomodulatory effect of ANE on T cell reactivity and the role of reactive oxygen species (ROS) in ANE-mediated effects in vitro. In addition, the immunomodulatory effect of ANE and polyphenol-enriched ANE (PANE) was examined in vivo. ANE induced a marked cytotoxic effect, and suppressed the production of IL-2 and IFN-γ by splenocytes, whereas the production of IL-4 was unaffected. The thiol antioxidant N-acetyl-L-cysteine (NAC) partially but significantly attenuated ANE-mediated cytotoxicity and suppression of IL-2 and IFN-γ production. In splenic T cells, ANE increased the cellular ROS levels, which was also attenuated by the presence of NAC. Concordantly, the cellular level of glutathione was diminished by ANE in splenic T cells pretreated with NAC. These results demonstrated that ANE markedly suppressed T-cell activation and Th1 cytokine production, which was mediated, at least in part, by the induction of oxidative stress.
ANE significantly enhanced splenocyte apoptosis. The depolarization of mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-9 were induced by ANE, indicating the activation of the mitochondrion-dependent apoptotic pathway. Moreover, an increased level in the intracellular ROS was detected in ANE-treated splenocytes undergoing apoptosis. NAC significantly attenuated ANE-mediated apoptosis, caspase-9 activation and ROS production but not mitochondrial membrane potential depolarization. These results demonstrated the pro-apoptotic effect of ANE in primary splenocytes, which was mediated by the activation of the mitochondrion-dependent pathway and oxidative stress. In addition, PANE and its fractionated oligomeric procyanidins from pentamers to decamers were active in inducing apoptosis. A marked diminishment in the level of intracellular thiols was revealed in splenocytes treated with pentamers to decamers. Pretreatment with NAC resulted in significant attenuation of both apoptosis and thiol diminishment induced by areca procyanidins. These results indicated that highly oligomeric procyanidins derived from areca nut induced a chain length-dependent pro-apoptotic effect in primary lymphocytes possibly via the diminishment of intracellular thiols. Intraperitoneal administration of antigen-sensitized BALB/c mice with ANE or PANE significantly increased the spleen index and the splenic cellularity of immature myeloid CD11b+ cells. The population of CD11b+Gr-1+ cells in the spleen and peripheral blood was markedly enhanced by ANE and PANE. In addition, ANE administration significantly augmented the production of IL-10, and the mRNA expression of iNOS and arginase I by splenocytes and splenic CD11b+ cells stimulated with lipopolysaccharide. These results suggested that ANE administration to antigen-sensitized mice enhanced the development of CD11b+Gr-1+ cells that exhibited a functional profile of myeloid-derived suppressor cells (MDSC). Taken together, this study demonstrated the direct immunomodulatory effect of ANE on the down-regulation of Th1 cytokines in vitro, induction of lymphocyte apoptosis in vitro and generation of MDSC in vivo. In addition, areca-derived procyanidins may be the potential candidates responsible for the ANE-mediated immunomodulatory effects. These results provide evidence to show that areca constituents may directly compromise the cell-mediated immunity which was previously reported to be down-regulated in areca quid chewers with oral precancer and cancer. | en |
dc.description.provenance | Made available in DSpace on 2021-05-20T21:55:05Z (GMT). No. of bitstreams: 1 ntu-99-D94629010-1.pdf: 4846498 bytes, checksum: c153e9878bbb18075969e9087673f565 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 中文摘要 ii
Abstract v List of Abbreviations viii Contents x List of Figures and Tables xiii Chapter 1. Background 1 1.1 Areca nut chewing related diseases 1 1.2 Areca quid ingredients 2 1.3 Polyphenols and procyanidins 3 1.4 T cell-mediated immune responses 6 1.5 Myeloid-derived suppressor cells 8 1.6 Apoptosis 10 1.7 Immune deterioration in AQ chewing-related oral diseases 13 1.7-1 Down-regulation of T cell responses 13 1.7-2 Alteration of cytokine profile 14 1.7-3 Dysfunction of humoral immunity 16 1.7-4 Immunosuppression associated with oral diseases 17 1.8 The direct effect of AQ components on oral and immune cells 18 1.8-1 Mitogenic and cytotoxic effect of AQ components on oral cells 18 1.8-2 Proinflammatory effect of AQ components 20 1.8-3 Immunomodulatory effect of AQ components 21 Chapter 2. Rationale 23 Chapter 3. Materiasl and Methods 25 3.1 Reagents and areca nut extract 25 3.2 Animals 26 3.3 Protocol of ANE treatment and OVA sensitization 27 3.4 Cell isolation and culture 27 3.5 Spleen index 28 3.6 MTT assay 28 3.7 Enzyme-linked immunosorbent assay (ELISA) for cytokine quantification 29 3.8 Cell cycle analysis of splenic lymphocytes 30 3.9 Terminal dUTP nick-end labeling (TUNEL) assay 31 3.10 Hoechst staining 32 3.11 Determination of mitochondria membrane potential by JC-1 staining 32 3.12 Western blotting analysis for cytochrome c 33 3.13 Detection of caspase activation 34 3.14 Measurement of ROS level 34 3.15 Detection of intracellular thiols using flow cytometry 35 3.16 Cellularity of PBMC and splenocytes 35 3.17 Measurement of Gr-1 expression and morphology of splenic CD11b+ cells 36 3.18 Detection of arginase-I activity 36 3.19 Reverse transcriptase-polymerase chain reaction (RT-PCR) 37 Chapter 4. Experimental Results 39 4.1 ANE suppresses T-cell activation and cytokine production via the induction of oxidative stress 39 4.1-1 Cytotoxicity of ANE on splenocytes 39 4.1-2 Differential effects of ANE on IFN-γ, IL-2 and IL-4 production by splenocytes 42 4.1-3 Induction of ROS and diminishment of cellular thiols by ANE in splenic T cells 47 4.2 Involvement of the mitochondrion-dependent pathway and oxidative stress in ANE-induced splenocyte apoptosis 51 4.2-1 Induction of apoptosis of splenocytes by ANE 51 4.2-2 Involvement of the mitochondrion-dependent pathway in ANE-mediated splenocyte apoptosis 58 4.2-3 The role of ROS in ANE-mediated splenocyte apoptosis 63 4.3 Areca-derived highly oligomeric procyanidins induce splenocyte apoptosis via the depletion of intracellular thiols 68 4.3-1 Polyphenol-enriched ANE (PANE) and areca-derived highly oligomeric procyanidins induced splenocyte apoptosis 68 4.3-2 Effect of areca-derived procyanidins on the level of intracellular thiols in splenocytes 77 4.4 ANE and PANE enhances the development of CD11b+Gr-1+ cells with the characteristics of myeloid-derived suppressor cells in OVA-sensitized BALB/c mice 83 4.4-1 Induction of CD11b+Gr-1+ cells by ANE and PANE in vivo 83 4.4-2 Functional characteristics of ANE-induced CD11b+Gr-1+ cells 89 Chapter 5. Discussion 94 5.1 ANE suppresses T-cell activation and IFN-γ production via the induction of oxidative stress 94 5.2 Involvement of the mitochondrion-dependent pathway and oxidative stress in the apoptosis of murine splenocytes induced by ANE 99 5.3 Highly oligomeric procyanidins derived from areca nuts induce lymphocyte apoptosis via the depletion of intracellular thiols 104 5.4 Induction of myeloid derived suppressor cells by ANE and PANE in vivo 109 Chapter 6. Summary and conclusions 116 Chapter 7. Future perspectives 118 References 121 | |
dc.language.iso | en | |
dc.title | 檳榔子萃取物抑制T細胞功能及促進骨髓衍生抑制性細胞生成之免疫調節作用 | zh_TW |
dc.title | The immunomodulatory effect of areca nut extract on the functionality of T cells and the induction of myeloid-derived suppressor cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 李志恆,劉宗榮,林嬪嬪,朱瑞民,戚謹文 | |
dc.subject.keyword | 檳榔子萃取物,前花青素,免疫抑制,細胞激素,凋亡,骨髓衍生抑制性細胞,氧化性傷害, | zh_TW |
dc.subject.keyword | areca nut extract,procyanidins,immunosuppression,cytokines,apoptosis,myeloid-derived suppressor cells,oxidative stress, | en |
dc.relation.page | 136 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2010-07-27 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
顯示於系所單位: | 獸醫學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-99-1.pdf | 4.73 MB | Adobe PDF | 檢視/開啟 |
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。