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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 賈景山(Jean-San Chia) | |
dc.contributor.author | Tzung-Fan Tang | en |
dc.contributor.author | 唐宗凡 | zh_TW |
dc.date.accessioned | 2021-05-20T19:59:14Z | - |
dc.date.available | 2012-09-09 | |
dc.date.available | 2021-05-20T19:59:14Z | - |
dc.date.copyright | 2010-09-09 | |
dc.date.issued | 2010 | |
dc.date.submitted | 2010-06-23 | |
dc.identifier.citation | Abe M, Kondo S, Hirano S, Ambo Y, Tanaka E, Morikawa T, Okushiba S, and Katoh H. 2003. Long-term survival after radical resection of advanced pancreatic cancer: a case report with special reference to CD8+ T-cell infiltration. Int J Gastrointest Cancer 33(2-3):107-110.
Achen MG, McColl BK, and Stacker SA. 2005. Focus on lymphangiogenesis in tumor metastasis. Cancer Cell 7(2):121-127. Achur RN, Freeman WM, and Vrana KE. 2010. Circulating cytokines as biomarkers of alcohol abuse and alcoholism. J Neuroimmune Pharmacol 5(1):83-91. Ahn JM, Huang CC, and Cho HT. 1993. Localization of interleukin-1 in human squamous carcinomas of the head and neck. Laryngoscope 103(5):529-532. Alvaro T, Lejeune M, Salvado MT, Bosch R, Garcia JF, Jaen J, Banham AH, Roncador G, Montalban C, and Piris MA. 2005. Outcome in Hodgkin's lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res 11(4):1467-1473. Annunziato F, Cosmi L, Liotta F, Lazzeri E, Manetti R, Vanini V, Romagnani P, Maggi E, and Romagnani S. 2002. Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. J Exp Med 196(3):379-387. Apte RN, Dotan S, Elkabets M, White MR, Reich E, Carmi Y, Song X, Dvozkin T, Krelin Y, and Voronov E. 2006a. The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev 25(3):387-408. Apte RN, Krelin Y, Song X, Dotan S, Recih E, Elkabets M, Carmi Y, Dvorkin T, White RM, Gayvoronsky L et al. . 2006b. Effects of micro-environment- and malignant cell-derived interleukin-1 in carcinogenesis, tumour invasiveness and tumour-host interactions. Eur J Cancer 42(6):751-759. Apte RN, and Voronov E. 2002. Interleukin-1--a major pleiotropic cytokine in tumor-host interactions. Semin Cancer Biol 12(4):277-290. Apte RN, and Voronov E. 2008. Is interleukin-1 a good or bad 'guy' in tumor immunobiology and immunotherapy? Immunol Rev 222:222-241. Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, Mosseri V, Laccourreye O, Bruneval P, Fridman WH et al. . 2006. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12(2):465-472. Balkwill F, Charles KA, and Mantovani A. 2005. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7(3):211-217. Beauchemin V, Villeneuve L, Rodriguez-Cimadevilla JC, Rajotte D, Kenney JS, Clark SC, and Hoang T. 1991. Interleukin-6 production by the blast cells of acute myeloblastic leukemia: regulation by endogenous interleukin-1 and biological implications. J Cell Physiol 148(3):353-361. Becker C, Fantini MC, and Neurath MF. 2006. TGF-beta as a T cell regulator in colitis and colon cancer. Cytokine Growth Factor Rev 17(1-2):97-106. Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, Burg J, Strand S, Kiesslich R, Huber S et al. . 2004. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21(4):491-501. Benitez-Bribiesca L, Wong A, Utrera D, and Castellanos E. 2001. The role of mast cell tryptase in neoangiogenesis of premalignant and malignant lesions of the uterine cervix. J Histochem Cytochem 49(8):1061-1062. Berger FG. 2004. The interleukin-6 gene: a susceptibility factor that may contribute to racial and ethnic disparities in breast cancer mortality. Breast Cancer Res Treat 88(3):281-285. Bergers G, and Benjamin LE. 2003. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401-410. Bian Y, Terse A, Du J, Hall B, Molinolo A, Zhang P, Chen W, Flanders KC, Gutkind JS, Wakefield LM et al. . 2009. Progressive tumor formation in mice with conditional deletion of TGF-beta signaling in head and neck epithelia is associated with activation of the PI3K/Akt pathway. Cancer Res 69(14):5918-5926. Bissell MJ, and Radisky D. 2001. Putting tumours in context. Nat Rev Cancer 1(1):46-54. Boccia S, Hashibe M, Galli P, De Feo E, Asakage T, Hashimoto T, Hiraki A, Katoh T, Nomura T, Yokoyama A et al. . 2009. Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach. Cancer Epidemiol Biomarkers Prev 18(1):248-254. Boffetta P. 2008. Tobacco smoking and risk of bladder cancer. Scand J Urol Nephrol Suppl(218):45-54. Bommert K, Bargou RC, and Stuhmer T. 2006. Signalling and survival pathways in multiple myeloma. Eur J Cancer 42(11):1574-1580. Bose A, Chakraborty T, Chakraborty K, Pal S, and Baral R. 2008. Dysregulation in immune functions is reflected in tumor cell cytotoxicity by peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients. Cancer Immun 8:10. Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini P, Zamboni P, Restifo NP, and Zanovello P. 2000. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96(12):3838-3846. Brunnemann KD, Prokopczyk B, Djordjevic MV, and Hoffmann D. 1996. Formation and analysis of tobacco-specific N-nitrosamines. Crit Rev Toxicol 26(2):121-137. Carpenter JM, Syms MJ, and Sniezek JC. 2005. Oral carcinoma associated with betel nut chewing in the Pacific: an impending crisis? Pac Health Dialog 12(1):158-162. Cesana GC, DeRaffele G, Cohen S, Moroziewicz D, Mitcham J, Stoutenburg J, Cheung K, Hesdorffer C, Kim-Schulze S, and Kaufman HL. 2006. Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol 24(7):1169-1177. Chang MC, Chiang CP, Lin CL, Lee JJ, Hahn LJ, and Jeng JH. 2005. Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit. Oral Oncol 41(8):757-775. Chauhan D, Uchiyama H, Akbarali Y, Urashima M, Yamamoto K, Libermann TA, and Anderson KC. 1996. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood 87(3):1104-1112. Chen ML, Pittet MJ, Gorelik L, Flavell RA, Weissleder R, von Boehmer H, and Khazaie K. 2005a. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci U S A 102(2):419-424. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, and Wahl SM. 2003. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198(12):1875-1886. Chen W, Perruche S, and Li J. 2007. CD4+CD25+ T regulatory cells and TGF-beta in mucosal immune system: the good and the bad. Curr Med Chem 14(21):2245-2249. Chen W, and Wahl SM. 2003. TGF-beta: the missing link in CD4+CD25+ regulatory T cell-mediated immunosuppression. Cytokine Growth Factor Rev 14(2):85-89. Chen YJ, Chang JT, Liao CT, Wang HM, Yen TC, Chiu CC, Lu YC, Li HF, and Cheng AJ. 2008. Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis. Cancer Sci 99(8):1507-1514. Chen YK, Huang HC, Lin LM, and Lin CC. 1999. Primary oral squamous cell carcinoma: an analysis of 703 cases in southern Taiwan. Oral Oncol 35(2):173-179. Chen YQ, Shi HZ, Qin XJ, Mo WN, Liang XD, Huang ZX, Yang HB, and Wu C. 2005b. CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion. Am J Respir Crit Care Med 172(11):1434-1439. Cheng YA, and Tsai CC. 1999. Nicotine- and arecoline-induced interleukin-1 secretion and intercellular adhesion molecular-1 expression in human oral epidermoid carcinoma cells in vitro. Arch Oral Biol 44(10):843-851. Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, Pathmanathan R, Prime SS, Teo SH, Patel V et al. . 2009. Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure. Oral Oncol 45(8):712-719. Chiba T, Ohtani H, Mizoi T, Naito Y, Sato E, Nagura H, Ohuchi A, Ohuchi K, Shiiba K, Kurokawa Y et al. . 2004. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis. Br J Cancer 91(9):1711-1717. Chikamatsu K, Sakakura K, Whiteside TL, and Furuya N. 2007. Relationships between regulatory T cells and CD8+ effector populations in patients with squamous cell carcinoma of the head and neck. Head Neck 29(2):120-127. Chung YJ, Song JM, Lee JY, Jung YT, Seo EJ, Choi SW, and Rhyu MG. 1996. Microsatellite instability-associated mutations associate preferentially with the intestinal type of primary gastric carcinomas in a high-risk population. Cancer Res 56(20):4662-4665. Correale P, Rotundo MS, Del Vecchio MT, Remondo C, Migali C, Ginanneschi C, Tsang KY, Licchetta A, Mannucci S, Loiacono L et al. . 2010. Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. J Immunother 33(4):435-441. Cotterchio M, Kreiger N, Sloan M, and Steingart A. 2001. Nonsteroidal anti-inflammatory drug use and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10(11):1213-1217. Coussens LM, and Werb Z. 2002. Inflammation and cancer. Nature 420(6917):860-867. Cozen W, Gill PS, Ingles SA, Masood R, Martinez-Maza O, Cockburn MG, Gauderman WJ, Pike MC, Bernstein L, Nathwani BN et al. . 2004. IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma. Blood 103(8):3216-3221. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M et al. . 2004. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9):942-949. Curotto de Lafaille MA, and Lafaille JJ. 2009. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30(5):626-635. Derynck R, Akhurst RJ, and Balmain A. 2001. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29(2):117-129. Desai PB. 1983. Clinical cancer research in India--present status and future prospects. Indian J Med Res 78 Suppl:8-28. Diederichsen AC, Hjelmborg JB, Christensen PB, Zeuthen J, and Fenger C. 2003. Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells. Cancer Immunol Immunother 52(7):423-428. Dikshit RP, Ramadas K, Hashibe M, Thomas G, Somanathan T, and Sankaranarayanan R. 2006. Association between diabetes mellitus and pre-malignant oral diseases: a cross sectional study in Kerala, India. Int J Cancer 118(2):453-457. Dinarello CA. 2002. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 20(5 Suppl 27):S1-13. Distel LV, Fickenscher R, Dietel K, Hung A, Iro H, Zenk J, Nkenke E, Buttner M, Niedobitek G, and Grabenbauer GG. 2009. Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease. Oral Oncol 45(10):e167-174. Duncan LM, Richards LA, and Mihm MC, Jr. 1998. Increased mast cell density in invasive melanoma. J Cutan Pathol 25(1):11-15. Dunn E, Sims JE, Nicklin MJ, and O'Neill LA. 2001. Annotating genes with potential roles in the immune system: six new members of the IL-1 family. Trends Immunol 22(10):533-536. Egeblad M, and Werb Z. 2002. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161-174. Fattorossi A, Battaglia A, Ferrandina G, Buzzonetti A, Legge F, Salutari V, and Scambia G. 2004. Lymphocyte composition of tumor draining lymph nodes from cervical and endometrial cancer patients. Gynecol Oncol 92(1):106-115. Ferlay J PP, Parkin DM. 2002. Cancer incidence, mortality and prevalence worldwide. IARC Cancer Base (2002 estimates) Lyon: IARC Press; 2004. Funada Y, Noguchi T, Kikuchi R, Takeno S, Uchida Y, and Gabbert HE. 2003. Prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in colorectal cancer. Oncol Rep 10(2):309-313. Gallo O, Gori AM, Attanasio M, Martini F, Giusti B, Boddi M, Gallina E, Fini O, and Abbate R. 1993. Interleukin-1 beta and interleukin-6 release by peripheral blood monocytes in head and neck cancer. Br J Cancer 68(3):465-468. Garcia-Rodriguez LA, and Huerta-Alvarez C. 2001. Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Epidemiology 12(1):88-93. Gasparoto TH, de Souza Malaspina TS, Benevides L, de Melo EJ, Jr., Costa MR, Damante JH, Ikoma MR, Garlet GP, Cavassani KA, da Silva JS et al. . 2010. Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment. Cancer Immunol Immunother 59(6):819-828. Ghiringhelli F, Menard C, Terme M, Flament C, Taieb J, Chaput N, Puig PE, Novault S, Escudier B, Vivier E et al. . 2005a. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med 202(8):1075-1085. Ghiringhelli F, Puig PE, Roux S, Parcellier A, Schmitt E, Solary E, Kroemer G, Martin F, Chauffert B, and Zitvogel L. 2005b. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med 202(7):919-929. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, and Karin M. 2004. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118(3):285-296. Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, and Ley TJ. 2004. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 21(4):589-601. Guh JY, Chen HC, Tsai JF, and Chuang LY. 2007. Betel-quid use is associated with heart disease in women. Am J Clin Nutr 85(5):1229-1235. Hanahan D, and Weinberg RA. 2000. The hallmarks of cancer. Cell 100(1):57-70. Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E et al. . 2009. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 18(2):541-550. Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, and McDonald DM. 2000. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol 156(4):1363-1380. Haura EB, Turkson J, and Jove R. 2005. Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer. Nat Clin Pract Oncol 2(6):315-324. Heldin CH, Rubin K, Pietras K, and Ostman A. 2004. High interstitial fluid pressure - an obstacle in cancer therapy. Nat Rev Cancer 4(10):806-813. Hirota SK, Braga FP, Penha SS, Sugaya NN, and Migliari DA. 2008. Risk factors for oral squamous cell carcinoma in young and older Brazilian patients: a comparative analysis. Med Oral Patol Oral Cir Bucal 13(4):E227-231. Hoffmann D, and Hoffmann I. 1997. The changing cigarette, 1950-1995. J Toxicol Environ Health 50(4):307-364. Houot R, Perrot I, Garcia E, Durand I, and Lebecque S. 2006. Human CD4+CD25high regulatory T cells modulate myeloid but not plasmacytoid dendritic cells activation. J Immunol 176(9):5293-5298. Ichimiya Y, Fuwa N, Kamata M, Kodaira T, Furutani K, Tachibana H, Tomita N, and Hidano S. 2005. Treatment results of stage I oral tongue cancer with definitive radiotherapy. Oral Oncol 41(5):520-525. Imada A, Shijubo N, Kojima H, and Abe S. 2000. Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma. Eur Respir J 15(6):1087-1093. Ishihara K, and Hirano T. 2002. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 13(4-5):357-368. Ito M, Minamiya Y, Kawai H, Saito S, Saito H, Nakagawa T, Imai K, Hirokawa M, and Ogawa J. 2006. Tumor-derived TGFbeta-1 induces dendritic cell apoptosis in the sentinel lymph node. J Immunol 176(9):5637-5643. Ivanov, II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, and Littman DR. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126(6):1121-1133. Izumoto S, Arita N, Ohnishi T, Hiraga S, Taki T, Tomita N, Ohue M, and Hayakawa T. 1997. Microsatellite instability and mutated type II transforming growth factor-beta receptor gene in gliomas. Cancer Lett 112(2):251-256. Jacob BJ, Straif K, Thomas G, Ramadas K, Mathew B, Zhang ZF, Sankaranarayanan R, and Hashibe M. 2004. Betel quid without tobacco as a risk factor for oral precancers. Oral Oncol 40(7):697-704. Jakowlew SB. 2006. Transforming growth factor-beta in cancer and metastasis. Cancer Metastasis Rev 25(3):435-457. Jego G, Bataille R, Geffroy-Luseau A, Descamps G, and Pellat-Deceunynck C. 2006. Pathogen-associated molecular patterns are growth and survival factors for human myeloma cells through Toll-like receptors. Leukemia 20(6):1130-1137. Jenkins BJ, Grail D, Nheu T, Najdovska M, Wang B, Waring P, Inglese M, McLoughlin RM, Jones SA, Topley N et al. . 2005. Hyperactivation of Stat3 in gp130 mutant mice promotes gastric hyperproliferation and desensitizes TGF-beta signaling. Nat Med 11(8):845-852. Jung YJ, Isaacs JS, Lee S, Trepel J, and Neckers L. 2003. IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J 17(14):2115-2117. Kawaida H, Kono K, Takahashi A, Sugai H, Mimura K, Miyagawa N, Omata H, Ooi A, and Fujii H. 2005. Distribution of CD4+CD25high regulatory T-cells in tumor-draining lymph nodes in patients with gastric cancer. J Surg Res 124(1):151-157. Khazaie K, and von Boehmer H. 2006. The impact of CD4+CD25+ Treg on tumor specific CD8+ T cell cytotoxicity and cancer. Semin Cancer Biol 16(2):124-136. Kiaris H, Chatzistamou I, Kalofoutis C, Koutselini H, Piperi C, and Kalofoutis A. 2004. Tumour-stroma interactions in carcinogenesis: basic aspects and perspectives. Mol Cell Biochem 261(1-2):117-122. Kim SJ, Im YH, Markowitz SD, and Bang YJ. 2000. Molecular mechanisms of inactivation of TGF-beta receptors during carcinogenesis. Cytokine Growth Factor Rev 11(1-2):159-168. Knutson KL, Disis ML, and Salazar LG. 2007. CD4 regulatory T cells in human cancer pathogenesis. Cancer Immunol Immunother 56(3):271-285. Ko YC, Huang YL, Lee CH, Chen MJ, Lin LM, and Tsai CC. 1995. Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 24(10):450-453. Koenders MI, Lubberts E, Oppers-Walgreen B, van den Bersselaar L, Helsen MM, Kolls JK, Joosten LA, and van den Berg WB. 2005. Induction of cartilage damage by overexpression of T cell interleukin-17A in experimental arthritis in mice deficient in interleukin-1. Arthritis Rheum 52(3):975-983. Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, Oukka M, and Kuchroo VK. 2007. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448(7152):484-487. Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH et al. . 2009. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141-1149. Kryczek I, Wei S, Zou L, Altuwaijri S, Szeliga W, Kolls J, Chang A, and Zou W. 2007. Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol 178(11):6730-6733. Kubo T, Hatton RD, Oliver J, Liu X, Elson CO, and Weaver CT. 2004. Regulatory T cell suppression and anergy are differentially regulated by proinflammatory cytokines produced by TLR-activated dendritic cells. J Immunol 173(12):7249-7258. Kusmartsev S, and Gabrilovich DI. 2002. Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother 51(6):293-298. Laso FJ, Vaquero JM, Almeida J, Marcos M, and Orfao A. 2007. Production of inflammatory cytokines by peripheral blood monocytes in chronic alcoholism: relationship with ethanol intake and liver disease. Cytometry B Clin Cytom 72(5):408-415. Lathers DM, Achille NJ, and Young MR. 2003. Incomplete Th2 skewing of cytokines in plasma of patients with squamous cell carcinoma of the head and neck. Hum Immunol 64(12):1160-1166. Lee KW, Kuo WR, Tsai SM, Wu DC, Wang WM, Fang FM, Chiang FY, Ho KY, Wang LF, Tai CF et al. . 2005. Different impact from betel quid, alcohol and cigarette: risk factors for pharyngeal and laryngeal cancer. Int J Cancer 117(5):831-836. Leong PP, Mohammad R, Ibrahim N, Ithnin H, Abdullah M, Davis WC, and Seow HF. 2006. Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast. Immunol Lett 102(2):229-236. Lewis AM, Varghese S, Xu H, and Alexander HR. 2006. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med 4:48. Li H, Nookala S, and Re F. 2007. Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1beta and IL-18 release. J Immunol 178(8):5271-5276. Li X, Ye DF, Xie X, Chen HZ, and Lu WG. 2005. Proportion of CD4+CD25+ regulatory T cell is increased in the patients with ovarian carcinoma. Cancer Invest 23(5):399-403. Liao CT, Chang JT, Wang HM, Ng SH, Hsueh C, Lee LY, Lin CH, Chen IH, Huang SF, Cheng AJ et al. . 2008. Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol 15(3):915-922. Liao CT, Kang CJ, Chang JT, Wang HM, Ng SH, Hsueh C, Lee LY, Lin CH, Cheng AJ, Chen IH et al. . 2007. Survival of second and multiple primary tumors in patients with oral cavity squamous cell carcinoma in the betel quid chewing area. Oral Oncol 43(8):811-819. Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, Drebin JA, Strasberg SM, Eberlein TJ, Goedegebuure PS et al. . 2002. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169(5):2756-2761. Llewellyn CD, Johnson NW, and Warnakulasuriya KA. 2001. Risk factors for squamous cell carcinoma of the oral cavity in young people--a comprehensive literature review. Oral Oncol 37(5):401-418. Lu CF, Huang CS, Tjiu JW, and Chiang CP. 2010. Infiltrating macrophage count: a significant predictor for the progression and prognosis of oral squamous cell carcinomas in Taiwan. Head Neck 32(1):18-25. Lu SL, Reh D, Li AG, Woods J, Corless CL, Kulesz-Martin M, and Wang XJ. 2004. Overexpression of transforming growth factor beta1 in head and neck epithelia results in inflammation, angiogenesis, and epithelial hyperproliferation. Cancer Res 64(13):4405-4410. Ma HL, Napierata L, Stedman N, Benoit S, Collins M, Nickerson-Nutter C, and Young DA. 2010. Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells. Arthritis Rheum 62(2):430-440. Maggi E, Cosmi L, Liotta F, Romagnani P, Romagnani S, and Annunziato F. 2005. Thymic regulatory T cells. Autoimmun Rev 4(8):579-586. Makitie AA, Koivunen P, Keski-Santti H, Tornwall J, Pukkila M, Laranne J, Luukkaa M, Vuola J, Joensuu T, Kajanti M et al. . 2007. Oral tongue carcinoma and its treatment in Finland. Eur Arch Otorhinolaryngol 264(3):263-267. Mantovani A, Sozzani S, Locati M, Allavena P, and Sica A. 2002. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23(11):549-555. Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B et al. . 1995. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 268(5215):1336-1338. Martinez FO, Sica A, Mantovani A, and Locati M. 2008. Macrophage activation and polarization. Front Biosci 13:453-461. Matsuura K, Yamaguchi Y, Ueno H, Osaki A, Arihiro K, and Toge T. 2006. Maturation of dendritic cells and T-cell responses in sentinel lymph nodes from patients with breast carcinoma. Cancer 106(6):1227-1236. McArthur JG, and Raulet DH. 1993. CD28-induced costimulation of T helper type 2 cells mediated by induction of responsiveness to interleukin 4. J Exp Med 178(5):1645-1653. McDonald DM, and Baluk P. 2002. Significance of blood vessel leakiness in cancer. Cancer Res 62(18):5381-5385. Merchant A, Husain SS, Hosain M, Fikree FF, Pitiphat W, Siddiqui AR, Hayder SJ, Haider SM, Ikram M, Chuang SK et al. . 2000. Paan without tobacco: an independent risk factor for oral cancer. Int J Cancer 86(1):128-131. Miescher S, Whiteside TL, Moretta L, and von Fliedner V. 1987. Clonal and frequency analyses of tumor-infiltrating T lymphocytes from human solid tumors. J Immunol 138(11):4004-4011. Miller LJ, Kurtzman SH, Anderson K, Wang Y, Stankus M, Renna M, Lindquist R, Barrows G, and Kreutzer DL. 2000. Interleukin-1 family expression in human breast cancer: interleukin-1 receptor antagonist. Cancer Invest 18(4):293-302. Moore S, Johnson N, Pierce A, and Wilson D. 1999. The epidemiology of lip cancer: a review of global incidence and aetiology. Oral Dis 5(3):185-195. Moore SR, Johnson NW, Pierce AM, and Wilson DF. 2000a. The epidemiology of mouth cancer: a review of global incidence. Oral Dis 6(2):65-74. Moore SR, Johnson NW, Pierce AM, and Wilson DF. 2000b. The epidemiology of tongue cancer: a review of global incidence. Oral Dis 6(2):75-84. Moutsopoulos NM, Wen J, and Wahl SM. 2008. TGF-beta and tumors--an ill-fated alliance. Curr Opin Immunol 20(2):234-240. Mueller MM, and Fusenig NE. 2004. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4(11):839-849. Muwonge R, Ramadas K, Sankila R, Thara S, Thomas G, Vinoda J, and Sankaranarayanan R. 2008. Role of tobacco smoking, chewing and alcohol drinking in the risk of oral cancer in Trivandrum, India: a nested case-control design using incident cancer cases. Oral Oncol 44(5):446-454. Nakakubo Y, Miyamoto M, Cho Y, Hida Y, Oshikiri T, Suzuoki M, Hiraoka K, Itoh T, Kondo S, and Katoh H. 2003. Clinical significance of immune cell infiltration within gallbladder cancer. Br J Cancer 89(9):1736-1742. Nakamura K, Kitani A, Fuss I, Pedersen A, Harada N, Nawata H, and Strober W. 2004. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol 172(2):834-842. Nakao S, Kuwano T, Tsutsumi-Miyahara C, Ueda S, Kimura YN, Hamano S, Sonoda KH, Saijo Y, Nukiwa T, Strieter RM et al. . 2005. Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth. J Clin Invest 115(11):2979-2991. Ness RB, and Cottreau C. 1999. Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 91(17):1459-1467. Numasaki M, Watanabe M, Suzuki T, Takahashi H, Nakamura A, McAllister F, Hishinuma T, Goto J, Lotze MT, Kolls JK et al. . 2005. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. J Immunol 175(9):6177-6189. O'Shea JJ, Gadina M, and Schreiber RD. 2002. Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell 109 Suppl:S121-131. Ochoa AC, Zea AH, Hernandez C, and Rodriguez PC. 2007. Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13(2 Pt 2):721s-726s. Okita R, Saeki T, Takashima S, Yamaguchi Y, and Toge T. 2005. CD4+CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer. Oncol Rep 14(5):1269-1273. Ormandy LA, Hillemann T, Wedemeyer H, Manns MP, Greten TF, and Korangy F. 2005. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res 65(6):2457-2464. Osborne J, Moore PS, and Chang Y. 1999. KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways. Hum Immunol 60(10):921-927. Oshikiri T, Miyamoto M, Shichinohe T, Suzuoki M, Hiraoka K, Nakakubo Y, Shinohara T, Itoh T, Kondo S, and Katoh H. 2003. Prognostic value of intratumoral CD8+ T lymphocyte in extrahepatic bile duct carcinoma as essential immune response. J Surg Oncol 84(4):224-228. Park S, Bae J, Nam BH, and Yoo KY. 2008. Aetiology of cancer in Asia. Asian Pac J Cancer Prev 9(3):371-380. Parsons R, Myeroff LL, Liu B, Willson JK, Markowitz SD, Kinzler KW, and Vogelstein B. 1995. Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. Cancer Res 55(23):5548-5550. Pelucchi C, Gallus S, Garavello W, Bosetti C, and La Vecchia C. 2008. Alcohol and tobacco use, and cancer risk for upper aerodigestive tract and liver. Eur J Cancer Prev 17(4):340-344. Petti S. 2009. Lifestyle risk factors for oral cancer. Oral Oncol 45(4-5):340-350. Pizarro TT, and Cominelli F. 2007. Cloning IL-1 and the birth of a new era in cytokine biology. J Immunol 178(9):5411-5412. Reichart PA, and Nguyen XH. 2008. Betel quid chewing, oral cancer and other oral mucosal diseases in Vietnam: a review. J Oral Pathol Med 37(9):511-514. Reichert TE, Strauss L, Wagner EM, Gooding W, and Whiteside TL. 2002. Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin Cancer Res 8(10):3137-3145. Rhodus NL, Ho V, Miller CS, Myers S, and Ondrey F. 2005. NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev 29(1):42-45. Rosenberg SA, Yang JC, and Restifo NP. 2004. Cancer immunotherapy: moving beyond current vaccines. Nat Med 10(9):909-915. Sakaguchi S. 2005. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6(4):345-352. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, and Toda M. 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155(3):1151-1164. Schaefer C, Kim GG, Albers A, Hoermann K, Myers EN, and Whiteside TL. 2005. Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br J Cancer 92(5):913-920. Schwarz S, Butz M, Morsczeck C, Reichert TE, and Driemel O. 2008. Increased number of CD25 FoxP3 regulatory T cells in oral squamous cell carcinomas detected by chromogenic immunohistochemical double staining. J Oral Pathol Med 37(8):485-489. Scully C. 2002. Oral squamous cell carcinoma; from an hypothesis about a virus, to concern about possible sexual transmission. Oral Oncol 38(3):227-234. Scully C. 2005. Oral cancer; the evidence for sexual transmission. Br Dent J 199(4):203-207. Scully C, Field JK, and Tanzawa H. 2000a. Genetic aberrations in oral or head and neck squamous cell carcinoma 2: chromosomal aberrations. Oral Oncol 36(4):311-327. Scully C, Field JK, and Tanzawa H. 2000b. Genetic aberrations in oral or head and neck squamous cell carcinoma 3: clinico-pathological applications. Oral Oncol 36(5):404-413. Scully C, Field JK, and Tanzawa H. 2000c. Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle contro | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8645 | - |
dc.description.abstract | 背景:口腔鱗狀上皮細胞癌(oral squamous cell carcinoma, OSCC)的發生以及生長與發炎反應有很高的相關性,而發炎反應則是由介白素-1β(interleukin-1β, IL-1β)以及介白素-6(interleukin-6, IL-6)等促發炎反應的細胞激素來調控。然而在腫瘤的微環境中適應性免疫細胞卻是被抑制的。調節性T細胞(regulatory T cell, Treg)的功能主要是藉由變形生長因子(Transforming growth factor-β, TGF-β)等細胞激素的調控,對免疫系統造成抑制。調節性T細胞的抗發炎能力,或許有助於腫瘤的控制,然而也有可能幫助腫瘤逃離免疫系統的監測,進而幫助腫瘤的生長。因此本研究欲觀察,能產生抗發炎反應的Treg細胞以及TGF-β,與能促進發炎反應的IL-1β以及IL-6於OSCC中的表現,以及其與臨床以及組織病理上各項參數之相關性。
材料與方法:本研究利用免疫組織化學染色方法,觀察Foxp3、TGF-β、IL-1β以及IL-6於71例於1999年至2004年間於台大口腔顎面外科接受手術切除治療之OSCC患者組織中的表現。並分別評估Foxp3、TGF-β、IL-1β以及IL-6於OSCC腫瘤細胞以及基質中的表現。Foxp3、TGF-β、IL-1β以及IL-6於OSCC中之表現與各項臨床與病理之參數的關係,則使用Pearson product-moment correlation coefficient、Student’s t test、Kruskal-Wallis H test以及Mann-Whitney U test來評估。Foxp3、TGF-β、IL-1β以及IL-6於OSCC中之表現與患者存活之關係則使用Kaplan-Meier survival analysis來評估。 結果:所有的病例皆表現Foxp3以及IL-6,而IL-1β以及TGF-β則各有一個病例未表現。Foxp3、TGF-β、IL-1β以及IL-6之各項表現於彼此之間或是細胞激素本身互有相關性。於早期的腫瘤中Foxp3的表現量較晚期腫瘤為高,而晚期的腫瘤中IL-1β於腫瘤細胞中表現則較早期為高。此外,TGF-β於超過50%的腫瘤細胞中表現則患者的累積存活率越好。 結論:OSCC是一高度發炎的腫瘤,IL-1β於較具侵犯性的腫瘤之腫瘤細胞中表現較高,Foxp3則於較早期的腫瘤細胞表現較高。具有菸酒檳榔等不良習慣的患者,IL-1β於腫瘤細胞中,而IL-6於腫瘤基質中的表現較高,但Treg的表現較低,使腫瘤偏向發炎的環境。另外,TGF-β於腫瘤中表現超過50%腫瘤細胞,則累積存活率較高,表示TGF-β對OSCC的預後是有幫助的。於本研究中,Foxp3、IL-1β以及IL-6對於OSCC的存活率以及預後是沒有影響的。 | zh_TW |
dc.description.abstract | Background: The occurrence and progression of oral squamous cell carcinoma (OSCC) are highly correlated with inflammation, which is mediated by pro-inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6). But the adaptive immune cells are suppressed in the tumor microenvironment. Regulatory T cells (Tregs) suppress immune response through transforming growth factor-β (TGF-β) mediation. Tregs may suppress inflammatory response and help the control of tumor, but also may support tumor to escape from immune surveillance and promote tumor progression. The study was to investigate the expression of Treg and TGF-β, which exert anti-inflammation, and IL-1β and IL-6, which promote inflammatory response in OSCC and their associations with clinical and pathological features.
Materials and methods: Surgical specimens from 71 patients treated for OSCC at Department of Oral and Maxillofacial Surgery, National Taiwan university hospital, were evaluated for Foxp3, TGF-β, IL-1β and IL-6 expression by immunihistochemical staining. The expression of Foxp3, TGF-β, IL-1β and IL-6 in OSCC cancer and stromal cells were evaluated respectively. Associations of Foxp3, TGF-β, IL-1β and IL-6 expression with clinical and pathological features were evaluated by using Pearson product-moment correlation coefficient, Student’s t test, Kruskal-Wallis H test and Mann-Whitney U test. Associations of Foxp3, TGF-β, IL-1β and IL-6 expression with survival of patients from OSCC were evaluated by using Kaplan-Meier survival analysis. Results: All patients showed Foxp3 and IL-6 expression. IL-1β and TGF-β have one case didn’t show any positive expression in tumor and stromal cells respectively. The expression of Foxp3, TGF-β, IL-1β and IL-6 were correlated with themselves or each others. Compared early stage with advanced stage tumor, the expression of Foxp3 was higher in early stage, and the expression of IL-1β in tumor cells was higher in advanced stage. The higher expression of TGF-β in tumor cells was associated with better cumulative proportion surviving. Conclusions:OSCC is a highly associated with inflammatory response, and the expression of IL-1β was higher in more invasively tumor, and Foxp3 expression was higher in early stage tumor. If the patients had smoking and/or alcohol drinking and/or betel quid chewing, the expression of IL-1β was higher in cancer cells and IL-6 was higher in stromal cells, but the amount of Tregs were lower. This result indicates that these habits deviate tumor to more inflammatory microenvironment. If over 50% tumor cells express TGF-β, the cumulative proportion surviving would be higher, indicating TGF-β associated with better prognosis. In this study, the expression of Foxp3, IL-1β, IL-6 have no impact on the survival and prognosis of OSCC. | en |
dc.description.provenance | Made available in DSpace on 2021-05-20T19:59:14Z (GMT). No. of bitstreams: 1 ntu-99-R97422028-1.pdf: 1912097 bytes, checksum: 95ab10acbd53503a3875eb5e22e6f052 (MD5) Previous issue date: 2010 | en |
dc.description.tableofcontents | 中文摘要……………………………………………………………………………6
英文摘要………………………………………………………………………… 8 第一章 序論及文獻回顧………………………………………………………10 1.1第一節 口腔鱗狀上皮細胞癌之概論………………………………………10 1.1.1 口腔鱗狀上皮細胞癌之流行病學………………………………………10 1.1.2 口腔鱗狀上皮細胞癌之危險因子………………………………………10 1.1.2.1 菸草製品………………………………………………………………11 1.1.2.2 酒精……………………………………………………………………11 1.1.2.3 檳榔……………………………………………………………………11 1.1.2.4 其他因素………………………………………………………………12 1.1.3 口腔鱗狀上皮細胞癌之治療及預後……………………………………12 1.2 第二節 免疫與癌症…………………………………………………………13 1.2.1 腫瘤的微環境……………………………………………………………13 1.2.2 腫瘤微環境中的免疫細胞………………………………………………13 1.2.3 發炎與癌症………………………………………………………………14 1.2.4 腫瘤逃逸的機制…………………………………………………………15 1.3 第三節 調節性T細胞………………………………………………………15 1.3.1 Treg細胞調控免疫的機制………………………………………………16 1.3.2 Treg細胞與癌症…………………………………………………………16 1.3.3 Treg細胞與口腔鱗狀上皮細胞癌………………………………………17 1.4 第四節 細胞激素的調控…………………………………………………17 1.4.1 介白素-1β(Interleukin-1β, IL-1β)……………………………18 1.4.1.1 IL- 1β對免疫反應的影響…………………………………………18 1.4.1.2 IL- 1β對細胞癌化的影響…………………………………………19 1.4.1.3 IL- 1β對腫瘤侵入性的影響………………………………………19 1.4.1.4 IL- 1β與口腔鱗狀上皮細胞癌……………………………………20 1.4.2 介白素-6(Interleulin-6, IL-6)……………………………………20 1.4.2.1 IL-6與口腔鱗狀上皮細胞癌…………………………………………21 1.4.3 變形生長因子-β(Transforming growth factor-β, TGF-β)……21 1.4.3.1 TGF-β對免疫系統的調控……………………………………………22 1.4.3.2 TGF-β與口腔鱗狀上皮細胞癌………………………………………22 第二章 材料與方法………………………………………………………………24 2.1 第一節 實驗樣本……………………………………………………………24 2.2 第二節 標本之固定與包埋…………………………………………………24 2.3 第三節 免疫組織化學染色…………………………………………………24 2.3.1 反應藥劑…………………………………………………………………24 2.3.2初級抗挺的選擇……………………………………………………………24 2.3.3 實驗步驟…………………………………………………………………25 2.4 第四節 免疫組織化學染色後之觀察與記錄………………………………26 第三章 結果………………………………………………………………………28 3.1 第一節 Interleukin-1β、interleukin-6、transforming growth factor-β以及Foxp3於口腔鱗狀上皮細胞癌之表現…………………………………………………28 3.2 第二節 Interleukin-1β、interleukin-6、transforming growth factor-β以及Foxp3免疫組織化學染色結果之間的相關性…………………………………………28 3.3 第三節Interleukin-1β、interleukin-6、transforming growth factor-β以及Foxp3免疫組織化學染色結果與各項臨床變數間及組織病理學參數的關係………28 3.4 第四節Interleukin-1β、interleukin-6、transforming growth factor-β以及Foxp3免疫組織化學染色結果與各項風險因子的關係………………………………30 3.5 第五節Interleukin-1β、interleukin-6、transforming growth factor-β以及Foxp3免疫組織化學染色結果與存活時間的關係……………………………………31 第四章 討論…………………………………………………………32 第五章 結論…………………………………………………………36 第六章 附表與附圖…………………………………………………37 參考文獻……………………………………………………………65 | |
dc.language.iso | zh-TW | |
dc.title | 調節性T細胞與介白素-1β、介白素-6以及變形生長因子-β於口腔鱗狀上皮細胞癌之表現 | zh_TW |
dc.title | Regulatory T Cells and the Expression of Interleukin-1β, Interleukin-6 and Transforming Growth Factor-β in Oral Squamous Cell Carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 98-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 李正?(Jang-Jaer Lee) | |
dc.contributor.oralexamcommittee | 江俊斌,高壽延,張龍昌 | |
dc.subject.keyword | 調節性T細胞,介白素-1β,介白素-6,變形生長因子-β,口腔鱗狀上皮細胞癌, | zh_TW |
dc.subject.keyword | Regulatory T Cell,Interleukin-1β,Interleukin-6,Transforming Growth Factor-β,Oral Squamous Cell Carcinoma, | en |
dc.relation.page | 79 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2010-06-23 | |
dc.contributor.author-college | 牙醫專業學院 | zh_TW |
dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
顯示於系所單位: | 臨床牙醫學研究所 |
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