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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 江俊斌,郭彥彬 | |
dc.contributor.author | Hsin-Hui Peng | en |
dc.contributor.author | 彭馨慧 | zh_TW |
dc.date.accessioned | 2021-06-16T23:32:24Z | - |
dc.date.available | 2012-09-17 | |
dc.date.copyright | 2012-09-17 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-30 | |
dc.identifier.citation | 1.Neville, et al., Oral and Maxillofacial Pathology. 2 ed2002. 315-76.
2.Shah, J., Head and Neck Surgery. 2nd ed2002. 143-234, 355-93,. 3.Ko, Y., Y. Huang, and C. Lee, Betal quid chewing, smoking and alcohol consumption realted to oral cancer in Taiwan. J Oral Pathol Med, 1995. 24: p. 450-3. 4.Chen, Y.K., et al., Primary oral squamous cell carcinoma: an analysis of 703 cases in southern Taiwan. Oral Oncol, 1999. 35(2): p. 173-9. 5.Liao, C.T., et al., Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol, 2008. 15(3): p. 915-22. 6.Chen, Y.J., et al., Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis. Cancer Sci, 2008. 99(8): p. 1507-14. 7.Watts, J.M., The importance of the Plummer-Vinson syndrome in the aetiology of carcinoma of the upper gastrointestinal tract. Postgrad Med J, 1961. 37: p. 523-33. 8.Sankaranarayanan, R., et al., Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment. Oral Oncol, 1997. 33(4): p. 231-6. 9.Krogh, P., B. Hald, and P. Holmstrup, Possible mycological etiology of oral mucosal cancer: catalytic potential of infecting Candida albicans and other yeasts in production of N-nitrosobenzylmethylamine. Carcinogenesis, 1987. 8(10): p. 1543-8. 10.Dickenson, A.J., W.J. Currie, and B.S. Avery, Screening for syphilis in patients with carcinoma of the tongue. Br J Oral Maxillofac Surg, 1995. 33(5): p. 319-20. 11.Niv, A., et al., Identification and typing of human papillomavirus (HPV) in squamous cell carcinoma of the oral cavity and oropharynx. J Laryngol Otol, 2000. 114(1): p. 41-6. 12.Leemans, C.R., B.J. Braakhuis, and R.H. Brakenhoff, The molecular biology of head and neck cancer. Nat Rev Cancer, 2011. 11(1): p. 9-22. 13.Partridge, M., et al., New insights into p53 protein stabilisation in oral squamous cell carcinoma. Oral Oncol, 1999. 35(1): p. 45-55. 14.Sheu, J.J., et al., Functional genomic analysis identified epidermal growth factor receptor activation as the most common genetic event in oral squamous cell carcinoma. Cancer Res, 2009. 69(6): p. 2568-76. 15.Slaughter, D.P., H.W. Southwick, and W. Smejkal, Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer, 1953. 6(5): p. 963-8. 16.Zahorowska, B., P.J. Crowe, and J.L. Yang, Combined therapies for cancer: a review of EGFR-targeted monotherapy and combination treatment with other drugs. J Cancer Res Clin Oncol, 2009. 135(9): p. 1137-48. 17.Kang, Y.J., M.O. Olson, and H. Busch, Phosphorylation of acid-soluble proteins in isolated nucleoli of Novikoff hepatoma ascites cells. Effects of divalent cations. J Biol Chem, 1974. 249(17): p. 5580-5. 18.Dingwall, C., et al., Nucleoplasmin cDNA sequence reveals polyglutamic acid tracts and a cluster of sequences homologous to putative nuclear localization signals. EMBO J, 1987. 6(1): p. 69-74. 19.Dutta, S., et al., The crystal structure of nucleoplasmin-core: implications for histone binding and nucleosome assembly. Mol Cell, 2001. 8(4): p. 841-53. 20.Frehlick, L.J., J.M. Eirin-Lopez, and J. Ausio, New insights into the nucleophosmin/nucleoplasmin family of nuclear chaperones. Bioessays, 2007. 29(1): p. 49-59. 21.Lindstrom, M.S., NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling. Biochem Res Int, 2011. 2011: p. 195209. 22.Ulanet, D.B., et al., Unique conformation of cancer autoantigen B23 in hepatoma: a mechanism for specificity in the autoimmune response. Proc Natl Acad Sci U S A, 2003. 100(21): p. 12361-6. 23.Okuwaki, M., et al., Function of nucleophosmin/B23, a nucleolar acidic protein, as a histone chaperone. FEBS Lett, 2001. 506(3): p. 272-6. 24.Dumbar, T.S., G.A. Gentry, and M.O. Olson, Interaction of nucleolar phosphoprotein B23 with nucleic acids. Biochemistry, 1989. 28(24): p. 9495-501. 25.Wang, D., et al., The nucleic acid binding activity of nucleolar protein B23.1 resides in its carboxyl-terminal end. J Biol Chem, 1994. 269(49): p. 30994-8. 26.Chang, J.H., et al., Evidence for the ability of nucleophosmin/B23 to bind ATP. Biochem J, 1998. 329 ( Pt 3): p. 539-44. 27.Hingorani, K., A. Szebeni, and M.O. Olson, Mapping the functional domains of nucleolar protein B23. J Biol Chem, 2000. 275(32): p. 24451-7. 28.Peculis, B.A. and J.G. Gall, Localization of the nucleolar protein NO38 in amphibian oocytes. J Cell Biol, 1992. 116(1): p. 1-14. 29.Zirwes, R.F., et al., Topogenesis of a nucleolar protein: determination of molecular segments directing nucleolar association. Mol Biol Cell, 1997. 8(2): p. 231-48. 30.Borer, R.A., et al., Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell, 1989. 56(3): p. 379-90. 31.Dundr, M. and M.O. Olson, Partially processed pre-rRNA is preserved in association with processing components in nucleolus-derived foci during mitosis. Mol Biol Cell, 1998. 9(9): p. 2407-22. 32.Zatsepina, O.V., et al., The nucleolar phosphoprotein B23 redistributes in part to the spindle poles during mitosis. J Cell Sci, 1999. 112 ( Pt 4): p. 455-66. 33.Spector, D.L., R.L. Ochs, and H. Busch, Silver staining, immunofluorescence, and immunoelectron microscopic localization of nucleolar phosphoproteins B23 and C23. Chromosoma, 1984. 90(2): p. 139-48. 34.Nishimura, Y., et al., Tryptophans 286 and 288 in the C-terminal region of protein B23.1 are important for its nucleolar localization. Biosci Biotechnol Biochem, 2002. 66(10): p. 2239-42. 35.Choi, J.W., et al., Lysine 263 residue of NPM/B23 is essential for regulating ATP binding and B23 stability. FEBS Lett, 2008. 582(7): p. 1073-80. 36.Grummitt, C.G., et al., Structural consequences of nucleophosmin mutations in acute myeloid leukemia. J Biol Chem, 2008. 283(34): p. 23326-32. 37.Wang, D., H. Umekawa, and M.O. Olson, Expression and subcellular locations of two forms of nucleolar protein B23 in rat tissues and cells. Cell Mol Biol Res, 1993. 39(1): p. 33-42. 38.Szebeni, A., et al., Role of protein kinase CK2 phosphorylation in the molecular chaperone activity of nucleolar protein b23. J Biol Chem, 2003. 278(11): p. 9107-15. 39.Krause, A. and I. Hoffmann, Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication. PLoS One, 2010. 5(3): p. e9849. 40.Peter, M., et al., Identification of major nucleolar proteins as candidate mitotic substrates of cdc2 kinase. Cell, 1990. 60(5): p. 791-801. 41.Okuda, M., et al., Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell, 2000. 103(1): p. 127-40. 42.Swaminathan, V., et al., Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin transcription. Mol Cell Biol, 2005. 25(17): p. 7534-45. 43.Shandilya, J., et al., Acetylated NPM1 localizes in the nucleoplasm and regulates transcriptional activation of genes implicated in oral cancer manifestation. Mol Cell Biol, 2009. 29(18): p. 5115-27. 44.Endo, A., et al., Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36. J Cell Sci, 2009. 122(Pt 5): p. 678-86. 45.Yun, C., et al., Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases. J Cell Biol, 2008. 183(4): p. 589-95. 46.Tago, K., S. Chiocca, and C.J. Sherr, Sumoylation induced by the Arf tumor suppressor: a p53-independent function. Proc Natl Acad Sci U S A, 2005. 102(21): p. 7689-94. 47.Kuo, M.L., et al., Arf-induced turnover of the nucleolar nucleophosmin-associated SUMO-2/3 protease Senp3. Cell Cycle, 2008. 7(21): p. 3378-87. 48.Lim, M.J. and X.W. Wang, Nucleophosmin and human cancer. Cancer Detect Prev, 2006. 30(6): p. 481-90. 49.Tanaka, M., et al., Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer. Cancer Res, 1992. 52(12): p. 3372-7. 50.Nozawa, Y., et al., Expression of nucleophosmin/B23 in normal and neoplastic colorectal mucosa. J Pathol, 1996. 178(1): p. 48-52. 51.Subong, E.N., et al., Monoclonal antibody to prostate cancer nuclear matrix protein (PRO:4-216) recognizes nucleophosmin/B23. Prostate, 1999. 39(4): p. 298-304. 52.Tsui, K.H., et al., Association of nucleophosmin/B23 mRNA expression with clinical outcome in patients with bladder carcinoma. Urology, 2004. 64(4): p. 839-44. 53.Tsui, K.H., et al., Association of nucleophosmin/B23 with bladder cancer recurrence based on immunohistochemical assessment in clinical samples. Acta Pharmacol Sin, 2008. 29(3): p. 364-70. 54.Yun, J.P., et al., Increased expression of nucleophosmin/B23 in hepatocellular carcinoma and correlation with clinicopathological parameters. Br J Cancer, 2007. 96(3): p. 477-84. 55.Naoe, T., et al., Nucleophosmin: a versatile molecule associated with hematological malignancies. Cancer Sci, 2006. 97(10): p. 963-9. 56.Redner, R.L., et al., The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood, 1996. 87(3): p. 882-6. 57.Morris, S.W., et al., Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science, 1994. 263(5151): p. 1281-4. 58.Yoneda-Kato, N., et al., The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. Oncogene, 1996. 12(2): p. 265-75. 59.Liu, Y., et al., Expression of Nucleophosmin/NPM1 correlates with migration and invasiveness of colon cancer cells. J Biomed Sci, 2012. 19(1): p. 53. 60.Coutinho-Camillo, C.M., et al., Nucleophosmin, p53, and Ki-67 expression patterns on an oral squamous cell carcinoma tissue microarray. Hum Pathol, 2010. 41(8): p. 1079-86. 61.Guo, Q.M., et al., Identification of c-myc responsive genes using rat cDNA microarray. Cancer Res, 2000. 60(21): p. 5922-8. 62.Neiman, P.E., et al., Analysis of gene expression during myc oncogene-induced lymphomagenesis in the bursa of Fabricius. Proc Natl Acad Sci U S A, 2001. 98(11): p. 6378-83. 63.Kim, S., et al., Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo. Proc Natl Acad Sci U S A, 2000. 97(21): p. 11198-202. 64.Zeller, K.I., et al., Characterization of nucleophosmin (B23) as a Myc target by scanning chromatin immunoprecipitation. J Biol Chem, 2001. 276(51): p. 48285-91. 65.Nesbit, C.E., J.M. Tersak, and E.V. Prochownik, MYC oncogenes and human neoplastic disease. Oncogene, 1999. 18(19): p. 3004-16. 66.Sears, R., et al., Ras enhances Myc protein stability. Mol Cell, 1999. 3(2): p. 169-79. 67.Sears, R., et al., Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev, 2000. 14(19): p. 2501-14. 68.Yung, B.Y., Oncogenic role of nucleophosmin/B23. Chang Gung Med J, 2007. 30(4): p. 285-93. 69.Yeh, C.W., et al., Ras-dependent recruitment of c-Myc for transcriptional activation of nucleophosmin/B23 in highly malignant U1 bladder cancer cells. Mol Pharmacol, 2006. 70(4): p. 1443-53. 70.Li, Z. and S.R. Hann, The Myc-nucleophosmin-ARF network: a complex web unveiled. Cell Cycle, 2009. 8(17): p. 2703-7. 71.Brunet, A., S.R. Datta, and M.E. Greenberg, Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol, 2001. 11(3): p. 297-305. 72.Stephens, R.M., et al., Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses. Neuron, 1994. 12(3): p. 691-705. 73.Postigo, A., et al., Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons. Genes Dev, 2002. 16(5): p. 633-45. 74.Onishi-Haraikawa, Y., et al., Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein. Biochem Biophys Res Commun, 2001. 288(2): p. 476-82. 75.Datta, S.R., A. Brunet, and M.E. Greenberg, Cellular survival: a play in three Akts. Genes Dev, 1999. 13(22): p. 2905-27. 76.Neri, L.M., et al., The nuclear phosphoinositide 3-kinase/AKT pathway: a new second messenger system. Biochim Biophys Acta, 2002. 1584(2-3): p. 73-80. 77.Borgatti, P., et al., Threonine 308 phosphorylated form of Akt translocates to the nucleus of PC12 cells under nerve growth factor stimulation and associates with the nuclear matrix protein nucleolin. J Cell Physiol, 2003. 196(1): p. 79-88. 78.Ahn, J.Y., et al., PIKE/nuclear PI 3-kinase signaling mediates the antiapoptotic actions of NGF in the nucleus. EMBO J, 2004. 23(20): p. 3995-4006. 79.Ahn, J.Y., et al., Nucleophosmin/B23, a nuclear PI(3,4,5)P(3) receptor, mediates the antiapoptotic actions of NGF by inhibiting CAD. Mol Cell, 2005. 18(4): p. 435-45. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65244 | - |
dc.description.abstract | 背景
NPM1(nucleophosmin 1)為NPM家族成員之一,在人體正常的生理機能如DNA之複製、轉錄與修復、細胞週期、核醣體合成系統、細胞凋亡、蛋白質之修飾、中心體複製等調控扮演重要角色。NPM1可能促進腫瘤生長(proliferation)及轉移(metastasis),在人體癌症如大腸癌、膀胱癌及肝癌等的表現量都有提高的情形。本研究欲探討NPM1蛋白於口腔癌病理組織中的表現量及與臨床各參數和存活時間的關係。 材料與方法 本研究利用免疫組織化學染色方法,探討NPM1於96例口腔鱗狀細胞癌(OSCC)、45例口腔上皮變異(OED)及29例正常口腔黏膜(NOM)中的表現,並以陽性染色指標Labeling index記錄其染色程度。利用卡方檢定(Chi-square test)、Kaplan-Meier 存活率方法及Cox proportional hazard regression model來分析NPM1的表現與口腔鱗狀細胞癌患者臨床病理參數及存活率之相關性,並試圖尋找影響存活時間的獨立預後因子。 結果 在正常口腔黏膜NPM1的平均陽性標記指數為15% (最低),口腔上皮變異組的平均陽性標記指數為29%,口腔癌組的平均陽性標記指數為58% (最高),從正常口腔黏膜、上皮變異至口腔癌的癌化過程,NPM1表現增加之情形已達統計意義(P < 0.001)。NPM1的表現和患者的腫瘤大小(T status)、淋巴結轉移與否(N status)、癌症臨床分期(Stage)有統計上相關。 各項臨床參數在Cox proportional hazard regression model分析中,單變數分析後發現,腫瘤大小、淋巴結轉移與否、腫瘤臨床分期及NPM1的陽性染色指標(LI)都與存活率有關;多變數分析腫瘤大小、淋巴結轉移與否及NPM1的陽性染色指標(LI)為影響存活時間的獨立因子(independent factor;p<0.05);NPM1陽性染色指標若>60%,影響病人存活的危險率(hazard ration)高達4.249倍(p=0.0029)。 若以Kaplan-Meier plots來觀察臨床病理各項參數、NPM1的陽性染色指標與病人總存活時間(overall survival),經Log-Rank Test分析後,腫瘤大小、淋巴結轉移與否、腫瘤臨床分期均影響病人的存活時間,且達統計上之意義(p<0.05)。而本研究探討的NPM1的陽性染色指標(LI)若>60%,則明顯降低了口腔癌病人的存活率(p=0.0017)。 結論 在本研究中,NPM1的陽性染色指標在口腔癌病理標本中的表現較高且具統計上意義,且與口腔細胞癌患者在臨床參數及存活時間有關。在口腔癌患者而言,NPM1的表現量較高者其存活時間較短;而NPM1在切片組織中的表現程度,或許可以做為口腔癌的預後指標(prognostic marker)。 | zh_TW |
dc.description.abstract | Background
Of the NPM family (nucleophosmin family), NPM1 involves broad physiological functions in the human body, such as DNA replication, transcription and repair, cell cycle control, ribosome biogenesis, apoptosis, protein synthesis and centrosome replication. NPM1 is also known for its effect on tumor cell proliferation and metastasis. Recent cancer research has shown increasingly significant expression of NPM1 in many human cancers, including colon, bladder, and liver. Focused in this research are expression of NPM1 in pathological specimens of oral cancer patients, and the correlation between expression of NPM1 and clinical, pathological parameters, and survival time. Materials and Methods Examined in this study were 96 specimens diagnosed as oral squamous cell carcinoma (OSCC) and 45 specimens of oral epithelial dysplasia (OED). 29 cases of normal oral mucosa (NOM) were also observed for comparison. With a NPM1 monoclonal antibody, immunohistochemistry (IHC) stain was performed for detecting expression of NPM1 in these tissue sections. The degree of positive staining was recorded and graded as labeling index (LI). Finally, the correlations between expression of NPM1, clinical and pathologic parameters, and the overall survival of OSCC patients were analyzed statistically via chi-square test, Cox proportional hazard regression model, and Kaplan-Meier plots. Results The labeling index of NPM1 was significantly higher in OSCC specimens (p<0.001). The average LI of NPM1 in OSCC specimens was 58%. In OED specimens, the average LI was 29%. In NOM, the average LI was only 15%. Meanwhile, higher NPM1 LIs indicated larger tumor size (T3 and T4 status), nodal metastasis and later clinical stage (Stage 3 and stage 4). These results were all revealed with statistical significance (Chi-square test; p<0.05). As Cox proportional hazard regression model, the tumor size (T status), nodal metastasis (N status), clinical stage, and the LIs of NPM1 were statistically significant. Multivariate analysis revealed that tumor size (T status), nodal metastasis (N status) and the LIs of NPM1 were independent factors of patient survival (p<0.05). Kaplan-Meier survival analysis showed that patients had shorter survival time with advanced tumor sizes, nodal metastasis, later clinical staging, and high LIs of NPM1. Conclusions The expression of NPM1 was higher in OSCC specimen. The labeling index of NPM1 has strong correlation with several clinicopathological parameters and survival time. In OSCC patients, higher NPM1 expression seemed to indicate shorter overall survival. Judging from the above analysis, NPM1 is probably a potential prognostic factor of OSCC. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:32:24Z (GMT). No. of bitstreams: 1 ntu-101-R99422013-1.pdf: 1470687 bytes, checksum: d4834d0ffd7d9e5d8d8d2cae5bf6d34b (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 目錄
中文摘要..................................................V 英文摘要................................................VII 第一章 序論及文獻回顧....................................9 1.1.口腔鱗狀細胞癌概論.................................. .9 1.1.1口腔鱗狀細胞癌簡介.................................9 1.1.2口腔鱗狀細胞癌之流行病學..........................10 1.1.2.1口腔鱗狀細胞癌之全球流行病學................10 1.1.2.2.口腔鱗狀細胞癌之台灣地區流行病學及疾病特色.10 1.1.3口腔鱗狀細胞癌之危險因子及基因變異................11 1.1.4口腔鱗狀細胞癌之臨床分期..........................13 1.1.5現行對口腔鱗狀細胞之治療及預後....................14 1.1.6口腔癌前病變......................................15 1.2 NPM1/B23蛋白概論.....................................17 1.2.1 NPM家族(Nucleoplasmin family)簡介................17 1.2.2 NPM1蛋白之結構與功能.............................17 1.2.3 NPM1之轉譯後蛋白質修飾(post-translational modification)....................................18 1.2.4 NPM1於中心體之調控...............................19 1.3 NPM1與癌症之關係.....................................20 1.3.1 NPM1於人類癌症之發現.............................20 1.3.2 NPM1致癌機轉之研究...............................22 1.3.2.1 NPM1於MAPK/ERK路徑調控之研究...............22 1.3.2.2 NPM1與細胞凋亡(Apoptosis)調控之研究........23 1.3.2.3 NPM1於PI3k-Akt路徑調控之研究...............23 第二章 材料與方法.......................................25 2.1實驗樣本..............................................25 2.2標本之固定與包埋......................................25 2.3免疫組織化學染色(immunohistochemistry stain) .........25 2.3.1反應原理..........................................25 2.3.2初級抗體的選擇....................................26 2.3.3 抗原抗體結合之偵測系統...........................26 2.3.4實驗步驟..........................................27 2.4免疫組織化學染色之觀察與記錄..........................29 2.4.1觀察..............................................29 2.4.2染色程度之定量....................................29 2.4.3臨床變數之記錄....................................29 2.4.4統計分析..........................................30 第三章 結果.............................................32 3.1 NPM1於口腔鱗狀細胞癌(OSCC)、口腔上皮變異(OED)及正常口 腔上皮(NOM)之表現....................................32 3.2 NPM1免疫組織化學染色結果與患者臨床及組織病理各項參數 之關係...............................................33 3.3 NPM1免疫組織化學染色與臨床、組織病理參數之單變數、多 變數分析.............................................37 3.4 NPM1表現與存活時間分析...............................37 第四章 討論.............................................39 第五章 結論.............................................43 第六章 附表與附圖.......................................44 參考文獻.................................................55 | |
dc.language.iso | zh-TW | |
dc.title | NPM1/B23於口腔鱗狀細胞癌中之表現 | zh_TW |
dc.title | Expression of NPM1/B23 in oral squamous cell carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 鄭世榮 | |
dc.contributor.oralexamcommittee | 張龍昌 | |
dc.subject.keyword | NPM1,口腔鱗狀細胞癌,口腔上皮變異, | zh_TW |
dc.subject.keyword | NPM1,oral squamous cell carcinoma,oral epithelial dysplasia, | en |
dc.relation.page | 60 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-07-30 | |
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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