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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 許輝吉(Hey-Chi Hsu) | |
dc.contributor.author | Yung-Ming Jeng | en |
dc.contributor.author | 鄭永銘 | zh_TW |
dc.date.accessioned | 2021-06-15T00:27:09Z | - |
dc.date.available | 2010-02-10 | |
dc.date.copyright | 2009-02-10 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2009-01-22 | |
dc.identifier.citation | 1.Johnson RC. Hepatocellular carcinoma. Hepatogastroenterology 1997;44:307-12.
2.Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. 3.Cancer registry annual report in Taiwan area 2003. Department of Health, the Execitove Yuan, Taiwan, R.O.C. (2006). 4.Chen PJ, Chen DS. Hepatitis B virus infection and hepatocellular carcinoma: molecular genetics and clinical perspectives. Semin Liver Dis 1999;19:253-62. 5.Blonski W, Reddy KR. Hepatitis C virus infection and hepatocellular carcinoma. Clin Liver Dis 2008;12:661-74. 6.Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan. Lancet 1981;2:1129-33. 7.Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med 1997;336:1855-9. 8.Bruix J, Barrera JM, Calvet X, Ercilla G, Costa J, Sanchez-Tapias JM, et al. Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis. Lancet 1989;2:1004-6. 9.Colombo M, Kuo G, Choo QL, Donato MF, Del Ninno E, Tommasini MA, et al. Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet 1989;2:1006-8. 10.Gatza ML, Chandhasin C, Ducu RI, Marriott SJ. Impact of transforming viruses on cellular mutagenesis, genome stability, and cellular transformation. Environ Mol Mutagen 2005;45:304-25. 11.Tao X, Shen D, Ren H, Zhang X, Zhang D, Gu B, et al. The role of hepatitis B virus x gene in development of primary hepatocellular carcinoma. Sci China C Life Sci. 2000 Jun;43(3):293-301. 12.Chung TW, Lee YC, Ko JH, Kim CH. Hepatitis B Virus X protein modulates the expression of PTEN by inhibiting the function of p53, a transcriptional activator in liver cells. Cancer Res 2003;63:3453-8. 13.Nijhara R, Jana SS, Goswami SK, Rana A, Majumdar SS, Kumar V, et al. Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo. J Virol 2001;75:10348-58. 14. Lee YI, Kang-Park S, Do SI, Lee YI. The hepatitis B virus-X protein activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade. J Biol Chem 2001;276:16969-77. 15. Ruggieri A, Murdolo M, Harada T, Miyamura T, Rapicetta M. Cell cycle perturbation in a human hepatoblastoma cell line constitutively expressing hepatitis C virus core protein. Arch Virol 2004;149:61-74. 16. Shimotohno K, Watashi K, Tsuchihara K, Fukuda K, Marusawa H, Hijikata M. Hepatitis C virus and its roles in cell proliferation. J Gastroenterol 2002;37:50-4. 17. El-Serag HB, Richardson PA, Everhart JE. The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans. Am J Gastroenterol 2001;96:2462-7. 18. Poynard T, Aubert A, Lazizi Y, Bedossa P, Hamelin B, Terris B, et al. Independent risk factors for hepatocellular carcinoma in French drinkers. Hepatology 1991;13:896-901. 19. Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, Tu JT, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992;339:943-6. 20. Smela ME, Currier SS, Bailey EA, Essigmann JM. The chemistry and biology of aflatoxin B1: from mutational spectrometry to carcinogenesis. Carcinogenesis 2001;22:535-45. 21. Wahl GM, Linke SP, Paulson TG, Huang LC. Maintaining genetic stability through TP53 mediated checkpoint control. Cancer Surv 1997;29:183-219. 22. Bressac B, Kew M, Wands J, Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature 1991;350:429-31. 23. Hsu HC, Tseng HJ, Lai PL, Lee PH, Peng SY. Expression of p53 gene in 184 unifocal hepatocellular carcinomas: association with tumor growth and invasiveness. Cancer Res 1993;53:4691-4. 24. Ozturk M. p53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet 1991;338:1356-9. 25. Greenblatt MS, Feitelson MA, Zhu M, Bennett WP, Welsh JA, Jones R, et al.. Integrity of p53 in hepatitis B X antigen-positive and -negative hepatocellular carcinomas. Cancer Res 1997;57:426-32. 26. Huo TI, Wang XW, Forgues M, Wu CG, Spillare EA, Giannini C, et al. Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis. Oncogene 2001;20:3620-8. 27. Zheng L, Lee WH. The retinoblastoma gene: a prototypic and multifunctional tumor suppressor. Exp Cell Res 2001;264:2-18. 28. Azechi H, Nishida N, Fukuda Y, Nishimura T, Minata M, Katsuma H, el al.. Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas. Oncology 2001;60:346-54. 29. Lin Y, Shi CY, Li B, Soo BH, Mohammed-Ali S, Wee A, et al. Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma. Ann Acad Med Singapore 1996;25:22-30. 30. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994;264:436-40. 31. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 1994;368:753-6. 32. Okamoto A, Demetrick DJ, Spillare EA, Hagiwara K, Hussain SP, Bennett WP, et al. Mutations and altered expression of p16INK4 in human cancer. Proc Natl Acad Sci U S A 1994;91:11045-9. 33. Serrano M, Gomez-Lahoz E, DePinho RA, Beach D, Bar-Sagi D. Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science 1995;267:249-52. 34. Liew CT, Li HM, Lo KW, Leow CK, Chan JY, Hin LY, et al. High frequency of p16INK4A gene alterations in hepatocellular carcinoma. Oncogene 1999;18:789-95. 35. Hsu LS, Lee HC, Chau GY, Yin PH, Chi CW, Lui WY. Aberrant methylation of EDNRB and p16 genes in hepatocellular carcinoma (HCC) in Taiwan. Oncol Rep 2006;15:507-11 36. Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol 2003;129:199-221. 37. Eberhart CG, Argani P. Wnt signaling in human development: β-catenin nuclear translocation in fetal lung, kidney, placenta, capillaries, adrenal, and cartilage. Pediatr Dev Pathol 2001;4:351-7. 38. Polakis P. The oncogenic activation of β-catenin. Curr Opin Genet Dev 1999;9:15-21. 39. Patrice JM, Andrew BS, Vladimir K, Nick B, Hans C, Bert V, et al. Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC. Science 1997;275:1787-90. 40. Karim R, Tse G, Putti T, Scolyer R, Lee S. The significance of the Wnt pathway in the pathology of human cancers. Pathology 2004;36:120-8. 41. Liu X, Lazenby AJ, Siegal GP. Signal transduction cross-talk during colorectal tumorigenesis. Adv Anat Pathol 2006;13:270-4. 42. Hsu HC, Jeng YM, Mao TL, Chu JS, Lai PL, Peng SY. β-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am J Pathol 2000;157:763-70. 43. Hsia CC, Axiotis CA, Di Bisceglie AM, Tabor E. Transforming growth factor-α in human hepatocellular carcinoma and coexpression with hepatitis B surface antigen in adjacent liver. Cancer 1992;70:1049-56. 44. Yamada T, De Souza AT, Finkelstein S, Jirtle RL. Loss of the gene encoding mannose 6-phosphate/insulin-like growth factor II receptor is an early event in liver carcinogenesis. Proc Natl Acad Sci U S A 1997;94:10351-5. 45. Buetow KH, Murray JC, Israel JL, London WT, Smith M, Kew M, et al. Loss of heterozygosity suggests tumor suppressor gene responsible for primary hepatocellular carcinoma. Proc Natl Acad Sci U S A 1989;86:8852-6. 46. Simon D, Knowles BB, Weith A. Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas. Oncogene 1991;6:765-70. 47. De Souza AT, Hankins GR, Washington MK, Fine RL, Orton TC, Jirtle RL. Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors. Oncogene 1995;10:1725-9. 48. Ding SF, Habib NA, Dooley J, Wood C, Bowles L, Delhanty JD. Loss of constitutional heterozygosity on chromosome 5q in hepatocellular carcinoma without cirrhosis. Br J Cancer 1991;64:1083-7. 49. Pineau P, Buendia MA. Studies of genetic defects in hepatocellular carcinoma: recent outcomes and new challenges. J Hepatol 2000;33:152-6. 50. Niketeghad F, Decker HJ, Caselmann WH, Lund P, Geissler F, Dienes HP, et al. Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis. Br J Cancer 2001;85:697-704. 51. Balsara BR, Pei J, De Rienzo A, Simon D, Tosolini A, Lu YY, et al. Human hepatocellular carcinoma is characterized by a highly consistent pattern of genomic imbalances, including frequent loss of 16q23.1-24.1. Genes Chromosomes Cancer 2001;30:245-53. 52. Kusano N, Shiraishi K, Kubo K, Oga A, Okita K, Sasaki K. Genetic aberrations detected by comparative genomic hybridization in hepatocellular carcinomas: their relationship to clinicopathological features. Hepatology 1999;29:1858-62. 53. Marchio A, Meddeb M, Pineau P, Danglot G, Tiollais P, Bernheim A, et al. Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer 1997;18:59-65. 54. Guan XY, Fang Y, Sham JS, Kwong DL, Zhang Y, Liang Q, et al. Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer 2000;29:110-6. 55. Sakakura C, Hagiwara A, Taniguchi H, Yamaguchi T, Yamagishi H, Takahashi T, et al. Chromosomal aberrations in human hepatocellular carcinomas associated with hepatitis C virus infection detected by comparative genomic hybridization. Br J Cancer 1999;80:2034-9. 56. Liang P, Pardee AB. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 1992;257:967-71. 57. Duguid JR, Rohwer RG, Seed B. Isolation of cDNAs of scrapie-modulated RNAs by subtractive hybridization of a cDNA library. Proc Natl Acad Sci U S A 1988;85:5738-42. 58. Velculescu VE, Zhang L, Vogelstein B, Kinzler KW. Serial analysis of gene expression. Science 1995;270:484-7. 59. Schena M, Shalon D, Davis RW, Brown PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995;270:467-70. 60. Huang LR, Hsu HC. Cloning and expression of CD24 gene in human hepatocellular carcinoma: a potential early tumor marker gene correlates with p53 mutation and tumor differentiation. Cancer Res 1995;55:4717-21. 61. Hsu HC, Cheng W, Lai PL. Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution. Cancer Res 1997;57:5179-84. 62. Pan HW, Ou YH, Peng SY, Liu SH, Lai PL, Lee PH, et al. Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer 2003;98:119-27. 63. Liu SH, Lin CY, Peng SY, Jeng YM, Pan HW, Lai PL, et al. Down-regulation of annexin A10 in hepatocellular carcinoma is associated with vascular invasion, early recurrence, and poor prognosis in synergy with p53 mutation. Am J Pathol 2002;160:1831-7. 64. Chen X, Cheung ST, So S, Fan ST, Barry C, Higgins J, et al. Gene expression patterns in human liver cancers. Mol Biol Cell 2002;13:1929-39. 65. Yuan RH, Jeng YM, Chen HL, Lai PL, Pan HW, Hsieh FJ, et al. Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 2006;209:549-58. 66. Jeng YM, Peng SY, Lin CY, Hsu HC. Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res 2004;10:2065-71. 67. Su MC, Hsu HC, Liu YJ, Jeng YM. Overexpression of pituitary tumor- transforming gene-1 in hepatocellular carcinoma. Hepatogastroenterol 2006;53:262-5. 68. Dreyfuss G, Kim VN, Kataoka N. Messenger-RNA-binding proteins and the messages they carry. Nat Rev Mol Cell Biol 2002;3:195-205. 69. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65:905-14. 70. Oleana VH, Salehi A, Swaab DF. Increased expression of the TIAR protein in the hippocampus of Alzheimer patients. Neuroreport 1998;9:1451-4. 71. Mueller-Pillasch F, Lacher U, Micha A, Zimmerhackl F, Hameister H, Varga G, et al. Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. Oncogene 1997;14:2729-33. 72. Riggi N, Cironi L, Suvà ML, Stamenkovic I. Sarcomas: genetics, signaling, and cellular origins. Part 1: The fellowship of TET. J Pathol 2007;213; 4–20. 73. Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR. The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 2007;14:185-93. 74. Ghigna C, Giordano S, Shen H, Benvenuto F, Castiglioni F, Comoglio PM, et al. G. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol Cell 2005;20:881-90. 75. Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T. Function of RNA-binding protein Musashi-1 in stem cells. Exp Cell Res 2005;306:349-56. 76. Götte M, Wolf M, Staebler A, Buchweitz O, Kelsch R, Schüring AN, et al. Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma. J Pathol 2008;215:317-29. 77. Kong DS, Kim MH, Park WY, Suh YL, Lee JI, Park K, et al. The progression of gliomas is associated with cancer stem cell phenotype. Oncol Rep 2008;19:639-43. 78. Clarke RB. Isolation and characterization of human mammary stem cells. Cell Prolif 2005;38:375-86. 79. Sureban SM, May R, George RJ, Dieckgraefe BK, McLeod HL, Ramalingam S, et al. Knockdown of RNA binding protein musashi-1 leads to tumor regression in vivo. Gastroenterology 2008;134:1448-58. 80. Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28. Science 2008;320:97-100. 81. Guo Y, Chen Y, Ito H, Watanabe A, Ge X, Kodama T, Aburatani H. Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene 2006;384:51-61. 82. Yaniv K, Yisraeli JK. The involvement of a conserved family of RNA binding proteins in embryonic development and carcinogenesis. Gene 2002;287:49-54. 83. Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC, et al. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol 1999;19:1262-70. 84. Nielsen J, Adolph SK, Rajpert-De Meyts E, Lykke-Andersen J, Koch G, Christiansen J, et al. Nuclear transit of human zipcode-binding protein IMP1. Biochem J 2003;376:383-91. 85. Mueller-Pillasch F, Lacher U, Wallrapp C, Micha A, Zimmerhackl F, Hameister H, et al. Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. Oncogene 1997;14:2729-33. 86. Havin L, Git A, Elisha Z, Oberman F, Yaniv K, Schwartz SP, et al. RNA-binding protein conserved in both microtubule- and microfilament-based RNA localization. Genes Dev 1998;12:1593-98. 87. Deshler JO, Highett MI, Abramson T, Schnapp BJ. A highly conserved RNA-binding protein for cytoplasmic mRNA localization in vertebrates. Curr Biol 1998;8:489-96. 88. Prokipcak RD, Herrick DJ, Ross J. Purification and properties of a protein that binds to the C-terminal coding region of human c-myc mRNA. J Biol Chem 1994;269:9261-69. 89. Vikesaa J, Hansen TV, Jonson L, Borup R, Wewer UM, Christiansen J, et al. RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO J 2006;25:1456-68. 90. Noubissi FK, Elcheva I, Bhatia N, Shakoori A, Ougolkov A, Liu J, Minamoto T, Ross J, Fuchs SY, Spiegelman VS. CRD-BP mediates stabilization of βTrCP1 and c-myc mRNA in response to β-catenin signalling. Nature 2006;441:898-901. 91. Runge S, Nielsen FC, Nielsen J, Lykke-Andersen J, Wewer UM, Christiansen J. H19 RNA binds four molecules of insulin-like growth factor II mRNA-binding protein. J Biol Chem. 2000;275:29562-9. 92. Atlas R, Behar L, Elliott E, Ginzburg I.The insulin-like growth factor mRNA binding-protein IMP-1 and the Ras-regulatory protein G3BP associate with tau mRNA and HuD protein in differentiated P19 neuronal cells. J Neurochem. 2004;89:613-26. 93. Hansen TV, Hammer NA, Nielsen J, Madsen M, Dalbaeck C, Wewer UM, et al. Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice. Mol Cell Biol 2004;24:4448-64. 94. Tessier CR, Doyle GA, Clark BA, Pitot HC, Ross J. Mammary tumor induction in transgenic mice expressing an RNA-binding protein. Cancer Res 2004;64:209-14. 95. Ioannidis P, Mahaira L, Papadopoulou A, Teixeira MR, Heim S, Andersen JA, et al. CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression. Anticancer Res 2003;23:2179-83. 96. Ioannidis P, Mahaira L, Papadopoulou A, Teixeira MR, Heim S, Andersen JA, et al. 8q24 Copy number gains and expression of the c-myc mRNA stabilizing protein CRD-BP in primary breast carcinomas. Int J Cancer 2003;104:54-9. 97. Ioannidis P, Trangas T, Dimitriadis E, Samiotaki M, Kyriazoglou I, Tsiapalis CM, et al. C-MYC and IGF-II mRNA-binding protein (CRD-BP/IMP-1) in benign and malignant mesenchymal tumors. Int J Cancer 2001;94:480-4. 98. Brants JR, Ayoubi TA, Chada K, Marchal K, Van de Ven WJ, Petit MM. Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2. FEBS Lett 2004;569:277-83. 99. Takada H, Imoto I, Tsuda H, Sonoda I, Ichikura T, Mochizuki H, et al. Screening of DNA copy-number aberrations in gastric cancer cell lines by array-based comparative genomic hybridization. Cancer Sci 2005;96:100-10. 100. Suzuki T, Maruno M, Wada K, Kagawa N, Fujimoto Y, Hashimoto N, et al. Genetic analysis of human glioblastomas using a genomic microarray system. Brain Tumor Pathol 2004;21:27-34. 101. Nessling M, Richter K, Schwaenen C, Roerig P, Wrobel G, Wessendorf S, et al. Candidate genes in breast cancer revealed by microarray-based comparative genomic hybridization of archived tissue. Cancer Res 2005;65:439-47. 102. Mueller-Pillasch F, Pohl B, Wilda M, Lacher U, Beil M, Wallrapp C, et al. Expression of the highly conserved RNA binding protein KOC in embryogenesis. Mech Dev 1999;88:95-9. 103. Yantiss RK, Woda BA, Fanger GR, Kalos M, Whalen GF, Tada H, et al. KOC (K homology domain containing protein overexpressed in cancer): a novel molecular marker that distinguishes between benign and malignant lesions of the pancreas. Am J Surg Pathol 2005;29:188-95. 104. Jiang Z, Chu PG, Woda BA, Rock KL, Liu Q, Hsieh CC, et al. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol 2006;7:556-64. 105. Sitnikova L, Mendese G, Liu Q, Woda BA, Lu D, Dresser K, et al. IMP3 predicts aggressive superficial urothelial carcinoma of the bladder. Clin Cancer Res 2008;14:1701-6. 106. Li C, Zota V, Woda BA, Rock KL, Fraire AE, Jiang Z, et al. Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations. Mod Pathol 2007;20:1263-8. 107. Schwartz SP, Aisenthal L, Elisha Z, Oberman F, Yisraeli JK. A 69-kDa RNA-binding protein from Xenopus oocytes recognizes a common motif in two vegetally localized maternal mRNAs. Proc Natl Acad Sci U S A 1992;89:11895-9. 108. Wagner M, Kunsch S, Duerschmied D, Beil M, Adler G, Mueller F, et al.. Transgenic overexpression of the oncofetal RNA binding protein KOC leads to remodeling of the exocrine pancreas. Gastroenterology 2003;124:1901-14. 109. Mori H, Sakakibara S, Imai T, Nakamura Y, Iijima T, Suzuki A, et al. Expression of mouse igf2 mRNA-binding protein 3 and its implications for the developing central nervous system. J Neurosci Res 2001;64:132-43. 110. Zhang J, Chan EK. Autoantibodies to IGF-II mRNA binding protein p62 and overexpression of p62 in human hepatocellular carcinoma. Autoimmun Rev 2002;1:146-53. 111. Edmonson HA, Steiner PE. Primary carcinoma of the liver: A study of 100 among 489,000 necropsies. Cancer (Phila) 1954;7:462-503. 112. Fleming ID, Cooper JS, Henson DE, et al. Liver AJCC Cancer Staging Manual (ed 5). Philadelphia: Lippincott-Raven, 1997, 98-126. 113. Jaffe EA, Hoyer LW, Nachman RL. Synthesis of anti-bemophilic factor antigen by cultured human endothelial cells. J Clin Invest 1973;52:2757-64. 114. Hosmer DW, Lemeshow S. Applied logistic regression. 2nd ed. New York: John Wiley & Sons, 2000. 115. Hosmer DW, Lemeshow S. Applied survival analysis: regression modeling of time to event data. New York: John Wiley & Sons, 1999. 116. Yuan RH, Jeng YM, Chen HL, Hsieh FJ, Yang CY, Lee PH, et al. Opposite roles of human pancreatitis-associated protein and REG1A expression in hepatocellular carcinoma: association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, β-catenin mutation, and favorable prognosis. Clin Cancer Res 2005;11:2568-75. 117. Peng SY, Ou YH, Chen WJ, Li HY, Liu SH, Pan HW, et al. Aberrant expressions of annexin A10 short isoform, osteopontin and α-fetoprotein at chromosome 4q cooperatively contribute to progression and poor prognosis of hepatocellular carcinoma. Int J Oncol 2005;26:1053-61. 118. Lee YC, Pan HW, Peng SY, Lai PL, Kuo WS, Ou YH, et al. Overexpression of tumour-associated trypsin inhibitor (TATI) enhances tumour growth and is associated with portal vein invasion, early recurrence and a stage-independent prognostic factor of hepatocellular carcinoma. Eur J Cancer 2007;43:736-44. 119. Yuan RH, Jeng YM, Pan HW, Hu FC, Lai PL, Lee PH, et al. Overexpression of KIAA0101 predicts high stage, early tumor recurrence, and poor prognosis of hepatocellular carcinoma. Clin Cancer Res 2007;13:5368-76. 120. Miyazaki H, Patel V, Wang H, Edmunds RK, Gutkind JS, Yeudall WA. Down-regulation of CXCL5 inhibits squamous carcinogenesis. Cancer Res 2006;66:4279-84. 121. Nutt CL, Matthews RT, Hockfield S. Glial tumor invasion: a role for the upregulation and cleavage of BEHAB/brevican. Neuroscientist 2001;7:113-22. 122. Wells A, Kassis J, Solava J, Turner T, Lauffenburger DA. Growth factor-induced cell motility in tumor invasion. Acta Oncol 2002;41:124-30. 123. Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K, Mori M. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res 2008;14:2334-40. 124. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004;117:927-39. 125. Li C, Rock KL, Woda BA, Jiang Z, Fraire AE, Dresser K. IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16(INK4a) expression. Mod Pathol. 2007;20:242-7. 126. Simon R, Bourne PA, Yang Q, Spaulding BO, di Sant'Agnese PA, Wang HL, et al. Extrapulmonary small cell carcinomas express K homology domain containing protein overexpressed in cancer, but carcinoid tumors do not. Hum Pathol. 2007;38:1178-83. 127. LeRoith D, Roberts CT Jr. The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127-37. 128. Wang B, Hendricks DT, Wamunyokoli F, Parker MI. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006 ;66:3071-7. 129. Neufeld G, Kessler O. The semaphorins: versatile regulators of tumour progression and tumour angiogenesis. Nat Rev Cancer. 2008;8:632-45. 130. Cleynen I, Van de Ven WJ. The HMGA proteins: a myriad of functions. Int J Oncol 2008;32:289-305. 131. Wood LJ, Maher JF, Bunton TE, Resar LM. The oncogenic properties of the HMG-I gene family. Cancer Res. 2000;60:4256-61. 132. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 2007;21:1025-30. 133. Ayala I, Baldassarre M, Caldieri G, Buccione R. Invadopodia: a guided tour. Eur J Cell Biol 2006;85:159-64. 134. Ross AF, Oleynikov Y, Kislauskis EH, Taneja KL, Singer RH. Characterization of a β-actin mRNA zipcode-binding protein. Mol Cell Biol 1997;17:2158-65. 135. Eom T, Antar LN, Singer RH, Bassell GJ. Localization of a b-actin messenger zipcode-binding protein modulates the density of filopodial synapses. J Neurosci 2003;23:10433-44. 136. Oleynikov Y, Singer RH. Real-time visualization of ZBP1 association with-actin mRNA during transcription and localization. Curr Biol 2003;13:199-207. 137. de Hoog CL, Foster LJ, Mann M. RNA and RNA binding proteins participate in early stages of cell spreading through spreading initiation centers. Cell 2004;117:649-62. 138. Nemunaitis J, Meyers T, Senzer N, Cunningham C, West H, Vallieres E, et al.Phase I Trial of sequential administration of recombinant DNA and adenovirus expressing L523S protein in early stage non-small-cell lung cancer. Mol Ther 2006;13:1185-91. 139. Belmont LD, Hyman AA, Sawin KE, Mitchison TJ. Real-time visualization of cell cycle-dependent changes in microtubule dynamics in cytoplasmic extracts. Cell 1990;62:579-89. 140. Rusan NM, Fagerstrom CJ, Yvon AM, Wadsworth P. Cellcycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-α tubulin. Mol Biol Cell 2001;12:971-80. 141. Wittmann T, Hyman A, Desai A. The spindle: a dynamic assembly ofmicrotubules and motors. Nat. Cell Biol 2001;3:E28-E34. 142. D'Avino PP, Savoian MS, Glover DM. Cleavage furrow formation and ingression during animal cytokinesis: a microtubule legacy. J Cell Sci 2001;118:1549-58. 143. Khmelinskii A, Scheibel E. Assembling the spindle midzone in the right place at the right time. Cell Cycle 2008;7:283-6. 144. Mishima M, Pavicic V, Grüneberg U, Nigg EA, Glotzer M. Cell cycle regulation of central spindle assembly. Nature 2004;430:908-13. 145. Sharp DJ, Rogers GC, Scholey JM. Microtubule motors in mitosis. Nature 2000;407:41-7. 146. Thein KH, Kleylein-Sohn J, Nigg EA, Gruneberg U. Astrin is required for the maintenance of sister chromatid cohesion and centrosome integrity. J Cell Biol 2007;178:345-54. 147. Wong J, Fang G. HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture. J Cell Biol 2006;173:879-91. 148. Wittmann T, Wilm M, Karsenti E, Vernos I. TPX2, A novel xenopus MAP involved in spindle pole organization. J Cell Biol 2000;149:1405-18. 149. Charrasse S, Schroeder M, Gauthier-Rouviere C, Ango F, Cassimeris L, Gard DL, Larroque C. The TOGp protein is a new human microtubule-associated protein homologous to the Xenopus XMAP215. J Cell Sci 1998;111:1371-83. 150. Ciciarello M, Mangiacasale R, Lavia P. Spatial control of mitosis by the GTPase Ran. Cell Mol Life Sci 2007;64:1891-914. 151. Gruss OJ, Carazo-Salas RE, Schatz CA, Guarguaglini G, Kast J, Wilm M, et al. Ran induces spindle assembly by reversing the inhibitory effect of importin α on TPX2 activity. Cell 2001;104:83-93. 152. Wittmann T, Boleti H, Antony C, Karsenti E, Vernos I. Localization of the kinesin-like protein Xklp2 to spindle poles requires a leucine zipper, a microtubule-associated protein, and dynein. J Cell Biol 1998;143:673-85. 153. Wilde A, Lizarraga SB, Zhang L, Wiese C, Gliksman NR, Walczak CE, et al. Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities. Nat Cell Biol 2001;3:221-7. 154. Durkacz B, Carr A, Nurse P. Transcription of the cdc2 cell cycle control gene of the fission yeast Schizosaccharomyces pombe. EMBO J 1986;5:369-373. 155. Clute P, Pines J. Temporal and spatial control of cyclin B1 destruction in metaphase. Nat Cell Biol 1999;1:82-7. 156. Blangy A, Lane HA, d'Hérin P, Harper M, Kress M, Nigg EA. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell. 1995;83:1159-69. 157. Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, et al. Targets of the cyclin-dependent kinase Cdk1. Nature 2003;425:859-64. 158. Masson D, Kreis TE. Binding of E-MAP-115 to microtubules is regulated by cell cycle-dependent phosphorylation. J Cell Biol 1995;131:1015-24. 159. Drewes G, Ebneth A, Mandelkow EM. MAPs, MARKs and microtubule dynamics. Trends Biochem Sci 1998;23:307-11. 160. Ookata K, Hisanaga S, Bulinski JC, Murofushi H, Aizawa H, Itoh TJ, Hotani H, Okumura E, Tachibana K, Kishimoto T. Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. J Cell Biol 1995;128:849-62. 161. Wolf F, Sigl R, Geley S. ‘The end of the beginning': cdk1 thresholds and exit from mitosis. Cell Cycle 2007;6:1408-11. 162. Tournebize R, Andersen SS, Verde F, Dorée M, Karsenti E, Hyman AA. Distinctroles of PP1 and PP2A-like phosphatases in control of microtubule dynamics during mitosis. EMBO J 1997;16:5537-49. 163. Cho HP, Liu Y, Gomez M, Dunlap J, Tyers M, Wang Y. The dual-specificity phosphatase CDC14B bundles and stabilizes microtubules. Mol Cell Biol 2005;25:4541-51. 164. Raemaekers T, Ribbeck K, Beaudouin J, Annaert W, Van Camp M, Stockmans I, et al. NuSAP, a novel microtubule-associated protein involved in mitotic spindle organization. J Cell Biol 2003;162:1017-29. 165. Ribbeck K, Groen AC, Santarella R, Bohnsack MT, Raemaekers T, Köcher T, et al. NuSAP, a mitotic RanGTP target that stabilizes and cross-links microtubules. Mol Biol Cell 2006;17:2646-60. 166. Li L, Zhou Y, Sun L, Xing G, Tian C, Sun J, et al. NuSAP is degraded by APC/C-Cdh1 and its overexpression results in mitotic arrest dependent of its microtubules' affinity. Cell Signal 2007;19:2046-55. 167. Fu C, Yan F, Wu F, Wu Q, Whittaker J, Hu H, Hu R, Yao X. Mitotic phosphorylation of PRC1 at Thr470 is required for PRC1 oligomerization and proper central spindle organization. Cell Res 2007;17:449-57. 168. Zhu C, Lau E, Schwarzenbacher R, Bossy-Wetzel E, Jiang W. Spatiotemporal control of spindle midzone formation by PRC1 in human cells. Proc Natl Acad Sci U S A 2006;103:6196-201. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41674 | - |
dc.description.abstract | 為了闡明肝細胞癌的分子病理機制,我們分析了網路上的微陣列資料庫,找出兩個前人較少研究的基因似胰島素生長因子mRNA結合蛋白3(IMP3)和NuSAP為肝細胞癌過度表現的基因。
IMP3是一個在胚胎組織和多種癌症所表現的RNA結合蛋白。之前的研究發現IMP3和它的同源蛋白牽涉到它們標的RNA的穩定度,轉譯和細胞內分佈。IMP3也被發現為侵犯足形成所必須的,但是它在腫瘤生成和進展的角色仍未為人所知。為了分析IMP3在肝細胞癌的角色,我們以免疫組織化學染色法分析人類肝細胞癌樣本中的蛋白質表現,使用RNA干擾法減少IMP3表現和穩定表現IMP3的細胞株以研究它對腫瘤生長和侵犯的影響,以及以cDNA微陣列分析法分析其分子機轉。我們以免疫組織化學染色法分析IMP3在377個手術切除的單病灶的肝細胞癌的表現(296男性,81女性,年齡分佈從7歲到88歲,平均55.49歲)。IMP3表現在其中255個腫瘤(67.6%)。IMP3蛋白較常表現在腫瘤周邊,和侵犯前緣。比起主要的腫瘤,IMP3較常表現在衛星結節和腫瘤栓子。IMP3的表現和血中高甲胎兒蛋白值(>200 ng/mL, P < 1 x 10-7),大的腫瘤(>5公分,P = 0.006),高的腫瘤級別(P < 1 x 10-7),高的腫瘤期別伴隨血管侵犯和各種程度的肝內轉移(P < 1 x 10-7)呈高度相關。 這些觀察提示IMP3的表現和腫瘤分化不良有關,因此,與高的甲胎兒蛋白值和高腫瘤級別呈正相關。更重要的是,我們的發現指出有IMP3表現的肝細胞癌有生長優勢和侵犯和轉移的潛能,因而造成高腫瘤期別和經常出現肝內轉移。IMP3的表現可以預測早期腫瘤復發(P < 1 x 10-7),並且是不良預後的強的預測因子(P<0.0001)。為了證實和闡明IMP3在肝細胞瘤生長和轉移的功能性角色及其分子機制,我們在肝細胞癌細胞株HA22T和子宮頸腺癌HeLa以RNA干擾法耗盡IMP3,並建立穩定表現IMP3的HEK293 細胞。過度表現IMP3會促進細胞的非貼附性生長能力,和HEK293細胞在裸鼠形成腫瘤的能力。反之,在HeLa細胞耗盡IMP3,會抑制在裸鼠體內的腫瘤生長。在肝細胞癌細胞株HA22T以RNA干擾耗盡IMP3造成細胞移動,侵犯,和經內皮移動能力的下降。微陣列分析發現IMP3的耗盡會造成許多和腫瘤侵犯有關的基因的表現量下降。其中,我們發現在肝細胞癌中,HMGA2和IMP3的表現和IMP3的表現呈高度相關(P =0.0002)。這些結果顯示IMP3 在腫瘤生成和侵犯扮演重要角色,並且是肝細胞癌病人的重要預後因子。 NuSAP一開始被發現是一個微管結合和成束蛋白並且被報導為有絲分裂晚期形成紡鍾體中央重要的蛋白質。在細胞周期進行中調節它的功能的機制仍不清楚。為了闡明NuSAP在肝細胞癌的角色,我們以反轉錄-聚合脢鏈反應分析177個肝細胞癌中NuSAP的表現。我們發現在肝細胞癌過度表現表現NuSAP與高腫瘤級別(P=0.045)和期別(P=0.0023)和不良的五年存活率(P=0.033)成正相關。NuSAP的mRNA和蛋白質表現量在晚G2期到有絲分裂期呈高峰,在細胞分裂後突然下降。使用nocodazole同步化的細胞,我們發現NuSAP在晚G2期到有絲分裂早期被磷酸化,而且此磷酸化對依賴循環子的激脢的抑制劑roscovitine敏感。體外磷酸化試驗證實NuSAP是cdk1/cyclin B1複合體的受質。使用對磷酸化NuSAP具特異性的抗體,我們以免疫螢光染色法發現磷酸化的NuSAP在有絲分裂開始時,出現在核仁。在有絲分裂前期和中期出現在染色體周圍層。在有絲分裂後期,末期和細胞周期間期完全消失。體外微管沉降試驗證實 NuSAP的磷酸化抑制其與微管的結合。我們的結果顯示經由NuSAP的磷酸化,NuSAP經由對微管動力學的影響調節有絲分裂紡鍾體的空間和時間控制。 | zh_TW |
dc.description.abstract | To elucidate the molecular pathogenesis of hepatocellular carcinoma (HCC), we analyzed the web-based microarray database and identified several previously uncharacterized genes that were overexpressed in HCC. In this study, two of these genes, insulin-like growth factor II mRNA-binding protein 3 (IMP3) and NuSAP, which remained largely unknown for their biological function, particularly in human cancer, were subjected to detailed clinicopathological and functional studies to elucidate their roles in tumor progression of HCC.
IMP3 is an mRNA-binding protein expressed in embryonic tissues and multiple cancers. Studies have shown that IMP3 and its homolog proteins are involved in the stability, translation and subcellular localization of their target RNAs. IMP3 has also been shown to be essential for invadopodia formation, but its roles in the tumor development and progression remain largely unknown. To elucidate the roles of IMP3 in HCC, we first examined its protein expression in human HCC samples by immunohistochemical stain to establish its clinical relevance, and then studied the functional role in the tumor cell growth and invasion of HCC cells by the gene knockdown assay using RNA interference (RNAi) and the overexpression of IMP3 using stable cell lines. Finally the molecular mechanisms of the roles of IMP3 in suppressing tumor growth and invasion by gene silencing and the tumor promotion by gene overexpression were investigated by cDNA microarray analysis. The IMP3 protein expression was examined in the surgically resected unifocal primary tumors of 377 HCC patients (296 men and 81 women) with ages ranging from 7 to 88 years (mean, 55.49 years) by immunohistochemistry. IMP3 was expressed in 255 HCCs (67.6%). In the main tumor mass, IMP3 protein was predominantly expressed in the tumor border and invasive front. IMP3 was more abundant in the satellite nodules and tumor thrombi as compared with the main tumors. These findings suggest that IMP3 is actively involved in the tumor invasion and metastasis. The IMP3 protein expression positivity correlated with high α-fetoprotein (AFP; >200 ng/mL, P < 1 x 10-7), larger tumor size (>5 cm; P = 0.006), high tumor grade (P < 1 x 10-7), and high tumor stage with vascular invasion and various degrees of intrahepatic metastasis (P < 1 x 10-7). These observations suggest that IMP3 expression correlates with poor tumor cell differentiation, and hence is associated with higher AFP expression and high tumor grade. Importantly, our findings indicate that HCCs with IMP3 protein expression possess growth advantage and invasion/metastasis potential, hence higher tumor stage with more frequent intrahepatic metastasis. IMP3 expression predicted early tumor recurrence (P < 1 x 10-7) and was a strong indicator of poor prognosis (P < 0.0001). To verify and elucidate the molecular mechanisms of the functional role of IMP3 in HCC growth and metastasis, we knocked down the expression of IMP3 using the RNA interference (RNAi) in HCC cell line HA22T and cervical adenocarcinoma cell line HeLa. We also established ectopic expression of IMP3 in HEK293 cells with stable transfection of IMP3. Overexpression of IMP3 enhanced anchorage-independent cell growth in soft agar and exhibited oncogenic potential of HEK293 cells in vivo in nude mice. On the other hand, knockdown of IMP3 in HeLa cells inhibited tumor growth in nude mice. Moreover, knockdown of IMP3 in HCC cell line HA22T caused a decrease in cell motility, invasion, and transendothelial migration. Microarray analysis revealed that knockdown of IMP3 was associated with downregulation of multiple genes involved in tumor invasion. Among them, we found the expression of HMGA2 was highly correlated with IMP3 expression in HCC (P =0.0002). Taking together, these results indicate that IMP3 plays important roles in tumor formation and invasion and is a strong prognostic factor for HCC. NuSAP was originally identified as a microtubule binding and bundling protein and an important protein for central spindle formation in late stages of mitosis. The regulatory mechanism for the function of NuSAP during cell cycle progression is still unclear. To elucidate the role of NuSAP in HCC, we analyzed its expression in 177 HCCs by reverse transcription-polymerase chain reaction. We found overexpression of NuSAP in HCC was associated with high tumor grade (P=0.045), stage (P=0.0023), and worse five-year survival (P=0.033). The mRNA and protein levels of NuSAP peaked at the transition of G2 phase to mitosis and abruptly declined after cell division. Using nocodazole synchronized HeLa cells, we found NuSAP was phosphorylated at the late G2 phase and early mitosis, and the phosphorylation was sensitive to cyclin-dependent kinase inhibitor roscovitine. The in vitro phosphorylation assay confirmed NuSAP was a substrate of cdk1/cyclin B1 complex. By immunofluorescence using a phospho-specific antibody, we found phosphorylated NuSAP was detected at nucleoli at the onset of mitosis, shifted to perichromosomal layer at prophase and metaphase and completely lost at anaphase, telophase, and interphase. Phosphorylation of NuSAP inhibited its binding to microtubules in the in-vitro microtubule sedimentation assay. Our results indicate that phosphorylation of NuSAP regulates the spatiotemporal control of mitotic spindle formation by modulating the dynamics of microtubules. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T00:27:09Z (GMT). No. of bitstreams: 1 ntu-97-D91444002-1.pdf: 2207506 bytes, checksum: 3204bf9e109daa54f6afd8188fb01c2a (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | Abstract in English 3
Abstract in Chinese 5 Abbreviation Table 7 Chapter 1: Introduction 8 Chapter 2: IMP3, an oncofetal RNA-binding protein promotes tumor invasion and predicts poor prognosis in hepatocellular carcinoma 15 Introduction 16 Materials and Methods 19 Results 24 Discussion 28 Tables 34 Figures 40 Chapter 3: NuSAP is a cell cycle-regulated microtubule-binding protein 52 Introduction 53 Materials and Methods 57 Results 61 Discussion 64 Tables 68 Figures 70 References 79 | |
dc.language.iso | en | |
dc.title | IMP3與NuSAP基因在肝細胞癌的表現及其臨床病理和功能研究 | zh_TW |
dc.title | Clinicopathological and functional studies of hepatocellular carcinoma overexpressed genesIMP3 and NuSAP | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 郭明良(Min-Laing Kuo),張美惠(Mei-Hwei),許金玉(Jin-Yuh Shew),呂勝春,周玉山 | |
dc.subject.keyword | 肝細胞癌: IMP3,NuSAP,侵犯, | zh_TW |
dc.subject.keyword | hepatocellular carcinoma,IMP3,NuSAP,Invasion, | en |
dc.relation.page | 92 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-01-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 病理學研究所 | zh_TW |
顯示於系所單位: | 病理學科所 |
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