請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72885
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李心予(Hsinyu Lee) | |
dc.contributor.author | Mati Kargren | en |
dc.contributor.author | 卡爾根馬緹 | zh_TW |
dc.date.accessioned | 2021-06-17T07:09:12Z | - |
dc.date.available | 2019-07-31 | |
dc.date.copyright | 2019-07-31 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-07-22 | |
dc.identifier.citation | 1. Cheung N-KV, Dyer MA. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer. 2013 Jun; 13(6):397–411.
2. Davidoff AM. Neuroblastoma. Semin Pediatr Surg. 2012 Feb;21(1):2–14. 3. Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010 Jun 10;362(23):2202–11. 4. Castel V, Segura V, Berlanga P. Emerging drugs for neuroblastoma. Expert Opin Emerg Drugs. 2013 Jun; 18(2):155–71. 5. Friedman GK, Castleberry RP. Changing trends of research and treatment in infant neuroblastoma. Pediatr Blood Cancer. 2007 Dec 1;49(S7):1060–5. 6. Hale G, Cula MJ, Blatt J. Impact of Gender on the Natural History of Neuroblastoma. Pediatric Hematology and Oncology. 1994 Jan 1;11(1):91–7. 7. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993 Aug;11(8):1466–77. 8. Cohn SL, Pearson ADJ, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report. J Clin Oncol. 2009 Jan 10;27(2):289–97. 9. Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nature Reviews Cancer. 2003 Mar;3(3):203–16. 10. Ambros PF, Ambros IM, Brodeur GM, Haber M, Khan J, Nakagawara A, et al. International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer. 2009 May 5;100(9):1471–82. 11. Westermark UK, Wilhelm M, Frenzel A, Henriksson MA. The MYCN oncogene and differentiation in neuroblastoma. Semin Cancer Biol. 2011 Oct;21(4):256–66. 12. Huang M, Weiss WA. Neuroblastoma and MYCN. Cold Spring Harb Perspect Med [Internet]. 2013 Oct;3(10). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784814/ 13. Esposito MR, Aveic S, Seydel A, Tonini GP. Neuroblastoma treatment in the post-genomic era. Journal of Biomedical Science. 2017 Feb 8;24:14. 14. Park JR, Bagatell R, London WB, Maris JM, Cohn SL, Mattay KK, et al. Children’s Oncology Group’s 2013 blueprint for research: neuroblastoma. Pediatr Blood Cancer. 2013 Jun;60(6):985–93. 15. DuBois SG, Kalika Y, Lukens JN, Brodeur GM, Seeger RC, Atkinson JB, et al. Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival. J Pediatr Hematol Oncol. 1999 Jun;21(3):181–9. 16. Ahmad A, Hart IR. Mechanisms of metastasis. Critical Reviews in Oncology / Hematology. 1997 Dec 1;26(3):163–73. 17. Noujaim D, van Golen CM, van Golen KL, Grauman A, Feldman EL. N-Myc and Bcl-2 coexpression induces MMP-2 secretion and activation in human neuroblastoma cells. Oncogene. 2002 Jul 4;21(29):4549–57. 18. Tanaka N, Fukuzawa M. MYCN downregulates integrin alpha1 to promote invasion of human neuroblastoma cells. Int J Oncol. 2008 Oct;33(4):815–21. 19. Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010 Mar;12(3):247–56. 20. Bénard J. Genetic alterations associated with metastatic dissemination and chemoresistance in neuroblastoma. Eur J Cancer. 1995;31A(4):560–4. 21. Goodman LA, Liu BC, Thiele CJ, Schmidt ML, Cohn SL, Yamashiro JM, et al. Modulation of N-myc expression alters the invasiveness of neuroblastoma. Clin Exp Metastasis. 1997 Mar;15(2):130–9. 22. Dobrenkov K, Cheung N-KV. GD2-targeted immunotherapy and radioimmunotherapy. Semin Oncol. 2014 Oct;41(5):589–612. 23. Heczey A, Louis CU. Advances in chimeric antigen receptor immunotherapy for neuroblastoma. Discov Med. 2013 Dec; 16(90):287–94. 24. Chen L, Zhao Y, Halliday GC, Berry P, Rousseau RF, Middleton SA, et al. Structurally diverse MDM2-p53 antagonists act as modulators of MDR-1 function in neuroblastoma. Br J Cancer. 2014 Aug 12;111(4):716–25. 25. Carpenter EL, Mossé YP. Targeting ALK in neuroblastoma--preclinical and clinical advancements. Nat Rev Clin Oncol. 2012 May 15;9(7):391–9. 26. Scaruffi P, Cusano R, Dagnino M, Tonini GP. Detection of DNA polymorphisms and point mutations of high-affinity nerve growth factor receptor (TrkA) in human neuroblastoma. Int J Oncol. 1999 May;14(5):935–8. 27. Nakagawara A, Liu XG, Ikegaki N, White PS, Yamashiro DJ, Nycum LM, et al. Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). Genomics. 1995 Jan 20;25(2):538–46. 28. Geoerger B, Kieran MW, Grupp S, Perek D, Clancy J, Krygowski M, et al. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Eur J Cancer. 2012 Jan;48(2):253–62. 29. Voges Y, Michaelis M, Rothweiler F, Schaller T, Schneider C, Politt K, et al. Effects of YM155 on survivin levels and viability in neuroblastoma cells with acquired drug resistance. Cell Death Dis. 2016 Oct 13;7(10):e2410. 30. Müller I, Larsson K, Frenzel A, Oliynyk G, Zirath H, Prochownik EV, et al. Targeting of the MYCN protein with small molecule c-MYC inhibitors. PLoS ONE. 2014;9(5):e97285. 31. Faisal A, Vaughan L, Bavetsias V, Sun C, Atrash B, Avery S, et al. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Mol Cancer Ther. 2011 Nov;10(11):2115–23. 32. Yang Z, He N, Zhou Q. Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. Mol Cell Biol. 2008 Feb;28(3):967–76. 33. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067–73. 34. Sims RJ, Belotserkovskaya R, Reinberg D. Elongation by RNA polymerase II: the short and long of it. Genes Dev. 2004 Oct 15;18(20):2437–68. 35. Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, et al. Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition. Cancer Discov. 2013 Mar 1;3(3):308–23. 36. Weiss WA, Aldape K, Mohapatra G, Feuerstein BG, Bishop JM. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J. 1997 Jun 2;16(11):2985–95. 37. Molenaar JJ, Domingo-Fernández R, Ebus ME, Lindner S, Koster J, Drabek K, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet. 2012 Nov;44(11):1199–206. 38. Henssen A, Althoff K, Odersky A, Beckers A, Koche R, Speleman F, et al. Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition. Clin Cancer Res. 2016 May 15;22(10):2470–81. 39. Kobayashi S, Ji H, Yuza Y, Meyerson M, Wong K-K, Tenen DG, et al. An Alternative Inhibitor Overcomes Resistance Caused by a Mutation of the Epidermal Growth Factor Receptor. Cancer Res. 2005 Aug 15;65(16):7096–101. 40. Kancha RK, von Bubnoff N, Bartosch N, Peschel C, Engh RA, Duyster J. Differential Sensitivity of ERBB2 Kinase Domain Mutations towards Lapatinib. PLoS One. 2011 Oct 28;6(10). 41. Nicholson RI, Gee JMW, Harper ME. EGFR and cancer prognosis. European Journal of Cancer. 2001 Sep 1;37:9–15. 42. Zheng C, Shen R, Li K, Zheng N, Zong Y, Ye D, et al. Epidermal growth factor receptor is overexpressed in neuroblastoma tissues and cells. Acta Biochim Biophys Sin (Shanghai). 2016 Aug 1;48(8):762–7. 43. Ho R, Minturn JE, Hishiki T, Zhao H, Wang Q, Cnaan A, et al. Proliferation of human neuroblastomas mediated by the epidermal growth factor receptor. Cancer Res. 2005 Nov 1;65(21):9868–75. 44. Richards KN, Zweidler-McKay PA, Van Roy N, Speleman F, Treviño J, Zage PE, et al. Signaling of ERBB Receptor Tyrosine Kinases Promotes Neuroblastoma Growth in vitro and in vivo. Cancer. 2010 Jul 1;116(13):3233–43. 45. Mao X, Chen Z, Zhao Y, Yu Y, Guan S, Woodfield SE, et al. Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma. Oncotarget. 2017 Jan 3;8(1):1555–68. 46. Tamura S, Hosoi H, Kuwahara Y, Kikuchi K, Otabe O, Izumi M, et al. Induction of apoptosis by an inhibitor of EGFR in neuroblastoma cells. Biochem Biophys Res Commun. 2007 Jun 22;358(1):226–32. 47. Donfrancesco A, De Ioris MA, McDowell HP, De Pasquale MD, Ilari I, Jenkner A, et al. Gefitinib in combination with oral topotecan and cyclophosphamide in relapsed neuroblastoma: pharmacological rationale and clinical response. Pediatr Blood Cancer. 2010 Jan;54(1):55–61. 48. Nalluri S, Peirce SK, Tanos R, Abdella HA, Karmali D, Hogarty MD, et al. EGFR signaling defines Mcl−1 survival dependency in neuroblastoma. Cancer Biol Ther. 2015;16(2):276–86. 49. Jakacki RI, Hamilton M, Gilbertson RJ, Blaney SM, Tersak J, Krailo MD, et al. Pediatric phase I and pharmacokinetic study of erlotinib followed by the combination of erlotinib and temozolomide: a Children’s Oncology Group Phase I Consortium Study. J Clin Oncol. 2008 Oct 20;26(30):4921–7. 50. Goji J, Nakamura H, Ito H, Mabuchi O, Hashimoto K, Sano K. Expression of c-ErbB2 in human neuroblastoma tissues, adrenal medulla adjacent to tumor, and developing mouse neural crest cells. Am J Pathol. 1995 Mar;146(3):660–72. 51. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–12. 52. Borst MP, Baker VV, Dixon D, Hatch KD, Shingleton HM, Miller DM. Oncogene alterations in endometrial carcinoma. Gynecol Oncol. 1990 Sep;38(3):364–6. 53. Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991 Feb 1;51(3):1034–8. 54. Beierle EA, Trujillo A, Nagaram A, Kurenova EV, Finch R, Ma X, et al. N-MYC regulates focal adhesion kinase expression in human neuroblastoma. J Biol Chem. 2007 Apr 27;282(17):12503–16. 55. Beierle EA, Massoll NA, Hartwich J, Kurenova EV, Golubovskaya VM, Cance WG, et al. Focal adhesion kinase expression in human neuroblastoma: immunohistochemical and real-time PCR analyses. Clin Cancer Res. 2008 Jun 1;14(11):3299–305. 56. Megison ML, Stewart JE, Nabers HC, Gillory LA, Beierle EA. FAK inhibition decreases cell invasion, migration and metastasis in MYCN amplified neuroblastoma. Clin Exp Metastasis. 2013 Jun;30(5):555–68. 57. Lutz W, Stöhr M, Schürmann J, Wenzel A, Löhr A, Schwab M. Conditional expression of N-myc in human neuroblastoma cells increases expression of alpha-prothymosin and ornithine decarboxylase and accelerates progression into S-phase early after mitogenic stimulation of quiescent cells. Oncogene. 1996 Aug 15;13(4):803–12. 58. Ferrari-Toninelli G, Bonini SA, Uberti D, Buizza L, Bettinsoli P, Poliani PL, et al. Targeting Notch pathway induces growth inhibition and differentiation of neuroblastoma cells. Neuro-oncology. 2010 Dec;12(12):1231–43. 59. Borowicz S, Van Scoyk M, Avasarala S, Karuppusamy Rathinam MK, Tauler J, Bikkavilli RK, et al. The Soft Agar Colony Formation Assay. J Vis Exp. 2014 Oct 27;(92). 60. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001 Dec;25(4):402–8. 61. Koontz L. Chapter One - TCA Precipitation. In: Lorsch J, editor. Methods in Enzymology [Internet]. Academic Press; 2014. p. 3–10. (Laboratory Methods in Enzymology: Protein Part C; vol. 541). Available from: http://www.sciencedirect.com/science/article/pii/B978012420119400001X 62. Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015 Jan 28;43(Database issue):D447–52. 63. Reynolds CP, Matthay KK, Villablanca JG, Maurer BJ. Retinoid therapy of high-risk neuroblastoma. Cancer Letters. 2003 Jul 18;197(1):185–92. 64. Veal GJ, Errington J, Rowbotham SE, Illingworth NA, Malik G, Cole M, et al. Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma. Clin Cancer Res. 2013 Jan 15;19(2):469–79. 65. Lloyd AC. Anchorage-Independent Growth. In: Brenner S, Miller JH, editors. Encyclopedia of Genetics [Internet]. New York: Academic Press; 2001. p. 65. Available from: http://www.sciencedirect.com/science/article/pii/B0122270800015445 66. Mori S, Chang JT, Andrechek ER, Matsumura N, Baba T, Yao G, et al. An Anchorage-Independent Cell Growth Signature Identifies Tumors with Metastatic Potential. Oncogene. 2009 Aug 6;28(31):2796–805. 67. Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta. 2010 Jan;1803(1):55–71. 68. Vanlandingham PA, Ceresa BP. Rab7 Regulates Late Endocytic Trafficking Downstream of Multivesicular Body Biogenesis and Cargo Sequestration. J Biol Chem. 2009 May 1;284(18):12110–24. 69. Cosker KE, Segal RA. Neuronal Signaling through Endocytosis. Cold Spring Harb Perspect Biol. 2014 Feb 1;6(2):a020669. 70. Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B, et al. The International Neuroblastoma Pathology Classification (the Shimada system). Cancer. 1999;86(2):364–72. 71. Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma. Lancet. 2007 Jun 23;369(9579):2106–20. 72. Nagase H, Murphy G. Tailoring TIMPs for Selective Metalloproteinase Inhibition. In: Edwards D, Høyer-Hansen G, Blasi F, Sloane BF, editors. The Cancer Degradome: Proteases and Cancer Biology [Internet]. New York, NY: Springer New York; 2008. p. 787–810. Available from: https://doi.org/10.1007/978-0-387-69057-5_37 73. Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. The FEBS Journal. 2011;278(1):16–27. 74. Duffy MJ, McKiernan E, O’Donovan N, McGowan PM. Role of ADAMs in cancer formation and progression. Clin Cancer Res. 2009 Feb 15;15(4):1140–4. 75. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006 Jan 1;11:529–43. 76. Lin EA, Liu C-J. The role of ADAMTSs in arthritis. Protein Cell. 2010 Jan;1(1):33–47. 77. Liu P, Sun M, Sader S. Matrix metalloproteinases in cardiovascular disease. Can J Cardiol. 2006 Feb;22(Suppl B):25B-30B. 78. Kelwick R, Desanlis I, Wheeler GN, Edwards DR. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome Biol. 2015;16(1). 79. GREENLEE KJ, WERB Z, KHERADMAND F. Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted. Physiol Rev. 2007 Jan;87(1):69–98. 80. Paulissen G, Rocks N, Gueders MM, Crahay C, Quesada-Calvo F, Bekaert S, et al. Role of ADAM and ADAMTS metalloproteinases in airway diseases. Respir Res. 2009;10(1):127. 81. Parrish AR. Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target. Prog Mol Biol Transl Sci. 2017;148:31–65. 82. Spurbeck WW, Ng CYC, Strom TS, Vanin EF, Davidoff AM. Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model. Blood. 2002 Nov 1;100(9):3361–8. 83. Michalowski MB, de Fraipont F, Plantaz D, Michelland S, Combaret V, Favrot M-C. Methylation of tumor-suppressor genes in neuroblastoma: The RASSF1A gene is almost always methylated in primary tumors. Pediatr Blood Cancer. 2008 Jan; 50(1):29–32. 84. Cruz-Muñoz W, Kim I, Khokha R. TIMP-3 deficiency in the host, but not in the tumor, enhances tumor growth and angiogenesis. Oncogene. 2006 Jan 26;25(4):650–5. 85. Das AM, Bolkestein M, van der Klok T, Oude Ophuis CMC, Vermeulen CE, Rens JAP, et al. Tissue inhibitor of metalloproteinase-3 (TIMP3) expression decreases during melanoma progression and inhibits melanoma cell migration. Eur J Cancer. 2016;66:34–46. 86. Anania MC, Sensi M, Radaelli E, Miranda C, Vizioli MG, Pagliardini S, et al. TIMP3 regulates migration, invasion and in vivo tumorigenicity of thyroid tumor cells. Oncogene. 2011 Jul;30(27):3011–23. 87. Kallio JP, Hopkins-Donaldson S, Baker AH, Kähäri V-M. TIMP-3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway. Int J Cancer. 2011 Feb 15;128(4):991–6. 88. Koers-Wunrau C, Wehmeyer C, Hillmann A, Pap T, Dankbar B. Cell Surface-Bound TIMP3 Induces Apoptosis in Mesenchymal Cal78 Cells through Ligand-Independent Activation of Death Receptor Signaling and Blockade of Survival Pathways. PLoS One. 2013 Jul 24;8(7). 89. Ara T, Fukuzawa M, Kusafuka T, Komoto Y, Oue T, Inoue M, et al. Immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in neuroblastoma: association with tumor progression and clinical outcome. J Pediatr Surg. 1998 Aug;33(8):1272–8. 90. Sugiura Y, Shimada H, Seeger RC, Laug WE, DeClerck YA. Matrix metalloproteinases-2 and -9 are expressed in human neuroblastoma: contribution of stromal cells to their production and correlation with metastasis. Cancer Res. 1998 May 15;58(10):2209–16. 91. Raetz EA, Kim MKH, Moos P, Carlson M, Bruggers C, Hooper DK, et al. Identification of genes that are regulated transcriptionally by Myc in childhood tumors. Cancer. 2003 Aug 15;98(4):841–53. 92. Gupta A, Williams BRG, Hanash SM, Rawwas J. Cellular retinoic acid-binding protein II is a direct transcriptional target of MycN in neuroblastoma. Cancer Res. 2006 Aug 15;66(16):8100–8. 93. Ellerbroek SM, Hudson LG, Stack MS. Proteinase requirements of epidermal growth factor-induced ovarian cancer cell invasion. Int J Cancer. 1998 Oct 29;78(3):331–7. 94. Cowden Dahl KD, Symowicz J, Ning Y, Gutierrez E, Fishman DA, Adley BP, et al. Matrix metalloproteinase (MMP)-9 is a mediator of epidermal growth factor dependent E-cadherin loss in ovarian carcinoma cells. Cancer Res. 2008 Jun 15;68(12):4606–13. 95. Symowicz J, Adley BP, Gleason KJ, Johnson JJ, Ghosh S, Fishman DA, et al. Engagement of Collagen-Binding Integrins Promotes Matrix Metalloproteinase-9–Dependent E-Cadherin Ectodomain Shedding in Ovarian Carcinoma Cells. Cancer Res. 2007 Mar 1;67(5):2030–9. 96. Grieve AG, Rabouille C. Extracellular cleavage of E-cadherin promotes epithelial cell extrusion. J Cell Sci. 2014 Aug 1;127(15):3331–46. 97. Kheradmand F, Rishi K, Werb Z. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2. J Cell Sci. 2002 Feb 15;115(Pt 4):839–48. 98. Covington MD, Burghardt RC, Parrish AR. Ischemia-induced cleavage of cadherins in NRK cells requires MT1-MMP (MMP-14). American Journal of Physiology-Renal Physiology. 2006 Jan 1;290(1):F43–51. 99. Lui ELH, Loo WTY, Zhu L, Cheung MNB, Chow LWC. DNA hypermethylation of TIMP3 gene in invasive breast ductal carcinoma. Biomedicine & Pharmacotherapy. 2005 Oct 1;59:S363–5. 100. Wilde CG, Hawkins PR, Coleman RT, Levine WB, Delegeane AM, Okamoto PM, et al. Cloning and Characterization of Human Tissue Inhibitor of Metalloproteinases-3. DNA and Cell Biology. 1994 Jul 1;13(7):711–8. 101. Olson MW, Bernardo MM, Pietila M, Gervasi DC, Toth M, Kotra LP, et al. Characterization of the monomeric and dimeric forms of latent and active matrix metalloproteinase-9. Differential rates for activation by stromelysin 1. J Biol Chem. 2000 Jan 28;275(4):2661–8. 102. Zucker S, Drews M, Conner C, Foda HD, DeClerck YA, Langley KE, et al. Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) Binds to the Catalytic Domain of the Cell Surface Receptor, Membrane Type 1-Matrix Metalloproteinase 1 (MT1-MMP). J Biol Chem. 1998 Jan 9;273(2):1216–22. 103. Hudson LG, Moss NM, Stack MS. EGF-receptor regulation of matrix metalloproteinases in epithelial ovarian carcinoma. Future Oncol. 2009 Apr;5(3):323–38. 104. Winer A, Adams S, Mignatti P. Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures Into Future Successes. Mol Cancer Ther. 2018 Jun;17(6):1147–55. 105. Mahller YY, Vaikunth SS, Ripberger MC, Baird WH, Saeki Y, Cancelas JA, et al. Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors. Cancer Res. 2008 Feb 15; 68(4):1170–9. 106. Eckhouse SR, Purcell BP, McGarvey JR, Lobb D, Logdon CB, Doviak H, et al. Local hydrogel release of recombinant TIMP-3 attenuates adverse left ventricular remodeling after experimental myocardial infarction. Sci Transl Med. 2014 Feb 12; 6(223):223ra21. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72885 | - |
dc.description.abstract | 神經母細胞瘤 (Neuroblastoma, NB) 是一種好發於兒童的交感神經顱外實體腫瘤。儘管可用的治療方案有所改善,高風險神經母細胞瘤患者的預後因為轉移性擴散仍然不是十分看好。在我們的研究中,我們測試了JQ1(一種Bromodomain和Extra-Terminal(BET)的抑制劑)和CL-387,785(EGFR / ErbB2受體酪氨酸磷酸激酶雙重抑制劑)阻斷神經母細胞瘤細胞轉移能力。 BET抑制劑主要的作用目標為癌基因MYCN,而該基因的擴增和高風險神經母細胞瘤有高度相關。另外,CL-387,785 的作用目標EGFR和ErbB2均在神經母細胞瘤腫瘤組織中有高度表達,並且之前研究已證明這兩個受體酪氨酸磷酸激酶的功能與其他類型腫瘤的轉移有高度相關。利用wound healing和transwell assay兩種檢測腫瘤細胞移動能力的方法,我們證明這兩種化合物都能顯著減少神經母細胞瘤細胞的遷移和侵入組織的能力。接著以colony formation assays檢測腫瘤細胞可懸浮生長形成聚落的特性,更證明這兩種化合物皆能顯著地抑制神經母細胞瘤細胞的腫瘤聚落生成的能力。使用人類腫瘤基因微陣列分析這兩種藥物是否可共同影響一個可控制神經母細胞瘤擴散能力的調控基因時,我們發現金屬蛋白酶組織抑制因子3(TIMP3),在被JQ1或CL-387,785處理過的神經母細胞瘤細胞中,TIMP3基因表現量比對照組有明顯上升的現象。這一結果我們也已利用 RT-qPCR、西方點墨法、和細胞免疫螢光染色法再次證實,JQ1和CL-387,785的確可引發神經母細胞瘤細胞TIMP3基因的高度表現。當我們使用網路R2生物資訊共享平台的神經母細胞瘤患者數據做進一步分析時更顯示,高度表現TIMP3的腫瘤患者其總體存活率(Overall Survival Probability)和無事件存活率(Event-free Survival Probability)均有顯著增加的現象。依此,我們使用台灣神經母細胞瘤患者的腫瘤樣本做獨立驗證分析時,也同樣發現TIMP3在分化程度高的神經母細胞瘤腫瘤中基因表現量與蛋白質表現量都比分化程度較低的腫瘤更高。綜合這些研究結果,我們發現JQ1和CL-387,785都能夠藉由促進TIMP3基因的高度表現後,顯著地抑制神經母細胞瘤的腫瘤轉移能力。這個現象也與在預後良好的神經母細胞瘤中TIMP3的表現量較高有一致的趨勢。我們的研究結果提供了初步且重要的證據,可支持將JQ1和CL-387,785進一步發展成為治療高風險神經母細胞瘤的藥物,也同時驗證了TIMP3在神經母細胞瘤中的預後價值及可開發為新穎的神經母細胞瘤藥物標的。 | zh_TW |
dc.description.abstract | Neuroblastoma is a tumor disease of the sympathetic nervous system and it is the most common type of extra-cranial solid tumors in children. Despite improvements in available treatment options, prognosis for high-risk neuroblastoma patients remains unfavorable, with metastatic spread being one of the reasons behind it. In our study we tested the ability of JQ1, a Bromodomain and Extra-Terminal (BET) inhibitor, and CL-387,785, an EGFR/ErbB2 dual inhibitor, to block metastatic properties of neuroblastoma cells. BET inhibitors target MYCN, an oncogene whose amplification is associated with high-risk neuroblastoma. Additionally, both EGFR and ErbB2 were shown to be highly expressed in NB cells and tissues, and have been implicated in metastasis of various tumors. Using wound healing and transwell assays, we were able to show that both of the compounds significantly reduce migration and invasion of neuroblastoma cells. Consistently, colony formation assays showed that both compounds are able to inhibit anchorage-independent growth of neuroblastoma cells. Using a human tumor gene microarray, we later identified tissue inhibitor of metalloproteinases 3 (TIMP3) as one of the significantly upregulated genes in neuroblastoma cells treated with JQ1 or CL-387,785. These results were confirmed by quantitative real-time PCR, Western blotting and immunocytochemistry. Furthermore, analysis of neuroblastoma patient data from the web-based R2 platform revealed that patients with tumors expressing high levels of TIMP3 have a significantly increased overall and event-free survival probability. Lastly, quantitative real-time PCR, Western blotting and immunohistochemical analysis of tumor samples from a Taiwanese cohort of neuroblastoma patients showed that TIMP3 is expressed at higher levels in more differentiated neuroblastoma tumors compared to less differentiated ones. In summary, our results show that JQ1 and CL-387,785 are able to significantly inhibit molecular processes involved in metastasis of NB, and that expression of TIMP3 is higher in cells treated by these compounds, as well as tumor samples from NB patients with favorable prognoses. Our findings provide the proof-of-principle evidence that JQ1 and CL-387,785 could be further developed to become the target therapies for high-risk neuroblastoma, and also verify the prognostic merit of TIMP3 in neuroblastoma. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T07:09:12Z (GMT). No. of bitstreams: 1 ntu-108-R06b21036-1.pdf: 20395196 bytes, checksum: 86bce3c7bc5f854464e64f146c9864bc (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員會審定書 ......i
Foreword ......ii 摘要 ......iii Abstract ......v Abbreviations ......1 1. Introduction ......2 1.1. High-risk neuroblastoma patients require new and effective treatment strategies ......2 1.2. Inhibition of Bromodomain and Extra-Terminal motif proteins in Neuroblastoma cells ......4 1.3. Inhibition of Epidermal Growth Factor Receptor as a novel treatment strategy for restricting metastasis and progression in neuroblastoma ......6 1.4. Targeting metastasis of NB cells via treatment with JQ1 and CL ......8 2. Materials and methods ......9 2.1. Cell lines and reagents ......9 2.2. Wound healing assay ......9 2.3. Cell viability (MTS) assay ......10 2.4. Transwell assays ......10 2.4.1. Cell migration assay ......10 2.4.2. Cell invasion assay ......11 2.5. Colony formation assay ......11 2.6. Human Tumor Metastasis Array ......12 2.7. Quantitative real-time PCR ......12 2.8. Preparation of protein samples ......13 2.8.1. Whole cell lysates ......13 2.8.2. Extraction of secreted proteins ......13 2.8.3. Tumor sample preparation ......14 2.9. SDS-Polyacrylamide gel electrophoresis and Western blot analysis ......14 2.10. Microscopic analysis ......15 2.10.1. Immunocytochemistry ......15 2.10.2. Immunohistochemistry ......16 2.11. STRING analysis ......17 2.12. R2 ......17 2.13. Statistical analysis ......17 3. Results ......18 3.1. JQ1 and CL reduce the wound healing ability of neuroblastoma cells ......18 3.2. JQ1 and CL reduce the wound healing ability of neuroblastoma cells despite a loss of viability ......21 3.3. JQ1 and CL reduce migration and invasion of neuroblastoma cells ......23 3.4. JQ1 and CL reduce anchorage-independent growth of neuroblastoma cells ......25 3.5. JQ1 and CL induce a differential expression of genes related to tumor metastasis in neuroblastoma cells ......27 3.6. Neuroblastoma tumors from patients with greater survivability and lower risk factors have higher expression of TIMP3 ......30 3.7. Treatment with JQ1 and CL increase expression of TIMP3 and TIMP3 in neuroblastoma cells ......33 3.8. Expression of TIMP3 is increased in neuroblastoma cells with lower expression of MYCN ......36 3.9. Secretion of TIMP3 from neuroblastoma cells ......38 3.10. Higher levels of TIMP3 in neuroblastoma cells treated with JQ1 and CL ......39 3.11. TIMP3 is expressed at higher levels in more differentiated neuroblastoma tumors ......41 3.12. TIMP3 protein expression is correlated with the differentiation status of neuroblastoma tumors ......44 4. Discussion ......46 4.1. JQ1 and CL limit metastatic properties of neuroblastoma cells ......46 4.2. TIMP3 prevents degradation of the extracellular matrix and is involved in a range of tumor diseases ......47 4.3. TIMP3 is a candidate marker limiting metastatic phenotypes of neuroblastoma ......49 4.4. Further investigating the role of TIMP3 in neuroblastoma ......52 References ......55 | |
dc.language.iso | en | |
dc.title | 鑑定TIMP3作為神經母細胞瘤轉移之調節因子 | zh_TW |
dc.title | Identification of TIMP3 as a regulator for metastasis in neuroblastoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 廖永豐(Yung-Feng Liao),許文明(Wen-Ming Hsu),劉彥麟(Yen-Lin Liu) | |
dc.subject.keyword | 神經母細胞瘤,轉移,JQ1,CL-387,785,TIMP3, | zh_TW |
dc.subject.keyword | Neuroblastoma,Metastasis,JQ1,CL-387,785,TIMP3, | en |
dc.relation.page | 67 | |
dc.identifier.doi | 10.6342/NTU201901345 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-07-23 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生命科學系 | zh_TW |
顯示於系所單位: | 生命科學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-108-1.pdf 目前未授權公開取用 | 19.92 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。