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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 | Wen-Chin Weng | en |
dc.contributor.author | 翁妏謹 | zh_TW |
dc.date.accessioned | 2021-05-14T17:48:29Z | - |
dc.date.available | 2018-03-13 | |
dc.date.available | 2021-05-14T17:48:29Z | - |
dc.date.copyright | 2015-03-13 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-02-05 | |
dc.identifier.citation | 1. Dorner AJ, Bole DG and Kaufman RJ. The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. The Journal of cell biology. 1987; 105(6 Pt 1):2665-2674.
2. Wiertz EJ, Tortorella D, Bogyo M, Yu J, Mothes W, Jones TR, Rapoport TA and Ploegh HL. Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature. 1996; 384(6608):432-438. 3. Rutkowski DT and Kaufman RJ. A trip to the ER: coping with stress. Trends in cell biology. 2004; 14(1):20-28. 4. Weng WC, Lee WT, Hsu WM, Chang BE and Lee H. Role of glucose-regulated Protein 78 in embryonic development and neurological disorders. Journal of the Formosan Medical Association 2011; 110(7):428-437. 5. Faitova J, Krekac D, Hrstka R and Vojtesek B. Endoplasmic reticulum stress and apoptosis. Cellular & molecular biology letters. 2006; 11(4):488-505. 6. Yoshida H, Haze K, Yanagi H, Yura T and Mori K. Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. The Journal of biological chemistry. 1998; 273(50):33741-33749. 7. Michalak M, Corbett EF, Mesaeli N, Nakamura K and Opas M. Calreticulin: one protein, one gene, many functions. The Biochemical journal. 1999; 344 Pt 2:281-292. 8. Michalak M, Corbett EF, Mesaeli N, Nakamura K and Opas M. Calreticulin: one protein, one gene, many functions. Biochem J. 1999; 344:281-292. 9. Martin V, Groenendyk J, Steiner SS, Guo L, Dabrowska M, Parker JM, Muller-Esterl W, Opas M and Michalak M. Identification by mutational analysis of amino acid residues essential in the chaperone function of calreticulin. J Biol Chem. 2006; 281(4):2338-2346. 10. Krause KH and Michalak M. Calreticulin. Cell. 1997; 88(4):439-443. 11. Corbett EF, Oikawa K, Francois P, Tessier DC, Kay C, Bergeron JJ, Thomas DY, Krause KH and Michalak M. Ca2+ regulation of interactions between endoplasmic reticulum chaperones. J Biol Chem. 1999; 274(10):6203-6211. 12. Michalak M, Milner RE, Burns K and Opas M. Calreticulin. Biochem J. 1992; 285 ( Pt 3):681-692. 13. White TK, Zhu Q and Tanzer ML. Cell surface calreticulin is a putative mannoside lectin which triggers mouse melanoma cell spreading. J Biol Chem. 1995; 270(27):15926-15929. 14. Raghavan M, Wijeyesakere SJ, Peters LR and Del Cid N. Calreticulin in the immune system: ins and outs. Trends Immunol. 2013; 34(1):13-21. 15. Lu YC, Chen CN, Wang B, Hsu WM, Chen ST, Chang KJ, Chang CC and Lee H. Changes in tumor growth and metastatic capacities of J82 human bladder cancer cells suppressed by down-regulation of calreticulin expression. The American journal of pathology. 2011; 179(3):1425-1433. 16. Qiu Y and Michalak M. Transcriptional control of the calreticulin gene in health and disease. The international journal of biochemistry & cell biology. 2009; 41(3):531-538. 17. Nguyen TO, Capra JD and Sontheimer RD. Calreticulin is transcriptionally upregulated by heat shock, calcium and heavy metals. Molecular immunology. 1996; 33(4-5):379-386. 18. Vera C, Tapia V, Kohan K, Gabler F, Ferreira A, Selman A, Vega M and Romero C. Nerve growth factor induces the expression of chaperone protein calreticulin in human epithelial ovarian cells. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2012; 44(8):639-643. 19. Shih YY, Nakagawara A, Lee H, Juan HF, Jeng YM, Lin DT, Yang YL, Tsay YG, Huang MC, Pan CY, Hsu WM and Liao YF. Calreticulin mediates nerve growth factor-induced neuronal differentiation. Journal of Molecular Neuroscience. 2012; 47(3):571-581. 20. Ni M and Lee AS. ER chaperones in mammalian development and human diseases. FEBS letters. 2007; 581(19):3641-3651. 21. Zamanian M, Veerakumarasivam A, Abdullah S and Rosli R. Calreticulin and cancer. Pathology oncology research : POR. 2013; 19(2):149-154. 22. Chiang WF, Hwang TZ, Hour TC, Wang LH, Chiu CC, Chen HR, Wu YJ, Wang CC, Wang LF, Chien CY, Chen JH, Hsu CT and Chen JY. Calreticulin, an endoplasmic reticulum-resident protein, is highly expressed and essential for cell proliferation and migration in oral squamous cell carcinoma. Oral oncology. 2013; 49(6):534-541. 23. Chahed K, Kabbage M, Ehret-Sabatier L, Lemaitre-Guillier C, Remadi S, Hoebeke J and Chouchane L. Expression of fibrinogen E-fragment and fibrin E-fragment is inhibited in the human infiltrating ductal carcinoma of the breast: the two-dimensional electrophoresis and MALDI-TOF-mass spectrometry analyses. Int J Oncol. 2005; 27(5):1425-1431. 24. Bini L, Magi B, Marzocchi B, Arcuri F, Tripodi S, Cintorino M, Sanchez JC, Frutiger S, Hughes G, Pallini V, Hochstrasser DF and Tosi P. Protein expression profiles in human breast ductal carcinoma and histologically normal tissue. Electrophoresis. 1997; 18(15):2832-2841. 25. Alfonso P, Nunez A, Madoz-Gurpide J, Lombardia L, Sanchez L and Casal JI. Proteomic expression analysis of colorectal cancer by two-dimensional differential gel electrophoresis. Proteomics. 2005; 5(10):2602-2611. 26. Alaiya A, Roblick U, Egevad L, Carlsson A, Franzen B, Volz D, Huwendiek S, Linder S and Auer G. Polypeptide expression in prostate hyperplasia and prostate adenocarcinoma. Anal Cell Pathol. 2000; 21(1):1-9. 27. Hellman K, Alaiya AA, Schedvins K, Steinberg W, Hellstrom AC and Auer G. Protein expression patterns in primary carcinoma of the vagina. Brit J Cancer. 2004; 91(2):319-326. 28. Chen CN, Chang CC, Su TE, Hsu WM, Jeng YM, Ho MC, Hsieh FJ, Lee PH, Kuo ML, Lee H and Chang KJ. Identification of calreticulin as a prognosis marker and angiogenic regulator in human gastric cancer. Annals of surgical oncology. 2009; 16(2):524-533. 29. Lwin ZM, Guo C, Salim A, Yip GW, Chew FT, Nan J, Thike AA, Tan PH and Bay BH. Clinicopathological significance of calreticulin in breast invasive ductal carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2010; 23(12):1559-1566. 30. Kageyama S, Isono T, Matsuda S, Ushio Y, Satomura S, Terai A, Arai Y, Kawakita M, Okada Y and Yoshiki T. Urinary calreticulin in the diagnosis of bladder urothelial carcinoma. International Journal of Urology. 2009; 16(5):481-486. 31. Sheng W, Chen C, Dong M, Zhou J, Liu Q, Dong Q and Li F. Overexpression of calreticulin contributes to the development and progression of pancreatic cancer. J Cell Physiol. 2014; 229(7):887-897. 32. Du XL, Hu H, Lin DC, Xia SH, Shen XM, Zhang Y, Luo ML, Feng YB, Cai Y, Xu X, Han YL, Zhan QM and Wang MR. Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma. J Mol Med (Berl). 2007; 85(8):863-875. 33. Yamamura Y, Tsuchikawa T, Miyauchi K, Takeuchi S, Wada M, Kuwatani T, Kyogoku N, Kuroda A, Maki T, Shichinohe T and Hirano S. The key role of calreticulin in immunomodulation induced by chemotherapeutic agents. International journal of clinical oncology. 2014. 34. Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M and Henson PM. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell. 2005; 123(2):321-334. 35. Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007; 13(1):54-61. 36. Chao MP, Jaiswal S, Weissman-Tsukamoto R, Alizadeh AA, Gentles AJ, Volkmer J, Weiskopf K, Willingham SB, Raveh T, Park CY, Majeti R and Weissman IL. Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Science translational medicine. 2010; 2(63):63ra94. 37. Clarke C and Smyth MJ. Calreticulin exposure increases cancer immunogenicity. Nat Biotechnol. 2007; 25(2):192-193. 38. Vaksman O, Davidson B, Trope C and Reich R. Calreticulin expression is reduced in high-grade ovarian serous carcinoma effusions compared with primary tumors and solid metastases. Human pathology. 2013; 44(12):2677-2683. 39. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. The New England journal of medicine. 2013; 369(25):2379-2390. 40. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P, Jones AV, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. The New England journal of medicine. 2013; 369(25):2391-2405. 41. Sun C, Zhang S and Li J. Calreticulin gene mutations in myeloproliferative neoplasms without Janus kinase 2 mutations. Leukemia & lymphoma. 2014:1-6. 42. Hsu WM, Hsieh FJ, Jeng YM, Kuo ML, Chen CN, Lai DM, Hsieh LJ, Wang BT, Tsao PN, Lee H, Lin MT, Lai HS and Chen WJ. Calreticulin expression in neuroblastoma--a novel independent prognostic factor. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2005; 16(2):314-321. 43. Chang HH, Lee H, Hu MK, Tsao PN, Juan HF, Huang MC, Shih YY, Wang BJ, Jeng YM, Chang CL, Huang SF, Tsay YG, Hsieh FJ, Lin KH, Hsu WM and Liao YF. Notch1 expression predicts an unfavorable prognosis and serves as a therapeutic target of patients with neuroblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010; 16(17):4411-4420. 44. Alur M, Nguyen MM, Eggener SE, Jiang F, Dadras SS, Stern J, Kimm S, Roehl K, Kozlowski J, Pins M, Michalak M, Dhir R and Wang Z. Suppressive roles of calreticulin in prostate cancer growth and metastasis. The American journal of pathology. 2009; 175(2):882-890. 45. Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nature reviews Cancer. 2003; 3(3):203-216. 46. Chang HH and Hsu WM. Neuroblastoma--a model disease for childhood cancer. Journal of the Formosan Medical Association = Taiwan yi zhi. 2010; 109(8):555-557. 47. Maris JM, Hogarty MD, Bagatell R and Cohn SL. Neuroblastoma. Lancet. 2007; 369(9579):2106-2120. 48. Israel MA. Disordered differentiation as a target for novel approaches to the treatment of neuroblastoma. Cancer. 1993; 71(10 Suppl):3310-3313. 49. Ijiri R, Tanaka Y, Kato K, Misugi K, Nishihira H, Toyoda Y, Kigasawa H, Nishi T, Takeuchi M, Aida N and Momoi T. Clinicopathologic study of mass-screened neuroblastoma with special emphasis on untreated observed cases: a possible histologic clue to tumor regression. The American journal of surgical pathology. 2000; 24(6):807-815. 50. Nishihira H, Toyoda Y, Tanaka Y, Ijiri R, Aida N, Takeuchi M, Ohnuma K, Kigasawa H, Kato K and Nishi T. Natural course of neuroblastoma detected by mass screening: s 5-year prospective study at a single institution. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000; 18(16):3012-3017. 51. Sidell N, Altman A, Haussler MR and Seeger RC. Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines. Experimental cell research. 1983; 148(1):21-30. 52. Nakagawara A, Arima-Nakagawara M, Scavarda NJ, Azar CG, Cantor AB and Brodeur GM. Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. The New England journal of medicine. 1993; 328(12):847-854. 53. Hoehner JC, Gestblom C, Olsen L and Pahlman S. Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma. British journal of cancer. 1997; 75(8):1185-1194. 54. Hurlin PJ. N-Myc functions in transcription and development. Birth defects research Part C, Embryo today : reviews. 2005; 75(4):340-352. 55. Strieder V and Lutz W. E2F proteins regulate MYCN expression in neuroblastomas. The Journal of biological chemistry. 2003; 278(5):2983-2989. 56. Wenzel A, Cziepluch C, Hamann U, Schurmann J and Schwab M. The N-Myc oncoprotein is associated in vivo with the phosphoprotein Max(p20/22) in human neuroblastoma cells. The EMBO journal. 1991; 10(12):3703-3712. 57. Melotte V, Qu X, Ongenaert M, van Criekinge W, de Bruine AP, Baldwin HS and van Engeland M. The N-myc downstream regulated gene (NDRG) family: diverse functions, multiple applications. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010; 24(11):4153-4166. 58. Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY and Hammond D. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. The New England journal of medicine. 1985; 313(18):1111-1116. 59. Hsu WM, Lee H, Juan HF, Shih YY, Wang BJ, Pan CY, Jeng YM, Chang HH, Lu MY, Lin KH, Lai HS, Chen WJ, Tsay YG, Liao YF and Hsieh FJ. Identification of GRP75 as an independent favorable prognostic marker of neuroblastoma by a proteomics analysis. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008; 14(19):6237-6245. 60. Hsu WM, Hsieh FJ, Jeng YM, Kuo ML, Tsao PN, Lee H, Lin MT, Lai HS, Chen CN, Lai DM and Chen WJ. GRP78 expression correlates with histologic differentiation and favorable prognosis in neuroblastic tumors. International journal of cancer Journal international du cancer. 2005; 113(6):920-927. 61. Weinreb I, Goldstein D, Irish J and Perez-Ordonez B. Expression patterns of Trk-A, Trk-B, GRP78, and p75NRT in olfactory neuroblastoma. Human pathology. 2009; 40(9):1330-1335. 62. Xiao G, Chung TF, Pyun HY, Fine RE and Johnson RJ. KDEL proteins are found on the surface of NG108-15 cells. Brain research Molecular brain research. 1999; 72(2):121-128. 63. Xiao G, Chung TF, Fine RE and Johnson RJ. Calreticulin is transported to the surface of NG108-15 cells where it forms surface patches and is partially degraded in an acidic compartment. Journal of neuroscience research. 1999; 58(5):652-662. 64. Johnson RJ, Liu N, Shanmugaratnam J and Fine RE. Increased calreticulin stability in differentiated NG-108-15 cells correlates with resistance to apoptosis induced by antisense treatment. Brain research Molecular brain research. 1998; 53(1-2):104-111. 65. Hoehner JC, Gestblom C, Hedborg F, Sandstedt B, Olsen L and Pahlman S. A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage. Lab Invest. 1996; 75(5):659-675. 66. Nijhawan D, Honarpour N and Wang X. Apoptosis in neural development and disease. Annual review of neuroscience. 2000; 23:73-87. 67. Breckenridge DG, Germain M, Mathai JP, Nguyen M and Shore GC. Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 2003; 22(53):8608-8618. 68. Zhang X, Szabo E, Michalak M and Opas M. Endoplasmic reticulum stress during the embryonic development of the central nervous system in the mouse. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 2007; 25(7):455-463. 69. Rauch F, Prud'homme J, Arabian A, Dedhar S and St-Arnaud R. Heart, brain, and body wall defects in mice lacking calreticulin. Experimental cell research. 2000; 256(1):105-111. 70. Ferrara N, Gerber HP and LeCouter J. The biology of VEGF and its receptors. Nature Medicine. 2003; 9(6):669-676. 71. Holmes DIR and Zachary I. The vascular endothelial growth factor (VEGF) family: Angiogenic factors in health and disease. Genome Biology. 2005; 6(2). 72. Robinson CJ and Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. Journal of cell science. 2001; 114(Pt 5):853-865. 73. Shibuya M. Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. Journal of biochemistry. 2013; 153(1):13-19. 74. Shweiki D, Itin A, Soffer D and Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992; 359(6398):843-845. 75. Eggert A, Ikegaki N, Kwiatkowski J, Zhao H, Brodeur GM and Himelstein BP. High-level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastomas. Clin Cancer Res. 2000; 6(5):1900-1908. 76. Ribatti D, Poliani PL, Longo V, Mangieri D, Nico B and Vacca A. Erythropoietin/erythropoietin receptor system is involved in angiogenesis in human neuroblastoma. Histopathology. 2007; 50(5):636-641. 77. Meitar D, Crawford SE, Rademaker AW and Cohn SL. Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma. J Clin Oncol. 1996; 14(2):405-414. 78. Dungwa JV, Uparkar U, May MT and Ramani P. Angiogenin up-regulation correlates with adverse clinicopathological and biological factors, increased microvascular density and poor patient outcome in neuroblastomas. Histopathology. 2012; 60(6):911-923. 79. Canete A, Navarro S, Bermudez J, Pellin A, Castel V and Llombart-Bosch A. Angiogenesis in neuroblastoma: Relationship to survival and other prognostic factors in a cohort of neuroblastoma patients. Journal of Clinical Oncology. 2000; 18(1):27-34. 80. Svensson A, Backman U, Fuchs D, Christofferson R and Azarbayjani F. Angiogenesis can be reduced without significant reduction of tumor growth. Anticancer research. 2007; 27(6b):3883-3889. 81. Poliani PL, Mitola S, Ravanini M, Ferrari-Toninelli G, D'Ippolito C, Notarangelo LD, Bercich L, Wagener C, Memo M, Presta M and Facchetti F. CEACAMI/VEGF cross-talk during neuroblastic tumour differentiation. Journal of Pathology. 2007; 211(5):541-549. 82. George ML, Tutton MG, Janssen F, Arnaoutz A, Abulafi AM, Eccles SA and Swift RI. VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia. 2001; 3(5):420-427. 83. Ribatti D, Marimpietri D, Pastorino F, Brignole C, Nico B, Vacca A and Ponzoni M. Angiogenesis in neuroblastoma. Annals of the New York Academy of Sciences. 2004; 1028:133-142. 84. Ribatti D, Vacca A, Nico B, De Falco G, Giuseppe Montaldo P and Ponzoni M. Angiogenesis and anti-angiogenesis in neuroblastoma. European journal of cancer (Oxford, England : 1990). 2002; 38(6):750-757. 85. Rossler J, Taylor M, Geoerger B, Farace F, Lagodny J, Peschka-Suss R, Niemeyer CM and Vassal G. Angiogenesis as a target in neuroblastoma. European journal of cancer (Oxford, England : 1990). 2008; 44(12):1645-1656. 86. Backman U, Svensson A and Christofferson R. Importance of vascular endothelial growth factor A in the progression of experimental neuroblastoma. Angiogenesis. 2002; 5(4):267-274. 87. Fakhari M, Pullirsch D, Paya K, Abraham D, Hofbauer R and Aharinejad S. Upregulation of vascular endothelial growth factor receptors is associated with advanced neuroblastoma. Journal of pediatric surgery. 2002; 37(4):582-587. 88. Becker J, Pavlakovic H, Ludewig F, Wilting F, Weich HA, Albuquerque R, Ambati J and Wilting J. Neuroblastoma progression correlates with downregulation of the lymphangiogenesis inhibitor sVEGFR-2. Clinical Cancer Research. 2010; 16(5):1431-1441. 89. Kim E, Moore J, Huang J, Soffer S, Manley CA, O'Toole K, Middlesworth W, Stolar CJ, Kandel JJ and Yamashiro DJ. All angiogenesis is not the same: Distinct patterns of response to antiangiogenic therapy in experimental neuroblastoma and wilms tumor. Journal of pediatric surgery. 2001; 36(2):287-290. 90. Pike SE, Yao L, Jones KD, Cherney B, Appella E, Sakaguchi K, Nakhasi H, Teruya-Feldstein J, Wirth P, Gupta G and Tosato G. Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. Journal of Experimental Medicine. 1998; 188(12):2349-2356. 91. Pike SE, Yao L, Setsuda J, Jones KD, Cherney B, Appella E, Sakaguchi K, Nakhasi H, Atreya CD, Teruya-Feldstein J, Wirth P, Gupta G and Tosato G. Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth. Blood. 1999; 94(7):2461-2468. 92. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B and Schilling TF. Stages of embryonic development of the zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 1995; 203(3):253-310. 93. Porebska I, Wyrodek E, Kosacka M, Adamiak J, Jankowska R and Harlozinska-Szmyrka A. Apoptotic markers p53, Bcl-2 and Bax in primary lung cancer. In vivo (Athens, Greece). 2006; 20(5):599-604. 94. Shimada H. The International Neuroblastoma Pathology Classification. Pathologica. 2003; 95(5):240-241. 95. Puppo M, Battaglia F, Ottaviano C, Delfino S, Ribatti D, Varesio L and Bosco MC. Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1alpha and -2alpha. Molecular cancer therapeutics. 2008; 7(7):1974-1984. 96. Fiore G, Ghelardini C, Bruni G, Guarna M and Bianchi E. Differentiation state affects morphine induced cell regulation in neuroblastoma cultured cells. Neuroscience letters. 2013; 555:51-56. 97. Peterson S and Bogenmann E. The RET and TRKA pathways collaborate to regulate neuroblastoma differentiation. Oncogene. 2004; 23(1):213-225. 98. Hsu WM, Huang CC, Wu PY, Lee H, Huang MC, Tai MH and Chuang JH. Toll-like receptor 3 expression inhibits cell invasion and migration and predicts a favorable prognosis in neuroblastoma. Cancer letters. 2013; 336(2):338-346. 99. Guhaniyogi J and Brewer G. Regulation of mRNA stability in mammalian cells. Gene. 2001; 265(1-2):11-23. 100. Wu X and Brewer G. The regulation of mRNA stability in mammalian cells: 2.0. Gene. 2012; 500(1):10-21. 101. Nickenig G, Michaelsen F, Muller C, Berger A, Vogel T, Sachinidis A, Vetter H and Bohm M. Destabilization of AT(1) receptor mRNA by calreticulin. Circ Res. 2002; 90(1):53-58. 102. Totary-Jain H, Naveh-Many T, Riahi Y, Kaiser N, Eckel J and Sasson S. Calreticulin destabilizes glucose transporter-1 mRNA in vascular endothelial and smooth muscle cells under high-glucose conditions. Circ Res. 2005; 97(10):1001-1008. 103. Lu YC, Chen CN, Chu CY, Lu J, Wang BJ, Chen CH, Huang MC, Lin TH, Pan CC, Chen SS, Hsu WM, Liao YF, Wu PY, Hsia HY, Chang CC and Lee H. Calreticulin activates beta1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells. The Biochemical journal. 2014; 460(1):69-78. 104. Mueller CF, Wassmann K, Berger A, Holz S, Wassmann S and Nickenig G. Differential phosphorylation of calreticulin affects AT1 receptor mRNA stability in VSMC. Biochem Biophys Res Commun. 2008; 370(4):669-674. 105. Singh NK, Atreya CD and Nakhasi HL. Identification of calreticulin as a rubella virus RNA binding protein. Proceedings of the National Academy of Sciences of the United States of America. 1994; 91(26):12770-12774. 106. Yokoyama M and Hirata K. New function of calreticulin: calreticulin-dependent mRNA destabilization. Circulation research. 2005; 97(10):961-963. 107. Arcondeguy T, Lacazette E, Millevoi S, Prats H and Touriol C. VEGF-A mRNA processing, stability and translation: a paradigm for intricate regulation of gene expression at the post-transcriptional level. Nucleic acids research. 2013; 41(17):7997-8010. 108. Ribatti D. Anti-angiogenesis in neuroblastoma. Critical reviews in oncology/hematology. 2013; 86(3):212-221. 109. Dungwa JV, Hunt LP and Ramani P. HIF-1alpha up-regulation is associated with adverse clinicopathological and biological factors in neuroblastomas. Histopathology. 2012; 61(3):417-427. 110. Jakovljević G, Čulić S, Stepan J, Bonevski A and Seiwerth S. Vascular endothelial growth factor in children with neuroblastoma: A retrospective analysis. Journal of Experimental and Clinical Cancer Research. 2009; 28(1). 111. Mackenzie F and Ruhrberg C. Diverse roles for VEGF-A in the nervous system. Development. 2012; 139(8):1371-1380. 112. Carmeliet P and De Almodovar CR. VEGF ligands and receptors: Implications in neurodevelopment and neurodegeneration. Cellular and Molecular Life Sciences. 2013; 70(10):1763-1778. 113. Meng H, Zhang Z, Zhang R, Liu X, Wang L, Robin AM and Chopp M. Biphasic effects of exogenous VEGF on VEGF expression of adult neural progenitors. Neuroscience letters. 2006; 393(2-3):97-101. 114. Chen J, Zacharek A, Li A, Zhang C, Ding J, Roberts C, Lu M, Kapke A and Chopp M. Vascular endothelial growth factor mediates atorvastatin-induced mammalian achaete-scute homologue-1 gene expression and neuronal differentiation after stroke in retired breeder rats. Neuroscience. 2006; 141(2):737-744. 115. Genetos DC, Cheung WK, Decaris ML and Leach JK. Oxygen tension modulates neurite outgrowth in PC12 cells through a mechanism involving HIF and VEGF. Journal of Molecular Neuroscience. 2010; 40(3):360-366. 116. Li Y, Luo J, Lau WM, Zheng G, Fu S, Wang TT, Zeng HP, So KF, Chung SK, Tong Y, Liu K and Shen J. Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway. PloS one. 2011; 6(8). 117. Liu YL, Miser JS and Hsu WM. Risk-directed therapy and research in neuroblastoma. Journal of the Formosan Medical Association = Taiwan yi zhi. 2014; 113(12):887-889. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/4840 | - |
dc.description.abstract | 神經母細胞瘤是幼兒期最常見的惡性腫瘤,其腫瘤形成的分子機制依然不清楚,有可能是胚胎交感神經系統發育異常使神經母細胞無法分化或無法凋亡而造成。我們過去的文獻回顧發現內質網伴護蛋白包括鈣網蛋白(Calreticulin, CRT)與葡萄糖調節蛋白(GRP)為神經系統的胚胎發過育過程所必需。我們的斑馬魚研究亦顯示CRT在神經系統的胚胎發育過程極具重要性。過去的研究發現CRT是神經母細胞瘤一項重要的預後指標,CRT的大量表現與神經母細胞瘤的分化程度呈正相關性,病人並有較佳的預後表現。因此,CRT也在神經母細胞瘤的分化上扮演了重要的角色。
血管內皮生長因子(VEGF-A)與其引導的血管新生現象亦被證實在神經母細胞瘤的形成具有重要的角色。而在胃癌研究發現CRT與VEGF-A具有相關性。因此,本研究希望藉由細胞實驗與動物實驗探討VEGF-A是否參與在CRT對於神經母細胞瘤的分化調控,並進一步探討VEGF-A對於人類神經母細胞瘤的分化調控與臨床意義。我們過去的研究結果發現在三種不同的神經母細胞瘤細胞株實驗,CRT的大量表現皆會正向調控VEGF-A與其上游調控分子缺氧誘導因子HIF-1a的表現量,並增加VEGF-A的蛋白質分泌。反之,利用shRNA抑制CRT的表現亦會造成VEGF-A及HIF-1a的表現下降。而在本研究中,我們進一步發現CRT的大量表現不會影響細胞凋亡,但會促進細胞分化並抑制細胞增生。此外,我們利用VEGF接受器抗體去抑制VEGF-A的作用,則神經母細胞瘤的神經分化指標包括GAP43、NSE、NFH及TrkA亦會受到抑制。以上結果顯示VEGF-A的確在CRT誘導的神經母細胞分化扮演重要角色。然而,我們利用神經母細胞瘤細胞株進行實驗發現CRT大量表現會促進細胞之神經分化無法增生,因此經由四環黴素誘導CRT表現之stNB-V1神經母細胞瘤細胞株來進行動物實驗。我們接著利用腫瘤異體移植實驗進一步證實CRT對於VEGF-A及HIF-1a的正向調控,實驗亦發現誘導CRT的表現可以顯著抑制腫瘤體積並促進腫瘤分化。除此之外,我們發現在病人腫瘤裡CRT的表現和VEGF-A的表現呈現顯著正相關。更重要的是,從病患的病理切片染色發現具有VEGF-A表現的病患其預後亦較佳。VEGF-A的表現與腫瘤的分化程度呈正相關,與MYCN的表現呈負相關,但與內皮血管形成無相關性,顯示VEGF-A可能透過與內皮血管新生無關之機轉來調控神經母細胞瘤的形成與分化。 總之,本研究證實在神經母細胞瘤中,CRT可正向調控VEGF-A表現並促進腫瘤的神經分化,且VEGF-A確實參與此神經分化調控。我們亦首次證實VEGF-A是神經母細胞瘤的一個獨立預後因子,具有VEGF-A表現的病患其預後亦較佳。我們的研究為神經母細胞瘤的腫瘤形成開啟嶄新的機轉,同時也有助於對神經母細胞瘤新治療的發展。 | zh_TW |
dc.description.abstract | Neuroblastoma (NB) is the most common malignant tumor of infancy. The tumorigenesis of NB could be a divergence of the embryonic development of sympathetic nervous system. ER chaperones including calreticulin (CRT) and GRP78 are suggested to participate during embryonic development in our previous review. Our present study in zebrafish also revealed that CRT is essential for embryonic and neuronal development. Previous study has identified CRT as an independent favorable prognostic factor which is related to differentiated histologies in NB. Taken together, CRT could play an important role in neuronal differentiation of NB. Recently evidence has suggested that vascular endothelial growth factor (VEGF)-A, a key regulator of physiological and pathologic angiogenesis, participates in the behavior of NB. Furthermore, recent studies have found a correlation between CRT and VEGF-A in gastric cancers. In the present study, we aimed to determine whether the CRT expression in NB was associated with the VEGF-A pathway and to determine the role of VEGF-A in regulating NB behavior focusing on angiogenesis and neuronal differentiation in vitro and in vivo. Our previous study clearly demonstrated that in different NB cell lines, CRT over-expression increases the expression and secretion of VEGF-A and HIF-1a, a major positive regulator of VEGF-A. In contrast, knockdown of CRT decreases VEGF-A and HIF-1a expression. In the present study, we further demonstrated that NB cell apoptosis was not affected by CRT over-expression in stNB-V1 cells. Nevertheless, over-expression of CRT suppressed cell proliferation and enhanced cell differentiation in stNB-V1 cells, whereas blockage of VEGFR-1 markedly suppressed the expression of neuron specific markers including GAP43, NSE and NFH as well as TrkA, a molecular marker indicative of NB cell differentiation. These results indicate an essential role of VEGF-A in CRT-related neuronal differentiation in NB. However, constitutive over-expression of CRT led to NB cell differentiation without proliferation. Thus, we used an inducible-CRT stNB-V1 cell line by a tetracycline-regulated gene system for further animal experiments. The mice xenograft models further confirmed the positive regulation of CRT on VEGF-A and HIF-1a, as well as the role of CRT in enhancing neuronal differentiation and suppressing tumor growth in NB. Furthermore, we have demonstrated a significantly positive correlation between CRT and VEGF-A expression in human NB tumors. Most important of all, we verified that VEGF-A expression predicts a favorable outcome in NB patients and are associated with differentiated histology and normal MYCN expression, both of which are favorable prognostic factors. On the other hand, there was no correlation between the expression of VEGF-A and CD34, a marker of endothelial cells, suggesting a novel mechanism of VEGF-A participating in NB formation through angiogenesis-independent pathway.
In conclusion, our study indicated that CRT-dependent VEGF-A up-regulation is critical for NB differentiation and VEGF-A is involved in CRT-related neuronal differentiation in NB. For the first time, we have demonstrated that VEGF-A is an independent prognostic factors and predicts favorable outcomes in NB patients with tight relationship with differentiated histology and MYCN status. Our findings also delineate a novel mechanism of VEGF-A in the biology of NB. This study provides important information that is needed for deciphering the crucial role of CRT and VEGF on the regulation of NB differentiation. Furthermore, our findings will shed light to a novel therapeutic strategy to improve the outcome of NB patients in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-05-14T17:48:29Z (GMT). No. of bitstreams: 1 ntu-104-D97b41013-1.pdf: 11453828 bytes, checksum: 96cb2166b295f36f7d9eba43ae2a868f (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract v List of Tables x List of Figures xi Chapter I. Introduction 1 1. ER stress and ER-resident chaperone proteins 2 1.1 ER stress and UPR 2 1.2 Multifunctional roles of ER-resident chaperone proteins 3 1.3 Calreticulin 3 1.3.1 Fundamental information of calreticulin 3 1.3.2 Regulation of calreticulin expression 4 2. Roles of calreticulin in neuroblastoma 5 2.1 ER chaperones in cancer development 5 2.2 Calreticulin in regulating cancer cell proliferation 7 2.3 The biology of Neuroblastoma 8 2.4 ER chaperones and calreticulin in neuroblastoma 10 3. Roles of calreticulin in embryonic and neuronal development 11 3.1 ER chaperones in embryonic and neuronal development 11 3.2 Roles of calreticulin in neuronal development and neuronal differentiation 12 3.2 Zebrafish as a model in studying embryonic development 13 4. VEGF-A and angiogenesis in neuroblastoma 13 4.1 Fundamental information of VEGF-A 13 4.2 Angiogenesis in neuroblastoma 14 4.3 VEGF-A in neuroblastoma 15 5. The relationship between calreticulin and VEGF-A-driven angiogenesis 16 6. Rationales 17 Chapter II. Materials and Methods 18 Chapter III. Results 31 Chapter IV. Discussions 44 Chapter V. Concluding remarks and future perspectives 53 References 57 Tables 67 Figures 68 Appendix I: Role of glucose-regulated Protein 78 in embryonic development and neurological disorders 98 Appendix II. Calreticulin Regulates VEGF-A in Neuroblastoma Cells 108 | |
dc.language.iso | en | |
dc.title | 鈣網蛋白與血管內皮生長因子於神經母細胞瘤分化調控之研究 | zh_TW |
dc.title | Study of Calreticulin and VEGF-A on the Regulation of
Neuronal Differentiation in Neuroblastoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 許文明,廖永豐,黃敏銓,李旺祚 | |
dc.subject.keyword | 鈣網蛋白,血管內皮生長因子,神經母細胞瘤,神經分化,血管新生, | zh_TW |
dc.subject.keyword | calreticulin,VEGF-A,neuroblastoma,neuronal differentiation,angiogenesis, | en |
dc.relation.page | 120 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2015-02-05 | |
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 |
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