請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47719
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 葉力森 | |
dc.contributor.author | Siou-Li Pan | en |
dc.contributor.author | 潘秀莉 | zh_TW |
dc.date.accessioned | 2021-06-15T06:14:33Z | - |
dc.date.available | 2016-08-22 | |
dc.date.copyright | 2011-08-22 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-19 | |
dc.identifier.citation | REFERENCE
1. Alexeev V, and Yoon K. Distinctive role of the cKit receptor tyrosine kinase signaling in mammalian melanocytes. J Invest Dermatol 126: 1102-1110, 2006. 2. Alexis JB, Martinez AE, and Lutzky J. An immunohistochemical evaluation of c-kit (CD-117) expression in malignant melanoma, and results of imatinib mesylate (Gleevec) therapy in three patients. Melanoma Res 15: 283-285, 2005. 3. Antonescu CR, Busam KJ, Francone TD, Wong GC, Guo T, Agaram NP, Besmer P, Jungbluth A, Gimbel M, Chen CT, Veach D, Clarkson BD, Paty PB, and Weiser MR. L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition. Int J Cancer 121: 257-264, 2007. 4. Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, Robson M, Maki R, Brennan MF, Ladanyi M, DeMatteo RP, and Besmer P. Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res 9: 3329-3337, 2003. 5. Ashida A, Takata M, Murata H, Kido K, and Saida T. Pathological activation of KIT in metastatic tumors of acral and mucosal melanomas. Int J Cancer 124: 862-868, 2009. 6. Beadling C, Jacobson-Dunlop E, Hodi FS, Le C, Warrick A, Patterson J, Town A, Harlow A, Cruz F, 3rd, Azar S, Rubin BP, Muller S, West R, Heinrich MC, and Corless CL. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res 14: 6821-6828, 2008. 7. Bergman PJ. Canine oral melanoma. Clin Tech Small Anim Pract 22: 55-60, 2007. 8. Bergman PJ, McKnight J, Novosad A, Charney S, Farrelly J, Craft D, Wulderk M, Jeffers Y, Sadelain M, Hohenhaus AE, Segal N, Gregor P, Engelhorn M, Riviere I, Houghton AN, and Wolchok JD. Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial. Clin Cancer Res 9: 1284-1290, 2003. 9. Besmer P. The kit ligand encoded at the murine Steel locus: a pleiotropic growth and differentiation factor. Curr Opin Cell Biol 3: 939-946, 1991. 10. Blackwood L, and Dobson JM. Radiotherapy of oral malignant melanomas in dogs. J Am Vet Med Assoc 209: 98-102, 1996. 11. Bolon B, Calderwood Mays MB, and Hall BJ. Characteristics of canine melanomas and comparison of histology and DNA ploidy to their biologic behavior. Vet Pathol 27: 96-102, 1990. 12. Bostock DE. Neoplasms of the skin and subcutaneous tissues in dogs and cats. Br Vet J 142: 1-19, 1986. 13. Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, and Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA 305: 2327-2334, 2011. 14. Chabot B, Stephenson DA, Chapman VM, Besmer P, and Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 335: 88-89, 1988. 15. Chen H, Isozaki K, Kinoshita K, Ohashi A, Shinomura Y, Matsuzawa Y, Kitamura Y, and Hirota S. Imatinib inhibits various types of activating mutant kit found in gastrointestinal stromal tumors. Int J Cancer 105: 130-135, 2003. 16. Chen LL, Trent JC, Wu EF, Fuller GN, Ramdas L, Zhang W, Raymond AK, Prieto VG, Oyedeji CO, Hunt KK, Pollock RE, Feig BW, Hayes KJ, Choi H, Macapinlac HA, Hittelman W, Velasco MA, Patel S, Burgess MA, Benjamin RS, and Frazier ML. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 64: 5913-5919, 2004. 17. Curtin JA, Busam K, Pinkel D, and Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24: 4340-4346, 2006. 18. Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, and Judson I. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42: 1093-1103, 2006. 19. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, and Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347: 472-480, 2002. 20. Dorn CR, and Priester WA. Epidemiologic analysis of oral and pharyngeal cancer in dogs, cats, horses, and cattle. J Am Vet Med Assoc 169: 1202-1206, 1976. 21. Downing S, Chien MB, Kass PH, Moore PE, and London CA. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am J Vet Res 63: 1718-1723, 2002. 22. Foale R, and Demetriou J. Small animal oncology. Elsevier Saunders, New York, 2010. 23. Frost MJ, Ferrao PT, Hughes TP, and Ashman LK. Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant. Mol Cancer Ther 1: 1115-1124, 2002. 24. Galli SJ, Tsai M, Wershil BK, Tam SY, and Costa JJ. Regulation of mouse and human mast cell development, survival and function by stem cell factor, the ligand for the c-kit receptor. Int Arch Allergy Immunol 107: 51-53, 1995. 25. Galli SJ, Zsebo KM, and Geissler EN. The kit ligand, stem cell factor. Adv Immunol 55: 1-96, 1994. 26. Garrido MC, and Bastian BC. KIT as a therapeutic target in melanoma. J Invest Dermatol 130: 20-27, 2010. 27. Geissler EN, Ryan MA, and Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell 55: 185-192, 1988. 28. Giuliano EA, Chappell R, Fischer B, and Dubielzig RR. A matched observational study of canine survival with primary intraocular melanocytic neoplasia. Vet Ophthalmol 2: 185-190, 1999. 29. Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, and Qin S. Phase II, Open-Label, Single-Arm Trial of Imatinib Mesylate in Patients With Metastatic Melanoma Harboring c-Kit Mutation or Amplification. J Clin Oncol 2011. 30. Guo T, Agaram NP, Wong GC, Hom G, D'Adamo D, Maki RG, Schwartz GK, Veach D, Clarkson BD, Singer S, DeMatteo RP, Besmer P, and Antonescu CR. Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor. Clin Cancer Res 13: 4874-4881, 2007. 31. Harvey HJ, MacEwen EG, Braun D, Patnaik AK, Withrow SJ, and Jongeward S. Prognostic criteria for dogs with oral melanoma. J Am Vet Med Assoc 178: 580-582, 1981. 32. Heinrich MC, Corless CL, Blanke CD, Demetri GD, Joensuu H, Roberts PJ, Eisenberg BL, von Mehren M, Fletcher CD, Sandau K, McDougall K, Ou WB, Chen CJ, and Fletcher JA. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 24: 4764-4774, 2006. 33. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, and Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21: 4342-4349, 2003. 34. Henry CJ, Brewer WG, Jr., Whitley EM, Tyler JW, Ogilvie GK, Norris A, Fox LE, Morrison WB, Hammer A, Vail DM, and Berg J. Canine digital tumors: a veterinary cooperative oncology group retrospective study of 64 dogs. J Vet Intern Med 19: 720-724, 2005. 35. Hodi FS, Friedlander P, Corless CL, Heinrich MC, Mac Rae S, Kruse A, Jagannathan J, Van den Abbeele AD, Velazquez EF, Demetri GD, and Fisher DE. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol 26: 2046-2051, 2008. 36. Hornick JL, and Fletcher CD. The role of KIT in the management of patients with gastrointestinal stromal tumors. Hum Pathol 38: 679-687, 2007. 37. Kim KB, Eton O, Davis DW, Frazier ML, McConkey DJ, Diwan AH, Papadopoulos NE, Bedikian AY, Camacho LH, Ross MI, Cormier JN, Gershenwald JE, Lee JE, Mansfield PF, Billings LA, Ng CS, Charnsangavej C, Bar-Eli M, Johnson MM, Murgo AJ, and Prieto VG. Phase II trial of imatinib mesylate in patients with metastatic melanoma. Br J Cancer 99: 734-740, 2008. 38. Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, and Kirkwood JM. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 26: 527-534, 2008. 39. Kosovsky JK, Matthiesen DT, Marretta SM, and Patnaik AK. Results of partial mandibulectomy for the treatment of oral tumors in 142 dogs. Vet Surg 20: 397-401, 1991. 40. Lasota J, and Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology 53: 245-266, 2008. 41. Lasota J, and Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol 23: 91-102, 2006. 42. London CA, Hannah AL, Zadovoskaya R, Chien MB, Kollias-Baker C, Rosenberg M, Downing S, Post G, Boucher J, Shenoy N, Mendel DB, McMahon G, and Cherrington JM. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 9: 2755-2768, 2003. 43. London CA, Malpas PB, Wood-Follis SL, Boucher JF, Rusk AW, Rosenberg MP, Henry CJ, Mitchener KL, Klein MK, Hintermeister JG, Bergman PJ, Couto GC, Mauldin GN, and Michels GM. Multi-center, Placebo-controlled, Double-blind, Randomized Study of Oral Toceranib Phosphate (SU11654), a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor Following Surgical Excision. Clinical Cancer Research 15: 3856-3865, 2009. 44. Lutzky J, Bauer J, and Bastian BC. Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation. Pigment Cell Melanoma Res 21: 492-493, 2008. 45. Ma Y, Zeng S, Metcalfe DD, Akin C, Dimitrijevic S, Butterfield JH, McMahon G, and Longley BJ. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Blood 99: 1741-1744, 2002. 46. MacEwen EG, Patnaik AK, Harvey HJ, Hayes AA, and Matus R. Canine oral melanoma: comparison of surgery versus surgery plus Corynebacterium parvum. Cancer Invest 4: 397-402, 1986. 47. Marino DJ, Matthiesen DT, Stefanacci JD, and Moroff SD. Evaluation of dogs with digit masses: 117 cases (1981-1991). J Am Vet Med Assoc 207: 726-728, 1995. 48. Medeiros F, Corless CL, Duensing A, Hornick JL, Oliveira AM, Heinrich MC, Fletcher JA, and Fletcher CD. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 28: 889-894, 2004. 49. Montone KT, van Belle P, Elenitsas R, and Elder DE. Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression. Mod Pathol 10: 939-944, 1997. 50. Natali PG, Nicotra MR, Winkler AB, Cavaliere R, Bigotti A, and Ullrich A. Progression of human cutaneous melanoma is associated with loss of expression of c-kit proto-oncogene receptor. Int J Cancer 52: 197-201, 1992. 51. North SM, and Banks TA. Small animal oncology : an introduction. Saunders/Elsevier, New York, 2009. 52. Orfao A, Garcia-Montero AC, Sanchez L, and Escribano L. Recent advances in the understanding of mastocytosis: the role of KIT mutations. Br J Haematol 138: 12-30, 2007. 53. Proulx DR, Ruslander DM, Dodge RK, Hauck ML, Williams LE, Horn B, Price GS, and Thrall DE. A retrospective analysis of 140 dogs with oral melanoma treated with external beam radiation. Vet Radiol Ultrasound 44: 352-359, 2003. 54. Pryer NK, Lee LB, Zadovaskaya R, Yu X, Sukbuntherng J, Cherrington JM, and London CA. Proof of target for SU11654: inhibition of KIT phosphorylation in canine mast cell tumors. Clin Cancer Res 9: 5729-5734, 2003. 55. Quintas-Cardama A, Lazar AJ, Woodman SE, Kim K, Ross M, and Hwu P. Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib. Nat Clin Pract Oncol 5: 737-740, 2008. 56. Ramos-Vara JA, Beissenherz ME, Miller MA, Johnson GC, Pace LW, Fard A, and Kottler SJ. Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases. Vet Pathol 37: 597-608, 2000. 57. Rassnick KM, Ruslander DM, Cotter SM, Al-Sarraf R, Bruyette DS, Gamblin RM, Meleo KA, and Moore AS. Use of carboplatin for treatment of dogs with malignant melanoma: 27 cases (1989-2000). J Am Vet Med Assoc 218: 1444-1448, 2001. 58. Rivera RS, Nagatsuka H, Gunduz M, Cengiz B, Gunduz E, Siar CH, Tsujigiwa H, Tamamura R, Han KN, and Nagai N. C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma. Virchows Arch 452: 27-32, 2008. 59. Ronnstrand L. Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci 61: 2535-2548, 2004. 60. Rothwell TL, Howlett CR, Middleton DJ, Griffiths DA, and Duff BC. Skin neoplasms of dogs in Sydney. Aust Vet J 64: 161-164, 1987. 61. Rubin BP, Singer S, Tsao C, Duensing A, Lux ML, Ruiz R, Hibbard MK, Chen CJ, Xiao S, Tuveson DA, Demetri GD, Fletcher CD, and Fletcher JA. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61: 8118-8121, 2001. 62. Satzger I, Schaefer T, Kuettler U, Broecker V, Voelker B, Ostertag H, Kapp A, and Gutzmer R. Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas. Br J Cancer 99: 2065-2069, 2008. 63. Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J, and Koki AT. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89: 2637-2645, 2000. 64. Spritz RA, Giebel LB, and Holmes SA. Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. Am J Hum Genet 50: 261-269, 1992. 65. Todoroff RJ, and Brodey RS. Oral and pharyngeal neoplasia in the dog: a retrospective survey of 361 cases. J Am Vet Med Assoc 175: 567-571, 1979. 66. Torres-Cabala CA, Wang WL, Trent J, Yang D, Chen S, Galbincea J, Kim KB, Woodman S, Davies M, Plaza JA, Nash JW, Prieto VG, Lazar AJ, and Ivan D. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol 22: 1446-1456, 2009. 67. Ugurel S, Hildenbrand R, Zimpfer A, La Rosee P, Paschka P, Sucker A, Keikavoussi P, Becker JC, Rittgen W, Hochhaus A, and Schadendorf D. Lack of clinical efficacy of imatinib in metastatic melanoma. Br J Cancer 92: 1398-1405, 2005. 68. Wallace J, Matthiesen DT, and Patnaik AK. Hemimaxillectomy for the treatment of oral tumors in 69 dogs. Vet Surg 21: 337-341, 1992. 69. Wardelmann E, Buttner R, Merkelbach-Bruse S, and Schildhaus HU. Mutation analysis of gastrointestinal stromal tumors: increasing significance for risk assessment and effective targeted therapy. Virchows Arch 451: 743-749, 2007. 70. Wardelmann E, Neidt I, Bierhoff E, Speidel N, Manegold C, Fischer HP, Pfeifer U, and Pietsch T. c-kit mutations in gastrointestinal stromal tumors occur preferentially in the spindle rather than in the epithelioid cell variant. Mod Pathol 15: 125-136, 2002. 71. Went PT, Dirnhofer S, Bundi M, Mirlacher M, Schraml P, Mangialaio S, Dimitrijevic S, Kononen J, Lugli A, Simon R, and Sauter G. Prevalence of KIT expression in human tumors. J Clin Oncol 22: 4514-4522, 2004. 72. Wilcock BP, and Peiffer RL, Jr. Morphology and behavior of primary ocular melanomas in 91 dogs. Vet Pathol 23: 418-424, 1986. 73. Williams LE, and Packer RA. Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987-2001). J Am Vet Med Assoc 222: 1234-1236, 2003. 74. Willmore-Payne C, Holden JA, Tripp S, and Layfield LJ. Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum Pathol 36: 486-493, 2005. 75. Withrow SJ, and Vail DM. Withrow & MacEwen's small animal clinical oncology. Saunders Elsevier, New York, 2007. 76. Woodman SE, and Davies MA. Targeting KIT in melanoma: a paradigm of molecular medicine and targeted therapeutics. Biochem Pharmacol 80: 568-574, 2010. 77. Wyman K, Atkins MB, Prieto V, Eton O, McDermott DF, Hubbard F, Byrnes C, Sanders K, and Sosman JA. Multicenter Phase II trial of high-dose imatinib mesylate in metastatic melanoma: significant toxicity with no clinical efficacy. Cancer 106: 2005-2011, 2006. 78. Yamada O, Kobayashi M, Sugisaki O, Ishii N, Ito K, Kuroki S, Sasaki Y, Isotani M, Ono K, Washizu T, and Bonkobara M. Imatinib elicited a favorable response in a dog with a mast cell tumor carrying a c-kit c.1523A>T mutation via suppression of constitutive KIT activation. Veterinary Immunology and Immunopathology 142: 101-106, 2011. 79. Zemke D, Yamini B, and Yuzbasiyan-Gurkan V. Mutations in the juxtamembrane domain of c-KIT are associated with higher grade mast cell tumors in dogs. Vet Pathol 39: 529-535, 2002. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47719 | - |
dc.description.abstract | 黑色素瘤(Melanoma)為犬的惡性腫瘤,致病的原因不明,對化療或放療反應不佳,目前有許多新療法如基因治療、標靶治療等正在研發。KIT是一個細胞膜上的RTK(Receptor tyrosine kinase),藉由與其配體SCF(Stem cell factor)的接合,可活化細胞內的訊息傳遞,進而促進特定的細胞功能;若KIT的功能失調(過度表現或出現突變)則會使細胞癌化,在活體上造成惡性腫瘤。KIT的過度表現甚至是突變已在人黑色素細胞瘤中發現,尤其是在黏膜或肢端指甲下的黑色素瘤,其c-kit基因型的表現與標靶治療的效果具有相關性。本實驗以免疫組織化學染色法,佐以PCR技術,來分析臺灣大學動物醫院組織病理資料庫中49個犬黑色素瘤病例的KIT表現及c-kit基因突變的情形,再併同臨床上如發生的位置及預後等相關資料,分析其相關性,以評估KIT作為治療犬黑色素瘤標的之可行性。本研究蒐集的病例平均年齡為12±2.9歲,雄性佔59%(24/49),雌性佔41%(20/49),在可以評估的40個免疫組織化學染色的切片中,KIT染色皆為陽性,其中40%(16/40)呈現弱陽性,60%(24/40)為強陽性;在統計學上,KIT蛋白表現的強弱與犬黑色素瘤的發生位置、復發率或患犬的存活時間都沒有顯著的關聯性,但與腫瘤的轉移則有顯著的關聯性(p<0.05);在49個檢體中,c-kit外顯子11皆沒有發現任何型式的內生性連續性複製(Internal tandem duplications; ITDs)突變,但在其中PCR產物的定序結果發現,一個C1743T的靜默突變(Silence mutation)存在於5個檢體中,這5個檢體中另發現一個T1736C的錯義突變(Missense mutation),造成一個L579P的胺基酸突變,這個突變的發現,將有機會使用標靶藥物來治療部分犬的惡性黑色素瘤。 | zh_TW |
dc.description.abstract | Melanoma is a malignant tumor in dogs, and can be found associated with skin, nail bed or oral cavity. The etiology of melanoma in dogs is largely unknown. Systemic chemotherapy for malignant melanoma in the dog has not shown any significant benefit. Coarse fraction radiotherapy has only been used for local control. However, most dogs with malignant disease succumb to systemic spread. Several novel therapeutic modalities have been investigated. These include methods of gene therapy, target therapy, etc. KIT is a receptor tyrosine kinase, and SCF(stem cell factor) is the ligand for KIT. SCF is capable of binding to KIT resulting in activation of intracellular domain and initiation of multiple downstream signal transductions. Mutation or overexpression of KIT can transform indolent tumors to aggressive tumors in vivo. In human, KIT have long been hypothesized to play key roles in melanoma development, especially in mucosal and acral melanomas. Importantly, expression of mutation was then found to correlate with the sensitivity of target therapy. In this study, there were 49 cases of canine melanomas collected from National Taiwan University Animal Hospital. KIT protein expression was determined by immunohistochemistry, and KIT gene mutations were analysed by PCR amplification and electrophoresis. Then we discussed the clinical relevance of canine melanomas and KIT, such as the location, prognosis, etc., and evaluate the possibility of the target therapy in canine melanoma. The average age of these 49 cases was 12±2.9 years old. In 40 slides of immunohistiochemistry, all the samples presented positive, then 40%(16/40) for weak positive and 60%(24/40) for strong positive. There were no statistical significances between KIT expression and canine melanoma location, local recurrence rate or survival times. However, these was statistical significance between KIT expression and canine melanoma metastasis rate. The stronger KIT expression, the higher metastasis rate was noted. In the PCR and electrophoresis results, there was no ITD (internal tandem duplications) found in exon 11 of c-kit. Otherwise, a C1743T silence mutation of exon 11 of c-kit was revealed in five canine oral mucosal melanomas by sequencing, and one of the five sample existed a T1736C in-frame missense (L579P) mutation. There is the possibility of target therapy for canine melanoma in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T06:14:33Z (GMT). No. of bitstreams: 1 ntu-100-R98643010-1.pdf: 1216512 bytes, checksum: 0b09ad9f22cdf960ae9d93a9744d6a3e (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書 #
中文摘要 i ABSTRACT ii 目錄 iv 表次 vii 圖次 viii Chapter 1 前言 1 Chapter 2 文獻探討 2 2.1 犬黑色素瘤 2 2.1.1 犬口腔黑色素瘤 2 2.1.2 犬皮膚黑色素瘤 4 2.1.3 犬肢端指甲下黑色素瘤 6 2.1.4 其他部位之犬黑色素瘤 6 2.2 KIT蛋白與c-kit致癌基因 7 2.2.1 KIT蛋白基本構造和功能 7 2.2.2 c-kit基因與人黑色素瘤相關性 8 2.3 標靶治療應用於KIT失調的人類腫瘤 9 2.3.1 標靶治療實際應用在人胃腸基質瘤 10 2.3.2 標靶治療實際應用在人黑色素瘤 12 Chapter 3 材料與方法 14 3.1 實驗設計與流程 14 3.2 材料來源 15 3.1 組織KIT蛋白表現之檢測 15 3.1.1 脫黑色素(Melanin bleach method) 15 3.1.2 免疫組織化學染色(Immunohistiochemistry) 16 3.1.3 免疫組織化學染色評估 17 3.2 c-kit基因突變 18 3.2.1 福馬林固定組織蠟塊樣本之DNA萃取 18 3.2.2 聚合酶連鎖反應與電泳 19 3.2.3 增幅產物之膠體萃取與定序 20 Chapter 4 實驗結果 22 4.1 病歷蒐集 22 4.2 免疫組織化學染色評估犬黑色素瘤KIT蛋白表現 22 4.2.1 KIT蛋白表現與犬黑色素瘤發生位置之相關性 23 4.2.2 KIT蛋白表現與犬黑色素瘤局部復發率之相關性 23 4.2.3 KIT蛋白表現與犬黑色素瘤轉移率之相關性 23 4.2.4 KIT蛋白表現與犬黑色素瘤存活時間之相關性 24 4.3 c-kit基因突變 24 4.3.1 聚合酶連鎖反應與電泳 24 4.3.2 增幅產物之定序 25 Chapter 5 討論 26 5.1 犬黑色素瘤與KIT蛋白表現 26 5.2 犬黑色素瘤與c-kit基因突變 27 5.3 標靶治療應用於KIT失調的犬黑色素腫瘤 30 Chapter 6 結論 32 REFERENCE 55 | |
dc.language.iso | zh-TW | |
dc.title | 犬隻黑色素瘤和c-kit致癌基因之臨床相關性研究 | zh_TW |
dc.title | Clinical relevance of canine melanomas and c-kit oncogene | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 廖泰慶 | |
dc.contributor.oralexamcommittee | 李繼忠 | |
dc.subject.keyword | 犬黑色素瘤,KIT蛋白,c-kit致癌基因,標靶治療, | zh_TW |
dc.subject.keyword | canine melanoma,KIT,c-kit oncogene,target therapy, | en |
dc.relation.page | 65 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-19 | |
dc.contributor.author-college | 獸醫專業學院 | zh_TW |
dc.contributor.author-dept | 臨床動物醫學研究所 | zh_TW |
顯示於系所單位: | 臨床動物醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-100-1.pdf 目前未授權公開取用 | 1.19 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。