請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61477
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 賈景山 | |
dc.contributor.author | Hsien-Neng Kao | en |
dc.contributor.author | 高賢能 | zh_TW |
dc.date.accessioned | 2021-06-16T13:03:51Z | - |
dc.date.available | 2018-09-24 | |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-05 | |
dc.identifier.citation | 1. Sonis ST. Mucositis: The impact, biology and therapeutic opportunities of oral
mucositis. Oral oncology 2009, 45(12): 1015-1020. 2. Nonzee N, Dandade N, Patel U, Markossian T, Agulnik M, Argiris A, et al. Evaluating the supportive care costs of severe radiochemotherapy-induced mucositis and pharyngitis : results from a Northwestern University Costs of Cancer Program pilot study with head and neck and nonsmall cell lung cancer patients who received care at a county hospital, a Veterans Administration hospital, or a comprehensive cancer care center. Cancer 2008, 113(6): 1446-1452. 3. Sonis S. Oral mucositis. Anti-cancer drugs 2011, 22(7): 607-612. 4. Logan RM, Stringer AM, Bowen JM, Yeoh AS, Gibson RJ, Sonis ST, et al. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer treatment reviews 2007, 33(5): 448-460. 5. Sonis S. New thoughts on the initiation of mucositis. Oral diseases 2010, 16(7): 597-600. 6. Rao K, Brown M. Mast cells: multifaceted immune cells with diverse roles in health and disease. Annals of the New York Academy of Sciences 2008, 1143: 83-104. 7. Heissig B, Rafii S, Akiyama H, Ohki Y, Sato Y, Rafael T, et al. Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. The Journal of experimental medicine 2005, 202(6): 739-750. 8. Blirando K, Milliat F, Martelly I, Sabourin J-C, Benderitter M, Francois A. Mast cells are an essential component of human radiation proctitis and contribute to experimental colorectal damage in mice. The American journal of pathology 2011, 178(2): 640-651. 9. Duncan M, Grant G. Oral and intestinal mucositis - causes and possible treatments. Alimentary pharmacology & therapeutics 2003, 18(9): 853-874. 10. Tran K, Griffith L, Wells A. Extracellular matrix signaling through growth factor receptors during wound healing. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue 20 Repair Society 2004, 12(3): 262-268. 11. Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. The New England journal of medicine 2004, 351(25): 2590-2598. 12. Tsirigotis P, Triantafyllou K, Girkas K, Giannopoulou V, Ioannidou E, Chondropoulos S, et al. Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study. Bone marrow transplantation 2008, 42(5): 337-343. 13. Kawashima R, Kawamura Y, Kato R, Mizutani N, Toyama-Sorimachi N, Dohi T. IL-13 receptor alpha2 promotes epithelial cell regeneration from radiation-induced small intestinal injury in mice. Gastroenterology 2006, 131(1): 130-141. 14. Spyropoulos B, Theodoropoulos G, Misiakos E, Stoidis C, Zapatis H, Diamantopoulou K, et al. The Effect of Synbiotics on Acute Radiation-Induced Diarrhea and Its Association with Mucosal Inflammatory and Adaptive Responses in Rats. Digestive diseases and sciences 2013. 15. Murray L, Kramer M, Hesson D, Watkins B, Fey E, Argentieri R, et al. Serum amyloid P ameliorates radiation-induced oral mucositis and fibrosis. Fibrogenesis & tissue repair 2010, 3: 11. 16. Burdelya L, Gleiberman A, Toshkov I, Aygun-Sunar S, Bapardekar M, Manderscheid-Kern P, et al. Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and-neck cancer radiotherapy. International journal of radiation oncology, biology, physics 2012, 83(1): 228-234. 17. Han G, Bian L, Li F, Cotrim A, Wang D, Lu J, et al. Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis. Nature medicine 2013, 19(4): 421-428. 18. Amin K. The role of mast cells in allergic inflammation. Respiratory medicine 2012, 106(1): 9-14. 19. Liao C-h, Akazawa H, Tamagawa M, Ito K, Yasuda N, Kudo Y, et al. Cardiac mast cells cause atrial fibrillation through PDGF-A-mediated fibrosis in pressure-overloaded mouse hearts. The Journal of clinical investigation 2010, 21 120(1): 242-253. 20. Iddamalgoda A, Le Q, Ito K, Tanaka K, Kojima H, Kido H. Mast cell tryptase and photoaging: possible involvement in the degradation of extra cellular matrix and basement membrane proteins. Archives of dermatological research 2008, 300 Suppl 1: 76. 21. Nocka K, Tan J, Chiu E, Chu T, Ray… P. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. The EMBO … 1990. 22. Volpato L, Silva T, Oliveira T, Sakai V, Machado MA. Radiation therapy and chemotherapy-induced oral mucositis. Brazilian journal of otorhinolaryngology 2007, 73(4): 562-568. 23. Li F, Zhou M. Local microenvironment provides important cues for cell differentiation in lingual epithelia. PloS one 2012, 7(4). 24. Adamson I, King G, Bowden D. Collagen breakdown during acute lung injury. Thorax 1988, 43(7): 562-568. 25. Sonis S, Peterson R, Edwards L, Lucey C, Wang L, Mason L, et al. Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral oncology 2000, 36(4): 373-381. 26. West M, Heagy W. Endotoxin tolerance: a review. Critical care medicine 2002, 30(1 Suppl): 73. 27. Biswas S, Lopez-Collazo E. Endotoxin tolerance: new mechanisms, molecules and clinical significance. Trends in immunology 2009, 30(10): 475-487. 28. Sandig H, Jobbings C, Roldan N, Whittingham-Dowd J, Orinska Z, Takeuchi O, et al. IL-33 causes selective mast cell tolerance to bacterial cell wall products by inducing IRAK1 degradation. European journal of immunology 2013, 43(4): 979-988. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61477 | - |
dc.description.abstract | 口腔黏膜炎是一種由化療或放療引起常見的副作用。在頭頸癌患者的治療中,放射線治療被廣泛地使用。由於放射線治療後口腔粘膜炎的高發病率,常造成患者沉重的經濟負擔,並因此開發一種有效的治療方法是迫切需要的。在這項研究中,我們展示了一個動物模型,可以穩定地在針對舌頭照射25Gy 的放射線之後產生口腔黏膜炎。照射後一個星期,體重會有明顯的下降,並且在大約相同的時間可以看到舌頭上產生紅斑。除此之外由組織學證實上皮的厚度變薄,以及上皮細胞的增殖受到阻礙。潰瘍形成於照射後10 天,會發生嗜中性細胞的浸潤。粘膜下層組織中的肥大細胞也增加,證明嗜中性細胞及肥大細胞可能參與在口腔黏膜炎的進程中。藉由肥大細胞缺陷的小鼠,我們觀察在口腔黏膜炎動物模式中,與肥大細胞缺陷的小鼠比較時,野生型小鼠有較大的潰瘍和較薄的上皮。因此有肥大細胞的參與可能會造成較為嚴重的口腔黏膜炎。然而促炎性細胞激素的表現量,在肥大細胞缺陷的小鼠舌頭內的表現量也較高,顯示較為嚴重的炎症反應可能不是造成較口腔黏膜炎嚴重性的原因。此外,在背側的上皮細胞顯示了一個特定的恢復模式,在舌頭尖端的上皮細胞較其他部位早開始增殖。這個區域特定的恢復情形可能來自於不同微環境之間的差異,但其中的機制仍不清楚。總結,此篇研究提供放射線導致口腔黏膜炎啟始和復原期之黏膜外觀、潰瘍及角質細胞增生病理變化,根據發炎前驅物和口腔黏膜炎嚴重程度在肥大細胞缺陷及野生型小鼠不一致的結果顯示發炎反應可能不是決定放射線引發口腔黏膜炎之決定因子。 | zh_TW |
dc.description.abstract | Oral mucositis is a common side-effect caused either by chemo- or radiotherapy. In the head-and-neck cancer patients, radiotherapy is widely used as the primary therapeutic approach or adjunctive therapy post-operationally. During radiotherapy, the oral mucositis is a heavy economic burden to the patient, but preventive or effective treatment is still in need. In this study, we
developed a mouse model of oral mucositis after 25Gy irradiation delivered restrictively to the tongue. One week after irradiation, the mouse body weight dropped significantly and the erythema on tongue emerged . The thickness of epithelium is reduced and the proliferation of the epithelial cells is hindered. The ulceration began 10 days after irradiation with infiltration of neutrophils. The tissue-resident mast cells also increase at the submucosa, suggesting their roles in the progression of oral mucositis. In the mast cells-deficient mice, epithelial damage or ulceration area was reduced comparing with the wild type mice, suggesting that mast cells may be harmful to the epithelium during radiation-induced inflammation. However, the level of pro-inflammatory cytokines was significantly higher in the mutant mice suggesting that epithelial damage may be induced by other inflammatory mediators. In addition, the recovery of the epithelial cells exhibited a site-specific pattern with the epithelial cells locate at the tip start to recover earlier than other regions of the dorsal side. This site-specific recovery might result from the differences between microenvironment yet the mechanism remains unclear. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T13:03:51Z (GMT). No. of bitstreams: 1 ntu-102-R00449008-1.pdf: 3163320 bytes, checksum: b3f58f03d73b77f766664ec537119088 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 目錄 I
Abstract III 中文摘要 IV Chapter 1. Introduction 1 1.1 Oral mucositis 2 1.1.1 The progression of oral mucositis 2 1.1.2 The treatment of oral mucositis 3 1.1.3 The animal models in the study of oral mucositis 4 1.2 Mast cell 4 Chapter 2. Purposes and Aims 6 Chapter 3. Material and method 7 3.1 Animals and radiation 7 3.2 Animal tissue 7 H&E stain 7 Toluidine blue staining 8 IHC staining 8 RNA extraction 9 Reverse transcription 9 Real-time quantity Polymerase chain reaction (qPCR) 10 Chapter 4. Results 11 4.1. Twenty-five Gy of irradiation is capable of inducing the oral mucositis,with significant loss of body weight, as well as erythema and ulcer formation observed on the tongue. 11 4.2. The radiation inhibited the proliferation of epithelial cells which and led to the thickness decrease of the epithelium and eventually the ulcer formation on the tongue. 11 4.3. No neutrophil infiltration to the submucosa until the ulcer was formed,and conversely, the amount of mast cells in the submucosa increased after irradiation. 12 4.4. The level of pro-inflammatory cytokines was transiently enhanced during the oral mucositis. 13 4.5 The mast cells deficient mice showed similar decrease of body weight comparing to the wild type mice after irradiation, but the erythema on the tongue exhibited less severity. 13 4.6 The smaller ulcer size suggested the less severe degree of oral mucositis in the mast cells deficient mice, the same was the true regarding the thicker epithelium. 14 II 4.7 The mast cells deficient mice had higher level of pro-inflammatory cytokines, however the infiltration of the neutrophil was comparable to the wild type littermates. 14 Chapter 5. Discussion 16 Chapter 6. Reference 19 Chapter 7. Figures 22 | |
dc.language.iso | en | |
dc.title | 肥大細胞於放射線引發之口腔潰瘍小鼠模式中之影響 | zh_TW |
dc.title | The effect of mast cells in a mouse model of
radiation-induced oral mucositis. | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 成佳憲,陳俊任,朱清良 | |
dc.subject.keyword | 肥大細胞,放射線,放射線治療,口腔黏膜炎, | zh_TW |
dc.subject.keyword | mast cells,radiation,radiotherapy,oral mucositis, | en |
dc.relation.page | 44 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-08-05 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 免疫學研究所 | zh_TW |
顯示於系所單位: | 免疫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-102-1.pdf 目前未授權公開取用 | 3.09 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。