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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山(Jean-San Chia) | |
| dc.contributor.author | Dai-Ling Wu | en |
| dc.contributor.author | 吳岱陵 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:10:34Z | - |
| dc.date.available | 2020-09-24 | |
| dc.date.copyright | 2015-09-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-18 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52264 | - |
| dc.description.abstract | 口腔黏膜炎(oral mucositis)是頭頸癌病患接受放射線治療後產生的主要副作用，其發生率高達八至九成，造成病患口腔黏膜發炎、紅腫和潰瘍等現象，此病症造成病患吞嚥和進食困難，嚴重甚至造成味覺喪失或唾液分泌異常，影響病患生活品質，造成後續癌症療程進行上的困難，及增加傷口感染的可能性，然而目前尚未有有效的治療或預防方式。 以往的研究中得知，口腔黏膜炎為一種發炎反應，有許多reactive oxygen species和發炎前驅細胞激素IL-1β、TNF-α參與其中，放射線使上皮組織損傷而造成潰瘍，待上皮細胞增生和移動，能使傷口癒合。而STIM1為細胞內質網上之鈣離子感受器，當STIM1感受到內質網內的鈣離子濃度下降，STIM1聚集並移動至和接近細胞膜的位置，和ORAI1進行蛋白質-蛋白質交互作用形成綜合體，激活鈣離子經由此鈣離子通道從細胞外進入內質網中。 以往研究發現，STIM1能夠促使表皮生長因子誘導之上皮細胞的細胞增生和細胞遷移能力，並且對於腸子上皮細胞之受傷後復原能力有重要的影響，並於許多癌症轉移現象中，STIM1的表現量顯著上升。我們預期STIM1會影響上皮細胞的細胞增生和細胞遷移的能力進而影響傷口癒合。 我們以口腔黏膜炎小鼠模型之舌頭組織進行實驗，利用B6小鼠舌頭經照射25 Gy放射線後誘發口腔黏膜炎，並於小鼠舌頭潰瘍部位水敷或利用舌下注射方式給予BTP2，觀察老鼠體重、舌頭外觀及舌頭發炎區塊計算值的變化。 首先我們使用HaCaT細胞株進行細胞實驗，給予SOC抑制劑後，其會影響細胞遷移和增生能力。而進一步使用口腔黏膜炎小鼠模型研究，小鼠舌頭在經過放射線照射後，STIM1於不同時間點其表現顯著改變。並進一步以SOC抑制劑的方式給予照射放射線後的小鼠舌頭，發現其舌頭破損的面積隨著給予濃度提高而產生延遲現象。 我們猜測，STIM1在放射引起之口腔黏膜炎中，對於其時程或許扮演重要的腳色。希望這個發現，能夠幫助未來病人在口腔黏膜炎的治療上。 | zh_TW |
| dc.description.abstract | Oral mucositis (OM) is the most common side-effect of radiotherapy in head-and-neck cancer patients. It leads to the oral mucosa inflammation, swelling and ulceration. The patient with OM might have eating difficulty, dysgeusia or silvery gland dysfunction. Due to open sores in the mucosa, it increases the risk of infection and has an influence on cancer therapy. The mechanism involved in the regeneration of epithelial cells to achieve wound healing was not clear. OM is an inflammatory process including reactive oxygen species and proinflammatory cytokine (IL-1β and TNF-α) is detected in mucositis tissue. The epithelium damage and tissue ulceration develop after irradiation. This wound could recover by the epithelial cell proliferation and migration. STIM1 functions as a calcium sensor in the endoplasmic reticulum. Upon activation of the IP3 receptor, the calcium concentration in the ER decreases, which is sensed by STIM1. STIM1 activates calcium ion channels in the plasma membrane, via intracellular STIM1 movement, clustering under plasma membrane and protein-protein interaction with ORAI isoforms. It has been reported that STIM1 can effect cell proliferation and migration. It is important for intestinal epithelial reconstitution. We hypothesized that STIM1 would play a role to epithelial cell proliferation and migration in OM. We successfully established an oral mucositis mouse model of tongue by 25 Gy radiation dose in B6 mice. The mice tongue was treated BTP2 by filter paper masking or sublingual injection. The mice weight and the appearance or inflammatory area measurement of the mice tongue changes can be observed. The cell migration and cell proliferation of HaCaT cell line were influenced by BTP2. STIM1 was dramatically changed in tongue too oral mucositis mice model by western blotting. Furthermore, the irradiated-tongue was treated by BTP2 caused that the delay-type phenomenon of the erosion area. We suggested that the SOC channel might play a important role in the period of oral mucositis. Hopefully in the near future, the candidate protein of this study can be used to treat patients who suffer from oral mucositis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:10:34Z (GMT). No. of bitstreams: 1 ntu-104-R02449013-1.pdf: 20938885 bytes, checksum: b51d71a8f88242f779484e814bbfc415 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 誌謝 2 中文摘要 5 Abstract 7 Chapter 1. Introduction 9 1.1 Oral cancer 9 1.2 Oral mucositis 10 1.2.1 The pathobiology of oral mucositis 11 1.2.2 The prevention and treatment of oral mucositis 14 1.2.3 The animal model of oral mucositis 16 1.3 STIM1 and its function 18 1.4 Oral mucositis and STIM1 19 Chapter 2. Purposes and Aims 21 Chapter 3. Material and method 22 3.1 Cell 22 3.1.1 Cell culture 22 3.1.2 Cell passage 22 3.1.3 Migration assay 22 3.1.4 Cell viability test/MTT assay 23 3.2 Animal 23 3.2.1 Animal model establish 23 3.2.2 The erosion area measuring 24 3.2.3Animal tissue 24 3.2.4 IHC staining 24 3.2.5 H E staining 26 3.2.6 Western blotting 26 3.3 Statistical analysis 27 Chapter 4. Results 28 4.1. The BTP2 can affect the HaCaT cell viability and migration. 28 4.2. The different expression of the STIM1 in the oral mucositis process. 29 4.3. 25 gray of irradiation can induce the oral mucositis. 29 4.4. The BTP2 displayed the delayed feature of the oral mucositis caused by a single radiation dosage of 25 gray. 30 4.5. The BTP2 can delayed the feature in oral mucositis caused by a single radiation dosage of 25 gray. 31 4.6. The high concentration of the BTP2 led to the animal toxicity in the oral mucositis model caused by a single radiation dosage of 25 gray. 33 4.7. The high concentration of the BTP2 reduced the erosion of the oral mucositis model caused by a single radiation dosage of 25 gray. 34 Chapter 5. Discussion 36 Chapter 6. References 41 Chapter 7. Figures 51 | |
| dc.language.iso | en | |
| dc.title | 內質網鈣離子儲存感受器基質交互分子1在放射線誘導之口腔黏膜炎動物模型中可能扮演的角色 | zh_TW |
| dc.title | The possible role of Stromal interaction molecule 1 (STIM1)in the animal model of irradiation-induced oral mucositis. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 蔡丰喬(Feng-Chiao Tsai),成佳憲(Chia-Hsien Cheng) | |
| dc.subject.keyword | 內質網鈣離子儲存感受器基質交互分子1,口腔黏膜炎, | zh_TW |
| dc.subject.keyword | Stromal interaction molecule 1,STIM1,oral mucositis, | en |
| dc.relation.page | 91 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-18 | |
| 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 | |
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