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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82109完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳信銘(Hsin-Ming Chen) | |
| dc.contributor.author | Yu-Ting Siao | en |
| dc.contributor.author | 蕭妤庭 | zh_TW |
| dc.date.accessioned | 2022-11-25T05:36:02Z | - |
| dc.date.available | 2026-10-25 | |
| dc.date.copyright | 2021-11-09 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-27 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82109 | - |
| dc.description.abstract | 實驗目的:近年的研究指出被破壞的癌組織所產生的細胞碎片，在機制上與疫苗相似，數百種來自癌症的特異性腫瘤細胞群會釋放出獨特抗原，可以刺激出抗腫瘤的抗體、毒殺性 T 細胞，從而製造出強大的免疫反應，不僅可以消除腫瘤亦可殺死遠處的轉移，此稱為遠端效應(Abscopal effect)。冷凍治療後原位破壞的腫瘤組織可以作為腫瘤抗原的來源，被抗原呈現細胞捕獲、處理並呈遞給 T 細胞， 從而有助於誘導抗腫瘤免疫，但是這種由此所產生出的腫瘤抗原在臨床上並無看到明顯的效果，推測是因為這不足以克服有些癌症已經發展的免疫反應檢查點的逃逸機制，如細胞程式死亡-配體( Programmed Cell Death-Ligand 1，PD-L1)。 除此之外，冷凍治療對於 PD-L1 也能產生直接或間接的影響，而薑黃素 (Curcumin)在不同的癌症中皆被研究出能夠抑制腫瘤 PD-L1 蛋白的表現量。本篇研究想要探討冷凍治療後 PD-L1 的表現變化與後續引發的細胞機制改變，以及使用 curcumin 是否能有抑制冷凍後口腔癌細胞中的 PD-L1 表現量，並使動動物模式實驗，當使用冷凍治療治療腫瘤時結合 curcumin 的施打會不會產生全身性的抗腫瘤反應。 實驗方法:本篇研究選取人類口腔癌細胞株 SAS 與 Ca9-22，與兩種由 4- Nitroquinoline-1-oxide (4NQO)誘導的 C57BL/6 小鼠舌癌細胞 MTC-Q1-GFP 與 MOC-L1，分別進行了加入薑黃素(0-20 μM)、冷凍治療(0-80 secs)、以及兩者合併使用的實驗。並以細胞存活率分析(MTT assay)、西方墨點法(Western Blot)、 傷口癒合試驗(Wound Healing Assay) 和動物實驗探討薑黃素在細胞上和動物上對 PD-L1、Epithelial-mesenchymal transition(EMT)、stemness 壓力是否有著調節作用。 實驗結果:薑黃素在細胞作用 24 小時後，濃度 10、20 μM 下 PD-L1 蛋白量有明顯下降，在 EMT 相關蛋白如 E-cadherin 上升，N-cadherin、vimentin、Snail、 Twist1/2 和幹性有關的蛋白如 ABCG2、Oct4 等的表現量都會隨著薑黃素的濃度升高而下降。然而在冷凍治療下，發現隨著噴液態氮的秒數增加，細胞中的 PD- L1、EMT 和幹性蛋白也都隨之增加，但是這種升高的現象是屬於短暫的，細胞約莫在五天後恢復各項數值。在細胞冷凍治療時同時給予薑黃素，可以抑制由冷凍刺激所照成的 PD-L1、N-cadherin、vimentin、Snail、Twist1/2、ABCG2、Oct4 上升，在傷口癒合試驗亦可以看到薑黃素能將細胞冷凍後遷移的能力提高給抑制下來，符合蛋白表限量的變化。在動物實驗中，冷凍治療噴 10、20 秒都是有效能縮減小鼠背上的腫瘤，將治療後殘留下的腫瘤放置，可以發現腫瘤的惡性程度增加。而在結合薑黃素給予小鼠冷凍治療後，並沒有發現預期的 Abscopal effect，沒有加速腫瘤的縮小，亦沒有察覺到遠端腫瘤的消減。 結論:在細胞上，液態氮冷凍後因爲微環境的改變會對細胞照成刺激，隨著秒數的增加蛋白如 E-cadherin 下降，N-cadherin、vimentin、Snail、Twist1/2、 ABCG2、Oct4 蛋白上升，而再結合薑黃素後，明顯可以看到抑制的效果。但在動物實驗上似乎沒有看到跟細胞實驗一樣的效果。這些初步結果，可以發現薑黃素對於口腔癌的一些效果，如若找出臨床上與細胞上的差異，對於口腔癌在遠端效應與冷凍治療的臨床應用和治療效果會有更多幫助。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T05:36:02Z (GMT). No. of bitstreams: 1 U0001-2210202109522800.pdf: 16714456 bytes, checksum: 6b590529d6e31f15558d41563f72a1cb (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員審定書 I 中文摘要 II ABSTRACT IV CONTENTS VII CHAPTER 1 導論（INTRODUCTION） 1 1.1 口腔癌 1 1.1.1 定義 1 1.1.2 致病因子 1 1.1.3 台灣口腔癌現況 2 1.1.4 治療與預後 2 1.2 冷凍治療（CRYOTHERAPY） 4 1.2.1 起源 4 1.2.2 細胞機制 4 1.2.3 口腔癌上的應用 5 1.2.4 優勢與限制 6 1.3 冷凍免疫（CRYO-IMMUNIZATION） 8 1.3.1 冷凍治療後產生的細胞碎片 8 1.3.2 冷凍治療後的免疫反應 8 1.3.3 冷凍治療的遠端效應（Abscopal effect） 9 1.4 PROGRAMMED CELL DEATH-LIGAND 1（PD-L1） 11 1.4.1 PD-L1介紹 11 1.4.2 PD-L1與細胞EMT和Stemness關聯 11 1.4.3 免疫檢查點阻斷療法 12 1.5 薑黃素（CURCUMIN） 14 1.5.1 薑黃素介紹 14 1.5.2 薑黃素與PD-L1關係 14 CHAPTER 2 實驗材料與方法(MATERIALS AND METHODS) 16 2.1細胞株來源及培養 16 2.2 西方點墨法（WESTERN BLOTTING） 18 2.3 冷凍治療 20 2.4 細胞活性測試（MTT ASSAY） 20 2.5 動物實驗 21 2.6 傷口癒合測定（WOUND HEALING ASSAY） 23 2.7 酵素結合免疫吸附分析法（ENZYME-LINKED IMMUNOSORBENT ASSAY, ELISA） 23 2.8 統計分析 24 CHAPTER 3 實驗結果（RESULTS） 25 3.1 不同種口腔癌細胞株PD-L1蛋白的表現量 25 3.2 薑黃素可以抑制細胞的生存率和PD-L1蛋白的表現量 26 3.3 薑黃素藉由JAK/STAT路徑抑制PD-L1的蛋白表現量 27 3.4 冷凍治療後細胞中的PD-L1蛋白表現量上升 28 3.5 冷凍後細胞PD-L1蛋白量上升造成EMT與幹性上升 29 3.6 冷凍治療後癌細胞引發的現象非永久持續性的 30 3.7 在細胞上使用薑黃素可以抑制冷凍治療造成的負面影響 33 3.8 薑黃素也可以抑制冷凍後微環境的細胞激素IL-1Β上升 35 3.9 冷凍治療在小鼠模型上能減少口腔癌大小，但也讓腫瘤上的PD-L1增加表現 37 3.10 冷凍治療後沒有處理乾淨的腫瘤會變得更惡性 38 3.11 在小鼠模型上無法看到薑黃素有抑制PD-L1上升達到ABSCOPAL EFFECT的效果 40 CHAPTER 4 討論（DISCUSSIONS） 41 CHAPTER 5 結論（CONCLUSION） 45 CHAPTER 6 圖與表（FIGURES＆TABLES ） 46 REFERENCE 75" | |
| dc.language.iso | zh-TW | |
| dc.subject | 冷凍治療 | zh_TW |
| dc.subject | 口腔鱗狀細胞癌 | zh_TW |
| dc.subject | 程序化死亡分子 | zh_TW |
| dc.subject | 薑黃素 | zh_TW |
| dc.subject | 腫瘤遠端效應 | zh_TW |
| dc.subject | 上皮間質轉化 | zh_TW |
| dc.subject | 免疫療法 | zh_TW |
| dc.subject | 細胞幹性 | zh_TW |
| dc.subject | Oral squamous cell carcinoma | en |
| dc.subject | cryotherapy | en |
| dc.subject | immunotherapy | en |
| dc.subject | Programmed Cell Death-Ligand (PD-L1) | en |
| dc.subject | curcumin | en |
| dc.subject | abscopal effect | en |
| dc.subject | EMT | en |
| dc.subject | stemness | en |
| dc.title | 薑黃素可抑制口腔癌細胞株經冷凍治療所致細胞程式死亡- 配體 1、上皮間質轉化和幹細胞特性相關蛋白表現過度表現 | zh_TW |
| dc.title | "Curcumin Can Inhibit Overexpression of Program Death-Ligand 1, Epithelial Mesenchymal Transition, and Stemness Related Proteins Induced by Cryotherapy in Oral Cancer Cell Lines" | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 江俊斌(Hsin-Tsai Liu),侯欣翰(Chih-Yang Tseng),黎萬君 | |
| dc.subject.keyword | 口腔鱗狀細胞癌,冷凍治療,免疫療法,程序化死亡分子,薑黃素,腫瘤遠端效應,上皮間質轉化,細胞幹性, | zh_TW |
| dc.subject.keyword | Oral squamous cell carcinoma,cryotherapy,immunotherapy,Programmed Cell Death-Ligand (PD-L1),curcumin,abscopal effect,EMT,stemness, | en |
| dc.relation.page | 88 | |
| dc.identifier.doi | 10.6342/NTU202104013 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-10-27 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-10-25 | - |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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