請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/34395
標題: | 五氨基酮戊酸光動力治療用於第一型神經纖維瘤病之研究探討 Investigation of 5-aminolevulinic acid-mediated photodynamic therapy in neurofibromatosis type 1 |
作者: | Shih-Hsuan Hung 洪士軒 |
指導教授: | 陳進庭(Chin-Tin Chen) |
關鍵字: | 五氨基酮戊酸,Protoporphyrin IX,神經纖維肉瘤,細胞吸收與排出, 5-Aminolevulinic acid,Protoporphyrin IX,Neurofibrosarcoma,Cellular uptake and efflux, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | 第一型神經纖維瘤病(neurofibromatosis type 1)是一種常見之神經性自體顯性遺傳疾病,由NF1基因突變所致。主要病徵為表皮上大小程度不一的神經纖維瘤(neurofibroma),且有機會發展成惡性神經纖維肉瘤(neurofibrosarcoma),除了造成生理上的病痛外,外觀上的不雅也嚴重影響患者的心理發展。目前,此病尚未發展出一套有效的治療方式,傳統的手術切除面臨的最大問題在於腫瘤細胞是交纏著周邊的正常細胞而生長,術後不僅造成正常神經的損傷,也會因清除不完全而產生腫瘤復發及轉移。在臨床研究上,五氨基酮戊酸之光動力治療(5-aminolevulinic acid-mediated photodynamic therapy, ALA-PDT)具有光感物質高度選擇性累積於腫瘤之特質,並透過局部範圍之光照進而產生單態氧及自由基專一地對腫瘤細胞造成破壞,引發細胞之死亡。同時,為了提升ALA-PDT的治療效率,本研究將人類神經纖維肉瘤細胞S462以ALA-PDT加上其他藥物進行合併處理,可觀察到細胞毒殺效果與單獨處理相比,其效果顯著提升且具有協同效應,而且對於正常細胞並不會造成嚴重傷害。另外,合併處理後的細胞存活率無法藉由細胞凋亡與細胞自噬的抑制而提升,同時在細胞內也觀察到PI染劑的出現,說明細胞壞死(necrosis)的發生。更值得注意的是,本研究成功地建構出一套有效對抗神經纖維肉瘤的混和型治療模式,而這一個模式也適用於其他腫瘤的治療,這象徵著未來將可以此調控機制作為藥物作用及臨床應用之新標的。 Neurofibromatosis type 1 (NF1) is one of the most common neurogenetic disorders with a high incidence, 1/3000. It is an autosomal dominant disease caused by a mutation in NF1 gene. Benign neurofibromas appeared in varied sizes on the skin are the major clinical symptoms in patients with NF1, and around 10% of neurofibromas would transform into malignant peripheral nerve sheath tumors (also named neurofibrosarcomas) with poor prognosis. In addition to physical pains, marked cosmetic disfigurements also serve patients as psychological traumas. Presently, no efficient therapy is available except for surgical resection. However, after surgery, the functions of nervous system may be destroyed or tumor recurrence and metastasis may occur due to the close cellular association between tumor and normal cells as well as growth along the nerve itself in neurofibromas. 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT), which involved the photochemical reactions based on the interaction of photosensitizing agents, light energy, and oxygen, has become a remarkable modality in anti-tumor therapy. Since the higher selective accumulation of ALA-derived PpIX in tumor cells, topical illumination can specifically induce oxidative stress followed by cell death to tumors. In this study, we tested ALA-PDT in combination with other compound to investigate the cytotoxic effects, cell death modes, and action mechanisms in human neurofibrosarcoma S462 cells. Photodynamic killing effect on tumor cells was synergistically induced, however, without severe damage to normal cells after exposure to 635 nm light. There was no rescue effect in applying the inhibition of apoptosis and autophagy and propidium iodide (PI) was shown inside the treated cells as well, indicating that necrotic cell death might be the major process caused by this treated model. Significantly, in this study, these results suggest that ALA-PDT has the potential for the treatment of neurofibrosarcoma. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/34395 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科技學系 |
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 | 5.43 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。