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研究生:沈哲標
研究生(外文):Che-piao Shen
論文名稱:評估合併兩種重組腺相關病毒分別攜帶HPV16E7融合heatshockprotein70gene及Angiostatingene對消除腫瘤的效果.
論文名稱(外文):EVALUATE THE COMBINED EFFICACY TO ELIMINATE TUMOR OF TWO RECOMBINANT ADENO-ASSOCIATED VIRUSES EXPRESSING HUMAN PAPILLOMA- VIRUS TYPE16 E7 PEPTIDE DNA FUSED WITH HEAT SHOCK PROTEIN 70 DNA AND ANGIOSTATIN GENE
指導教授:陳小梨陳小梨引用關係
指導教授(外文):Show-Li Chen
學位類別:碩士
校院名稱:國防醫學院
系所名稱:微生物及免疫學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:58
中文關鍵詞:重組腺相關病毒血管阻生素疫苗
外文關鍵詞:recombinant adeno-associated virusangiostatinvaccine
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根據衛生署最近公佈的民國89年台灣地區主要死因,其中在女性中排名第一位的是惡性腫瘤,在女性惡性腫瘤中,子宮頸癌排第四位。其主要致病原為人類乳突瘤病毒16、18型,它們的E5、E6、E7為主要致癌基因,目前已有許多針對這些基因發展出的腫瘤疫苗。對於腫瘤疫苗而言,主要必須藉細胞性免疫反應(特別為CTL反應),才可達清除腫瘤目的。
之前本實驗室證實了利用重組腺相關病毒(adeno-associatedvirus;AAV)攜帶E7CTL-hsp DNA可誘發對抗腫瘤的良好免疫反應,在本研究中則嘗試將這種重組腺相關病毒攜帶E7CTL-hsp DNA的疫苗合併另一種攜帶血管阻生素(angiostatin)基因的重組腺相關病毒,來觀察以此合併治療方法對抗腫瘤生長的效果。本實驗針對recombinant AAV-E7CTL-hsp疫苗在C57BL/6J老鼠體內引發的免疫反應,另以流式細胞計數儀的方式來分析,不同於本實驗室之前所採用的51Cr-releas CTL assay,但同樣證明其的確在老鼠動物實驗模式中可誘發特異性的CTL immune response。
在合併兩種重組腺病毒疫苗對抗腫瘤的動物實驗模式方面,本實驗以誘發老鼠的原發性腫瘤模式及轉移腫瘤為主軸,實驗結果指出以肌肉注射方式,給予老鼠重組腺相關病毒攜帶E7CTL-hsp DNA的疫苗又合併重組腺相關病毒攜帶血管阻生素(angiostatin)基因的疫苗,不論在老鼠上誘發原位腫瘤及轉移腫瘤的模式,相較於單獨給予老鼠注射重組腺相關病毒攜帶E7CTL-hsp DNA的疫苗,均對於消除腫瘤沒有產生加成的效用,但此結果並不表示此種合併免疫治療及抗血管新生策略的基因治療模式一定不可行,只是仍需進一步的檢討這種治療模式的各種細節,修改並且再多嘗試實驗。

According to the newest report about the major death causes in Taiwan from the Department of Health in 2000 ,the first one is carcinoma ,and cervical cancer is the fourth in carcinoma. human papilloma virus(HPV) type16 and type18 are the main pathogens, their E5,E6,E7gene are also major oncogenes. At pesent,there are many tumor vaccines based on these genes in the world. A tumor vaccine, it must induce cellular immunity especially in cytotoxic T lymphocyte effect to clear the tumor.
Our lab had proved that adeno-associated virus expressing E7CTL-hsp DNA(rAAV-E7CTL-hsp) will initiate well immune responses to inhibit the growth of tumor before.on the basis of rAAV-E7CTL-hsp,this report will try to combine another adeno-associated viral vectors expressing angiostatin gene ( rAAV-mAng-HA),to observe the efficacy to eliminate tumor of this combined therapy.this experiment also evaluate the immune response in C57BL/6J mice induced from rAAV-E7CTL-hsp injection by flow cytometry analysis. it indicated that rAAV-E7CTL-hsp indeed can induce E7-specific CTL immune response in mice ,and the same as the result by 51Cr-release CTL assay.
On the combined therapy of animal model, the core are induced in situ tumor model and induced metastsis tumor model. results told that if we give mice rAAV-E7CTL-hsp and rAAV-mAng-HA at the same time by intramuscular injection, compared to that with only rAAV-E7CTL-hsp injection, we were not see the enhanced effect to eliminate tumor growth. although results are not the same as which we expect, combined therapy will have synergetic effect, this strategy which combined immunotherapy and antiangiogenesis theories still have it’s potential to develop if we try hard to find out the knack.

1. 目錄 ………………………………….....1
2. 圖目錄 …………………………………… 2
3. 中文摘要 ………………………………… 3
4. 英文摘要 ………………………………… 5
5. 第一節: 前言 …………………………….7
6. 第二節: 實驗材料與方法 ……………… 14
7. 第三節: 結果 …………………………… 35
8. 第四節: 討論 …………………………… 47
9. 第五節: 結論 …………………………… 52
10. 第六節: 參考文獻 ……………………… 53

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