研究生: |
謝承霖 Chen-lin Hsieh |
---|---|
論文名稱: |
結合放射治療與腺病毒-細胞激素3基因治療以治療攝護腺癌 Combining Radiotherapy and Adv-IL3 Gene Therapy for Prostate Cancer Therapy |
指導教授: |
江啟勳
Chi-shiun Chiang |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2003 |
畢業學年度: | 91 |
語文別: | 中文 |
論文頁數: | 77 |
中文關鍵詞: | 細胞激素3 、腺病毒 、放射治療 、攝護腺癌 |
外文關鍵詞: | IL-3, adenovirus, radiotherapy, prostate cancer, Interleukin-3 |
相關次數: | 點閱:147 下載:0 |
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本論文嘗試以放射治療結合腺病毒-IL3基因治療的方式對小鼠攝護腺癌 (TRAMP C-1) 進行治療,IL-3不但是調控幹細胞增生及分化成各型細胞的重要造血因子,也是癌症的免疫基因療法中可有效讓細胞毒性T細胞侵入腫瘤組織,引發毒殺腫瘤細胞免疫反應的重要因子,過去基因治療的相關實驗多是建立IL-3基因轉殖的腫瘤細胞來治療,耗時較久,若以腺病毒載體將IL-3基因帶入腫瘤細胞則更適合於臨床上的應用。雖然從受治療小鼠腫瘤生長曲線中看出放射治療結合腺病毒-IL3基因治療與單獨放射治療相比沒有明顯成效,但從RNA層面的RT-PCR結果可以得知是因為此款腺病毒載體引起的宿主免疫反應超過了IL3基因治療的效果所造成,可以改用其他類型的腺病毒載體來降低宿主免疫反應。
本論文另一主題是不同週齡攝護腺癌基因轉殖鼠 (TRAMP,transgenic adenocarcinoma of the mice prostate) 的基因表現與切片觀察,TRAMP轉殖鼠的轉殖基因段是以大鼠PB (probasin) 基因為啟動子,SV 40-Tag當致癌基因而製造出來的基因轉殖鼠,藉由RNA層面的RT-PCR結果可以看出TRAMP轉殖鼠的攝護腺及肺臟確實都攜帶SV 40-Tag致癌基因,而原本只應該在攝護腺組織才會表現的PB基因卻也能在肺臟裡找到。另一欲觀察的基因mSTEAP原本只特異表現於攝護腺、腎臟及睪丸,但卻在正常小鼠肺臟組織中也可發現,使用mSTEAP當攝護線治療目標的方式是否可行仍須再評估。而mTEM1基因應只會較高程度的表現於血管新生時的腫瘤中,但我們卻從RT-PCR結果可以看到TRAMP轉殖鼠連肺臟都有很大量的mTEM1表現。
TRAMP轉殖鼠攝護腺切片H & E stain的部分可明顯看出其攝護腺管體在癌化過程中上皮細胞增生的情況,細部觀察更可看出其細胞核逐漸變形,逐步邁向未分化完全的癌細胞及微指狀突起消失的現象。
The aim of this research is to combine radiation therapy and adenovirus-IL3 gene therapy for TRAMP C-1 prostate cancer. Interleukin 3 (IL-3) is known as a hematopoietic factor. Its function is not only to stimulate stem cell proliferation and differentiation, but is also able to stimulate cytotoxic T cell recognizing and killing cancer cells in the model of cancer immunogene therapy. Adenovirus vector is a useful vector to deliver genes into cancer cells in situ and is more practical for clinical application. This study showed that there was not significant difference between the group of combining radiation therapy and adenovirus-IL3 gene therapy and the group of radiation therapy only. The results of RT-PCR suggested that adenovirus vector induced stronger host immune response than IL-3 gene therapy. The choice of other vectors that do not elicit host immune response is suggested.
The second topic of this research is to study the histological changes and the pattern of gene expression profile in TRAMP mice (transgenic adenocarcinoma of the mice prostate) at different ages. RT-PCR results showed that both prostate and lung tissues expressed SV 40-Tag oncogene and probasin mRNAs. The mSTEAP gene should be expressed only in prostate, kidney and testis, but its expression was also found in lung tissue. mTEM1 gene should be expressed and up-regulated only in angiogenesis tumors. However, the result showed that mTEM1 was also highly expressed in lung tissue in TRAMP mice.
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