國立臺灣大學醫學院外科曾勝弘2006-07-262018-07-112006-07-262018-07-112004-07-31http://ntur.lib.ntu.edu.tw//handle/246246/24527本研究計畫為三年計畫，主要在探討IL-12及IL-18免疫基因療法，以及抗血管生成基因 療法等不同作用機轉的組合基因療法對於神經膠質瘤的療效。我們建立多種重組腺病毒， 包括Ad/IL-12、Ad/IL-18、Ad/Endo，其titer在1011-1012 pfu。接著進行動物實驗，以這些重 組腺病毒，單獨或合併，來治療腦瘤，結果發現對照組及Ad/IL-18組大鼠全部死亡，Ad/IL-12 組有50%存活率，Ad/ME組有30%存活率，Ad/IL-12+Ad/IL-18有50%存活率， Ad/IL-12+Ad/ME有70%存活率，Ad/IL-18+Ad/ME有30%存活率，Ad/IL-12+Ad/IL-18+Ad/ME 有70%存活率。Ad/IL-12、Ad/IL-12+Ad/IL-18、Ad/IL-12+Ad/ME、Ad/IL-12+Ad/IL-18+Ad/ME 組都比對照組存活率高(P<0.05)；但Ad/IL-18、Ad/ME、Ad/IL-18+ Ad/ME組則與對照組存 活率沒有差別(P>0.05)；此外，Ad/IL-12+Ad/IL-18+Ad/ME組比Ad/IL-18、Ad/ME、 Ad/IL-18+Ad/ME組存活率高(P<0.05)，但與Ad/IL-12、Ad/IL-12+Ad/IL-18、Ad/IL-12+Ad/ME 則無差別(P>0.05)。這結果証明單獨以Ad/IL-12治療對於腦部神經膠質瘤有療效，但單獨以 Ad/IL-18治療則沒有療效，合併二者並無加成效果。此外，合併Ad/IL-12及Ad/ME則有加成 效果，但再加上Ad/IL-18則亦未能提高療效。This 3-year project is intended to investigate the effects of combined interleukin-12 (IL-12)- and IL-18-based gene therapy and anti-angiogenesis gene therapy on the intracerebral gliomas in rats. We constructed several recombinant adenoviral vectors, including Ad/IL-12, Ad/IL-18, Ad/Endo, with the titers in the range of 1011 to 1012 pfu. Then these adenoviral vectors were used to treat the intracerebral gliomas. All the control rats and the rats treated with Ad/IL-18 died. By contrast, the survival rate of the rats treated with Ad/IL-12 was 50%, Ad/ME was 30%, Ad/IL-12+Ad/IL-18 was 50%, Ad/IL-12+Ad/ME was 70%, Ad/IL-18+Ad/ME was 30%, and Ad/IL-12+Ad/IL-18+Ad/ME was 70%. The Ad/IL-12, Ad/IL-12+Ad/IL-18, Ad/IL-12+Ad/ME, and Ad/IL-12+Ad/IL-18+Ad/ME groups had higher survival rate than the control groups (P<0.05). However, the Ad/IL-18, Ad/ME, Ad/IL-18+ Ad/ME groups showed no significant difference from the control groups (P>0.05). on the other hand, Ad/IL-12+Ad/IL-18+Ad/ME group had higher survival rate than Ad/IL-18, Ad/ME, or Ad/IL-18+Ad/ME groups (P<0.05), but showed no difference from the Ad/IL-12, Ad/IL-12+Ad/IL-18, or Ad/IL-12+Ad/ME groups (P>0.05). The results indicated that Ad/IL-12 alone was effective for the treatment of intracerebral gliomas, by contrast, Ad/IL-18 had no therapeutic effect on the glioma. Combined Ad/IL-12 and Ad/IL-18 showed no synergistic effects. Combined Ad/IL-12 and Ad/ME shoed synergistic effects on the intracerebral gliomas, however, addition of Ad/IL-18 did not enhance the therapeutic effects.application/pdf46254 bytesapplication/pdfzh-TW國立臺灣大學醫學院外科神經膠質瘤免疫基因療法抗血管生成基因療法interleukin-12interleukin-18endostatin腺病毒載體gliomaimmunogene therapyanti-angiogenesis gene therapyadenoviral vectorreporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/24527/1/922314B002253.pdf