臺灣博碩士論文加值系統

Fas-L (CD95-Ligand) 屬於腫瘤壞死因子 (TNF) 家族 (family)的一員，分子量為40-KD的type II transmembrance protein，Fas-L和攜有Fas 的細胞作用，並藉此導致細胞凋亡 (apoptosis)。本研究論文主要在探討影響Fas-L作用在腫瘤生長的可能因子。本研究係利用F10-Vector和F10-Fas-Lribozyme二株Fas-L表現量差異的黑色素瘤細胞株 (B16-F10-melamoma cell)，以幾種不同的處理方式給予小鼠 (B6 mice) 腫瘤細胞，並觀察腫瘤生長之異同。
當在小鼠背部以皮下注射給予腫瘤細胞，表現高量Fas-L的F10-Vector黑色素瘤細胞在生長速度及腫瘤大小上皆較F10-Fas-Lribozyme細胞來的快且大。但在背部皮下傷口及背部皮下氣囊 ，則Fas-Lribozyme腫瘤的生長加速。而注射能表現抗血管新生物質 (angiostatin) 的腺病毒 (adenovirus) 或冬蟲夏草 (cordyceps sinensis) 則都不會抑制腫瘤細胞的生長。低劑量 (20μg/mice) 的尿調理素 (uromodulin) 能抑制F10-Fas-Lribozyme的生長。但在體外 (in vitro)， 尿調理素 (uromodulin) 對腫瘤細胞並沒有細胞毒殺作用 (cytotoxicity)。
腫瘤細胞注射在小鼠皮下氣囊 (air pouch) 後，皮下氣囊 (air pouch) 回抽液中的免疫細胞以嗜中性球 (neutrophils) 及單核球 (monocytes) 為主，且F10-Vector處理組浸潤的免疫細胞比F10-Fas-Lribozyme多。在施打尿調理素 (uromodulin) 後，其皮下氣囊 (air pouch) 回抽液內的嗜中性球表現較多CD11b。綜合以上結果，我們認為尿調理素 (uromodulin) 影響Fas-L作用在腫瘤生長，可能藉由激發某些未知的因子，進而活化免疫細胞。

Fas ligand (Fas-L, CD95L, APO-1L) expresses in a variety of tumors and has been proposed to play a role in tumor formation and metastasis. Our preliminary results showed that down-regulation of Fas-L in B16F10, reduced its tumorigenic property accompanied with decreased cell infiltration. In this study we try to explore whether tissue injury and local application of uromodulin, might affect the tumoregenicity of B16F10 having different amount of Fas-L. When tissue was damaged, cut wounding or air pouch formation, growth of tumors having low Fas-L was enhanced, but not that having high amount of Fas-L. Application of uromodulin had various tumor-inhibiting effects on melanoma. Serial injections of 20 g/mice suppressed the growth of tumors, regardless they carry Fas-Lribozyme or not. Subantanous administration natural cordyceps (Cordyceps sp.) or angiostatin did not effect tumor growth. We further investigated the role of uromodulin and how tumor Fas-L affects tumorigenicity. In vitro, uromodulin was not cytotoxic to melanoma cells. Administration of uromodulin did not enhance the number of infiltreated immune cells in air pouch inoculated with tumors, but the percentage of activated neutrophils among infiltrated cells was increased. Activation of neutrophil by uromodulin was evident in vivo. However, casein-enriched peritoneal neutrophils were not directly activated upon uromodulin treatment in vitro. These results indicate that the effect of uromodulin on tumor growth may be through the activation of several types of immune cells.

目錄
頁數
中文摘要 1
英文摘要 3
前言 4
實驗設計 9
儀器與試劑 11
材料和方法 14
結果 23
討論 29
參考文獻 36
Fig (圖) 45

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