2004-08-012024-05-15https://scholars.lib.ntu.edu.tw/handle/123456789/663461摘要：我們先前的研究 (衛生署科技計畫 DOH92-TD-1087; 我國專利申請中, 案號: 092136094) 發現口服金針菇免疫調節蛋白 FIP-fve (fungal immunomodulatory protein from Flammulina velutipes) 可顯著延長罹癌小鼠的存活率與存活時間，並提高小鼠之非特異性免疫反應與腫瘤特異性免疫反應。在非特異性免疫方面，餵食 FIP-fve 可促進小鼠的腹腔巨噬細胞產生 TNF-alpha 及 nitric oxide (NO)，並提高腹腔巨噬細胞毒殺腫瘤細胞的能力。在特異性免疫方面，餵食 FIP-fve可增加罹癌小鼠血清內腫瘤特異性 IgG 之濃度，提高脾細胞的腫瘤特異性細胞增生反應及干擾素IFN-agmma 分泌，並提高脾細胞的腫瘤特異性毒殺反應。 本計畫擬進一步深入研究口服 FIP-fve 產生抗腫瘤作用的各種機轉，以便有利於FIP-fve 在醫藥或是健康食品領域的應用與發展。首先，將探討口服 FIP-fve 如何影響腫瘤在小鼠體內的生長，以組織切片配合免疫染色法 (staining of incoporated<br> Abstract: Our previous study (DOH92-TD-1087) has demonstrated that oral administration of FIP-fve (fungal immunomodulatory protein from Flammulina velutipes) significantly increases the life span of BNL 1MEA.7R.1 hepatoma-bearing mice. Additionally, oral administration of FIP-fve can activate peritoneal macrophages, increase their TNF-alpha and nitric oxide production and enhance the tumoricidal activity of the cells. Furthermore, oral administration of FIP-fve also activates the tumor-specific immunity of the host. In hepatoma-bearing mice, the tumor-specific IgG levels in serum were markedly increased. When the splenocytes, which were also obtained from FIP-fve fed hepatoma-bearing mice, were treated with the tumor cells in vitro, the tumor-specific proliferation and IFN- / TNF- production of the splenocytes, which were obtained from FIP-fve fed hepatoma-bearing mice, were greatly promoted. These result suggests that FIP-fve displays anti-tumor activities in vivo associated with activating both non-specific and specific immunity of its host. The goal of this proposal is to further study the anti-tumor mechanism and explore the pharmaceutical potentials of FIP-fve. This project will be divided into 3 parts. The first part will study whether oral administration of FIP-fve inhibits the growth and angiogenesis of tumor or not. Immunohistochemistry technique will be used for staining the incorporation of BrdU and CD31 in the tissues. The second part will investigate the change of MHC molecules and co-stimulatory molecule B7 in the periphery blood of FIP-fve fed mice for understanding how FIP-fve strength their specific immunity. The third part will evaluate the role of gamma-interferon in the anti-tumor activity of FIP-fve. Antibodies against mouse IFN-gamma will be used to neutralize the IFN-gamma produced by FIP-fve administration. The survival, tumor size and life span of mice will be determined as evaluation markers to ensure the IFN-gamma is the major factor contribute to the anti-tumor activity of FIP-fve.金針菇免疫調節蛋白免疫調節抗癌