請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/40222
標題: A combination of the metabolic enzyme inhibitor APO866 and the immune adjuvant L-1-methyl tryptophan induces additive antitumor activity
作者: Yang, H.J.
林季千
Yen, M.C.
Lin, C.C.
Lin, C.M.
Chen, Y.L.
Weng, T.Y.
Huang, T.T.
Wu, C.L.
Lai, M.D.
關鍵字: indoleamine 2,3-dioxygenase
1-methyl tryptophan
APO866 (FK866, WK175)
cancer therapy
combination therapy
gastric cancer
bladder cancer
adenine-dinucleotide biosynthesis
plasmacytoid dendritic cells
draining lymph-nodes
indoleamine 2,3-dioxygenase
nad biosynthesis
cancer
angiogenesis
apoptosis
depletion
degradation
期刊/報告no:: Experimental Biology and Medicine, Volume 235, Issue 7, Page(s) 869-876.
摘要: Many types of malignant cells have a higher nicotinamide adenine dinucleotide (NAD) turnover rate than normal cells, as well as the ability to escape immune responses. Indoleamine 2,3-dioxygenase (IDO) is reported to be a negative immune regulator. Overexpression of IDO in dendritic cells is observed in tumor-draining lymph nodes. IDO-expressing dendritic cells suppress T-cell activation and promote immune tolerance. The nicotinamide phosphoribosyl transferase (NAMPT) inhibitor APO866 (also called FK866 or WK175) selectively inhibits tumor growth through intracellular NAD depletion. The IDO-specific inhibitor L-1-methyl-tryptophan (L-1MT) activates immune responses and reduces tumor volume in murine tumor models. We combined L-1MT and APO866 treatments and tested their antitumor effects in the murine gastric and bladder tumor models. In immune-competent mice, a combination of APO866 and L-1MT had a better therapeutic effect than did either L-1MT or APO866 alone. The intracellular level of NAD was suppressed by APO866 but not L-1MT. However, an additive inhibitory effect on tumor growth was not observed in tumor-bearing immune-deficient mice. The new strategy of combining a metabolic inhibitor and an immune adjuvant induced a potent therapeutic effect.
URI: http://hdl.handle.net/11455/40222
ISSN: 1535-3702
文章連結: http://dx.doi.org/10.1258/ebm.2010.010001
顯示於類別:生物醫學研究所

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