Tryptophan catabolism is dysregulated in leiomyomas

平滑肌瘤中的色氨酸分解代谢失调

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作者:Tsai-Der Chuang, Derek Quintanilla, Drake Boos, Omid Khorram

Objective

To determine the expression and functional roles of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) in leiomyoma. Design: Experimental study. Setting: Academic research laboratory. Patient(s): Women undergoing hysterectomy for leiomyoma. Intervention(s): Blockade of IDO1 and TDO2. Main outcome measure(s): Expression of IDO1 and TDO2 in leiomyoma and the effects of their inhibitors on the extracellular matrix. Result(s): Leiomyoma expressed significantly higher levels of IDO1 and TDO2 messenger ribonucleic acid (mRNA; 60.3%, 35/58 pairs and 98.3%, 57/58 pairs, respectively) and protein (54%, 27/50 pairs and 92%, 46/50 pairs, respectively) as well as the enzyme activity marker kynurenine (78.3%, 36/46 pairs for IDO1/TDO2) compared with levels in matched myometrium. The expression of TDO2 but not IDO1 mRNA was significantly higher in fibroids from African American compared with that in Caucasian and Hispanic patients. The TDO2 but not the IDO1 protein and mRNA levels were more abundant in fibroids bearing the MED12 mutation compared with

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