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[二胺氧化酶作为大鼠和人类胃肠道对氟尿嘧啶抗癌药物毒性的血液生物标志物]

[Diamine oxidase as blood biomarker in rats and humans to GI tract toxicity of fluorouracil anti-cancer drugs].

作者信息

Goto Tetsuhiro, Matsubara Taketo, Yoshizawa Yasuo, Sasaya Shouji, Nemoto Hiroshi, Sanada Yutaka, Moriyama Kenji, Kouchi Yasuhide

机构信息

Dept. of Digestive Apparatus Surgery, Showa University, Fujigaoka Hospital.

出版信息

Gan To Kagaku Ryoho. 2011 May;38(5):765-9.

Abstract

Diarrhea is a side effect of a 5-fluorouracil (5-FU) anti-cancer drug-induced intestinal mucosal disorder, which sometimes becomes more severe. Blood diamine oxidase (DAO; EC1. 4. 3. 6) activity is reported to be significantly correlated with activity in the small intestinal mucosal tissue, and to be a reliable indicator of small intestinal mucosal integrity and maturity. Here, we investigated whether blood DAO activity can be a biomarker for the gastrointestinal (GI) mucosal disorder caused by 5-FU anti-cancer drugs, both in rats and humans. From results of the rat study, the degree of jejunal mucosal disorder caused by the 5-FU anti-cancer drug was well correlated with a decrease in blood DAO activity. Clinically, 12 out of 28 patients (43%) administered 5-FU anti-cancer drug suffered from diarrhea. The plasma DAO activity within one week of the onset of diarrhea significantly decreased compared with that before the administration. Furthermore, before drug administration, plasma DAO activity in patients suffering from diarrhea was higher than those in patients without diarrhea. Although DAO activity differs by the individual, it is a useful biomarker for estimating the degree of intestinal mucosal disorder, and possibly for estimating manifestations of diarrhea induced by 5-FU anti-cancer drug administration.

摘要

腹泻是5-氟尿嘧啶(5-FU)抗癌药物引起的肠道黏膜紊乱的一种副作用,有时会变得更加严重。据报道,血液中二胺氧化酶(DAO;EC1.4.3.6)活性与小肠黏膜组织活性显著相关,是小肠黏膜完整性和成熟度的可靠指标。在此,我们研究了血液DAO活性是否可作为5-FU抗癌药物引起的胃肠道(GI)黏膜紊乱在大鼠和人类中的生物标志物。从大鼠研究结果来看,5-FU抗癌药物引起的空肠黏膜紊乱程度与血液DAO活性降低密切相关。临床上,28例接受5-FU抗癌药物治疗的患者中有12例(43%)出现腹泻。腹泻发作一周内的血浆DAO活性与给药前相比显著降低。此外,在给药前,腹泻患者的血浆DAO活性高于无腹泻患者。尽管DAO活性因个体而异,但它是评估肠道黏膜紊乱程度以及可能评估5-FU抗癌药物给药引起的腹泻表现的有用生物标志物。

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