Serum biomarkers of cell death for monitoring therapy response of gastrointestinal carcinomas
Serum biomarkers of cell death for monitoring therapy response of gastrointestinal carcinomas
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DOI：
10.1016/j.ejca.2010.01.037
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发表时间：
2010-05-01
影响因子：
8.4
通讯作者：
Bantel, Heike
中科院分区：
文献类型：
--
作者：
Brandt, Doreen;Volkmann, Xandra;Bantel, Heike
目的：抗肿瘤治疗主要通过诱导肿瘤细胞凋亡来发挥作用。在上皮细胞中，凋亡的关键酶caspase将中间丝蛋白细胞角蛋白(CK)-18切割成特定片段，释放到循环血液中，可以通过特异性ELISA检测。实验设计：为了研究CK-18片段作为治疗反应的潜在生物标志物的使用，我们检测了35例胃肠道癌症患者血清CK-18水平与临床反应的关系。结果：虽然肿瘤患者的cleaved和total CK-18水平在本质上升高，但在以5-氟尿嘧啶（5-FU）为基础的治疗中，它们进一步升高。重要的是，CK-18水平的升高可以区分不同临床反应的患者。与进展性癌症患者相比，部分缓解或病情稳定的癌症患者在化疗期间cleaved CK-18的增加明显更高。结论：我们的研究结果表明，检测循环caspase裂解的CK-18可能是监测治疗反应的有用血清生物标志物，值得在更大的患者群体中进一步评估。(C) 2010 Elsevier Ltd.版权所有。
Purpose: Antitumour treatments are thought to exert their therapeutic efficacy mainly by induction of apoptosis in tumour cells. In epithelial cells, caspases, the key enzymes of apoptosis, cleave the intermediate filament protein cytokeratin (CK)-18 into specific fragments that are released into circulating blood and can be detected by a specific ELISA.Experimental design: To investigate the use of CK-18 fragments as a potential biomarker for the treatment response, we examined the association of serum CK-18 levels and clinical response in 35 patients with gastrointestinal cancers.Results: While both cleaved and total CK-18 levels were intrinsically elevated in tumour patients, they were further increased during 5-fluorouracil (5-FU)-based therapy. Importantly, the increased levels of CK-18 could discriminate between patients with different clinical response. Cancer patients with a partial response or stable disease revealed a significantly higher increase of cleaved CK-18 during chemotherapy as compared to patients with progressive disease.Conclusions: Our results suggest that detection of circulating caspase-cleaved CK-18 might be a useful serum biomarker for monitoring treatment response and should merit further evaluation in larger patient groups. (C) 2010 Elsevier Ltd. All rights reserved.