Department of Gastroenterology, Hannover Medical School, Hannover, Germany.
Eur J Cancer. 2010 May;46(8):1464-73. doi: 10.1016/j.ejca.2010.01.037. Epub 2010 Mar 2.
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.
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.
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.
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.
抗肿瘤治疗被认为主要通过诱导肿瘤细胞凋亡来发挥其治疗效果。在上皮细胞中，细胞凋亡的关键酶 caspase 将中间丝蛋白细胞角蛋白（CK）-18 切割成特定片段，这些片段释放到循环血液中，并可以通过特定的 ELISA 检测到。
为了研究 CK-18 片段作为治疗反应的潜在生物标志物的用途，我们检查了 35 名胃肠道癌患者的血清 CK-18 水平与临床反应的相关性。
虽然肿瘤患者的裂解和总 CK-18 水平本身就升高，但在基于 5-氟尿嘧啶（5-FU）的治疗过程中进一步升高。重要的是，CK-18 的升高水平可以区分具有不同临床反应的患者。与进展性疾病患者相比，部分缓解或稳定疾病的癌症患者在化疗期间裂解 CK-18 的增加水平明显更高。
我们的结果表明，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。
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