Korse Catharina M, Bonfrer Johannes M G, Prevoo Warner, Baas Paul, Taal Babs G
Department of Clinical Chemistry, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands.
Tumour Biol. 2011 Aug;32(4):647-52. doi: 10.1007/s13277-011-0164-7. Epub 2011 Mar 5.
In the event of diffuse hepatic metastases, hepatic artery embolization (HAE) can be a successful treatment option in patients with well-differentiated neuroendocrine tumours (NET). However, embolization causes hypoxia which stimulates angiogenesis and therefore tumour growth. This study investigates angiogenesis activity following HAE by measuring vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and C-terminal proendothelin-1 (proET-1) in blood. Twelve patients with well-differentiated NET and liver metastases underwent HAE. VEGF, ET-1 and proET-1 were measured before embolization and the days following treatment during hospitalization. Mean levels during treatment were compared with those at baseline. From 12 patients, 90 blood samples were obtained before and daily for 8 days following HAE. Mean (± SE) VEGF level at baseline was 116 (± 33)ng/l which increased after HAE to 313 (± 46)ng/l at day 6, followed by a gradual decrease. ProET-1 showed a similar pattern, with a mean baseline level of 9.2 (± 2.0)pmol/l and the highest level of 40.8 (± 5.7)pmol/l at day 6. Some fluctuations were observed for ET-1, with maximum levels at day 3 compared to baseline levels. In patients with well-differentiated NET who underwent hepatic arterial embolization, angiogenic growth factors increase temporarily. This implies a need to investigate the effect of anti-angiogenic drugs as an adjuvant therapy to embolization.
对于发生弥漫性肝转移的患者，肝动脉栓塞术（HAE）对于高分化神经内分泌肿瘤（NET）患者可能是一种成功的治疗选择。然而，栓塞会导致缺氧，进而刺激血管生成，从而促进肿瘤生长。本研究通过测量血液中的血管内皮生长因子（VEGF）、内皮素-1（ET-1）和C末端前内皮素-1（proET-1）来研究HAE后的血管生成活性。12例高分化NET伴肝转移患者接受了HAE。在栓塞前以及住院治疗后的几天测量VEGF、ET-1和proET-1。将治疗期间的平均水平与基线水平进行比较。从12例患者中，在HAE前及术后8天每天采集90份血样。基线时VEGF平均（±标准误）水平为116（±33）ng/l，HAE后第6天升至313（±46）ng/l，随后逐渐下降。ProET-1呈现类似模式，基线平均水平为9.2（±2.0）pmol/l，第6天最高水平为40.8（±5.7）pmol/l。ET-1观察到一些波动，与基线水平相比，第3天达到最高水平。在接受肝动脉栓塞的高分化NET患者中，血管生成生长因子会暂时增加。这意味着需要研究抗血管生成药物作为栓塞辅助治疗的效果。
