Wu Francis P K, Westphal Johan R, Hoekman Klaas, Mels Anneke K, Statius Muller Markwin G, de Waal Robert W, Beelen Rob H J, van Leeuwen Paul A M, Meijer Sybren, Cuesta Miguel A
Department of Surgery, VU Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Cytokine. 2004 Jan 21;25(2):68-72. doi: 10.1016/j.cyto.2003.09.010.
Wound healing is a process with immunological and angiogenic aspects. rhGM-CSF is known to stimulate the immune system and angiogenesis via multiple pathways. In this study we investigated the combined effects of surgery, with or without rhGM-CSF, on angiogenic parameters in patients with a colorectal carcinoma. In this phase II randomized, placebo-controlled trial, 16 patients were assigned to perioperative rhGM-CSF (2.8 microg/kg body weight) treatment or saline. Patients received subcutaneous injections from three days before surgery until four days after. IL-6, VEGF, endostatin and angiostatin levels were measured perioperatively. rhGM-CSF enhanced the production of IL-6 and VEGF, but had no effect on the antiangiogenic agents endostatin and angiostatin. Surgery induced a transient decrease of endostatin. Two types of angiostatin (kringle 1-3 and kringle 1-4) became visible postoperatively. We conclude that this study demonstrated the immediate initiation of angiogenesis postoperatively, reflected by the increase of VEGF and a transient decrease of endostatin, followed by the appearance of two angiostatin bands, which confirms physiological wound healing in these cancer patients.
伤口愈合是一个涉及免疫和血管生成方面的过程。已知重组人粒细胞巨噬细胞集落刺激因子（rhGM-CSF）可通过多种途径刺激免疫系统和血管生成。在本研究中，我们调查了手术联合或不联合rhGM-CSF对结直肠癌患者血管生成参数的影响。在这项II期随机、安慰剂对照试验中，16名患者被分配接受围手术期rhGM-CSF（2.8微克/千克体重）治疗或生理盐水治疗。患者从手术前三天至手术后四天接受皮下注射。围手术期测量白细胞介素-6（IL-6）、血管内皮生长因子（VEGF）、内皮抑素和血管抑素水平。rhGM-CSF增强了IL-6和VEGF的产生，但对血管生成抑制剂内皮抑素和血管抑素没有影响。手术导致内皮抑素短暂下降。术后出现了两种类型的血管抑素（kringle 1-3和kringle 1-4）。我们得出结论，本研究证明了术后血管生成立即启动，表现为VEGF增加和内皮抑素短暂下降，随后出现两条血管抑素条带，这证实了这些癌症患者的生理性伤口愈合。
