Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA.
Anticancer Agents Med Chem. 2011 Oct;11(8):756-61. doi: 10.2174/187152011797378805.
Data from past research is presented showing that neutrophils are active participants in new vessel formation in normal physiology, in proliferating human endometrium, in non-cancer pathologies as in the pannus of rheumatoid arthritis, and in various cancers, among them glioblastoma. These data show that interleukin-8 (IL-8) is a major chemokine attracting neutrophil infiltrates in these states. Since the old anti-Hansen's disease drug dapsone inhibits neutrophil migration along an IL-8 gradient towards increasing concentrations, and is used therapeutically for this attribute to good effect in dermatitis herpetiformis, bullous pemphigoid and rheumatoid arthritis, we suggest dapsone may deprive glioblastoma of neutrophil-mediated growth promoting effects. We review past research showing that vascular endothelial growth factor, VEGF, is carried predominantly intracellularly within neutrophils--only 2% of circulating VEGF is found free in serum. Based on the available evidence summarized by the authors, dapsone has a strong theoretical potential to become a useful anti-VEGF, anti-angiogenic agent in glioblastoma treatment.
过去的研究数据表明,中性粒细胞是正常生理中新血管形成、增殖的人类子宫内膜、非癌性病理(如类风湿关节炎的滑膜)以及各种癌症(包括神经胶质瘤)中的活跃参与者。这些数据表明,白细胞介素-8(IL-8)是吸引这些状态中性粒细胞浸润的主要趋化因子。由于旧的抗麻风病药物氨苯砜抑制中性粒细胞沿着 IL-8 梯度向浓度增加的方向迁移,并且由于其在疱疹样皮炎、大疱性类天疱疮和类风湿关节炎中的这种属性而被很好地用于治疗,我们认为氨苯砜可能剥夺神经胶质瘤中由中性粒细胞介导的促进生长的作用。我们回顾了过去的研究,表明血管内皮生长因子(VEGF)主要在中性粒细胞内携带——只有 2%的循环 VEGF 在血清中是游离的。基于作者总结的现有证据,氨苯砜具有成为神经胶质瘤治疗中有用的抗 VEGF、抗血管生成剂的强大理论潜力。