Sterescu Anca E, Rousseau-Harsany Elizabeth, Farrell Catherine, Powell Julie, David Michelle, Dubois Josee
Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ont., Canada.
Med Hypotheses. 2006;66(6):1121-4. doi: 10.1016/j.mehy.2005.12.040. Epub 2006 Feb 24.
Hemangiomas of infancy are benign vascular tumors frequently encountered in pediatrics. Medical treatment (corticosteroids, interferon, chemotherapy, embolization and radiation) in high-risk hemangioma cases could greatly benefit from the addition of new and safer therapies. The rapid growth of hemangiomas during the proliferative phase occurs secondary to a process of local uncontrolled angiogenesis, involving potent mediators such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We hypothesize that omega-3 fatty acids, naturally occurring nutrients of proven health benefit to infants, could become an alternative or an adjuvant treatment for hemangiomas, by slowing down their rapid proliferation phase through anti-angiogenic and anti-tumoral effects. Suggested mechanisms of action of omega-3 fatty acids include the downregulation of VEGF and bFGF, and the suppression of pro-angiogenic eicosanoids such as cylooxygenase-2. In this article, we review recent animal and human studies using dietary omega-3 fatty acids supplements, alone or in conjunction with chemotherapy, for the treatment of a variety of tumors dependent on angiogenesis for growth. Available murine hemangioma models offer the opportunity to determine optimal omega-3 fatty acid dose, while taking in account related immunohistochemical markers, clinical outcome and secondary effects, before planning clinical trials. Lessons learned in hemangiomas of infancy may have a broad impact in understanding the phenomenon of dysregulated angiogenesis in cancer research.
婴儿血管瘤是儿科常见的良性血管肿瘤。在高危血管瘤病例中,药物治疗(皮质类固醇、干扰素、化疗、栓塞和放疗)若能增加新的更安全的治疗方法,将大有裨益。血管瘤在增殖期的快速生长继发于局部不受控制的血管生成过程,涉及血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)等强效介质。我们推测,ω-3脂肪酸作为已证实对婴儿健康有益的天然营养素,可通过抗血管生成和抗肿瘤作用减缓血管瘤的快速增殖期,从而成为血管瘤的替代或辅助治疗方法。ω-3脂肪酸的作用机制包括下调VEGF和bFGF,以及抑制促血管生成的类花生酸如环氧化酶-2。在本文中,我们综述了近期使用膳食ω-3脂肪酸补充剂单独或联合化疗治疗多种依赖血管生成生长的肿瘤的动物和人体研究。现有的小鼠血管瘤模型为在开展临床试验前确定最佳ω-3脂肪酸剂量提供了机会,同时要考虑相关的免疫组化标志物、临床结果和副作用。在婴儿血管瘤方面获得的经验教训可能对理解癌症研究中血管生成失调现象产生广泛影响。