Yunmbam M K, Wellstein A
V.T. Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
Oncol Rep. 2001 Jan-Feb;8(1):161-4.
The growth of supportive tissue during the progression of solid tumors is an absolute requirement for the nourishment of the tumor. The blockade of this proliferative response of normal tissues to the growing tumor should hence inhibit tumor progression. We have shown earlier, that the heparinoid pentosan polysulfate (PPS) can block tumor growth and neoangiogenesis induced by Kaposi's FGF as well as by other heparin-binding growth factors (HBGFs). We now report on the effects of a bacterial polysaccharide, tecogalan, on tumor xenografts of human breast cancer cells. Tecogalan inhibited FGF-dependent SW-13 cells in vitro very similarly to PPS. Growth factor-independent MDA-MB 231 cells were used in animal studies to assess the in vivo potential of tecogalan. Subcutaneous growth of tumors was inhibited by once weekly i.v. administration of tecogalan. PPS single weekly administration showed a similar effect. No gross side effects were observed. Based on our previous studies with these models, we conclude, that tecogalan acts by blocking HBGFs released from tumor cells. Interestingly, single weekly dosing of either PPS or tecogalan appears to be strikingly more efficacious than spreading the dose over several administrations. These findings with a novel compound, tecogalan, and a novel treatment regimen, PPS, suggests a different approach to planning of therapies with these types of drugs.
实体瘤进展过程中支持性组织的生长是肿瘤营养供应的绝对必要条件。因此,阻断正常组织对生长中肿瘤的这种增殖反应应能抑制肿瘤进展。我们之前已经表明,类肝素戊聚糖多硫酸盐(PPS)能够阻断卡波西成纤维细胞生长因子(Kaposi's FGF)以及其他肝素结合生长因子(HBGFs)诱导的肿瘤生长和新生血管形成。我们现在报告一种细菌多糖teco galan对人乳腺癌细胞异种移植瘤的影响。Tecogalan在体外对FGF依赖的SW - 13细胞的抑制作用与PPS非常相似。在动物研究中使用不依赖生长因子的MDA - MB 231细胞来评估teco galan的体内潜力。通过每周一次静脉注射teco galan可抑制肿瘤的皮下生长。每周单次给予PPS也显示出类似效果。未观察到明显的副作用。基于我们之前对这些模型的研究,我们得出结论,teco galan通过阻断肿瘤细胞释放的HBGFs发挥作用。有趣的是,每周单次给予PPS或teco galan似乎比将剂量分散在几次给药中更有效。这些关于新型化合物teco galan和新型治疗方案PPS的发现,为这类药物的治疗规划提出了一种不同的方法。