新方法可抑制卵巢癌发展并降低化疗剂量

  近日，一篇刊登于国际杂志The FASEB Journal上的研究论文中，来自圭尔夫大学(university of guelph)的研究人员开发了一种新方法，其可以在改善药物运输的同时来促进卵巢肿瘤收缩，从而帮助有效改善卵巢癌患者的5年生存率；这种新方法利用一种名为凝血酶敏感蛋白1（TSP-1）的血管发生蛋白抑制剂的重组形式来实现抑制卵巢癌的目的；而这个蛋白抑制剂重组形式名为3TSR，其可以同另一种名为CD36的蛋白相互作用阻断癌细胞生长并且促进其死亡，而CD36则可以促进肿瘤形成新的血管。

  研究者Jim Petrik表示，我们希望本研究为开发新型疗法来治疗恶性卵巢癌的女性提供一定的帮助；目前利用抗血管生成疗法结合节律化疗方法或可潜在地改善治疗卵巢癌的效率，同时也会减少疗法对患者带来的副作用。

  文章中，研究者将小鼠卵巢癌细胞注射入小鼠的卵巢中，研究人员让这些肿瘤不断生长直至其和恶性卵巢癌患者机体中的肿瘤形态类似，包括让小型肿瘤扩散至整个小鼠腹部；研究者发现，利用3TSR对小鼠进行预处理可以改善化疗药物的运输，而当结合低剂量的化疗时就会导致肿瘤发生明显的萎缩；因此这样的方法就可以促进肿瘤减小从而导致其发生异常性毁灭。

  杂志主编Gerald Weissmann博士说道，当Judah Folkman首次发现肿瘤的生长依赖于血管生成时，众多同行并不认为如此；然而今天有很多证据证明的确如此，当然本研究也证实了这一点，文章揭示，基于血管生成抑制剂和化疗药物一同作用可以有效抑制肿瘤的生长，从而为改善患者的生存率和生活质量提供了巨大的帮助。（转化医学网360zhyx.com）

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Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer
The FASEB Journal doi:10.1096/fj.14-261636
Samantha Russell*, Mark Duquette†, Joyce Liu‡, Ronny Drapkin‡, Jack Lawler† and Jim Petrik*,1
Most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage, where therapies have limited effectiveness and the long-term survival rate is low. We evaluated the effects of combined antiangiogenic and chemotherapy treatments on advanced stage EOC. Treatment of EOC cells with a recombinant version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell death (36.5 ± 9.6%) in vitro compared to untreated controls (4.1 ± 1.4). In vivo, tumors were induced in an orthotopic, syngeneic mouse model of advanced stage EOC. Mice were treated with 3TSR (4 mg/kg per day) alone or in combination with chemotherapy drugs delivered with maximum tolerated dose or metronomic scheduling. Pretreatment with 3TSR induced tumor regression, normalized tumor vasculature, and improved uptake of chemotherapy drugs. Combination 3TSR and metronomic chemotherapy induced the greatest tumor regression (6.2-fold reduction in size compared to PBS-treated controls) and highest survival when treatment was initiated at advanced stage. 3TSR binding to its receptor, CD36 (cluster of differentiation 36), increased binding of CD36 and SHP-1, which significantly inhibited phosphorylation of the VEGF receptor. In this study, we describe a novel treatment approach and mechanism of action with 3TSR and chemotherapy that induces regression of advanced stage EOC and significantly improves survival.—Russell, S., Duquette, M., Liu, J., Drapkin, R., Lawler, J., Petrik, J. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer.