Zhang Xuefeng, Connolly Caitlin, Duquette Mark, Lawler Jack, Parangi Sareh
Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Stoneman 934, Boston, MA 02215, USA.
Cancer Lett. 2007 Mar 8;247(1):143-9. doi: 10.1016/j.canlet.2006.04.003. Epub 2006 Jun 6.
Thrombospondin-1 is one of most important natural angiogenic inhibitors. The three thrombospondin-1 type 1 repeats (3TSR), an anti-angiogenic domain of thrombospondin-1, is a promising novel agent for anti-angiogenic treatment. In the present study, we showed 3TSR was biologically stable at least for 7 days in mini-osmotic pumps in vivo, and continuous administration of 3TSR decreased the dosage and improved the potency of therapy in an orthotopic pancreatic cancer model. By using different dosage and delivery routes, we proved that the anti-tumor efficacy of 3TSR was correlated with its anti-angiogenic efficacy. 3TSR treatment also decreased tumor vessel patency and blood flow. The results indicate the advantage of continuous administration of angiogenic inhibitors and provide rationale for using such delivery methods for cancer treatment.
血小板反应蛋白-1是最重要的天然血管生成抑制剂之一。血小板反应蛋白-1的三个1型重复序列（3TSR）是血小板反应蛋白-1的抗血管生成结构域，是一种有前景的新型抗血管生成治疗药物。在本研究中，我们表明3TSR在体内微型渗透泵中至少7天具有生物学稳定性，并且在原位胰腺癌模型中持续给予3TSR可降低剂量并提高治疗效果。通过使用不同的剂量和给药途径，我们证明3TSR的抗肿瘤功效与其抗血管生成功效相关。3TSR治疗还降低了肿瘤血管的通畅性和血流量。结果表明了持续给予血管生成抑制剂的优势，并为使用这种给药方法治疗癌症提供了理论依据。
