血管靶向药物治疗恶性浆膜腔积液研究进展.ppt

特别是针对VEGF、MMPs为靶点的治疗（血管靶向治疗）可能会成为治疗恶性腹腔积液的有效途径。 * * 1997年，Folkman教授发现了一种强有力的抑制因子——内皮抑素。是一种在动物体内天然存在的蛋白，含有184个氨基酸，分子量为20KD 试验研究发现内皮抑素具有强烈抑制血管生成作用。 图为动物试验的大体观，将肿瘤细胞接种在小鼠皮下后，对照组用生理盐水处理，肿瘤迅速长大，表面有溃烂，试验组用endostatin治疗，肿瘤生长几乎被完全抑制，显示了良好的抑瘤效果。 * 以上临床研究证实：恩度联合化疗，突破含铂一线化疗瓶颈，改写了晚期NSCLC治疗图景。恩度联合化疗给一线NSCLC患者带来更多生存获益！ 所以，恩度联合化疗已连续四年被NCCN（中国版）推荐为晚期NSCLC一线治疗选择。 KDR/Flk-1恩度抑制VEGF诱导的胞内酪氨酸激酶磷酸化信号 * 迄今为止作用最强的内源性血管生成抑制因子：endostatin 也主要是通过VEGF信号通路来抑制血管生成的。 恩度可以下调基质金属蛋白酶MMP2/9的表达 Endostar Suppresses Invasion Through Downregulating the Expression of Matrix Metalloproteinase-2/9 in MDA-MB-435 Human Breast Cancer Cells NA ? Cancer Treat Rev.?2014 May;40(4):548-57. doi: 10.1016/j.ctrv.2013.11.009. Epub 2013 Dec 6. Antiangiogenesis?beyond?VEGF?inhibition: a?journey?from?antiangiogenic?single-target?to?broad-spectrum?agents. Mechanisms of angiogenesis inhibition by single-target, multi-target and broad spectrum agents. Single-targets agents, like the monoclonal antibody bevacizumab,inhibit angiogenesis by blocking the interaction between the ligand (e.g., VEGF) and receptor (e.g., VEGFR). Multi-target agents, like tyrosine kinase inhibitors (e.g., axitinib),act through direct competition with ATP or by stabilizing the inactive conformation of the kinase domain, thus blocking the angiogenic signaling downstream the receptor.Tyrosine kinase inhibitors are usually able to block more than one growth factor receptor due to the degree of conservation among the kinase domains. By inhibiting thePDGFR in pericytes, axitinib may also block pericyte recruitment by angiogenic endothelial cells. Broad-spectrum receptors, like endostatin, inhibit several pathways in theangiogenic endothelial cell: besides blocking the signaling of angiogenic factors, endostatin upregulates the expression of anti-angiogenic genes, such as thrombospondin-1,and downregulates many signaling pathways associated with proangiogenic activity, significantly reducing the expression of HIF1-a. It was shown that endostatin affec