Evaluate the response of Apoptosis, Angiogenesis and Cancer Therapies

Chathura Gayan
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Abstract

Angiogenesis, the growth of new blood vessels from the existing vasculature, and is maintained in adult tissues by the balanced presence of both angiogenic inducers and inhibitors in the tissue milieu. When inducers predominate, vascular endothelial cells (VECs) become activated and in this activated VECs, distinct cell signaling pathways are initiated providing the specificity of anti-angiogenic therapies to the tumor vasculature. VEC apoptosis has been well documented in regressing vessels, and it has been shown that, in addition to activating the VECs, some inducers such as vascular endothelial growth factor also up-regulate Fas expression, thus sensitizing the cell to apoptotic stimuli. Endogenous angiogenesis inhibitors, such as thrombospondin-1(TSP-1) and pigment epithelium-derived factor (PEDF), stimulate signaling cascades within the VECs and also induce the expression of Fas ligand in activated VECs. Therefore, when inhibitors predominate, the apoptotic cascade is initiated ,thus anti-angiogenic therapies can target the inducer supply or directly target the VECs. Although clinical studies suggest that anti-angiogenic therapies may prove to be most effective when used in combination with traditional therapies
评估细胞凋亡,血管生成和肿瘤治疗的反应
血管生成是指现有血管系统中新生血管的生长,在成人组织中通过组织环境中血管生成诱导剂和抑制剂的平衡存在而得以维持。当诱导剂占主导地位时,血管内皮细胞(VECs)被激活,在这种激活的VECs中,不同的细胞信号通路被启动,为肿瘤血管系统提供抗血管生成治疗的特异性。VEC凋亡在退化血管中已经有了很好的记录,并且研究表明,除了激活VEC外,一些诱导剂如血管内皮生长因子也上调Fas表达,从而使细胞对凋亡刺激敏感。内源性血管生成抑制剂,如血栓反应蛋白-1(TSP-1)和色素上皮衍生因子(PEDF),刺激VECs内的信号级联反应,并诱导活化的VECs中Fas配体的表达。因此,当抑制剂占主导地位时,凋亡级联被启动,因此抗血管生成治疗可以靶向诱导剂供应或直接靶向VECs。尽管临床研究表明,抗血管生成疗法与传统疗法联合使用时可能最有效
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