Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the systemic administration of a number of different gene products has been shown to result in the inhibition of angiogenesis and tumor growth in different animal tumor models, the relative potency of those gene products has not been studied rigorously. To address this issue, recombinant adenoviruses encoding angiostatin, endostatin, and the ligand-binding ectodomains of the vascular endothelial growth factor receptors Flk1, Flt1, and neuropilin were generated and used to systemically deliver the different gene products in several different preexisting murine tumor models. Single i.v. injections of viruses encoding soluble forms of Flk1 or Flt1 resulted in approximately 80% inhibition of preexisting tumor growth in murine models involving both murine (Lewis lung carcinoma, T241 fibrosarcoma) and human (BxPC3 pancreatic carcinoma) tumors. In contrast, adenoviruses encoding angiostatin, endostatin, or neuropilin were significantly less effective. A strong correlation was observed between the effects of the different viruses on tumor growth and the activity of the viruses in the inhibition of corneal micropocket angiogenesis. These data underscore the need for comparative analyses of different therapeutic approaches that target tumor angiogenesis and provide a rationale for the selection of specific antiangiogenic gene products as lead candidates for use in gene therapy approaches aimed at the treatment of malignant and ocular disorders.
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PMID:Comparative evaluation of the antitumor activity of antiangiogenic proteins delivered by gene transfer. 1127 74

Angiogenesis, the development of new vessels from a pre-existing vasculature, accompanies the growth and malignant transformation of astrocytic brain tumors. Neovascularization is essential for sustained tumor growth, and with increasing grade, astrocytic tumors undergo an, angiogenic switch, manifested by marked increases in vessel density and changes in vascular morphology. In the quiescent state, endogenous anti-angiogenic factors including endostatin, thrombospondin, and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) balance the actions of pro-angiogenic stimuli and restrain the angiogenic switch. Once activated, pro-angiogenic factors including most notably basic fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF-A), and platelet-derived growth factor (PDGF) incite robust astrocytoma neovascularization. Recent studies have also explored the expression patterns and functional importance of the angiopoietins, Tie2 and neuropilin receptors, and hepatocyte growth factor/scatter factor (HGF). Together these angiogenic factors have diverse actions on endothelium and perivascular supporting cells that engender tumor neovessels with a unique phenotype, distinct from normal vessels. Properties of the astrocytoma neovasculature contribute to tumor growth, malignant progression, invasion, hemorrhage, and edema formation. Thus, the mechanistic actions of angiogenic factors on cerebral microvessels and the nature of the resultant tumor neovasculature establish a framework for understanding many of the characteristic behaviors of astrocytoma tumors.
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PMID:Angiogenesis and its role in the behavior of astrocytic brain tumors. 1535 41

Since the approval of the first antiangiogenic agent bevacizumab, a neutralizing antibody against the vascular endothelial growth factor (VEGF), antiangiogenic therapies augmented the standard armamentarium of anticancer therapies and proved their clinical efficacy. Nevertheless, antiangiogenic strategies could not fulfill the expected hopes. In clinical routine, therapy responses to antiangiogenic therapies were mostly transient and most of the patients developed evasive resistance mechanisms during therapy. Further, no predictive biomarker for therapy response could be developed, hampering the clinical development of these agents and triggering skepticism. In the past years, knowledge on the biology of angiogenesis increased and the role of tumor hypoxia was better characterized and identified as the driver for angiogenic regulation mechanisms. Besides VEGF, new angiogenic and antiangiogenic factors were characterized and the process of endothelial cell migration, proliferation and vessel formation was better elucidated. Thus, a strong connection to neural development and axon guidance molecules like netrins, Slit proteins, semaphorins, ephrins and their cognate receptors UNC5, Robo1-4, neuropilin and EphB was identified. The aim of this review is to present the importance of these axon guidance molecules with special focus on Robo4 and semaphorins in tumor angiogenesis and to highlight their value as potential targets for new antiangiogenic therapies.
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PMID:New antiangiogenic strategies beyond inhibition of vascular endothelial growth factor with special focus on axon guidance molecules. 2440 53