Term
Angiogenesis may be the “switch” that controls tumor promotion and progression
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Definition
-Angiogenesis: recruitment of endothelial cells from existing vessels
-Vasculogenesis: activation of endothelial cell precursors
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Term
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Definition
-Basement membrane is remodeled during angiogenesis; essential to motility of endothelial cells and re-forming new vessels
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Term
Tumor vasculature is fundamentally different from normal vasculature
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Definition
(A) illustrates well branched and coiled, large vessels growing into the tumor, similar to human malignant brain tumors. Penicillamine treated brain (B) has delicate, orderly vessels resembling normal human brain vasculature.
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Term
critical feature for growth |
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Definition
Heterogeneous abilities of cells to induce angiogenesis; critical feature for growth
possible lack of clinical response
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Term
The expression of angiogenic markers |
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Definition
The expression of angiogenic markers can be used as surrogate markers for clinical prediction
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Term
Anti-angiogenic molecules: an example of “rational drug design”
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Definition
•Antibodies against positive regulators--VEGF or FGF-2 or their receptors
•Inhibitors of MMPs that aid in tissue remodeling
•Natural compounds—curcumin, antioxidants
•Suramin-urea derivative, inhibits FGF-2
Angiostatin--38 kDa internal Kringle domain fragment of plasminogen; directly decreased proliferation of endothelial cells, increased apoptosis
Endostatin--20kDa C-terminal proteolytic peptide fragment of collagen 18; does not affect proliferation, but does increase apoptosis and decrease number of vessels in animal tumors
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Term
Angiogenesis inhibitors can affect any point in the pathway; generally grouped in “direct” and “indirect” methods
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Definition
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1.Direct inhibitors affect endothelium and its response to stimuli
2.Indirect inhibitors affect the tumor cell expression of angiogenic growth factors
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