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Table of ContentsIntroduction Angiogenesis, the construction of new vasculature, has been recognized as a key step in cancer for over 100 years, but it was not until the 1970's that Judah Folkman suggested that the abnormal development of vasculature could be used to target malignant tumors.1 Anti-angiogenic therapies, including antibodies to key angiogenic growth factors and small molecule inhibitors, are now being developed by pharmaceutical companies as a way to stop angiogenesis and prevent tumor growth and metastasis. The creation of new blood vessels is normal and occurs routinely as part of wound healing, pregnancy, and menarche. As with normal tissue, solid tumors require oxygen and nutrients to continue growth, and tumors obtain oxygen from a nearby circulatory capillary. Since the diffusion distance of oxygen is 100-200 μm, tumor cells farther than that distance from the capillary evolve into a hypoxic (oxygen-starved) state. This hypoxia leads to expression of vascular endothelial growth factor (VEGF) and other factors to initiate angiogenesis. Read More...
Malignant AngiogenesisIn normal tissues, the balance of pro-angiogenic and anti-angiogenic growth factors and proteins favors inhibition of angiogenesis, so that as new capillaries are needed, the balance can be adjusted to stimulate vascular growth. This corresponds to the angiogenic switch and the balance hypothesis proposed by Hananah and Folkman in 1996 (see Figure 1).1 The critical angiogenic activator is vascular endothelial growth factor (VEGF), but several other growth factors participate in the process. Basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP), transforming growth factor-α (TGF-α), platelet derived growth factor (PDGF), placenta growth factor (PlGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and hepatocyte growth factor (HGF) are all pro-angiogenic factors. Endogenous angiogenic inhibitors are proteins including endostatin, angiostatin, thrombospondin-1 (Tsp-1), tumstatin, platelet factor 4, and certain interleukins, including IL-12. Some of these proteins, including endostatin, angiostatin, and Tsp-1, are known to promote apoptosis in addition to preventing angiogenesis. Read More
Protocol: IntroductionIn recent years Quantitative PCR has reached a level of sensitivity, accuracy, and ease to support use as a routine assay for measuring gene level expression. The field of cancer research is currently validating a number of applications showing that qPCR can be a reliable tool for both researchers and clinicians concerning the behavior of tumors.1 Quantitative PCR is one of the molecular techniques providing the tools necessary to investigate tumor biology and to discover the genetic and epigenetic causes of cancer. qPCR is being used to analyze the biological differences between tumors that account for variations in morphology and clinical behavior. Quantitative PCR is playing an increasingly important role in clinical testing, providing information about gene expression, gene amplification or loss, and small alterations. It is also being used for detection and quantification of viral causes of cancer. qPCR has proven to be an extremely valuable diagnostic resource due to its objectivity, speed, versatility, and cost-effectiveness.2 Read More
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