It is generally accepted that directional growth occurs from a region where a chemical substance is in low concentration toward a zone containing this substance in high concentration. In 1893, Loeb (477) first postulated that some trophic chemical might be responsible for vascularization in general. In 1907 Goldman (298) provided the first clear suggestion that neoplasms produced an angiogenic agent, when he noted that neovascularization could easily be traced to regions in which the tumor had not yet advanced and he stated that “the impetus which gives rise to the proliferation of blood vessels emanates from the invading cell”. That an angiogenic substance might be liberated by nonperfused or ischemic retina was proposed by Michaelson in 1948 (534). Using hamster cheek pouches Greenblatt and Shubik (320) provided convincing evidence that tumors produce a diffusible angiogenic factor in 1968.
KeywordsMigration Arthritis Lymphoma Adenocarcinoma Heparin
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