An Italian pioneer in the study of tumor angiogenesis.

I t is generally accepted that the role of angio-genesis in the progression of human solid tumors was originally postulated by Folkman in 1971. 1 The central component in this revolutionary paradigm was that tumor cells undergo an angiogenic switch and generate vasculariza-tion intimate to the tumor. 2 Prior to this switch, tumors are less than 3 mm 3 and thus this new vascularization allows them to grow rapidly, invade and spread. The switch to an angiogenic phenotype is essentially an outcome of a change in the pro-and anti-angiogenic vascular factors produced by tumor cells, such that the micro-environment is altered and tumor-related micro-vessels proliferate. Research on tumor angio-genesis, however, was really started by Virchow 3 who recognized that the stroma of tumors has a distinctive capillary network. Many investigators subsequently showed that vessels induced by tumor are different from normal vessels. 4 The growth of these vessels is related to that of the tumor and they may thus be targets for therapy. 5 Tumor vascularization was first studied systematically by Goldmann, 6 who described the vasoproliferative response of the organ in which a tumor develops as follows: " The normal blood vessels of the organs in which the tumor is developing are disturbed by chaotic growth, there is a dilatation and spiralling of the affected vessels, marked capillary budding and new vessel formation , particularly at the advancing border ". When Clark et al. 7,8 perfected the implantation of transparent chambers in a rabbit's ear, the morphologic characteristics of blood vessels could be studied in vivo, including the use of contrast media. In 1939 Ide et al. 9 were the first to suggest that tumors release specific factors that stimulate the growth of blood vessels, while in 1945 Algire and Chalkley 10 used a transparent chamber implanted in the skin of a cat to study the vaso-proliferative reaction secondary to a wound or implantation of normal or neoplastic tissues and showed that the vasoproliferative response induced by tumor tissues was more substantial and earlier than that induced by normal tissues or following a wound. They concluded that the growth of a tumor is closely connected to the development of an intrinsic vascular network. In his treatise Il Cancro, published by Ambrosiana in 1946, 11 Pietro Ron-doni, Professor of General Pathology at the University of Milan, and Director of the Milan Cancer Institute, stated with regard to the stroma of …