Milestones in tumor vascularization and its therapeutic targeting.

Research into the mechanisms and manifestations of solid tumor vascularization was launched more than 50 years ago with the proposition and experimental demonstrations that angiogenesis is instrumental for tumor growth and was, therefore, a promising therapeutic target. The biological knowledge and therapeutic insights forthcoming have been remarkable, punctuated by new concepts, many of which were not foreseen in the early decades. This article presents a perspective on tumor vascularization and its therapeutic targeting but does not portray a historical timeline. Rather, we highlight eight conceptual milestones, integrating initial discoveries and recent progress and posing open questions for the future.

Looking for the Word "Angiogenesis" in the History of Health Sciences: From Ancient Times to the First Decades of the Twentieth Century.

This review deals with the origin of the term "angiogenesis", with an attention to John Hunter who is credited with this neologism. A part of the literature refers to a Hunter's work dating 1787, and the other part claims the first use of the term "angiogenesis" in the Hunter's masterpiece published in 1794. Since we were unable to find the term "angiogenesis" in Hunter's works, this review attempts to bring a new contribution to the historical research of this important concept, moving from ancient times to the first decades of the twentieth century, when "angiogenesis" begun to appear on titles of scientific articles. The development of the knowledge on the cardiocirculatory system and the principal steps of this fascinating subject were examined, with particular regard to microvascular bed and vessel sprouting, and to the intriguing observations on blood vessel neoformation that have been also made in the premicroscopic era. In Hunter's works, the concept of angiogenesis indeed emerges, but not the term "angiogenesis". The scientific language occurring during Hunter's time was still old-fashioned, and the term "angiogenesis" was not one of those he used, rather a much later neologism that sounds too modern to appear in that context. Would the first appearance of the term "angiogenesis" occur in late nineteenth century in studies dealing with embryogenesis and organ vascularization? The present study aims to explore the scientific literature and to open a debate to better define this matter.

25 Years On: A Retrospective on Migration Inhibitory Factor in Tumor Angiogenesis.

Twenty-five years ago marked the publication of the first report describing a functional contribution by the cytokine, macrophage migration inhibitory factor (MIF), to tumor-associated angiogenesis and growth. Since first appearing, this report has been cited 304 times (as of this writing), underscoring not only the importance of this landmark study but also the importance of MIF in tumor neovascularization. Perhaps more importantly, this first link between MIF and stromal cell-dependent tumor angiogenesis presaged the subsequent identification of MIF in mediating protumorigenic contributions to several solid tumor stromal cell types, including monocytes, macrophages, T lymphocytes, NK cells, fibroblasts, endothelial progenitors and mesenchymal stem cells. This retrospective review will broadly evaluate both past and present literature stemming from this initial publication, with an emphasis on cellular sources, cellular effectors, signal transduction mechanisms and the clinical importance of MIF-dependent tumor vascularization.

The seminal work of Werner Risau in the study of the development of the vascular system.

Werner Risaus work had a decisive impact on defining the overall nature of neovascularization processes during development and had the capability to integrate different directions in the field of endothelial cell biology research. In particular, he had a special interest in understanding the development, differentiation and maintenance of the blood-brain barrier. Risau very successfully propagated the concept that the same factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), which are essential for the formation of blood vessels during embryonic development, also influence pathological angiogenesis during tumor growth. This review is dedicated to a retrospective analysis of the most important contributions of Risaus work in the field of angiogenesis during embryonic development and in post-natal life, in both physiological and pathological conditions.

The scientific contributions of M. Judah Folkman to cancer research.

Dr Judah Folkman was frequently described as a highly compassionate physician who served his patients not only by performing surgery and offering them comfort and reassurance, but also by working tirelessly in the laboratory to find new approaches to the treatment of disease. His dedication to understanding the role of angiogenesis, the formation of new blood vessels, in human disease has given rise to new treatments for several diseases, including inflammatory diseases, vision-threatening diseases of the eye and, as will be emphasized in this Perspective, cancer.