caa a22 4500 475806077 CHVBK 20180406123747.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1023/A:1026525121027 doi (NATIONALLICENCE)springer-10.1023/A:1026525121027 Soff Gerald Division of Hematology/Oncology and the Robert Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, Galter 4-102, The Blood Center, Chicago, IL, USA aut Angiostatin and Angiostatin-related Proteins [Elektronische Daten] [Gerald Soff] The study of angiogenesis, and the promise of angiogenesis inhibition as a means of cancer therapy, has dramatically accelerated in the last several years. The discovery and publication of angiostatin by O'Reilly and colleagues in Judah Folkman's lab in 1994 has greatly contributed to this progress. Angiostatin is a kringle-containing fragment of plasminogen, which is a potent inhibitor of angiogenesis in-vivo, and selectively inhibits endothelial cell proliferation and migration in-vitro. There have been a number of proposed proteolytic mechanisms by which plasminogen is cleaved to form angiostatin, and the resulting cleavage products contain different NH2 and COOH termini of the angiostatin. Therefore, it is possible that there are more than one angiostatin isoforms (or angiostatin-related proteins) which occur in one or more normal or pathophysiological situations. It is also possible that some of the proteolytic processes which can convert plasminogen to angiostatin-like proteins are simply laboratory artifacts. Angiostatin-related proteins exert potent endothelial cell inhibitory activity, including the induction of apoptosis, and inhibition of migration, and the intact kringle structures are believed to be necessary for the antiangiogenic activity. Efforts are now underway to translate the understanding of the biology of angiostatin to clinical practice, which includes phase 1 clinical trials with recombinant angiostatin K1-3 (kringles 1-3) as well as phase 1 trials of an Angiostatin Cocktail, which induces the direct in vivo conversion of plasminogen to angiostatin 4.5 (kringles 1-4, plus most of kringle 5). The translation of the basic science of angiostatin and angiostatin-related proteins to clinical trial promises to provide an important new tool in the treatment of cancer by inhibition of angiogenesis. Kluwer Academic Publishers, 2000 angiogenesis nationallicence angiostatin nationallicence cancer biology nationallicence cancer therapy nationallicence proteolysis nationallicence apoptosis nationallicence Cancer and Metastasis Reviews Kluwer Academic Publishers 19/1-2(2000-06-01), 97-107 0167-7659 19:1-2<97 2000 19 10555 https://doi.org/10.1023/A:1026525121027 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1026525121027 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Soff Gerald Division of Hematology/Oncology and the Robert Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, Galter 4-102, The Blood Center, Chicago, IL, USA aut NATIONALLICENCE 773 0- Cancer and Metastasis Reviews Kluwer Academic Publishers 19/1-2(2000-06-01), 97-107 0167-7659 19:1-2<97 2000 19 10555 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer