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A very productive meeting of the LICR Angiogenesis Program was held at the New York Office on the 18th and 19th of September. The Angiogenesis Program was developed (refer NewsLink June 30, 2003) to facilitate a more comprehensive and interdisciplinary study of the biological processes of angiogenesis and lymphangiogenesis, and represents a concerted effort to leverage and maximize resources to empower both laboratory and development phases towards novel therapies. The Program has a very strong focus on the areas of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) signaling, which are central to angiogenesis and lymphangiogenesis. Many of the VEGF and PDGF ligands and receptors were originally identified by LICR Scientists and Affiliates, and several strategies are being used to selectively and specifically dissect the precise signaling of the different receptor-ligand combinations. At the meeting, Dr. Ulf Eriksson (Stockholm Branch) discussed his team’s research on the roles of the ligands VEGF-B and PDGF-C in angiogenesis. Dr. Kari Alitalo (Affiliate, Helsinki) outlined his team's use of VEGF soluble domains, knockout mice, and small interfering RNA (siRNA) in the zebra-fish model to block VEGF-C signaling through vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3. From the Melbourne Branch, Drs. Steven Stacker and Mark Achen presented data from their research into lymphangiogenesis and vascular development, including recent findings on the Ryk receptor, isolated as part of a screen to identify all receptors involved in vascular development. Angiogenic factors secreted by tumor cells bind to VEGFR and PDGFR receptors on endothelial cells, thus the characterization of endothelial cells is an important aspect of the Angiogenesis Program. Dr. Pipsa Saharinen, a member of Dr. Alitalo’s team, presented data from ongoing genetic analyses of lymphatic and vascular endothelial cells. Dr. Anne Ridley (London University College Branch) extended her seminal studies of Rho activity in ECs, but presented data on effects under flow conditions. These results may explain why the effects of VEGF on cultured endothelial cells are so disparate from those expected based on in vivo data. Dr. Seppo Ylä-Herttuala (Affiliate, Kuopio) presented his work in which adenovirus constructs of VEGF isoforms are delivered direct to the heart using an electromagnetically guided injection catheter. The use of pro-angiogenic factors with this technique is a potential, minimally-invasive therapy for ischemic cardiomyopathy. Additionally, Dr. Arne Östmann (Uppsala Branch) presented recent results from his findings that PDGF receptor (PDGFR) inhibitors lower interstitial tumor pressure and concomitantly increase the activity of chemotherapies. Dr. Östmann’s research has led to the initiation of clinical trials, conducted in Uppsala, that test PDGFR inhibitors in this context. There are many opportunities for translating the Angiogenesis Program’s foundation science into the clinical arena. Drs. Pauline Stasiak and Deborah Carter from the LICR Office of Intellectual Property (London Office) presented the intellectual property portfolio related to angiogenesis, which covers various ligands and receptors. Finally, new tumor and VEGFR/PDGFR model systems are also under development, and these will allow preclinical evaluation of the Institute’s reagents, as well as those of industrial collaborators, prior to their inclusion in the LICR’s Clinical Trials Program. |
Ludwig Institute for Cancer Research ©2003