This program project application focuses on tumor angiogenesis. Tumor growth depends critically on angiogenesis, and angiogenesis inhibitors have been shown to reduce the size and even eradicate tumors in mice. The program is a collaborative effort among four investigators at the Burnham Institute. It is based on recent discoveries. It is based on recent discoveries about vascular specialization and tumor targeting made by these investigators. The group has developed a unique in vivo screening method for peptides displayed on phage to identify peptides capable of homing to tumor vasculature. Peptides obtained in this manner will be used as probes to identify new markers in tumor blood vessels. The expression of these tumor vascular markers during progression of malignancy will be studied. In a complementary approach, angiogenic markers identified by the program participants will be used to isolate binding peptides in vitro. Promising peptides, and improved versions of these peptides to be designed within the program, will be used to probe the functional roles of their vascular target molecules in angiogenesis. The peptides will also be evaluated for their ability to serve as vehicles in the targeting of drugs to tumors. A peptide chemistry core will provide the necessary peptides to the program participants, and an angiogenesis core will provide the assays necessary for the evaluation of functional aspects of angiogenesis. New insights to the biology of angiogenesis and new, improved ways of targeting tumor vasculature in cancer treatments are likely to result form this work.
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| Mitra, Sayantan; Duggineni, Srinivas; Koolpe, Mitchell et al. (2010) Structure-activity relationship analysis of peptides targeting the EphA2 receptor. Biochemistry 49:6687-95 |
| Järvinen, Tero A H; Ruoslahti, Erkki (2010) Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice. Proc Natl Acad Sci U S A 107:21671-6 |
| Richardson, Robyn D; Ma, Gil; Oyola, Yatsandra et al. (2008) Synthesis of novel beta-lactone inhibitors of fatty acid synthase. J Med Chem 51:5285-96 |
| Jarvinen, Tero A H; Ruoslahti, Erkki (2007) Molecular changes in the vasculature of injured tissues. Am J Pathol 171:702-11 |
| Zhang, Lianglin; Giraudo, Enrico; Hoffman, Jason A et al. (2006) Lymphatic zip codes in premalignant lesions and tumors. Cancer Res 66:5696-706 |
| Browne, Cecille D; Hindmarsh, Elizabeth J; Smith, Jeffrey W (2006) Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitor. FASEB J 20:2027-35 |
| Zhang, Lianglin; Hoffman, Jason A; Ruoslahti, Erkki (2005) Molecular profiling of heart endothelial cells. Circulation 112:1601-11 |
| Komatsu, Masanobu; Ruoslahti, Erkki (2005) R-Ras is a global regulator of vascular regeneration that suppresses intimal hyperplasia and tumor angiogenesis. Nat Med 11:1346-50 |
| Ruoslahti, E; Duza, T; Zhang, L (2005) Vascular homing peptides with cell-penetrating properties. Curr Pharm Des 11:3655-60 |
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