) There is a growing number of diseases characterized by the uncontrolled growth of new capillaries. These are now considered to be """"""""angiogenic diseases"""""""". These diseases include solid tumor growth and metastases, rheumatoid arthritis and many others. The availability of a drug which could prevent the spread of vascularization would have broad applicability as a therapy for these diseases. Cartilage has been studied as a potential source of an angiogenesis inhibitor(s) because of its avascularity and its tumor-resistance. The use of cartilage as a potential source of angiogenesis inhibitor is not limited to mammalian sources. For example, we have demonstrated the presence of angiogenesis inhibitors in shark cartilage, however this factor(s) has yet to be purified or identified. In this application, we propose to bring our experience in the purification and characterization of cartilage-derived angiogenesis inhibitors to the study of shark cartilage as a source of anti- angiogenic factors in the context of the following Specific Aims: (1) Purification of a shark cartilage-derived inhibitor(s) of angiogenesis. Using a purification strategy based on size exclusion, ion exchange, RP-HPLC, and mass spectrometry, we will purify anti-angiogenic factors from shark cartilage using an in vitro angiogenesis inhibitor assay. (2) Determination of the anti-angiogenic activity of the shark carti1age- derived inhibitor in vitro. We have developed and utilized a number of angiogenesis assays that will be used to study the samples obtained in the course of the purification protocol. These state-of-the-art assays are based on the use of capillary endothelial cells and the some of the processes that these cells undergo during successful neovascularization, such as growth factor-stimulated proliferation and migration. (3) Determination of the anti-angiogenic activity of purified shark inhibitor in vivo. After screening in the in vitro assays mentioned above, potential anti-angiogenic activity from shark cartilage will be assayed in vivo using the chick chonoallantoic assay and the rabbit corneal pocket assay.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT000650-02
Application #
6512037
Study Section
Special Emphasis Panel (ZCA1-SRRB-3 (J1))
Program Officer
Sorkin, Barbara C
Project Start
2001-09-25
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$355,500
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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Rickert, Dorothee; Franke, R-P; Fernandez, Cecilia A et al. (2007) Establishment and biochemical characterization of primary cells of the upper aerodigestive tract. Clin Hemorheol Microcirc 36:47-64
Harper, Jay; Moses, Marsha A (2006) Molecular regulation of tumor angiogenesis: mechanisms and therapeutic implications. EXS :223-68
Moses, Marsha A; Harper, Jay; Fernandez, Cecilia A (2004) A role for antiangiogenic therapy in breast cancer. Curr Oncol Rep 6:42-8
Zhang, Bo; Moses, Marsha A; Tsang, Paul C W (2003) Temporal and spatial expression of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2) in the bovine corpus luteum. Reprod Biol Endocrinol 1:85
Moses, Marsha A; Brem, Henry; Langer, Robert (2003) Advancing the field of drug delivery: taking aim at cancer. Cancer Cell 4:337-41