Abstract

The long-term goal of the Principal Investigator is the exploration of three questions: (1) What is the role of angiogenesis in tumor growth? (2) How is tumor angiogenesis mediated? (3) How can tumor angiogenesis bbe inhibited? The principal investigator has recently discovered a new class of steroids which inhibit angiogenesis in the presence of heparin. These are named """"""""angiostatic"""""""" steroids. There is a sub-set of these steroids which have no other known function except for the inhibition of angiogenesis. Angiostatic steroids are normally present at low levels in the circulation, and they can now be made synthetically. The overall objective of this grant proposal is two-fold: (1) to delineate the mechanism of action of angiostatic steroids at the cellular and molecular level; and (2) to test these compounds in tumor-bearing mice, so that a Phase I clinical trial can be designed. An additional objective is to test our hypothesis that the high survival rate and low metastatic rate in patients with a thin cutaneous melanoma (e.g., less than 0.76 mm), is because these lesions are avascular.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA037395-06
Application #
3175266
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1983-01-01
Project End
1990-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Folkman, Judah (2006) Angiogenesis. Annu Rev Med 57:1-18
Satchi-Fainaro, Ronit; Mamluk, Roni; Wang, Ling et al. (2005) Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin. Cancer Cell 7:251-61
Sternlicht, M D; Werb, Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463-516
O'Reilly, M S; Brem, H; Folkman, J (1995) Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM-1470. J Pediatr Surg 30:325-9;discussion 329-30
Nguyen, M; Watanabe, H; Budson, A E et al. (1994) Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst 86:356-61
Li, V W; Folkerth, R D; Watanabe, H et al. (1994) Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumours. Lancet 344:82-6
Nguyen, M; Watanabe, H; Budson, A E et al. (1993) Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients. J Natl Cancer Inst 85:241-2
Brem, H; Gresser, I; Grosfeld, J et al. (1993) The combination of antiangiogenic agents to inhibit primary tumor growth and metastasis. J Pediatr Surg 28:1253-7
Folkman, J; Szabo, S; Stovroff, M et al. (1991) Duodenal ulcer. Discovery of a new mechanism and development of angiogenic therapy that accelerates healing. Ann Surg 214:414-25;discussion 426-7
Li, W W; Grayson, G; Folkman, J et al. (1991) Sustained-release endotoxin. A model for inducing corneal neovascularization. Invest Ophthalmol Vis Sci 32:2906-11

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