Abstract

This research proposal seeks information about the mechanism(s) for fibrin deposition in cancer. Such information is critical for the design of treatment regimens aimed at this host defense mechanism. The proposal focuses on developing an understanding of the relative importance of tumor-associated procoagulants (PCA) and macrophage tissue factor (MO-TF) in this process. There are four specific goals: 1. Identification of antigens related to tissue factor (TF) (TF:RAg), other tumor PCA, and fibrin in human tumors in situ. 2. Identification and molecular characterization of TF (and other PCA) in isolated human tumor cells and tumor-associated MO. 3. Production and characterization of monoclonal antibodies to rabbit TF. 4. Determination of the in vivo effects of TF-specific, monoclonal antibodies on the expression of MO-TF, the deposition of fibrin and tumor growth in a rabbit tumor model. (A)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA022202-09
Application #
3165768
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Tallman, M S; Lefebvre, P; Baine, R M et al. (2004) Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia. J Thromb Haemost 2:1341-50
Rickles, F R; Falanga, A (2001) Molecular basis for the relationship between thrombosis and cancer. Thromb Res 102:V215-24
Hayzer, D J; Shoji, M; Hanson, S R (2000) cDNAs encoding the baboon thrombin receptor indicate a primate transcription start site upstream of putative sites reported for the human gene. Thromb Res 98:195-201
Abe, K; Shoji, M; Chen, J et al. (1999) Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci U S A 96:8663-8
Shoji, M; Hancock, W W; Abe, K et al. (1998) Activation of coagulation and angiogenesis in cancer: immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer. Am J Pathol 152:399-411
Contrino, J; Goralnick, S; Qi, J et al. (1997) Fibrin induction of tissue factor expression in human vascular endothelial cells. Circulation 96:605-13
Contrino, J; Hair, G; Kreutzer, D L et al. (1996) In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nat Med 2:209-15
Hair, G A; Padula, S; Zeff, R et al. (1996) Tissue factor expression in human leukemic cells. Leuk Res 20:1-11
Bilgrami, S; Greenberg, B R; Weinstein, R E et al. (1995) Recurrent venous thrombosis as the presenting manifestation of acute lymphocytic leukemia: leukemic cell procoagulant activity is not responsible for the hypercoagulable state. Med Pediatr Oncol 24:40-5
Contrino, J; Hair, G A; Schmeizl, M A et al. (1994) In situ characterization of antigenic and functional tissue factor expression in human tumors utilizing monoclonal antibodies and recombinant factor VIIa as probes. Am J Pathol 145:1315-22

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