Method for inhibiting brain tumor growth

Abstract

The present invention describes methods for inhibition of tumor growth in the brain, using antagonists of integrins such as alphavbeta3 or alphavbeta5. Antagonists of the present invention can inhibit angiogenesis in brain tumor tissue. They can also inhibit vitronectin and tenascin-mediated cell adhesion and migration in brain tumor cells. They can further induce direct brain tumor cell death.

Description

[0001] related application

[0002] This application claims priority to Provisional Application Serial No. 60 / 118,126, filed February 1, 1999, which is incorporated herein by reference. Background of the invention

[0003] Field

[0004] The present invention relates generally to the inhibition of tumor growth, particularly brain tumors.

[0005] Description of prior art

[0006] Individual references throughout this application are shown in parentheses. All of the above publications are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. A full bibliography of all of the above references is found at the end of the application, before the claims.

[0007] Like other solid tumors, brain tumors require a growing blood supply to maintain their continued growth beyond 1-2mm 3 (1, 2). This is achieved through angiogenesis. Angiogenesis is a process in response to endothelial growth fact...

Examples

example

[0070] Materials and methods

[0071] Materials: Active cyclic RGD pentapeptide EMD 121974, cyclic (Arg-Gly-Asp-D-Phe-[N-Me]-Val) and inactive Control peptide cRAD (EMD 135981). Monoclonal antibodies LM609 and P1F6 have been described (13). Brain tumor cell lines DAOY and U87MG were purchased from ATCC Dr. Rockville. The basic culture medium of human brain capillary endothelial cells was provided by Dr. M. Stins from Children's Hospital of Los Angeles, USA (49). Human vitronectin was purchased from Promega, Madison, Wisconsin, USA.

[0072] FACS analysis: FACScan cell counter (Becton-Dickinson, SanJose) was used. Conditions were as previously described (43). The primary antibody was LM609 and P1F6 at a ratio of 1:100, and the secondary antibody was FITC-labeled goat anti-mouse IgG at a ratio of 1:250. Apoptosis was determined according to the manufacturer's instructions (Apo Alert Annexin V-FITC Apoptosis Kit, Clontech, Palo Alto, CA, USA).

[0073...

[0001] related application

[0002] This application claims priority to Provisional Application Serial No. 60 / 118,126, filed February 1, 1999, which is incorporated herein by reference. Background of the invention

[0003] Field

[0004] The present invention relates generally to the inhibition of tumor growth, particularly brain tumors.

[0005] Description of prior art

[0006] Individual references throughout this application are shown in parentheses. All of the above publications are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. A full bibliography of all of the above references is found at the end of the application, before the claims.

[0007] Like other solid tumors, brain tumors require a growing blood supply to maintain their continued growth beyond 1-2mm 3 (1, 2). This is achieved through angiogenesis. Angiogenesis is a process in response to endothelial growth fact...

Examples

example

[0070] Materials and methods

[0071] Materials: Active cyclic RGD pentapeptide EMD 121974, cyclic (Arg-Gly-Asp-D-Phe-[N-Me]-Val) and inactive Control peptide cRAD (EMD 135981). Monoclonal antibodies LM609 and P1F6 have been described (13). Brain tumor cell lines DAOY and U87MG were purchased from ATCC Dr. Rockville. The basic culture medium of human brain capillary endothelial cells was provided by Dr. M. Stins from Children's Hospital of Los Angeles, USA (49). Human vitronectin was purchased from Promega, Madison, Wisconsin, USA.

[0072] FACS analysis: FACScan cell counter (Becton-Dickinson, SanJose) was used. Conditions were as previously described (43). The primary antibody was LM609 and P1F6 at a ratio of 1:100, and the secondary antibody was FITC-labeled goat anti-mouse IgG at a ratio of 1:250. Apoptosis was determined according to the manufacturer's instructions (Apo Alert Annexin V-FITC Apoptosis Kit, Clontech, Palo Alto, CA, USA).

[0073...

Images