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Methods for inhibiting brain tumor growth

a brain tumor and growth inhibition technology, applied in the field of tumor growth inhibition, can solve the problems that no study has examined the effect of integrin antagonism on brain tumor invasion and angiogenesis

Inactive Publication Date: 2003-08-21
CHILDRENS HOSPITAL OF LOS ANGELES
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, to date, no study has examined the effect of integrin antagonism on brain tumor invasion and angiogenesis.

Method used

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  • Methods for inhibiting brain tumor growth
  • Methods for inhibiting brain tumor growth
  • Methods for inhibiting brain tumor growth

Examples

Experimental program
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Embodiment Construction

Materials and Methods

[0066] Materials: The active cyclic RGD pentapeptide EMD 121974, cyclo(Arg-Gly-Asp-D-Phe-[N-Me]-Val), and the inactive control peptide cRAD (EMD 135981) were provided by A. Jonczyk, Ph.D., Merck KgaA, Darmstadt, Germany. The monoclonal antibodies LM609 and P1F6 have been described (13). The brain tumor cell lines DAOY and U87MG were purchased from ATCC, Rockville, Md. Primary cultures of human brain capillary endothelial cells were provided by M. Stins, Ph.D., Childrens Hospital, Los Angeles (49). Human vitronectin was purchased from Promega, Madison, Wis.

[0067] FACS analysis: A FACScan cytometer (Becton-Dickinson, San Jose) was used. Conditions were as previously described (43). Primary antibodies were LM 609 and P1F6 at 1:100, and secondary Ab was FITC labeled goat anti-mouse IgG at 1:250. Apoptosis determination was as per the manufacturer's instruction (Clontech, Palo Alto, Calif., Apo Alert Annexin V-FITC Apoptosis kit).

[0068] Adhesion: Assay conditions wer...

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Abstract

The present invention describes methods for inhibition of tumor growth in the brain, using antagonists of integrins such as alphavbeta3 and 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] This application is a division of U.S. patent application Ser. No. 09 / 489,391 filed on Jan. 21, 2000, now U.S. Pat. No. 6,521,593, which application claims the benefit of U.S. Provisional Patent Application Serial No. 60 / 118,126 filed on Feb. 1, 1999.AREA OF THE ART[0002] The invention relates generally to inhibition of tumor growth and specifically to inhibition of brain tumor growth.DESCRIPTION OF THE PRIOR ART[0003] Throughout this application various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims.[0004] Brain tumors, like other solid tumors, require a perpetually increasing blood supply to maintain continuous growth beyond 1-2 mm.sup.3 (1,2). This is accomplished through ...

Claims

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Application Information

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IPC IPC(8): A61K38/00A61K45/00A61K38/39A61K39/395A61P35/00A61P43/00C07K14/47C07K16/18C07K16/28
CPCA61K38/39C07K16/2848C07K16/2839A61K2039/505A61P35/00A61P43/00A61K39/395
Inventor LAUG, WALTER E.
Owner CHILDRENS HOSPITAL OF LOS ANGELES
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