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Use of vascular endothelial growth factor receptor 1+ cells in treating and monitoring cancer and in screening for chemotherapeutics

A growth factor receptor, vascular endothelium technology, applied in the application of vascular endothelial growth factor receptor 1+ cells in the treatment and monitoring of cancer and in the screening of chemotherapy drugs, can solve the problem of unclear precise role of tumor metastasis and other issues

Inactive Publication Date: 2008-01-16
CORNELL RES FOUNDATION INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These and other tumor-associated cells have been found to enhance primary tumor growth and promote tumor spread, but their precise role in tumor metastasis is currently unknown (Pollard, "Tumor-educated Macrophages Promote TumorProgression and Metastasis cells promote tumor development and metastasis), "Nat.Rev.Cancer.4:71-78 (2004) and Hiratsuka et al., "MMP9 Induction by Vascular Endothelial Growth Factor Receptor-1 is Involved in Lung-specific Metastasis (vascular endothelial growth factor receptor-1 MMP9 induction of body-1, involved in lung-specific tumor metastasis), "Cancer Cell.2: 289-300(2002))

Method used

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  • Use of vascular endothelial growth factor receptor 1+ cells in treating and monitoring cancer and in screening for chemotherapeutics
  • Use of vascular endothelial growth factor receptor 1+ cells in treating and monitoring cancer and in screening for chemotherapeutics
  • Use of vascular endothelial growth factor receptor 1+ cells in treating and monitoring cancer and in screening for chemotherapeutics

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preparation example Construction

[0054] Methods for preparing polyclonal antibodies are also well known. Usually, vascular endothelial growth factor receptor 1 can be + Subcutaneous administration of New Zealand white rabbits (which had previously been bled to obtain preimmune serum) produced such antibodies. Antigen was injected at 6 different sites with a total volume of 100 μl per site. Each injected material contained pluronic polyol, a synthetic surfactant adjuvant, or ground acrylamide gel containing protein or polypeptide after SDS polyacrylamide gel electrophoresis. Rabbits were bled 2 weeks after the first injection, and then boosted 3 times with the same antigen regularly every 6 weeks. Serum samples were collected 10 days after each booster immunization. Polyclonal antibodies are then recovered from the serum by affinity chromatography using the corresponding antigen-capture antibodies. Finally, rabbits were anesthetized with 150 mg / Kg IV pentobarbital. The above and other methods for producin...

Embodiment 1

[0087] Wild-type C57B1 / 6 mice were lethally irradiated (950 rads) and then transplanted with 1×10 6 β-galactosidase + or GFP + BM cells (Rosa-26 mice) (Lyden et al., "Impaired Recruitment of Bone-marrow-derived Endothelial and Hematopoietic Precursor Cells Blocks Tumor Angiogenesis and Growth" and Growth), "Nat. Med. 7: 1194-1201 (2001), which is hereby incorporated by reference in its entirety). After 4 weeks, mice were intradermally injected with 2×10 6 LLC (ATCC) or B-16 cells (ATCC).

Embodiment 2

[0088] Tissues and femurs were fixed in 4% paraformaldehyde (PFA) for 4 hours. Samples were stained in X-gal solution at 37°C for 36 hours, see Tam et al., "The Allocation of Epiblast Cells to the Embryonic Heart and other Mesodermal Lineages: The Role of Ingression and Tissue Movement during Gastrulation" Other mesoderm lineages: role of inward migration and tissue motility during gastrulation)," Development. 124: 1631-1642 (1999), which is hereby incorporated by reference in its entirety. X-gal stained tumors and BM were embedded as described in: Lyden et al., "Impaired Recruitment of Bone-marrow-derived Endothelial and Hematopoietic Precursor Cells Blocks TumorAngiogenesis and Growth can block tumor angiogenesis and growth)," Nat. Med. 7: 1194-1201 (2001), which is hereby incorporated by reference in its entirety.

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Abstract

The present invention is directed to a method of inhibiting tumor formation in a cancer patient at a site remote from sites of prior tumor formation and to a method of preventing metastases. These methods involve administering to the cancer patient an inhibitor of vascular endothelial growth factor receptor 1+ bone marrow-derived cells under conditions effective either to inhibit tumor formation in the cancer patient at a site remote from sites of prior tumor formation or to prevent metastases. Candidate compounds useful for such purposes can be screened depending on whether they bind to vascular endothelial growth factor receptor 1+ bone marrow-derived cells and comparing the level of vascular endothelial growth factor receptor 1+ bone marrow-derived cells to prior levels.

Description

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial Nos. 60 / 629,662, filed November 19, 2004, and 60 / 723,770, filed October 5, 2005, the entire disclosures of which are incorporated herein by reference in their entirety middle. [0002] The subject of this application was made with United States government support (grant number 1 R01CA098234-01 from the National Institutes of Health). The US Government may have certain rights in this invention. field of invention [0003] The present invention relates to vascular endothelial growth factor receptor 1 + Use of cells in treating and monitoring cancer and in screening chemotherapy drugs. Background of the invention [0004] Cancer is the second leading cause of death in the United States after heart attacks. Significant progress has been made in the development of new treatments for this devastating disease. Much of these advances are due to a greater understanding of cell proliferation i...

Claims

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Application Information

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IPC IPC(8): A61K39/395A01N1/02G01N33/53
Inventor D·利登R·N·卡普兰R·D·里巴S·拉菲
Owner CORNELL RES FOUNDATION INC
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