Heparin compostions and selectin inhibition

A technology of selectin and composition, applied in the field of molecular biology, can solve problems such as ineffective survival

Inactive Publication Date: 2009-11-18
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, human experiments using vitamin K antagonists as an alternati

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  • Heparin compostions and selectin inhibition
  • Heparin compostions and selectin inhibition
  • Heparin compostions and selectin inhibition

Examples

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example 1

[0108] Materials: The following materials were obtained from UCSD Medical Center Pharmacy: Unfractionated Sodium Heparin (UFH) from American Pharmaceutical Partners (20,000 U / ml; lot numbers 302523, 333246); Innohep from Pharmion, USA (Tinzaparin, TINZ ) (licensed by LEO Pharmaceutical Products, Denmark, 20,000 IU / ml; lot numbers E9867A and G3371A); Fragamine (dalteparin, DALT) from Pharmacia (5000IU / 0.2ml; lot numbers 94250A51, 94683A02 and 94802A01); Noparin (enoxaparin, ENOX) (30 mg / 0.3 ml; lot numbers 30324, 9367 and 9369); and Arixtra (fondaparinux, FOND) (2.5 mg / 0.5 ml; lot numbers 0010000003 and 0170000010) from Sanofi-Synthelabo. All other chemicals were purchased from Sigma Chemical Company, St. Louis unless otherwise noted.

[0109] Cell lines: LS180 human colon adenocarcinoma cells and MC38GFP cells (a mouse colon cancer cell line stably transfected with EGFP) were cultured. Mouse melanoma B16F1 cells were cultured in DMEM with 10% FCS. All media and supplements w...

example 2

[0135] Cell line: MC38GFP cells are mouse colon carcinoma cells stably transfected with enhanced green fluorescent protein (GFP), which are cultured and prepared for injection.

[0136] Mice: C57BL / 6J (WT) mice were from Jackson Laboratories (Bar Harbor, Maine) or from housekeeping of these mice. When all purchased mice arrive, they are acclimatized in the vivarium for a minimum of one week before starting the experiment. Mice lacking both P- and L-selectin (PL- / -) and homologous to the C57BL / 6J background are known in the art. All mice were fed standard chow and water ad libitum and maintained on a 12 hour light / dark cycle. Experiments were performed in an AAALAC licensed vivarium. Consistent with IACUC recommendations, "survival" studies did not use death as an endpoint, but instead used euthanasia when mice reached an apparently moribund state (basically immobile, arched, breathing rapidly, and not seeking food or water).

[0137] Experimental metastasis assay of carcino...

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Abstract

The disclosure provides in vitro and in vivo methods for identifying Heparins and Heparinoids that modulate the activity of selectins . The disclosure also provides Heparins and Heparinoids that modulate the activity of selectins . The identification and isolation of these heparin formulations has the potential to mediate a wide variety of pathologies mediated by P- and/or L-selectin, including hematogenous metastasis, diseases associated with inflammation (e.g., asthma, arthritis, allergic dermatitis), ischemia-reperfusion injury, or other pathologies such as sickle cell anemia. Selectin inhibition can be achieved at plasma concentrations lower than those that cause excessive anticoagulation or unwanted bleeding in a human subject.

Description

[0001] Related Application Cross Reference [0002] This application claims priority over US Provisional Application Serial No. 60 / 701,893, filed July 22, 2005, the disclosure of which is incorporated herein by reference. [0003] Statement Regarding Federally Funded Research [0004] This invention was made in part by grant number R01CA38701 awarded by the National Institutes of Health. The government may have certain rights in this invention. technical field [0005] The present invention relates generally to molecular biology, and more particularly to identifying and / or isolating compounds that block L-selectin and / or P-selectin binding activity and attenuate selectin-mediated transfer or other selectin-mediated A method of inducing a heparin variant for a disease or disorder. Background technique [0006] P- and L-selectins are C-type lectins that recognize sialylated, fucosylated, sulfated ligands. P-selectin is stored in resting platelets and endothelial cells a...

Claims

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Application Information

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IPC IPC(8): A01N43/04A61K31/727
CPCG01N2500/10G01N33/566G01N2500/02G01N2800/224A61K31/727G01N2400/40G01N33/66G01N2333/70564G01N33/86A61P35/00A61P35/04A61P43/00A61K2300/00
Inventor 阿吉特·瓦尔基珍妮弗·L·史蒂文森
Owner RGT UNIV OF CALIFORNIA
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