Phospholipase A2 inhibitors as mediators of gene expression
AssigneeArch Development Corporation
InventorsDennis E. Hallahan, Ralph R. Weichselbaum, Donald W. Kufe
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Abstract
A signaling pathway is identified that involves the activation of phospholipase A2 and protein kinase C in human cells, which in turn confers x-ray induction of the tumor necrosis factor α (TNF) gene. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, as well as the subsequent activation of protein kinase C and TNF gene expression. These phospholipase A2 inhibitors may be used to ameliorate the adverse-effects of radiotherapy associated with TNF production.
Claims8
A method of inhibiting tumor necrosis factor production in a cell exposed to ionizing radiation comprising contacting the cell with an amount of a phospholipase A2 inhibitor, prior to said irradiation, effective to inhibit tumor necrosis factor production in said cell.
A method of inhibiting tumor necrosis factor production in a patient in need of ionizing radiotherapy comprising administering to the patient a dose of a phospholipase A2 inhibitor, prior to said ionizing radiotherapy, effective to inhibit tumor necrosis factor production in said patient.
A method of reducing acute ionizing radiation a sequelae in a patient comprising administering to the patient, prior to said radiation dose of a phospholipase A2 inhibitor effective to reduce said sequelae in said patient.
Dependencies are inferred from the claim text.