There is disclosed a diagnostic assay for determining the presence of a neoplasia or a tumor burden in a mammal comprising (a) measuring the amount of unsaturated free fatty acids (FFAs) linolenate and arachidonate in a body fluid, and (b) determining a ratio value comprising the sum of linolenate and the sum of arachidonate.

Cell Therapeutics, Inc.

Neoplasia diagnostic method

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 .alpha. (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.

CORNING INCORPORATED

Arch Development Corporation

Phospholipase A2 inhibitors as mediators of gene expression

Treatment of cells with ionizing radiation is associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, protein kinase C induction and tumor necrosis factor gene expression. The addition of inhibitors of lipoxygenase, such as ketoconazole, prior to irradiation reduces the expression of of tumor necrosis factor while maintaining the expression of other radiation inducible genes, such as Egr-1 and c-jun. In contrast, indomethacin, an inhibitor of cyclooxygenase, enhanced the expression of tumor necrosis factor as well as other radiation inducible genes. The results show that lipoxygenase inhibitors are useful in the treatment of radiation-induced mucositis, dermatitis, pneumonitis, proctitis, and esophagitis. which may be due to the production of cytokines such as TNF.

arachidonate/kansè

Neoplasia diagnostic method

Phospholipase A2 inhibitors as mediators of gene expression

Phospholipase A2 inhibitors as mediators of gene expression

Regulation of x-ray mediated gene expression

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