Inhibition of Glioma Growth by Lipoxygenase Inhibitors and PAF-Antagonists

Products of the arachidonic acid cascade have been implied to play a role in growth and in the clinical manifestations of malignant brain tumors. These indications are based on the findings of elevated levels of prostaglandins and leukotrienes in operative specimen (5, 2, 9) and on the observation of antitumoral effects of prostaglandin and leukotriene inhibitors in experimental models (11). Besides the potentially modulatory effects on growth, the common findings of peritumoral edema, in many cases the direct cause of death in brain tumor patients, might be related to release of arachidonic acid metabolites. Thus, intracranial infusion of leukotrienes do induce edema (3), and the amount of peritumoral edema was observed to relate to amounts of leukotrienes in the tumor tissue (2). Finally, the first hand treatment of brain tumors is the administration of corticosteroids. This is necessary for the control of the brain edema and could potentially mediate its effects by inhibiting phospholipase A2 and thereby inhibit the release of arachidonic acid.