Interstitial quinacrine for elimination of abnormal tissue; therapy of experimental glioma

Background. When quinacrine is injected interstitially, an intense migratio n of leukocytes and accumulation of various lymphokines is obtained locally , and the reaction is followed by cicatricial fibrosis. This property has b een used in humans to induce tubal fibrosis in women and pleurodesis in pat ients with I pleural effusion. Methods. In a controlled study, a single dose of 150 mg of quinacrine was i njected interstitially into a CG glioma implanted in the subcutaneous tissu e of Wistar rats. Changes in size, histologic variations, and microscopic c haracteristics of leukocyte subpopulations infiltrating the tumor were stud ied by immunohistochemistry. Tumor necrosis factor and interleukin-1 beta w ere measured at different times in tumor homogenates. Results. The day after the injection of quinacrine, infiltration of leukocy tes and macrophages was observed, accompanied by an accumulation of proinfl ammatory endogenous cytokines. Tumoral necrosis soon ensued; complete tumor disappearance iuds obtained in 72% of the animals. Cicatrization proceeded without injury of perilesional structures. In all controls injected with t he vehicle, a large tumor developed (P < .0001). Conclusions. Quinacrine, when administered interstitially in a single dose, elicits an intense local recruitment and proliferation of activated immune cells that, at the dose used in this study, induces tissue necrosis within a radius of 1 cm around the site of quinacrine injection, leaving the surr ounding tissue unharmed.