Antifibrinolytic therapy of experimentally grown malignant brain tumors

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✓ This study was designed to evaluate the effect of an inhibitor of plasminogen activation on the growth of a human glioblastoma line grown in nude mice up to the seventh passage. The tumors produced plasminogen activators and showed histological characteristics similar to those of the original tumor. Three groups of mice were studied. Group A received 5% epsilon aminocaproic acid (EACA); Group B received 2.5% EACA; and Group C served as a control. There was no statistical difference among the three groups with regard to: 1) age at time of tumor transplantation; 2) the interval between implant and treatment; or 3) tumor volume at time of treatment. Blood measurements of EACA, performed in a limited number of animals, have shown that the drug at 5% concentration had reached toxic levels. Statistically significant differences between the three groups were noted in the following categories: 1) rate of tumor growth; 2) tumor volume at time of death, where Group A had smaller tumors than Group C; and 3) mean survival times of Groups A and B as compared to Group C.

A statistically significant negative correlation was found between the rate of tumor growth and the length of survival of animals in Group C, while no correlation could be found for either Group A or B, indicating that the antifibrinolytic therapy modified this important biological variable. This study supports the hypothesis that the fibrinolytic system plays a role in the growth and development of malignant gliomas and that interference with the fibrinolytic system may retard the growth of these tumors grown in nude mice.

Article Information

Address reprint requests to: Raymond Sawaya, M.D., Department of Neurosurgery, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267.

© AANS, except where prohibited by US copyright law.

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Figures

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    Electrophoretic gel of the human tumor after transplantation in nude mice demonstrating several lytic bands (white bands) corresponding to the various molecular-weight plasminogen activators contained in this tumor.

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    Representative animals from Group A (left) and Group C (right) photographed at 12 weeks postimplantation and 6 weeks after the start of therapy.

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    Survival time curves for each of the three therapy groups (left), and for Groups A and B combined (right) in which the significance of difference (shaded area) is p < 0.05.

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    Photomicrograph of a section of the human tumor grown in nude mice demonstrating small anaplastic cells and palisading necrosis (lower right). H & E, × 94.

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