Artikel
Enhancement of antineoplastic immune response in malignant glioma by administration of inactivated staphylococci
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Veröffentlicht: | 20. Mai 2009 |
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Gliederung
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Objective: Several anecdotal reports deal with the complete regression of malignant brain tumors following postoperative infectious complications that in turn are potentially life-threatening. We wondered whether the antineoplastic properties of bacteria could be modified into a safe and effective therapy against malignant glioma.
Methods: 22 male Wistar rats were used for the implantation of 105 9L gliosarcoma cells (n=7), 105 inactivated staphylococci (IS) without tumor cells (n=4), or in the treatment groups 105 9L cells mixed with 105 and 104 IS, respectively (n=11). Tumor growth was monitored by serial magnetic resonance imaging (MRI) studies ± gadolineum-DTPA and quantified by computer-assisted volumetry of the lesions. During the observation period of 90 days, the animals were monitored daily for signs of discomfort. In case of infirmity by the tumor burden, the brains were removed after perfusion-fiaxtion and immunostained for CD45, CD68, CD4 and CD8a. Survival was determined by Kaplan-Meier-estimates. Cell culture experiments were performed to study a potential in vitro antitumorigenic effect of IS.
Results: Whereas IS exhibited no significant antineoplastic effect on 9L cell growth in vitro, there was a significant increase in average survival time in the treatment groups by 77%. Lesion volumes were smaller in the animals treated, and contrast enhancement was reduced in comparison to pure 9L gliosarcoma without adminsitration of IS. Histopathological specimen showed a distinct infiltration and dissociation of the tumors by abundant immunopcompetent cells in the animals treated. Interestingly, one of these animasl showed a considerable tumor growth in serial MRI and subsequently its spontaneous and complete regression. The exclusive application of the IS without tumor cells was well tolerated with no signs of discomfort or intracranial infection in any animal during the observation period.
Conclusions: IS administered intracerebrally harbor a substantial therapeutic potential in experimental glioma. They probably act by an unspecific stimulation of the local antineoplastic immune responses, thus overcoming the immunosuppressive properties of the tumor.