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Abstract
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, and available experimental and routine therapies result in limited survival benefits. A vulnerability of GBM cells to catastrophic vacuolization and cell death, a process termed methuosis, induced by Vacquinol-1 (VQ-1) has been described earlier. In the present study, we investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1. VQ-1 treatment affected growth of both RG2 and NS1 cells in vitro. Intracranially, significant reduction in RG2 tumor size was observed, although no effect was seen on overall survival. No survival advantage or effect on tumor size was seen in animals carrying the NS1 models compared to untreated controls. Furthermore, immunological staining of FOXP3, CD4 and CD8 showed no marked difference in immune cell infiltrate in tumor environment following treatment. Taken together, a survival advantage of VQ-1 treatment alone could not be demonstrated here, even though some effect upon tumor size was seen. Staining for immune cell markers did not indicate that VQ-1 either reduced or increased host anti-tumor immune response.
Highlights
Glioblastoma multiforme (GBM) or grade IV astrocytoma is the most common primary brain tumor with a prevalence of approximately 3 cases per 100 000 [1]
We investigate the efficacy of VQ-1 treatment in two syngeneic rat GBM models, RG2 and NS1
There were no apparent differences in size or pattern of tumor necrosis in the inspected material, as well as in intensity of staining in these areas. This data suggests VQ-1 lacks any strong immunological or immunomodulatory effect relevant to the current study. Both RG2 and NS1 are aggressive glioblastoma models used in fully immunocompetent rats, where animals quickly develop symptoms and the number of days available for treatment are reduced as compared to many other models
Summary
Glioblastoma multiforme (GBM) or grade IV astrocytoma is the most common primary brain tumor with a prevalence of approximately 3 cases per 100 000 [1]. It is one of the most aggressive among brain tumors. With the standard treatment consisting of surgical resection of the tumor if possible, radiotherapy and chemotherapy with concomitant and adjuvant Temozolomide (TMZ), the average survival time is approximately 15 months [2] Diverse factors such as age, Karnofsky performance score, tumor localization and mutational pattern of the O6alkylguanine DNA alkyltransferase (MGMT) promoter affect the prognosis. It would be attractive to find a more general function gained by GBM cells that is present in most tumor cells and patients
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