Oncotarget

Research Papers:

Evaluating vacquinol-1 in rats carrying glioblastoma models RG2 and NS1

Jonatan Ahlstedt _, Karolina Förnvik, Shaian Zolfaghari, Dongoh Kwak, Lars G.J. Hammarström, Patrik Ernfors, Leif G. Salford, Henrietta Nittby Redebrandt

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Oncotarget. 2018; 9:8391-8399. https://doi.org/10.18632/oncotarget.23842

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Abstract

Jonatan Ahlstedt1, Karolina Förnvik1, Shaian Zolfaghari1, Dongoh Kwak2, Lars G.J. Hammarström3, Patrik Ernfors2, Leif G. Salford1 and Henrietta Nittby Redebrandt1

1Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences Lund, Lund University, Lund, Sweden, Lund University, Sweden

2Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm, Sweden

3Chemical Biology Consortium Sweden, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Division of Molecular Translational Medicine and Chemical Biology, Karolinska Institutet, Stockholm, Sweden

Correspondence to:

Jonatan Ahlstedt, email: jonatan.ahlstedt@med.lu.se

Keywords: glioblastoma; vacquinol-1; RG2; NS1; rat

Received: July 04, 2017     Accepted: October 28, 2017     Published: January 03, 2018

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.


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