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Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models

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An Erratum to this article was published on 14 March 2009

Abstract

Malignant gliomas have a dismal prognosis despite multi-modality treatments like neurosurgical resection, radiation therapy and chemotherapy. Evidence has indicated that gastrin-releasing peptide (GRP) and its receptor (GRPR) play a role in the development of a variety of cancers including gliomas. In the present study, we investigated the effects of RC-3095, a selective GRPR antagonist, alone or in combination with temozolomide (TMZ), a DNA alkylating agent, in in vitro and in vivo experimental rat C6 glioma models. Cellular proliferation was significantly reduced by all treatments with the combined administration of TMZ and RC-3095 being the most effective treatment. In in vivo experiments, the control group displayed the largest tumors (52 ± 15.5 mm3), whereas RC-3095 reduced the tumor size, with the most significant effect at the dose of 0.3 mg/kg (21 ± 9.7 mm3). The combined therapy produced further reduction in tumor size (10 ± 7.5 mm3). Our results show that the combination of RC-3095 with TMZ produced an important reduction in in vitro and in vivo glioma growth therefore making RC-3095 a candidate drug to potentiate the effects of the DNA alkylating agent TMZ in the treatment of glioma.

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Acknowledgements

This research was supported by CNPq grants 400839/2005-9; the South American Office for Anticancer Drug Development (SOAD, Porto Alegre, Brazil); and the Childrens Cancer Institute (ICI-RS, Porto Alegre, Brazil). Authors thank Caroline B. Farias, Débora G. Flores and Gustavo K. Reolon for excellent technical assistance.

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Authors and Affiliations

  1. Cancer Research Laboratory, Academic Hospital Research Center, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-003, Porto Alegre, RS, Brazil

    Marianne Schrader de Oliveira, Giovana Cechim, Cláudio Galvão de Castro Jr, Algemir Lunardi Brunetto, Gilberto Schwarstmann & Rafael Roesler

  2. Cellular and Molecular Neuropharmacology Research Group, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90046-900, Porto Alegre, RS, Brazil

    Marianne Schrader de Oliveira & Rafael Roesler

  3. Laboratory of Cellular Signaling and Plasticity, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, 901501-970, Porto Alegre, RS, Brazil

    Giovana Cechim & Guido Lenz

  4. Laboratory of Enzimology, Department of Biochemistry, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Elisandra Braganhol & Ana Maria Oliveira Battastini

  5. Immunogenetics Research group, Department of Genetics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, 901501-970, Porto Alegre, RS, Brazil

    Daniel Garcia Santos

  6. Faculty of Medicine, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Luise Meurer & Gilberto Schwarstmann

  7. Children’s Cancer Institute and Pediatric Oncology Unit, Academic Hospital, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Cláudio Galvão de Castro Jr & Algemir Lunardi Brunetto

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  1. Marianne Schrader de Oliveira
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Correspondence to Rafael Roesler.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s11060-009-9851-2

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de Oliveira, M.S., Cechim, G., Braganhol, E. et al. Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models. J Neurooncol 93, 191–201 (2009). https://doi.org/10.1007/s11060-008-9775-2

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  • DOI: https://doi.org/10.1007/s11060-008-9775-2

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