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Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy

Cancer Gene Therapy volume 10, pages 396–402 (2003)Cite this article

Abstract

Since neural progenitor cells can engraft stably into brain tumors and differentiate along the neuronal and glial line, we tested the hypothesis that transplanted cytosine deaminase (CD)-expressing ST14A cells (an immortalized neural progenitor cell line) can convert locally 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU) and produce a regression of glioma tumors. ST14A, retrovirally transduced with the E. coli CD gene, showed a strong bystander effect on glioma cells as assessed by in vitro assay. Intracerebral injection of C6 glioma cells generated a rapidly growing tumoral mass. DiI prelabeled ST14A, coinjected into the rat brain with C6 glioma cells, survived in the tumoral mass up to 10 days and their number was not affected by in vivo 5-FC treatment. In contrast, a significant decrease of the glioma tumoral mass (−50%) was observed in 5-FC-treated rats. 5-FC had no effect on the tumor in the absence of CD-expressing ST14A cells. Our results support the feasibility of systems based on intratumoral transplantation of prodrug-converting cells for brain tumor therapy.

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Acknowledgements

We thank Prof. AM Giuffrida Stella for her continuous support and encouragement during all the stages of this work. Barresi V was supported by a postdoctoral fellowship (borsa post-dottorato ed assegno di ricerca) of the University of Catania (Italy) and a travel grant by the Italian Interuniversity Consortium for Biotechnologies (CIB). Portions of this work were presented at the Joint 18th Biennal Meeting of the International Society for Neurochemistry (ISN) and the 32nd Annual Meeting of the American Society for Neurochemistry (ASN) 26–31 August 2001, Buenos Aires (Argentina).

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Authors and Affiliations

  1. Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, University of Catania, Italy

    Vincenza Barresi & Daniele Filippo Condorelli

  2. Department of Experimental Medicine, University of Palermo, Italy

    Natale Belluardo & Giuseppa Mudó

  3. Department of Pharmacological Sciences, University of Milan, Italy

    Simonetta Sipione & Elena Cattaneo

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  1. Vincenza Barresi
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  2. Natale Belluardo
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  3. Simonetta Sipione
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  4. Giuseppa Mudó
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  5. Elena Cattaneo
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  6. Daniele Filippo Condorelli
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Correspondence to Daniele Filippo Condorelli.

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Barresi, V., Belluardo, N., Sipione, S. et al. Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy. Cancer Gene Ther 10, 396–402 (2003). https://doi.org/10.1038/sj.cgt.7700580

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