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Rat Model of Malignant Brain Tumors: Implantation of Doxorubicin Using Drug Eluting Beads for Delivery

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Tumors of the Central Nervous System, Volume 4

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 4))

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Abstract

In this chapter we describe the use of a rat model of malignant glioma for the evaluation of a novel doxorubicin drug eluting bead (DEB) technology. The rationale for locoregional therapy for treatment of glioma is presented in the context of a review of the shortcomings of the currently available therapies. The BT4Ca syngeneic glioma model in BDIX rats is described, together with the intricacies that must be considered when using this model to assess Doxorubicin DEB intratumoral implantation. An overview of the results obtained are presented in the context of other work reported with this drug in the treatment of brain tumors.

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References

  • Abe T, Hasegawa S, Taniguchi K, Yokomizo A, Kuwano T, Ono M, Mori T, Hori S, Kohno K, Kuwano M (1994) Possible involvement of multidrug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine, etoposide and adriamycin in human glioma cells. Int J Cancer 58:860–864

    Article  PubMed  CAS  Google Scholar 

  • Affronti ML, Heery CR, Herndon JE 2nd, Rich JN, Reardon DA, Desjardins A, Vredenburgh JJ, Friedman AH, Bigner DD, Friedman HS (2009) Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy. Cancer 115:3501–3511

    Article  PubMed  CAS  Google Scholar 

  • Baltes S, Freund I, Lewis AL, Nolte I, Brinker T (2010) Doxorubicin and irinotecan drug-eluting beads for treatment of glioma: a pilot study in a rat model. J Mater Sci Mater Med 21:1393–1402

    Article  PubMed  CAS  Google Scholar 

  • Barth RF, Kaur B (2009) Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J Neurooncol 94:299–312

    Article  PubMed  Google Scholar 

  • Benjamin RS, Wiernik PH, Bachur NR (1974) Adriamycin chemotherapy – efficacy, safety, and pharmacologic basis of an intermittent single high-dosage schedule. Cancer 33:19–27

    Article  PubMed  CAS  Google Scholar 

  • Boiardi A, Eoli M, Salmaggi A, Lamperti E, Botturi A, Broggi G, Bartolomei M, Silvani A (2003) New approach in delivering chemotherapy: locoregional treatment for recurrent glioblastoma (rGBM). J Exp Clin Cancer Res 22:123–127

    PubMed  CAS  Google Scholar 

  • Boiardi A, Eoli M, Salmaggi A, Lamperti E, Botturi A, Solari A, Di Meco F, Broggi G, Silvani A (2005) Local drug delivery in recurrent malignant gliomas. Neurol Sci 26(Suppl. 1):S37–39

    Article  PubMed  Google Scholar 

  • Buahin KG, Brem H (1995) Interstitial chemotherapy of experimental brain tumors: comparison of intratumoral injection versus polymeric controlled release. J Neurooncol 26:103–110

    Article  PubMed  CAS  Google Scholar 

  • Darling JL, Thomas DG (2001) Response of short-term cultures derived from human malignant glioma to aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trial. Anticancer Drugs 12:753–760

    Article  PubMed  CAS  Google Scholar 

  • Giglio P, Villano JL (2010) Newly diagnosed high-grade gliomas. Curr TreatOpt Neurol 12:309–320

    Article  Google Scholar 

  • Gonzalez MV, Tang Y, Phillips GJ, Lloyd AW, Hall B, Stratford PW, Lewis AL (2008) Doxorubicin eluting beads-2: methods for evaluating drug elution and in-vitro:in-vivo correlation. J Mater Sci Mater Med 19:767–775

    Article  PubMed  CAS  Google Scholar 

  • Hart MG, Grant R, Garside R, Rogers G, Somerville M, Stein K (2008) Chemotherapeutic wafers for High Grade Glioma. Cochrane Database Syst Rev CD007294

    Google Scholar 

  • Irwin C, Hunn M, Purdie G, Hamilton D (2007) Delay in radiotherapy shortens survival in patients with high grade glioma. J Neurooncol 85:339–343

    Article  PubMed  Google Scholar 

  • Khan A, Jallo GI, Liu YJ, Carson BS, Guarnieri M (2005) Infusion rates and drug distribution in brain tumor models in rats. J Neurosurg 102:53–58

    PubMed  Google Scholar 

  • Kikuchi T, Saito R, Sugiyama S, Yamashita Y, Kumabe T, Krauze M, Bankiewicz K, Tominaga T (2008) Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin: characterization and efficacy in rat intracranial glioma models. J Neurosurg 109:867–873

    Article  PubMed  CAS  Google Scholar 

  • Lawson HC, Sampath P, Bohan E, Park MC, Hussain N, Olivi A, Weingart J, Kleinberg L, Brem H (2007) Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience. J Neurooncol 83:61–70

    Article  PubMed  CAS  Google Scholar 

  • Lesniak MS, Upadhyay U, Goodwin R, Tyler B, Brem H (2005) Local delivery of doxorubicin for the treatment of malignant brain tumors in rats. Anticancer Res 25:3825–3831

    PubMed  CAS  Google Scholar 

  • Lewis AL, Gonzalez MV, Lloyd AW, Hall B, Tang Y, Willis SL, Leppard SW, Wolfenden LC, Palmer RR, Stratford PW (2006) DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization. J Vasc Interv Radiol 17:335–342

    Article  PubMed  Google Scholar 

  • Menei P, Capelle L, Guyotat J, Fuentes S, Assaker R, Bataille B, Francois P, Dorwling-Carter D, Paquis P, Bauchet L, Parker F, Sabatier J, Faisant N, Benoit JP (2005) Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of malignant glioma: a randomized phase II trial. Neurosurgery 56:242–248

    Article  PubMed  Google Scholar 

  • Menei P, Jadaud E, Faisant N, Boisdron-Celle M, Michalak S, Fournier D, Delhaye M, Benoit JP (2004) Stereotaxic implantation of 5-fluorouracil-releasing microspheres in malignant glioma. Cancer 100:405–410

    Article  PubMed  CAS  Google Scholar 

  • Namur J, Wassef M, Millot JM, Lewis AL, Manfait M, Laurent A (2010) Drug-eluting beads for liver embolization: concentration of doxorubicin in tissue and in beads in a pig model. J Vasc Interv Radiol 21:259–267

    Article  PubMed  Google Scholar 

  • Neuwelt EA, Glasberg M, Frenkel E, Barnett P (1983) Neurotoxicity of chemotherapeutic agents after blood-brain barrier modification: neuropathological studies. Ann Neurol 14:316–324

    Article  PubMed  CAS  Google Scholar 

  • Quant EC, Drappatz J, Wen PY, Norden AD (2010) Recurrent high-grade glioma. Curr Treat Opt Neurol 12:321–333

    Article  Google Scholar 

  • Ranganath SH, Kee I, Krantz WB, Chow PK, Wang CH (2009) Hydrogel matrix entrapping PLGA-paclitaxel microspheres: drug delivery with near zero-order release and implantability advantages for malignant brain tumour chemotherapy. Pharm Res 26:2101–2114

    Article  PubMed  CAS  Google Scholar 

  • Vinchon-Petit S, Jarnet D, Michalak S, Lewis A, Benoit JP, Menei P (2010) Local implantation of doxorubicin drug eluting beads in rat glioma. Int J Pharm 402:184–189

    Google Scholar 

  • von Eckardstein KL, Reszka R, Kiwit JC (2005) Intracavitary chemotherapy (paclitaxel/carboplatin liquid crystalline cubic phases) for recurrent glioblastoma – clinical observations. J Neurooncol 74:305–309

    Article  Google Scholar 

  • Voulgaris S, Partheni M, Karamouzis M, Dimopoulos P, Papadakis N, Kalofonos HP (2002) Intratumoral doxorubicin in patients with malignant brain gliomas. Am J Clin Oncol 25:60–64

    Article  PubMed  Google Scholar 

  • Weinberg BD, Blanco E, Gao J (2008) Polymer implants for intratumoral drug delivery and cancer therapy. J Pharm Sci 97:1681–1702

    Article  PubMed  CAS  Google Scholar 

  • Zhou R, Mazurchuk R, Straubinger RM (2002) Antivasculature effects of doxorubicin-containing liposomes in an intracranial rat brain tumor model. Cancer Res 62:2561–2566

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. International Neuroscience Institute GmbH, D-30625, Hannover, Germany

    Thomas Brinker & Andrew Lewis

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  1. Thomas Brinker
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  2. Andrew Lewis
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Correspondence to Thomas Brinker .

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Editors and Affiliations

  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Brinker, T., Lewis, A. (2012). Rat Model of Malignant Brain Tumors: Implantation of Doxorubicin Using Drug Eluting Beads for Delivery. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 4. Tumors of the Central Nervous System, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1706-0_25

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  • DOI: https://doi.org/10.1007/978-94-007-1706-0_25

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  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-1705-3

  • Online ISBN: 978-94-007-1706-0

  • eBook Packages: MedicineMedicine (R0)

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