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Pathology Oncology Research

, Volume 10, Issue 3, pp 133–141 | Cite as

Human osteosarcoma xenografts and their sensitivity to chemotherapy

  • Skjalg Bruheim
  • Oyvind S. Bruland
  • Knut Breistol
  • Gunhild M. Maelandsmo
  • Øystein Fodstad
Article

Abstract

Despite the increased survival rates of osteosarcoma patients attributed to adjuvant chemotherapy, at least one third of the patients still die due to their disease. Further improvements in the management of osteosarcoma may rely on a more individualised treatment strategy, as well as on the introduction of new drugs. To aid in the preclinical evaluation of new candidate substances against osteosarcoma, we have established 11 human osteosarcoma xenograft lines and characterised them with regard to response to five different reference drugs. Doxorubicin, cisplatin methotrexate, ifosfamide and lomustine were effective in 3/11, 3/11, 1/10, 5/11 and 4/11 of the xenografts, respectively. Five xenografts were resistant to all compounds tested. We also assessed the mRNA expression levels of the xenografts for the O6-Methylguanine DNA Methyltransferase (MGMT), DNA topoisomerase II-(Topo II)-α, Gluthathione-S-transferase (GST)-π, Multidrug-resistance related protein (MRP) 1 and Multidrug-resistance (MDR) 1 genes. There was an inverse correlation between the transcript levels of GST-π and doxorubicin growth inhibition (r= −0.66; p<0.05), and between the transcript levels of MGMT and the effect of lomustine (r= −0.72; p<0.01), whereas the expression of MRP1 and cisplatin growth inhibition was positively correlated (r=0.82; p<0.005. This panel of xenografts should constitute a good tool for pharmacological and molecular studies in osteosarcoma.

Keywords

osteosarcoma human tumor xenograft chemotherapy drug resistance 

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Copyright information

© Arányi Lajos Foundation 2004

Authors and Affiliations

  • Skjalg Bruheim
    • 2
  • Oyvind S. Bruland
    • 1
  • Knut Breistol
    • 2
  • Gunhild M. Maelandsmo
    • 2
  • Øystein Fodstad
    • 2
  1. 1.Department of OncologyThe Norwegian Radium HospitalOsloNorway
  2. 2.Department of Tumor Biology, Institute for Cancer ResearchThe Norwegian Radium HospitalOsloNorway

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