PATHOLOGY & ONCOLOGY RESEARCHVol. 10 No. 3, 2004

 Article

Human Osteosarcoma Xenografts and Their Sensitivity to Chemotherapy

Skjalg BRUHEIM1, Oyvind S BRULAND2, Knut BREISTOL1, Gunhild M MAELANDSMO1, Oystein FODSTAD2

1Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
2Department of Oncology, The Norwegian Radium Hospital, Oslo, Norway

 

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)-a, Gluthathione-S-transferase (GST)-p, Multidrug-resistance related protein (MRP) 1 and Multidrug-resistance (MDR) 1 genes. There was an inverse correlation between the transcript levels of GST-p 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. Pathology & Oncology Research, Vol 10, Nr 3, 133-141, 2004

Key words: osteosarcoma; human tumor xenograft; chemotherapy; drug resistance


Received: Jun 30, 2004; accepted: Aug 10, 2004
Correspondence: Skjalg BRUHEIM, Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello Oslo 0310, Norway; E-mail: skjalg.bruheim@labmed.uio.no

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