HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Human osteosarcoma xenografts and their sensitivity to chemotherapy.

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 O(6)-Methylguanine DNA Methyltransferase (MGMT), DNA topoisomerase II- (Topo II)-alpha, Gluthathione-S-transferase (GST)-pi, Multidrug-resistance related protein (MRP) 1 and Multidrug-resistance (MDR) 1 genes. There was an inverse correlation between the transcript levels of GST-pi 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.
AuthorsSkjalg Bruheim, Oyvind S Bruland, Knut Breistol, Gunhild M Maelandsmo, Oystein Fodstad
JournalPathology oncology research : POR (Pathol Oncol Res) Vol. 10 Issue 3 Pg. 133-41 ( 2004) ISSN: 1219-4956 [Print] England
PMID15448748 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Multidrug Resistance-Associated Proteins
  • P-Glycoprotein
  • RNA, Messenger
  • O(6)-Methylguanine-DNA Methyltransferase
  • Glutathione Transferase
  • DNA Topoisomerases, Type II
Topics
  • Adolescent
  • Adult
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Blotting, Northern
  • Bone Neoplasms (drug therapy, metabolism)
  • Child
  • DNA Topoisomerases, Type II (metabolism)
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Female
  • Glutathione Transferase (metabolism)
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Multidrug Resistance-Associated Proteins (metabolism)
  • Neoplasm Transplantation
  • O(6)-Methylguanine-DNA Methyltransferase (metabolism)
  • Osteosarcoma (drug therapy, metabolism)
  • P-Glycoprotein (metabolism)
  • RNA, Messenger
  • Transplantation, Heterologous

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: