These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Efficacy of a nitrogen-containing bisphosphonate, minodronate, in conjunction with a p38 mitogen activated protein kinase inhibitor or doxorubicin against malignant bone tumor cells.
    Author: Kubo T, Shimose S, Matsuo T, Sakai A, Ochi M.
    Journal: Cancer Chemother Pharmacol; 2008 Jun; 62(1):111-6. PubMed ID: 17874104.
    Abstract:
    PURPOSE: We recently reported the sarcoma-selective antitumor effects of a newly developed nitrogen-containing bisphosphonate, minodronate (MIN), on malignant bone tumors. The aim of this study was to develop efficient combination MIN therapy in malignant bone tumors. METHODS: We examined downstream molecular events of MIN in osteosarcoma and Ewing's sarcoma cells to search for a partner to combine with MIN. Furthermore, we evaluated the combined effects of MIN and clinically available Doxorubicin (DOX). RESULTS: We found that MIN inhibited Rap 1A prenylation, and extracellular signal-regulated kinase (ERK) or Akt phosphorylation in osteosarcoma (Saos-2) and Ewing's sarcoma (SK-ES-1) cells. Interestingly, MIN activated p38 mitogen activated protein kinase (MAPK) only in SK-ES-1 cells and a p38 MAPK inhibitor augmented MIN-induced growth inhibition in SK-ES-1 cells. Doxorubicin (DOX) exerted synergistic effects on Saos-2 and SK-ES-1 cell lines. Daily injection of MIN enhanced the growth inhibition of SK-ES-1 xenograft sarcoma treated by DOX in nude mice. CONCLUSIONS: These findings suggest that the inhibition of the p38 MAPK pathway may be attractive in overcoming cellular resistance against MIN. In the light of clinical settings, MIN may have a beneficial adjuvant role in the DOX treatment.
    [Abstract] [Full Text] [Related] [New Search]