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Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits macrophage inflammatory protein 1alpha expression and secretion in mouse myeloma cells.

Cancer science 2007 Nov 4; 99(1):152-8

Link to PubMed abstract

Tsubaki M M, Kato C C, Nishinobo M M, Ogaki M M, Satou T T, Ito T T, Kusunoki T T, Fujiwara K K, Yamazoe Y Y, Nishida S S

Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan.

Macrophage inflammatory protein 1alpha (MIP-1alpha) is detected at high concentrations in patients with multiple myeloma, and it is thought to play an important role in the etiology of multiple myeloma and osteolysis. Thus, we investigated whether or not YM529/ONO-5920, a new bisphosphonate, inhibited MIP-1alpha mRNA expression in, and MIP-1alpha secretion from, mouse myeloma cells. When the cells were stimulated by lipopolysaccharide, increased MIP-1alpha mRNA expression and MIP-1alpha secretion were observed. YM529/ONO-5920 inhibited MIP-1alpha mRNA expression and MIP-1alpha secretion in a concentration-dependent manner. A transient increase in the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) and Akt was observed after lipopolysaccharide stimulation. After YM529/ONO-5920 was given, there was no transient increase in the phosphorylation of ERK1/2 or Akt. These results indicated that YM529/ONO-5920 inhibited the expression and secretion of MIP-1alpha through blocking the signaling pathway of the Ras/mitogen-activated protein kinase kinase/ERK and Ras/phosphatidylinositol-3 kinase/Akt. Accordingly, YM529/ONO-5920 appears to have promise for use in effective future therapy for osteolysis and myeloma cell growth that depends on MIP-1alpha.

Keywords: myeloma