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Clinical Competence↗
Biomedical subjects
Morten Salomo
Publications and source records attributed to Morten Salomo.
How myeloma cells escape bisphosphonate-mediated killing: development of specific resistance with preserved sensitivity to conventional chemotherapeutics.
Although amino-bisphosphonates (N-BPs) induce apoptosis of myeloma cells in vitro, most in-vivo studies fail to demonstrate a corresponding antitumour effect. This discrepancy might reflect the development of resistance to the antitumour effects of N-BP in myeloma cells when they are exposed to N-BP for a prolonged time. To test this hypothesis, two N-BP-sensitive human myeloma cell lines were continuously exposed to increasing concentrations of the N-BP alendronate for 6 weeks. During this treatment period, 10 out of 10 sublines developed reduced apoptotic and antiproliferative responses to alendronate treatment. This de novo alendronate resistance was accompanied by resistance to another N-BP (zoledronate) but not to an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase or Fas ligand. Importantly, N-BP-resistant myeloma cells also remained sensitive to conventional myeloma chemotherapeutics (melphalan, doxorubicin and vincristine). Further analysis of the N-BP-resistant cells revealed an increased activity of the N-BP-specific target enzyme farnesyl pyrophosphate synthase, without upregulation of its gene transcription. Our results suggest that continuous exposure of myeloma cells to alendronate leads to the development of N-BP resistance. This is associated with an increased activity of farnesyl pyrophosphate synthase and does not evolve from defective apoptotic pathways. Importantly, the antitumour effects of conventional myeloma chemotherapeutics are preserved in the N-BP-resistant myeloma cells.
Alendronate↗
Simple method for quantification of Bence Jones proteins.
BACKGROUND: Quantification of free monoclonal light chains in urine [Bence Jones proteins (BJPs)] is used to diagnose multiple myeloma and to evaluate response to treatment. We have developed and evaluated an optimized approach for quantification of BJPs. METHODS: High-resolution gel electrophoresis of unconcentrated urine and albumin calibrators was carried out on Sebia's Hydrasys instrument with Hydragel HR agarose gels. After staining with acid violet, the gels were scanned densitometrically. The staining intensities of BJP bands relative to the staining intensities of albumin solutions were used to determine the BJP concentrations. Results for patient samples were compared with conventional agarose gel electrophoresis on concentrated samples. RESULTS: The relationships between staining intensity and the protein concentrations of albumin and BJPs were linear up to protein concentrations of approximately 2000 mg/L. The detection limit was approximately 20 mg/L. The interassay imprecision (CV) was approximately 8% (n = 23, duplicate analysis), and the results (y) showed a close positive relationship to the comparison method: slope = 0.82 (confidence interval, 0.75-0.88); y-intercept = 34 (-14 to 81) mg/L; n = 29; r(2) = 0.96. CONCLUSIONS: Agarose gel electrophoresis of unconcentrated urine samples together with a series of albumin calibrators followed by acid violet staining and densitometric scanning is sufficiently reproducible and sensitive to quantify clinically relevant BJPs.
Bence Jones Protein↗