Background:Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the ‘Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition.Methods:Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib.Results:We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5–10 mℳ) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10–25 mℳ) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice.Conclusion:Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.

Twenty-two recurrent calcium stone formers had 24-h urinary oxalate excretions on their home diets which were significantly greater than those of 30 normal subjects «()·4X±()·23 rnrnol/d; mean±SD compared with 0·31±0·11; P

A calcium loading test performed on seven of eight children with idiopathic hypercalciuria identified the hyperabsorptive form of hypercalciuria in five and renal hypercalciuria in one. The type of hypercalciuria was not identified in the other patient. Three children presented with hematuria without calculus formation. Chlorothiazide reduced the urinary calcium excretion level in two of six patients to the normal range. The addition of cellulose phosphate to chlorothiazide reduced the urinary calcium excretion level to the normal range in those four patients who showed an incomplete response to chlorothiazide alone. There was clinical improvement with cellulose phosphate in another child whose symptoms did not disappear after chlorothiazide had reduced urinary calcium level to the normal range. Cellulose phosphate is effective in children with recurrent stone formation who have shown inadequate response to chlorothiazide.