menaquinone-6 and maxacalcitol

The kidney deeply takes part in phosphorus and vitamin D metabolism. The chronic kidney disease patients usually suffer from serious bone disease. They are prescribed the glucocorticoid medication for primary kidney disease, as nephrotic syndrome and collagen renal disease, with aging. The end of therapeutic target is normal bone structure with normal bone turnover in CKD patients. The control of serum Ca and phosphorus level is important step and also another target. This issue describes the problem and the advancement of treatment and the measurement of the bone mass from this viewpoint.

Topics: Absorptiometry, Photon; Bone Density; Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Deferoxamine; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Parathyroidectomy; Phosphorus; Vitamin K 2

We originally reported that vitamin K(2) (VK2) effectively induces apoptosis in various types of primary cultured leukemia cells and leukemia cell lines in vitro. In addition, VK2 was shown to induce differentiation of leukemia cells when the cells were resistant against VK2-inducing apoptosis. A novel synthetic vitamin D(3)derivative, 22-oxa-1,25-dihydroxyvitamin D(3) (OCT: oxacarcitriol) shows a more potent differentiation-inducing ability among myeloid leukemia cells in vitro with much lesser extent of the induction of hypercalcemia in vivo as compared to the effects of 1alpha,25(OH)(2)D(3). In the present study, we focused on the effects of a combination of OCT plus VK2 on leukemia cells. Treatment of HL-60 cells with OCT for 72 h induces monocytic differentiation. A combination of OCT plus VK2 dramatically enhances monocytic differentiation as assessed by morphologic features, positivity for non-specific esterase staining, and cell surface antigen expressions. This combined effect far exceeds the maximum differentiation induction ability at the optimal concentrations of either OCT or VK2 alone. In addition, pronounced accumulation of the cells in the G0/G1 phase is observed by combined treatment with OCT plus VK2 as compared with each vitamin alone. In contrast to cell differentiation, caspase-3 activation and apoptosis induction in response to VK2 are significantly suppressed in the presence of OCT in HL-60 cells. These data suggest that monocytic differentiation and apoptosis induction of HL-60 cells are inversely regulated. Furthermore, pronounced induction of differentiation by combined treatment with VK2 plus OCT was also observed in four out of six cases of primary cultured acute myeloid leukemia cells in vitro, suggesting that VK2 plus OCT might be a potent combination for the differentiation-based therapy for acute myeloid leukemias.

Topics: Acute Disease; Antineoplastic Agents; Apoptosis; Calcitriol; Cell Differentiation; Drug Screening Assays, Antitumor; Drug Synergism; Female; Gene Expression Regulation, Leukemic; HL-60 Cells; Humans; Leukemia, Myeloid; Male; Middle Aged; Neoplasms, Second Primary; Neoplastic Stem Cells; Tumor Cells, Cultured; Vitamin K 2