A vitamin D analogue (EB1089) inhibits parathyroid hormone-related peptide production and prevents the development of malignancy-associated hypercalcemia in vivo.

摘要: We have examined the effects of 1,25 dihydroxyvitamin D3 (1,25[OH]2D3) and a low calcemic analogue EB1089 on parathyroid hormone-related peptide (PTHRP) production development hypercalcemia in Fischer rats implanted with Leydig cell tumor H-500. tumors were subcutaneously into male rats, which received constant infusions intraperitoneally either 1,25(OH)2D3 (50-200 pmol/24 h), (50-400 or vehicle for up to 4 wk. A control group animals similar without implantation. Plasma calcium, plasma levels immunoreactive iPTHRP, PTHRP mRNA determined as well size, animal body weight, survival time. Non-tumor-bearing receiving > 50 h became hypercalcemic, whereas no significant change calcium was observed severely hypercalcemic within 15 d. However, treated dose all doses maintained near-normal normal Additionally, reduced iPTHRP compared controls both vitamin D- EB1089-treated rats. Infusion 200 significantly volume by end experiment. The but not substantially prolonged time tumor-bearing longer achieved at highest dose, 400 h, EB1089. These studies demonstrate that D are potent inhibitors vivo. Low analogues may therefore represent important alternative therapy malignancy-associated hypercalcemia.