al tumor volume, each week, was statistically analyzed. Results showed the ability of EB1089 to bind to the vitamin D receptor, the effects on breast cancer cell proliferation in vitro, and the effects on rat mammary tumor progression. Oral treatment was tested at three doses. The lower dose resulted in significant inhibition of tumor growth with the absence of serum calcium increase. The same dose of 1,25-(OH)2D3 resulted in hypercalcaemia with no tumor growth effect. Higher dose caused tumor regression with increased serum calcium.
The authors concluded that EB1089 is an anti-tumor agent with reduced calcaemic effects relative to dose; it is considered to have anti-tumor therapeutic potential. It is also noted that EB1089 is a striking inhibitor of rat mammary tumor growth in vivo, in a dose-dependent manner. The dose of 0.5 ug/kg body weight was found to inhibit tumor growth with an absence of increased serum calcium. High dose demonstrated tumor regression more than 50 percent in over 80 percent of treated rats; however serum calcium was also increased.
The vitamin D analogue is characterized by a modification at the C17 side chain. The structural modification of the vitamin D molecule leads to different activity profile; it remains unclear how this takes place. Previous evidence does not indicate multiple forms of vitamin D receptor. The current study shows a single gene for VDR and a single translated receptor molecule. Differences in receptor phosphorylation state and tissue mRNA size heterogeneity were shown. It is concluded that it may be possible that interaction of the vitamin D analogue with VDR results in "alternative conformational changes in the receptor-ligand complex leading to altered transcription in different spectrum of target genes" (p. 2279).
Colston et al. (1992) designed their current investigation based on possible problems with previous study methodologies and limited information re...