Eight of the 10 learn more subjects showed significant upregulation of VDR and E-cadherin, a downstream target of vitamin D action, suggesting that the chemopreventive action of hormone replacement therapy on colon cancer may result partially from

changes in vitamin D activity. As no effective regimens are available for advanced HCC at the present time, new strategies are urgently needed. In this regards, 1α,25(OH)2D3 and its analogs have been shown to possess an antiproliferative effect on HCC in vivo and in vitro, 1α,25(OH)2D3 will be a promising therapeutic regimen for advanced HCC. Knowing that a pharmacological dose of 1α,25(OH)2D3 is usually required to be therapeutically effective in treating cancers, and the serious hypercalcemic side-effect accompanying the massive dose of 1α,25(OH)2D3, Morris DL et al.51 conducted a phase I clinical trial, in which 1α,25(OH)2D3 was dissolved in 5 mL lipiodol and was injected through the hepatic artery. They reasoned that lipiodol would be preferentially retained by HCC, and by injecting 1α,25(OH)2D3 into the hepatic artery they could avoid the 24-OHase-mediated degradation of 1α,25(OH)2D3 in the liver before reaching the tumor, and therefore could obtain higher concentrations of 1α,25(OH)2D3 in HCC.52–54 Eight cases of refractory

HCC were included in this study. The subjects were administered with either 50, 75, or 100 µg 1α,25(OH)2D3. Although three out of eight patients developed hypercalcemia, this website none of them was over grade III hypercalcemia, indicating this was a safe way to deliver 1α,25(OH)2D3. However, no obvious benefit on survival was observed in spite of transient stabilization of tumor marker, alpha-fetoprotein. EB 1089 has also been investigated in a clinical trial.55 In this trial, 56 patients with inoperable HCC were treated with EB1089

orally for up to one year with doses of EB 1089 titrated according to their serum calcium concentrations. Most of the patients could tolerate 10 µg/day of EB1089 orally. Although the survival benefit could not be obtained because no controls were included in this study, however, two patients did have the size of tumor decreased and 12 patients selleck inhibitor had stable disease.55 Further control studies are warranted to determine the survival benefit of EB 1089 on HCC. Human VDR cDNA was cloned in 1988 by Baker et al.,56 and the major parts of the genomic structures of the human VDR gene was described 10 years later by Miyamoto et al.57 The location of the VDR gene was later determined at the chromosome 12q13.1 region.58 The gene itself is quite large (just over 100 kb). The VDR gene has an extensive promoter region with capability of generating multiple tissue-specific transcripts.59 Recent studies have provided the existence of many subtle sequence variations (polymorphisms) in the VDR gene.