Effects of calcitriol, seocalcitol, and medium-chain triglyceride on a canine transitional cell carcinoma cell line.

BACKGROUND: Transitional cell carcinoma (TCC) in dogs is associated with high morbidity and mortality. Calcitriol and its analog seocalcitol, combined with medium-chain triglyceride (MCT), have potential for the treatment of this disease. MATERIALS AND METHODS: TCC cells were treated with calcitriol or seocalcitol, alone or combined with MCT. Cell growth, cell cycle kinetics, vitamin D receptor (VDR) localization and expression, and Bcl-2 expression were measured. RESULTS: Canine TCC expresses high levels of nuclear VDR. Furthermore, calcitriol and seocalcitol significantly inhibited cell growth and calcitriol caused G0/G1 cell cycle arrest. Bcl-2 expression was slightly decreased in cells treated with these compounds, although no significant changes in VDR expression were observed. MCT enhanced the growth inhibitory effect of both compounds. CONCLUSION: Calcitriol and seocalcitol inhibited TCC cell growth via induction of cell cycle arrest and MCT enhanced this effect. Therefore, calcitriol and seocalcitol with MCT may have therapeutic potential for canine bladder cancer.

Synthesis of novel hapten derivatives of 1alpha,25-dihydroxy-vitamin D3 and its 20-epi analogue.

Hapten derivatives of 1alpha,25-dihydroxyvitamin D(3) and its 20-epimer were synthesized and conjugated to a carrier protein for raising polyclonal antibodies. The haptens were linked through spacers at C-16, thereby exposing both the A-ring and the side chain of the molecules, to maximize antibody specificity. The spacers were introduced via stereoselective hydroboration of 16-ene intermediates as the key step. In immunoassays, the antibodies raised toward the natural hormone were selective to this compound over derivatives with modifications in the A-ring or the side chain. The antibodies toward the 20-epimer, however, were unable to recognize modifications in the side chain.

Synthesis and testing of 2alpha-modified 1alpha,25-dihydroxyvitamin D(3) analogues with a double side chain: marked cell differentiation activity.

The 2alpha-methyl-, 2alpha-(3-hydroxypropyl)-, and 2alpha-(3-hydroxypropoxy)-derivatives of the 'double side chain' analogue of 1alpha,25-dihydroxyvitamin D(3) were synthesized using Trost A-ring/CD-ring connective strategy. Regarding the requisite A-ring building blocks, a new, high yield and stereoselective route to the 2alpha-methyl compound starting from D-glucose was developed. All three new analogues showed potent HL-60 cancer cell differentiation activity.

Emerging drugs in psoriasis.

Psoriasis is a relatively common, chronic skin disease affecting 1-2% of the population in the developed countries. It is an inflammatory, autoimmune skin disorder characterised by an accelerated rate of epidermal proliferation and disordered differentiation. Since our last review in 1999, considerable progress has been made in understanding the immunopathogenesis of this disease, and new drugs have become available for its treatment. Recent clinical trials showed the efficacy of novel biotechnology approaches, such as blocking tumour necrosis factor-alpha or T-cell-mediated immune response by the anti-CD2, anti-CD11a, anti-B7, anti-CD4 or anti-CD25 approaches. Agents which block type 1 cytokines or skew immune reactions into type 2 are other promising approaches. Other possible targets are chemokines and their receptors, the cytokines and receptors involved in T cell trafficking into the skin, and peroxisome proliferator-activated receptors. Relatively little development is reported of the drugs targeting the keratinocyte or the classical antipsoriatic compounds which include glucocorticoids, vitamin D derivatives and cytostatic agents.