Proton beam irradiation promises therapeutic utility in the management of uveal melanoma. Calcitriol (1,25(OH)₂D₃)—the biologically active metabolite of vitamin D₃—and its precursor, calcidiol (25(OH)D₃), exert pleiotropic effects on melanoma cells. The aim of the study was to evaluate the effect of both calcitriol and calcidiol on melanoma cell proliferation and their response to proton beam irradiation. Three melanoma cell lines (human SKMEL-188 and hamster BHM Ma and BHM Ab), pre-treated with 1,25(OH)₂D₃ or 25(OH)D₃ at graded concentrations (0, 10, 100 nM), were irradiated with 0–5 Gy and then cultured in vitro. Growth curves were determined by counting the cell number every 24 h up to 120 h, which was used to calculate surviving fractions. The obtained survival curves were analysed using two standard models: linear-quadratic and multi-target single hit. Calcitriol inhibited human melanoma proliferation at 10 nM, while only calcidiol inhibited proliferation of hamster lines at 10 and 100 nM doses. Treatment with either 1,25(OH)₂D₃ or 25(OH)D₃ radio sensitized melanoma cells to low doses of proton beam radiation. The strength of the effect increased with the concentration of vitamin D₃. Our data suggest that vitamin D₃ may be an adjuvant that modifies proton beam efficiency during melanoma therapy.

Purpose: Molecular oxygen, besides a photosensitizer and light of appropriate wavelength, is one of the three factors necessary for photodynamic therapy (PDT). In tumor tissue, PDT leads to the killing of tumor cells, destruction of endothelial cells and vasculature collapse, and the induction of strong immune responses. All these effects may influence the oxygenation levels, but it is the vasculature changes that have the main impact on pO₂. The purpose of our study was to monitor changes in tumor oxygenation after PDT and explore its significance for predicting long-term treatment response. Procedures: Electron paramagnetic resonance (EPR) spectroscopy enables direct, quantitative, and sequential measurements of partial pressure of oxygen (pO₂) in the same animal. The levels of chlorophyll derived photosensitizers in tumor tissue were determined by transdermal emission measurements. Results: The noninvasive monitoring of pO₂ in the tumor tissue after PDT showed that the higher ΔpO₂ (pO₂ after PDT minus pO₂ before PDT), the greater the inhibition of tumor growth. ΔpO₂ also correlated with higher levels of the photosensitizers in the tumor and with the occurrence of a severe edema/erythema after PDT. Conclusion: Monitoring of PDT-induced changes in tumor oxygenation is a valuable prognostic factor and could be also used to identify potentially resistant tumors, which is important in predicting long-term treatment response.