Păsărică, Mihai Adrian, Curcă, Paul Filip, Maria Dragosloveanu, Christiana Diana, Dinu, Valentin, Burcea, Marian, and Grigorescu, Alexandru Călin
Introduction. Cutaneous and uveal malignant melanomas (MM) show different metastasis characteristics, with no approved systemic treatment for metastatic uveal melanoma. Melanocytes are particularly susceptible to oxidative stress, defined as an imbalance between the formation of prooxidants and their removal by antioxidant systems. A better understanding of oxidative stress markers (lipid peroxides, albumin thiols, total antioxidants) differences between cutaneous and uveal melanoma could be useful in quantifying the different response to treatment. Materials and method. In a prospective study, 45 patients diagnosed with cutaneous MM (PC), as well as a cohort of 44 patients diagnosed with uveal MM (PU) were enrolled and separated into three distinct subgroups according to the received treatment: radiotherapy (14), enucleation (18), enucleation with postoperative systemic chemotherapy. All patients were followed-up for two years after diagnosis, obtaining seven determinations of biochemical parameters of oxidative stress – markers of lipid peroxidation inferement via malondialdehyde measurement, total thiol-albumin groups (Shoshinsky method), for the inferement of oxidative proteic degradation. Results. All levels were elevated compared to baseline in cutaneous and uveal melanoma patients: serum lipid peroxides PC 8.229, PU 8.377 versus baseline 4 μmol/100 ml, serum albumin thiols 511.8 PC, PU 479.9 versus baseline 450 μmol/L, serum total antioxidants 2.768 PC, 3.040 PU versus baseline 1.2 μmol/L, suggesting oxidative stress increase in the presence of a malign tumor. The levels in uveal melanoma patients varied more compared to those from cutaneous melanoma. Conclusions. The results indicate an increase of lipid peroxidation reaction, serum albumin thiols and serum total antioxidants, in correlation with tumor evolution, both in uveal and cutaneous melanoma compared to baseline values. As such, the presence of the tumor is an oxidative stress inductor, with anti-tumor treatment also having the ability to induce oxidative stress through the destruction of tumor cells. Changes between the two groups indicate different molecular signaling mechanisms of endogenous antioxidant activity. They are continuously increasing in cutaneous melanoma, however in uveal melanoma, at the end of the treatment, there is a decrease of recorded serum levels of oxidative parameters. It is thus suggested that uveal melanoma leads to the installation of a more pronounced oxidative stress compared to cutaneous melanoma, with an intensification of oxygen metabolism and a lower response capacity of the body, possibly related to the increased aggressiveness of this malign cell type. This could explain the increased resistance to immunotherapy of uveal melanoma when compared to cutaneous melanoma. Our results can be useful in monitoring the tumor evolution under treatment. [ABSTRACT FROM AUTHOR]