Klin Onkol 2001; 14(1): 25-30.
Abstract:
Summary:The tumour suppressor protein p53 is a stress-activated transcription factor the activity of which is required for regulating cellular response to stress and DNA damage. This protein is inactivated in many sporadic human tumours by point mutations in the p53 gene, leading to disruption of its ability to function at DNA damage checkpoint. Asubset of tumours expressing wild-type p53 protein exists that are not able to induce G1-cell cycle arrest allowing DNA reparation or apoptosis in response to DNA damage. Melanoma cells are highly radioresistant, in spite of expressing wild-type p53 protein and they also do not respond to cytotoxic treatment.
Subject: The current therapeutic protocols available for the treatment of patients with high-risk melanoma remain ineffective. Similarly, the search for new more potentagents has not been successful. The goal of our study was to employ the short term cultivation of melanoma fragments and evaluate this system for testing the response to different potential anticancer drugs. Material and methods:We analyzed the p53 and MDM2 proteins using immunohistochemistry and immunochemistry in melanoma fragments cultured in media with addition of roscovitine and cisplatin.
Results:The inhibitor of cyclin-dependent protein kinases roscovitine is able to induce functional p53 protein in studied melanoma fragments in comparison with the cisplatin acting viaDNA damage that is unable to induce the p53 protein.
Conclusions:Short term cultivation of tumour fragments and evaluation of biochemical parameters show usability of this tool for studying effect of cytotoxic drugs as well as for prediction of particular tumour response to therapy.
