Abstrakt
Brain tumors are the leading cause of cancer-related death in the US in patients under age of 35. They are divided into primary and secondary (metastatic) that are more frequent in adults (melanoma, lung carcinoma, renal cell carcinoma and thyroid carcinoma as into brain mostly metastasizing).
Metallomics can be defined as comprehensive analysis of the entirety of metal and metals containing proteins within cells and tissues. Approximately 1/3 of proteins are associated with some metals.
Moreover, some drugs contain a metal in their structure and are referred to as metallodrugs.Up-to-date, the greatest knowledge has been gathered in the field of metalloproteins containing zinc because it has been shown to be not only a structural component, but also a signaling substance in number of cascades and a cofactor of many important enzymes. On cellular level, key cellular processes such as proliferation, differentiation and apoptosis have been connected with its signaling.
In the field of metallomics of brain tumor, there is still little known but our knowledge is rapidly growing. On other metals in brain tumors, there are only limited reports as the grade of glioma correlated with the Fe(II) to Fe(III) ratio in the tissue.
However, this relationship cannot be explained by the occurrence of hypoxic regions in the tissue because of lack of correlation between the average oxidation state of iron and hypoxia. In the case of non-essential metallomics, the cytotoxic effect of platinum drugs consists of DNA adducts formation, especially to the most nucleophilics bases - guanine and adenine.
This phenomenon cases DNA strands crossing and subsequent interference with normal transcription and/or replication. Moreover, platinum drugs influence the cell cycle of tumor cells, which can also influence their effect.
In addition, many potential platinum- binding molecules are available including RNA and sulfur-containing biomolecules such as glutathione and metallothioneins in the cyto