Michal Masarik

Insight to physiology and pathology of zinc(II) ions and their actions in breast and prostate carcinoma.

Zinc(II) ions contribute to a number of biological processes e.g. DNA synthesis, gene expression, enzymatic catalysis, neurotransmission, and apoptosis. Zinc(II) dysregulation, deficiency and over-supply are connected with various diseases, particularly cancer. 98 % of human body zinc(II) is localized in the intracellular compartment, where zinc(II) is bound with low affinity to metallothionein (MT). Zinc transporters ZIP and ZnT maintain transmembrane transport from/to cells or organelles. Imbalance of their regulation is described in cancers, particularly prostate (down-regulated zinc transporters ZIP1, 2, 3 and ZnT-2) and breast, notably its high-risk variant (up-regulated ZIP6, 7, 10). As a result, intracellular and even blood plasma zinc(II) levels are altered. MT protects cells against oxidative stress, because it cooperates with reduced glutathione (GSH). Recent studies indicate elevated serum level of MT in a number of malignancies, among others in breast, and prostate. MT together with zinc(II) affect apoptosis and proliferation, thus together with its antioxidative effects it may affect cancer. To date, only little is known about the influence of zinc(II) and MT on cancer, while these compounds may play an important role in pathogenesis. This review concludes current data regarding the impact of zinc(II) on the pathogenesis of breast and prostate cancers with potential outlines of new, targeted therapy and prevention. Moreover, blood plasma zinc(II) and MT levels and dietary zinc(II) intake are discussed in relation to breast and prostate cancer risk.

Relevance of infection with human papillomavirus: The role of the p53 tumor suppressor protein and E6/E7 zinc finger proteins (Review)

Human papillomaviruses (HPV) are small circular, double-stranded DNA viruses infecting epithelial tissues. HPV types can be classified both as high-risk or low-risk. Of the more than 120 different identified types of HPV, the majority are involved in infections of the genital tract, cancer of the cervix, vulva, vagina and penis, and of non-anogenital localizations, such as the head and neck areas. From the point of view of the infection, human papillomaviruses have developed several molecular mechanisms to enable infected cells to suppress apoptosis. This review provides a comprehensive and critical summary of the current literature that focuses on cervical carcinoma and cancer of the head and neck caused by HPV. In particular, we discuss HPV virology, the molecular mechanisms of carcinogenesis, the role of the tumor suppressor protein p53 and the E6/E7 zinc finger proteins. Classification of HPV according to diagnosis is also described.

Prostate Cancer, miRNAs, Metallothioneins and Resistance to Cytostatic Drugs

MicroRNAs (miRNAs) translationally repressing their target messenger RNAs due to their gene-regulatory functions play an important but not unexpected role in a tumour development. More surprising are the findings that levels of various miRNAs are well correlated with presence of specific tumours and formation of metastases. Moreover, these small regulatory molecules play a role in the resistance of cancer cells to commonly used anti-cancer drugs, such as cisplatin, anthracyclines, and taxanes. In that respect, miRNAs become very attractive target for potential therapeutic interventions. Improvements in the sensitivity of miRNAs detection techniques led to discovery of circulating miRNAs which became very attractive non-invasive biomarker of cancer with a substantial predictive value. In this review, the authors focus on i) oncogenic and anti-tumour acting miRNAs, ii) function of miRNAs in tumour progression, iii) possible role of miRNAs in resistance to anticancer drugs, and iv) diagnostic potential of miRNAs for identification of cancer from circulating miRNAs with special emphasis on prostate cancer. Moreover, relationship between miRNAs and expression of metallothionein is discussed as a possible explanation of resistance against platinum based drugs.

Determination of common urine substances as an assay for improving prostate carcinoma diagnostics

Recently, interest in the identification of non-invasive markers for prostate carcinoma detectable in the urine of patients has increased. In this study, we monitored the abundance of potential non-invasive markers of prostate carcinoma such as amino acid sarcosine, involved in the metabolism of amino acids and methylation processes, ongoing during the progression of prostate carcinoma. in addition, other potential prostate tumor markers were studied. The most significant markers, prostate-specific antigen (PSA) and free PSA (fPSA), already used in clinical diagnosis, were analyzed using an immunoenzymometric assay. Whole amino acid profiles were also determined to evaluate the status of amino acids in patient urine samples and to elucidate the possibility of their utilization for prostate carcinoma diagnosis. To obtain the maximum amount of information, the biochemical parameters were determined using various spectrophotometric methods. All results were subjected to statistical processing for revealing different correlations between the studied parameters. We observed alterations in most of the analyzed substances. Based on the results obtained, we concluded that the specificity of prostate carcinoma diagnosis could be improved by determination of common urine metabolites, since we compiled a set of tests, including the analysis of sarcosine, proline, PSA and uric acid in the urine. These metabolites were not observed in the urine obtained from healthy subjects, while their levels were elevated in all patients suffering from prostate carcinoma.