Head and neck squamous cell carcinoma (HNSCC) is the sixth most common human malignancy in the world, with high mortality and poor prognosis for patients. Among the risk factors are tobacco and alcohol intake, human papilloma virus, and also genetic and epigenetic modifications. Many studies show that epigenetic events play an important role in HNSCC development and progression, including DNA methylation, chromatin remodeling, histone posttranslational covalent modifications, and effects of non-coding RNA. Epigenetic modifications may influence silencing of tumor suppressor genes by promoter hypermethylation, regulate transcription by microRNAs and changes in chromatin structure, or induce genome instability through hypomethylation. Moreover, getting to better understand aberrant patterns of methylation may provide biomarkers for early detection and diagnosis, while knowledge about target genes of microRNAs may improve the therapy of HNSCC and extend overall survival. The aim of this review is to present recent studies which demonstrate the role of epigenetic regulation in the development of HNSCC.

A phenomenon of increasing resistance of Candida spp. to azoles has been observed for several years now. One of the mechanisms of lack of sensitivity to azoles is associated with CDR1, CDR2, MRD1 genes (their products are active transport pumps conditioning drug efflux from pathogen's cell), and ERG11 gene (encoding lanosterol 14α-demethylase). Test material was 120 strains of Candida albicans (60 resistant and 60 susceptible to azole drugs) obtained from clinical samples. The first stage of experiment assessed the expression of CDR1, CDR2, MDR1 and ERG11 genes by Q-PCR. The impact of ERG11 gene's mutations on the expression of this gene was analysed. The final stage of the experiment assessed the level of genome methylation of Candida albicans strains. An increase in the expression of CDR2, MDR1 and ERG11 was observed in azole-resistant strains of Candida albicans in comparison to strains sensitive to this class of drugs. Furthermore, 19 changes in the sequence of ERG11 were detected in tested strains. Four of the discovered mutations: T495A, A530C, G622A and A945C led to the following amino acid substitutions: D116E, K128T, V159I and E266D, respectively. It has also been found that statistically five mutations: T462C, G1309A, C216T, C1257T and A945C affected the expression of ERG11. The applied method of assessing the level of methylation of Candida albicans genome did not confirm its role in the development of resistance to azoles. The results indicate however, that resistance of Candida albicans strains to azole drugs is multifactorial.

Epigenetics is a branch of science that focuses on mechanisms related to control and modification of expression of genetic material without any changes to its sequences. Such mechanisms include post-translational modifications of histones. It is widely known that carcinogenesis is related to...

Background: Oral squamous cell carcinoma (OSCC) is one of the most commonly detected neoplasms worldwide. Not all mechanisms associated with cell cycle disturbances are known in OSCC. Examples of genes involved in the control of the cell cycle are CDKN2A, MDM2, E2F2 and LTF. The aim of this study was to examine the possible association between CDKN2A, MDM2, E2F2 and LTF mRNA expression and influence on clinical variables. Methods: The study group consisted of 88 Polish patients. The gene expression levels were assessed by quantitative reverse transcription PCR. Results: We found no statistically significant differences in the expression level of CDKN2A, MDM2, E2F2 and LTF genes in tumour samples compared to margin samples. No association was found between the gene expression levels and clinical parameters, except E2F2. The patients with G2 tumours had a significantly higher gene expression level of E2F2 than patients with low-grade G1 tumours. Conclusions: We have not demonstrated that a change in expression profiles of genes has a significant impact on the pathogenesis of OSCC. It may also be useful to conduct further studies on the use of E2F2 expression profile changes as a factor to describe the invasiveness and dynamics of OSCC development.

Numerous investigations, and especially in vitro studies, indicate that TGF-β1 may act as an important regulator of bone remodelling. Thus, it could be expected that disturbances of this cytokine production observed by several researchers might play a role in the mechanism leading to the development of osteoporosis in girls with anorexia nervosa (AN). The aim of the study was to determine whether 1) girls with AN exhibited a relationship between TGF-β1 and bone metabolism (as assessed based on serum OC and CTx concentrations) and 2) whether OPG and sRANKL might modify the possible relationship between TGF-β1 and bone metabolism. Serum concentrations of TGF-β, OC, CTx, OPG, and its soluble ligand sRANKL were determined by ELISA in 60 girls with AN and in 20 healthy controls (C). All study participants were aged 13 to 17 years. Body weight, BMI, BMI-SDS and the Cole index, serum TGF-β1, OC, CTx, and the OPG/sRANKL ratio were significantly reduced, while OPG and sRANKL levels were significantly increased, in girls with AN compared to healthy participants. BMI and the Cole index correlated negatively and significantly with serum CTx and OPG (AN group) or CTx only (groups C and C + AN). Girls with AN showed a positive and significant correlation between the Cole index and serum TGF-β1. The combination group (C + AN) showed a positive and significant correlation between BMI, the Cole index, and the OPG/sRANKL ratio and TGF-β1 concentration, while TGF-β1 correlated positively and significantly with OC concentrations and the OPG/sRANKL ratio. The Cole index and BMI were identified to be significant and independent predictors of CTx (C, AN, and C+AN groups) and OPG (AN group); the Cole index, BMI, and TGF-β1 independently predicted the OPG/sRANKL ratio (C, AN, and C + AN groups); TGF-β1 was found to be an independent predictor of OC (C + AN group). Changes in bone markers, OPG, and/or OPG/sRANKL ratio observed in girls with AN are associated with changes in serum TGF-β1 concentrations. TGF-β1 suppression in girls with AN might lead to disturbances in the relationship between bone metabolism and the OPG/sRANKL system, which, in turn, might compromise the mechanism compensating for bone remodelling disturbances. (Endokrynol Pol 2016; 67 (5): 493-500).