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Background: Epigenetic modifications have been recognized as an important mechanism underlying carcinoma progression. DNA methylation plays an important role in cancer biology and represents potentially heritable changes in gene expression that do not involve DNA sequence. The aim of this study was to investigate promoter methylation of selected genes in sinonasal carcinoma by comparison with noncancerous sinonasal tissue. Methods: To search for epigenetic events (methylation in 25 tumor suppressor genes) we used MS-MLPA (Methylation-specific multiplex ligation-dependent probe amplification) to compare methylation status of 59 formalin fixed, paraffin embedded tissue samples of sinonasal carcinomas with 18 control samples. The most important changes in methylation were confirmed using MSP (Methylation specific PCR). Detected alterations in methylation were compared with clinicopathological characteristics. Results: Using a 20% cut-off for methylation (MS-MLPA), we found significantly higher methylation in GATA5 (P=0.0005), THSB1 (P=0.0002) and PAX5 (P=0.03) genes in the sinonasal cancer group compared to the control group. Methylation in five or more genes was associated with impaired overall survival (P=0.017). Conclusion: These findings provide evidence that alterations in methylation profile may be one of the major mechanisms in sinonasal carcinogenesis. In addition, changes in methylation could potentially be used as prognostic factors of sinonasal carcinoma and may have implications for future individualized therapy based on epigenetic changes.

Aims: Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA. Methods: Adenoma specimens were obtained from 206 patients during transsphenoidal resection. For quantitative analysis, reverse transcription and consequent real-time PCR with synthetic multilocus calibrators (SMC) were used. The obtained data were normalized to the number of transcripts of the beta-glucuronidase gene. Results: The use of SMC enabled the alignment of individual calibration functions for all the receptors. No relationships between the expression of the receptors and the tumor size, site of extension, gender or age at diagnosis were significant. In growth hormone-secreting adenomas, D2R and SSTR2 transcripts were extensively expressed, followed by ER1, SSTR5, SSTR3, and SSTR1. In patients with macroprolactinomas, transsphenoidal resection was indicated because dopamine agonists did not normalize prolactin levels. D2R, ER1 and SSTR1 transcripts were significantly transcribed. Corticotroph adenomas showed high levels of D2R and ER1 transcripts and lower amounts of SSTR2 and SSTR1 transcripts. SSTR5 transcripts were very low. Subjects with CNFA dominantly expressed D2R and ER1, followed by SSTR2 and SSTR3 mRNA. Conclusion: We evaluated SSTR1-SSTR5, D2R, and ER1 expressions in a large group of pituitary adenomas and we found that determining their individual expression profiles could help when choosing the optimal postoperative treatment.

Background: Activation of the immune system plays a pathogenic role in the process of myocardial remodeling in patients with supraventricular arrhythmias. The intensity of this process is associated with the effectiveness of electrical cardioversion and radiofrequency catheter ablation (RFA). The aim of this study was to test the ability of the biochip microarray to detect immune parameters in patients with supraventricular arrhythmias undergoing RFA treatment. Methods: We used a biochip-based microarray system to determine multiple immune parameters in a group of 35 patients who had undergone RFA for atrioventricular nodal reentry tachycardia (AVNRT), atrial flutter (AFL) and atrial fibrillation (AF). Results: Before the procedure, serum IL-6 and VEGF levels were significantly increased in patients with atrial fibrillation compared to patients with AVNRT (IL-6: 6.4±6.3 ng/L vs. 1.5±0.7 ng/L, P < 0.01; VEGF: 132.4±74 ng/L vs. 88.5±56.4 ng/L, P < 0.01). After the procedure, serum IL-6, VEGF, IFN-γ and MCP-1 levels significantly increased compared to baseline (IL-6: 5.2±4.8 ng/L vs. 2.9±2.1 ng/L, P < 0.01; VEGF: 195.8±160 ng/L vs. 119.8± 110 ng/L, P < 0.05; IFN-γ: 3.1±1.2 ng/L vs. 2.3±0.6 ng/L, P < 0.05; MCP-1: 104.1±84.5 ng/L vs. 54.5±50 ng/L, P < 0.05). Serum IL-6 and IFN-γ were associated with the number of RFA applications (IL-6: r = 0.56, n 33; IFN-γ: r = 0.47, n 33). Conclusions: This study showed that biochip-based microarray can be useful in the detection of immune activation in patients with arrhythmias and can detect myocardial injury after RF procedures.

Aims: While most antiepileptic drugs (AEDs) have been associated with various adverse effects on bone health, for the recently introduced lacosamide (LCM) no corresponding data have been published. The present study evaluates the effect of LCM on bone mineral density, bone turnover markers, and bone mechanical strength in a rat model. Methods: 16 orchidectomized Wistar rats were divided into control and experimental groups, 8 rats each. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). As bone metabolism markers, the concentrations of bone markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Results: Compared to the control group, we found lower BMD in the experimental group in the area of the left (8%) as well as the right femur (12%), all differences being statistically significant. In both femur diaphyses, but not in lumbar vertebrae, BMD was lower in the LCM group, suggesting a preferential effect on cortical bone. However, neither the thickness of the diaphyseal cortical bone nor the fragility in biomechanical testing was different between the groups. Of the bone metabolism markers, the significant decline was in procollagen type I N-terminal peptide (PINP) levels (37.4%), suggesting a decrease in osteoid synthesis. Conclusion: We assume then that long-lasting exposure to LCM can represent a certain risk to the health of bone in the setting of gonadal insufficiency. Further studies will be needed to confirm these findings and to determine how high the risk will be in comparison to the other AEDs.