[Selenium: its antioxidant effects and issues in selenium supply]. / A szelén antioxidáns hatásai és a szelénellátottság kérdései.

The author first summarizes briefly the antioxidant effects attributed to selenium. Literature data on the selenium supply in Hungary are reviewed in detail, also noting some important international reports. Hungarian soils are selenium deficient and this is reflected partly in selenium content of the plants, too. Selenium supplementation has been generally applied to most livestock since the 1980s in Hungary in order to prevent diseases associated with selenium deficiency. There are little data on the selenium content of Hungarian foodstuffs; therefore, selenium content of important foodstuffs available in the European Union is reviewed in detail. Data on selenium concentrations in human plasma or serum are scarce, and the results depend substantially on the analytical methods applied. In conclusion, Hungary is a country with marginal selenium deficiency, and this may play a role in the pathogenesis and poor treatment results of several diseases.

Increase of α-SMA(+) and CK (+) cells as an early sign of epithelial-mesenchymal transition during colorectal carcinogenesis.

Our aim was to examine cell transition events by detecting the frequency of intrapithelial α-smooth muscle actin (SMA)(+)/cytokeratin (CK)(+) cells during colorectal adenoma-carcinoma sequence, in relation to E-cadherin expression. Our further aim was to determine the proliferative activity of intraepithelial α-SMA(+) cells. Histologically healthy, adenoma, and colorectal cancer (CRC) biopsy samples were taken during routine colonoscopy and were included into tissue microarrays (TMAs). Slides immunostained for Ki-67, α-SMA, E-cadherin and pan-cytokeratin were digitalized and analyzed by using a digital microscope software. The proportion of α-SMA(+)/CK(+) cells was significantly higher in CRC samples (3.34 ± 1.01%) compared to healthy (1.94 ± 0.69%) or adenoma (1.62 ± 0.78%) samples (p < 0.01). E-cadherin expression negatively correlated with the number of α-SMA(+) cells. The majority of intraepithelial α-SMA(+) cells were in the proliferative phase. During tumor progression, the appearance of dot-like α-SMA staining in CK positive cells may indicate the initial phase of the epithelial-to-mesenchymal transition (EMT). The high proportion of intraepithelial α-SMA(+) proliferating cells may refer to their increased plasticity compared to differentiated cells. The negative correlation between E-cadherin and intraepithelial α-SMA expression suggests that EMT is facilitated by a loss of epithelial cell contact.

[Age-related microscopic and molecular changes of the human colon, and their role in the development of colorectal cancer in elderly people]. / Az öregedés mikroszkópos és molekuláris jelei a vastagbélben, valamint ezek lehetséges szerepe az idoskori vastagbélrák kialakulásában.

The gastrointestinal effect of aging, the recognition of its molecular background and the mapping its connections with several diseases like sporadic colorectal cancer of elder people are a new and promising area of molecular gastroenterology. Nowadays, it is a well-known fact that some age-related molecular changes (e.g.: DNA methylation, telomere shortening) can be detected in several types of colorectal cancers. The known epidemiologic and molecular biologic features of sporadic colorectal cancer are not enough to explain the genetic, gene expression or epigenetic changes that may be involved in the increase of the disease over 45-50 age years. The connections of these alterations to the process of aging are also unclear. The understanding and custom-tailored modification of these mechanisms are of great clinical importance regarding of prevention and modern therapeutic strategies. In this review, we aimed to summarize the age-related microscopic and molecular changes of the human colon, as well as their role in the development of colorectal cancer of the elder people.

Elevated osteopontin expression and proliferative/apoptotic ratio in the colorectal adenoma-dysplasia-carcinoma sequence.

Colorectal cancer progression is characterized by altered epithelial proliferation and apoptosis and by changed expression of tumor development regulators. Our aims were to determine the proliferative/apoptotic epithelial cell ratio (PAR) in the adenoma-dysplasia-carcinoma sequence (ADCS), and to examine its association with osteopontin (OPN), a previously identified protein product related to cancer development. One mm diameter cores from 13 healthy colons, 13 adenomas and 13 colon carcinoma samples were included into a tissue microarray (TMA) block. TUNEL reaction and Ki-67 immunohistochemistry were applied to determine the PAR. The osteopontin protein was also immunodetected. Stained slides were semiquantitatively evaluated using digital microscope and statistically analyzed with logistic regression and Fisher's exact test. The PAR continuously increased along the ADCS. It was significantly (p < 0.001) higher in cancer epithelium (8.84 ± 7.01) than in adenomas (1.40 ± 0.78) and in normal controls (0.89 ± 0.21) (p < 0.001). Also, significant positive correlation was observed between elevated PAR and the expression of osteopontin. Cytoplasmic OPN expression was weak in healthy samples. In contrast, cytoplasmic immunoreaction was moderately intensive in adenomas, while in colon cancer strong, diffuse cytoplasmic immune staining was detected. Increasing PAR and OPN expression along ADCS may help monitoring colorectal cancer progression. The significantly elevated OPN protein levels we found during normal epithelium to carcinoma progression may contribute to the increased fibroblast-myofibroblast transition determining stem cell niche in colorectal cancer.

Applicability of antibody and mRNA expression microarrays for identifying diagnostic and progression markers of early and late stage colorectal cancer.

The exact molecular background and the connection between protein and mRNA expression in colorectal cancer (CRC) development and progression are not completely elucidated. Our purposes were the identification of protein markers of colorectal carcinogenesis and progression using protein arrays and validation on tissue microarrays. The connection between antibody and mRNA expression array results was also examined. Using cancerous and adjacent normal samples from 10 patients with early and 6 with advanced CRC, 67 differentially expressed genes were identified between normal and cancerous samples. A marker set containing 6 proteins (CCNA1, AR, TOP1, TGFB, HSP60, ERK1) was developed which could differentiate normal specimen, early and late stage CRC with high sensitivity and specificity. Dukes D stage samples were analyzed on HGU133plus2.0 microarrays. In these samples, mRNA and protein expression of 143 genes showed strong positive correlations (R2>0.8), while a negative correlation (R2>0.9) was found in case of 95 genes. Based on our results a correlation could be established between transcriptome and antibody array results, hence the former may be used as a high-capacity screening method before applying antibody arrays containing already planned targets. Antibody microarrays may have a fundamental importance in testing of marker combinations and future application in diagnostics of tumorous diseases.

[Free circulating DNA based colorectal cancer screening from peripheral blood: the possibility of the methylated septin 9 gene marker]. / Szabad DNS-alapú vastagbéldaganat-szurés perifériás vérbol: a metilált szeptin-9 génmarker lehetoségei.

DNA methylation acts in early tumorigenesis. Its detection is possible either from tissue, stool or peripheral blood. Septin 9 is a sensitive methylation marker, which has been studied in several cancers such as breast and ovarian tumors and in neurological or hematological diseases. Septin proteins have an important role from cytoskeleton organisation to development of embryonal pattern. Nowadays intensive researches are going on about the relation between the septin 9 gene hypermethylation and colorectal cancer development.

Serum selenium concentrations correlate significantly with inflammatory biomarker high-sensitive CRP levels in Hungarian gestational diabetic and healthy pregnant women at mid-pregnancy.

Selenium is an essential trace element and a component of various enzymes with antioxidant functions. High-sensitive C-reactive protein (hsCRP) is an early indicator of increased lipid peroxidation. The serum selenium concentration, lipid parameters, and hsCRP values of gestational diabetic pregnant women (GD), control pregnant women (CP), and healthy nonpregnant controls (HC) were compared. Blood was taken between the 24th and the 28th week of pregnancy when the oral glucose tolerance test was performed. Selenium concentration was determined by atomic absorption spectrometry after hydride generation. HsCRP was measured by immunturbidimetry. HC had significantly higher serum selenium concentrations than GD and CP women (HC = 77.4 +/- 14.82, GD = 51.7 +/- 11.62, and CP = 40.5 +/- 8.03 microg/l, respectively). HsCRP values of both GD and nondiabetic pregnant women were significantly higher compared to controls. Significant negative correlations were found between serum selenium and total cholesterol, low-density lipoprotein cholesterol, and hsCRP values indicating that low selenium levels are associated with increased lipid peroxidation. Serum selenium concentrations of Hungarian pregnant women are low compared to internationally published data.