Meta-Analysis of DNA Methylation and Expression in Liver Cancer Patients

Hepatocellular carcinoma (HCC), the most common liver cancer, is the second leading cause of cancer-related death worldwide. HCC is often diagnosed at late stages, for which there are no effective chemotherapies. Biomarkers unique to HCC patients could be used to detect HCC early and improve treatment. In the present project, we have performed a meta-analysis to compare the gene-specific DNA methylation and gene expression patterns of HCC patients as reported by four independent studies. Our goal was to discover the strongest changes that distinguish HCC from normal tissue. The relationship between methylation and expression in HCC was examined and genes epigenetically regulated in HCC were identified. The top changes within genes, gene families and pathways could be of interest in further investigations of potential HCC biomarkers. A significant correlation between DNA hypomethylation and gene activation and between DNA hypermethylation and gene silencing was found. CpG islands, commonly found in promoter regions, are predominantly hypermethylated in HCC, while CpGs outside of CpG islands are predominantly hypomethylated in gene bodies. 149 genes were found to be significantly differentially methylated between tumors and normal adjacent tissue, and 169 genes were found to be significantly differentially expressed. Genes identified for further research are GNG7, WNT5B, RXRG, HOXB7, and SMARCB1. No overlap was found between differentially expressed and methylated genes. Nevertheless, common gene families and pathways were identified where more potential biomarkers could be found in future studies

Loss of heterozygosity for Rb locus and pRb immunostaining in laryngeal cancer: a clinicopathologic, molecular and immunohistochemical study.

Several risk factors for the development of laryngeal cancer have been identified, such as smoking and alcohol consumption, but the molecular mechanisms related to the carcinogenesis in the larynx remain under investigation. In this context, deregulations of the cell-cycle-controling mechanisms, Rb-pathway in particular, have been suggested to be involved in the pathogenesis of laryngeal carcinoma. Our purpose was to investigate 13q14 LOH and the expression of Rb protein and their possible prognostic value in laryngeal cancer. The group of 67 patients with laryngeal cancer, surgically treated with minimum 5 years observation, was multi-variously analysed. LOH for Rb was investigated by PCR-based techniques using two microsatellite markers, D13S263 and D13S126, flanking the Rb locus. Amplification products from each polymorphism were fractionated by denaturing gel electrophoresis and detected by audioradiography. Immunohistochemical staining of paraffin specimens of laryngeal cancers was supervised by the use of monoclonal mouse antibodies IgG1 (Anti-Human Retinoblastoma Gene Product of Dako) in dilution of 1:50. Inactivation of Rb protein was assumed to represent the expression in 0.05). There was a strong association between the loss of Rb and supraglottic localisation of tumour in the larynx (p0.05 respectively). The genetic data were correlated with the expression of the Rb protein (p=0.001). All tumours with Rb-LOH were immunohistochemically Rb-negative. Inactivation of Rb protein was observed in 9/67 cases (13.49%) and was significantly correlated with the polymorphism of cancer cells, but not with the histological grading. We also found the correlation between reduction of Rb protein and the size of primary tumour (T) (p=0.03) and local recurrence (p=0.035). There was no significant dependence between the level of Rb protein and other histopathological and clinical features (p>0.05). To conclude, analysis of 13q14 LOH enables the assessment of biology of laryngeal cancer and it can be a prognostic factor in overall survival. Immunohistochemical analysis of Rb protein expression in neoplastic cells made it easier to evaluate the mechanisms of cancerogenesis in laryngeal cancer and is closely related to genetic alteration in Rb locus

Input of heavy metals to the forest floor as the result of zinc smelter pollution in southern Poland

The aim of this study was to assess the impact of zinc smelter on heavy metals concentration in the litter fall collected from three different sites in Olkusz Forest located in southern Poland. Furthermore the study was designed to investigate the input of these metals to the forest floor. Three forest areas Podlesie I and Podlesie II located 3 and 4 km south-east from Bukowno zinc smelter and Cegielnia situated 6 km north-east from the smelter were selected. At the beginning of September 2006 five litter traps were set at each site. The quantity of litter fall, along with percent age composition of each species, were estimated for an area of 1m^2. The concentration of Cd, Pb, Cu, Zn and Fe in the litter fall and leaves of four main tree species were analysed. The input of these metals to the forest floor were determined. The input of cadmium ranged from 204 μg m^2 at Cegielnia to 1340 μg m^2 at Podlesie I. The input of lead was higher than cadmium and varied from 1031 μg m^2 at Cegielnia to 3252 μg m^2 at Podlesie II. The input of zinc and iron were about 10 times than cadmium and lead. The less input of all invesigated metals was noticed in control site located at WNP. for those metals. The high input of heavy metals to the forest floor may have negative effects on investigated part of Olkusz forest ecosystem

Modelling of the Knitting Process during the Knitting-in of Elastomeric Threads Using Knitting Machines with Relanit and Classic Knitting Zone

An analysis of the knitting process during the knitting-in of elastomeric threads using knitting machines with a Relanit and classic knitting zone was made on the basis of simulations considering a numerical model which takes into account the most important parameters of the knitting process, viscoelastic properties of the thread and geometrical parameters of the knitting zone. The conditions of forming stitches from classic cotton yarn were presented for comparison. The results of the simulation tests were verified experimentally on a computer-aided knitting machine with a classic knitting zone

Application of primary cell cultures of laryngeal carcinoma and laser scanning cytometry in the evaluation of tumor reactivity to cisplatinum.

Unsatisfactory effects of treatment of laryngeal carcinoma patients stimulate the clinicians as well as researchers to develop new more effective treatment models and to find new reliable prognostic factors. The aim of the present study was the evaluation of the use of primary cell cultures of the laryngeal carcinoma and laser scanning cytometry (LSC) in the assessment of tumor reactivity to cisplatinum. Nineteen primary cultures of laryngeal carcinoma cells established from fragments of laryngeal carcinoma infiltrations were cultured with or without cisplatin, stained with monoclonal antibodies against P53 and BCL-2 proteins and analyzed by LSC. Cisplatin added to the culture medium leads to the significant increase of P53 expression and decrease of BCL-2 expression. Moreover, changes of P53 and BCL-2 expressions were significantly correlated. Our findings of apoptosis regulatory mechanisms could be useful in patient qualification for the chemotherapeutic follow-up treatment

Strategia leczenia ANN w obliczu zagrożeń współczesnego świata

Alergiczny nieżyt nosa (ANN) jest najczęstszą postacią alergii, która dotyczy – jak wykazały badania epidemiologiczne – prawie 25% populacji. ANN wpływa znacząco na jakość życia chorego, a im cięższa postać choroby, tym większe ryzyko rozwoju astmy oskrzelowej. Jednym z czynników wpływających na nasilenie objawów i stopień ich kontroli jest zanieczyszczenie powietrza. U niektórych chorych, mimo właściwego leczenia, obserwuje się utrzymywanie lub tylko częściowe ustąpienie dolegliwości (niekontrolowany alergiczny nieżyt nosa). Może prowadzić to do nasilenia chorób towarzyszących – zapalenia zatok przynosowych, zapalenia ucha środkowego i astmy – zarówno u dzieci, jak i u dorosłych. Postępowanie w alergicznym nieżycie nosa, zgodnie ze standardami, polega na: edukacji chorego, eliminacji z otoczenia alergenu i czynników nasilających przebieg choroby, dobraniu właściwej farmakoterapii oraz swoistej immunoterapii alergenowej. Na wybór stosowanego leku przeciwhistaminowego wpływa wiele czynników, m.in. możliwość bezpiecznego zwiększenia jego dawki

Lymphocytes Studied by Raman Microspectroscopy

The Raman spectroscopy detects the interaction of the incident light with the electrons in the illuminated molecule. The use of Raman spectroscopy to investigate biological molecular structures and the recognition of their particular functional groups have been growing rapidly, and nowadays the use of Raman spectroscopy has expanded toward the cellular level. The activation of lymphocytes occurs when they are exposed to viruses or other foreign antigens. We have observed that Raman spectroscopy can be used to screen the activation of lymphocytes during viral infection. We have indicated the bands that reveal differences between activated and intact cells. The most important marker of the lymphocyte activation process is the prominent 521 cm−1 disulfide band which marks the immunoglobulin formation. The blood from the patients with viral infections, e.g., mononucleosis, and from healthy volunteers was obtained by venipuncture during hospitalization in the University Hospital in Kraków

Genetic polymorphisms in DNA base excision repair gene XRCC1 and the risk of squamous cell carcinoma of the head and neck

<p>Abstract</p> <p>Background</p> <p>The genes of base excision repair (BER) pathway have been extensively studied in the association with various human cancers. We performed a case-control study to test the association between two common single nucleotide polymorphisms (SNPs) of <it>XRCC1 </it>gene with human head and neck squamous cell carcinoma (HNSCC).</p> <p>Methods</p> <p>The genotype analysis of Arg194Trp and Arg399Gln gene polymorphisms for 92 HNSCC patients and 124 controls of cancer free subjects, in Polish population were performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP) with endonuclease <it>Msp</it>I.</p> <p>Results</p> <p>No altered risk has been found individually for these SNPs, however haplotypes analysis showed high association with head and neck cancer. The highest frequency, according to wild-type of Arg194Arg and Arg399Arg genotypes, was identified for Arg194Trp-Arg399Arg haplotype (OR, 2.96; 95% CI, 1.01–8.80).</p> <p>Conclusion</p> <p>Finally, we identified the combined Arg194Trp-Arg399Arg genotype of base excision repair gene <it>XRCC1 </it>that was associated with HNSCC and may have an impact on identification of a high-risk cancer population.</p

Digit ratio (2D:4D), laryngeal cancer and vocal fold leukoplakia

Background - To date, there are no studies that have analyzed the possible influence of exposure to prenatal sex hormones on the risk of laryngeal cancer (LC) and premalignant laryngeal lesion—vocal fold leukoplakia (VFL). Digit ratio (2D:4D) is suggested to be a proxy of prenatal sex hormone exposure. Objective - To examine 2D:4D in patients with LC and clarify if it could add to the verified risk factors in estimating the overall risk of LC. Methods - 511 subjects participated in the study. The study group included 269 patients: with LC (N = 114, 64 men) and VFL (N = 155, 116 men). Controls included 242 healthy individuals (66.40 ± 4.50 years (106 men)). Results - Predictive models estimating the risk of VFL and LC in women, based solely on predictors like smoking and alcohol consumption had a lower area under the ROC curve (AUC) than the model with left 2D:4D. AUC for the model estimating the likelihood of VFL increased from 0.83 to 0.85, and for LC from 0.76 to 0.79. Conclusions - Low left 2D:4D may be associated with an increased risk of developing leukoplakia and laryngeal cancer in women. In the case of laryngeal cancer, left 2D:4D may serve as additional variable (to other known risk factors, such as smoking and/or alcohol consumption), which can improve cancer risk prediction