Anton Dzian

GENE POLYMORPHISMS OF BIOTRANSFORMING ENZYMES (GSTS) AND THEIR ASSOCIATION WITH LUNG CANCER IN THE SLOVAKIAN POPULATION

ObjectiveThe aim of present study was to present the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, and P1) and to investigate the association of these polymorphisms with lung cancer risk in the Slovakian population.Material and methodsThe study encompassed 160 lung cancer cases and 220 controls. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods. We determined the genotype distribution of all these genes and their combinations. The association between specific genotypes and the development of lung cancer were examined using logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI).ResultsWe found that the GSTM1 null genotype (OR = 1.6; 95% CI = 1.03-2.4; χ2 = 4.08, and P = 0.04) was associated with elevated risk. A significant correlation also was found for the combined genotypes of GSTM1 null and GSTP1 Ile/Val and Val/Val (OR = 2.01; 95% CI = 1.1-6.1; χ2 = 3.6, and P = 0.02) and GSTM1 null and GSTT1 positive (OR = 2.00; 95% CI = 1.2-3.2; χ2 = 7.3, and P = 0.006).ConclusionsWe conclude that the genotype of metabolizing enzymes and allelic combinations underscore the risk for lung cancer. Individual risk assessment may be further improved by increasing the number of polymorphisms studied and combining them with the traditional epidemiological risk factor.

Implantation of a 3D-printed titanium sternum in a patient with a sternal tumor

BackgroundPrimary malignant or metastatic sternal tumors are uncommon. A subtotal or total sternectomy can offer a radical form of treatment. The issue is to restore the structural integrity of the chest wall.Case presentationWe report the implantation of an individualized 3D–printed titanium sternum in a patient with a sternal tumor.ConclusionsWe believe that tridimensional print technologies may also change the strategy of chest wall reconstruction.

The Role of Dysregulated MicroRNA Expression in Lung Cancer

MicroRNAs (miRNAs) are a class of small single-stranded non-protein-coding RNAs that play important regulatory roles in many cellular processes including cell proliferation, differentiation, growth control, and apoptosis. They regulate gene expression on the posttranscriptional level by translational repression, mRNA cleavage, or mRNA degradation in various physiological and pathological processes. In addition, some miRNAs can function as oncogenes or tumor suppressors, so they can regulate several genes that play important roles in tumorigenesis. It was found that miRNAs are directly involved in many types of cancer, including lung cancer. Lung cancer is the leading cause of cancer mortality worldwide with a substantially low survival rate. In this work, we summarize recent findings related to miRNAs mechanisms of action and the role of their dysregulated expression in lung tumorigenesis. We describe the most important miRNAs involved in lung cancer development and targets of their activity. The understanding of the miRNA regulation in cancer may help better understand the molecular mechanisms of tumorigenesis and their importance in cancerous transformation.

Endovascular stenting in malignant obstruction of superior vena cava

Highlights • Lymphomas are a common cause of SVCS in young age.• HL may present as SVCS.• Pathological confirmation of diagnosis should be done before initiating therapy while dealing with a case of SVCS.• SVC stenting is effective and has few complications in patients with SVCS.

Polymorphisms of Selected DNA Repair Genes and Lung Cancer in Chromium Exposure

Chromium is a well-known mutagen and carcinogen involved in lung cancer development. DNA repair genes play an important role in the elimination of genetic changes caused by chromium exposure. In the present study, we investigated the polymorphisms of the following DNA repair genes: XRCC3, participating in the homologous recombination repair, and hMLH1 and hMSH2, functioning in the mismatch repair. We focused on the risk the polymorphisms present in the development of lung cancer regarding the exposure to chromium. We analyzed 106 individuals; 45 patients exposed to chromium with diagnosed lung cancer and 61 healthy controls. Genotypes were determined by a PCR-RFLP method. We unravelled a potential for increased risk of lung cancer development in the hMLH1 (rs1800734) AA genotype in the recessive model. In conclusion, gene polymorphisms in the DNA repair genes underscores the risk of lung cancer development in chromium exposed individuals.

Association of EGF and p53 gene polymorphisms and colorectal cancer risk in the Slovak population

During the transformation process single nucleotide polymorphisms (SNPs) of key genes, such as p53 Arg72Pro or EGF A61G, may mediate various cellular processes. These variants may be associated with colorectal cancer risk (CRC), but conflicting findings have been reported. The purpose of this study was to determine the association of the SNPs in 5′ UTR of EGF A61G and p53 Arg72Pro and CRC in the Slovak population. The present case-control study was carried out in 173 confirmed CRC patients and 303 healthy subjects. Genotyping was performed by PCR-RFLP methods. Significant association was observed between age and CRC risk (p=0.001). Lower CRC risk was seen in younger patients carrying genotype p53 Arg72Pro (0.14; 95% CI 0.02–0.99, p=0.049). Gender-stratified analysis showed a significant inverse association of the polymorphism EGF G61G with CRC risk (0.48; 95% CI 0.2–0.9, p=0.04) only in male patients. Tumour site genotype distribution revealed that female patients with localized colon cancer were significantly associated with p53 Pro72Pro genotype (4.0; 95% CI 1.27–12.7, p=0.04) whereas the cancer of rectosigmoid junction was associated with the EGF G61G genotype (4.5; 95% CI 1.2–16.97, p=0.02). Combination of p53 Arg72Pro or EGF A61G polymorphisms were not associated with CRC risk by using logistic regression.

Differential mRNA expression of the main apoptotic proteins in normal and malignant cells and its relation to in vitro resistance

BackgroundApoptosis plays an important role in the development and homeostasis of multicellular organisms and its deregulation may result in many serious diseases, including cancer. Now it is clear that some oncogenic mutations disrupt apoptosis, leading to tumour initiation, progression or metastasis. Here, expression of apoptotic genes in context of drug resistance was investigated.MethodsWe examined total of 102 samples from leukemic patients (n = 60) and patients with solid tumours (n = 42). We used RT-PCR to determine the levels of mRNA expression and the in vitro chemoresistance of leukemic cells was evaluated using the MTT assay.ResultsWe found statistically significant increase in mRNA expression of all investigated proteins (p53, BAX, Bcl-2 and Bcl-XL) between the leukemia samples and leukocytes from healthy volunteers. We did not find any significant difference in mRNA levels among the solid tumour samples. Notably, we showed a significant positive correlation in both leukemic and solid tumour patient groups between p53 and BAX mRNA. We found that the highest values for the Bcl-2/BAX ratio were in solid tumours in comparison to leukemic cells or normal leukocytes. Moreover, we assessed the impact of p53 and BAX mRNA levels on the sensitivity of the leukemic cells to selected cytostatics.ConclusionsElevated levels of p53 and BAX mRNA may indicate cellular response to possible changes in genomic DNA integrity associated with malignant transformation. We suggest that the BAX gene is regulated by the p53 protein but the initiation of apoptosis through the transcription activation of BAX is blocked by the high levels of Bcl-2. Given that the apoptosis resistance mechanisms are different among oncological patients as well as stages of identical malignancy cases, personalized and specific combination therapy is proposed to be more effective in clinical application.

Gene polymorphisms of selected biotransformation enzymes and lung cancer development with respect to chromium exposure

Introduction: Formamidines pesticides have been described to induce permanent effects on development of monoaminergic neurotransmitters systems. The mechanisms that induce these effects are not known but it has been suggested that these effects could be related to monoamino oxidase (MAO) inhibition. Chlordimeform is a formamidine pesticide which is a very weak inhibitor of MAO although it has been also described to produce neurodevelopmental toxicity. Objectives and methods: The effects of maternal exposure to chlordimeform on brain region serotonin levels of male and female offspring rats at 60 days of age were evaluated. Maternal and offspring body weight, physical and general activity development were unaffected by the exposure of dams to chlordimeform (5 mg/kg bw, orally on days 6–21 of pregnancy and 1–10 of lactation). Male and female offspring were sacrificed at 60 days of age and possible alterations in the content and metabolism of 5-HT was determined in brain regions by HPLC. Results: The results showed that this neurotransmitter system was altered in a brain regional-related manner. In male and female offspring, chlordimeform induced a significant decrease in the striatum and prefrontal cortex 5-HT and its metabolite 5-HIAA levels. This effect was with statistical distinction of sex in the prefrontal cortex. In contrast, chlordimeform caused an increase in 5-HT and 5-HIAA content in the hippocampus in male and female offspring with sex interaction. Chlordimeform evoked increases in 5-HT turnover in the prefrontal cortex and hippocampus from females and males respectively but evoked a decrease in these regions from males and females respectively. Conclusions: The present findings indicated that maternal exposure to chlordimeform altered serotonergic neurochemistry in their offspring in prefrontal cortex, striatum and hippocampus, and those variations show that other mechanisms different from MAO inhibition are implicated.B thuringiensis kurstaki is a soil bacterium that produces insecticidal toxins called delta-endotoxins. In order to increase the toxic crystal concentrations in a low-cost culture medium and thus improve the biopesticide quality to control insect pests, the Plackett–Burman screening method was applied. It is a tool to evaluate the significance of the selected seven factors (KH2PO4, K2HPO4, MgSO4, MnSO4, FeSO4, soybean meal, starch) which are necessary for the production of the deltaendotoxins. This was performed into two different shake flasks (250 and 500 ml). The main factors that affected the production of delta-endotoxins are soybean meal, starch, and FeSO4 in 250 ml culture flasks. In 500 ml culture flasks, soybean meal and FeSO4 are the principal factors influencing the delta-endotoxin production. The multiple linear regressions, a method that was applied as the merging dataset of the two Plackett–Burman designs, established that soybean meal and starch are the factors positively affecting the production of delta-endotoxins, in contrast to FeSO4. Furthermore, the available oxygen in culture flasks showed no significant negative effect on delta-endotoxin production. This study revealed that mixed method designs were useful to identify the significance and the effect of hidden culture parameters.

Intercostal hemangioma of the chest wall

The authors describe a case of a 36-year-old patient who had six months’ pain of the thoracic spine and left chest. A soft slowly growing resistance was present on the dorso-lateral side of the left chest wall, in the range of the seventh to ninth rib. According to the medical history, the patient did not have any prior trauma and malignancy. A well-defined tumor of the left chest wall with calcifications, which grew to the seventh and eighth intercostal space, was present on computed tomography (CT) and magnetic resonance (MR) scans. The patient underwent resection of the tumor with the chest wall and reconstruction with polypropylene mesh. Histologically, it was a venous hemangioma, one of very rare tumors of the chest wall.

Posterior mediastinotomy as an unordinary method of mediastinal drainage in patient with descending necrotizing mediastinitis: a case report.

The authors present a case report of severe descending necrotizing mediastinitis (DNM) of posterior mediastinum, etiologically of vertebral osteomyelitis treated by the drainage through the posterior mediastinotomy. Mediastinitis caused by vertebral osteomyelitis is very rare. The most important diagnostic and surveillance tool for descending mediastinitis is a CT scan of chest and neck. Every surgical approach to the mediastinum has its advantages and disadvantages, so each patient has to be treated individually and the most suitable type of drainage must be chosen. The posterior mediastinotomy is an unusual alternative of drainage of pre- and paravertebrally localized DNM in posterior mediastinum but it is not recommended as a routine strategy.