Oncologic diseases are among leading cause of mortality in developed countries. Despite significant progress, the use of standard cytotoxic chemotherapy has reached a therapeutical plateau. Currently, the process of selecting chemotherapy represents a trial and error method neglecting biological individuality of tumor and its bearer. The improvement of treatment results is expected from ex vivo drug sensitivity testing which may allow to choose the most effective drug for individual patient and to exclude agents to which the tumor cells exert resistance. New techniques and rapidly increasing knowledge about the molecular basis of malignant diseases provide important opportunities for the future of chemotherapy. This paper reviews current methods used to test the resistance of tumor cells to a panel of anticancer agents in vitro. In addition, we focused on the in vitro MTT assay which represents one of major technique for testing of tumor cell resistance to anticancer agents.

BackgroundIt has been suggested that polymorphisms in glutathione-S-transferases (GST) could predispose to prostate cancer through a heritable deficiency in detoxification pathways for environmental carcinogens. Yet, studies linking GST polymorphism and prostate cancer have so far failed to unambiguously establish this relation in patients. A retrospective study on healthy, unrelated subjects was conducted in order to estimate the population GST genotype frequencies in the Slovak population of men and compare our results with already published data (GSEC project-Genetic Susceptibility to Environmental Carcinogens). A further aim of the study was to evaluate polymorphisms in GST also in patients with prostate cancer in order to compare the evaluated proportions with those found in the control subjects.MethodsWe determined the GST genotypes in 228 healthy, unrelated subjects who attended regular prostate cancer screening between May 2005 and June 2007 and in 129 histologically verified prostate cancer patients. Analysis for the GST gene polymorphisms was performed by PCR and PCR-RFLP.ResultsWe found that the GST frequencies are not significantly different from those estimated in a European multicentre study or from the results published by another group in Slovakia. Our results suggest that Val/Val genotype of GSTP1 gene could modulate the risk of prostate cancer, even if this association did not reach statistical significance. We did not observe significantly different crude rates of the GSTM1 and GSTT1 null genotypes in the men diagnosed with prostate cancer and those in the control group.ConclusionUnderstanding the contribution of GST gene polymorphisms and their interactions with other relevant factors may improve screening diagnostic assays for prostate cancer. We therefore discuss issues of study feasibility, study design, and statistical power, which should be taken into account in planning further trials.

Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01).

Apoptosis is the fundamental process necessary for eliminating damaged or mutated cells. Alterations in the apoptotic pathway appear to be key events in cancer development and progression. Bcl-2 is the key member of the Bcl-2 family of apoptosis regulator proteins with anti-apoptotic effects. Survivin acts as an inhibitor of apoptosis as well and has been implicated in both inhibition of apoptosis and mitosis regulation. p53 is one of the tumor suppressor proteins, prevents tumor formation through cell cycle blocking and eliminates damaged cells via the activation of apoptosis. The Ki-67 protein is a cellular marker for proliferation. To investigate the possible interactions of the aforementioned proteins, we examined their expression in 76 patients with diagnosed lung cancer using immunohistochemical visualisation. Ki-67 protein was expressed in the cancer cells of all patients with small cell lung cancer (SCLC). We found a negative correlation between survivin and p53 expression. A decreased intensity of survivin expression and fewer cells positive for survivin (66.7%) in SCLC in comparison with other lung cancer types (98.0%) was detected. Reversely, expression of Bcl-2 was found in more than 90% of cases with SCLC. We hypothesize that high expression and intensity of Bcl-2 protein could be a factor behind a bad prognosis in SCLC.

Cold atmospheric plasma has great potential for use in modern medicine. It has been used in the clinical treatment of skin diseases and chronic wounds, and in laboratory settings it has shown effects on selective decrease in tumour-cell viability, reduced tumour mass in animal models and stem-cell proliferation. Many researchers are currently focusing on its application to internal structures and the use of plasma-activated liquids in tolerated and effective human treatment. There has also been analysis of plasma’s beneficial synergy with standard pharmaceuticals to enhance their effect. Cold atmospheric plasma triggers various responses in tumour cells, and this can result in epigenetic changes in both DNA methylation levels and histone modification. The expression and activity of non-coding RNAs with their many important cell regulatory functions can also be altered by cold atmospheric plasma action. Finally, there is ongoing debate whether plasma-produced radicals can directly affect DNA damage in the nucleus or only initiate apoptosis or other forms of cell death. This article therefore summarises accepted knowledge of cold atmospheric plasma’s influence on epigenetic changes, the expression and activity of non-coding RNAs, and DNA damage and its effect in synergistic treatment with routinely used pharmaceuticals.

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Polymorphisms in tobacco carcinogen metabolizing enzymes may generate interindividual variations towards the risk of developing prostate cancer. One of these enzymes is microsomal epoxide hydrolase (EPHX1) which metabolizes polycyclic aromatic hydrocarbons, or PAH, carcinogens found in cigarette smoke. The activity of this enzyme is affected by two polymorphisms, a substitution of Tyr113 by His in exon 3 and a substitution of His139 by Arg in exon 4. The aim of this study was to use a population-based case-control study to investigate whether or not such genetic polymorphisms in EPHX1 gene can modify the relationship between smoking status and the risk of developing prostate cancer. We used restriction fragment length polymorphism, or PCR-RFLP to determine EPHX1 genotypes in subjects comprising 194 patients with histologically verified prostate cancer and 305 healthy individuals as control. We found no overall association between prostate cancer risk and functional polymorphisms of EPHX1 gene in exon 3 and exon 4. We further analysed the association between the EPHX1 genotypes and smoking. Smokers carrying the exon 3 Tyr/Tyr and Tyr/His genotypes were at no significant risk compared to non-smokers with the "rapid" Tyr/Tyr genotype. By contrast, a significant interaction of smoking and the exon 4 polymorphism was present.

Although no apparent increase in chromosomal damage was recorded in chromium-exposed welders in comparison with controls, genetic make-up in DNA repair genes may increase susceptibility toward adverse effect of chromium.