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Background: One of the most important strategies in research and development of new anticancer agents is the tumor-specific induction of apoptosis. The effects of semisynthetic derivative of vitamin E, (α-TOS, D-α-tocopheryl succinate), appear to be largely restricted to malignant cells. Methods: We investigated the in vivo effects of intraperitoneally administered α-TOS on vitality of Ehrlich ascites carcinoma cells (EAC) in mice, as well as the influence of α-TOS on specific activity of enzymes involved in antioxidative mechanisms in EAC cells. Results: According to our results, the intraperitoneal application of α-TOS induces the decrease of the EAC vitality, and the statistically significant alteration of the glutathione-dependent enzyme activity in EAC cells. Conclusion: We may conclude that α-TOS is an important micronutrient, with significant impact on vitality and metabolism of malignant cells.

Background. One of the critical limitations for the administration of the chemotherapy is the toxicity affecting normal tissue. The main target organs for 5-fluorouracil (5-FU) toxicity in humans and experimental animals are the gastrointestinal tract, bone marrow, and skin. The cytotoxic effects of antimetabolite chemotherapy are based on their role as substrates for the same transport processes and enzymes involved in anabolism and catabolism as the natural substrates. The main goal of our study was to analyze the dose-dependent antiproliferative effects of 5-FU on intestinal mucosa, enterotoxic potential of 5-FU in experimental animals and to test possible protective role of glutamine. Methods. In our study, we used Sprague Dawley rats. The control group of rats included 50 animals, while the groups where either 5-fluorouracil (5-FU) alone or 5-FU and glutamine were administered included 200 animals. All experimental animals were further stratified according to the experimental model (25 animals in each of 8 experimental subgroups of animals). The 5-FU was administered by intraperitoneal application in single dose of 0, 100, 200, 300, and 400 mg of 5-FU per kg of body weight. Water solution of 1% glutamine was prepared daily and administered orally, in volume of 200 ml, for 7 days continuously, after the 7th day of 5-FU administration. Experimental animals were sacrificed 7 days after the administration of 5-FU. The isolation of enterocytes was performed according to the method of Kralovansky et al. In cell homogenate obtained by described method, we determined the protein content using the Biuret method and the DNA content using the Burton reagent. The activities of enzymes alkaline phosphatase (ALP), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPX) were determined by kinetic method. All paraffin samples of the small intestine were stained by haematoxiline and eosine(HE method). All the experiments were done in duplicate and analyzed by standard statistical methods. All the experiments were done in duplicate and analyzed by standard statistical methods. Results: Our results of enterotoxicity induced by intraperitonealy administered 5-FU showed statistically significant decrease of DNA content in small intestine samples of experimental animals, decrease in activity of intestinal alkaline phosphatase enzyme and the increase in glutathione-dependent enzymes. The glutamine supplementation reduced 5-FU intestinal toxicity. Conclusion: Intestinal alkaline phosphatase is a good marker of the dose-dependent enterotoxicity induced by 5-fluorouracil.

In last ten years, significant advances have occurred in thyroid endocrinology, as a consequence of the generalized use of molecular biology techniques. New genes involved in the development of thyroid cancer have been identified, which had a great impact on our understanding of thyroid cancer predisposition. All cancers are genetic in origin because they arise from mutations in a single somatic cell, but the genetic changes in sporadic cancers are confined to a particular tissue. In inherited cancers, a predisposing mutation is present in all somatic cells and in the germ line, which enables the transmission of risk to the next generation. Cancer genetics offers a model of how information on the genetics of inherited cancers could affect identification of individuals at increased genetic risk.

Early detection is essential for the control and prevention of many diseases, particularly cancer, which is the reason why the need for new disease markers with improved sensitivity and specificity continues to grow. Utilization of sophisticated bioinformatic tools enables the increased specificity and a relatively large quantity of high quality assays for any gene of interest. Understanding the molecular characteristics of diseases, such as cancer and the detection of mutations or changes in gene expression patterns that occur as a result of the disease, will bring researchers one step closer to achieving the predictive power needed for the development of new therapies, the design of clinical trials, and specific patient treatment planning. Genetic screening is one of the fastest moving areas of medical science, particularly in oncology, and as more genes are cloned, and more disease-associated mutations discovered, the workload is set to increase considerably with the utilization of bioinformatics tools used in integration and analysis of genomic, proteomic and metabolomic profiles of cancer. .

BACKGROUND: Rapidly proliferating crypt cells of the intestinal epithelium, the precursors of the mature enterocytes, are extremely sensitive to the effects of cytostatic agents. We investigated the effects of the methotrexate on rat intestinal mucosa in order to get the information on biochemical indicators of intestinal damage. METHODS: Biochemical parameters were investigated in isolated intestinal mucosa of Sprague-Dawley rats, previously treated with methotrexate by intraperitoneal administration. Glutamine was dissolved in water and administered orally. RESULTS: The activity of glutaminase and alkaline phosphatase showed the enzymatic response to different doses of methotrexate. The activity of both enzymes was significantly lower in the mucosa of treated animals, compared to control group. CONCLUSION: Minimal mucosal damage and regeneration time is dose dependent and influenced by the dosage schedule of antitumor therapy.

Background: Single-walled carbon nanotubes (SWCNTs) have been reported to induce cytotoxicity in different cell lines. Although the mechanisms underlying cytotoxicity are not fully understood, accumulation of reactive oxygen species (ROS) and oxidative damage is considered to be a likely contributing factor. Methods: Human lung carcinoma cells, A549, and human fetal lung fibroblasts, MRC-5 were used to assess the cytotoxicity of SWCNT in the presence and absence of a redox status regulator, N-acetylcysteine (NAC), via the MTT assay. Results: SWCNT induced a nearly three-fold greater loss of viability in A594 vs. MRC-5 cells at ≤250 μg/ml. SWCNT cytotoxicity at higher concentrations was similar for both cell lines, while NAC alone was non-toxic. The cytotoxicity of SWCNT (250 μg/ml) in combination with NAC to A549 cells was significantly decreased at the lowest NAC concentration (1.5 µg/ml), and was similar to NAC treatment alone at that concentration. Higher concentrations of NAC in combination with SWCNT (250 μg/ml) resulted in increased cytotoxicity in both A549 and MRC-5 cells. Conclusion: A549 malignant lung cells are more susceptible to low concentrations of SWCNT vs. normal lung cells, and low concentrations of N-acetylcysteine appear to be cytoprotective, possibly due to its antioxidant properties. [Projekat Ministarstva nauke Republike Srbije, br. 173014: Molecular mechanisms of redoxsignaling in homeostasis: Adaptation and pathology]

Oxyphilic tumors of the thyroid gland are rare tumors characterized by the presence of Hürthle cells - mitochondrion-rich, eosinophilic epithelial cells. Hürthle cell carcinomas (HCC) of the thyroid behave in a more aggressive fashion as compared to other well-differentiated thyroid cancers. Many recent studies have been focused on the further elucidation of pathogenesis and the role of mitochondrial hyperplasia in carcinogenesis of these neoplasms. The importance of combining morphological and genetic approaches in the study of HCC has been emphasized by the difficulties encountered in establishing adequate differential diagnostic criteria between benign and malignant forms, as well as by the resistance of HCC to radio and chemotherapy. It has been well documented that the Hürthle cells are characterized by profound aberrations in the nuclear and mitochondrial genome and by alterations in oncogenes, tumor suppressor genes and other key genes involved in energy metabolism, proliferation and apoptosis.

Background: In order to test the possibility of association between GSTT1 and M1 (glutathione S-transferase) null allele variant, in which the entire gene is absent, and the risk of TCO (thyroid carcinoma with cell oxyphilia), the case-control study was carried out. Methods: Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR in the DNA from 108 healthy individuals and in DNA from samples of thyroid tumors from 130 patients of the same race and origin as the control group (Caucasian, Italian). The following types of NMTC were analyzed: oxyphilic adenoma (OA), oxyphilic carcinoma (OC) papillary thyroid carcinoma with oxyphilic features (PTCof), follicular adenoma (FA), follicular carcinoma (FC), follicular variant of PTC (fvPTC) and classical PTC. Associations between prevalence of particular genotypes and the occurrence of TCO (versus controls) and other subtypes of NMTC were tested. Associations were quantified by calculating OR (odds ratio) with 95% confidence interval. StatGraphics Plus v. 5 software (Manugistics) was used for statistical analysis. Results: In this study of the association between the GSTT1 and M1 null genotype and the increased risk of TCO, the frequency of GSTT1 null genotype of 19.2% in cases and 15.7% in controls was found with an adjusted odds ratio (OR) of 1.4 (95% confidence interval (CI) 0.70-2.81), and the frequency of GSTM1 null genotype of 59% in cases with oxyphilic tumors and of 55.6% in controls (OR 1.24; 95% CI, 0.62-2.48). Conclusion: These results indicate that the GSTT1 and M1 null genotypes do not increase the risk of development of oxyphilic tumors, as well as other types of NMTC that have been included in this study.