Antiproliferative and antimigratory effects of 3-(4-substituted benzyl)-5- isopropyl-5-phenylhydantoin derivatives in human breast cancer cells.

In this study, a series of synthesized 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives as a potential antiproliferative and antimigratory agents were investigated. The possible antitumor mechanisms of investigated hydantoin derivatives were examined on human breast cancer cell line MDA-MB-231. The cells were treated with different concentrations of compounds (from 0.01 µM to 100 µM) during 24 h and 72 h. The proliferation index, nitric oxide production, apoptosis rate, and migration capacity were measured. The cell invasion potential was examined by measuring the level of MMP-9 and COX-2 gene expression. All tested compounds expressed antiproliferative activity and induced dose- and time-dependent increase in the level of nitrites. The investigated molecules significantly decreased cell survival rate, migration capacity and the expression levels of genes included in the process of tumor invasion. Obtained data suggest that the tested hydantoin derivatives express considerable antitumor activity by reducing cell division rate, elevating apoptosis level, and inhibiting the motility and invasiveness of breast cancer cells. The results obtained in this study indicate that investigated compounds express potential as a novel chemotherapeutic agents against breast cancer growth and progression.

Anti-Tumor Mechanisms of Novel 3-(4-Substituted Benzyl)-5-Isopropil-5- Phenylhydantoin Derivatives in Human Colon Cancer Cell Line.

BACKGROUND: Hydantoin and its newly synthesized derivatives have recently become a focus of interest due to their numerous biological activities and newly emerging beneficial effects in different pathological conditions, including cancer. OBJECTIVE: The aim of this study was to evaluate the possible anti-tumor mechanisms of a series of newly synthesized 3-(4-substituted benzyl)-5-isopropyl-5-phenylhydantoin derivatives in different aspects of cell physiology of human colon cancer cell line, HCT-116. METHODS: The increasing concentrations of derivatives (0.01µM up to 100µM) were applied to cells during 24h, 48h, and 72h after which the evaluation of proliferation, apoptosis, oxidative/anti-oxidative status, nitrite production, and migration/invasion potential of treated cells was performed. RESULTS: All tested compounds expressed the dose- and time-dependent anti-proliferative and pro-apoptotic activities against HCT-116 cells. The investigated derivatives induced a decrease in levels of oxidative stress parameters and an increase in levels of nitrite production by treated cells suggesting their significant antioxidative effects. The cell migration index and expression level of tumor invasion-promoting metalloproteinase- 9 (MMP-9) gene were significantly decreased after treatment with the tested hydantoin derivatives implicating their inhibitory role in colon cancer cell motility and invasion processes. The mRNA level of cyclooxygenase-2 (COX-2) gene as a pro-inflammatory gene related to colorectal carcinogenesis was reduced compared to values in the non-treated control cells indicating the significant anti-inflammatory/anti-tumor effects of these compounds. CONCLUSION: The obtained results show the significant anti-tumor potential of tested derivatives, especially 3- benzyl-5-isopropyl-5-phenylhydantoin and 3-(4-chlorobenzyl)-5-isopropyl-5-phenylhydantoin, suggesting their potential usage in the development of more effective chemotherapies.

Computer simulation of speciation of trivalent aluminum, gadolinium and yttrium ions in human blood plasma.

The speciation of Al3+, Gd3+ and Y3+ ions in human plasma has been studied by computer simulation using the program HySS2009. A literature computer model of blood plasma was updated and comprised 9 metals, 43 ligands and over 6100 complexes. To this model critically evaluated data of Al3+, Gd3+ and Y3+ constants with blood plasma ligands have been added. Low molecular mass (LMM) speciation of Al3+ ion strongly depends upon the chosen equilibrium model of the metal - phosphate and metal - citrate systems. The obtained computer simulation of LMM speciation data of Al3+ ion were: AlPO4Cit (40.7%), AlPO4CitOH (22.9%), AlCitOH (19.2%) and AlPO4(OH) (12.7%) (% of total LMM Al species pool); for Gd3+ ion: GdAspCit (30%) and GdCit(OH)2 (20%) (% of total [Gd]) and for Y3+ ion: YCit (48%), Y(CO3)2 (32%) and Y(CO3) (11%) (% of total [Y]). Citrate appears as the important binding and mobilizing ligand for all examined ions, while the dominating species are the ternary ones.

Evaluation of matrix effect in determination of some bioflavonoids in food samples by LC-MS/MS method.

In the present work the LC-MS/MS method with solid phase extraction for simultaneous determination of bioflavonoids rutin, quercetin, hesperidin, hesperetin and kaempferol in some food samples (red onion, orange peel and honey) was developed and the matrix effect accompanying this determination was quantified. The matrix effect evaluated using a postextraction addition method was found to be negative in the range -44 to -0.5%, indicating ionization suppression and strongly depended on bioflavonoid concentration. The observed matrix effect was explained taking into account the co-elution of phenolic acids, in terms of their acid-base and hydrophilic properties. The efficacy of extraction expressed as the absolute recoveries of flavonoids were 88-96%, indicating very good efficiency of extraction. The extracts of food samples obtained either by Soxhlet or ultrasonic extraction were analyzed for bioflavonoid content by the LC-MS/MS method in selected reaction monitoring mode using a triple quadrupole detector and standard addition method, which was found to be the most suitable calibration approach for these samples. The optimized separation was achieved on a Phenomenex Gemini C18 column with gradient elution and mobile phase composition A: 2% acetic acid in water and B: acetonitrile. R(s) values were in the range from 1.3 to 3.1, indicating good selectivity of the method. The obtained results (mg/100g fresh weight) for different bioflavonids were for rutin 0.16, for quercetin in the range 0.65-56, for hesperidin 0.016-24, for hesperetin 0.0068-36.4 and for kaempferol 0.14-1.63 and generally show good agreement with published data. Low detection limits (0.014-0.063 µg/mL) were obtained with acceptable recoveries (86-114%). Total time of analysis was less than 40 min, therefore the proposed method represents significant improvement over existing methods.

[Radiation-induced lung damage--etiopathogenesis, clinical features, imaging findings and treatment].

INTRODUCTION: This review is related to the mechanism of development of radiation induced pneumonitis, its pathological, clinical and radiological features and therapy. The team treating cancer patients consists of radiation oncologists and oncologists, as well as general practitioners, pulmologists and radiologists for monitoring effects of therapy. Therefore, a different number of specialists should be familiar with the importance of diagnosis in order to avoid differential diagnostic error in relation to infection, relapse or metastasis, chemotherapeutic adverse effects. LUNG DAMAGE BY IONIZING RADIATION: Factors that influence the development of radiation pneumonitis are numerous: (1) the volume of irradiated parenchyma (2) the absorbed dose, (3) the number of fractions which divided the absorbed dose. (4) the size ofindividual doses per fraction, (5) radiation dose rate (the radiotherapy output device). Acute radioneumonitis is characterized by dyspnea, cough, and, rarely fever and chest pain. The timely treatment of the symptoms makes it easier for patients and reduces the likelihood of developing pulmonary fibrosis. DIAGNOSIS OF RADIATION PNEUMONITIS: There are no specific markers in serum or sputum that would definitely indicate the development of acute pneumnonitis. Changes in lung radiography and computed tomography may suggest its development; however, extra diagnostics information sometime needs to be obtained from magnetic resonance images and positron emission tomography to make diagnosis and choose the treatment. CONCLUSION: The longer survival results from new modalities of treatment applied in cancer patients, and the prevention of adverse effects of radiation therapy is getting more important since longlasting toxicity affects the life quality.

[Phagocytic activity of peripheral blood leukocytes during acute myocardial infarction]. / Fagocitna aktivnost leukocita periferne krvi tokom akutnog infarkta miokarda.

INTRODUCTION: Coronary occlusion may cause acute myocardial infarction associated with many cellular and humoral disturbances of the immune system. The aim of this investigation was to examine phagocytic activity of peripherial blood monocytes and neutrophils as potential cellular markers of systemic immunological events in acute myocardial infarction. MATERIAL AND METHODS: This study included thirty patients following first acute myocardial infarction and thirty healthy volunteers. Immunological analyses were performed on admission and repeated on the second and seventh days after the acute event. Monocytes and neutrophils were obtained from heparinized whole blood after centrifugation and separation on density gradient and incubated with fixed number of heat inactivated and painted particles of yeast. We investigated the following parameters of phagocytic activity: percentage of phagocytosis, phagocytic index, absolute phagocytic index, phagocyte count in a fixed volume of peripherial blood and phagocytic capacity. RESULTS: Except phagocytic index, all phagocytic parameters of monocytes and neutrophils were increased in acute myocardial infarction patients on admission and on the second day of hospitalization. On the seventh day after acute event only the mononuclear phagocyte count in fixed volume of peripheral blood showed significant increase in acute myocardial infarction patients, while percentage of phagocytosis, phagocyte count in fixed volume of peripheral blood and phagocyte capacity of neutrophils were increased during the whole investigated period. CONCLUSION: These data suggest that acute myocardial infarction was followed with strong systemic inflammatory response to myocardial damage. Furthermore, activated monocytes and neutrophils could be a significant source of free radicals, which might be involved in lipid peroxidation and cause tissue damage in early postinfarction period.