Botla S.K.,German Cancer Research Center |
Gholami A.M.,TU Munich |
Malekpour M.,Tehran University of Medical Sciences |
Malekpour M.,Vanderbilt University |
And 15 more authors.
Breast Cancer Research and Treatment | Year: 2012
DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (n = 52, p<2.1 × 10 -4) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (n = 65, p<1.9 × 10-7). The signature is associated with SFRP2 and GHSR genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the GHSR methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion. © Springer Science+Business Media, LLC. 2012.
Goreshnik E.A.,Jozef Stefan Institute |
Gelmboldt V.O.,Odessa State Medical University |
Koroeva L.V.,Physico Chemical Institute of Environment and Human Protection |
Ganin E.V.,Odessa State Environmental University
Journal of Fluorine Chemistry | Year: 2011
3,5-Diamino-1,2,4-triazolium tetrafluoroborate (LH)BF4 and hexafluorosilicate (LH)2SiF6 have been isolated and characterized by single-crystal X-ray structure determination, IR spectroscopy, mass spectrometry, solubility data, potentiometry. The N-H⋯F and N-H⋯N hydrogen bonds play an important role in a formation of 3-D structures of two compounds. The relationship between the salts structure and some properties is discussed. © 2010 Elsevier B.V. All rights reserved.
Shandra A.,Odessa State Medical University |
Shandra P.,Odessa I I Mechnikov National University |
Kaschenko O.,Odessa State Medical University |
Matagne A.,UCB Pharma |
Stohr T.,UCB Pharma
Epilepsia | Year: 2013
Purpose Lacosamide (LCM, Vimpat) is an anticonvulsant with a unique mode of action. This provides lacosamide with the potential to act additively or even synergistically with other antiepileptic drugs (AEDs). The objective of this study was to determine the presence of such interactions by isobolographic analysis. Methods The anticonvulsant effect of LCM in combination with other AEDs including carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), lamotrigine (LTG), topiramate (TPM), gabapentin (GBP), and levetiracetam (LEV) at fixed dose ratios of 1:3, 1:1, and 3:1, was evaluated in the 6-Hz-induced seizure model in mice. In addition, the impact of the combinations of LCM with the other AEDs on motor coordination was assessed in the rotarod test. Finally, AED concentrations were measured in blood and brain to evaluate potential pharmacokinetic drug interactions. Key Findings All studied AEDs produced dose-dependent anticonvulsant effects against 6-Hz-induced seizures. Combinations of LCM with CBZ, LTG, TPM, GBP, or LEV were synergistic. All other LCM/AED combinations displayed additive effects with a tendency toward synergism. Furthermore, no enhanced adverse effects were observed in the rotarod test by combining LCM with other AEDs. No pharmacokinetic interactions were seen on brain AED concentrations. Coadministration of LCM and TPM led to an increase in plasma levels of LCM, whereas the plasma concentration of PHT was increased by coadministration of LCM. Significance The synergistic anticonvulsant interaction of LCM with various AEDs, without exacerbation of adverse motor effects, highlights promising properties of LCM as add-on therapy for drug refractory epilepsy. © 2013 Wiley Periodicals, Inc.
Orlovskaya S.G.,Odessa I I Mechnikov National University |
Kalinchak V.V.,Odessa I I Mechnikov National University |
Zuy O.N.,Odessa I I Mechnikov National University |
Mandel O.V.,Odessa State Medical University |
Kachan S.V.,The National Pedagogical University
Ukrainian Journal of Physics | Year: 2011
The influence of internal reactions on the characteristics of hightemperature heat and mass transfer and the critical conditions for the ignition and the extinction in gas suspensions of carbon particles are researched. It is found that the internal reactions lead to a significant decrease in the ignition delay and critical diameters, which determines the ignition and the extinction of particles of a gas suspension. It is proven that the porous particle extinguishes when its mass achieves some critical value. The intervals of initial diameters and mass concentrations of particles are determined corresponding to the most complete burnout of carbon fuel. © 2011.
Moskalev E.A.,German Cancer Research Center |
Moskalev E.A.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Jandaghi P.,German Cancer Research Center |
Fallah M.,German Cancer Research Center |
And 19 more authors.
Oncotarget | Year: 2015
Identification of a single molecular trait that is determinant of common malignancies may serve as a powerful diagnostic supplement to cancer type-specific markers. Here, we report a DNA methylation mark that is characteristic of seven studied malignancies, namely cancers of lung, breast, prostate, pancreas, colorectum, glioblastoma and B cell chronic lymphocytic leukaemia (CLL) (n = 137). This mark was defined by substantial hypermethylation at the promoter and first exon of growth hormone secretagouge receptor (GHSR) through bisulfite pyrosequencing. The degree of aberrant methylation was capable of accurate discrimination between cancer and control samples. The highest sensitivity and specificity of cancer detection was achieved for cancers of pancreas, lung, breast and CLL yielding the area under the curve (AUC) values of 1.0000, 0.9952, 0.9800 and 0.9400, respectively. Narrowing to a single CpG site within the gene's promoter or four consecutive CpG units of the highest methylation levels within the first exon improved the detection power. GHSR hypermethylation was detected already at the early stage tumors. The accurate performance of this marker was further replicated in an independent set of pancreatic cancer and control samples (n = 78). These findings support the candidature of GHSR methylation as a highly accurate pan-cancer marker.
Gelmboldt V.O.,Odessa State Medical University |
Ganin E.V.,Odessa State Environmental University |
Koroeva L.V.,Ukrainian Academy of Sciences |
Botoshansky M.M.,Technion - Israel Institute of Technology |
Fonari M.S.,Moldova Academy of Sciences
Journal of Fluorine Chemistry | Year: 2010
Interaction of hexafluorosilicic acid with sulfa drugs sulfathiazole (stz) and sulfalen (2-sulfanilamido-3-methoxypyrazine, sl) results in the crystalline salts of the compositions [stzH]2[SiF6] (I) and [4-H 2NO2SPhNH3]2[SiF6] (II). Complex I is characterized by IR, mass spectrometry data and single crystal X-ray diffraction. The crystal structure of I is stabilized by a network of charge-assisted hydrogen bonding. The relationship between the solubility and H-bonding system in I, II and related "onium" hexafluorosilicates is discussed. The formation of complex II, previously reported as an interaction product of hexafluorosilicic acid with 4-aminobenzenesulfonamide (sulfanilamide), is the result of cleavage of the C-N bond in sulfalen in acidic medium.© 2010 Elsevier B.V. All rights reserved.
Nicholas S.A.,University of Kent |
Bubnov V.V.,Odessa State Medical University |
Yasinska I.M.,University of Kent |
Sumbayev V.V.,University of Kent
Cellular and Molecular Life Sciences | Year: 2011
Inflammatory reactions to ssRNA viruses are induced by the endosomal Toll-like receptors (TLRs) 7 and 8. TLR7/8-mediated inflammatory reaction results in activation of the Nalp3 inflammasome via an unknown mechanism. Here we report for the first time that TLR7/8 mediate activation of xanthine oxidase (XOD) in an HIF-1α-dependent manner. XOD produces uric acid and reactive oxygen species, which could activate Nalp3 and therefore induce activation of caspase 1, known to convert inactive pro-IL-1β into active IL-1β. Specific inhibition of the XOD activity attenuates TLR7/8-mediated activation of caspase 1 and IL-1β release. These results were obtained using human THP-1 myeloid macrophages. The findings were verified by conducting in vivo experiments on mice. © 2010 Springer Basel AG.
Zaporozhan V.,Odessa State Medical University |
Ponomarenko A.,Odessa State Medical University
International Journal of Environmental Research and Public Health | Year: 2010
Recent studies demonstrate distinct changes in gene expression in cells exposed to a weak magnetic field (MF). Mechanisms of this phenomenon are not understood yet. We propose that proteins of the Cryptochrome family (CRY) are "epigenetic sensors" of the MF fluctuations, i. e., magnetic field-sensitive part of the epigenetic controlling mechanism. It was shown that CRY represses activity of the major circadian transcriptional complex CLOCK/BMAL1. At the same time, function of CRY, is apparently highly responsive to weak MF because of radical pairs that periodically arise in the functionally active site of CRY and mediate the radical pair mechanism of magnetoreception. It is known that the circadian complex influences function of every organ and tissue, including modulation of both NF-κB- and glucocorticoids- dependent signaling pathways. Thus, MFs and solar cycles-dependent geomagnetic field fluctuations are capable of altering expression of genes related to function of NF-κB, hormones and other biological regulators. Notably, NF-κB, along with its significant role in immune response, also participates in differential regulation of influenza virus RNA synthesis. Presented data suggests that in the case of global application (example-geomagnetic field), MF-mediated regulation may have epidemiological and other consequences. © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
Aryayev M.,Odessa State Medical University |
Lowe J.B.,University of The Sunshine Coast |
Kuzmenko T.,Odessa State Medical University
European Journal of Public Health | Year: 2014
We investigated prevalence of and knowledge about tobacco use among physicians, and their counselling of patients in the Odessa region (Ukraine). Paediatricians (40), family doctors (40) and interns (70) were selected from the physician population of the Odessa region. The proportion of smokers was unacceptably high for health care professionals: paediatricians, 32.5%; family doctors, 37.5%; and interns, 50%. Majority of smokers were men. Less than half of smokers had considered quitting or seriously attempted to quit. Interns least frequently asked their patients about smoking (52.5 vs. 80% paediatricians and 72.5% family doctors). Ukrainian universities need to better educate medical students on tobacco control measures. © 2014 The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
PubMed | Odessa State Medical University
Type: Journal Article | Journal: Epilepsia | Year: 2013
Lacosamide (LCM, Vimpat) is an anticonvulsant with a unique mode of action. This provides lacosamide with the potential to act additively or even synergistically with other antiepileptic drugs (AEDs). The objective of this study was to determine the presence of such interactions by isobolographic analysis.The anticonvulsant effect of LCM in combination with other AEDs including carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), lamotrigine (LTG), topiramate (TPM), gabapentin (GBP), and levetiracetam (LEV) at fixed dose ratios of 1:3, 1:1, and 3:1, was evaluated in the 6-Hz-induced seizure model in mice. In addition, the impact of the combinations of LCM with the other AEDs on motor coordination was assessed in the rotarod test. Finally, AED concentrations were measured in blood and brain to evaluate potential pharmacokinetic drug interactions.All studied AEDs produced dose-dependent anticonvulsant effects against 6-Hz-induced seizures. Combinations of LCM with CBZ, LTG, TPM, GBP, or LEV were synergistic. All other LCM/AED combinations displayed additive effects with a tendency toward synergism. Furthermore, no enhanced adverse effects were observed in the rotarod test by combining LCM with other AEDs. No pharmacokinetic interactions were seen on brain AED concentrations. Coadministration of LCM and TPM led to an increase in plasma levels of LCM, whereas the plasma concentration of PHT was increased by coadministration of LCM.The synergistic anticonvulsant interaction of LCM with various AEDs, without exacerbation of adverse motor effects, highlights promising properties of LCM as add-on therapy for drug refractory epilepsy.