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Bilous N.,Research Center for Radiation Medicine | Abramenko I.,Research Center for Radiation Medicine | Saenko V.,Nagasaki University | Chumak A.,Research Center for Radiation Medicine | And 3 more authors.
Leukemia Research | Year: 2017

Objectives To analyze the distribution of single nucleotide polymorphisms (SNPs) in the TP53 gene in chronic lymphocytic leukemia (CLL) patients and to evaluate their associations with clinical behavior of the disease. Methods SNPs in exons and parts of adjacent introns of the TP53 gene were analyzed in 235 CLL patients observed during 2005-2012 years. Data on individuals of European descent from the 1000 Genomes Project data set were used as a reference. Results In the recessive model of inheritance, we found borderline associations between CLL risk and C/C genotype of rs1642785 (p = 0.048); G/G genotype of rs2909430 (in men only; p = 0.036) and Pro72Pro genotype of rs1042522 (in men only; p = 0.045). Risk of CLL was increased also in carriers of rare haplotypes (p = 0.0049). Besides, genotypes Pro72Pro of rs1042522, C/C of rs1642785, and G/G of rs2909430 were associated with an increased incidence of TP53 mutations. Median of overall survival in rs1800372 carriers was comparable to that of patients with TP53 mutations. Other evaluated SNPs were not associated with survival. Conclusion Our data suggest that some TP53 variants may affect the risk of CLL. rs1800372 polymorphism might be the marker of unfavorable prognosis of the disease. © 2017 Elsevier Ltd


Ainsbury E.A.,Public Health England | Bakhanova E.,Research Center for Radiation Medicine | Barquinero J.F.,Unitat dAntropologia Biologica | Brai M.,University of Palermo | And 30 more authors.
Radiation Protection Dosimetry | Year: 2011

The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements. © The Author 2010. Published by Oxford University Press. All rights reserved.


Fattibene P.,Instituto Superiore Of Sanita | Wieser A.,Helmholtz Center Munich | Adolfsson E.,Linköping University | Benevides L.A.,Naval Dosimetry Center | And 36 more authors.
Radiation Measurements | Year: 2011

This paper presents the results of the 4th International Comparison of in vitro electron paramagnetic resonance dosimetry with tooth enamel, where the performance parameters of tooth enamel dosimetry methods were compared among sixteen laboratories from all over the world. The participating laboratories were asked to determine a calibration curve with a set of tooth enamel powder samples provided by the organizers. Nine molar teeth extracted following medical indication from German donors and collected between 1997 and 2007 were prepared and irradiated at the Helmholtz Zentrum München. Five out of six samples were irradiated at 0.1, 0.2, 0.5, 1.0 and 1.5 Gy air kerma; and one unirradiated sample was kept as control. The doses delivered to the individual samples were unknown to the participants, who were asked to measure each sample nine times, and to report the EPR signal response, the mass of aliquots measured, and the parameters of EPR signal acquisition and signal evaluation. Critical dose and detection limit were calculated by the organizers on the basis of the calibration-curve parameters obtained at every laboratory. For calibration curves obtained by measuring every calibration sample three times, the mean value of the detection limit was 205 mGy, ranging from 56 to 649 mGy. The participants were also invited to provide the signal response and the nominal dose of their current dose calibration curve (wherever available), the critical dose and detection limit of which were also calculated by the organizers. © 2011 Elsevier Ltd. All rights reserved.


Little M.P.,U.S. National Institutes of Health | Azizova T.V.,Southern Urals Biophysics Institute | Bazyka D.,Research Center for Radiation Medicine | Bouffler S.D.,Public Health England | And 24 more authors.
Environmental Health Perspectives | Year: 2012

Background: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels. Objectives: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures. Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms "radiation" AND "heart" AND "disease," OR "radiation" AND "stroke," OR "radiation" AND "circulatory" AND "disease." Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries. R esults: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia. C onclusions: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation- related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).


Kryachok I.,National Cancer Institute | Abramenko I.,Research Center for Radiation Medicine | Bilous N.,Research Center for Radiation Medicine | Chumak A.,Research Center for Radiation Medicine | And 2 more authors.
Medical Oncology | Year: 2011

Important characteristics of chronic lymphocytic leukaemia (CLL) cells are biased immunoglobulin variable heavy chain (IGHV) gene repertoire and expression of stereotyped B-cell receptors (BCRs); however, their prognostic value (in contrast to the impact of IGHV gene mutational status) is less clear. To evaluate the impact of separate IGHV gene usage and expression of stereotyped BCRs in CLL prognosis. Clinical data and IGHV gene configuration were analysed in 319 consecutive patients with CLL. We found that the majority of clinical parameters of patients were defined by IGHV mutational status. Our data also provided new evidence supporting the prognostic relevance of separate IGHV genes or stereotyped BCR in CLL, namely: (a) a restricted non-mutated (UM) IGHV gene repertoire in CLL patients with autoimmune haemolytic anaemia (AIHA) (more frequent expression of UM IGHV1-69, IGHV3-11 and IGHV4-59 genes, P = 0.001), a shorter period of AIHA development for expressors of these genes (P = 0.001) and a tendency towards expression of a stereotypic HCDR3 (P = 0.029), (b) a high incidence of second solid tumour development in IGHV3-21-expressing patients (P = 0.005) and (c) differences in overall survival (OS) of UM CLL patients depending on the BCR structure. Further research of specific IGHV gene usage and subsets of stereotyped BCRs in CLL may be helpful in more precise prediction of CLL prognosis in individual patients. © 2011 Springer Science+Business Media, LLC.


Belyi D.,Research Center for Radiation Medicine | Kovalenko A.,Research Center for Radiation Medicine | Bazyka D.,Research Center for Radiation Medicine | Bebeshko V.,Research Center for Radiation Medicine
Health Physics | Year: 2010

The 1986 Chernobyl Nuclear Power Plant accident that occurred is known as the most severe nuclear disaster in the history of humankind. Acute radiation syndrome (ARS) was diagnosed in 237 persons but only 134 of those were confirmed, including 28 patients who died due to lethal total-body gamma-irradiation and severe skin injuries caused by beta/gamma-emitting radionuclides. A small group of ARS survivors offers an interesting observational insight pertinent to the on-going discussions about long-term non-cancer effects of ionizing radiation. This descriptive study summarizes more than 20 y of follow-up, makes attempts to offer a prognosis for the Chernobyl ARS survivors' health, and explores the link between the outcomes of interest and radiation exposure. Copyright © 2010 Health Physics Society.

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