Publications by authors named "Alexander E Nosyrev"

7 Publications

  • Page 1 of 1

Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements.

Cells 2019 10 14;8(10). Epub 2019 Oct 14.

I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia.

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients' prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients' samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.
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http://dx.doi.org/10.3390/cells8101251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829588PMC
October 2019

Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics.

Cells 2019 08 9;8(8). Epub 2019 Aug 9.

Centre of Toxicology Science and Research, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece.

Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.
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http://dx.doi.org/10.3390/cells8080863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721640PMC
August 2019

Indicator PCBs in farmed and wild fish in Greece - Risk assessment for the Greek population.

Food Chem Toxicol 2019 May 18;127:260-269. Epub 2019 Mar 18.

Centre of Toxicology Science and Research, University of Crete, School of Medicine, Crete, Greece.

Health benefits of fish consumption could be counterbalanced by the intake of contaminants after long term fish consumption, burdened even in trace levels. The presence of the indicator PCBs (NDL-PCBs and PCB 118) in farmed and wild seabream and seabass was evaluated. For the determination of PCB, a GC-MS method was developed and evaluated. The association of PCB accumulation in fish with seasonality, locality, production mode and species was also investigated. A new approach for the risk characterisation after exposure to NDL-PCB through fish consumption in Greece was developed, based on the real exposure and the permitted maximum levels of both aggregated dietary exposure and exposure through fish consumption. PCB levels determined in fish were below established permitted limits (6.24 ng/g 95th percentile), while PCB levels and congener distribution varied significantly between farmed and wild fish (p = 0.001). Seasonality was highlighted as an important factor affecting NDL-PCBs accumulation, with high levels coinciding with the reproduction period of each species. Differences were also depicted for sampling sites, with PCB 118 presenting significantly higher values in open seas while NDL-PCB congeners in closed seas. Risk assessment of NDL-PCB intake through fish consumption corrected for the aggregated exposure revealed no risk for the consumers.
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http://dx.doi.org/10.1016/j.fct.2019.03.027DOI Listing
May 2019

CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides.

Toxicol Rep 2017 26;4:335-341. Epub 2017 May 26.

Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Greece.

The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases.
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http://dx.doi.org/10.1016/j.toxrep.2017.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615117PMC
May 2017

Environmental exposure to organophosphorus nerve agents.

Environ Toxicol Pharmacol 2017 Dec 7;56:163-171. Epub 2017 Sep 7.

Faculty of Agriculture, University of Belgrade, Institute for Phytomedicine, Serbia. Electronic address:

Exposure to organophosphorus nerve agents, the most deadly chemical warfare agents, is possible in a variety of situations, such as destruction of chemical warfare agents, terrorist attacks, armed conflicts or accidents in research laboratories and storage facilities. Hundreds of thousands of tons of chemical munitions were disposed of at the sea in the post World War II period, with European, Russian, Japanese and US coasts being the most affected. Sulfur mustard, Lewisite and nerve agents appear to be the most frequently chemical warfare agents disposed of at the sea. Addressing the overall environmental risk, it has been one of the priorities of the world community since that time. Aside from confirming exposure to nerve agents in the alleged use for forensic purposes, the detection and identification of biological markers of exposure are also needed for the diagnosis and treatment of poisoning, in addition to occupational health monitoring for specific profiles of workers. When estimating detrimental effects of acute or potential chronic sub-lethal doses of organophosphorus nerve agents, released accidentally or intentionally into the environment, it is necessary to understand the wide spectra of physical, chemical and toxicological properties of these agents, and predict their ultimate fate in environmental systems.
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http://dx.doi.org/10.1016/j.etap.2017.09.004DOI Listing
December 2017

Application of metabolomics: Focus on the quantification of organic acids in healthy adults.

Int J Mol Med 2017 Jul 10;40(1):112-120. Epub 2017 May 10.

Laboratory of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003, Greece.

Metabolomics, a 'budding' discipline, may accurately reflect a specific phenotype which is sensitive to genetic and epigenetic interactions. This rapidly evolving field in science has been proposed as a tool for the evaluation of the effects of epigenetic factors, such as nutrition, environment, drug and lifestyle on phenotype. Urine, being sterile, is easy to obtain and as it contains metabolized or non‑metabolized products, is a favored study material in the field of metabolomics. Urine organic acids (OAs) reflect the activity of main metabolic pathways and have been used to assess health status, nutritional status, vitamin deficiencies and response to xenobiotics. To date, a limited number of studies have been performed which actually define reference OA values in a healthy population and as reference range for epigenetic influences, and not as a reference to congenital metabolic diseases. The aim of the present study was thus the determination of reference values (RVs) for urine OA in a healthy adult population. Targeted metabolomics analysis of 22 OAs in the urine of 122 healthy adults by gas chromatography‑mass spectrometry, was conducted. Percentile distributions of the OA concentrations in urine, as a base for determining the RVs in the respective population sample, were used. No significant differences were detected between female and male individuals. These findings can facilitate the more sensitive determination of OAs in pathological conditions. Therefore, the findings of this study may contribute or add to the information already available on urine metabolite databases, and may thus promote the use of targeted metabolomics for the evaluation of OAs in a clinical setting and for pathophysiological evaluation. However, further studies with well‑defined patients groups exhibiting specific symptoms or diseases are warranted in order to discern between normal and pathological values.
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http://dx.doi.org/10.3892/ijmm.2017.2983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466383PMC
July 2017

Quantification of 4-Methylimidazole in soft drinks, sauces and vinegars of Greek market using two liquid chromatography techniques.

Food Chem Toxicol 2017 Sep 19;107(Pt B):565-571. Epub 2017 Mar 19.

Laboratory of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Greece. Electronic address:

The substance 4-methylimidazole (4-MEI) has raised several concerns regarding its toxicity to humans, although no harmonized classification has yet been decided. The regulatory limits for food products set by various authorities in Europe and the USA differ considerably. The purpose of the present study is to compare two liquid chromatography techniques in order to determine the levels of 4-MEI in food products from the Greek market and roughly estimate the possible exposure and relevant health risk for the consumers. A total of thirty-four samples (soft drinks, beers, balsamic vinegars, energy drinks and sauces) were collected and analyzed. The quality parameters for both analytical methodologies (linearity, accuracy, inter day precision, recovery) are presented. No detectable levels of 4-MEI are found in beers and soft drink samples, other than cola type. On the other hand, 4-MEI was detected in all cola type soft drinks (15.8-477.0 ng/ml), energy drinks (57.1%, 6.6-22.5 ng/ml) and vinegar samples (66.7%, 9.7-3034.7 ng/ml), while only one of the sauce samples was found to have a detectable level of 17.5 ng/ml 4-MEI.
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http://dx.doi.org/10.1016/j.fct.2017.03.028DOI Listing
September 2017