Publications by authors named "Aleksandr Popov"

6 Publications

  • Page 1 of 1

Molecular dynamics approach to identification of new OGG1 cancer-associated somatic variants with impaired activity.

J Biol Chem 2021 Jan-Jun;296:100229. Epub 2021 Jan 7.

Laboratory of Genome and Protein Engineering, SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia; Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia. Electronic address:

DNA of living cells is always exposed to damaging factors. To counteract the consequences of DNA lesions, cells have evolved several DNA repair systems, among which base excision repair is one of the most important systems. Many currently used antitumor drugs act by damaging DNA, and DNA repair often interferes with chemotherapy and radiotherapy in cancer cells. Tumors are usually extremely genetically heterogeneous, often bearing mutations in DNA repair genes. Thus, knowledge of the functionality of cancer-related variants of proteins involved in DNA damage response and repair is of great interest for personalization of cancer therapy. Although computational methods to predict the variant functionality have attracted much attention, at present, they are mostly based on sequence conservation and make little use of modern capabilities in computational analysis of 3D protein structures. We have used molecular dynamics (MD) to model the structures of 20 clinically observed variants of a DNA repair enzyme, 8-oxoguanine DNA glycosylase. In parallel, we have experimentally characterized the activity, thermostability, and DNA binding in a subset of these mutant proteins. Among the analyzed variants of 8-oxoguanine DNA glycosylase, three (I145M, G202C, and V267M) were significantly functionally impaired and were successfully predicted by MD. Alone or in combination with sequence-based methods, MD may be an important functional prediction tool for cancer-related protein variants of unknown significance.
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http://dx.doi.org/10.1074/jbc.RA120.014455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948927PMC
January 2021

Non-Invasive Diagnosis of Malignancies Based on the Analysis of Markers in Exhaled Air.

Diagnostics (Basel) 2020 Nov 11;10(11). Epub 2020 Nov 11.

School of Nuclear Science & Engineering, National Research Tomsk Polytechnic University, 30 Lenin Avenue, 634050 Tomsk, Russia.

Novel non-invasive methods for the diagnosis of malignancies should be effective for early diagnosis, reproducible, inexpensive, and independent from the human factor. Our aim was to establish the applicability of the non-invasive method, based on the analysis of air exhaled by patients who are at different stages of oropharyngeal, larynx and lung cancer. The diagnostic device includes semiconductor sensors capable of measuring the concentrations of gas components in exhaled air, with the high sensitivity of 1 ppm. The neural network uses signals from these sensors to perform classification and identify cancer patients. Prior to the diagnostic procedure of the non-invasive method, we clarified the extent and stage of the tumor according to current international standards and recommendations for the diagnosis of malignancies. The statistical dataset for neural network training and method validation included samples from 121 patients with the most common tumor localizations (lungs, oropharyngeal region and larynx). The largest number of cases (21 patients) were lung cancer, while the number of patients with oropharyngeal or laryngeal cancer varied from 1 to 9, depending on tumor localization (oropharyngeal, tongue, oral cavity, larynx and mucosa of the lower jaw). In the case of lung cancer, the parameters of the diagnostic device are determined as follows: sensitivity-95.24%, specificity-76.19%. For oropharyngeal cancer and laryngeal cancer, these parameters were 67.74% and 87.1%, respectively. This non-invasive method could lead to relevant medicinal findings and provide an opportunity for clinical utility and patient benefit upon early diagnosis of malignancies.
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http://dx.doi.org/10.3390/diagnostics10110934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696783PMC
November 2020

Cancer Diagnosis by Neural Network Analysis of Data from Semiconductor Sensors.

Diagnostics (Basel) 2020 Sep 5;10(9). Epub 2020 Sep 5.

School of Nuclear Science & Engineering, National Research Tomsk Polytechnic University, 30 Lenin Avenue, 634050 Tomsk, Russia.

"Electronic nose" technology, including technical and software tools to analyze gas mixtures, is promising regarding the diagnosis of malignant neoplasms. This paper presents the research results of breath samples analysis from 59 people, including patients with a confirmed diagnosis of respiratory tract cancer. The research was carried out using a gas analytical system including a sampling device with 14 metal oxide sensors and a computer for data analysis. After digitization and preprocessing, the data were analyzed by a neural network with perceptron architecture. As a result, the accuracy of determining oncological disease was 81.85%, the sensitivity was 90.73%, and the specificity was 61.39%.
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http://dx.doi.org/10.3390/diagnostics10090677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555125PMC
September 2020

Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic.

Proc Biol Sci 2019 12 27;286(1916):20191929. Epub 2019 Nov 27.

Holmenkollen Ski Museum, Oslo, Norway.

Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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http://dx.doi.org/10.1098/rspb.2019.1929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939252PMC
December 2019

Acute myeloid leukemia with t(10;11)(p11-12;q23.3): Results of Russian Pediatric AML registration study.

Int J Lab Hematol 2019 Apr 9;41(2):287-292. Epub 2019 Jan 9.

Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Introduction: Translocations involving the KMT2A gene (also known as MLL) are frequently diagnosed in pediatric acute leukemia cases with either lymphoblastic or myeloid origin. KMT2A is translocated to multiple partner genes, including MLLT10/AF10 localizing at chromosomal band 10p12. KMT2A-MLLT10 is one of the common chimeric genes diagnosed in acute leukemia with KMT2A rearrangement (8%), especially in acute myeloid leukemia (AML; 18%). MLLT10 is localized in very close proximity to two other KMT2A partner genes at 10p11-12-NEBL and ABI1, so they could not be distinguished by conventional cytogenetics.

Methods: In this work, we present a cohort of 28 patients enrolled into Russian Pediatric AML registration study carrying rearrangements between chromosomal regions 11q23.3 and 10p11-12. G-banding, FISH, reverse transcription PCR, and long-distance inverse PCR were used to characterize the KMT2A gene rearrangements in these patients.

Results: We demonstrate that 25 patients harbor the KMT2A-MLLT10 rearrangement, while three patients show the rare KMT2A rearrangements (2× KMT2A-NEBL; 1× KMT2A-ABI1).

Conclusions: Therefore, the combination of cytogenetic and molecular genetic methods is of high importance in diagnosing cases with t(10;11)(p11-12;q23.3).
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http://dx.doi.org/10.1111/ijlh.12969DOI Listing
April 2019

A novel regiospecific cascade synthesis of sulfonamide derivatives from N-(2-polychloroethyl)sulfonamides via chloroaziridine intermediates in the presence of mercaptoethanol.

Mol Divers 2010 Aug 25;14(3):533-41. Epub 2010 Mar 25.

AE Favorsky Irkutsk Institute of Chemistry, Siberian Branch of Russian Academy of Sciences, 1 Favorsky Str, 664033, Irkutsk, Russia.

N-(1-Aryl-2-polychloroethyl)arenesulfonamides obtained on the basis of N,N-dichlorosulfoamides and polychloroethenes or phenylacetylene undergo a reaction cascade in the presence of mercaptoethanol. The reaction cascade opens a new route to the series of cyclic or open-chain sulfonamide derivatives. The process includes cyclization to aziridine intermediates, their further recyclization, and isomerization to imidoylchlorides or chloroimines, followed by substitution or reduction under the action of mercaptoethanol or hydrolysis. The final sulfonamide structures depend on the starting N-(polychloroethyl)sulfonamides. N-(2,2-Dichloroethyl)sulfonamides were transformed into sulfonamide-containing 1,4-oxathians while N-(2,2,2-trichloroethyl)sulfonamides were converted to N-(2-arylacetyl)arenesulfonamides. N-(2-Phenyl-2,2-dichloroethyl)sulfonamides form enamide derivatives that were transformed into aromatic ketones.
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http://dx.doi.org/10.1007/s11030-010-9231-zDOI Listing
August 2010
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