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  1. Article ; Online: Cancer: Bad Luck or Punishment?

    Lichtenstein, A V

    Biochemistry. Biokhimiia

    2017  Volume 82, Issue 1, Page(s) 75–80

    Abstract: Contrasting opinions on the role of extrinsic and intrinsic factors in cancer etiology (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81; Wu, S., et al. (2016) Nature, 529, 43-47) variously define priorities in the war on cancer. The ... ...

    Abstract Contrasting opinions on the role of extrinsic and intrinsic factors in cancer etiology (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81; Wu, S., et al. (2016) Nature, 529, 43-47) variously define priorities in the war on cancer. The correlation between the lifetime risk of several types of cancer and the total number of divisions of normal self-renewing cells revealed by the authors has given them grounds to put forward the "bad luck" hypothesis. It assumes that ~70% of cancer variability is attributed to random errors arising during DNA replication in normal, noncancerous stem cells, i.e. to internal factors, which is impossible either to expect or to prevent. This assumption caused many critical responses that emphasize, on the contrary, the defining role of extrinsic factors in cancer etiology. The analysis of epidemiological and genetic data presented in this work testifies in favor of the "bad luck" hypothesis.
    MeSH term(s) Animals ; DNA Replication/genetics ; DNA, Neoplasm/genetics ; DNA, Neoplasm/metabolism ; Humans ; Neoplasms/genetics ; Neoplasms/metabolism
    Chemical Substances DNA, Neoplasm
    Language English
    Publishing date 2017-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297917010084
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Response to Comments by V. N. Manskikh: "Do External or Internal Factors Lead to Tumor Development? It Is Still Unknown".

    Lichtenstein, A V

    Biochemistry. Biokhimiia

    2017  Volume 82, Issue 1, Page(s) 86–87

    Abstract: The opinion is presented according to which the "bad luck" hypothesis (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81), which has recently received experimental confirmation, has the right to exist, and its criticisms are largely unfounded. ...

    Abstract The opinion is presented according to which the "bad luck" hypothesis (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81), which has recently received experimental confirmation, has the right to exist, and its criticisms are largely unfounded.
    MeSH term(s) Animals ; DNA Replication/genetics ; DNA, Neoplasm/genetics ; DNA, Neoplasm/metabolism ; Humans ; Neoplasms/genetics ; Neoplasms/metabolism
    Chemical Substances DNA, Neoplasm
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297917010102
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cancer research: a hurdle race.

    Lichtenstein, A V

    Biochemistry. Biokhimiia

    2014  Volume 79, Issue 5, Page(s) 385–390

    Abstract: Cancer research has shifted in recent years from studying intracellular processes (identification of damaged genes and signaling pathways) to extracellular (hierarchy of tumor cells, cell transitions, clone competition) and tissue (interactions of a ... ...

    Abstract Cancer research has shifted in recent years from studying intracellular processes (identification of damaged genes and signaling pathways) to extracellular (hierarchy of tumor cells, cell transitions, clone competition) and tissue (interactions of a tumor with its environment) research. But then the next step seems to be logical: studying biochemistry of tumor-bearing organisms (namely, cancer-induced changes in cellular and tissue metabolism leading to the organism's death). These data can help to develop new methods of cancer treatment. This article discusses some of the challenges of contemporary oncology and possible ways to overcome them.
    MeSH term(s) Antibodies/therapeutic use ; Antineoplastic Agents, Alkylating/therapeutic use ; Carcinogenesis ; Humans ; Neoplasms/diagnosis ; Neoplasms/mortality ; Neoplasms/therapy ; Research ; Tumor Microenvironment
    Chemical Substances Antibodies ; Antineoplastic Agents, Alkylating
    Language English
    Publishing date 2014-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297914050010
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  4. Article ; Online: SLAM-MS: Mutation scanning of stem-loop amplicons with TaqMan probes by quantitative DNA melting analysis.

    Kondratova, V N / Botezatu, I V / Shelepov, V P / Lichtenstein, A V

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 5476

    Abstract: DNA Melting Analysis (DMA) with a TaqMan probe covering the mutation "hot spot" is a simple, sensitive, and "closed tube" method of mutation detection. However, DMA requires asymmetric PCR to produce single-stranded amplicons capable of interacting with ... ...

    Abstract DNA Melting Analysis (DMA) with a TaqMan probe covering the mutation "hot spot" is a simple, sensitive, and "closed tube" method of mutation detection. However, DMA requires asymmetric PCR to produce single-stranded amplicons capable of interacting with TaqMan probes. This makes quantitative analysis impossible owing to low amplification efficiency. Moreover, bi-strand mutation detection necessitates two independent PCRs. The SLAM-MS (Stem-Loop AMplicon Mutation Scanning) assay, in which symmetric PCR is performed using primers with 5'-universal primer sequence (UPS), has been developed to detect KRAS mutations. Some of the resulting amplicons, sense and antisense, adopt single-stranded stem-loop conformation and become unable to renature, but able to hybridize with TaqMan probes. Hybrids of stem-loops and complementary TaqMan probes are suitable for melting analysis and simultaneous bi-strand mutation scanning. In addition, the areas under the melting peaks are determined by the PeakFit software, a non-linear iterative curve fitting program, to evaluate the wild-type/mutant allele ratio. Thus, the SLAM-MS assay permits quantification of both the number of copies of the target sequence and the percentage of mutant alleles. For mutant enrichment, the SLAM-MS assay uses TaqMan probes as PCR blocking agents allowing an ~10 times higher mutation detection sensitivity than High Resolution Melting (HRM) assay.
    MeSH term(s) Colonic Neoplasms/genetics ; DNA Mutational Analysis/methods ; DNA Probes ; Humans ; Mutation/genetics ; Nucleic Acid Denaturation ; Polymerase Chain Reaction/methods ; Proto-Oncogene Proteins p21(ras)/genetics
    Chemical Substances DNA Probes ; KRAS protein, human ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2020-03-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-62173-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Carcinogenesis: evolution of concepts.

    Lichtenstein, A V

    Biochemistry. Biokhimiia

    2009  Volume 74, Issue 4, Page(s) 353–361

    Abstract: Cancer is considered as an unintended consequence of internal imperfection of multicellular organisms: Darwinian evolution "does not foresee the future and does not plan for it", it is forced to handle only anything that it has at a given moment "at hand" ...

    Abstract Cancer is considered as an unintended consequence of internal imperfection of multicellular organisms: Darwinian evolution "does not foresee the future and does not plan for it", it is forced to handle only anything that it has at a given moment "at hand", which makes inevitable compromises and restrictions. In this case, there are a number of founding dogmas including mutagenesis as the main driving force of carcinogenesis; the environment as the main source of mutagenic effects; tumor monoclonality; cancer cell multistage transformation as Darwinian process of successive mutation-selection cycles. Recent discoveries complicate, supplement, and sometimes transform into an opposite fixed concepts. As a result, a new "image" of carcinogenesis is formed as a biological phenomenon whose conservation is indicative of its evolutionary utility.
    MeSH term(s) Animals ; Biological Evolution ; Humans ; Mutagenesis ; Neoplasms/etiology ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplastic Processes
    Language English
    Publishing date 2009-04-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/s0006297909040014
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  6. Article: Cancer as a programmed death of an organism.

    Lichtenstein, A V

    Biochemistry. Biokhimiia

    2005  Volume 70, Issue 9, Page(s) 1055–1064

    Abstract: The hypothesis introduces the idea that there is a critical level of mutagenesis that triggers a program of organism death by means of proliferation of killer cells. Similarly to apoptosis, which is an altruistic suicidal act of a faulty cell threatening ...

    Abstract The hypothesis introduces the idea that there is a critical level of mutagenesis that triggers a program of organism death by means of proliferation of killer cells. Similarly to apoptosis, which is an altruistic suicidal act of a faulty cell threatening the stability of a multicellular organism, a malignant tumor is an altruistic suicide of an individual carrier of harmful alleles threatening genetic stability of the population.
    MeSH term(s) Alleles ; Animals ; Apoptosis ; Evolution, Molecular ; Humans ; Mutagenesis ; Neoplasms/genetics
    Language English
    Publishing date 2005-09-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1007/s10541-005-0224-y
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  7. Article: Carcinogenesis: Evolution of concepts

    Lichtenstein, A. V

    Biochemistry. 2009 Apr., v. 74, no. 4

    2009  

    Abstract: Cancer is considered as an unintended consequence of internal imperfection of multicellular organisms: Darwinian evolution “does not foresee the future and does not plan for it”, it is forced to handle only anything that it has at a given moment “at hand” ...

    Abstract Cancer is considered as an unintended consequence of internal imperfection of multicellular organisms: Darwinian evolution “does not foresee the future and does not plan for it”, it is forced to handle only anything that it has at a given moment “at hand”, which makes inevitable compromises and restrictions. In this case, there are a number of founding dogmas including mutagenesis as the main driving force of carcinogenesis; the environment as the main source of mutagenic effects; tumor monoclonality; cancer cell multistage transformation as Darwinian process of successive mutation--selection cycles. Recent discoveries complicate, supplement, and sometimes transform into an opposite fixed concepts. As a result, a new “image” of carcinogenesis is formed as a biological phenomenon whose conservation is indicative of its evolutionary utility.
    Language English
    Dates of publication 2009-04
    Size p. 353-361.
    Publisher SP MAIK Nauka/Interperiodica
    Publishing place Dordrecht
    Document type Article
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297909040014
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: [Scanning for KRAS, NRAS, BRAF, and PIK3CA mutations by DNA melting analysis with TaqMan probes].

    Botezatu, I V / Panchuk, I O / Stroganova, A M / Senderovich, A I / Kondratova, V N / Shelepov, V P / Lichtenstein, A V

    Molekuliarnaia biologiia

    2017  Volume 51, Issue 1, Page(s) 50–58

    Abstract: Scanning for mutations by DNA melting analysis (DMA) is based on asymmetric PCR followed by the melting of duplexes formed by single-stranded amplicons with TaqMan probes. The method is optimally suited for clinical genetic testing; it is easy to perform, ...

    Abstract Scanning for mutations by DNA melting analysis (DMA) is based on asymmetric PCR followed by the melting of duplexes formed by single-stranded amplicons with TaqMan probes. The method is optimally suited for clinical genetic testing; it is easy to perform, high-throughput, and sensitive. The detection limit of mutant alleles by the DMA method is about 3%, which is much higher than the sensitivity of Sanger sequencing. In addition, the DMA method is realized in a closed-tube format, while 2-h assay is carried out in a single tube without any intermediate or additional procedures thereby minimizing the risk of cross contamination of the samples. The validation of the DMA method was performed by scanning for mutations of clinically significant genes KRAS, NRAS, BRAF, and   PIK3CA in 324 DNA samples from tumors of patients with melanoma, colorectal and lung cancer. DNA was isolated either directly from tumor tissues, or from formalin-fixed paraffin-embedded tumor tissues. The detected mutations were verified by Sanger sequencing. The spectra of mutations identified in each tumor type correspond to the literature data and, thus, validate the use of DMA.
    MeSH term(s) Class I Phosphatidylinositol 3-Kinases/genetics ; Colorectal Neoplasms/genetics ; DNA Mutational Analysis ; GTP Phosphohydrolases/genetics ; Humans ; Lung Neoplasms/genetics ; Melanoma/genetics ; Membrane Proteins/genetics ; Mutation ; Nucleic Acid Denaturation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics
    Chemical Substances KRAS protein, human ; Membrane Proteins ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; GTP Phosphohydrolases (EC 3.6.1.-) ; NRAS protein, human (EC 3.6.1.-) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language Russian
    Publishing date 2017-02-28
    Publishing country Russia (Federation)
    Document type Journal Article
    ZDB-ID 213542-5
    ISSN 0026-8984
    ISSN 0026-8984
    DOI 10.7868/S0026898417010062
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  9. Article ; Online: EPSTEIN-BARR VIRUS AND NASOPHARYNGEAL CARCINOMA: VIRAL MARKERS FOR DIAGNOSTICS AND ASSESSMENT OF CLINICAL STATUS OF PATIENTS.

    Kondratova, V N / Lomaya, M V / Ignatova, A V / Dushenkina, T E / Smirnova, K V / Mudunov, A M / Lichtenstein, A V / Gurtsevitch, V E / Senyuta, N B

    Voprosy virusologii

    2018  Volume 63, Issue 2, Page(s) 77–84

    Abstract: The etiological role of the Epstein-Barr virus (EBV) in the development of an undifferentiated histological variant of nasopharyngeal carcinoma (uNPC) found for the first time in regions with a high incidence of this pathology, the Southern provinces of ... ...

    Abstract The etiological role of the Epstein-Barr virus (EBV) in the development of an undifferentiated histological variant of nasopharyngeal carcinoma (uNPC) found for the first time in regions with a high incidence of this pathology, the Southern provinces of China and the countries of Southeast Asia, and later in the rest of the world, has served as a basis for the widespread use of EBV serological markers for the diagnosis of this form of tumor. In recent years, the use of a test based on the quantitative determination of the EBV DNA concentration in the blood plasma of uNPC patients for early detection and monitoring of the disease has become widespread in endemic regions. In non-endemic regions, such studies virtually have not been carried out, and moreover, the comparative evaluation of the significance of two viral markers, serological and EBV DNA load in the bloodstream of uNPC patients, for diagnostics and evaluation of the therapeutic effect was not investigated. The aim of this study was to compare the clinical value of two serological markers and plasma EBV DNA load in uNPC patients from non-endemic region (Russia). The obtained results indicate that IgA antibodies to the viral capsid antigen (IgA/VCA) and plasma EBV DNA concentration can be successfully used for the diagnosis of uNPC, while IgG/VCA antibodies have no practical significance as an uNPC marker. In addition, it was found that plasma EBV DNA load is more sensitive marker of uNPC than IgA/VCA titers because DNA copy numbers reflect more accurately the effect of the therapy and the clinical state of patients at the stages of remission or relapse. It was shown for the first time that in the non-endemic region the simultaneous evaluation of IgA/VCA antibody levels and the plasma EBV DNA loads are the most effective markers for the diagnostics of uNPC. However, we believe, that it is more practical to use IgA/VCA antibody levels for uNPC screening, and plasma EBV DNA copies - for monitoring of the disease.
    Language English
    Publishing date 2018-04-20
    Publishing country Russia (Federation)
    Document type Journal Article
    ZDB-ID 201241-8
    ISSN 2411-2097 ; 0507-4088
    ISSN (online) 2411-2097
    ISSN 0507-4088
    DOI 10.18821/0507-4088-2018-63-2-77-84
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Isotachophoresis of nucleic acids in agarose gel rods.

    Kondratova, V N / Botezatu, I V / Shelepov, V P / Lichtenstein, A V

    Biochemistry. Biokhimiia

    2009  Volume 74, Issue 11, Page(s) 1285–1288

    Abstract: A new method of electrophoresis (isotachophoresis in agarose gel rods) in which nucleic acid molecules are not separated but, oppositely, are brought together into one band, was elaborated. Heterogeneous in size DNA and RNA polymers present in a few ... ...

    Abstract A new method of electrophoresis (isotachophoresis in agarose gel rods) in which nucleic acid molecules are not separated but, oppositely, are brought together into one band, was elaborated. Heterogeneous in size DNA and RNA polymers present in a few milliliters of a solution at so low concentration that their isolation by other methods is hardly attainable and fraught with losses are brought together into one visible narrow band when put in a discontinuous electric field. Polynucleotides migrate in dilute (0.1%) semifluid agarose gel that permits easy quantitative isolation of the band of interest. Resulting DNA can be used directly in PCR. The suggested method for isolation of micro amounts of nucleic acids from dilute solutions can be applied to forensic and clinical research and cancer gene diagnostics by the analysis of fragmented circulating DNA from bodily fluids.
    MeSH term(s) Blood Chemical Analysis ; DNA/chemistry ; DNA/genetics ; Electrophoresis, Agar Gel/methods ; Humans ; RNA/chemistry ; RNA/genetics
    Chemical Substances RNA (63231-63-0) ; DNA (9007-49-2)
    Language English
    Publishing date 2009-11-11
    Publishing country United States
    Document type Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/s0006297909110169
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