“Delayed death” phenomenon: A synergistic action of cyclophosphamide and exogenous DNA

Долгова, Е. В.; Proskurina, Anastasia S.; Николин, В. П.; Попова, Н. А.; Alyamkina, E. A.; Orishchenko, Кonstantin E.; Рогачев, В. А.; Efremov, Yaroslav R.; Dubatolova, T. D.; Prokopenko, Anastasia V.; Черных, Е. Р.; Останин, А. А.; Taranov, Oleg S.; Омигов, В. В.; Zagrebelniy, Stanislav N.; Богачев, С. С.; Shurdov, Mikhail A.

doi:10.1016/j.gene.2011.12.032

Cited by 31 publications

(46 citation statements)

References 30 publications

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“…At the same time, we showed that synergistic action of CP and dsDNA may alter hematopoietic stem cells so that some of their pluripotency properties are lost 15 , 16 …”

Section: Resultsmentioning

confidence: 96%

“…Studies of exogenous dsDNA fragment internalization by mouse bone marrow cells reported an interesting fact that up to 40% of hematopoietic CD34 + progenitors can incorporate DNA 15 , 16 . Subsequent analysis suggested that internalization of dsDNA fragments is a general feature of undifferentiated cells with stem cell potential.…”

Section: Resultsmentioning

confidence: 99%

“…Southern blot and gel images are shown. Bone marrow cells were used as a positive control, where DNA internalization is well-documented 15 . ( E ) FACS profiles showing dsDNA internalization upon increasing concentration of the labeled substrate in the medium.…”

Section: Resultsmentioning

confidence: 99%

“…These data suggested that presence of dsDNA inside bone marrow cells while they are trying to repair CP-induced ICLs interferes with this repair, resulting in a severely compromised pluripotency of hematopoietic stem cells 15 , 16 . It was suggested that dsDNA fragments internalized into nuclei of tumor-forming cells (in the context of Krebs-2 ascites) may similarly interfere with the repair process.…”

Section: Resultsmentioning

confidence: 99%

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Identification of cancer stem cells and a strategy for their elimination

Долгова

Alyamkina

Efremov

et al. 2014

Cancer Biology & Therapy

100

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It has been established previously that up to 40% of mouse CD34+ hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential.

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“…At the same time, we showed that synergistic action of CP and dsDNA may alter hematopoietic stem cells so that some of their pluripotency properties are lost 15 , 16 …”

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Identification of cancer stem cells and a strategy for their elimination

Долгова

Alyamkina

Efremov

et al. 2014

Cancer Biology & Therapy

100

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“…Во-вторых, нахождение свободных, несвязанных фрагментов дцДНК в системном кровотоке в те-чение длительного периода времени может при-водить к увеличению ее уровня в органах и тка-нях, расположенных дистантно от первичного очага повреждения, например, в костномозговых нишах, где дцДНК может интернализоваться в стволовые клетки. Установлено, что интерна-лизованные фрагменты ДНК участвуют в репа-ративно-рекомбинационных процессах, идущих в стволовые клетки [20,47,48]. Предполагается, что если в ходе нормальной репликации стволо-вых клеток образуются временные аберрантные двуцепочечные концы [50,61], то фрагменты экстраклеточной ДНК, находящиеся в ядерном пространстве, могут интерферировать коррект-ное восстановление целостности хромосомы, что приведет к катастрофическим для стволовых клеток последствиям, например, нарушению их дифференцировочного потенциала или сниже-нию способности к самоподдержанию.…”

Section: цитозольные сенсоры нуклеиновых кислотunclassified

Intracellular Systems for Detection of Exogenous Nucleic Acids and Triggering Mechanisms of Immune Response to Dna Internalization

Алямкина¹,

Долгова²,

Proskurina³

et al. 2014

Med.Imm.Rus

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Резюме. В защитной системе клетки существуют специфические механизмы, детектирующие про-никновение чужеродных молекул, так называемых патоген-ассоциированных молекулярных паттер-нов (ПАМП), в ее внутреннее пространство. Распознавание ПАМП происходит или с участием Tolllike рецепторов, или сопряжено с активностью цитозольных сенсоров. В последнее время большое внимание уделяется изучению процесса детекции нуклеиновых кислот, доставленных в цитозоль эу-кариотической клетки. К настоящему времени идентифицированы такие внутриклеточные сенсоры двуцепочечной ДНК, как STING, DAI, семейство NOD-like белков, RLH-геликазы, белки семейства HIN-200. Одни из этих факторов непосредственно взаимодействуют с двуцепочечной ДНК, другие являются охарактеризованными посредниками в передаче сигнала с неизвестного ДНК-сенсора. Результатом активации каскада событий, запускаемых цитозольной двуцепочечной ДНК, является индукция ядерных транскрипционных факторов NF-κB и IRF3/IRF7 и усиление продукции интер-ферона-бета, а также процессинг предшественников провоспалительных цитокинов IL-1β и IL-18 путем формирования инфламмасом. В настоящем обзоре обобщена информация, характеризующая пути реализации сигнала от момента определения внутриклеточной двуцепочечной ДНК до форми-рования клеточного иммунного ответа. Россия, г. Новосибирск, пр. акад. Лаврентьева, 10.

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The Basics of Molecular Pathology

2013

In Situ Molecular Pathology and Co-Expression Analyses

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2As we will learn, hydrogen bonding is also important in understanding the interaction of proteins with each other and with other types of macromolecules. However, since proteins have many side chains that can be ionically charged, whereas DNA and RNA have only two and one such ionically charged units, respectively, on the entire macromolecule, the ionic potential will be much greater for proteins than for nucleic acids. Similarly, proteins will be able to form hydrophobic and hydrophilic pockets in regions of their sequence, which DNA and RNA macromolecules cannot do. The bottom line is that two related phenomenon will dictate the strength of the hybridization between DNA/DNA and cDNA/RNA: Hydrogen bonds 2. Breathability of the macromoleculeWe discuss the concept of breathability in much more detail later in this book. For now, let's simply understand the term as a way to denote the fact that hybridized macromolecules will have a tendency to separate and reattach. When in this state, they are more susceptible to complete separation. This tendency of RNA/cDNA and DNA/DNA hybrids to separate and reattach (and separate and reattach again) we call "breathability." THE BASIC UNITS OF DNA AND RNALet's look at how an understanding of the structure of DNA and RNA can help us when doing in situ hybridization. First, let's discuss the phosphodiester bond. Although the phosphodiester bond is strong, high temperatures can cause a small percentage of these bonds to break in formalin-fixed, paraffin-embedded tissues. During the paraffin embedding process, prolonged exposure to temperatures at 65°C are used. If you extract the DNA from such samples and compare it to fresh, unfixed samples of the same tissues, it will be evident that the high temperatures have induced rare nicks among the doublestranded human DNA or, as shown by multiple groups, in the doubled-stranded HPV DNA. The term "nick" simply refers to breakage of the phosphodiester bond. Since the two DNA strands are perfectly matched strands in parallel and antiparallel orientation, they certainly would be able to stay hybridized if a small percentage of the phosphodiester bonds were broken, much the same way that a zipper

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“Delayed death” phenomenon: A synergistic action of cyclophosphamide and exogenous DNA

Cited by 31 publications

References 30 publications

Identification of cancer stem cells and a strategy for their elimination

Identification of cancer stem cells and a strategy for their elimination

Intracellular Systems for Detection of Exogenous Nucleic Acids and Triggering Mechanisms of Immune Response to Dna Internalization

The Basics of Molecular Pathology

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