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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Ozerskaya A. V., Zamay T. N., Kolovskaya O. S., Tokarev N. A., Belugin K. V., Chanchikova N. G., Badmaev O. N., Zamay G. S., Shchugoreva I. A., Moryachkov R. V., Zabluda V. N., Khorzhevskii V. A., Shepelevich N., Gappoev S. V., Karlova E. A., Saveleva A. S., Volzhentsev A. A., Blagodatova A. N., Lukyanenko K. A., Veprintsev D. V., Smolyarova T. E., Tomilin F. N., Zamay S. S., Silnikov V. N., Berezovski M. V., Kichkailo A. S.
Заглавие : 11C-radiolabeled aptamer for imaging of tumors and metastases using positron emission tomography-computed tomography
Место публикации : Mol. Ther. Nucl. Acids. - 2021. - Vol. 26. - P.1159-1172. - ISSN 21622531 (ISSN), DOI 10.1016/j.omtn.2021.10.020
Примечания : Cited References: 44
Аннотация: Identification of primary tumors and metastasis sites is an essential step in cancer diagnostics and the following treatment. Positron emission tomography-computed tomography (PET/CT) is one of the most reliable methods for scanning the whole organism for malignancies. In this work, we synthesized an 11C-labeled oligonucleotide primer and hybridized it to an anti-cancer DNA aptamer. The 11C-aptamer was applied for in vivo imaging of Ehrlich ascites carcinoma and its metastases in mice using PET/CT. The imaging experiments with the 11C-aptamer determined very small primary and secondary tumors of 3 mm2 and less. We also compared 11C imaging with the standard radiotracer, 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), and found better selectivity of the 11C-aptamer to metastatic lesions in the metabolically active organs than 18F-FDG. 11C radionuclide with an ultra-short (20.38 min) half-life is considered safest for PET/CT imaging and does not cause false-positive results in heart imaging. Its combination with aptamers gives us high-specificity and high-contrast imaging of cancer cells and can be applied for PET/CT-guided drug delivery in cancer therapies.
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Вид документа : Статья из сборника (однотомник)
Шифр издания :
Автор(ы) : Moryachkov R. V., Zabluda V. N., Shchugoreva, Irina A., Artyushenko P. V., Kichkaylo A.S., Spiridonova V. A., Berlina A. N., Sokolov A. Е.
Заглавие : Investigation of the spatial structure of bionanoconjugates based on DNA aptamers by synchrotron methods
Коллективы : "Functional materials", International conference, Крымский федеральный университет имени В.И. Вернадского
Место публикации : Ovchinnikov S. G. International conference "Functional materials": book of abstracts/ ed. V. N. Berzhansky ; org. com. S. G. Ovchinnikov [et al.]. - Simferopol, 2021. - P.310
Примечания : Библиогр.: 3 назв. - The research was carried out with a grant from the Russian Science Foundation № 21-12-00226, https://rscf.ru/project/21-12-00226/
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Mironov, Vladimir, Shchugoreva I. A., Artyushenko P. V., Morozov D. I., Borbone N., Oliviero G., Zamay T. N., Moryachkov R. V., Kolovskaya, ., Lukyanenko K. A., Song Y. L., Merkuleva I. A., Zabluda V. N., Peters G., Koroleva L. S., Veprintsev D. V., Glazyrin Y. E., Volosnikova E. A., Belenkaya S. V., Esina T. I., Isaeva A. A., Nesmeyanova, ., Shanshin D. V., Berlina A. N., Komova N. S., Svetlichnyi V. A., Silnikov V. N., Shcherbakov D. N., Zamay G. S., Zamay S. S., Smolyarova T. E., Tikhonova E. P., Chen U. S., Jeng G., Condorelli V., Franciscis G., Groenhof C. Y., Yang A. A., Moskovsky D. G., Fedorov F. N., Tomilin F. N., Tan Y., Alexeev M. V., Berezovski A. S., Kichkailo A.S.
Заглавие : Structure- and interaction-based design of anti-SARS-CoV-2 Aptamers
Коллективы : Aptamerlab LCC; U.S. Department of Energy, Office of ScienceUnited States Department of Energy (DOE) [DE-AC02-06CH11357]; European UnionEuropean Commission [H2020-INFRAEDI-02-2018-823830, H2020-EINFRA-2015-1-675728, 872391, PRISAR2 872860]; CSC-IT center in Espoo, Finland; PRACE; Russian Foundation for Basic ResearchRussian Foundation for Basic Research (RFBR) [19-03-00043]; Ministry of Science and Higher Education of Russian Federation (state assignment of the Research Center of Biotechnology RAS); Italian Ministry of Education and ResearchMinistry of Education, Universities and Research (MIUR) [FISR2020 _00177]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [OV1-170353]; Russian Science FoundationRussian Science Foundation (RSF) [21-73-20240]
Место публикации : Chem. - Eur. J. - 2022. - Vol. 28, Is. 12. - Ст.e202104481. - ISSN 0947-6539, DOI 10.1002/chem.202104481. - ISSN 1521-3765(eISSN)
Примечания : Cited References: 85. - The authors are grateful to JCSS Joint Super Computer Center of the Russian Academy of Sciences – Branch of Federal State Institution “Scientific Research Institute for System Analysis of the Russian Academy of Sciences” for providing supercomputers for computer simulations. The authors thank the RSC Group (www.rscgroup.ru) and personally Mr. Oleg Gorbachev for the constant support and establishment of “The Good Hope Net Project” (www.thegoodhope.net) multifunctional non-profit anti-CoVID research project. The authors also thank the Helicon Company (www.helicon.ru) and personally Olesya Kucenko, Alexander Kolobov, Leonid Klimov for instrumental support and help with conducting fluorescence polarization assays, which were performed on a demo instrument Clariostar Plus microplate reader (BMG LABTECH, Germany). We thank Dr. Yong-Zhen Zhang for providing the genome sequence of 2019-nCoV and Dr. Xinquan Wang for providing the crystal structure of the binding domain of the SARS-2 Spike protein. The authors are grateful to Aptamerlab LCC financial support (www.aptamerlab.com). Y.A.’s work at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, under contract DE-AC02-06CH11357. The work of D.M. and G.G. has been done as part of the BioExcel CoE (www.bioexcel.eu), a project funded by the European Union contracts H2020-INFRAEDI-02-2018-823830 and H2020-EINFRA-2015-1-675728. D.M. and G.G. also thank the CSC-IT center in Espoo, Finland, as well as PRACE for awarding access to resource Curie-Rome based in France at GENCI. V.M. thanks Russian Foundation for Basic Research (project number 19-03-00043). A.B.’s and N.K.’s work was supported by the Ministry of Science and Higher Education of Russian Federation (state assignment of the Research Center of Biotechnology RAS). V. deF. G.C., N.B and G.O. are grateful to FISR2020 _00177 Shield, Italian Ministry of Education and Research, for funding. GC is grateful to the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement: cONCReTE 872391; PRISAR2 872860. Use of the 13 A BioSAXS beamtime at the Taiwan Photon Source is acknowledged. The work of M.V.B was funded by the Canadian Institutes of Health Research grant OV1-170353. SAXS measurements and PIEDA analyses were funded by the Russian Science Foundation (project No 21-73-20240 for A.S.K.)
Предметные рубрики: BIOLOGICAL MACROMOLECULES
SOLUTION SCATTERING
BINDING
SPIKE
Аннотация: Aptamer selection against novel infections is a complicated and time-consuming approach. Synergy can be achieved by using computational methods together with experimental procedures. This study aims to develop a reliable methodology for a rational aptamer in silico et vitro design. The new approach combines multiple steps: (1) Molecular design, based on screening in a DNA aptamer library and directed mutagenesis to fit the protein tertiary structure; (2) 3D molecular modeling of the target; (3) Molecular docking of an aptamer with the protein; (4) Molecular dynamics (MD) simulations of the complexes; (5) Quantum-mechanical (QM) evaluation of the interactions between aptamer and target with further analysis; (6) Experimental verification at each cycle for structure and binding affinity by using small-angle X-ray scattering, cytometry, and fluorescence polarization. By using a new iterative design procedure, structure- and interaction-based drug design (SIBDD), a highly specific aptamer to the receptor-binding domain of the SARS-CoV-2 spike protein, was developed and validated. The SIBDD approach enhances speed of the high-affinity aptamers development from scratch, using a target protein structure. The method could be used to improve existing aptamers for stronger binding. This approach brings to an advanced level the development of novel affinity probes, functional nucleic acids. It offers a blueprint for the straightforward design of targeting molecules for new pathogen agents and emerging variants.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Moryachkov R. V., Nikolaeva P. A., Spiridonova V. A.
Заглавие : Structure approaches to study of DNA aptamers in solution
Место публикации : Sib. Med. Rev. - 2021. - Vol. 2021, Is. 2. - P.76-78. - ISSN 18199496 (ISSN), DOI 10.20333/2500136-2021-2-76-78; Сиб. мед. обозрение
Примечания : Cited References: 5. - The reported study was funded by RFBR, project number 19-32-90266
Аннотация: The high potential of aptamers – specific molecular agents based on short single-stranded nucleic acids – makes high demands on the molecules under development for the efficiency of interaction with target biomolecules. In this work, approaches are considered for studying the spatial structure of DNA aptamers in solution using various complementary methods, which make it possible to obtain a more complete picture of the formation of the structure and conformational changes, to track the interaction with the target protein, the tendency to oligomerization, and to characterize the spatial structure of both individual molecules and complexes.
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Вид документа : Статья из сборника (однотомник)
Шифр издания :
Автор(ы) : Sokolov A. Е., Zabluda V. N., Sherepa A. V., Knyazev Yu. V., Volochaev M. N., Kurilina A., Velikanov D. A., Goncharova D. A., Shabalina A., Svetlichnyi V.
Заглавие : Magnetic properties of iron oxide nanoparticles to create aptamer bionanoconjugates
Коллективы : Aptamers in Russia, international conference
Место публикации : Aptamers in Russia, international conference (1 ; 2019 ; Aug. 27-30 ; Krasnoyarsk). Molecular Therapy - Nucleic Acids: book of abstracts of the 1st Int. conf. "Aptamers in Russia 2019". - 2019. - Vol. 17, Suppl. 1. - P.12
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Вид документа : Статья из сборника (однотомник)
Шифр издания :
Автор(ы) : Denissenko P., Denisenko V. V., Denisov I., Kantsler V., Kolovskaya O. S., Lapin I. N., Sokolov A. Е., Svetlichnyi V., Zabluda V. N., Zamay S. S., Kichkailo A.S.
Заглавие : Magnetic sorting of tumor cells with attached magnetic nanoparticles in a microchannel
Коллективы : Aptamers in Russia, international conference
Место публикации : Aptamers in Russia, international conference (1 ; 2019 ; Aug. 27-30 ; Krasnoyarsk). Molecular Therapy - Nucleic Acids: book of abstracts of the 1st Int. conf. "Aptamers in Russia 2019". - 2019. - Vol. 17, Suppl. 1. - P.14
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Artyushenko P. V., Mironov V. A., Morozov D. I., Shchugoreva I. A., Borbone N., Tomilin F. N., Kichkailo A. S.
Заглавие : Computational approach to design of aptamers to the receptor binding domain of sars-cov-2
Место публикации : Sib. Med. Rev. - 2021. - Vol. 2021, Is. 2. - P.66-67. - ISSN 18199496 (ISSN), DOI 10.20333/2500136-2021-2-66-67; Сиб. мед. обозрение
Примечания : Cited References: 5
Аннотация: The aim of the research. In this work, in silico selection of DNA-aptamers to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was performed using molecular modeling methods. Material and methods. A new computational approach to aptamer in silico selection is based on a cycle of simulations, including the stages of molecular modeling, molecular docking, molecular dynamic simulations, and quantum chemical calculations. To verify the obtained calculated results flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods were applied. Results. An initial library consisted of 256 16-mer oligonucleotides was modeled. Based on molecular docking results, the only one aptamer (Apt16) was selected from the library as a starting aptamer to the RBD protein. For Apt16/RBD complex, molecular dynamic and quantum chemical calculations revealed the pairs of nucleotides and amino acids whose contribution to the binding between aptamer and RBD is the largest. Taking into account these data, Apt16 was subjected to the structure modifications in order to increase the binding with the RBD. Thus, a new aptamer Apt25 was designed. The procedure of 1) aptamer structure modeling/modification, 2) molecular docking, 3) molecular dynamic simulations, 4) quantum chemical calculations was performed sev-eral times. As a result, four aptamers (Apt16, Apt25, Apt27, Apt31) to the RBD were designed in silico without any preliminary experimental data. Binding of the each modeled aptamer to the RBD was studied in terms of interactions between residues in protein and nucleotides in the aptamers. Based on the simulation results, the strongest binding with the RBD was predicted for two Apt27 and Apt31aptamers. The calculated results are in good agreement with experimental data obtained by flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods. Conclusion. The proposed computational approach to selection and refinement of aptamers is universal and can be used for wide range of molecular ligands and targets.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Nikolaeva P. A., Moryachkov R. V., Raldugina V. N., Naumova Iu. O., Novikova T. M., Spiridonova V. A.
Заглавие : Structural analysis of thrombin-binding G-aptamers in presence of bivalent ions
Место публикации : Sib. Med. Rev. - 2022. - Is. 5. - P.111-113. - ISSN 18199496 (ISSN), DOI 10.20333/25000136-2022-5-111-113; Сиб. мед. обозрение
Примечания : Cited References: 4. - The study was supported by a grant from the Russian Science Foundation (project number 21-73-20240)
Аннотация: The aim of this study was to examine 3D structures of DNA aptamers, thrombin inhibitors. The main objective was to study 3D structure 15TBA, RE31, NU172 aptamers using the small-angle X-ray scattering method. The size of 15TBA was 4.5 nm, which corresponds to a partially unfolded conformation. The CD spectrum of Nu172 in the presence of 50 mM strontium ions indicates the presence of an antiparallel G-quadruplex, the concentration o f which drops at 50°C. NU172 does not have a rigid structure, apparently due to the presence of a guanine residue in the GT loop. The NU172 aptamer does not form a stable conformation in solution either without ions or with Ba2+ and Sr2+ ions. It was shown that there is possibility of aptamers transition from one conformation to another dependently on concentration and temperature confirms that the potassium ion is a unique stabilizing ion of natural molecules containing G-quadruplexes.
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Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Zamay, Tatiana, Zamay, Sergey, Luzan, Natalia, Fedotovskaya, Victoriya, Masyugin, Albert, Zelenov F., Koshmanova, Anastasia, Nikolaeva, Elena, Kirichenko, Daria, Veprintsev, Dmitry, Kolovskaya, Olga, Shchugoreva, Irina, Zamay, Galina, Lapin I. N., Lukyanenko A. V., Borus, Andrey, Sukhachev A. L., Volochaev M. N., Lukyanenko, Kirill, Shabanov, Alexandr, Zabluda V. N., Zhizhchenko, Alexey, Kuchmizhak, Aleksandr, Sokolov A. Е., Narodov, Andrey, Prokopenko, Vladimir, Galeev, Rinat, Svetlichnyi, Valery, Kichkailo, Anna
Заглавие : Magnetic nanoscalpel for the effective treatment of ascites tumors
Место публикации : J. Funct. Biomater. - 2023. - Vol. 14, Is. 4. - Ст.179. - ISSN 20794983 (eISSN), DOI 10.3390/jfb14040179
Примечания : Cited References: 36. - This research was funded by the Regional State Autonomous Institution “Krasnoyarsk Regional Fund for Support of Scientific and Scientific and Technical Activities”, Competition of scientific, technical, and innovative projects in the interests of the first world-class climate scientific and educational center “Yenisei Siberia”, grant “Carrying out applied research and development aimed at creating technologies for the production of nanoscalpels based on magnetic nanodisks for microsurgery of glial brain tumors” No. 2022060108781 and with the support of a partner company JSC «NPP «Radiosviaz»
Аннотация: One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument (“smart nanoscalpel”) at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the “Nanoscalpel” in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a “smart nanoscalpel” is practical for the microsurgery of malignant neoplasms.
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10.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Kichkailo A. S., Narodov A. A., Komarova M. A., Zamay T. N., Zamay G. S., Kolovskaya O. S., Erakhtin E. E., Glazyrin Y. E., Veprintsev D. V., Moryachkov R. V., Zabluda V. N., Shchugoreva I., Artyushenko P., Mironov V. A., Morozov D. I., Gorbushin A. V., Khorzhevskii V. A., Koshmanova A. A., Nikolaeva E. D., Grinev I. P., Voronkovskii I. I., Grek D. S., Belugin K. V., Volzhentsev A. A., Badmaev O. N., Luzan N., Lukyanenko K. A., Peters G., Lapin I. N., Kirichenko A. K., Konarev P. V., Morozov E. V, Mironov G. G., Gargaun A., Muharemagic D., Zamay S. S., Kochkina E. V., Dymova M. A., Smolyarova T. E., Sokolov A. Е., Modestov A. A., Tokarev N. A., Shepelevich N., Ozerskaya A. V., Chanchikova N. G., Krat A. V., Zukov R. A., Bakhtina V. I., Shnyakin P. G., Shesternya P. A., Svetlichnyi V. A., Petrova M. M., Artyukhov I. P., Tomilin F. N., Berezovski, Maxim V.
Заглавие : Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells
Место публикации : Mol. Ther. - Nucleic Acids. - 2023. - Vol. 32. - P.267-288. - ISSN 21622531 (eISSN), DOI 10.1016/j.omtn.2023.03.015
Примечания : Cited References: 69. - The authors are grateful to all the patients and hospital staff participating in this research. We acknowledge the assistance of the AptamerLab LCC (www.aptamerlab.com) and personally Mr. Vasily Mezko for the aptamer 3D structure optimization and financial and technical support. The authors thank Mr. Alexey Kichkailo, Dr. Arkady B. Kogan, and Dr. Rinat G. Galeev for their general support. Mrs. Valentina L. Grigoreva, and Irina V. Gildebrand for the help with histological staining. Technical and instrumental support was provided by the Multiple-Access Center at Tomsk State University; the Krasnoyarsk Inter-District Ambulance Hospital, named after N.S. Karpovich; John L. Holmes Mass Spectrometry Facility at the University of Ottawa; Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency; Shared Core Facilities of Molecular and Cell Technologies at Krasnoyarsk State Medical University and Krasnoyarsk Regional Centre for Collective Use at the Federal Research Centre “KSC SB RAS”. The confocal fluorescence microscopy research was carried out with the equipment of the Tomsk Regional Core Shared Research Facilities Center of the National Research Tomsk State University. The Center was supported by the Ministry of Science and Higher Education of the Russian Federation, grant no. 075-15-2021-693 (no. 13.RFC.21.0012). Acute toxicity studies were performed in a laboratory certified for preclinical studies, Laboratory of Biological Testing, Institute of Bioorganic Chemistry named after academics M.M. Shemyakin and Y.A. Ovchinnikov Russian Academy of Sciences. The authors are grateful to the Joint Super Computer Center of the Russian Academy of Sciences for providing supercomputers for computer simulations. Development of the glioma tumor model in immunosuppressed mice was supported by the Russian Science Foundation grant No. 22-64-00041 (M.A.D.), https://rscf.ru/en/project/22-64-00041/. Synthesis of 11C-aptamer and PET/CT visualization was funded by the Federal Medical Biological Agency; project 122041800132-2 (A.V.O.). Aptamer selection and their clinical applications were funded by the Ministry of Healthcare of the Russian Federation; project АААА-Б19-219090690032-5 (T.N.Z.). The Ministry of Science and Higher Education of the Russian Federation project FWES-2022-0005 (A.S.K.) supported aptamer characterization, molecular modelling, and in vivo experiments. Mass spectrometry analyses, DNA sequencing, and synthesis were supported by NSERC Discovery Grant (M.V.B.). We acknowledge the European Synchrotron Radiation Facility for SAXS experiments and thank Dr. Bart Van Laer for assistance in using a beamline BM29. SAXS measurements were supported by RFBR № 18-32-00478 for young scientists (R.V.M.). The synchrotron SEC-SAXS data for Gli-55 aptamer were also collected at beamline P12 operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany)
Аннотация: Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro, ex vivo, and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors.
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11.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Дымова М. А., Кулигина Е. В., Рихтер В. А., Артюшенко П. В., Рогова А. В., Щугорева И. А., Томилин, Феликс Николаевич, Кичкайло А. С., Замай Т. Н.
Заглавие : Получение высокоселективных аптамеров к онколитическому вирусу VV-GMCSF-Lact. Теоретические и экспериментальные подходы
Колич.характеристики :7 с
Место публикации : Сиб. мед. обозрение. - 2023. - № 5. - С. 95-101. - ISSN 18199496 (ISSN), DOI 10.20333/25000136-2023-5-95-101; Sib. Med. Rev. - ISSN 25000136 (eISSN)
Примечания : Библиогр.: 21. - Исследование выполнено за счет гранта Российского научного фонда № 22-64-00041, https://rscf.ru/project/22-64-00041/. Работа также поддержана в рамках государственного задания ИХБФМ СО РАН No121030200173-6 (наработка вируса). Авторы благодарят Межведомственный суперкомпьютерный центр Российской академии наук (МСЦ РАН) за предоставление вычислительных мощностей
Аннотация: Введение. Деструкция злокачественных опухолей с помощью онколитических вирусов – один из наиболее эффективных и безопасных способов противоопухолевой терапии. Для получения доступа к опухолевым клеткам вирус должен длительное время циркулировать в кровотоке, избегая действия иммунной системы. Однако при введении вируса в организм он провоцирует выработку вируснейтрализующих антител, снижающих его противоопухолевый эффект. Наиболее эффективным способом защиты вируса от нейтрализующих антител является его экранирование, в частности, с помощью селективных к нему ДНК-аптамеров. Цель исследования. С помощью экспериментальных методов и теоретических расчётов разработать подходящие для создания противоопухолевого препарата на основе онколитического вируса VV-GMCSF-Lact ДНК-аптамеры, эффективно экранирующие вирусы и способные защитить их от вируснейтрализующих антител. Материал и методы. Моделирование вторичных структур аптамеров выполнено в программе для фолдинга нуклеиновых кислот mFold, моделирование соответствующих пространственных полноатомных структур аптамеров – в программах SimRNA и VMD. Расчёты молекулярной динамики проведены в программном пакете GROMACS 2018.8. Кластерный анализ полученных молекулярно-динамических траекторий выполнен в программе VMD. Оценка связывания Cy5-модифицированных аптамеров с вирусом проведена с помощью проточной цитометрии на цитофлуориметре BD FACSCanto II (Becton Dickinson, г. Франклин Лейкс, Нью-Джерси, США). Результаты. Модификация аптамеров, экспериментально полученных с помощью технологии SELEX, позволила получить пять укороченных олигонуклеотидов NV1t_72, NV4t_64, NV4t_53, NV14t_41 и NV14t_57, экранирующих онколитический вирус VV-GMCSF-Lact, самым эффективным из которых оказался аптамер NV14t_57. Теоретические расчёты показали, что аффинность аптамеров определяется их трёхмерной структурой, зависящей от способа модификации. Заключение. Получен высокоселективный аптамер NV14t_57, который является наиболее перспективным кандидатом для дальнейшей работы по созданию препарата для противоопухолевой терапии онкологических заболеваний на основе онколитического вируса осповакцины VVGMCSF-Lact.Introduction. Destruction of malignant tumours with oncolytic viruses is one of the most effective and safe methods of antitumor therapy. To gain access to tumour cells, the virus must circulate in the bloodstream for a long time, avoiding the action of the immune system. However, when a virus is introduced into the body, it provokes the production of virus-neutralising antibodies that reduce its antitumor effect. The most effective way to protect a virus from antibodies that neutralise it is to screen it: in particular, using selective DNA aptamers. The aim of the research. Using experimental methods and theoretical calculations, to develop DNA aptamers suitable for creating an antitumor drug based on the VV-GMCSF-Lact oncolytic virus, which effectively screen viruses and can protect them from virus-neutralising antibodies. Material and methods. Modelling of the secondary structures of aptamers was performed using the mFold program for nucleic acid folding, modelling of the corresponding spatial full-atom structures of aptamers was performed using the SimRNA and VMD programs. Molecular dynamics calculations were carried out using the GROMACS 2018.8 software package. Cluster analysis of the obtained molecular dynamic trajectories was performed using the VMD program. Binding of Cy5-modified aptamers to the virus was assessed using flow cytometry on a BD FACSCanto II cytometer (Becton Dickinson, Franklin Lakes, New Jersey, USA). Results. Modification of aptamers experimentally obtained using the SELEX technology made it possible to obtain five truncated oligonucleotides NV1t_72, NV4t_64, NV4t_53, NV14t_41, and NV14t_57, which screen the oncolytic virus VV-GMCSF-Lact, the most effective of which was the NV14t_57 aptamer. Theoretical calculations have shown that the affinity of aptamers is determined by their three-dimensional structure, which depends on the method of modification. Conclusion. A highly selective aptamer NV14t_57 has been obtained, which is the most promising candidate for further work on the creation of a drug for antitumor therapy of oncological diseases based on the VV-GMCSF-Lact oncolytic vaccinia virus.
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12.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Poolsup S., Zaripov E., Huttmann N., Minic Z., Artyushenko P. V., Shchugoreva I. A., Tomilin F. N., Kichkailo A. S., Berezovski M. V.
Заглавие : Discovery of DNA aptamers targeting SARS-CoV-2 nucleocapsid protein and protein-binding epitopes for label-free COVID-19 diagnostics
Место публикации : Mol. Ther. Nucleic Acids. - 2023. - Vol. 31. - P.731-743. - ISSN 21622531 (eISSN), DOI 10.1016/j.omtn.2023.02.010
Примечания : Cited References: 74. - M.V.B. thanks the Canadian Institutes of Health Research grant OV1-170353 for providing financial support. Molecular modeling and docking were supported by a grant from the Russian Science Foundation (project number 21-73-20240) for A.S.K. S.P. is thankful to Dr. Bob Dass, Dylan Tanner, and Dr. Degang Liu, Sartorius for generously providing excellent technical training and consumable support for binding assay on BLI, and Aldo Jordan for assisting with creating the figures. The authors also thank John L. Holmes’s mass spectrometry facility for providing access to perform nLC-MS/MS. Lastly, the authors thank the JCSS Joint Super Computer Center of the Russian Academy of Sciences for providing supercomputers for computer simulations
Аннотация: The spread of COVID-19 has affected billions of people across the globe, and the diagnosis of viral infection still needs improvement. Because of high immunogenicity and abundant expression during viral infection, SARS-CoV-2 nucleocapsid (N) protein could be an important diagnostic marker. This study aimed to develop a label-free optical aptasensor fabricated with a novel single-stranded DNA aptamer to detect the N protein. The N-binding aptamers selected using asymmetric-emulsion PCR-SELEX and their binding affinity and cross-reactivity were characterized by biolayer interferometry. The tNSP3 aptamer (44 nt) was identified to bind the N protein of wild type and Delta and Omicron variants with high affinity (KD in the range of 0.6–3.5 nM). Utilizing tNSP3 to detect the N protein spiked in human saliva evinced the potential of this aptamer with a limit of detection of 4.5 nM. Mass spectrometry analysis was performed along with molecular dynamics simulation to obtain an insight into how tNSP3 binds to the N protein. The identified epitope peptides are localized within the RNA-binding domain and C terminus of the N protein. Hence, we confirmed the performance of this aptamer as an analytical tool for COVID-19 diagnosis.
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13.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Zamay S. S., Narodov A. A., Galeev R. G., Prokopenko V. S., Sokolov A. Е., Borus A. A., Zabluda V. N., Lukyanenko A. V., Baron F. A., Garifullin V. F., Masyugin A. N., Zelenov F. V., Grek D. S., Voronkovskii I. I., Gorbushin A., Kolovskaya O. S., Lukyanenko K. A., Nikolaeva E. D., Luzan N. A., Kichkailo A. S.
Заглавие : "Smart" nanoscalpel for microsurgery of glial tumors of the human brain
Место публикации : Sib. Med. Rev. - 2022. - Is. 5. - P.109-110. - ISSN 18199496 (ISSN), DOI 10.20333/25000136-2022-5-109-110; Сиб. мед. обозрение
Примечания : Cited References: 2. - This research was funded by the Regional State Autonomous Institution "Krasnoyarsk Regional Fund for Support of Scientific and Scientific and Technical Activities", Competition of scientific, technical and innovative projects in the interests of the first world-class climate scientific and educational center "Yenisei Siberia", grant “Carrying out applied research and development aimed at creating technologies for the production of nanoscalpels based on magnetic nanodisks for microsurgery of glial brain tumors” № 2022060108781 and with the support of a partner company JSC «NPP «Radiosviaz»
Аннотация: We studied the effectiveness of magnetomechanical therapy in the treatment of brain glial tumors using magnetic nanodiscs functionalized with DNA aptamers to human brain tumor glial cells. Materials and methods. The formation of a model of human glioblastoma was carried out by intracranial injection of tumor cells of glioblastoma obtained from a patient with glioblastoma. Antitumor therapy was carried out using nanodiscs modified with the Gli233 aptamer. The growth of the glial tumor was monitored using NMR tomography. Results and discussion. Therapy of a glial tumor during 4 sessions of magnetomechanical therapy using a "smart" nanoscalpel in MF (10Hz, 100Oe) led to a significant reduction in its size, while glial tumors in mice that were treated with nanodiscs modified with nonspecific aptamers continued to increase in size. Conclusion. Microsurgery using three-layer magnetic nanodisks with a quasi-dipole structure (Au/Ni/Au) modified with the specific for glial cells Gli233 aptamer (“smart” nanoscalpel) is effective for the treatment of human glial tumors in the brain.
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14.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Zamay T. N., Starkov A. K., Kolovskaya O. S., Zamay G. S., Veprintsev D. V., Luzan N., Nikolaeva E. D., Lukyanenko K. A., Artyushenko P. V., Shchugoreva I. A., Glazyrin Y. E., Koshmanova A. A., Krat A. V., Tereshina D. S., Zamay S. S., Pats Y. S., Zukov R. A., Tomilin F. N., Berezovski M. V., Kichkailo A. S.
Заглавие : Nucleic acid aptamers increase the anticancer efficiency and reduce the toxicity of cisplatin-arabinogalactan conjugates in vivo
Место публикации : Nucleic Acid Ther. - 2022. - Vol. 32, Is. 6. - P.497-506. - ISSN 21593337 (ISSN), DOI 10.1089/nat.2022.0024. - ISSN 21593345 (eISSN)
Примечания : Cited References: 42
Аннотация: Cisplatin is an effective drug for treating various cancer types. However, it is highly toxic for both healthy and tumor cells. Therefore, there is a need to reduce its therapeutic dose and increase targeted bioavailability. One of the ways to achieve this could be the coating of cisplatin with polysaccharides and specific carriers for targeted delivery. Nucleic acid aptamers could be used as carriers for the specific delivery of medicine to cancer cells. Cisplatin-arabinogalactan-aptamer (Cis-AG-Ap) conjugate was synthesized based on Cis-dichlorodiammineplatinum, Siberian larch arabinogalactan, and aptamer AS-42 specific to heat-shock proteins (HSP) 71?kDa (Hspa8) and HSP 90-beta (Hsp90ab1). The antitumor effect was estimated using ascites and metastatic Ehrlich tumor models. Cis-AG-Ap toxicity was assessed by blood biochemistry on healthy mice. Here, we demonstrated enhanced anticancer activity of Cis-AG-Ap and its specific accumulation in tumor foci. It was shown that targeted delivery allowed a 15-fold reduction in the therapeutic dose of cisplatin and its toxicity. Cis-AG-Ap sufficiently suppressed the growth of Ehrlich's ascites carcinoma, the mass and extent of tumor metastasis in vivo. Arabinogalactan and the aptamers promoted cisplatin efficiency by enhancing its bioavailability. The described strategy could be very promising for targeted anticancer therapy.
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15.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Ivanova O. S., Edelman I. S., Lin, Chun-Rong, Svetlitsky E. S., Sokolov A. Е., Lukyanenko, Kirill A., Sukhachev A. L., Shestakov N. P., Chen, Ying-Zhen, Spivakov, Aleksandr A.
Заглавие : Core–shell Fe3O4@C nanoparticles for the organic dye adsorption and targeted magneto-mechanical destruction of Ehrlich ascites carcinoma cells
Место публикации : Materials. - 2023. - Vol. 16, Is. 1. - Ст.23. - ISSN 19961944 (eISSN), DOI 10.3390/ma16010023
Примечания : Cited References: 65. - This research was funded partly by the Ministry of Science and Higher Education of the Russian Federation, project FWES-2021-0035. C.-R.L., Y.-Z.C. and A.A.S. thank the National Science and Technology Council of Taiwan for the financial support, Grants NSTC № 108-2923-M-153-001-MY3 and № 110-2112-M-153-005-. Magnetic investigations were carried out in the Center for Collective Use of the Krasnoyarsk Regional Center of Research Equipment of Federal Research Center “Krasnoyarsk Science Center SB RAS”
Аннотация: The morphology, structure, and magnetic properties of Fe3O4 and Fe3O4@C nanoparticles, as well their effectiveness for organic dye adsorption and targeted destruction of carcinoma cells, were studied. The nanoparticles exhibited a high magnetic saturation value (79.4 and 63.8 emu/g, correspondingly) to facilitate magnetic separation. It has been shown that surface properties play a key role in the adsorption process. Both types of organic dyes—cationic (Rhodomine C) and anionic (Congo Red and Eosine)—were well adsorbed by the Fe3O4 nanoparticles’ surface, and the adsorption process was described by the polymolecular adsorption model with a maximum adsorption capacity of 58, 22, and 14 mg/g for Congo Red, Eosine, and Rhodomine C, correspondingly. In this case, the kinetic data were described well by the pseudo-first-order model. Carbon-coated particles selectively adsorbed only cationic dyes, and the adsorption process for Methylene Blue was described by the Freundlich model, with a maximum adsorption capacity of 14 mg/g. For the case of Rhodomine C, the adsorption isotherm has a polymolecular character with a maximum adsorption capacity of 34 mg/g. To realize the targeted destruction of the carcinoma cells, the Fe3O4@C nanoparticles were functionalized with aptamers, and an experiment on the Ehrlich ascetic carcinoma cells’ destruction was carried out successively using a low-frequency alternating magnetic field. The number of cells destroyed as a result of their interaction with Fe3O4@C nanoparticles in an alternating magnetic field was 27%, compared with the number of naturally dead control cells of 6%.
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16.

Вид документа : Статья из сборника (однотомник)
Шифр издания :
Автор(ы) : Smolyarova T. E., Tarasov A. S., Lukyanenko A. V., Shanidze L. V., Yakovlev I. A., Volkov N. V.
Заглавие : Biocompatible nanostructures fabricated by Dip-Pen nanolithography
Коллективы : Aptamers in Russia, international conference
Место публикации : Aptamers in Russia, international conference (1 ; 2019 ; Aug. 27-30 ; Krasnoyarsk). Molecular Therapy - Nucleic Acids: book of abstracts of the 1st Int. conf. "Aptamers in Russia 2019". - 2019. - Vol. 17, Suppl. 1. - P.8-9
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17.

Вид документа : Статья из сборника (однотомник)
Шифр издания :
Автор(ы) : Sokolov A. Е., Ivanova O. S., Zabluda V. N., Dubinina A. V., Semina P. N., Zamay G. S., Zamay T. N., Zamay S. S., Volochaev M. N., Svetlichnyi V., Lapin I. N., Shabalina A., Solodova O. V.
Заглавие : Magnetic nanoparticles and DNA-aptamers conjugates for cancer therapy
Коллективы : International Baltic Conference on Magnetism: Focus on funcshionalized magnetic structures for energy and biotechnology , Балтийский федеральный университет им. И. Канта
Место публикации : Int. Baltic Conf. Magnet. (IBCM-2017) : Focus on funcshionalized magnetic struct. for energy and biotech.: book of abstracts. - 2017. - P.77
Примечания : Библиогр.: 4
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18.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Belyanina I. V., Zamay T. N., Zamay G. S., Zamay S. S., Kolovskaya, Olga S., Ivanchenko, Tatiana I., Denisenko, Valery V., Kirichenko, Andrey K., Glazyrin, Yury E., Garanzha, Irina V., Grigorieva, Valentina V., Shabanov A. V., Veprintsev, Dmitry V., Sokolov A. E., Sadovskii, Vladimir M., Gargaun, Ana, Berezovski M. V., Kichkailo, Anna S.
Заглавие : In vivo cancer cells elimination guided by aptamer-functionalized gold-coated magnetic nanoparticles and controlled with low frequency alternating magnetic field
Коллективы : Russian Scientific Fund [14-15-00805]
Место публикации : Theranostics. - 2017. - Vol. 7, Is. 13. - P.3326-3337. - ISSN 1838-7640, DOI 10.7150/thno.17089
Примечания : Cited References:35. - The authors are grateful to George Y. Vorogeikin, Yuri I. Vorogeikin and "OKB ART". Andrey Barinov and "OPTEC Group" for help with 3D laser scanning imaging. Microscopic analyses using Carl Zeiss LSM 800 were done in the "Center for bioassay, nanotechnology and nanomaterials safety" ("Biotest-Nano") (Multiple-Access Center, Tomsk State University, Tomsk, Russia). Toxicity studies have been performed in Multiple-Access Center, Central Scientific Research Laboratory in Krasnoyarsk State Medical University named after prof. V.F. Voino-Yasenecky. This work was supported by the Russian Scientific Fund (grant #14-15-00805).
Предметные рубрики: PHOTOTHERMAL THERAPY
INTEGRIN ACTIVATION
FIBRONECTIN
STIMULATION
Ключевые слова (''Своб.индексиров.''): cancer therapy--gold coated magnetic nanoparticles--dna aptamers--low--frequency alternating magnetic field--fibronectin--integrin--apoptosis--necrosis
Аннотация: Biomedical applications of magnetic nanoparticles under the influence of a magnetic field have been proved useful beyond expectations in cancer therapy. Magnetic nanoparticles are effective heat mediators, drug nanocarriers, and contrast agents; various strategies have been suggested to selectively target tumor cancer cells. Our study presents magnetodynamic nanotherapy using DNA aptamer-functionalized 50 nm gold-coated magnetic nanoparticles exposed to a low frequency alternating magnetic field for selective elimination of tumor cells in vivo. The cell specific DNA aptamer AS-14 binds to the fibronectin protein in Ehrlich carcinoma hence helps deliver the gold-coated magnetic nanoparticles to the mouse tumor. Applying an alternating magnetic field of 50 Hz at the tumor site causes the nanoparticles to oscillate and pull the fibronectin proteins and integrins to the surface of the cell membrane. This results in apoptosis followed by necrosis of tumor cells without heating the tumor, adjacent healthy cells and tissues. The aptamer-guided nanoparticles and the low frequency alternating magnetic field demonstrates a unique non-invasive nanoscalpel technology for precise cancer surgery at the single cell level.
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19.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Tomilin F. N., Moryachkov R., Shchugoreva I., Zabluda V. N., Peters G., Platunov M. S., Spiridonova V., Melnichuk A., Atrokhova A., Zamay S. S., Ovchinnikov S. G., Zamay G. S., Sokolov A. Е., Zamay T. N., Berezovski M. V., Kichkailo A. S.
Заглавие : Four steps for revealing and adjusting the 3D structure of aptamers in solution by small-angle X-ray scattering and computer simulation
Место публикации : Anal. Bioanal. Chem. - 2019. - Vol. 411, Is. 25. - P.6723-6732. - ISSN 16182642 (ISSN), DOI 10.1007/s00216-019-02045-0
Примечания : Cited References: 51. - Authors are grateful to Ana Gargaun for English grammar correction. This work was funded in parts by the Ministry of Science and Higher Education of the Russian Federation; project 0287-2019-0007 the Council of the President of the Russian Federation for Support of Young Scientists and Leading Scientific Schools (project no. SP-938.2015.5) and the grant of KSAI “Krasnoyarsk Regional Fund of Supporting Scientific and Technological Activities” for M.P., the internship “The study of the stacking of the secondary structure of DNA aptamers to thrombin” for R.M.
Аннотация: Nucleic acid (NA) aptamers bind to their targets with high affinity and selectivity. The three-dimensional (3D) structures of aptamers play a major role in these non-covalent interactions. Here, we use a four-step approach to determine a true 3D structure of aptamers in solution using small-angle X-ray scattering (SAXS) and molecular structure restoration (MSR). The approach consists of (i) acquiring SAXS experimental data of an aptamer in solution, (ii) building a spatial distribution of the molecule’s electron density using SAXS results, (iii) constructing a 3D model of the aptamer from its nucleotide primary sequence and secondary structure, and (iv) comparing and refining the modeled 3D structures with the experimental SAXS model. In the proof-of-principle we analyzed the 3D structure of RE31 aptamer to thrombin in a native free state at different temperatures and validated it by circular dichroism (CD). The resulting 3D structure of RE31 has the most energetically favorable conformation and the same elements such as a B-form duplex, non-complementary region, and two G-quartets which were previously reported by X-ray diffraction (XRD) from a single crystal. More broadly, this study demonstrates the complementary approach for constructing and adjusting the 3D structures of aptamers, DNAzymes, and ribozymes in solution, and could supply new opportunities for developing functional nucleic acids. [Figure not available: see fulltext.]. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
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20.

Вид документа : Статья из журнала
Шифр издания :
Автор(ы) : Дубынина А. В., Замай Т. Н., Коловская О. С., Кичкайло, Анна Сергеевна, Белянина И. В., Чанчикова Н. Г., Токарев Н. А., Карлова Е. А., Александровский, Александр Сергеевич, Шепелевич Н. В., Озерская А. В., Бадрин Е. А., Белугин К. В., Белкин С. А.
Заглавие : Адресная деструкция злокачественных опухолей биоконъюгатами на основе аптамеров
Коллективы : Красноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого
Место публикации : Сиб. мед. обозрение. - Красноярск, 2016. - Т. 101, № 5. - С. 88-90. - ISSN 1819-9496
Примечания : Библиогр.: 2
Ключевые слова (''Своб.индексиров.''): аптамеры--золотые наночастицы--магнитные микродиски--гипертермия--плазмонный--резонанс--aptamers--gold nanoparticles--magnetic microdiscs--hyperthermia--plasmon resonance
Аннотация: Широкое распространение в терапии онкологических заболеваний в последние годы получили методы, основанные на применении различных типов наночастиц. Для повышения адресности Адресная деструкция злокачественных опухолей биоконъюгатами на основе аптамеров воздействия применяют различные молекулы, обладающие высокой специфичностью, одними из которых являются аптамеры. В работе исследовался эффект воздействия на опухоль конъюгатов наночастиц золота с аптамерами при воздействии лазера, а также оценивалась гибель клеток опухоли при использовании конъюгатов магнитных микродисков с аптамерами в условиях переменного магнитного поля. Исследование показало возможность применения исследуемых конъюгатов в качестве средств адресной деструкции опухоли.Widespread in cancer therapy in recent years have become the methods based on the use of different types of nanoparticles. To improve the targeting of the impact are used various molecules having high specificity, some of them are aptamers. The paper studied the effect of influence on the tumor the conjugates of gold nanoparticles with aptamers at laser exposure, as well as tumor cell death was assessed after using the conjugates of magnetic microdiscs with aptamers in a variable magnetic field. The study showed the possibility of using the studied conjugates as agents of targeted destruction of tumor.
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