Publications by authors named "Anna Kazakova"

23 Publications

  • Page 1 of 1

Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models.

Eur J Med Chem 2021 Mar 16;213:113168. Epub 2021 Jan 16.

Laboratory of Growth Regulators, Faculty of Science, Palacký University and the Institute of Experimental Botany of the Czech Academy of Sciences, Šlechtitelů 27, CZ-78371, Olomouc, Czech Republic; Department of Neurology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, CZ-775 20, Olomouc, Czech Republic. Electronic address:

Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-β-d-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-β-d-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 μM, but this derivative suffered from cytotoxicity at higher concentrations. Both compounds modulated oxidative stress and caspase-3,7 activity, but 10 showed a superior effect comparable to the Ac-DEVD-CHO inhibitor. Interestingly, while both 4 and 10 outperformed the positive controls in blocking mitochondrial permeability transition pore opening, only 4 demonstrated potent restoration of the mitochondrial membrane potential (MMP) in the model. Derivatives 4 and 10 also showed neuroprotection in the Glu model, with 10 exhibiting the strongest oxidative stress reducing effect among the tested compounds, while the neuroprotective activity of 4 was probably due recovery of the MMP.
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http://dx.doi.org/10.1016/j.ejmech.2021.113168DOI Listing
March 2021

GATA1 mutation analysis and molecular landscape characterization in acute myeloid leukemia with trisomy 21 in pediatric patients.

Int J Lab Hematol 2021 Jan 2. Epub 2021 Jan 2.

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

Introduction: Accurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions.

Methods: The DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high-throughput sequencing (HTS).

Results: Acquired GATA1 mutations were identified in 43 cases (98%). Additional mutations in the genes of JAK/STAT signaling, cohesin complex, and RAS pathway activation were revealed by HTS in 48%, 36%, and 16% of the cases, respectively.

Conclusions: The GATA1 mutations were reliably determined by fragment analysis and/or Sanger sequencing in a single PCR amplicon manner. For patients with extremely low blast counts and/or rare variants, the rapid screening with simple molecular approaches must be complemented with HTS. The JAK/STAT and RAS pathway-activating mutations may represent an extra option of targeted therapy with kinase inhibitors.
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http://dx.doi.org/10.1111/ijlh.13451DOI Listing
January 2021

Protective Properties of Attenuated Strains of African Swine Fever Virus Belonging to Seroimmunotypes I-VIII.

Pathogens 2020 Apr 9;9(4). Epub 2020 Apr 9.

Federal Research Center for Virology and Microbiology (FRCVM), 601125 Volginsky, Petushki area, Vladimir region, Russia.

This article summarizes the study results on the generation of attenuated strains of African swine fever virus (ASFV) of seroimmunotypes I-VIII and the creation of live vaccines for temporary protection of pigs during a period of epizootics in the surveillance zone (a zone adjacent to the area of outbreak). These studies were initiated at the Federal Research Center for Virology and Microbiology (FRCVM, formerly VNIIVViM) at the time of introduction of the pathogen to the Iberian Peninsula in the middle of the 20th century. The developed experimental vaccines against ASFV seroimmunotypes I-V provided protection against virulent strains of homologous seroimmunotypes by day 14 after vaccination, lasting at least four months.
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http://dx.doi.org/10.3390/pathogens9040274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238197PMC
April 2020

Gene rearrangements in consecutive series of pediatric inflammatory myofibroblastic tumors.

Pediatr Blood Cancer 2020 05 16;67(5):e28220. Epub 2020 Feb 16.

N.N. Petrov Institute of Oncology, St. Petersburg, Russia.

Background: Inflammatory myofibroblastic tumors (IMTs) are exceptionally rare neoplasms, which are often driven by rearranged tyrosine kinases.

Methods: This study considered 33 consecutive patients with IMT (median age, 6.6; age range, 0.6-15.8 years). RNA and cDNA were successfully obtained in 29 cases. The molecular analysis included sequential tests for 5'/3'-end unbalanced gene expression, variant-specific PCR, and next-generation sequencing (NGS).

Results: 5'/3'-end unbalanced ALK expression was revealed in 15/29 (52%) IMTs. Strikingly, all these tumors demonstrated high amount of ALK protein detected by immunohistochemistry. Variant-specific PCR was capable of identifying the type of ALK rearrangement in 11/15 IMTs with 5'/3'-end unbalanced ALK expression. The remaining four tumors were analyzed by NGS; two known and two novel (CLTC-ins6del84-ALK and EEF1G-ALK) ALK rearrangements were detected. Five IMTs demonstrated 5'/3'-end unbalanced ROS1 expression, and all these tumors carried TFG-ROS1 fusion. Nine tumors, which were negative for 5'/3'-end unbalanced ALK/ROS1 expression, were subjected to further analysis. Variant-specific PCR revealed two additional tumors with gene rearrangements (TFG-ROS1 and ETV6-NTRK3). The remaining seven IMTs were tested by NGS; single instances of TFG-ROS1 and novel SRF-PDGFRb translocations were detected.

Conclusions: Twenty-four of 29 IMTs (83%) were shown to have druggable rearrangements involving tyrosine kinases, 20 of these 24 gene fusions were detectable by simple and inexpensive PCR assay, which is based on the detection 5'/3'-end unbalanced gene expression.
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http://dx.doi.org/10.1002/pbc.28220DOI Listing
May 2020

Pandemic influenza A(H1N1pdm09) vaccine induced high levels of influenza-specific IgG and IgM antibodies as analyzed by enzyme immunoassay and dual-mode multiplex microarray immunoassay methods.

Vaccine 2020 02 24;38(8):1933-1942. Epub 2020 Jan 24.

Institute of Biomedicine/Virology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Turku University Hospital, Clinical Microbiology, Kiinamyllynkatu 10, 20520 Turku, Finland. Electronic address:

Influenza A viruses continue to circulate throughout the world as yearly epidemics or occasional pandemics. Influenza infections can be prevented by seasonal multivalent or monovalent pandemic vaccines. In the present study, we describe a novel multiplex microarray immunoassay (MAIA) for simultaneous measurement of virus-specific IgG and IgM antibodies using Pandemrix-vaccinated adult sera collected at day 0 and 28 and 180 days after vaccination as the study material. MAIA showed excellent correlation with a conventional enzyme immunoassay (EIA) in both IgG and IgM anti-influenza A antibodies and good correlation with hemagglutination inhibition (HI) test. Pandemrix vaccine induced 5-30 fold increases in anti-H1N1pdm09 influenza antibodies as measured by HI, EIA or MAIA. A clear increase in virus-specific IgG antibodies was found in 93-97% of vaccinees by MAIA and EIA. Virus-specific IgM antibodies were found in 90-92% of vaccinees by MAIA and EIA, respectively and IgM antibodies persisted for up to 6 months after vaccination in 55-62% of the vaccinees. Pandemic influenza vaccine induced strong anti-influenza A IgG and IgM responses that persisted several months after vaccination. MAIA was demonstrated to be an excellent method for simultaneous measurement of antiviral IgG and IgM antibodies against multiple virus antigens. Thus the method is well suitable for large scale epidemiological and vaccine immunity studies.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.022DOI Listing
February 2020

Serological Array-in-Well Multiplex Assay Reveals a High Rate of Respiratory Virus Infections and Reinfections in Young Children.

mSphere 2019 09 11;4(5). Epub 2019 Sep 11.

Institute of Biomedicine, University of Turku, Turku, Finland.

Serological assays are used to diagnose and characterize host immune responses against microbial pathogens. Microarray technologies facilitate high-throughput immunoassays of antibody detection against multiple pathogens simultaneously. To improve survey of influenza A virus (IAV), influenza B virus (IBV), respiratory syncytial virus (RSV), and adenovirus (AdV) antibody levels, we developed a microarray consisting of IAV H1N1, IAV H1N1pdm09 (vaccine), IAV H3N2, IBV Victoria, IBV Yamagata, RSV, AdV type 5 hexon protein, and control antigens printed on the bottom of a microtiter plate well. Bound IgG antibodies were detected with anti-human IgG-coated photon-upconverting nanoparticles and measured with a photoluminescence imager. The performance of the microarray immunoassay (MAIA) was evaluated with serum samples ( = 576) collected from children ( = 288) at 1 and 2 years of age and tested by standard enzyme immunoassays (EIAs) for antibodies to IAV vaccine and RSV. EIAs and MAIA showed substantial to almost perfect agreement (Cohen's κ, 0.62 to 0.83). Applying MAIA, we found seroprevalences of 55% for IAV H1N1, 54% for IAV vaccine, 30% for IAV H3N2, 24% for IBV Victoria, 25% for IBV Yamagata, 38% for RSV, and 26% for AdV in 1-year-old children ( = 768). By the age of 2 years, IgG seropositivity rates ( = 714) increased to 74% for IAV H1N1, 71% for IAV vaccine, 49% for IAV H3N2, 47% for IBV Yamagata, 49% for IBV Victoria, 68% for RSV, and 58% for AdV. By analyzing increases in antibody levels not biased by vaccinations, we found a reinfection rate of 40% for RSV and 31% for AdV in children between 1 and 2 years of age. The multiplex immunoassay was successfully used to simultaneously detect antibodies against seven different viruses. The developed serological microarray is a new promising tool for diagnostic, epidemiological, and seroprevalence analyses of virus infections.
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http://dx.doi.org/10.1128/mSphere.00447-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739493PMC
September 2019

Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research.

Eur J Med Chem 2019 Nov 30;182:111653. Epub 2019 Aug 30.

Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinská 5, 779 00, Olomouc, Czech Republic. Electronic address:

Triterpenoids are natural products from plants and many other organisms that have various biological activities, such as antitumor, antiviral, antimicrobial, and protective activities. This review covers the synthesis and biological evaluation of pentacyclic triterpene (PT) conjugates with other molecules that have been found to increase the IC or improve the pharmacological profile of the parent PT. Some of these molecules are designed to target specific proteins or cellular organelles, which has resulted in highly selective lead structures for drug development. Other PT conjugates are useful for investigating their mechanism of action. This concept has been very successful: 1) Many compounds, especially mitochondria-targeting PT conjugates, have reached a selective cytotoxicity at low nanomolar concentrations in cancer cells. 2) A number of PT conjugates have had high activity against HIV or the influenza virus. 3) Fluorescent PT conjugates have been able to visualize the PT in living cells, which has allowed quantification of the uptake and distribution of the PT within the cell. 4) Biotinylated PT conjugates have been used to identify target proteins, which may help to show their mechanism of action. 5) A large number of PT conjugates with polyethylene glycol (PEG), polyamines, etc. form nanometer-sized micelles that have a much better pharmacological profile than the PT alone. In summary, the connection of a PT to an appropriate modifying molecule has resulted in extremely useful semisynthetic compounds with a high potential to treat cancer or viral infections or compounds that are useful for the study of the mechanism of action of PTs at the molecular level.
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http://dx.doi.org/10.1016/j.ejmech.2019.111653DOI Listing
November 2019

Heterogeneity of childhood acute leukemia with mature B-cell immunophenotype.

J Cancer Res Clin Oncol 2019 Nov 28;145(11):2803-2811. Epub 2019 Aug 28.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela St., GSP-7, Moscow, 117997, Russia.

Background: Flow cytometry (FCM) plays a crucial role in the differential diagnosis of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The presence of surface IgM (sIgM) alone or with light chain restriction indicates a mature blast phenotype (BIV by EGIL) and is usually observed in BL. However, sIgM expression could also be detected in transitional BCP-ALL cases. These similarities in immunophenotype and ambiguous correspondence with other laboratory findings may challenge the correct BL diagnostics.

Methods: We retrospectively reviewed the available data from immunophenotypic, morphological, cytogenetic, and molecular genetic studies of 146 children (85 boys and 61 girls) with a median age of 10 years (range 0-18 years) who were diagnosed with BL and BCP-ALL. The blasts' immunophenotype was studied by multicolor FCM. The conventional cytogenetic analysis included G-banded karyotyping and fluorescence in situ hybridization (FISH).

Results: In 54 children classified as BIV-ALL according to the EGIL, it was demonstrated that sIgM in a minority of cases can be associated with various types of BCP-ALL. Analysis of the antigen expression profile of 105 patients with verified BL (n = 21) and BCP-ALL (n = 84) showed significant differences in BL and the sIgM(+) vs BCP-ALL immunophenotype. Thus, even in cases of ambiguous sIgM expression, these two diseases could be reliably discriminated by complex immunophenotyping. Moreover, 10 patients (7 boys and 3 girls) with BL leukemic cells did not express sIgM, and they were diagnosed with BL on the basis of other laboratory and clinical signs.

Conclusions: In conclusion, our study shows that BIV subtype is heterogeneous group of leukemia including not only the BL, but also BCP-ALL. In ambiguous cases, only a combination of multiple immunophenotypic, cytomorphologic, and genetic diagnostic technologies can allow the precise discrimination of BL and BCP-ALL and selection of the appropriate treatment scheme.
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http://dx.doi.org/10.1007/s00432-019-03010-1DOI Listing
November 2019

The First Conducting Spin-Crossover Compound Combining a Mn Cation Complex with Electroactive TCNQ Demonstrating an Abrupt Spin Transition with a Hysteresis of 50 K.

Chemistry 2019 Aug 4;25(43):10204-10213. Epub 2019 Jul 4.

Lomonosov Moscow State University, Moscow, 119991, Russia.

We present herein the synthesis, crystal structure, and electric and magnetic properties of the spin-crossover salt [Mn(5-Cl-sal-N-1,5,8,12)]TCNQ ⋅2 CH CN (I), where 5-Cl-sal-N-1,5,8,12=N,N'-bis(3-(2-oxy-5-chlorobenzylideneamino)propyl)-ethylenediamine, containing distinct conductive and magnetic blocks along with acetonitrile solvent molecules. The Mn complex with a Schiff-base ligand, [Mn(5-Cl-sal-N-1,5,8,12)] , acts as the magnetic unit, and the π-electron acceptor 7,7,8,8-tetracyanoquinodimethane (TCNQ ) is the conducting unit. The title compound (I) exhibits semiconducting behavior with room temperature conductivity σ ≈1×10  ohm  cm and activation energy Δ ≈0.20 eV. In the temperature range 73-123 K, it experiences a hysteretic phase transition accompanied by a crossover between the low-spin S=1 and high-spin S=2 states of Mn and changes in bond lengths within the MnN O octahedra. The pronounced shrinkage of the basal Mn-N bonds in I at the spin crossover suggests that the d orbital is occupied/deoccupied in this transition. Interestingly, the bromo isomorphic counterpart [Mn(5-Br-sal-N-1,5,8,12)]TCNQ ⋅2 CH CN (II) of the title compound evidences no spin-crossover phenomena and remains in the high-spin state in the temperature range 2-300 K. Comparison of the chloro and bromo compounds allows the thermal and spin-crossover contributions to the overall variation in bond lengths to be distinguished. The difference in magnetic behavior of these two salts has been ascribed to intermolecular supramolecular effects on the spin transition. Discrete hydrogen bonding exists between cations and cations and anions in both compounds. However, the hydrogen bonding in the crystals of II is much stronger than in I. The relatively close packing arrangement of the [Mn(5-Br-sal-N-1,5,8,12)] cations probably precludes their spin transformation.
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http://dx.doi.org/10.1002/chem.201901792DOI Listing
August 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

TfOH-Promoted Reaction of 2,4-Diaryl-1,1,1-Trifluorobut-3-yn-2-oles with Arenes: Synthesis of 1,3-Diaryl-1-CF₃-Indenes and Versatility of the Reaction Mechanisms.

Molecules 2018 Nov 25;23(12). Epub 2018 Nov 25.

Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University, Universitetskaya nab., 7/9, Saint Petersburg 199034, Russia.

The TfOH-mediated reactions of 2,4-diaryl-1,1,1-trifluorobut-3-yn-2-oles (CF₃-substituted diaryl propargyl alcohols) with arenes in CH₂Cl₂ afford 1,3-diaryl-1-CF₃-indenes in yields up to 84%. This new process for synthesis of such CF₃-indenes is complete at room temperature within one hour. The synthetic potential, scope, and limitations of this reaction were illustrated by more than 70 examples. The proposed reaction mechanism invokes the formation of highly reactive CF₃-propargyl cation intermediates that can be trapped at the two mesomeric positions by the intermolecular nucleophilic attack of an arene partner with a subsequent intramolecular ring closure.
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http://dx.doi.org/10.3390/molecules23123079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321356PMC
November 2018

A case of pediatric acute myeloid leukemia with t(11;16)(q23;q24) leading to a novel KMT2A-USP10 fusion gene.

Genes Chromosomes Cancer 2018 10 14;57(10):522-524. Epub 2018 Aug 14.

Laboratory of Cytogenetics and Molecular Genetics, Dmitry Rogachev Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

We present a leukemia case that exhibits a chromosomal translocation t(11;16)(q23;q23), which results in the expression of a novel KMT2A fusion gene. This novel fusion, KMT2A-USP10, was found in a relapse of acute myeloid leukaemia M5a. USP10 belongs to a protein family that deubiquitinates a distinct set of target proteins, and thus, increases the steady state protein levels of its target subproteome. One of the USP10 targets is TP53. Wildtype TP53 is usually rescued from proteasomal degradation by USP10. As most KMT2A leukemias display wildtype p53 alleles, one might argue that the disruption of an USP10 allele can be classified as a pro-oncogenic event.
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http://dx.doi.org/10.1002/gcc.22646DOI Listing
October 2018

Clinical significance of cytogenetic changes in childhood T-cell acute lymphoblastic leukemia: results of the multicenter group Moscow-Berlin (MB).

Leuk Lymphoma 2019 02 1;60(2):426-432. Epub 2018 Aug 1.

i Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Charité CVK, Universitätsmedizin Berlin , Berlin , Germany.

The prognostic significance of genetic lesions in T-cell ALL still needs to be elucidated. Karyotyping and FISH were performed in samples from 120 patients with T-cell ALL registered in the trial Moscow-Berlin 2008. Most frequent rearrangements were TLX3 (N = 29; 24%) and TAL1 (N = 18; 15%), followed by KMT2A (N = 6; 5%), TLX1 (N = 5; 4.2%), and 11p13-15 (N = 5; 4.2%). In 16.7% of patients, the karyotype was normal, and in 30.8% 'other' aberrations were seen. Patients with a normal karyotype, TAL1, or KMT2A rearrangements had the most favorable outcome (probability of event free survival (pEFS): 82% ± 6%), while prognosis for patients with TLX3 and TLX1 rearrangements and 'other' aberrations was less favorable (pEFS: 62% ± 6%). Worst outcome was observed for five patients with 11p rearrangements (pEFS: 20% ± 18%). In summary, three subgroups of patients with T-cell ALL with significantly different outcomes could be defined by cytogenetic profiling.
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http://dx.doi.org/10.1080/10428194.2018.1485904DOI Listing
February 2019

Molecular characteristic of acute leukemias with t(16;21)/FUS-ERG.

Ann Hematol 2018 Jun 9;97(6):977-988. Epub 2018 Feb 9.

Dmitry Rogachev Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Samora Mashela str., 1, Moscow, 117997, Russia.

T(16;21)(p11;q22)/FUS-ERG is a rare but recurrent translocation in acute leukemias and in some types of solid tumors. Due to multiple types of FUS-ERG transcripts, PCR-based minimal residual disease detection is impeded. In this study, we evaluated a cohort of pediatric patients with t(16;21)(p11;q22)/FUS-ERG and revealed fusion gene breakpoints. We implemented next-generation sequencing (NGS) on long PCR amplicons for the detection of fusion genes with unknown partners or DNA breakpoints. That allowed us to describe different fusion variants of FUS/ERG in different patients and to detect MRD on both RNA and DNA levels. We also found several accompanying mutations in epigenetic regulators (DNMT3A, ASXL1, BCOR) by targeted NGS approach in AML cases. These mutations preceded full transformation by t(16;21)(p11;q22)/FUS-ERG and allowed us to trace clonal evolution on all steps of therapy. As a casual observation, the ASXL1 mutation was found in the unrelated donor hematopoietic cells.
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http://dx.doi.org/10.1007/s00277-018-3267-zDOI Listing
June 2018

Acid-promoted cyclization of 2,4-diaryl-1,1,1-trifluorobut-3-en-2-oles and their TMS-ethers into CF-indenes.

Org Biomol Chem 2017 Mar;15(12):2541-2550

Institute of Chemistry, Saint Petersburg State University, Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia and Department of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per., 5, Saint Petersburg, 194021, Russia.

2,4-Diaryl-1,1,1-trifluorobut-3-en-2-oles and their TMS-ethers in HSO at room temperature in just 2 min are quantitatively cyclized into 1-aryl-3-trifluoromethyl-1H-indenes. The reaction proceeds through an intermediate formation of the corresponding CF-allyl cations, which are cyclized regioselectively at the allyl carbon atom most remote from the CF-group. The obtained CF-indenes in solution of EtOAc in the presence of silica gel at room temperature over 4 h are quantitatively isomerized into 3-aryl-1-trifluoromethyl-1H-indenes.
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http://dx.doi.org/10.1039/c7ob00406kDOI Listing
March 2017

Third-generation percutaneous vertebral augmentation systems.

J Spine Surg 2016 Mar;2(1):13-20

Neurotraumatology and Vertebro-Medullary Surgery, "Renzetti Hospital", Lanciano, Italy ;

Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting(®) (VBS), OsseoFix(®) and Spine Jack(®). VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix(®) and Spine Jack(®) are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix(®) has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting(®) and Spine Jack(®), the OsseoFix(®) has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack(®) is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039833PMC
http://dx.doi.org/10.21037/jss.2016.02.01DOI Listing
March 2016

Technical note: microdiscectomy and translaminar approach.

J Spine Surg 2015 Dec;1(1):44-9

Neurotraumatology and Vertebro-Medullary Surgery, Renzetti Hospital, Lanciano, Italy.

Lumbar disk herniation (LDH) is a degenerative pathology. Although LDH generally occurs without migration of the fragment to the levels above or below, in 10% of the cases, this circumstance might happen. In these cases, the standard interlaminar approach, described by Caspar cannot be performed without laminotomies, interlaminectomies, or partial or total facetectomies. The translaminar approach is the only "tissue-sparing" technique viable in cases of cranially migrated LDH encroaching on the exiting nerve root in the preforaminal zones, for the levels above L2-L3, and in the preforaminal and foraminal zones, for the levels below L3-L4 (L5-S1 included, if a total microdiscectomy is unnecessary). This approach is more effective than the standard one, because it resolves the symptoms; it is associated with less postoperative pain and faster recovery times without the risk of iatrogenic instability, and it can also be used in cases with previous signs of radiographic instability. The possibility to spare the flavum ligament is one of the main advantages of this technique. For these reasons, the translaminar approach is a valid technique in terms of safety and efficacy. In this article the surgical technique will be extensively analyzed and the tips and tricks will be highlighted.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039873PMC
http://dx.doi.org/10.3978/j.issn.2414-469X.2015.10.03DOI Listing
December 2015

Friedel-Crafts Alkylation of Arenes with 2-Halogeno-2-CF3-styrenes under Superacidic Conditions. Access to Trifluoromethylated Ethanes and Ethenes.

J Org Chem 2016 06 9;81(12):5032-45. Epub 2016 Jun 9.

Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University , Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia.

The formation of the corresponding benzyl cations [ArHC(+)-CH(X)CF3] takes place under protonation of E-/Z-2-halogeno-2-CF3 styrenes [ArCH═C(X)CF3, X = F, Cl, Br] in superacids. The structures of these new electrophiles were studied by means of NMR and theoretical DFT calculations. According to these data, in the case of bromo derivatives, the formed cations, most probably, exist as cyclic bromonium ions; however, in the cases of chloro and fluoro derivatives, open forms are more preferable. Subsequent reaction of these benzyl cations with arenes proceeds as Friedel-Crafts alkylation to afford 1,1-diaryl-2-halo-3,3,3-trifluoropropanes [Ar(Ar')CH-CH(X)CF3] in high yields (up to 96%) as a mixture of two diastereomers. The prepared halogenopropanes were easily converted into the corresponding mixtures of E-/Z-trifluoromethylated diarylethenes [Ar(Ar')C═CCF3] (in yields up to 96%) by dehydrohalogenation with base (KOH or t-BuOK). The mechanism of elimination (E2 and Ecb) depends on the nature of the leaving group and reaction conditions.
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http://dx.doi.org/10.1021/acs.joc.6b00419DOI Listing
June 2016

Intraforaminal ozone therapy and particular side effects: preliminary results and early warning.

Acta Neurochir (Wien) 2016 05 15;158(5):991-3. Epub 2016 Mar 15.

Orthopaedic and Traumatology Department, "G.d'Annunzio" University, Chieti, Italy.

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http://dx.doi.org/10.1007/s00701-016-2755-yDOI Listing
May 2016

Acid-Promoted Reaction of Trifluoromethylated Allyl Alcohols with Arenes. Stereoselective Synthesis of CF3-Alkenes and CF3-Indanes.

J Org Chem 2015 Oct 30;80(19):9506-17. Epub 2015 Sep 30.

Department of Organic Chemistry, Institute of Chemistry, Saint Petersburg State University , Universitetskaya nab., 7/9, Saint Petersburg, 199034, Russia.

Reaction of 4-aryl-1,1,1-trifluorobut-3-en-2-ols [CF3-allyl alcohols, ArCH═CHCH(OH)CF3] with arenes under activation with anhydrous FeCl3 or FSO3H was studied. We found that the transformation led to trifluoromethylated alkenes [Ar(Ar')CHCH═CHCF3] or 1-trifluoromethylated indanes (CF3-indanes). The formation of these two types of reaction products strongly depends on the nucleophilicity of the starting arene and the electrophilicity of cationic intermediates generated from CF3-allyl alcohols under reaction conditions. Benzene, anisole, veratrole, and ortho-xylene lead exclusively to CF3-alkenes with an E-configuration. More π-donating polymethylated arenes (pseudocumene, mesitylene) afford only CF3-indanes with a predominantly cis-orientation of substituents at positions 1 and 3 of the indane ring. Meta- and para-xylenes show an intermediate behavior; they may form both CF3-alkenes and/or CF3-indanes. The mechanisms of the investigated transformations are discussed.
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http://dx.doi.org/10.1021/acs.joc.5b01398DOI Listing
October 2015

Intraforaminal ozone therapy and particular side effects: preliminary results and early warning.

Acta Neurochir (Wien) 2016 Mar 21;158(3):491-6. Epub 2015 Aug 21.

Vertebral Surgery Department, ASL 2 Lanciano Vasto, Chieti, Italy.

Background: The term "low back pain syndrome" represents a complex nosological entity. The therapeutic approach is often only symptomatic and not etiologic.

Methods: Since 2013, 186 patients (97 males and 89 females, mean age 59.8 years) have undergone microsurgery for lumbar disc hernia or lumbar segmental stenosis. Among these patients, 23 had been previously treated with ozone therapy by the intraforaminal approach and 28 by intraforaminal steroid injections in other hospitals between 12 and 24 months before our clinical evaluation. These patients received 16 applications in an 8-week period (standard therapy).

Results: During the surgery, many hard adhesions between the soft tissues and bony structures were unexpectedly discovered. In particular, it was noted that the root contracted and had firm adhesions to the dural sac and/or fragmented disc, which were difficult to resolve. These specific pathological patterns were observed only in the patients who received ozone injections by the intraforaminal approach. We did not find any pathological abnormalities in the patients who did not receive any injections or who received intraforaminal steroid injections. Thus, we could exclude that the tissue damage was due to the mechanical action of the needle.

Conclusion: It is important to assert that ozone therapy procedures can be associated with several major complications. Therefore, performing a revision of the guidelines and protocols for ozone therapy application is indispensable.
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http://dx.doi.org/10.1007/s00701-015-2545-yDOI Listing
March 2016

Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands.

Org Biomol Chem 2015 Sep 17;13(33):8827-42. Epub 2015 Jul 17.

Institute of Chemistry, Saint-Petersburg State University, 198504 Saint-Petersburg, Petrodvorets, Universitetsky pr., 26, Russia.

4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.
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http://dx.doi.org/10.1039/c5ob01072aDOI Listing
September 2015

A new variant of KMT2A(MLL)-FLNA fusion transcript in acute myeloid leukemia with ins(X;11)(q28;q23q23).

Cancer Genet 2015 Apr 7;208(4):148-51. Epub 2015 Mar 7.

Federal Scientifc Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

The KMT2A gene (previously known as MLL) located at 11q23 is often involved in recurrent chromosomal translocations that lead to the development of acute leukemia, particularly in infants. Acute leukemias with KMT2A rearrangements have different prognoses, which depend on the partner gene involved in the translocation. The detection of all possible types of KMT2A gene rearrangements is of key importance for the identification of biological subgroups, which may differ in clinical outcome. In this report, we describe a case study of a 7-month-old boy who presented with AML-M4; however, no obvious 11q23 rearrangement was detected in the analyzed karyotype. Fluorescence in situ hybridization evaluation showed a nonstandard signal distribution in blast cells, corresponding to the presence of two KMT2A copies and one additional copy of 5'-KMT2A inserted into the long arm of the X chromosome (ins(X;11)(q28;q23q23)). Subsequent molecular analysis showed a novel variant form of the previously described KMT2A-FLNA fusion gene, in which the KMT2A intron 9 is fused to the FLNA exon 16.
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http://dx.doi.org/10.1016/j.cancergen.2015.03.001DOI Listing
April 2015
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