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1.
Dalton Trans ; 52(47): 17861-17872, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37975537

RESUMO

A joint structural and spectroscopic study of simple bis-cyclometataled rhodium(III) and iridium(III) complexes with 2-phenylpyridine and aromatic ß-diketones (dibenzoylmethane, benzoylacetone, benzoyltrifluoroacetone, and 2-thenoyltrifluoroacetone) reveals an interplay between the solid-state emission efficiency and crystal packing peculiarities of the complexes. Although the prepared rhodium(III) cyclometalates are isostructural with iridium(III) analogues, different types of π-π interactions are responsible for the aggregation-induced emission (AIE) of the complexes depending on the metal ion. For iridium(III) complexes, pyridyl-pyridyl contacts are essential for AIE because they lower the energy of the emissive metal-to-ligand charge transfer state below that of the non-emissive state located at the ancillary ligand. Enabled by phenyl-pyridyl interactions partially blocking the population of non-emissive d-d states, solid-state phosphorescence enhancement is successfully achieved in a rhodium(III) complex with ancillary benzoyltrifluoroacetone, which is the first example of a rhodium complex exhibiting AIE.

2.
Plant Dis ; 107(2): 493-499, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36265157

RESUMO

Wheat stem rust, caused by Puccinia graminis f. sp. tritici, which used to be a harmful disease of winter wheat in the southern part of Russia, has been largely affecting the yield of spring bread wheat in the territories of the temperate climate zone since 2009. In total, 222 P. graminis f. sp. tritici isolates were obtained from samples of susceptible cultivars of spring bread wheat in Central and Volga regions and Omsk and Novosibirsk provinces in 2019. Genotyping of the isolates was carried out at 16 simple-sequence repeat (SSR) loci. Number of alleles, proportion of heterozygotes, and deviation from Hardy-Weinberg equilibrium were determined at each SSR locus. Based on genetic variability of SSR genotypes, it was shown that the P. graminis f. sp. tritici population is subdivided into two large clusters in the territory of the Russian temperate climate zone: the "European" population (the Central region) and the "Asian" one (the Volga region and two main wheat provinces of Western Siberia). Both of the P. graminis f. sp. tritici populations are characterized by a mixed mode of reproduction (sexual and clonal) but different sources of inoculum seem to shape a genotype structure within them. A group of P. graminis f. sp. tritici genotypes with high variability, the inbreeding coefficient closed to zero, and low observed heterozygosity was revealed among samples from Omsk. Moreover, two singular SSR genotypes identified among the Asian samples of P. graminis f. sp. tritici isolates should attract special attention in the monitoring of stem rust in order to disclose unexpected rapid changes of the pathogen in the corresponding regions and to prevent disease outbreak.


Assuntos
Basidiomycota , Pão , Doenças das Plantas , Basidiomycota/genética , Genótipo , Federação Russa
3.
Molecules ; 27(10)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35630677

RESUMO

Though 2-arylperimidines have never been used in iridium(III) chemistry, the present study on structural, electronic and optical properties of N-unsubstituted and N-methylated 2-(2-thienyl)perimidines, supported by DFT/TDDFT calculations, has shown that these ligands are promising candidates for construction of light-harvesting iridium(III) complexes. In contrast to N-H perimidine, the N-methylated ligand gave the expected cyclometalated µ-chloro-bridged iridium(III) dimer which was readily converted to a cationic heteroleptic complex with 4,4'-dicarboxy-2,2'-bipyridine. The resulting iridium(III) dye exhibited panchromatic absorption up to 1000 nm and was tested in a dye-sensitized solar cell.

4.
Acta Crystallogr E Crystallogr Commun ; 78(Pt 2): 169-172, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35145745

RESUMO

The title compounds, 2-(4-methylphenyl)-1H-perimidine hemihydrate (1, C18H14N2·0.5H2O) and 1-methyl-2-(4-methylphenyl)-1H-perimidine (2, C19H16N2), were prepared and characterized by 1H NMR and single-crystal X-ray diffraction. The organic mol-ecule of the hemihydrate lies on a twofold rotation axis while the water mol-ecule lies on the inter-section of three twofold rotation axes (point group symmetry 222). As a consequence, the hydrogen atoms that are part of the N-H group and the water mol-ecule as well as the CH3 group of the p-tolyl ring are disordered over two positions. In compound 1, the perimidine and the 2-aryl rings are slightly twisted while its N-methyl-ated derivative 2 has a more distorted conformation because of the steric repulsion between the N-methyl group and the 2-aryl ring. In the crystal structures, mol-ecules of perimidine 2 are held together only by C-H⋯π contacts while the parent perimidine 1 does not exhibit this type of inter-action. Its crystal packing is established by inter-molecular N-H⋯O hydrogen bonds with the solvent water mol-ecules and additionally stabilized by π-π stacking.

5.
Acta Crystallogr E Crystallogr Commun ; 77(Pt 2): 96-100, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33614133

RESUMO

The title compounds, 2-(pyridin-2-yl)-1H-perimidine (C16H11N3; 1), 1-methyl-2-(pyridin-2-yl)-1H-perimidine (C17H13N3; 2), and 1,3-dimethyl-2-(pyridin-2-yl)-1H-perimidinium iodide (C18H16N3 +·I-; 3) were synthesized under mild conditions and their structures were determined by 1H NMR spectroscopy and single-crystal X-ray analysis. The N-methyl-ation of the nitro-gen atom(s) at the perimidine moiety results in a significant increase of the inter-plane angle between the pyridin-2-yl ring and the perimidine system. The unsubstituted perimidine (1) forms a weak intra-molecular N-H⋯N bond that consolidates the mol-ecular conformation. In the crystal structures of 1-3, the mol-ecular entities all are assembled through π-π and C-H⋯π inter-actions.

6.
Gynecol Endocrinol ; 36(sup1): 33-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33305670

RESUMO

OBJECTIVE: study the levels of proinflammatory mediators and their correlation with reproductivefailure in women with uterine fibroids (UF). MATERIALS AND METHODS: 90 women aged 18 - 45 years (mean age - 33.9 ± 0.31) were recruited in the study: 60 women with UF were included in the study group and 30 healthy women were included in the control group. The lymphocyte count was performed with laser-based flow cytofluorimetry. The levels of C-reactive protein (CRP), interferon IFN-ß (IFN-ß), interferon-γ (IFN-γ), tumor necrotizing factor α (TNF-α) and basic fibroblast growth factor (FGF basic) were detected with ELISA test. The diagnosis of UF was confirmed with histological examination of biopsy specimen. RESULTS: Typical clinical features of UF (abnormal uterine bleeding, pelvic pains, symptoms of adjacent organs compression) were found in 66.67% women in the study group while 18.33% of them had miscarriages and 26.67% had infertility. Women with UF had significantly higher absolute count of lymphocytes: CD3+, CD19+, CD16+CD56+, CD4+, CD8+, CD95+CD3+, proinflammatory mediators: TNF-α, IFN-ß, CRP, FGF basic and decreased levels of IFN-γ compared with the control group. CONCLUSION: In women of reproductive age, typical symptoms of UF are associated with reproductive failure with activation of adaptive immunity, angiogenic factors, inflammatory cell reactions, deficit of human antitumor factors, that is why detection of TNF-α, СРБ, IFN-γ in serum is necessary to perform in pregravid preparation of women, including IVF program.


Assuntos
Infertilidade Feminina/sangue , Mediadores da Inflamação/sangue , Leiomioma , Neoplasias Uterinas , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/etiologia , Leiomioma/sangue , Leiomioma/complicações , Leiomioma/epidemiologia , Pessoa de Meia-Idade , Federação Russa/epidemiologia , Neoplasias Uterinas/sangue , Neoplasias Uterinas/complicações , Neoplasias Uterinas/epidemiologia , Adulto Jovem
7.
BMC Med Genomics ; 13(Suppl 8): 125, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948182

RESUMO

BACKGROUND: Carotid and vagal paragangliomas (CPGLs and VPGLs) are rare neoplasms that arise from the paraganglia located at the bifurcation of carotid arteries and vagal trunk, respectively. Both tumors can occur jointly as multiple paragangliomas accounting for approximately 10 to 20% of all head and neck paragangliomas. However, molecular and genetic mechanisms underlying the pathogenesis of multiple paragangliomas remain elusive. CASE PRESENTATION: We report a case of multiple paragangliomas in a patient, manifesting as bilateral CPGL and unilateral VPGL. Tumors were revealed via computed tomography and ultrasound study and were resected in two subsequent surgeries. Both CPGLs and VPGL were subjected to immunostaining for succinate dehydrogenase (SDH) subunits and exome analysis. A likely pathogenic germline variant in the SDHD gene was indicated, while likely pathogenic somatic variants differed among the tumors. CONCLUSIONS: The identified germline variant in the SDHD gene seems to be a driver in the development of multiple paragangliomas. However, different spectra of somatic variants identified in each tumor indicate individual molecular mechanisms underlying their pathogenesis.


Assuntos
Doenças das Artérias Carótidas/genética , Neoplasias dos Nervos Cranianos/genética , Neoplasias Primárias Múltiplas/genética , Paraganglioma/genética , Doenças do Nervo Vago/genética , Neoplasias Vasculares/genética , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , Neoplasias dos Nervos Cranianos/diagnóstico , Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Neoplasias dos Nervos Cranianos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Paraganglioma/diagnóstico , Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Succinato Desidrogenase/genética , Doenças do Nervo Vago/diagnóstico , Doenças do Nervo Vago/diagnóstico por imagem , Doenças do Nervo Vago/patologia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/patologia
8.
BMC Med Genomics ; 13(Suppl 8): 129, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948204

RESUMO

BACKGROUND: Prostate cancer is one of the most common and socially significant cancers among men. The aim of our study was to reveal changes in miRNA expression profiles associated with lymphatic dissemination in prostate cancer and to identify the most prominent miRNAs as potential prognostic markers for future studies. METHODS: High-throughput miRNA sequencing was performed for 44 prostate cancer specimens taken from Russian patients, with and without lymphatic dissemination (N1 - 20 samples; N0 - 24 samples). RESULTS: We found at least 18 microRNAs with differential expression between N0 and N1 sample groups: miR-182-5p, miR-183-5p, miR-96-5p, miR-25-3p, miR-93-5p, miR-7-5p, miR-615-3p, miR-10b, miR-1248 (N1-miRs; elevated expression in N1 cohort; p < 0.05); miR-1271-5p, miR-184, miR-222-3p, miR-221-5p, miR-221-3p, miR-455-3p, miR-143-5p, miR-181c-3p and miR-455-5p (N0-miRs; elevated expression in N0; p < 0.05). The expression levels of N1-miRs were highly correlated between each other (the same is applied for N0-miRs) and the expression levels of N0-miRs and N1-miRs were anti-correlated. The tumor samples can be divided into two groups depending on the expression ratio between N0-miRs and N1-miRs. CONCLUSIONS: We found the miRNA expression signature associated with lymphatic dissemination, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.


Assuntos
Metástase Linfática/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/metabolismo , RNA-Seq
9.
Mar Drugs ; 18(2)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102373

RESUMO

A bifunctional alginate lyase (ALFA3) and mannuronate-specific alginate lyase (ALFA4) genes were found in the genome of polysaccharide-degrading marine bacterium Formosa algae KMM 3553T. They were classified to PL7 and PL6 polysaccharide lyases families and expressed in E. coli. The recombinant ALFA3 appeared to be active both on mannuronate- and guluronate-enriched alginates, as well as pure sodium mannuronate. For all substrates, optimum conditions were pH 6.0 and 35 °C; Km was 0.12 ± 0.01 mg/ml, and half-inactivation time was 30 min at 42 °C. Recombinant ALFA4 was active predominately on pure sodium mannuronate, with optimum pH 8.0 and temperature 30 °C, Km was 3.01 ± 0.05 mg/ml. It was stable up to 30 °C; half-inactivation time was 1h 40 min at 37 °C. 1H NMR analysis showed that ALFA3 degraded mannuronate and mannuronate-guluronate blocks, while ALFA4 degraded only mannuronate blocks, producing mainly disaccharides. Products of digestion of pure sodium mannuronate by ALFA3 at 200 µg/ml inhibited anchorage-independent colony formation of human melanoma cells SK-MEL-5, SK-MEL-28, and RPMI-7951 up to 17% stronger compared to native polymannuronate. This fact supports previous data and suggests that mannuronate oligosaccharides may be useful for synergic tumor therapy.


Assuntos
Flavobacteriaceae/enzimologia , Polissacarídeo-Liases/metabolismo , Clonagem Molecular , Flavobacteriaceae/genética , Flavobacteriaceae/metabolismo , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Polissacarídeo-Liases/química , Polissacarídeo-Liases/genética , Conformação Proteica
10.
J Contemp Brachytherapy ; 11(4): 349-355, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31523236

RESUMO

PURPOSE: To report characteristics of our treatment scheme of high-dose-rate (HDR) brachytherapy of breast cancer and to show the first outcomes of dosimetric planning analysis based on dose-volume histogram (DVH). MATERIAL AND METHODS: Since August 2017, 25 patients diagnosed with T1N0M0 breast cancer have received a treatment in our center. There was lumpectomy and following breast HDR brachytherapy (10 fractions of 3.4 Gy) administered to each patient. A planning target volume (PTV) and organs at risk (OARs) were recorded with DVH analysis. RESULTS: The study describes the full procedure of breast HDR brachytherapy with the lumpectomy. Twenty-five patients were treated, including 9 with cancer of the left breast and 16 of the right breast. The median age was 65 years. The first analysis of DVH data shows that the main OARs were ribs and skin. Mean value of Dmax (ribs) for all patients was 19.90 Gy (55.88% of prescribed dose) and for the skin 30.88 Gy (90.74% of prescribed dose). During the treatment, there was only one case of toxic effects, which was pigmentation on the skin due to excess of dose limit of 1.4 Gy. Therefore, the limit exceeding of 1 Gy does not give any significant toxic effects. CONCLUSIONS: This study is the first stage of the dosimetric evaluation of a new method. The analysis allows treating complex localizations of the breast cancer, for example, in a close position to the skin or ribs. In order to minimize the toxic effects, it is necessary to consider patient selection, catheter administration, and dose optimization.

11.
Front Genet ; 10: 730, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447885

RESUMO

Older age is one of the main risk factors for cancer development. The incidence of prostate cancer, as a multifactorial disease, also depends upon demographic factors, race, and genetic predisposition. Prostate cancer most frequently occurs in men over 60 years of age, indicating a clear association between older age and disease onset. Carcinogenesis is followed by the deregulation of many genes, and some of these changes could serve as biomarkers for diagnosis, prognosis, prediction of drug therapy efficacy, as well as possible therapeutic targets. We have performed a bioinformatic analysis of a The Cancer Genome Atlas (TCGA) data and RNA-Seq profiling of a Russian patient cohort to reveal prognostic markers of locally advanced lymph node-negative prostate cancer (lymph node-negative LAPC). We also aimed to identify markers of the most common molecular subtype of prostate cancer carrying a fusion transcript TMPRSS2-ERG. We have found several genes that were differently expressed between the favorable and unfavorable prognosis groups and involved in the enriched KEGG pathways based on the TCGA (B4GALNT4, PTK6, and CHAT) and Russian patient cohort data (AKR1C1 and AKR1C3). Additionally, we revealed such genes for the TMPRSS2-ERG prostate cancer molecular subtype (B4GALNT4, ASRGL1, MYBPC1, RGS11, SLC6A14, GALNT13, and ST6GALNAC1). Obtained results contribute to a better understanding of the molecular mechanisms behind prostate cancer progression and could be used for further development of the LAPC prognosis marker panel.

12.
BMC Med Genet ; 20(Suppl 1): 48, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967136

RESUMO

BACKGROUND: Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from the paraganglion at the bifurcation of the carotid artery and are responsible for approximately 65% of all head and neck paragangliomas. CPGLs can occur sporadically or along with different hereditary tumor syndromes. Approximately 30 genes are known to be associated with CPGLs. However, the genetic basis behind the development of these tumors is not fully elucidated, and the molecular mechanisms underlying CPGL pathogenesis remain unclear. METHODS: Whole exome and transcriptome high-throughput sequencing of CPGLs was performed on an Illumina platform. Exome libraries were prepared using a Nextera Rapid Capture Exome Kit (Illumina) and were sequenced under 75 bp paired-end model. For cDNA library preparation, a TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold (Illumina) was used; transcriptome sequencing was carried out with 100 bp paired-end read length. Obtained data were analyzed using xseq which estimates the influence of mutations on gene expression profiles allowing to identify potential causative genes. RESULTS: We identified a total of 16 candidate genes (MYH15, CSP1, MYH3, PTGES3L, CSGALNACT2, NMD3, IFI44, GMCL1, LSP1, PPFIBP2, RBL2, MAGED1, CNIH3, STRA6, SLC6A13, and ATM) whose variants potentially influence their expression (cis-effect). The strongest cis-effect of loss-of-function variants was found in MYH15, CSP1, and MYH3, and several likely pathogenic variants in these genes associated with CPGLs were predicted. CONCLUSIONS: Using the xseq probabilistic model, three novel potential causative genes, namely MYH15, CSP1, and MYH3, were identified in carotid paragangliomas.


Assuntos
Artérias Carótidas/patologia , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Paraganglioma/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Transcriptoma , Sequenciamento do Exoma
13.
BMC Med Genet ; 20(Suppl 1): 52, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967137

RESUMO

BACKGROUND: CpG island methylator phenotype (CIMP) is found in 15-20% of malignant colorectal tumors and is characterized by strong CpG hypermethylation over the genome. The molecular mechanisms of this phenomenon are not still fully understood. The development of CIMP is followed by global gene expression alterations and metabolic changes. In particular, CIMP-low colon adenocarcinoma (COAD), predominantly corresponded to consensus molecular subtype 3 (CMS3, "Metabolic") subgroup according to COAD molecular classification, is associated with elevated expression of genes participating in metabolic pathways. METHODS: We performed bioinformatics analysis of RNA-Seq data from The Cancer Genome Atlas (TCGA) project for CIMP-high and non-CIMP COAD samples with DESeq2, clusterProfiler, and topGO R packages. Obtained results were validated on a set of fourteen COAD samples with matched morphologically normal tissues using quantitative PCR (qPCR). RESULTS: Upregulation of multiple genes involved in glycolysis and related processes (ENO2, PFKP, HK3, PKM, ENO1, HK2, PGAM1, GAPDH, ALDOA, GPI, TPI1, and HK1) was revealed in CIMP-high tumors compared to non-CIMP ones. Most remarkably, the expression of the PKLR gene, encoding for pyruvate kinase participating in gluconeogenesis, was decreased approximately 20-fold. Up to 8-fold decrease in the expression of OGDHL gene involved in tricarboxylic acid (TCA) cycle was observed in CIMP-high tumors. Using qPCR, we confirmed the increase (4-fold) in the ENO2 expression and decrease (2-fold) in the OGDHL mRNA level on a set of COAD samples. CONCLUSIONS: We demonstrated the association between CIMP-high status and the energy metabolism changes at the transcriptomic level in colorectal adenocarcinoma against the background of immune pathway activation. Differential methylation of at least nine CpG sites in OGDHL promoter region as well as decreased OGDHL mRNA level can potentially serve as an additional biomarker of the CIMP-high status in COAD.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Ilhas de CpG/genética , Metilação de DNA , Metabolismo Energético/genética , Idoso , Biologia Computacional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Regiões Promotoras Genéticas , Reprodutibilidade dos Testes , Federação Russa
14.
J Bioinform Comput Biol ; 17(1): 1950003, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30866732

RESUMO

Prostate cancer (PCa) is one of the primary causes of cancer-related mortality in men worldwide. Patients with locally advanced PCa with metastases in regional lymph nodes are usually marked as a high-risk group. One of the chief concerns for this group is to make an informed decision about the necessity of conducting adjuvant androgen deprivation therapy after radical surgical treatment. During the oncogenic transformation and progression of the disease, the expression of many genes is altered. Some of these genes can serve as markers for diagnosis, predicting the prognosis or effectiveness of drug therapy, as well as possible therapeutic targets. We undertook bioinformatic analysis of the RNA-seq data deposited in The Cancer Genome Atlas consortium database to identify possible prognostic markers. We compared the groups with favorable and unfavorable prognosis for the cohort of patients with PCa showing lymph node metastasis (pT2N1M0, pT3N1M0, and pT4N1M0) and for the most common molecular type carrying the fusion transcript TMPRSS2-ERG. For the entire cohort, we revealed at least six potential markers (IDO1, UGT2B15, IFNG, MUC6, CXCL11, and GBP1). Most of these genes are involved in the positive regulation of immune response. For the TMPRSS2-ERG subtype, we also identified six genes, the expression of which may be associated with prognosis: TOB1, GALNT7, INAFM1, APELA, RAC3, and NNMT. The identified genes, after additional studies and validation in the extended cohort, could serve as a prognostic marker of locally advanced lymph node-positive PCa.


Assuntos
Metástase Linfática/genética , Metástase Linfática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Estudos de Coortes , Biologia Computacional , Citocinas/genética , Citocinas/imunologia , Humanos , Metástase Linfática/fisiopatologia , Masculino , Redes e Vias Metabólicas/genética , Prognóstico , Neoplasias da Próstata/fisiopatologia , Transcriptoma
15.
BMC Med Genomics ; 12(Suppl 2): 39, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871634

RESUMO

BACKGROUND: Carotid body tumor (CBT) is a rare neoplasm arising from paraganglion located near the bifurcation of the carotid artery. There is great intra-tumor heterogeneity, and CBT development could be associated with both germline and somatic allelic variants. Studies on the molecular genetics of CBT are limited, and the molecular mechanisms of its pathogenesis are not fully understood. This work is focused on the estimation of mutational load (ML) in CBT. METHODS: Using the NextSeq 500 platform, we performed exome sequencing of tumors with matched lymph node tissues and peripheral blood obtained from six patients with CBT. To obtain reliable results in tumors with low ML, we developed and successfully applied a complex approach for the analysis of sequencing data. ML was evaluated as the number of somatic variants per megabase (Mb) of the target regions covered by the Illumina TruSeq Exome Library Prep Kit. RESULTS: The ML in CBT varied in the range of 0.09-0.28/Mb. Additionally, we identified several pathogenic/likely pathogenic somatic and germline allelic variants across six patients studied (including TP53 variants). CONCLUSIONS: Using the developed approach, we estimated the ML in CBT, which is much lower than in common malignant tumors. Identified variants in known paraganglioma/pheochromocytoma-causative genes and novel genes could be associated with the pathogenesis of CBT. The obtained results expand our knowledge of the mutation process in CBT as well as the biology of tumor development.


Assuntos
Tumor do Corpo Carotídeo/patologia , Mutação em Linhagem Germinativa , Adulto , Idoso , Tumor do Corpo Carotídeo/genética , Análise Mutacional de DNA/métodos , Feminino , Humanos , Mutação INDEL , Linfonodos/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética
16.
BMC Genomics ; 19(Suppl 3): 113, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29504907

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism. Although several EMT-related metabolic changes have been described in CRC, the mechanism is still poorly understood. RESULTS: Using CrossHub software, we analyzed RNA-Seq expression profile data of CRC derived from The Cancer Genome Atlas (TCGA) project. Correlation analysis between the change in the expression of genes involved in glycolysis and EMT was performed. We obtained the set of genes with significant correlation coefficients, which included 21 EMT-related genes and a single glycolytic gene, HK3. The mRNA level of these genes was measured in 78 paired colorectal cancer samples by quantitative polymerase chain reaction (qPCR). Upregulation of HK3 and deregulation of 11 genes (COL1A1, TWIST1, NFATC1, GLIPR2, SFPR1, FLNA, GREM1, SFRP2, ZEB2, SPP1, and RARRES1) involved in EMT were found. The results of correlation study showed that the expression of HK3 demonstrated a strong correlation with 7 of the 21 examined genes (ZEB2, GREM1, TGFB3, TGFB1, SNAI2, TWIST1, and COL1A1) in CRC. CONCLUSIONS: Upregulation of HK3 is associated with EMT in CRC and may be a crucial metabolic adaptation for rapid proliferation, survival, and metastases of CRC cells.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Hexoquinase/genética , Feminino , Perfilação da Expressão Gênica , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima
17.
BMC Med Genomics ; 11(Suppl 1): 17, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29504908

RESUMO

BACKGROUND: Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Paragangliomas are commonly associated with germline and somatic mutations involving at least one of more than thirty causative genes. However, the specific functionality of a number of these genes involved in the formation of paragangliomas has not yet been fully investigated. METHODS: Exome library preparation was carried out using Nextera® Rapid Capture Exome Kit (Illumina, USA). Sequencing was performed on NextSeq 500 System (Illumina). RESULTS: Exome analysis of 52 CBTs revealed potential driver mutations (PDMs) in 21 genes: ARNT, BAP1, BRAF, BRCA1, BRCA2, CDKN2A, CSDE1, FGFR3, IDH1, KIF1B, KMT2D, MEN1, RET, SDHA, SDHB, SDHC, SDHD, SETD2, TP53BP1, TP53BP2, and TP53I13. In many samples, more than one PDM was identified. There are also 41% of samples in which we did not identify any PDM; in these cases, the formation of CBT was probably caused by the cumulative effect of several not highly pathogenic mutations. Estimation of average mutation load demonstrated 6-8 mutations per megabase (Mb). Genes with the highest mutation rate were identified. CONCLUSIONS: Exome analysis of 52 CBTs for the first time revealed the average mutation load for these tumors and also identified potential driver mutations as well as their frequencies and co-occurrence with the other PDMs.


Assuntos
Biomarcadores Tumorais/genética , Tumor do Corpo Carotídeo/genética , Sequenciamento do Exoma/métodos , Exoma , Mutação , Tumor do Corpo Carotídeo/diagnóstico , Humanos
18.
BMC Genet ; 18(Suppl 1): 117, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29297384

RESUMO

BACKGROUND: Neuropilin and tolloid-like 2 (NETO2) is a single-pass transmembrane protein that has been shown primarily implicated in neuron-specific processes. Upregulation of NETO2 gene was also detected in several cancer types. In colorectal cancer (CRC), it was associated with tumor progression, invasion, and metastasis, and seems to be involved in epithelial-mesenchymal transition (EMT). However, the mechanism of NETO2 action is still poorly understood. RESULTS: We have revealed significant increase in the expression of NETO2 gene and deregulation of eight EMT-related genes in CRC. Four of them were upregulated (TWIST1, SNAIL1, LEF1, and FOXA2); the mRNA levels of other genes (FOXA1, BMP2, BMP5, and SMAD7) were decreased. Expression of NETO2 gene was weakly correlated with that of genes involved in the EMT process. CONCLUSIONS: We found considerable NETO2 upregulation, but no significant correlation between the expression of NETO2 and EMT-related genes in CRC. Thus, NETO2 may be involved in CRC progression, but is not directly associated with EMT.


Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima
19.
Nat Prod Commun ; 10(7): 1243-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26411021

RESUMO

6,8,9-Trihydroxy-2-methyl-2H-naphtho[2,3-b]pyran-5,10-dion, a pigment of the sea urchin Echinothrix diadema, and six analogs were synthesized. The cytotoxic activity and contraceptive properties of the synthesized pyranonaphthazarins have been investigated using the sperm and eggs of the sea urchin Strongylocentrotus intermedius.


Assuntos
Anticoncepcionais/síntese química , Naftoquinonas/química , Pigmentos Biológicos/química , Pironas/síntese química , Ouriços-do-Mar/química , Animais , Anticoncepcionais/toxicidade , Masculino , Naftoquinonas/toxicidade , Óvulo/efeitos dos fármacos , Pigmentos Biológicos/toxicidade , Pironas/análise , Pironas/toxicidade , Espermatozoides/efeitos dos fármacos
20.
Gynecol Endocrinol ; 30 Suppl 1: 30-1, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25200825

RESUMO

To present preliminary results of autotransplantation of vitrified human ovarian tissue to thyroid cancer patient, who underwent radioiodine treatment, performed at MRRC. Cryopreservation of ovarian tissue is increasingly used in the multi-modality treatment of cancer patients. The main purpose of ovarian tissue cryopreservation is to preserve the patient's fertility before gonadotoxic chemo- and radiotherapy. In 2012, the first orthotopic transplantation of ovarian tissue to the patient previously treated with radioactive iodine was performed at the MRRC in Russia. Monitoring changes in the ovarian reserve allowed us to assess efficacy of the orthotopic transplantation. The results demonstrated a trend to recovery of the patient's reproductive potential.


Assuntos
Carcinoma/radioterapia , Criopreservação/métodos , Preservação da Fertilidade/métodos , Radioisótopos do Iodo/uso terapêutico , Ovário/transplante , Neoplasias da Glândula Tireoide/radioterapia , Hormônio Antimülleriano/sangue , Carcinoma/cirurgia , Carcinoma Papilar , Feminino , Preservação da Fertilidade/normas , Hormônio Foliculoestimulante/sangue , Humanos , Radioisótopos do Iodo/efeitos adversos , Ovário/diagnóstico por imagem , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/cirurgia , Ultrassonografia , Adulto Jovem
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