IDENTIFICATION OF CLINICALLY RELEVANT GENE VARIANTS IN COLON ADENOCARCINOMA SAMPLES OF UKRAINIAN PATIENTS USING A COMPREHENSIVE CANCER PANEL: A PILOT STUDY.

Unlabelled: The study aimed to identify the clinically relevant gene variants in colon adenocarcinoma samples of Ukrainian patients using the NGS Comprehensive Cancer Panel (CCP) to implement them conveniently in clinical practice.

Methods: We have studied 20 samples of Ukrainian patients with colorectal adenocarcinomas of various differentiation grades. To identify the clinically relevant gene variants, the CCP data were filtered using the Franklin by Genoox database.

Tristetraprolin affects invasion-associated genes expression and cell motility in triple-negative breast cancer model.

Tristetraprolin (TTP) is an RNA-binding protein that negatively regulates its target mRNAs and has been shown to inhibit tumor progression and invasion. Tumor invasion requires precise regulation of cytoskeletal components, and dysregulation of cytoskeleton-associated genes can significantly alter cell motility and invasive capability. Several genes, including SH3PXD2A, SH3PXD2B, CTTN, WIPF1, and WASL, are crucial components of the cytoskeleton reorganization machinery and are essential for adequate cell motility.

Electrochemical Biosensors for the Detection of Antibiotics in Milk: Recent Trends and Future Perspectives.

Antibiotics have emerged as ground-breaking medications for the treatment of infectious diseases, but due to the excessive use of antibiotics, some drugs have developed resistance to microorganisms. Because of their structural complexity, most antibiotics are excreted unchanged, polluting the water, soil, and natural resources. Additionally, food items are being polluted through the widespread use of antibiotics in animal feed.

α7 Nicotinic acetylcholine receptors regulate translocation of HIF-1α to the cell nucleus and mitochondria upon hypoxia.

Nicotinic acetylcholine receptors (nAChRs), initially characterized as ligand-gated ion channels mediating fast synaptic transmission, are now found in many non-excitable cells and mitochondria where they function in ion-independent manner and regulate vital cellular processes like apoptosis, proliferation, cytokine secretion. Here we show that the nAChRs of α7 subtype are present in the nuclei of liver cells and astrocytoma U373 cell line. As shown by lectin ELISA, the nuclear α7 nAChRs are mature glycoproteins that follow the standard rout of post-translational modifications in Golgi; however, their glycosylation profile is non-identical to that of mitochondrial nAChRs.

Comparative characteristics of DNA loop domains rearrangement in glioblastoma multiforme T98G and glioblastoma astrocytoma U373 cell lines under different culture conditions.

Background: The loop domain organization of chromatin, which plays an important role in transcription regulation, may depend on the cell functional state. The aim of this work was to investigate DNA loop reorganization upon functional transitions in two cell lines ‒ glioblastoma multiforme T98G and glioblastoma astrocytoma U373.

Materials And Methods: Single cell gel electrophoresis (the comet assay) was used to analyze the kinetics of the DNA loop migration from the nucleoids obtained from the lysed cells.

Empty nose syndrome pathogenesis and cell-based biotechnology products as a new option for treatment.

Empty nose syndrome (ENS) is a rare complication that develops after partial or complete turbinectomy. The main feature of ENS is paradoxical nasal obstruction feeling despite objectively wide nasal airway. ENS pathogenesis is multifactorial and includes changes in laminar physiological airflow, disruption of mucosa functions and deficient neural sensation.

The geometry of diphtheria toxoid CRM197 channel assessed by thiazolium salts and nonelectrolytes.

The geometry of the channel formed by nontoxic derivative of diphtheria toxin CRM197 in lipid bilayer was determined using the dependence of single-channel conductance upon the hydrodynamic radii of different nonelectrolytes. It was found that the cis entrance of CRM197 channel on the side of membrane to which the toxoid was added at pH 4.8 and the trans entrance on the opposite side at pH 6.

Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study.

We assessed the predictive ability of a combined genetic variant panel for the risk of recurrent pregnancy loss (RPL) through a case-control study. Our study sample was from Ukraine and included 114 cases with idiopathic RPL and 106 controls without any pregnancy losses/complications and with at least one healthy child. We genotyped variants within 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood coagulation (, , , ), hormonal regulation (, ), endometrium and placental function (, ), folate metabolism () and inflammatory response (, , ).

Inhibition of USP1, a new partner of Bcr-Abl, results in decrease of Bcr-Abl level in K562 cells.

Aim: To analyze interaction of ubiquitin specific peptidase 1 (USP1) with Bcr-Abl and to assess the relation between USP1 functional activity and Bcr-Abl expression in K562 chronic myeloid leukemia cells.

Materials And Methods: The interaction between USP1 and Bcr-Abl in K562 cells was analyzed by co-immunoprecipitation, Western blot analysis, and confocal microscopy.

Results: A direct interaction between Bcr-Abl oncoprotein and USP1 protein in K562 cells was established by co-immunoprecipitation.

Stabilization of AIMP1/p43 and EMAP II recombinant proteins in the complexes with polysaccharide dextran-70.

Background: Protein-based pharmaceuticals are among the fastest growing categories of therapeutic agents in the clinic and as commercial products, and typically target high-impact areas such as various cancers, autoimmune diseases and metabolic disorders. The aim of our work was to explore the possibility of reducing the level of aggregation and improve the stability of the recombinant proteins AIMP1/p43 (aminoacyl-tRNA synthetase complex component of the higher eukaryotes) and antitumor cytokine EMAP II (proteolytic cleavage product of AIMP1/p43) in combination with dextran-70 polysaccharide for structural-functional research and development of new sustainable biomedical products.

Methods: We studied interaction strength between these recombinant proteins with polymer by fluorescence spectroscopy and molecular docking.

Dietary lipids and environmental xenobiotics as risk factors for prostate cancer: The role of cytochrome P450.

Prostate cancer is one of the most common malignant neoplasms in men. Because of the increase in the number of cases as well as development of cancers resistant to conventional therapy, identification of the new molecular targets for the treatment and prevention is of great importance. For this purpose, many studies are aimed on revealing of molecular mechanisms of prostate cancer development.

Mesenchymal Stem Cells or Interleukin-6 Improve Episodic Memory of Mice Lacking α7 Nicotinic Acetylcholine Receptors.

Nicotinic acetylcholine receptors of α7 subtype (α7 nAChRs) are involved in regulating cognition, inflammation and cell survival. Neuroinflammation is accompanied by the decrease of α7 nAChRs in the brain and impairment of memory. We show here that α7-/- mice possess pro-inflammatory phenotype and demonstrate worse episodic memory compared to wild-type mice.

Intravenously Injected Mesenchymal Stem Cells Penetrate the Brain and Treat Inflammation-Induced Brain Damage and Memory Impairment in Mice.

Neuroinflammation is regarded as one of the pathogenic factors of Alzheimer disease (AD). Previously, we showed that mice regularly injected with bacterial lipopolysaccharide (LPS) possessed the AD-like symptoms like episodic memory decline, elevated amounts of amyloid beta (Aβ) peptide (1-42), and decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain. The use of mesenchymal stem cells (MSCs), which can differentiate into multiple cell types, including neurons, is an attractive idea of regenerative medicine, in particular, for neurodegenerative disorders like AD.

Comparative Analysis of Biological Properties of Large-Scale Expanded Adult Neural Crest-Derived Stem Cells Isolated from Human Hair Follicle and Skin Dermis.

Introduction: The adult neural crest-derived stem cells (NCSCs) have significant perspectives for use in regenerative medicine. The most attractive sources for adult NCSC isolation are the hair follicles (HF) and skin dermis (SD) because of easy access and minimally invasive biopsy. The aim of this study was to compare the biological properties of HF- and SD-derived NCSCs after their large-scale expansion.

Conductometric biosensor for arginine determination in pharmaceutics.

A new conductometric biosensor based on coimmobilized urease and arginase has been developed for arginine determination in pharmaceutics. First, the main parameters of the selected method of immobilization (concentrations of arginase, urease, and glutaraldehyde, time of incubation) were optimized. An influence of the solution parameters (buffer ionic strength, capacity, pH, Mn concentration) on the biosensor operation was studied, working conditions were optimized.

Expression of steroid and peptide hormone receptors, metabolic enzymes and EMT-related genes in prostate tumors in relation to the presence of the TMPRSS2/ERG fusion.

Aim: To analyze an expression pattern of the steroid and peptide hormone receptors, metabolic enzymes and EMT-related genes in prostate tumors in relation to the presence of the TMPRSS2/ERG fusion; and to examine a putative correlation between gene expression and clinical characteristics, to define the molecular subtypes of prostate cancer.

Materials And Methods: The relative gene expression (RE) of 33 transcripts (27 genes) and the presence/absence of the TMPRSS2/ERG fusion were analyzed by a quantitative PCR. 37 prostate cancer tissues (T) paired with conventionally normal prostate tissue (CNT) and 21 samples of prostate adenomas were investigated.

Synthesis, spectral characterization of novel Pd(II), Pt(II) π-coordination compounds based on N-allylthioureas. Cytotoxic properties and DNA binding ability.

Four novel Pd and Pt mononuclear π-coordination compounds with general formula [M(HL)Cl], M=Pd, Pt have been synthesized by reaction of [PdCl], [PtCl] anions with N-allyl-4-morpholinethiocarboxamide (HL) and N-Allyl-N'-tert-butylthiourea (HL). All complexes have been characterized by single-crystal X-ray diffraction study and H, C NMR spectroscopy. Cytotoxic, cytostatic and proapoptotic activities of compounds have been determined in vitro on HeLa cell line and compared with cisplatin as etalon drug.

An Epigenetic Reprogramming Strategy to Resensitize Radioresistant Prostate Cancer Cells.

Radiotherapy is a mainstay of curative prostate cancer treatment, but risks of recurrence after treatment remain significant in locally advanced disease. Given that tumor relapse can be attributed to a population of cancer stem cells (CSC) that survives radiotherapy, analysis of this cell population might illuminate tactics to personalize treatment. However, this direction remains challenging given the plastic nature of prostate cancers following treatment.

Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1.

Fibroblast grow factor receptor 1 (FGFR1) is an important anti-cancer target that plays crucial role in oncogenesis and oncogenic angiogenesis. The structure-activity relationship (SAR) of N-phenylthieno[2,3-d]pyrimidin-4-amines was investigated. Binding of active compounds with FGFR1 kinase was analyzed by molecular modeling studies.

Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells.

Radiotherapy is a curative treatment option in prostate cancer. Nevertheless, patients with high-risk prostate cancer are prone to relapse. Identification of the predictive biomarkers and molecular mechanisms of radioresistance bears promise to improve cancer therapies.

In search of molecular approaches to improving cancer therapy efficacy.

The study of genome rearrangement sites using full genome sequences is an important approach to revealing the nature of cancer and finding effective ways for cancer treatment. The progress in DNA sequencing could make the procedure of whole genome reading close to routine procedure of lower cost. The personal analysis of rearranged ends (PARE) method used for rearrangement study is reviewed.

Serological analysis of SEREX-defined medullary breast carcinoma-associated antigens.

Medullary breast carcinoma (MBC) despite anaplastic features and high grade has a good prognosis that can be related to prominent lymphocytic infiltration. We analyzed the frequency of antibody response toward 41 SEREX (serological recombinant expression cloning)-defined MBC antigens in sera of allogeneic MBC patients using serological plaque-spot assay and examined the mRNA expression profile of some antigens in MBC tissues. This preliminary study allowed us to select 18 autoantigens as potential MBC-associated antigens.

Preliminary study of thyroid and colon cancers-associated antigens and their cognate autoantibodies as potential cancer biomarkers.

Background: Autoantibodies, which are produced against tumor-associated antigens, are potential tumor markers and attract a growing interest for cancer detection, differential diagnostics and prognosis.

Objective: To evaluate the diagnostic significance of 40 antigens identified by immunoscreening of cDNA libraries from thyroid and colon cancers by allogenic screening with different tumor types patients' sera.

Method: Plaque-spot serological assay.

Immunohistochemical analysis of NaPi2b protein (MX35 antigen) expression and subcellular localization in human normal and cancer tissues.

Aim: To study the expression profile of the NaPi2b protein and its localization in breast, ovarian and lung cancer cells in relation to normal tissues adjacent to tumor.

Methods: Immunohistochemical analysis with monoclonal antibody MX35 was applied for investigation of NaPi2b protein expression in breast, lung and ovarian carcinomas. Intensity of NaPi2b protein expression was calculated with semiquantitative scores.

Novel role of pleckstrin homology domain of the Bcr-Abl protein: analysis of protein-protein and protein-lipid interactions.

The Bcr-Abl protein is a marker for malignant transformation in chronic myeloid leukemia and in acute lymphoblastic leukemia. There are three Bcr-Abl chimeras known so far, p190, p210 and p230. The only structural difference between the three Bcr-Abl proteins is the presence of DH and PH domains from the Bcr gene in p210 and p230.