Epigenomic Profiling Advises Therapeutic Potential of Leukotriene Receptor Inhibitors for a Subset of Triple-Negative Breast Tumors.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes.

Major Contribution of c.[1622T>C;3113C>T] Complex Allele and c.5882G>A Variant in -Related Retinal Dystrophy in an Eastern European Population.

Inherited retinal diseases (IRDs) constitute a prevalent group of inherited ocular disorders characterized by marked genetic diversity alongside moderate clinical variability. Among these, -related eye pathology stands as a prominent form affecting the retina. In this study, we conducted an in-depth analysis of 96 patients harboring variants in the European part of Russia.

Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary Mutations.

We showed previously that inhibition of KIT signaling in GISTs activates FGFR-signaling pathway rendering cancer cells resistant to receptor tyrosine kinase inhibitor (RTKi) imatinib mesylate (IM) (Gleevec) despite of absence of secondary mutations and thereby illustrating a rationale for the combined (e.g., KIT- and FGFR-targeted) therapies.

Influence of Synthesis Conditions on the Properties of Zinc Oxide Obtained in the Presence of Nonionic Structure-Forming Compounds.

This work investigated the influence of synthesis conditions, including the use of nonionic structure-forming compounds (surfactants) with different molecular weights (400-12,600 g/mol) and various hydrophilic/hydrophobic characteristics, as well as the use of a glass substrate and hydrothermal exposure on the texture and structural properties of ZnO samples. By X-ray analysis, it was determined that the synthesis intermediate in all cases is the compound Zn(OH)(NO)∙2HO. It was shown that thermolysis of this compound at 600 °C, regardless of the physicochemical properties of the surfactants, leads to the formation of ZnO with a wurtzite structure and spherical or oval particles.

HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?

Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens.

Simple and Efficient Synthesis of Oligoetherdiamines: Hardeners of Epoxyurethane Oligomers for Obtaining Coatings with Shape Memory Effect.

In this work, new polymers with a shape memory effect for self-healing coatings based on oligomers with terminal epoxy groups, synthesized from oligotetramethylene oxide dioles of various molecular weights, were developed. For this purpose, a simple and efficient method for the synthesis of oligoetherdiamines with a high yield of the product, close to 94%, was developed. Oligodiol was treated with acrylic acid in the presence of a catalyst, followed by the reaction of the reaction product with aminoethylpiperazine.

Specific Features of Focal Cortical Dysplasia in Tuberous Sclerosis Complex.

Patients with tuberous sclerosis complex present with cognitive, behavioral, and psychiatric impairments, such as intellectual disabilities, autism spectrum disorders, and drug-resistant epilepsy. It has been shown that these disorders are associated with the presence of cortical tubers. Tuberous sclerosis complex results from inactivating mutations in the or genes, resulting in hyperactivation of the mTOR signaling pathway, which regulates cell growth, proliferation, survival, and autophagy.

DNA Methylation and Prospects for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy for Triple-Negative and Luminal B Breast Cancer.

Despite advances in the diagnosis and treatment of breast cancer (BC), the main cause of deaths is resistance to existing therapies. An approach to improve the effectiveness of therapy in patients with aggressive BC subtypes is neoadjuvant chemotherapy (NACT). Yet, the response to NACT for aggressive subtypes is less than 65% according to large clinical trials.

Pediatric chordoma associated with tuberous sclerosis complex: A rare case report with a thorough analysis of potential therapeutic molecular targets.

Chordoma associated with tuberous sclerosis complex (TSC) is an extremely rare tumor that was described only in 13 cases since 1975. Сhordoma itself is a malignant slow-growing bone tumor thought to arise from vestigial or ectopic notochordal tissue. Chordoma associated with TSC differs from chordoma in the general pediatric population in the median age, where the diagnosis of TSC-associated chordoma is 6.

Synthesis and Study of Physical and Mechanical Properties of Urethane-Containing Elastomers Based on Epoxyurethane Oligomers with Controlled Crystallinity.

The influence of the molecular weight of oligoamine, oligoether, and the type of diisocyanate on the physical and mechanical properties of elastomers with urethane hydroxyl hard segments was studied. For this purpose, oligoetherdiamines with molecular weights ~1008 and ~1400 g mol were synthesized by a three-stage method. Epoxyurethane oligomers were synthesized according to a two-step route with an oligodiisocyanate as an intermediate product.

Effect of asymmetric cooling of sessile droplets on orientation of the freezing tip.

Hypothesis: The shape of the "freezing tip" formed by the crystallization of water droplets demonstrated remarkable universality - no dependence on the cooling rate and physico-chemical properties of the substrate has been observed. At the same time, the spatial orientation of the freezing cone may be varied. We hypothesized that the orientation of the freezing tip is determined by the direction of heat flux at the base of the sessile droplet.

Preparation, Structure and Properties of Urethane-Containing Elastomers Based on Epoxy Terminal Oligomers.

The effect of polyester oligoethylene adipate molecular weight, diisocyanate structure, and chain extender on the properties of epoxyurethane-based oligomer elastomers was studied in this research. Oligoethylene adipates were obtained via polycondensation of adipic acid and ethylene glycol. Epoxyurethane oligomers were synthesized according to a two-step route with an oligodiisocyanate as an intermediate product.

New Regions With Molecular Alterations in a Rare Case of Insulinomatosis: Case Report With Literature Review.

Insulinomatosis is characterized by monohormonality of multiple macro-tumors and micro-tumors that arise synchronously and metachronously in all regions of the pancreas, and often recurring hypoglycemia. One of the main characteristics of insulinomatosis is the presence of insulin-expressing monohormonal endocrine cell clusters that are exclusively composed of proliferating insulin-positive cells, are less than 1 mm in size, and show solid islet-like structure. It is presumed that insulinomatosis affects the entire population of β-cells.

Parental Origin of the Gene Mutations in Families with Low Penetrance Hereditary Retinoblastoma.

Our aim was to identify alterations causing hereditary low penetrance retinoblastoma and to evaluate how the parental origin of an mutation affects its phenotypic expression. By NGS and MLPA, mutations were found in 191 from 332 unrelated retinoblastoma patients. Among patients with identified mutations but without clinical family history of retinoblastoma, 7% (12/175) were found to have hereditary disease with one of the parents being an asymptomatic carrier of an mutation.

Mutations in Epigenetic Regulation Genes in Gastric Cancer.

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority ( = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority ( = 41), in histone modifier genes, among which mutations were most commonly found in and .

Long noncoding RNA landscapes specific to benign and malignant thyroid neoplasms of distinct histological subtypes.

The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma (clPTC and fvPTC), and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour. Specific patterns of lncRNAs involved in the development of clinical and morphological features can be presumed. LncRNA landscapes within distinct benign and malignant histological variants of thyroid neoplasms were not investigated.

Robust icephobic coating based on the spiky fluorinated AlO particles.

Omniphobic and icephobic twin-scale surfaces based on the "urchin"-like fluorinated AlO particles are presented. Combined effect of hierarchical topography and fluorination supplied to the surfaces omniphobic and icephobic properties. The study of the stability of the Cassie wetting state is reported.

Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer.

Cell transmembrane receptors and extracellular matrix components play a pivotal role in regulating cell activity and providing for the concerted integration of cells in the tissue structures. We have assessed DNA methylation in the promoter regions of eight integrin genes, two nidogen genes, and the dystroglycan gene in normal breast tissues and breast carcinomas (BC). The protein products of these genes interact with the basement membrane proteins LAMA1, LAMA2, and LAMB1; abnormal hypermethylation of the LAMA1, LAMA2, and LAMB1 promoters in BC has been described in our previous publications.

Multiple Chromoanasynthesis in a Rare Case of Sporadic Renal Leiomyosarcoma: A Case Report.

We present the genetic profile of kidney giant leiomyosarcoma characterized by sequencing of 409 cancer related genes and chromosomal microarray analysis. Renal leiomyosarcomas are extremely rare neoplasms with aggressive behavior and poor survival prognosis. Most frequent somatic events in leiomyosarcomas are mutations in the TP53, RB1, ATRX, and PTEN genes, chromosomal instability (CIN) and chromoanagenesis.

DNA methylation markers panel can improve prediction of response to neoadjuvant chemotherapy in luminal B breast cancer.

Despite the advantages of neoadjuvant chemotherapy (NACT), associated toxicity is a serious complication that renders monitoring of the patients' response to NACT highly important. Thus, prediction of tumor response to treatment is imperative to avoid exposure of potential non-responders to deleterious complications. We have performed genome-wide analysis of DNA methylation by XmaI-RRBS and selected CpG dinucleotides differential methylation of which discriminates luminal B breast cancer samples with different sensitivity to NACT.

Abnormal Hypermethylation of CpG Dinucleotides in Promoter Regions of Matrix Metalloproteinases Genes in Breast Cancer and Its Relation to Epigenomic Subtypes and HER2 Overexpression.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) substantially contribute to the regulation of intercellular interactions and thereby play a role in maintaining the tissue structure and function. We examined methylation of a subset of 5'-cytosine-phosphate-guanine-3' (CpG) dinucleotides in promoter regions of the , , and genes by methylation-sensitive restriction enzyme digestion PCR. In our collection of 183 breast cancer samples, abnormal hypermethylation was observed for CpGs in , and promoter regions.

Case of Hereditary Papillary Renal Cell Carcinoma Type I in a Patient With a Germline Mutation in Russia.

Hereditary papillary renal carcinoma (HPRC) is a rare autosomal dominant disease characterized by the development of multiple papillary type I renal cell carcinomas. This hereditary kidney cancer form is caused by activating mutations in . Descriptions of patients with HPRC are scarce in the world literature, and no cases have been described in open sources in Russia.

Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing.

Somatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel.