A New Approach of Detecting Fusion Oncogenes by RNA Sequencing Exon Coverage Analysis.

Background: In clinical practice, various methods are used to identify gene rearrangements in tumor samples, ranging from "classic" techniques, such as IHC, FISH, and RT-qPCR, to more advanced highly multiplexed approaches, such as NanoString technology and NGS panels. Each of these methods has its own advantages and disadvantages, but they share the drawback of detecting only a restricted (although sometimes quite extensive) set of preselected biomarkers. At the same time, whole transcriptome sequencing (WTS, RNAseq) can, in principle, be used to detect gene fusions while simultaneously analyzing an incomparably wide range of tumor characteristics.

Bioinformatic and clinical experimental assay uncovers resistance and susceptibility mechanisms of human glioblastomas to temozolomide and identifies new combined and individual survival biomarkers outperforming promoter methylation.

Background: Glioblastoma (GBM) is the most aggressive and lethal central nervous system (CNS) tumor. The treatment strategy is mainly surgery and/or radiation therapy, both combined with adjuvant temozolomide (TMZ) chemotherapy. Historically, methylation of gene promoter is used as the major biomarker predicting individual tumor response to TMZ.

Pan-cancer experimental characteristic of human transcriptional patterns connected with telomerase reverse transcriptase () gene expression status.

The gene encodes the reverse transcriptase subunit of telomerase and is normally transcriptionally suppressed in differentiated human cells but reactivated in cancers where its expression is frequently associated with poor survival prognosis. Here we experimentally assessed the RNA sequencing expression patterns associated with transcription in 1039 human cancer samples of 27 tumor types. We observed a bimodal distribution of expression where ∼27% of cancer samples did not express and the rest showed a bell-shaped distribution.

Sample-Wise and Gene-Wise Comparisons Confirm a Greater Similarity of RNA and Protein Expression Data at the Level of Molecular Pathways and Suggest an Approach for the Data Quality Check in High-Throughput Expression Databases.

Identification of genes and molecular pathways with congruent profiles in the proteomic and transcriptomic datasets may result in the discovery of promising transcriptomic biomarkers that would be more relevant to phenotypic changes. In this study, we conducted comparative analysis of 943 paired RNA and proteomic profiles obtained for the same samples of seven human cancer types from The Cancer Genome Atlas (TCGA) and NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) [two major open human cancer proteomic and transcriptomic databases] that included 15,112 protein-coding genes and 1611 molecular pathways. Overall, our findings demonstrated statistically significant improvement of the congruence between RNA and proteomic profiles when performing analysis at the level of molecular pathways rather than at the level of individual gene products.

Human Blood Serum Counteracts EGFR/HER2-Targeted Drug Lapatinib Impact on Squamous Carcinoma SK-BR-3 Cell Growth and Gene Expression.

Lapatinib is a targeted therapeutic inhibiting HER2 and EGFR proteins. It is used for the therapy of HER2-positive breast cancer, although not all the patients respond to it. Using human blood serum samples from 14 female donors (separately taken or combined), we found that human blood serum dramatically abolishes the lapatinib-mediated inhibition of growth of the human breast squamous carcinoma SK-BR-3 cell line.

Algorithmically Reconstructed Molecular Pathways as the New Generation of Prognostic Molecular Biomarkers in Human Solid Cancers.

Individual gene expression and molecular pathway activation profiles were shown to be effective biomarkers in many cancers. Here, we used the human interactome model to algorithmically build 7470 molecular pathways centered around individual gene products. We assessed their associations with tumor type and survival in comparison with the previous generation of molecular pathway biomarkers (3022 "classical" pathways) and with the RNA transcripts or proteomic profiles of individual genes, for 8141 and 1117 samples, respectively.

Distinct Traits of Structural and Regulatory Evolutional Conservation of Human Genes with Specific Focus on Major Cancer Molecular Pathways.

The evolution of protein-coding genes has both structural and regulatory components. The first can be assessed by measuring the ratio of non-synonymous to synonymous nucleotide substitutions. The second component can be measured as the normalized proportion of transposable elements that are used as regulatory elements.

and genes modulate sensitivity of breast cancer cells to ferroptosis.

Relapse of breast cancer is one of the key obstacles to successful treatment. Previously we have shown that low expression of and genes in breast cancer tissue corresponded to poor prognosis. participates directly in the elongation of polyunsaturated fatty acids (PUFAs) that are considered to play an important role in cancer cell metabolism.

Reclassification of TCGA Diffuse Glioma Profiles Linked to Transcriptomic, Epigenetic, Genomic and Clinical Data, According to the 2021 WHO CNS Tumor Classification.

In 2021, the fifth edition of the WHO classification of tumors of the central nervous system (WHO CNS5) was published. Molecular features of tumors were directly incorporated into the diagnostic decision tree, thus affecting both the typing and staging of the tumor. It has changed the traditional approach, based solely on histopathological classification.

Coagulation removal of nickel (II) ions by ferric chloride: Efficiency and mechanism.

Removal of heavy metal ions, in particular, divalent nickel ions from natural and wastewater, is of great importance for the environment. Nickel (II) ions are very toxic and provoke many diseases. The purpose of this work was to study the possibility of removing toxic nickel (II) ions from polluted water using an iron (III) chloride (FeCl3) coagulant.

Specificity of viscumin revised. As probed with a printed glycan array.

Viscumin, a lectin used in anti-cancer therapy, was originally considered as βGal recognizing protein; later, an ability to bind 6'-sialyl N-acetyllactosamine (6'SLN) terminated gangliosides was found. Here we probed viscumin with a printed glycan array (PGA) containing a large number of mammalian sulfated glycans, and found a strong binding to glycans with 6-O-SuGal moiety as lactose, N-acetyllactosamine (LN), di-N-acetyllactosamine (LacdiNAc), and even 6-O-SuGalNAcα (but not SiaTn). Also, the ability to bind some of αGal terminated glycans, including Galα1-3Galβ1-4GlcNAc, was observed.

Better Agreement of Human Transcriptomic and Proteomic Cancer Expression Data at the Molecular Pathway Activation Level.

Previously, we have shown that the aggregation of RNA-level gene expression profiles into quantitative molecular pathway activation metrics results in lesser batch effects and better agreement between different experimental platforms. Here, we investigate whether pathway level of data analysis provides any advantage when comparing transcriptomic and proteomic data. We compare the paired proteomic and transcriptomic gene expression and pathway activation profiles obtained for the same human cancer biosamples in The Cancer Genome Atlas (TCGA) and the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) projects, for a total of 755 samples of glioblastoma, breast, liver, lung, ovarian, pancreatic, and uterine cancers.

Differences in Medium-Induced Conformational Plasticity Presumably Underlie Different Cytotoxic Activity of Ricin and Viscumin.

Structurally similar catalytic subunits A of ricin (RTA) and viscumin (MLA) exhibit cytotoxic activity through ribosome inactivation. Ricin is more cytotoxic than viscumin, although the molecular mechanisms behind this difference are still poorly understood. To shed more light on this problem, we used a combined biochemical/molecular modeling approach to assess possible relationships between the activity of toxins and their structural/dynamic properties.

Effect of the Expression of and Genes on the Metastatic Potential of Breast Cancer Cells.

Breast cancer (BC) is the leading cause of death from malignant neoplasms among women worldwide, and metastatic BC presents the biggest problems for treatment. Previously, it was shown that lower expression of and genes is associated with a higher risk of the formation of distant metastases in BC. In this work, we studied the change in phenotypical traits, as well as in the transcriptomic and proteomic profiles of BC cells as a result of the stable knockdown of and genes.

DNA repair pathway activation features in follicular and papillary thyroid tumors, interrogated using 95 experimental RNA sequencing profiles.

DNA repair can prevent mutations and cancer development, but it can also restore damaged tumor cells after chemo and radiation therapy. We performed RNA sequencing on 95 human pathological thyroid biosamples including 17 follicular adenomas, 23 follicular cancers, 3 medullar cancers, 51 papillary cancers and 1 poorly differentiated cancer. The gene expression profiles are annotated here with the clinical and histological diagnoses and, for papillary cancers, with gene V600E mutation status.

[Hereditary cancer syndromes: a modern paradigm].

About 5-10% of malignant neoplasms (MN) are hereditary. Carriers of mutations associated with hereditary tumor syndromes (HTS) are at high risk of developing tumors in childhood and young age and synchronous and metachronous multiple tumors. At the same time, this group of diseases remains mainly an oncological problem, and clinical decisions are made only when MNs are detected in carriers of pathogenic mutations.

Impedance Spectroscopy as a Tool for Monitoring Performance in 3D Models of Epithelial Tissues.

In contrast to traditional 2D cell cultures, both 3D models and organ-on-a-chip devices allow the study of the physiological responses of human cells. These models reconstruct human tissues in conditions closely resembling the body. Translation of these techniques into practice is hindered by associated labor costs, a need which may be remedied by automation.

Specific refolding pathway of viscumin A chain in membrane-like medium reveals a possible mechanism of toxin entry into cell.

How is a water-soluble globular protein able to spontaneously cross a cellular membrane? It is commonly accepted that it undergoes significant structural rearrangements on the lipid-water interface, thus acquiring membrane binding and penetration ability. In this study molecular dynamics (MD) simulations have been used to explore large-scale conformational changes of the globular viscumin A chain in a complex environment - comprising urea and chloroform/methanol (CHCl/MeOH) mixture. Being well-packed in aqueous solution, viscumin A undergoes global structural rearrangements in both organic media.

Interprotein Coupling Enhances the Electrocatalytic Efficiency of Tobacco Peroxidase Immobilized at a Graphite Electrode.

Covalent immobilization of enzymes at electrodes via amide bond formation is usually carried out by a two-step protocol, in which surface carboxylic groups are first activated with the corresponding cross-coupling reagents and then reacted with protein amine groups. Herein, it is shown that a modification of the above protocol, involving the simultaneous incubation of tobacco peroxidase and the pyrolytic graphite electrode with the cross-coupling reagents produces higher and more stable electrocatalytic currents than those obtained with either physically adsorbed enzymes or covalently immobilized enzymes according to the usual immobilization protocol. The remarkably improved electrocatalytic properties of the present peroxidase biosensor that operates in the 0.

Formation and photovoltaic performance of few-layered graphene-decorated TiO2 nanocrystals used in dye-sensitized solar cells.

Few-layer graphene/TiO2 nanocrystal composites are successfully in situ synthesized at a low temperature of 400 °C using C28H16Br2 as the precursor. Raman mapping images show that the TiO2 nanocrystals are very uniformly dispersed in the composite films, and the in situ coating during the thermal decomposition process will favor the formation of a good interface combination between the few-layered graphene and the TiO2 nanocrystals. The few-layer graphene/TiO2 nanocrystal composites are used as photoanodes in dye-sensitized solar cells (DSSCs), and the conversion efficiency of 8.