Human Melanoma and Glioblastoma Cells Express Cathepsins Supporting Reovirus Moscow Strain Infection.

This study evaluates the oncolytic potential of the Moscow strain of reovirus against human metastatic melanoma and glioblastoma cells. The Moscow strain effectively infects and replicates within human melanoma cell lines and primary glioblastoma cells, while sparing non-malignant human cells. Infection leads to the selective destruction of neoplastic cells, mediated by functional viral replication.

[Sensitivity of Primary Human Glioblastoma Cell Lines to the Mumps Virus Vaccine Strain].

The sensitivity of human glioblastoma cells to virus-mediated oncolysis was investigated on five patient-derived cell lines. Primary glioblastoma cells (Gbl13n, Gbl16n, Gbl17n, Gbl25n, and Gbl27n) were infected with tenfold serial dilutions of the Leningrad-3 strain of the mumps virus, and virus reproduction and cytotoxicity were monitored for 96-120 h. Immortalized human non-tumor NKE cells were used as controls to determine the virus specificity.

Genomic Profiling in Glioma Patients to Explore Clinically Relevant Markers.

Gliomas are a heterogeneous group of brain tumors, among which the most aggressive subtype is glioblastoma, accounting for 60% of cases in adults. Available systemic treatment options are few and ineffective, so new approaches to therapies for glioblastoma are in high demand. In total, 131 patients with diffuse glioma were studied.

High- and Moderate-Risk Variants Among Breast Cancer Patients and Healthy Donors Enrolled in Multigene Panel Testing in a Population of Central Russia.

Assessments of breast cancer (BC) risk in carriers of pathogenic variants identified by gene panel testing in different populations are highly in demand worldwide. We performed target sequencing of 78 genes involved in DNA repair in 860 females with BC and 520 age- and family history-matched controls from Central Russia. Among BC patients, 562/860 (65.

Intratumoral Cell Heterogeneity in Patient-Derived Glioblastoma Cell Lines Revealed by Single-Cell RNA-Sequencing.

Glioblastoma cell lines derived from different patients are widely used in tumor biology research and drug screening. A key feature of glioblastoma is the high level of inter- and intratumor heterogeneity that accounts for treatment resistance. Our aim was to investigate whether intratumor heterogeneity is maintained in cell models.

Diagnostics of Mutations in Intracranial Chondroid Tumors: Comparison of Molecular Genetic Methods and Immunohistochemistry.

Intracranial chondroid tumors are a heterogeneous group of neoplasms characterized by the presence of a cartilage matrix. These tumors exhibit overlapping clinical and histological features. Mutations in genes serve as important diagnostic markers of tumor type, particularly chondrosarcoma.

The Influence of Structural Variants of the Gene on the Pharmacokinetics of Enalapril, Presumably Due to Linkage Disequilibrium with the Intronic rs2244613.

Variants in the gene encoding carboxylesterase 1 may affect the metabolism of enalapril to the active metabolite enalaprilat. It was shown that the A allele of rs71647871 and the C allele of rs2244613 led to a decrease in plasma enalaprilat concentrations. This study aimed to estimate the effect of structural haplotypes of containing the pseudogene or a hybrid of the gene and the pseudogene on the pharmacokinetics of enalapril.

Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus.

Glioblastoma multiforme (GBM) accounts for almost half of all primary malignant brain tumors in adults and has a poor prognosis. Here we demonstrated the oncolytic potential of the L-16 vaccine strain of measles virus (MV) against primary human GBM cells and characterized the genetic patterns that determine the sensitivity of primary human GBM cells to oncolytic therapy. MV replicated in all GBM cells, and seven out of eight cell lines underwent complete or partial oncolysis.

Genetic Association Study and Machine Learning to Investigate Differences in Platelet Reactivity in Patients with Acute Ischemic Stroke Treated with Aspirin.

Aspirin resistance (AR) is a pressing problem in current ischemic stroke care. Although the role of genetic variations is widely considered, the data still remain controversial. Our aim was to investigate the contribution of genetic features to laboratory AR measured through platelet aggregation with arachidonic acid (AA) and adenosine diphosphate (ADP) in ischemic stroke patients.

The Influence of the Genotype on the Pharmacokinetics of Enalapril in Patients with Arterial Hypertension.

The angiotensin-converting enzyme inhibitor enalapril is hydrolysed to an active metabolite, enalaprilat, in the liver via carboxylesterase 1 (CES1). Previous studies show that variant rs71647871 in the CES1 gene affects the pharmacokinetics of enalapril on liver samples as well as healthy volunteers. This study included 286 Caucasian patients with arterial hypertension who received enalapril.

[Determination of the Subclonal Tumor Structure in Childhood Acute Myeloid Leukemia and Acral Melanoma by Next-Generation Sequencing].

Intratumoral heterogeneity and clonal variability are among the central problems of clinical oncology, leading to resistance to therapy, relapse, and metastasis. High-throughput sequencing of the tumor exome makes it possible to investigate the subclonal tumor organization. Target panel, clinical exome, and complete exome sequencing data were compared in tumors with different mutational burden, acute myeloid leukemia (AML) in children and acral melanoma.

[Monitoring of nocturnal penile tumescence in healthy volunteers by the Androscan MIT registrar to establish reliable normal physiological values in a multicenter study].

Aim: To evaluate the normal numerical and graphic values of nocturnal penile tumescence (NPT) test using Androscan MIT in healthy males in order to use the collected data as reference standard.

Materials And Methods: NPT monitoring was carried out in 38 healthy male volunteers by fixing a sensor designed for 20 measurements on their penis. During the NPT test the following parameters were recorded: 1) total sleep time; 2) minimal penis diameter (PD) in the flaccid state recorded by the apparatus; 3) maximum PD during effective penile tumescence; 4) absolute PD increase during effective erections; 5) increase in PD in %; 6) the overall time of the rigid-erection phase; 7) the number of penile rigidity episodes; 8) the average duration of each effective erection; 9) the percentage of rigid erections during the whole monitoring period.

[Germline and Somatic Mutations in Archived Breast Cancer Specimens of Different Subtypes].

Molecular profiling of tumors may provide promising options for personalized treatment. We have examined the spectrum of germline and somatic mutations in 23 breast cancers (ВС) of various molecular subtypes, including tumors 1) with expression of estrogen, progesterone and/or epidermal growth factor receptor HER2/neu, and 2) with a triple negative phenotype. Genomic DNA specimens were isolated from archived tumor and normal tissue samples and subjected to targeted sequencing of the coding regions of 25 cancer-associated genes with a mean coverage of x 1000.

Biochip-based approach for comprehensive pharmacogenetic testing.

Objectives: Individual sensitivity to many widely used drugs is significantly associated with genetic factors. The purpose of our work was to develop an instrument for simultaneous determination of the most clinically relevant pharmacogenetic markers to allow personalized treatment, mainly in patients with cardiovascular diseases.

Methods: Multiplex one-step polymerase chain reaction (PCR) followed by hybridization on a low-density biochip was applied to interrogate 15 polymorphisms in the following eight genes:  -1639 G>A 1297 G>A 2374 C>G *2,*3 (430 C>T, 1075 A>C) (2549delA, 1846 G>A, 1707delT, 2615_2617delAAG, 2988 G>A), (681 G>A, 636 G>A, -806 C>T) (3435 C>T).

[Driver Mutations in Acute Myeloid Leukemia with Inversion of Chromosome 16].

Certain subtypes of acute myeloid leukemia occur as a result of the cooperation of several events these are, the formation of fusion genes as a result of chromosomal rearrangements, which leads to the disruption of cell differentiation, and the emergence of mutations that enhance cellular proliferation by activating intracellular signaling pathways. High-throughput sequencing methods reveal characteristic mutation spectra in leukemia associated with different chromosomal disorders. However, the role of mutation events in malignant cell transformation processes remains obscure.

The Susceptibility of Human Melanoma Cells to Infection with the Leningrad-16 Vaccine Strain of Measles Virus.

Oncolytic viruses, including live attenuated measles virus (MV) vaccine strains, have recently been shown as promising therapeutic agents against human malignancies. In this study, the oncolytic potential of the attenuated vaccine strain Leningrad-16 (L-16) of MV was evaluated in a panel of human metastatic melanoma cell lines. The L-16 measles virus was shown to replicate within melanoma cells mediating direct cell killing of tumor cells, although all melanoma cell lines varied in regard to their ability to respond to L-16 MV infection, as revealed by the different pattern of the Interferon Stimulated Gene expression, cytokine release and mechanisms of cell death.

[Somatic Mutations Associated with Metastasis in Acral Melanoma].

Acral melanoma is one of the most aggressive and fast-growing forms of cutaneous melanoma and is characterized by a predominant location on the palms and feet. Primary tumors, metastases, and normal tissue samples from five acral melanoma patients were examined by massive parallel sequencing, focusing on the coding regions of 4100 genes involved in the origin and progression of hereditary and oncology diseases. Somatic mutations were found in genes related to cell division, proliferation, and apoptosis (BRAF, NRAS, VAV1, GATA1, and GCM2); cell adhesion (CTNND2 and ITGB4); angiogenesis (VEGFA); and the regulation of energy metabolism (BCS1L).

[A clinical and genetic analysis of risk factors for the development of acute and chronic cerebral ischemia].

To study the association between polymorphic markers in the ACE, SERPINE1, FGB, F5, F7, F12, GP1BA, GPIIIa, MTHFR, CYP11B2, PON1, PON2, NOS2, NOS2, HIFla, LTA, ALOX5AP genes and clinical characteristics of acute and chronic forms of circulatory disorders of the brain. MATERIAL AND METHODS: The analysis of polymorphic variants in ACE, FGB, F5, F7, F12, GP1BA, GPIIIa, SERPINE1, MTHFR, CYP11B2, PON1, PON2, NOS2, NOS3, PDE4D, HIF1a, LTA, ALOX5AP in 81 patients with chronic cerebral ischemia (CCI) and 69 patients with ischemic stroke (IS), and their interrelation with clinical manifestations of disease were investigated. RESULTS AND CONCLUSION: The association between the T/T genotype of the PDE4D SNP 83C>T polymorphism and a rapid progression of hypertensive disease (GB) was revealed (OR=6.

[Mutational Profiling of Pediatric Myeloid Leukemia Subtypes without Clinically Significant Chromosomal Aberrations].

The discovery of novel significant molecular and genetic markers is important for the diagnostics, prognosis, and therapy selection in hematological malignancies. Distinct cytogenetic aberrations leading to the formation of fusion genes are found in more than 40% of pediactric cases of acute myeloid leukemia (AML); however, the tumor cells in approximately 20% of these patients display cytogenetically normal karyotype (NK-AML). Here we present the analysis of the mutational profiles of leukemic cells collected from pediatric AML cases without known clinically significant chromosomal aberrations aimed at identifying AML specific markers.

Reduced vs. standard dose native E. coli-asparaginase therapy in childhood acute lymphoblastic leukemia: long-term results of the randomized trial Moscow-Berlin 2002.

Purpose: Favorable outcomes were achieved for children with acute lymphoblastic leukemia (ALL) with the first Russian multicenter trial Moscow-Berlin (ALL-MB) 91. One major component of this regimen included a total of 18 doses of weekly intramuscular (IM) native Escherichia coli-derived asparaginase (E. coli-ASP) at 10000 U/m during three consolidation courses.

Melanoma arising in a Giant congenital melanocytic nevus: two case reports.

Background: A giant congenital melanocytic nevus (GCMN) is found in 0.1% of live-born infants. If present, the lesion has a chance of about 6% to develop into malignant melanoma.

The EIMB Hydrogel Microarray Technology: Thirty Years Later.

 Biological microarrays (biochips) are analytical tools that can be used to implement complex integrative genomic and proteomic approaches to the solution of problems of personalized medicine (e.g., patient examination in order to reveal the disease long before the manifestation of clinical symptoms, assess the severity of pathological or infectious processes, and choose a rational treatment).

[Multiplex Assay to Evaluate the Genetic Risk of Developing Human Melanoma].

A genotyping procedure based on single-step PCR and subsequent allele-specific hybridization on a hydrogel biochip was developed to address the polymorphisms of HERC2, OCA2, SLC24A4, SLC45A2, TYR, IRF4, MC1R,MITF, PIGU, MYH7B, NCOA6, and CDK10. Amplified gene fragments were fluorescently labeled in PCR, and fluorescent signals from biochip cells were detected to evaluate how efficiently the PCR product formed a perfect duplex with an immobilized probe. The analytical characteristics of hybridization analysis were estimated for several fluorophores with different optical spectra.