Ten Hypermethylated lncRNA Genes Are Specifically Involved in the Initiation, Progression, and Lymphatic and Peritoneal Metastasis of Epithelial Ovarian Cancer.

Our work aimed to evaluate and differentiate the role of ten lncRNA genes (, , , , , , , , , and ) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues ( < 0.

Combined Predictors of Long-Term Outcomes of Kasai Surgery in Infants with Biliary Atresia.

Purpose: Biliary atresia (BA) is the leading cause of neonatal cholestasis (25-45%). The primary treatment is hepatic portoenterostomy (Kasai procedure), but only 20-40% provide long-term benefits. This study aimed to develop a predictive model for surgical efficacy by comparing preoperative and early postoperative indicators in infants with different outcomes.

Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous -Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.

Purpose: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II).

Newly Described Mutations of the UNC45A Gene in Infants with Jaundice and Pruritus.

Background: Cholestatic liver disease is an important cause of morbidity and mortality and a leading indication for liver transplantation in children. These include diseases, such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, sclerosing cholangitis, bile acid synthesis defects, and many others.

Case Presentation: NGS was used as a diagnostic tool to identify the genetic cause in the patient with cholestatic syndrome and to figure out and describe what mutation will be found.

Prediction of Distant Metastases in Patients with Kidney Cancer Based on Gene Expression and Methylation Analysis.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive histological type of cancer in this location. Distant metastases are present in approximately 30% of patients at the time of first examination. Therefore, the ability to predict the occurrence of metastases in patients at early stages of the disease is an urgent task aimed at personalized treatment.

Dietary stress remodels the genetic architecture of lifespan variation in outbred Drosophila.

Evolutionary theory suggests that lifespan-reducing alleles should be purged from the gene pool, and yet decades of genome-wide association and model organism studies have shown that they persist. One potential explanation is that alleles that regulate lifespan do so only in certain environmental contexts. We exposed outbred Drosophila to control and high-sugar diets and genotyped more than 10,000 adult flies to track allele frequency changes over the course of a single adult lifespan.

Regulation of the Key Epithelial Cancer Suppressor miR-124 Function by Competing Endogenous RNAs.

A decrease in the miR-124 expression was observed in various epithelial cancers. Like a classical suppressor, miR-124 can inhibit the translation of multiple oncogenic proteins. Epigenetic mechanisms play a significant role in the regulation of miR-124 expression and involve hypermethylation of the genes and the effects of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) according to the model of competing endogenous RNAs (ceRNAs).

Dysregulation of lncRNA-miRNA-mRNA Interactome as a Marker of Metastatic Process in Ovarian Cancer.

Ovarian cancer (OC) is one of the most common types of cancer among malignancies of the female reproductive system. This pathology is asymptomatic until advanced stages and has a poor prognosis. Our study aimed to search for lncRNA-miRNA-mRNA competing triplets that promote ovarian tumorigenesis.

Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases.

Our work aimed to differentiate 20 aberrantly methylated miRNA genes that participate at different stages of development and metastasis of ovarian carcinoma (OvCa) using methylation-specific qPCR in a representative set of clinical samples: 102 primary tumors without and with metastases (to lymph nodes, peritoneum, or distant organs) and 30 peritoneal macroscopic metastases (PMM). Thirteen miRNA genes (, , , , , , , , , , , , and ) were hypermethylated already at the early stages of OvCa, while hypermethylation of , , , and was pronounced in metastatic tumors, and showed high methylation levels specifically in PMM. We confirmed the significant relationship between methylation and expression levels for 11 out of 12 miRNAs analyzed by qRT-PCR.

LncRNAs in the Regulation of Genes and Signaling Pathways through miRNA-Mediated and Other Mechanisms in Clear Cell Renal Cell Carcinoma.

The fundamental novelty in the pathogenesis of renal cell carcinoma (RCC) was discovered as a result of the recent identification of the role of long non-coding RNAs (lncRNAs). Here, we discuss several mechanisms for the dysregulation of the expression of protein-coding genes initiated by lncRNAs in the most common and aggressive type of kidney cancer-clear cell RCC (ccRCC). A model of competitive endogenous RNA (ceRNA) is considered, in which lncRNA acts on genes through the lncRNA/miRNA/mRNA axis.

Long Noncoding RNA GAS5 in Breast Cancer: Epigenetic Mechanisms and Biological Functions.

Long noncoding RNAs (lncRNAs) have been identified as contributors to the development and progression of cancer through various functions and mechanisms. LncRNA GAS5 is downregulated in multiple cancers and acts as a tumor suppressor in breast cancer. GAS5 interacts with various proteins (e.

Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study.

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use.

Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program.

Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)).

LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms.

Ovarian cancer (OvCa) develops asymptomatically until it reaches the advanced stages with metastasis, chemoresistance, and poor prognosis. Our review focuses on the analysis of regulatory long non-coding RNAs (lncRNAs) competing with protein-coding mRNAs for binding to miRNAs according to the model of competitive endogenous RNA (ceRNA) in OvCa. Analysis of publications showed that most lncRNAs acting as ceRNAs participate in OvCa progression: migration, invasion, epithelial-mesenchymal transition (EMT), and metastasis.

Long-Term Effects of Kasai Portoenterostomy for Biliary Atresia Treatment in Russia.

This prospective study enrolled 144 patients after surgical treatment of biliary atresia in early infancy. We analyzed the immediate effectiveness of the surgery and the age-related structure of complications in the up to 16-year follow-up. The immediate 2-year survival rate after the surgery constituted 49.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Unlabelled: Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib.

The Relationship between the Conscious Self-Regulation of Schoolchildren's Learning Activity, Their Test Anxiety Level, and the Final Exam Result in Mathematics.

This article presents the results of a study on the relationship between conscious self-regulation of learning activity, test anxiety and performance in the Unified State Exam in mathematics in a sample of Russian students (N = 231). The Self-Regulation Profile of Learning Activity Questionnaire (SRPLAQ, 2015) and Spielberger's Test Anxiety Inventory (TAI) (Russian adaptation, 2004) were used to measure self-regulation and anxiety, respectively. The study also took into account the students' results for the Unified State Exam in mathematics.

Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia.

Both heritability and environment contribute to risk for schizophrenia. However, the molecular mechanisms of interactions between genetic and non-genetic factors remain unclear. Epigenetic regulation of neuronal genome may be a presumable mechanism in pathogenesis of schizophrenia.

Overall Survival of Patients With -Positive Metastatic Non-Small-Cell Lung Cancer in the Russian Federation: Nationwide Cohort Study.

Purpose: The overall survival (OS) results in patients with -positive metastatic non-small-cell lung cancer (NSCLC) have rarely been reported. The aim of this prospective-retrospective cohort study was to obtain real-world data on the use of crizotinib or chemotherapy in patients with -positive metastatic NSCLC in Russia.

Patients And Methods: Patients with epidermal growth factor receptor-negative metastatic NSCLC were screened in 23 cancer centers.

Epigenetic-genetic chromatin footprinting identifies novel and subject-specific genes active in prefrontal cortex neurons.

Human prefrontal cortex (PFC) is associated with broad individual variabilities in functions linked to personality, social behaviors, and cognitive functions. The phenotype variabilities associated with brain functions can be caused by genetic or epigenetic factors. The interactions between these factors in human subjects is, as of yet, poorly understood.

Variability in lung cancer response to ALK inhibitors cannot be explained by the diversity of ALK fusion variants.

Multiple laboratory evidences indicate that distinct variants of ALK translocations differ in their biochemical properties and responsiveness to ALK tyrosine kinase inhibitors (TKIs). These data are supported by some clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation. We retrospectively considered 64 Russian patients with ALK-rearranged NSCLC, who were treated by crizotinib (n = 23), ceritinib (n = 39) or alectinib (n = 2).

Targeting CCR8 Induces Protective Antitumor Immunity and Enhances Vaccine-Induced Responses in Colon Cancer.

CCR8 is a chemokine receptor expressed principally on regulatory T cells (Treg) and is known to be critical for CCR8 Treg-mediated immunosuppression. Recent studies have demonstrated that CCR8 is uniquely upregulated in human tumor-resident Tregs of patients with breast, colon, and lung cancer when compared with normal tissue-resident Tregs. Therefore, CCR8 tumor-resident Tregs are rational targets for cancer immunotherapy.

Novel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasis.

Methylation of promoter CpG islands may suppress the function of miRNAs by inhibiting their expression. Our work analyzes the role of promoter methylation in altering the expression of 12 miRNAs associated with epithelial ovarian cancer (EOC): miR-124-3p, -125b-5p, -127-5p, -129-5p, -132-3p, -137, -148a-3p, -191-5p, -193a-5p, -203a, -339-3p, and -375. The role of methylation in the deregulation of these miRNAs has not been previously assessed in a representative set of EOC samples.

Safety and efficacy of p62 DNA vaccine ELENAGEN in a first-in-human trial in patients with advanced solid tumors.

Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors.

Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration.

The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C-->T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106.