MOLECULAR-BIOLOGICAL FEATURES OF MEDULLOBLASTOMA AND THEIR PROGNOSTIC SIGNIFICANCE

2017 ◽  
Vol 63 (4) ◽  
pp. 536-544
Author(s):  
Aleksandr Druy ◽  
Lyudmila Papusha ◽  
Yekaterina Salnikova ◽  
Yuliya Olshanskaya ◽  
Aleksey Maschan
Keyword(s):  
Central Nervous System ◽  
Molecular Genetic ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Clinical Heterogeneity ◽  
Biological Features ◽  
Wide Range ◽  
Central Nervous System Malignancy ◽  
Distinct Source ◽  
Genetic Techniques

Medulloblastoma is more frequent central nervous system malignancy in childhood. It is characterized by wide range of clinical heterogeneity, response to therapy and outcome. Many authors demonstrated prognostic significance of clinical, morphological, cytogenetic and molecular-biological features of the tumor. Implementation of high-throughput molecular-genetic techniques allows the medulloblastoma patients discrimination into 4 independent subgroups with distinct source of histogenesis, molecular pathogenesis, clinical manifestation and outcome. This review is devoted to molecular-biological features of medulloblastoma, underlying its clinical heterogeneity and forming the basis for individualized risk adapted and targeted treatment.

scholarly journals Analysis of platelet RNA: a non-invasive method for studying the expression of tumor genes

2021 ◽  
Vol 20 (1) ◽  
pp. 207-217
Author(s):  
I. P. Tesakov ◽  
A. A. Martyanov ◽  
A. E. Drui ◽  
A. N. Sveshnikova
Keyword(s):  
Clinical Practice ◽  
Tumor Cells ◽  
Molecular Genetic ◽  
Cancer Diagnostics ◽  
Response To Therapy ◽  
Genetic Characteristics ◽  
Non Invasive ◽  
Wide Range ◽  
Oncological Diseases ◽  
Invasive Method

Nowadays much attention is paid to non-invasive methods of cancer diagnostics and monitoring. One of the promising methods is the sequencing of platelet RNA (tumor-educated platelets), in which, as it was previously established, the mRNA repertoire changes in various oncological diseases. Thus, platelets can contain information about the molecular genetic characteristics of tumor. This review summarizes the current understanding of the mechanisms of interaction between tumor cells and platelets, and also discusses the possibilities of using platelet transcriptome analysis methods for diagnosing and assessing the dynamics of the tumor state, in particular, in response to therapy, as well as the current limitations for a wide range of introduction of this method into clinical practice. 

DIAGNOSTIC VALUE OF SPECIFIC ANTIBODY SYNTHESIS IN BRAIN OF PATIENTS WITH NEUROINFECTIONS

2019 ◽  
Vol 72 (8) ◽  
pp. 1437-1441
Author(s):  
Pavel Dyachenko ◽  
Igor Filchakov ◽  
Anatoly Dyachenko ◽  
Victoria Kurhanskaya
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Manifestations ◽  
Diagnostic Value ◽  
Diagnostic Challenge ◽  
Specific Antibodies ◽  
Intrathecal Synthesis ◽  
Varicella Zoster ◽  
Mrz Reaction ◽  
Wide Range

Introduction: Viral encephalitis accounts for 40-70% of all cases worldwide, central nervous system infections pose a diagnostic challenge because clinical manifestations are not typically pathognomonic for specific pathogens, and a wide range of agents can be causative. The aim: To assess the diagnostic value of intrathecal synthesis of specific antibodies in patients with inflammatory lesions of the central nervous system. Materials and methods: Within the framework of the study, two groups of 90 people in each were formed from the patients with neuroinfections admitted to our Center. Intrathecal synthesis (ITS) of total (unspecific) IgG in members of one of group (group of compare) was determined. Brain synthesis of specific antibodies (Ab) to some neurotropic pathogens (herpes simplex virus 1/2, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, rubella virus, Borrelies) was studied in the second group of patients (group of interest). There were no statistically significant differences between groups by gender and age. Encephalitis and encephalomyelitis prevailed among patients of both groups Results: ITS of total IgG was established in 30 (33.3 ± 6.1 %) patients of the first group with IgG index more than 0.6 indicating on inflammatory process in CNS and no marked changes of CSF. ITS of specific Ab was determined in 23 of 90 (25.6 ± 4.6 %) patients included into group of interest. In more than half of cases Ab to several infectious agents were detected simultaneously. ITS of various specificity, in particular, to measles and rubella viruses, and VZV, known as MRZ-reaction, is characteristic of some autoimmune lesions of CNS, multiple sclerosis first of all. In fact, further research of 5 patients with MRZ-reaction confirmed their autoimmune failure of CNS. Detection of ITS in the CSF samples didn’t depend on concentration of specific Ab in serum and CSF and wasn’t followed by HEB dysfunctions which were observed with the same frequency in patients with or without ITS (13.0 % and 13.6 % respectively). Conclusion: Specific Ab synthesis to several neurotropic pathogens in the CSF of significant part of examined patients was established. Thus, diagnostic value of ITS of specific immunoglobulins seems to be limited to cases in which autoimmune damage of the CNS is suspected.

scholarly journals GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii330-iii331
Author(s):  
Hirokazu Takami ◽  
Koichi Ichimura ◽  
Kohei Fukuoka ◽  
Akitake Mukasa ◽  
Nobuhito Saito ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Basal Ganglia ◽  
Pineal Gland ◽  
Germ Cell ◽  
Prognostic Significance ◽  
Germ Cell Tumors ◽  
Molecular Data ◽  
Molecular Heterogeneity ◽  
Intracranial Germ Cell Tumor

Abstract BACKGROUND We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews. RESULTS All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

Epigenetics and Applied Anthropology

2021 ◽  
Author(s):  
Charles H. Klein
Keyword(s):  
Social Inequalities ◽  
Homo Sapiens ◽  
Single Gene ◽  
Molecular Genetic ◽  
Healthcare Providers ◽  
Basic Research ◽  
Sufficient Information ◽  
Theoretical Frameworks ◽  
Noncoding Dna ◽  
Wide Range

Since Francis Crick and James D. Watson’s discovery of DNA in 1953, researchers, policymakers, and the general public have sought to understand the ways in which genetics shapes human lives. A milestone in these efforts was the completion of the Human Genome Project’s (HGP) sequencing of Homo sapiens’ nearly three million base pairs in 2003. Yet, despite the excitement surrounding the HGP and the discovery of the structural genetic underpinnings of several debilitating diseases, the vast majority of human health outcomes have not been linked to a single gene. Moreover, even when genes have been associated with particular diseases (e.g., breast and colon cancer), it is not well understood why certain genetically predisposed individuals become ill and others do not. Nor has the HGP’s map provided sufficient information to understand the actual functioning of the human genetic code, including the role of noncoding DNA (“junk DNA”) in regulating molecular genetic processes. In response, a growing number of scientists have shifted their attention from structural genetics to epigenetics, the study of how genes express themselves in particular situations and environments. Anthropologists play roles in these applications of epigenetics to real-world settings. Their new theoretical frameworks unsettle the nature-versus-nurture binary and support biocultural anthropological research demonstrating how race becomes biology and embodies social inequalities and health disparities across generations. Ethnographically grounded case studies further highlight the diverse epigenetic logics held by healthcare providers, researchers, and patient communities and how these translations of scientific knowledge shape medical practice and basic research. The growing field of environmental epigenetics also offers a wide range of options for students and practitioners interested in applying the anthropological toolkit in epigenetics-related work.

MOLECULAR GENETIC STUDIES OF CENTRAL NERVOUS SYSTEM TUMORS

2020 ◽  
pp. 42-50
Author(s):  
B.B. Zhetpisbaev ◽  
A.Zh. Doskaliyev ◽  
M.P. Solodovnikov ◽  
A.B. Kasymova ◽  
N.I. Tursynov ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Genetic ◽  
Central Nervous System Tumors ◽  
Genetic Studies ◽  
Nervous System Tumors

scholarly journals Immunogenicity of high-dose influenza vaccination in patients with primary central nervous system malignancy

2018 ◽  
Vol 5 (3) ◽  
pp. 176-183
Author(s):  
Roy E Strowd ◽  
Gregory Russell ◽  
Fang-Chi Hsu ◽  
Annette F Carter ◽  
Michael Chan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Influenza Vaccine ◽  
Elderly Patients ◽  
Influenza Vaccination ◽  
Standard Dose ◽  
High Grade Glioma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Central Nervous System Malignancy

Abstract Background For cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity. Methods A prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results. Results Twenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort. Conclusions The immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

scholarly journals Prognostic Significance of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography in Anal Squamous Cell Carcinoma: A Systematic Review and a Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ramin Sadeghi ◽  
Sara Harsini ◽  
Mohammad Ali Qodsi Rad ◽  
Vahid Reza Dabbagh ◽  
Giorgio Treglia
Keyword(s):  
Fdg Pet ◽  
Metabolic Response ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Emission Tomography ◽  
Anal Squamous Cell Carcinoma ◽  
Positron Emission ◽  
Fluorine 18 Fluorodeoxyglucose ◽  
Fluorodeoxyglucose Positron Emission

Purpose. Prognostic significance of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in anal squamous cell carcinoma (SCC) has been evaluated in several studies; however, the results seem to be controversial and no consensus exists about its predictive capability. The current meta-analysis was carried out to comprehensively investigate the prognostic significance of 18F-FDG-PET parameters in patients with anal SCC. Methods. A comprehensive literature search of PubMed/MEDLINE and Scopus databases was performed to retrieve pertinent articles published until August 5th 2018, concerning the prognostic significance of 18F-FDG-PET in patients with anal SCC. No language restriction was used. Several prognostic factors were reported for progression-free survival (PFS) and overall survival (OS) including pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), inguinal nodal uptake, and metabolic response to therapy. Results. Eleven studies (741 patients) were included. The pooled hazard ratio (HR) for the probability of PFS was 5.36 (95% confidence interval (95% CI): 3.12–9.21, p<0.001) for metabolic response to therapy and 1.98 (95% CI: 1.26–3.12, p=0.003) for SUVmax. The pooled HR for the probability of OS was 5.87 (3.02–11.39, p<0.0001) for metabolic response to therapy. On the other hand, the study revealed that the pooled HRs of MTV and inguinal nodal uptake for PFS were 1.56 (95% CI: 0.96–2.53, p=0.072) and 1.79 (95% CI: 1–3.21, p=0.051), respectively. Conclusions. Our findings propose that some 18F-FDG-PET parameters could serve as prognostic indicators in anal SCC, but further larger studies are needed in this setting.

scholarly journals Application of the real-time PCR in veterinary practice

2020 ◽  
Vol 2020 (2) ◽  
pp. 5-12
Author(s):  
Maksim Doronin ◽  
Dmitriy Lozovoy ◽  
Aleksey Scherbakov ◽  
Vladimir Makarov
Keyword(s):  
Infectious Diseases ◽  
Real Time ◽  
Quantitative Pcr ◽  
Biological Material ◽  
Molecular Genetic ◽  
The Body ◽  
Suspected Infection ◽  
Virus Content ◽  
Wide Range ◽  
Pathogenic Agents

To date the molecular genetic methods of analysis are widely used for laboratory diagnostic tests in various infectious diseases of animals. This discourse reflects information about the history of the invention of real-time polymerase chain reaction (PCR-RV), the nature of the processes that occur during this reaction, the main stages of the reaction, the preparation of biological material for research in PCR-RV. The spectrum of possibilities of using the PCR-RV method for a qualitative study of biological material in cases of suspected infection of animals with certain viral and bacterial agents, as well as a quantitative assessment of the virus content in tissues, organs or in the body by analogy with conventional methods for titrating infectiousness without direct manipulation with pathogenic agents, is presented. . A quantitative PCR-RV option allows veterinarians to evaluate the pathogenetic dynamics of the development of the disease, monitor the effect of antiviral and antibacterial therapy, and monitor the emergence of pathogen variants with high resistance to the drugs used. Thanks to the development of ARRIAH, the qualitative and quantitative PCR-RV method can now be used in domestic veterinary science and laboratory practice for the diagnosis of a wide range of animal infectious diseases.

scholarly journals CSNK2 in cancer: pathophysiology and translational applications

2021 ◽  
Author(s):  
Scott W. Strum ◽  
Laszlo Gyenis ◽  
David W. Litchfield
Keyword(s):  
Human Cancer ◽  
Cell Cycle Control ◽  
Prognostic Significance ◽  
Hematologic Malignancies ◽  
Protein Levels ◽  
Wide Range ◽  
Positive Treatment ◽  
Extensive Body

AbstractProtein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of biological and clinically oriented data from this unique kinase in cancer, this systematic review summarises existing knowledge from in vitro, in vivo and pre-clinical studies on CSNK2 across 24 different human cancer types. CSNK2 mRNA transcripts, protein levels and activity were found to be routinely upregulated in cancer, and commonly identified phosphotargets included AKT, STAT3, RELA, PTEN and TP53. Phenotypically, it frequently influenced evasion of apoptosis, enhancement of proliferation, cell invasion/metastasis and cell cycle control. Clinically, it held prognostic significance across 14 different cancers, and its inhibition in xenograft experiments resulted in a positive treatment response in 12. In conjunction with commentary on preliminary studies of CSNK2 inhibitors in humans, this review harmonises an extensive body of CSNK2 data in cancer and reinforces its emergence as an attractive target for cancer therapy. Continuing to investigate CSNK2 will be crucial to advancing our understanding of CSNK2 biology, and offers the promise of important new discoveries scientifically and clinically.

scholarly journals The issue of nosocomial infection caused by Klebsiella pneumoniae blaNDM-type

2020 ◽  
Vol 15 (2) ◽  
pp. 124-133
Author(s):  
Olga Mironenko ◽  
◽  
Victoria Selnitseva ◽  
Lidia Soprun ◽  
Elena Shmushkevich ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Nosocomial Infection ◽  
Molecular Genetic ◽  
Mechanisms Of Resistance ◽  
Infectious Process ◽  
Saint Petersburg ◽  
Microbiological Study ◽  
Wide Range ◽  
Almost All ◽  
Emergence Of Resistance

The article presents information about circulating isolates Klebsiella pneumoniae in a hospital megapolis with properties of hypervirulence and simultaneous multiresistance. The resulting K. pneumonia isolates are of particular importance due to the emergence of resistance to almost all β-lactams due to the presence of carbapenemase metal-β-lactamase. Furthermore, the isolated strains producing carbapenemases possess mechanisms of resistance to a wide range of antimicrobial preparations, and the types of infectious process caused by carbapenemazo-producing enterobacteries are characterized by a high lethality level. Microbiological, biochemical, biophysical, molecular-genetic, biological, bioinformational and statistical methods of research were used in the work. A prospective method was used to identify the source of the infections. In the first stage, a microbiological study was carried out on biomaterials obtained from patients treated in a hospital in Saint Petersburg. After a microbiological study, 52 isolates of K. pneumoniae were obtained, 53.8 % of isolates had a hypermucoid phenotype and 98 % had carbapenemases:blaNDM type — 49 (92 %), blaNDM+OXA-48-like — 3 (8 %). Isolates with two new phenotypes have been isolated (no. 2511 and no. 2512). Isolates of no. 2512 LD50 had 10*2 BAC/ml, and plasmids such as Incfib(Mar), Inchi1b, and Incr were also found, with Incr-A plasmid emitted encoding resistance to fluoroquinolone: aac(6’)-Ib-cr and to β-lactam antibiotics: blaTEM-1B. The described data confirm the opinions of the researchers about the possible formation of a new “super pathogen” — instantaneously hypervirulent and plural resistant strain of K. pneumoniae.

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