scholarly journals Microsatellite instability (MSI, EMAST) in the pathogenesis of follicular lymphoma

2021 ◽  
Vol 16 (2) ◽  
pp. 56-69
Author(s):  
K. A. Sychevskaya ◽  
S. K. Kravchenko ◽  
N. V. Risinskaya ◽  
А. Е. Misyurina ◽  
E. E. Nikulina ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Microsatellite Instability ◽  
Genetic Instability ◽  
Prognostic Value ◽  
Checkpoint Inhibitors ◽  
Microsatellite Repeats ◽  
Nucleotide Mismatch ◽  
Dna Microsatellite

Background. Genetic instability, an important phenomenon involved in oncogenic transformation and tumor progression, is associated with the insufficiency of the multicomponent DNA repair complex, in particular, the nucleotide mismatch repair (MMR) system. The MMR defect manifests itself as abnormalities in DNA microsatellite repeats, or microsatellite instability (MSI). In the studies of colorectal cancer, the role of MSI in prognostication of the disease, and defining the choice of specific therapy with immune checkpoint inhibitors has been proven.However, in lymphatic system tumors, the significance of this phenomenon is poorly understood. Determination of genetic instability in the onset of follicular lymphoma, a disease characterized by a heterogeneous course, may have prognostic value.Objective: to determine the genetic instability at the onset of follicular lymphoma.Materials and methods. Here we report an analysis of 24 microsatellite repeats and amelogenin loci in tumor cells of 46 follicular lymphoma patients.Results. In the studied cohort, lesions in microsatellite repeats were presented by MSI in 9 cases (19.6 %) and the loss of heterozygosity (LOH) in 19 cases (41.3 %). Most frequent lesions were found for the SE33 marker located at the q14 locus of chromosome 6. A significant association was shown between MSI and the double-hit follicular lymphoma group with rearrangements of the MYC and BCL2/BCL6 genes.Conclusion. Thus, our data indicate that the MSI phenomenon might be involved in the pathogenesis of the lymphatic tumors and particularly follicular lymphoma. However further studies on the expanded cohorts of patients are required to define the possible prognostic value of MSI in lymphatic tumors.

scholarly journals The Mismatch Repair System (MMR) in Head and Neck Carcinogenesis and Its Role in Modulating the Response to Immunotherapy: A Critical Review

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3006
Author(s):  
Maria Cilona ◽  
Luca Giovanni Locatello ◽  
Luca Novelli ◽  
Oreste Gallo
Keyword(s):  
Microsatellite Instability ◽  
Head And Neck ◽  
Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Precancerous Lesions ◽  
Second Primary ◽  
Repair System ◽  
Primary Tumors ◽  
Wide Range

The mismatch repair (MMR) system has a major role in the detection and correction of DNA replication errors, resulting from DNA polymerase slippage or nucleotides misincorporation. Specific inherited/acquired alterations or epigenetic inactivation of MMR genes are associated with microsatellite instability (MSI): the loss of crucial function in repairing DNA alterations can promote carcinogenesis by favoring the accumulation of thousands of mutations in a broad spectrum of different anatomic sites such as colon, stomach, prostate, esophagus, endometrium, lung and head and neck. Recent extensive data suggest that tumor mutational burden strongly correlates with a clinical response to immunotherapy using checkpoint inhibitors and this response is influenced by MMR deficiency in a wide range of human solid cancers. In this context, few data about this crucial point are available for head and neck cancer (HNC). In this review, we discuss the role of MMR alterations and the resulting MSI in HNC pathogenesis. Furthermore, by summarizing the clinical available data on how they influence the progression of precancerous lesions and the risk of recurrence or second primary tumors, we want to define the current role of MSI in the management of HNC. Finally, we analyze the complex interaction between cancer cells and the immune system addressing the data now available about a potential correlation between microsatellite instability and immunotherapy response in HNC.

scholarly journals Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II—The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer

2017 ◽  
Vol 142 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Esmeralda Celia Marginean ◽  
Barbara Melosky
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Microsatellite Instability ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Context.— The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti–programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability–high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability–high CRC. Objectives.— To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.— A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.— Exciting success with anti–PD-1/PD-L1 and anticytotoxic T-lymphocyte–associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability–high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti–PD-1 or anti–PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability–high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

1981 ◽  
Author(s):  
M Yamamoto ◽  
K Watanabe ◽  
Y Ando ◽  
H Iri ◽  
N Fujiyama ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Marked Enhancement ◽  
Matrix Bound ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

ІНТЕРПРЕТАЦІЯ КАТЕГОРІЇ РОЗВИТКУ В СУЧАСНІЙ ПСИХОЛОГІЇ

1970 ◽  
Vol 8 (1) ◽  
pp. 22-30
Author(s):  
Анжеліка Шамне
Keyword(s):  
Cultural Context ◽  
Developmental Psychology ◽  
Structure And Dynamics ◽  
Modern Psychology ◽  
Development Site ◽  
Approaches To Study ◽  
Methodological Approaches ◽  
Self Motion

У статті розглянуто сучасні підходи до інтерпретації категорії розвитку, розкрито теоретичні  та методологічні підходи до вивчення категорії розвитку у сучасній психології, визначено її психологічний  зміст,   моделі,   структуру   та   динаміку.   Категорія   розвитку   розглядається   як   епіцентр   наукової  проблематики у психології та як поняття інтегративного типу. Розвиток проаналізовано як категорію,  явище і проблему психології розвитку в різних аспектах аналізу. Розглянуто місце розвитку в системі  споріднених психологічних понять. У статті також аналізуються психологічні аспекти теоретичних та  методологічних  постнекласичних  тенденцій  вивчення  природи,  характеру  та  визначення  психічного  розвитку. Постнекласична парадигма та плюралістична методологія пізнання визначають розмитість  дисциплінарної мови  та  врахування  ролі  соціокультурного  контексту  при  вивченні  психологічних явищ.  Важливими тенденціями сучасного теоретико-методологічного стану психологічних досліджень розвитку  також є визнання неефективності моністичного підходу до його вивчення, взаємозв'язок теоретичних ідей  та   спроби   створення   метатеоретичних   схем,   постнекласичне   розуміння   розвитку   як   принципово  незавершеного   процесу   саморуху,   актуалізація   антропологічного   діапазону   проблем   та   посилення  спрямованості на роль культурного контексту в дослідженні розвитку людини.  The article deals with the modern approaches to the interpretation of the category of development, reveals  the theoretical and methodological approaches to study of development in modern psychology, its psychological  content, patterns, structure and dynamics. Category of development is viewed as an epicenter of scientific issues in  modern  psychology  and  the  concept  of  the  integrative  type.  Category  of  development  is  considered  as  the  phenomenon  and  the  problem  of  developmental  psychology  in  various  aspects  of  the  analysis.  Analyzed  the  development site in the related psychological concepts. The article analyzes the psychological aspects of theoretical  and methodological postnonclassical contemporary trends in the study of nature, character, and determination of  mental  development.  Postnonclassical  paradigm  and  pluralistic  methodology  of  knowledge  determine  the  disciplinary blurring and increase of the role of the analysis of socio-cultural context in the study of psychological  phenomenon. The important tendencies of modern theoretical and methodological state of psychological researches  of development are facts of inefficiency of the monistic approach to its study, interconnection of theoretical ideas  and   attempts   of  creating   metatheoretical   schemes,   postnonclassical   understanding   of   development   as   a  fundamentally  uncompleted  process  of  self-motion,  actualization  of  anthropological  range  of  problems  and  strengthening of focus on the role of cultural context in research of human development.   

Role of the family focused technologies in the clinical course of pregnancy at women of high obstetric risk

2016 ◽  
pp. 64-66
Author(s):  
S.Yu. Vdovichenko ◽  
Keyword(s):  
Comparison Group ◽  
Traditional Approach ◽  
Married Couple ◽  
Premature Births ◽  
Individual Support ◽  
The Family ◽  
Risk Patients ◽  
Individual Preparation

The objective: to show a role of the family focused technologies in depression of frequency of pathology of pregnancy at women of high obstetric risk. Patients and methods. For determination of efficiency of prophylaxis of pathology of pregnancy on the basis of use of the family focused technologies complex clinical-psychological and laboratory and tool examination of 300 women with factors of obstetric risk which were divided into two groups was conducted. In the main group – 182 women with motivation on partner labors to which provided training on system of individual preparation of married couple to labors. The comparison group consisted of 118 women who were not in prenatal training and had individual support in childbirth, with the traditional approach to pain management. Results. Use of the family focused technologies during pregnancy allows to reduce significantly the frequency of the main complications of pregnancy, especially not incubation and premature births. Conclusion. In our opinion, the technique is simple, available and can widely be used in practical health care at women with high obstetric risk. Key words: obstetric risk, the family focused technologies, prophylaxis.

PERANAN INSPEKTORAT KABUPATENSUMENEP DALAM MENCEGAH DAN MENDETEKSI FRAUD DI DINAS PENDIDIKAN SUMENEP

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Astri Furqani ◽  
Hafidhah .
Keyword(s):  
Local Government ◽  
Qualitative Study ◽  
Asset Management ◽  
Sampling Technique ◽  
Research Data ◽  
Qualitative Approach ◽  
Primary Data ◽  
The Government

In this era, a lot of activities that can not be separated from the practice of cheating or fraud , no exception In the government . Inspektorat Sumenep is the leading institution of internal Local Government in preventing and detecting fraud in the Local Government appropiate Perbup Sumenep No. 29 of 2008 . Dinas Pendidikan Sumenep need attention on the issue . This is due to Dinas Pendidikan Sumenep an agency with the largest number of assets and managing large budgets . These conditions led to the formulation of the problem is How Inspektorat Sumenep role in preventing and detecting fraud in Dinas Pendidikan Sumenep. This study used a qualitative approach in which the focus of this study is Inspektorat role in preventing and detecting fraud at Dinas Pendidikan Sumenep . Primary data obtained by direct interviews with the parties directly related to the determination of the source of research data in a qualitative study using nonprobability sampling . The sampling technique used was purposive sampling . The conclusion of this study, role of the Inspektorat Sumenep in the prevention of fraud in Dinas Pendidikan Sumenep still not maximal . This is due to Inspektorat Sumenep not supervise from the planning / budgeting and not optimal in overseeing and assisting the implementation of the SPIP as an instrument of fraud prevention in Dinas Pendidikan Sumenep . The role of Inspektorat Sumenep in the detection of fraud in Dinas Pendidikan Sumenep done by conducting an audit of financial and asset management in each financial year.Keywords: fraud, government, inspektorat.

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