RESUMEN
Nowadays, anthropogenic inflow of heavy metals (HM) into the environment far exceeds their natural quantities in Ukraine. The main sources of HM inflow are enterprises that use high-temperature processes in the production cycle-combustion of fuel and thermal processing of raw materials. Examples of such enterprises are Avdiivka Coke and Chemical Plant (the largest in Europe) and the Zmiiv Thermal Power Plant (the largest in Ukraine), which use high-temperature processes associated with the use of black coal that are considered as important sources of heavy metals in the soil. On the basis of analytical data of 3000 samples of surface layer of Ukrainian soils, which form the basis of the nationwide GIS "Microelements in soils of Ukraine," it was established that the spatial distribution of the content of accessible forms of copper in the upper soil layer in Ukraine varies greatly and practically does not depend on the type of soil formation and is determined mainly by geochemical factors such as saturation of parent rocks with copper, as well as anthropogenic influence. The emissions from the Avdiivka Coke and Chemical Plant resulted in the formation of a clearly defined contamination range of soil and vegetation by HM in the adjoining territories exceeding the threshold levels of copper. In the zone of influence of the Zmiiv Thermal Power Plant, the technogenic load on agricultural lands is much less and does not exceed the medical and sanitary indicators of the content of heavy metals in the soils, but due to the high pipe height (180-250 m), the toxic emissions of the enterprise dissipate to a large area and form a regional technogenic background of available copper in soils.
Asunto(s)
Cobre/análisis , Productos Agrícolas/química , Metales Pesados/análisis , Contaminantes del Suelo/análisis , Suelo/química , Agricultura , Cobre/química , Monitoreo del Ambiente/métodos , Metales Pesados/química , Centrales Eléctricas , UcraniaRESUMEN
The Epstein-Barr virus (EBV) plays a key role in the development of undifferentiated nasopharyngeal carcinoma (uNPC). In uNPC endemic regions EBV-specific antibodies and plasma EBV DNA load are used as markers for the early detection of uNPC and monitoring of the disease. In non-endemic regions, such studies were practically not conducted. The aim of this study was to compare the clinical significance of EBV serological markers and plasma EBV DNA levels for uNPC patients in a non-endemic region, Russia. The results obtained indicate that both viral capsid antigen/immunoglobulin A (VCA/IgA) antibodies and plasma EBV DNA copies can effectively be used for nasopharyngeal carcinoma (NPC) diagnosis. Besides, plasma EBV DNA load was found to be a more sensitive marker of uNPC than VCA/IgA antibody titres, as it reflected the effect of the therapy in stages of remission and relapse of the disease more precisely. Our study, for the first time, demonstrates that the simultaneous use of plasma EBV DNA loads and VCA/IgA antibody levels are indispensable markers for uNPC in non-endemic regions: a serological marker can be more effectively used for NPC screening, but EBV DNA copies are better for monitoring the disease. However, both markers turned out to be practically unsuitable for assessing the clinical status of patients. Serological markers did not correlate with any signs of the tumour process estimated by tumour, node and metastasis (TNM) classification and the plasma EBV DNA loads correlated only with the size of the pathologically altered lymph nodes (N). Additional study is required to confirm these findings.
Asunto(s)
Carcinoma/virología , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Nasofaríngeas/virología , Adulto , Anticuerpos Antivirales/sangre , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Carcinoma/sangre , ADN Viral/genética , ADN Viral/metabolismo , Infecciones por Virus de Epstein-Barr/sangre , Femenino , Herpesvirus Humano 4/clasificación , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangre , Federación de RusiaRESUMEN
Epstein-Barr virus (EBV) - the etiological agent of a number of human benign and malignant tumors including infectious mononucleosis (IM), Burkitt lymphoma (BL), Hodgkin (HL) and non-Hodgkin (NLH) lymphomas, nasopharyngeal carcinoma (NPC), and many other tumors. Latent membrane protein 1 (LMPl) encoded by the gene of the same name (LMP I) is the main oncoprotein of EBV. LMP1 is a transmembrane protein capable of activating many signaling pathways and transcription factors of the cells, which leads to its transformation. Molecular analysis of LMP1 of various clinical origins identified many variants with different types of amino acid mutations that influence its biological activity. Since the role of LMPl in the development of NPC is still not fully understood, it is important to find out how LMPl samples from patients with EBV-associated form of NPC differ from those of patients with other tumors also located in the oral cavity (OTOC), but not associated with this virus. Unlike most investigations conducted in endemic regions, the present work is intended to compare the genetic structure and the transforming activity of LMPl variants from NPC and OTOC patients has been carried out in a non-endemic region of Russia, where NPC is rarely diagnosed. The obtained data show structural and functional similarities of LMP1 variants in the two groups of patients and, accordingly, a genetic relationship of EBV strains persisting in these patients. Our work suggests that in non-endemic regions any EBV strain with any structure of LMP1 may become the etiologic agent of NPC. However, based on modem concepts, the cancer can occur only if EBV-infected persons have a unique pattern of HLA associated with a high sensitivity to the development of NPC combined with exposure to harmful environmental factors (chemical or physical carcinogens) and lifestyle.
Asunto(s)
Infecciones por Virus de Epstein-Barr/genética , Variación Genética , Herpesvirus Humano 4/genética , Neoplasias/genética , Proteínas Oncogénicas/genética , Proteínas de la Matriz Viral/genética , Infecciones por Virus de Epstein-Barr/metabolismo , Infecciones por Virus de Epstein-Barr/patología , Femenino , Herpesvirus Humano 4/metabolismo , Humanos , Masculino , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/virología , Proteínas Oncogénicas/metabolismo , Proteínas de la Matriz Viral/metabolismoRESUMEN
Recent studies indicate that the latent membrane protein 1 (LMP1) encoded by the same name gene of the Epstein-Barr virus (EBV) plays an extremely important role in the pathogenesis of a number of malignant neoplasia. Specifically, LMP1 has the ability to transform human B-lymphocytes in vivo and in vitro and rodent fibroblasts (Rat-1) in vitro. The introduction of the latter into athymic mice leads to tumor development. In addition, expression of the oncoprotein has been often found in EBV-associated tumors at the DNA and constantly at the RNA levels. Having pleiotropic effects, LMP1, participates in the transmission and activation of multiple intracellular signals. It is also involved in the inhibition of key tumor suppressors, has significant influence on proliferation, apoptosis and morphological alteration of the infected cells finally resulting in their transformation. General characteristics of EBV and LMP1 gene as well as functional activity of the encoded LMP1 protein and a brief description of human pathologies associated with the virus have been discussed in this review. The questions concerning the polymorphism LMP1 in EBV-associated pathologies have been also analyzed in details.
Asunto(s)
Linfoma de Burkitt/virología , Infecciones por Virus de Epstein-Barr/virología , Regulación Viral de la Expresión Génica , Herpesvirus Humano 4/genética , Polimorfismo Genético , Proteínas de la Matriz Viral/genética , Animales , Linfocitos B/inmunología , Linfocitos B/patología , Linfocitos B/virología , Linfoma de Burkitt/genética , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/patología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/patogenicidad , Interacciones Huésped-Patógeno , Humanos , Ratones , Ratones Desnudos , Ratas , Transducción de Señal , Proteínas de la Matriz Viral/química , Proteínas de la Matriz Viral/inmunología , Latencia del VirusRESUMEN
The Epstein-Barr virus, widespread herpesvirus among the population of the planet, is also the etiologic agent for a number of malignancies. One of the oncoproteins encoded by the virus, the latent membrane protein 1 (LMP1I), through activation of the complex signaling pathways is involved in the processes of cell immortalization and transformation. The goal of this work was to study the level of the EBV infection in Russian population and LMP1 polymorphism in patients with benign and malignant EBV-associated diseases and healthy virus carriers. Studies have shown that by the age of 5-9 years the percentage of the infected persons and the level of antibody titers reaches almost the maximum values. With the age, virus specific antibody titers are decreased (with a high percentage of infected persons) and increased again in groups of older persons. The analysis of the nucleotide sequences of the gene LMP1 translated in amino acid (aa) sequences unexpectedly revealed the dominance a low divergent variant LMP1 B95.8A not only in healthy individuals but also in patients with all forms of EBV-associated diseases. Highly divergent variants Ch1 and Med +, containing a deletion of 10 aa, and characterized by elevated transforming activity more often were detected in the tumor tissue samples than in the blood samples/mouth washes of the same patients. Detection of highly transforming variant LMP1 Ch1 in blood samples of healthy individuals indicates that this analog of Chinese variant Cao may persist in any population and is not necessarily associated with the occurrence of the EBV-associated disorders.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Virus de Epstein-Barr , Variación Genética , Herpesvirus Humano 4/genética , Proteínas de la Matriz Viral/genética , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/genética , Femenino , Humanos , Masculino , Federación de Rusia , Proteínas de la Matriz Viral/sangreRESUMEN
The role of the Epstein-Barr virus (EBV), a ubiquitous lymphotropic human herpesvirus type 4, in the etiology of nasopharyngeal carcinoma (NPC) is not fully understood. The mechanism of NPC carcinogenesis, associated with the virus, is also not clear. The objective of present investigation was to carry out comparative analysis of the structure of an LMP1 oncogene of EBV in viral isolates obtained from patients with two types of tumors of the oral cavity: (a) associated (i.e., NPC) and (b) not associated (other tumors of the same anatomical region, OTOC) with EBV. Comparative analysis of C-terminal regions of LMP1 variants that was based on a sequence analysis of LMP1 from tumor, blood and throat washing samples of NPC and OTOC patients showed that all structural characteristics of LMP1 in both groups of patients were genetically similar, and differences found between compared parameters were statistically insignificant. Thus, for the first time it has been revealed that in NPC and OTOC patients in Russia genetically related EBV strains with structurally similar LMP1 variants are persisting that are likely to reflect a polymorphism of the virus circulating in population. The findings allow us to suggest that in non-NPC-endemic regions of the world, which include Russia, the risk of NPC development does not depend on the EBVstrain and its variant of LMP1 so much, but mostly from the genetic predisposition of infected persons to the disease and the exposure to other, as yet unknown agents.
Asunto(s)
Herpesvirus Humano 4/genética , Neoplasias de la Boca/genética , Neoplasias Nasofaríngeas/genética , Proteínas de la Matriz Viral/genética , Adulto , Carcinoma , Femenino , Variación Genética , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/patogenicidad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Persona de Mediana Edad , Neoplasias de la Boca/patología , Neoplasias de la Boca/virología , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Federación de RusiaRESUMEN
INTRODUCTION: The discovery of two types of Epstein-Barr virus (EBV) (EBV-1 and EBV-2) that have different biological properties stimulated the search for neoplasms associated with each type of the virus. The aim of the work is to study the nature of the association of nasopharyngeal cancer (NPC) with EBV-1 and EBV-2, serological activity for each viral type and the concentration of EBV DNA in the blood plasma of two gender, age and ethnic groups of NPC patients that represent geographically and climatically different regions of Russia,. MATERIALS AND METHODS: In the blood plasma of patients with NPC and other non- EBV associated tumors of oral cavity (OTOCEBV-) from the North Caucasian (NCFD) and Central (CFD) Federal Districts of Russia, the types of EBV and the concentration of viral DNA were determined using respectively «nested¼ and real time PCR; titers of IgG and IgA antibodies to viral capsid antigen (VCA) were measured in indirect immunofluorescence assay. RESULTS: The blood plasma samples testing showed that NPC and OTOCEBV- patients were infected with both types of EBV in approximately equal proportions. In two groups of NPC patients infected with one of the virus types only, EBV-1 or EBV-2, respectively, no statistically significant differences were found between the geometric mean values of IgG and IgA anti-EBV antibody titers and viral DNA concentrations in blood plasma. The distribution of virus types was not affected by either patient gender or ethnogeographic origin. The difference was found only between age groups: EBV-2 dominated in NPC patients up to 60 years, and EBV-1 was prevalent in patients over 60 years. CONCLUSION: The lack of the predominance of one of EBV types in NPC patients that are the representatives of different ethnic groups from geographically and climatically different regions, suggests that none of these factors play an important role in the NPC carcinogenesis. Evidently, each type of EBV, EBV-1 or EBV-2, if the necessary conditions arise, are able to exhibit its oncogenic potential to initiate tumor development.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Lymphocryptovirus , Neoplasias Nasofaríngeas , Humanos , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/epidemiología , Lymphocryptovirus/genética , ADN Viral/genética , Biomarcadores , Antígenos Virales/genética , Anticuerpos Antivirales , Inmunoglobulina A , Inmunoglobulina GRESUMEN
One of the latent proteins encoded by the Epstein-Barr virus (EBV), the latent membrane protein 1 (LMP1), plays a key role in developing of EBV-associated human malignancies. Polymorphism of LMP1 protein is its characteristic feature. Some specific mutations in LMP1 genome have previously been detected in different geographic regions, however, the influence of these mutations on functional activity of LMP1 was not still determined. In this study we demonstrated for the first time the significance of individual point mutations among common ones observed in LMP1 and their combination on activation of the inducible form of nitric oxide synthase (iNOS). In addition, the influence of above mutations localized in the CTAR regions of the LMP1 molecule has also been investigated on structural components of the fibroblasts of the Rat1cell line.
Asunto(s)
Citoesqueleto/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Proteínas de la Matriz Viral/genética , Animales , Línea Celular , Activación Enzimática , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Mutación Puntual , Ratas , Transfección , Proteínas de la Matriz Viral/metabolismoRESUMEN
The review analyzes recent data and current ideas on the enzyme cyclooxygenase 2 (COX-2) as a possible biomarker of virus-associated human malignant neoplasm. Possible mechanisms of COX-2 activation in the cells infected with oncogenic human viruses, such as hepatitis B virus, Epstein-Barr virus, and human papillomavirus are considered in detail.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Ciclooxigenasa 2/metabolismo , Infecciones Tumorales por Virus/diagnóstico , Diagnóstico Precoz , Virus de la Hepatitis B/metabolismo , Herpesvirus Humano 4/metabolismo , Humanos , Papillomaviridae/metabolismo , Infecciones Tumorales por Virus/enzimología , Infecciones Tumorales por Virus/virologíaRESUMEN
INTRODUCTION: The discovery of the Epstein-Barr virus types (Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4) (EBV) - EBV-1 and EBV-2, which have different transforming abilities in vitro, stimulated the study of their prevalence in populations in order to elucidate the relationship with malignant neoplasms.The aims of the work are to study the prevalence of EBV-1 and EBV-2 among representatives of 2 ethnic groups of Russia, Kalmyks and Slavs, sequencing analysis of the LMP1 oncogene in virus isolates, and analysis of the correlation between virus types and the incidence of certain forms of tumors. MATERIALS AND METHODS: DNA samples were isolated from the biological material of oral swabs obtained from ethnic Kalmyks of the Republic of Kalmykia (RK) (n = 50) and Slavs, residents of the Moscow Region (MR) (n = 40). DNA samples were used to amplify EBV DNA, followed by determination of its concentration per 1 cell of washout, amplification of the LMP1 oncogene in viral samples, their sequencing, and determination of LMP1 protein variants. RESULTS: It has been established that with the same burden of EBV among representatives of both ethnic groups in the Kalmyk group, the ratio of persons infected with transforming and non-transforming types of the virus was almost the same (EBV-1 - 51%; and EBV-2 - 49%). Meanwhile, in the group of Slavs the transforming EBV-1 type virus dominated (80.6%). The predominance of EBV-1 type in representatives of the Slavs correlated with increased incidence of certain forms of tumors in the population of the MR when compared with similar values in the population of the RK, where both types of the virus were prevalent. Differences between the compared rates of cancer incidence were not statistically significant. Analysis of viral isolates showed a similar set of LMP1 variants in both ethnic groups. CONCLUSION: In order to establish the influence of EBV types on the incidence of malignant tumors, additional studies involving representatives of various ethnic groups from different geographical regions are needed.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Gammaherpesvirinae , Lymphocryptovirus , Neoplasias , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/patología , Gammaherpesvirinae/genética , Herpesvirus Humano 4/metabolismo , Humanos , Lymphocryptovirus/genética , Oncogenes , Federación de Rusia/epidemiología , Proteínas de la Matriz Viral/genéticaRESUMEN
Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal pro- cessing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on be- yond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.
RESUMEN
The investigation was undertaken to study the molecular characteristics of Epstein-Barr virus (EBV) LMP1 gene samples amplified from the tumor and intact tissues of patients with EBV-negative forms of gastric carcinoma (GC). The genetic structure of these samples determined by their sequencing was compared with that of the gene samples isolated from the cells of oropharyngeal washing specimens from the same patients with GC, as well as peripheral blood lymphocytes of patients with infectious mononucleosis (IM) and blood donors. The findings suggest that the samples of tumor tissue LMP1 from patients with GC have higher divergence than those from patients with IM and blood donors although no specific variants of the gene for GC were found. Comparison of LMP1 sequences from tumor tissue and cells of oropharyngeal washing specimens from the same patients with EBV-negative GC revealed the common LMP1 variant in 2 cases while they differed in 3 cases. The findings are an initial step in studying the role of EBV in the carcinogenesis of EBV-negative GC that is likely to be established by investigations on representative clinical material, by applying the up-to-date technologies.
Asunto(s)
Carcinoma/virología , Herpesvirus Humano 4/genética , Neoplasias Gástricas/virología , Proteínas de la Matriz Viral/genética , Adulto , Anciano , Carcinoma/química , Femenino , Técnica del Anticuerpo Fluorescente , Genes Virales/genética , Herpesvirus Humano 4/química , Humanos , Masculino , Persona de Mediana Edad , Faringe/virología , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Estómago/virología , Neoplasias Gástricas/química , Proteínas de la Matriz Viral/metabolismoRESUMEN
INTRODUCTION: Molecular studies have shown that viruses appeared in the early stages of the evolution of life. For millions of years, viruses have evolved by changing old and acquiring new sequences in their RNA or DNA. It is assumed that most viruses have common ancestors. Such an ancestor, an ancient strain, probably existed for Epstein-Barr virus (EBV) as well. AIM: To find out whether ancient strains of EBV persist in modern Russian ethnic groups today. MATERIAL AND METHODS: The object of the study was the EBV LMP1oncogene, which is most suitable for molecular genetic analysis. LMP1 was amplified from the oral cavity washings obtained from representatives of two ancient ethnic groups of Russia - Tatars and Slavs. The LMP1 amplicons were sequenced in both directions; their nucleotide sequences translated into amino acid (LMP1) were evaluated using the classification suggested by Edwards et al. 1999. To establish genetic relationships between LMP1 variants, a phylogenetic tree was constructed by the neighbor-joining method using the MEGA software package. RESULTS AND DISCUSSION: Analysis of LMP1 sequences from washings of the Slavs oral cavity demonstrated the presence of LMP1 variants with varying degrees of transforming potential: B98.5/A, China1, Med-, and NC. The analysis of LMP1 sequences from washings of Tatar oral cavity also made it possible to identify oncoprotein variants such as B95.8/A, China1, Med-, as well as a group of variants out of classifications (LMP1-OK). An important finding was the identification of 7 variants of LMP1 from Tatars, designated as LMP1-TatK, that contained two unique deletions of 5 aa in codons 312-316 and 382-386, which were absent in the LMP1 variants from Slavs and from previously examined cancer patients and healthy individuals, as well as in sequences from open computer databases. The uniqueness of the LMP1-TatK variant is confirmed both by phylogenetic analysis of LMP1 sequences of Tatar origin and by the analysis of 11 aa repeats and 5 aa insertions in the C-terminal region of the oncoprotein. The morbidity and mortality rates from neoplasms, including EBV-associated pathologies, did not differ significantly between two studied ethnic groups infected with different EBV strains. CONCLUSION: The data obtained allowed us to suggest that: 1) LMP1-TatK could be refered to an evolutionarily ancient EBV strain that persists among Tatars and; 2) LMP1-TatK belongs to the so-called "Volga" EBV virus strain, the common strain among the population of the Volga region. Extended studies of EBV isolates from residents of this region may probably shed the light on the origin of LMP1-TatK.
Asunto(s)
Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/genética , Filogenia , Proteínas de la Matriz Viral/genética , Secuencia de Aminoácidos/genética , Infecciones por Virus de Epstein-Barr/genética , Etnicidad/genética , Femenino , Variación Genética/genética , Herpesvirus Humano 4/patogenicidad , Humanos , Masculino , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/virología , Federación de Rusia/epidemiologíaRESUMEN
INTRODUCTION: The reasons of late diagnosis of nasopharyngeal carcinoma (NPC) are the long asymptomatic course of the pathological process, the anatomical structure of the nasopharynx, often small, visually and endoscopically undetectable tumor and other factors. It is proved that the Epstein-Barr virus (EBV) is an etiological agent in the most common undifferentiated non-keratinizing histological type of NPC (uNPC). OBJECTIVES: The aim of the work was to assess the significance of diagnostic markers of EBV (titers of humoral antibodies to the virus and the concentration of viral DNA in plasma) for the diagnosis of uNPC in a group of patients with metastatic lesions of the cervical lymph nodes without an identified localization of the primary tumor focus. MATERIAL AND METHODS: The material for the study was blood plasma of 83 patients with metastatic lesions of the cervical lymph nodes and not established localization of the primary tumor. Plasma samples were tested for the anti-EBV IgG and IgA antibody content and titers and the concentration of viral DNA. RESULTS AND DISCUSSION: The data obtained indicate that the parallel testing of blood plasma for EBV-specific antibodies and viral load is a useful tool for preliminary screening of uNPC patients. The final diagnosis is confirmed by the data of subsequent morphological and instrumental studies. Several examples also show that the concentration of viral DNA in the blood plasma of patients with uNPC reflects the effect of the therapy and the prognosis of the disease: remission, stabilization of the tumor process, relapse or metastasis. CONCLUSION: Although the titers of virus-specific antibodies are found to reflect clinical manifestations of the disease less accurately than the plasma concentrations of viral DNA, serological markers are extremely important for the preliminary diagnostics of uNPC in cases of undetected primary tumor location. They are also useful for primary screening of this neoplasm among individuals at risk.
Asunto(s)
Anticuerpos Antivirales/sangre , Biomarcadores de Tumor/sangre , ADN Viral/sangre , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/patogenicidad , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Estudios de Casos y Controles , Convalecencia , ADN Viral/genética , ADN Viral/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/virología , Femenino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Ganglios Linfáticos/virología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/virología , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Nasofaringe/inmunología , Nasofaringe/patología , Nasofaringe/virología , Recurrencia , Carga Viral/genética , Carga Viral/inmunologíaRESUMEN
Latent membrane protein 1 (LMP1) of the Epstein-Barr virus is a constitutively activated analog of the tumor necrosis factor receptor TNF-R1. LMP1 serves as a viral oncogene able to transform human B-lymphocytes and rodent fibroblasts via activation of numerous cellular signal cascades. Two specific motifs within LMP1 are responsible for interaction of this viral protein with the receptor protein beta-TrCP/HOS SCF of the ubiquitin ligase E3 complex, playing an important role in degradation of numerous cellular proteins including NF-kappaB inhibitor IkappaBalpha. In this study, we demonstrate for the first time the importance of point mutations affecting HOS-recognizing motifs of LMP1 for activation of NF-kappaB, AP1, and PI3K/Akt signaling pathways. It has also been shown that rat fibroblast cell lines (Rat-1) expressing different HOS mutants of LMP1 produce different amounts of reactive nitrogen species. Our data confirm the hypothesis that point mutations in the C-terminal region of the LMP1 cytoplasmic domain can influence the transforming potential of the Epstein-Barr virus.
Asunto(s)
Mutación , Transducción de Señal/genética , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/metabolismo , Secuencias de Aminoácidos , Animales , Línea Celular Transformada , Células Cultivadas , Fibroblastos/metabolismo , Humanos , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Proteínas con Repetición de beta-Transducina/genética , Proteínas con Repetición de beta-Transducina/metabolismoRESUMEN
Epstein-Barr virus (EBV) is an etiological agent of a number of benign and malignant human diseases, such as infectious mononucleosis (IM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). EBV latent membrane protein 1 (LMP1) gene (recognized as a viral oncoprotein) of various clinical and geographical origin was found to have different types of amino acid mutations affecting its biological activity. Since there was no information on the strain differences in LMP1 of EBV persisting in Russia, the authors made a sequence analysis of LMP1 samples amplified from the biological materials of Russian patients with IM, HL, and NHL and healthy individuals. The studies have shown that LMP1 variants of Russian origin are a mixed heterogeneous group containing both the earlier characterized and presumably new genetic variants. Among the point amino avid substitutions, the mutations S366T, F106Y, 185L, and E328Q associated with the enhanced transforming activity of a LMP1 molecule and its reduced cytotoxicity. There was no specific association between the certain Russian variants of LMP1 and the specific forms of the disease (IM, HL, and NHL).
Asunto(s)
Infecciones por Virus de Epstein-Barr/virología , Genes Virales , Herpesvirus Humano 4/genética , Proteínas de la Matriz Viral/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Portador Sano/virología , Variación Genética , Herpesvirus Humano 4/química , Herpesvirus Humano 4/patogenicidad , Enfermedad de Hodgkin/virología , Humanos , Mononucleosis Infecciosa/virología , Linfoma no Hodgkin/virología , Datos de Secuencia Molecular , Proteínas Oncogénicas Virales/genética , Mutación Puntual , Reacción en Cadena de la Polimerasa , Federación de Rusia , Alineación de Secuencia , VirulenciaRESUMEN
The etiological role of the Epstein-Barr virus (EBV) in the development of an undifferentiated histological variant of nasopharyngeal carcinoma (uNPC) found for the first time in regions with a high incidence of this pathology, the Southern provinces of China and the countries of Southeast Asia, and later in the rest of the world, has served as a basis for the widespread use of EBV serological markers for the diagnosis of this form of tumor. In recent years, the use of a test based on the quantitative determination of the EBV DNA concentration in the blood plasma of uNPC patients for early detection and monitoring of the disease has become widespread in endemic regions. In non-endemic regions, such studies virtually have not been carried out, and moreover, the comparative evaluation of the significance of two viral markers, serological and EBV DNA load in the bloodstream of uNPC patients, for diagnostics and evaluation of the therapeutic effect was not investigated. The aim of this study was to compare the clinical value of two serological markers and plasma EBV DNA load in uNPC patients from non-endemic region (Russia). The obtained results indicate that IgA antibodies to the viral capsid antigen (IgA/VCA) and plasma EBV DNA concentration can be successfully used for the diagnosis of uNPC, while IgG/VCA antibodies have no practical significance as an uNPC marker. In addition, it was found that plasma EBV DNA load is more sensitive marker of uNPC than IgA/VCA titers because DNA copy numbers reflect more accurately the effect of the therapy and the clinical state of patients at the stages of remission or relapse. It was shown for the first time that in the non-endemic region the simultaneous evaluation of IgA/VCA antibody levels and the plasma EBV DNA loads are the most effective markers for the diagnostics of uNPC. However, we believe, that it is more practical to use IgA/VCA antibody levels for uNPC screening, and plasma EBV DNA copies - for monitoring of the disease.
RESUMEN
Estrogen, progesterone and glucocorticoid receptors were determined in samples obtained by trepanobiopsy before treatment and in surgical material following chemo- or radiotherapy in 131 Stage III a, b, c breast cancer patients. The levels and distribution of the receptors in bioptates coincided with the data obtained earlier for the surgical material from patients, who didn't receive presurgical therapy. It is concluded that breast tumor trepanobioptates may be used for the determination of tumor receptor status. Radiotherapy affected the level and frequency of occurrence of steroid hormone receptors. The degree of variations depended on the dosage of irradiation and after exposure period. After presurgical chemotherapy the percent of receptor-positive tumors increased.
Asunto(s)
Neoplasias de la Mama/análisis , Receptores de Esteroides/análisis , Anciano , Antineoplásicos/uso terapéutico , Biopsia , Neoplasias de la Mama/terapia , Femenino , Humanos , Menopausia , Persona de Mediana Edad , Dosificación Radioterapéutica , Receptores de Estrógenos/análisis , Receptores de Glucocorticoides/análisis , Receptores de Progesterona/análisisRESUMEN
For the functional activity evaluation of glucocorticoid receptors (GR) a specific method for their activated form determination was developed on the experimental model of the rat liver. The method is based on the interaction of GR with DNA-cellulose. It has been shown that 26-41% of the total rat liver GR are able of undergoing activation and being bound to DNA-cellulose. Activated GR were studied in 88 renal tumours and in 37 melanomas. 20% of renal tumours and 33% of melanomas contain GR which are not able to undergo activation. The number of activated GR in most cases is much lower than the total GR number. There is no direct correlation between the concentrations of total and activated GR, as well as between the total GR content and the percent of activated forms in the whole receptor pool. It appears that the study of activated GR may give more reliable information about the hormone sensitivity of tumours than the determination of the total receptor content.
Asunto(s)
Neoplasias Renales/metabolismo , Melanoma/metabolismo , Receptores de Glucocorticoides/metabolismo , Neoplasias Cutáneas/metabolismo , Animales , Biotransformación/fisiología , Cromatografía en Capa Delgada/métodos , Citosol/análisis , Citosol/metabolismo , Dexametasona/farmacocinética , Humanos , Neoplasias Renales/análisis , Hígado/análisis , Hígado/metabolismo , Melanoma/análisis , Ensayo de Unión Radioligante/métodos , Ratas , Receptores de Glucocorticoides/análisis , Neoplasias Cutáneas/análisis , Temperatura , TritioRESUMEN
Glucocorticoid receptor (GR) levels of bone marrow blast cells were measured in 29 pediatric patients suffering different forms of acute leukemia. A decrease in GR level was registered immediately after prednisolone treatment. Differences in cell GR levels in patients with lymphoblastic and myeloblastic leukemia were not significant. The level of GR of bone marrow blast cells was found to be of prognostic significance in acute lymphoblastic leukemia: 4 out of 5 patients with GR levels under 3,000 sights per cell relapsed within 5-7 months of follow-up whereas all 7 cases with higher levels continue in remission. No correlation between GR level and prognosis was established in 5 patients with various forms of acute myeloblastic leukemia.