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1.
Rev. Asoc. Méd. Argent ; 137(1): 4-10, mar. 2024.
Artículo en Español | LILACS | ID: biblio-1552830

RESUMEN

Se exponen los hallazgos históricos y la importancia biológica de los telómeros en la vida celular y en los aspectos genéticos del ADN humano. (AU)


The discovery and the biological importance of the telomeres are exposed. (AU)


Asunto(s)
Humanos , ADN/genética , Telómero/fisiología , Telómero/genética , Telomerasa/fisiología , Telomerasa/genética , Envejecimiento/fisiología , ADN/metabolismo , Senescencia Celular , Telomerasa/metabolismo , Replicación del ADN/fisiología , Acortamiento del Telómero , Neoplasias/fisiopatología
2.
Chinese Journal of Pathology ; (12): 1216-1222, 2023.
Artículo en Chino | WPRIM | ID: wpr-1012396

RESUMEN

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.


Asunto(s)
Humanos , Neoplasias de la Vejiga Urinaria/genética , Carcinoma de Células Transicionales/patología , Vejiga Urinaria/patología , Diagnóstico Diferencial , Estudios Retrospectivos , Mutación , Cistitis/genética , Neoplasias Glandulares y Epiteliales/diagnóstico , Papiloma/diagnóstico , Telomerasa/genética
3.
Chinese Journal of Pathology ; (12): 153-159, 2023.
Artículo en Chino | WPRIM | ID: wpr-970150

RESUMEN

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.


Asunto(s)
Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Neoplasias Fibroepiteliales/patología , Tumor Filoide/genética , Células del Estroma , Fibroadenoma/patología , Neoplasias de la Mama/patología , Mutación , Telomerasa/genética
4.
Arq. bras. neurocir ; 40(2): 186-189, 15/06/2021.
Artículo en Inglés | LILACS | ID: biblio-1362256

RESUMEN

The most common mixed glioma encountered in routine surgical practice is oligoastrocytoma (OA); however, its is currently considered a vanishing entity. The 2016 classification of the World Health Organization (WHO) discourages the diagnosis of tumors as mixed glioma. The recommendations are that diffuse gliomas, including those withmixed or ambiguous histological features, should be subjected tomolecular testing. Dual-genotype OAs are not yet a distinct entity or variant in the classification. We report a case ofmixed glioma: a pleomorphic xanthoastrocytoma (PXA)mixed with an oligodendroglioma. The immunohistochemistry (IHC) pattern of isocitrate dehydrogenase 1 (IDH1) negativity with retained nuclear expression of the alpha-thalassemia x-linked intellectual disability syndrome (ATRX) protein, and 1p19q co-deletion negativity in both the components enabled its identification as a mixed glioma rather than a collision tumor. To the best of our knowledge, the case herein presented is the fourth case of PXA with oligodendroglioma. Out of the other three reported cases, only one was of a collision tumor with a dual genotype, and the other two showed similar molecular signatures in both components. The present article discusses the histological, immunohistochemical and molecular features of the aforementioned case.


Asunto(s)
Humanos , Masculino , Adulto , Oligodendroglioma/cirugía , Astrocitoma/cirugía , Neoplasias Encefálicas/terapia , Neoplasias Primarias Múltiples/cirugía , Oligodendroglioma/patología , Oligodendroglioma/diagnóstico por imagen , Astrocitoma/patología , Lóbulo Temporal/cirugía , Aconitato Hidratasa/genética , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 19 , Deleción Cromosómica , Telomerasa/genética , Craneotomía/métodos
5.
Clinics ; 76: e2432, 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1153954

RESUMEN

OBJECTIVES: Telomeres are a terminal "DNA cap" that prevent chromosomal fusion and degradation. However, aging is inherent to life, and so is the loss of terminal sequences. Telomerase is a specialized reverse transcriptase encoded by self-splicing introns that counteract chromosome erosion. Telomerase activity is observed during early embryonic development, but after the blastocyst stage, the expression of telomerase reduces. The consequences of either insufficient or unrestrained telomerase activity underscore the importance of ongoing studies aimed at elucidating the regulation of telomerase activity in humans. In the present study, we aimed to standardize a simplified telomerase repeat-amplification protocol (TRAP) assay to detect telomerase activity in unstimulated and PHA-stimulated mononuclear cells. METHODS and RESULTS: Our optimized qPCR-based can efficiently evaluate telomerase activity. Quantification of protein and DNA between unstimulated and PHA-stimulated peripheral blood mononuclear cells revealed cellular activation and cell-cycle entry. The assay also showed that relative telomerase activity is significantly different between these two conditions, supporting the applicability of the assay. Furthermore, our findings corroborated that telomerase activity decreases with age. CONCLUSIONS: Telomeres and telomerase are implicated in aging and development of chronic diseases and cancer; however, difficulty in accessing commercial kits to investigate these aspects is a critical constraint in health surveillance studies. Our optimized assay was successfully used to differentiate telomerase activity between unstimulated and stimulated cells, clearly showing the reactivation of telomerase upon cell activation. This assay is affordable, reproducible, and can be executed in resource-limited settings.


Asunto(s)
Humanos , Femenino , Embarazo , Telomerasa/genética , Telomerasa/metabolismo , Neoplasias , Envejecimiento , Leucocitos Mononucleares/metabolismo , Enfermedad Crónica , Análisis Costo-Beneficio
6.
Arch. endocrinol. metab. (Online) ; 63(2): 107-112, Mar.-Apr. 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1001216

RESUMEN

ABSTRACT Objectives: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAFV600E mutation. Subjects and methods: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAFV600E and pTERT mutations. Results: We found coexistence of pTERTC228T and BRAFV600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAFV600E positives. There was a significant association between pTERTC228T/BRAFV600E with older age and advanced stage compared with the group negative for either mutation. Conclusions: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERTC228T/BRAFV600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Neoplasias de la Tiroides/genética , Nódulo Tiroideo/genética , Telomerasa/genética , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo/genética , Pronóstico , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Análisis Mutacional de ADN , Valor Predictivo de las Pruebas , Factores de Edad , Regiones Promotoras Genéticas/genética , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/patología , Biopsia con Aguja Fina , Periodo Preoperatorio , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Metástasis Linfática/diagnóstico , Mutación/genética , Estadificación de Neoplasias
7.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 40(1): 19-25, Jan.-Mar. 2018. tab, graf
Artículo en Inglés | LILACS | ID: biblio-899400

RESUMEN

Objective: The findings of telomere length (TL) studies in bipolar disorder (BD) are controversial. The aim of the present study was to detect TL, human telomerase reverse transcriptase (hTERT), and brain derived neurotrophic factor (BDNF) in severe mania and subsequent remission. Methods: Twenty-one medication-free male patients and 20 age and gender matched controls were recruited. The patients were followed in the inpatient clinic, and comparisons were made between the same patients in their remission state and controls. Patients received lithium plus antipsychotics during the follow-up period. Quantitative real-time polymerase chain reaction was performed to verify leukocyte TL and whole blood hTERT gene expression levels. Serum BDNF levels were verified by enzyme-linked immunosorbent assay (ELISA). Results: Compared to controls, manic patients presented shorter telomeres (p < 0.001) whose length increased with treatment (p = 0.001). Patients in the late stages showed shorter TL than those in the early stages and controls (p < 0.001). hTERT gene expression levels were up-regulated in mania and remission compared to controls (p = 0.03 and p = 0.01, respectively). BDNF changes did not reach statistically significant levels. Conclusions: TL and hTERT gene expression might reflect a novel aspect of BD pathophysiology and TL might represent a novel biomarker for BD staging.


Asunto(s)
Humanos , Masculino , Adulto , Trastorno Bipolar/diagnóstico , Telómero/genética , Telomerasa/genética , Trastorno Bipolar/genética , Marcadores Genéticos , Estudios de Casos y Controles , Reacción en Cadena en Tiempo Real de la Polimerasa , Acortamiento del Telómero/genética
8.
Rev. chil. dermatol ; 34(2): 60-67, 2018. ilus, tab
Artículo en Español | LILACS | ID: biblio-994875

RESUMEN

En la última década se ha avanzado en la caracterización genética y mapeo molecular del melanoma cutáneo con el objetivo de identificar y comprender mejor los mecanismos patogénicos propios de cada subgrupo y así desarrollar tratamientos específicos. El melanoma lentiginoso acral (MLA) constituye un subtipo de melanoma con características clínicas, epidemiológicas, histopatológicas, pronósticas y terapéuticas distintivas y su perfil mutacional no es la excepción. A diferencia del melanoma ubicado en zonas fotoexpuestas, el MLA presenta una baja tasa de mutaciones BRAF (15%) y mayor frecuencia de amplificaciones y ganancias genéticas de KIT (15-30%), CCND1 (15-40%) y TERT (20%). En esta revisión se describen las características más relevantes del MLA con énfasis en el rol que cumplen los principales genes que participan en la patogenia del MLA.


Over the last decade, the genetic characterization and molecular mapping of cutaneous melanoma has been developed in order to identify and better understand the pathogenic mechanisms of each subgroup and to develop specific treatments. Acral lentiginous melanoma (ALM) is a melanoma subtype with distinctive clinical, epidemiological, histopathological, prognostic and therapeutic features and its mutational profile is not an exception. Unlike melanoma located in photoexposed areas, MLA has a low rate of BRAF mutations (15%) and a higher frequency of amplifications and genetic gains at KIT (15-30%), CCND1 (15-40%) and TERT (20%). In this review we will describe the most relevant characteristics of MLA with emphasis on the role of the main genes involved in its pathogenesis.


Asunto(s)
Humanos , Neoplasias Cutáneas/genética , Melanoma/genética , Pronóstico , Neoplasias Cutáneas/patología , Telomerasa/genética , Proteínas Proto-Oncogénicas c-kit/genética , Ciclina D1/genética , Melanoma/patología , Mutación
9.
Mem. Inst. Oswaldo Cruz ; 112(8): 572-576, Aug. 2017. graf
Artículo en Inglés | LILACS | ID: biblio-1040575

RESUMEN

The Telomeric Repeat-containing RNAs (TERRA) participate in the homeostasis of telomeres in higher eukaryotes. Here, we investigated the expression of TERRA in Leishmania spp. and Trypanosoma brucei and found evidences for its expression as a specific RNA class. The trypanosomatid TERRA are heterogeneous in size and partially polyadenylated. The levels of TERRA transcripts appear to be modulated through the life cycle in both trypanosomatids investigated, suggesting that TERRA play a stage-specific role in the life cycle of these early-branching eukaryotes.


Asunto(s)
Trypanosoma brucei brucei/genética , ARN/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Telomerasa/genética , Leishmania/genética
10.
Int. braz. j. urol ; 41(2): 337-343, Mar-Apr/2015. tab, graf
Artículo en Inglés | LILACS | ID: lil-748301

RESUMEN

Objectives To examine the usefulness of an absorbable hemostatic gelatin sponge for hemostasis after transrectal prostate needle biopsy. Subjects and Methods The subjects comprised 278 participants who underwent transrectal prostate needle biopsy. They were randomly allocated to the gelatin sponge insertion group (group A: 148 participants) and to the non-insertion group (group B: 130 participants). In group A, the gelatin sponge was inserted into the rectum immediately after biopsy. A biopsy-induced hemorrhage was defined as a case in which a subject complained of bleeding from the rectum, and excretion of blood clots was confirmed. A blood test was performed before and after biopsy, and a questionnaire survey was given after the biopsy. Results Significantly fewer participants in group A required hemostasis after biopsy compared to group B (3 (2.0%) vs. 11 (8.5%), P=0.029). The results of the blood tests and the responses from the questionnaire did not differ significantly between the two groups. In multivariate analysis, only “insertion of a gelatin sponge into the rectum” emerged as a significant predictor of hemostasis. Conclusion Insertion of a gelatin sponge into the rectum after transrectal prostate needle biopsy significantly increases hemostasis without increasing patient symptoms, such as pain and a sense of discomfort. .


Asunto(s)
Adulto , Humanos , Glioma/genética , Polimorfismo de Nucleótido Simple/genética , ARN , Telomerasa/genética , Telómero/genética , Estudios de Casos y Controles , Estudio de Asociación del Genoma Completo , Genotipo , Glioma/patología , Leucocitos/metabolismo , Leucocitos/patología , Clasificación del Tumor , Pronóstico , Factores de Riesgo
11.
Rev. méd. Chile ; 143(1): 63-68, ene. 2015. graf, tab
Artículo en Español | LILACS | ID: lil-742552

RESUMEN

Background: Vildagliptin is a dipeptidyl peptidase IV inhibitor (DPP4i). Its efficacy and safety of DPP4i in Chilean real life type 2 diabetic (T2D) patients is not well known. Aim: To assess the safety profile and effectiveness of 12 weeks of treatment with Vildagliptin for glycemic control in T2D Chilean patients with a poor glycemic control. Patients and Methods: Retrospective assessment of the effects of Vildagliptin treatment during 12 weeks in 103 T2D patients aged 29 to 92 years (47% males). The main outcomes were changes in glycosylated hemoglobin and the occurrence of adverse effects. Results: After 12 weeks of Vildagliptin use, glycosylated hemoglobin decreased from 8.3 ± 1.4 to 7.2 ± 1.1% (p < 0.01). Fasting plasma glucose and the number of hypoglycemic events also decreased significantly. No significant weight change was observed. The treatment had good compliance, tolerance and patient satisfaction. Conclusions: Vildagliptin treatment reduced glycosylated hemoglobin by 1.1% and was well tolerated in this group of diabetic patients.


Asunto(s)
Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Telomerasa/metabolismo , Mutación , Unión Proteica , Estructura Terciaria de Proteína , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Telomerasa/genética
12.
The Korean Journal of Internal Medicine ; : 719-726, 2015.
Artículo en Inglés | WPRIM | ID: wpr-76671

RESUMEN

BACKGROUND/AIMS: A number of genome-wide and candidate gene association studies have identified polymorphisms associated with telomere length in Caucasian populations. This study was conducted to determine the impacts of 17 polymorphisms identified in Caucasians on telomere length in a Korean population. METHODS: Ninety-four healthy individuals were enrolled in this study. Relative telomere length of chromosomes from peripheral blood samples was measured using quantitative polymerase chain reaction. RESULTS: Two polymorphisms, rs10936599 of MYNN and rs412658 of ZNF676, were found to be associated w ith telomere length (under dominant model, p = 0.04; under recessive model, p = 0.001). Three polymorphisms, rs2853669, rs7705526, and rs2736108, at the TERT locus were also associated with telomere length (under recessive model, p = 0.01, p = 0.02, and p = 0.01, respectively). The genotypes of the five polymorphisms associated with short telomere length were considered bad genotypes; telomere length was significantly decreased with increasing number of bad genotypes (p= 1.7 x 10(-5)). CONCLUSIONS: We have identified polymorphisms associated with telomere length in a Korean population.


Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico/genética , Estudios de Casos y Controles , Proteínas de Unión al ADN/genética , Estudio de Asociación del Genoma Completo , Genotipo , Factores de Transcripción de Tipo Kruppel/genética , Fenotipo , Polimorfismo de Nucleótido Simple , República de Corea , Telomerasa/genética , Telómero/genética , Homeostasis del Telómero , Dedos de Zinc
13.
Journal of Korean Medical Science ; : 1423-1428, 2015.
Artículo en Inglés | WPRIM | ID: wpr-183079

RESUMEN

Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.


Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma/epidemiología , Estudios de Casos y Controles , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Neoplasias Pulmonares/epidemiología , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , República de Corea/epidemiología , Telomerasa/genética , Telómero/fisiología , Homeostasis del Telómero/genética
14.
Rev. Esc. Enferm. USP ; 48(spe): 102-108, 08/2014. tab
Artículo en Inglés | LILACS, BDENF | ID: lil-731295

RESUMEN

Exploratory and descriptive study based on quantitative and qualitative methods that analyze the phenomenon of violence against adolescents based on gender and generational categories. The data source was reports of violence from the Curitiba Protection Network from 2010 to 2012 and semi-structured interviews with 16 sheltered adolescents. Quantitative data were analyzed using SPSS software version 20.0 and the qualitative data were subjected to content analysis. The adolescents were victims of violence in the household and outside of the family environment, as victims or viewers of violence. The violence was experienced at home, mostly toward girls, with marked overtones of gender violence. More than indicating the magnitude of the issue, this study can give information to help qualify the assistance given to victimized people and address how to face this issue.


Objetivo Analizar la violencia contra los adolescentes a la luz de las categorías de género y generación. Método Estudio exploratorio, descriptivo, de abordaje cuantitativo y cualitativo que. Las fuentes de datos fueron las denuncias de violencia mantenidos por la Red de Protección en Curitiba entre los años 2010-2012 y entrevistas semi-estructuradas con 16 adolescentes alojados. Las variables cuantitativas se analizaron mediante el programa SPSS y los cualitativos por la análisis de contenido. Resultados Los adolescentes fueron sometidos a la violencia en el hogar y en el exterior, como víctimas o espectadores. La violencia fue más frecuente en el hogar, centrándose principalmente en las chicas con matices marcados de violencia de género. Conclusión Más que encontrar la magnitud del problema, el estudio puede servir de base para calificar la asistencia a las personas víctimas de este fenómeno.

 .


Objetivo Analisar a violência contra o adolescente à luz das categorias gênero e geração. Método Estudo exploratório, descritivo, de abordagem quantitativa e qualitativa. As fontes de dados foram as notificações de violência da Rede de Proteção do município de Curitiba, de 2010 a 2012, e entrevistas semiestruturadas com 16 adolescentes abrigados. As variáveis quantitativas foram analisadas pelo software SPSS e os dados qualitativos através da análise de conteúdo. Resultados Os adolescentes foram submetidos à violência no ambiente doméstico e fora dele, como vítimas ou como espectadores. Prevaleceu no domicílio, incidindo principalmente sobre as meninas, com marcada conotação de violência de gênero. Conclusão Mais que constatar a magnitude do problema, o estudo pode fornecer subsídios para qualificar a assistência prestada aos sujeitos vitimizados e subsidiar o enfrentamento do fenômeno. .


Asunto(s)
Adulto , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Telomerasa/genética , Proteínas de Unión al ADN , Expresión Génica , Inmunidad Celular , Células Asesinas Naturales/inmunología , Lesiones Precancerosas/enzimología , Lesiones Precancerosas/genética , Lesiones Precancerosas/inmunología , ARN Mensajero/genética , ARN Neoplásico/genética , Neoplasias Gástricas/enzimología , Subgrupos de Linfocitos T/inmunología
15.
Medicina (B.Aires) ; 74(1): 69-76, ene.-feb. 2014. ilus
Artículo en Español | LILACS | ID: lil-708560

RESUMEN

La telomerasa es la enzima responsable del mantenimiento de la longitud de los telómeros mediante la adición de secuencias repetitivas ricas en guanina, y su actividad se observa principalmente en gametos, células madre y células tumorales. En las células somáticas humanas el potencial de proliferación es limitado, alcanzando la senescencia luego de 50-70 divisiones celulares, debido a que la ADN polimerasa no es capaz de copiar el ADN en los extremos de los cromosomas. Por el contrario, en la mayoría de las células tumorales el potencial de replicación es ilimitado debido al mantenimiento de la longitud telomérica dado por la telomerasa. Los telómeros tienen proteínas adicionales que regulan la unión de la telomerasa. De la misma manera la telomerasa también se asocia con un complejo de proteínas que regulan su actividad. Este trabajo se centra en la estructura y función del complejo telómero/telomerasa y a cómo las alteraciones en su comportamiento conducen al desarrollo de diversas enfermedades, principalmente cáncer. El desarrollo de inhibidores del sistema telómero / telomerasa podría ser un blanco con posibilidades prometedoras.


Telomerase is the enzyme responsible for the maintenance of telomere length by adding guanine-rich repetitive sequences. Its activity can be seen in gametes, stem cells and tumor cells. In human somatic cells the proliferative potential is limited, reaching senescence after 50-70 cell divisions, because the DNA polymerase is not able to copy the DNA at the ends of chromosomes. By contrast, in most tumor cells the replicative potential is unlimited due to the maintenance of the telomeric length given by telomerase. Telomeres have additional proteins that regulate the binding of telomerase, likewise telomerase associates, with a protein complex that regulates its activity. This work focuses on the structure and function of the telomere/telomerase complex and how changes in its behavior lead to the development of different diseases, mainly cancer. Development of inhibitors of the telomere/telomerase complex could be a target with promising possibilities.


Asunto(s)
Animales , Humanos , Neoplasias/genética , Telomerasa/genética , Telómero/fisiología , Senescencia Celular/genética , División Celular/fisiología , Neoplasias/enzimología , Telomerasa/metabolismo , Proteína 1 de Unión a Repeticiones Teloméricas/fisiología , /fisiología
16.
Yonsei Medical Journal ; : 1-8, 2014.
Artículo en Inglés | WPRIM | ID: wpr-188830

RESUMEN

Telomerase reverse transcriptase (TERT) is the protein component of telomerase and combined with an RNA molecule, telomerase RNA component, forms the telomerase enzyme responsible for telomere elongation. Telomerase is essential for maintaining telomere length from replicative attrition and thus contributes to the preservation of genome integrity. Although diverse mouse models have been developed and studied to prove the physiological roles of telomerase as a telomere-elongating enzyme, recent studies have revealed non-canonical TERT activities beyond telomeres. To gain insights into the physiological impact of extra-telomeric roles, this review revisits the strategies and phenotypes of telomerase mouse models in terms of the extra-telomeric functions of telomerase.


Asunto(s)
Animales , Ratones , Ratones Noqueados , Telomerasa/genética , Telómero/metabolismo
17.
Braz. j. med. biol. res ; 44(2): 100-104, Feb. 2011. ilus, tab
Artículo en Inglés | LILACS | ID: lil-573652

RESUMEN

The objective of this study was to determine the levels of TERT mRNA and TERT protein expression in stomach precancerous lesions such as intestinal metaplasia (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30 of GU, and 22 of GC and their respective normal mucosas. TERT protein was detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC. Increased TERT mRNA expression levels were observed in a significant number of cases, i.e., 46 percent of IM, 50 percent of GU, and 79 percent of GC. The relative mean level of TERT mRNA after normalization with the β-actin reference gene and comparison with the respective adjacent normal mucosa was slightly increased in the IM and GU groups, 2.008 ± 2.605 and 2.730 ± 4.120, respectively, but high TERT mRNA expression was observed in the GC group (17.271 ± 33.852). However, there were no statistically significant differences between the three groups. TERT protein-positive immunostaining was observed in 38 percent of IM, 39 percent of GU, and 55 percent of GC. No association of TERT mRNA and protein expression with Helicobacter pylori infection or other clinicopathological variables was demonstrable, except for the incomplete type vs the complete type of IM. This study confirms previous data of the high expression of both TERT mRNA and protein in gastric cancer and also demonstrates this type of changed expression in IM and GU, thus suggesting that TERT expression may be deregulated in precursor lesions that participate in the early stages of gastric carcinogenesis.


Asunto(s)
Humanos , Persona de Mediana Edad , Lesiones Precancerosas/metabolismo , ARN Mensajero/análisis , Neoplasias Gástricas/metabolismo , Úlcera Gástrica/metabolismo , Telomerasa/análisis , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Helicobacter pylori , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Inmunohistoquímica , Intestinos/patología , Metaplasia/metabolismo , Proteínas de Neoplasias/metabolismo , Lesiones Precancerosas/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias Gástricas/patología , Úlcera Gástrica/patología , Telomerasa/genética
18.
BCCR-Basic and Clinical Cancer Research. 2011; 3 (1): 14-22
en Inglés | IMEMR | ID: emr-137510

RESUMEN

The present study was performed to investigate the effects of trace elements particularity Se, Zn and Cu on tumor genesis in breast cancer. The inhibitory effect of Se, Zn and Cu, on telomerase activity was analyzed in human breast tumor tissues and breast cancer [T47D] cells. Tissue specimens from 24 women with benign breast disease and 32 women with breast cancer specimens [ductal carcinoma, lobular carcinoma] were collected during surgery. In addition venous blood samples were obtained for assessing the trace elements. T47D cell line was cultured and treated with trace elements. Telomerase activity then was measured with TRAP assay in cell line and tissue extracts. There was a significant difference between tissue and serum levels of Cu, Se and the ratio of Cu/Zn in patients and controls [P<0.001]. After treating with 100 microm/L Zn So4, 10 um /L Cu So4 for 6 hours, telomerase activity of T47D cells was markedly increased. But after treating with 10, and 30 um /L selenium-L- methionin, telomerase activity was markedly inhibited. Telomerase activity of T47D cells for 24 hours were 0.93, 0.60 and for 48 hours were 0.76, 0.12 respectively [control 49.2%]. There were variations in serum level of Zn and Cu in breast cancer patients. Association between trace elements level and telomerase activity level can be exploited as prognostic and diagnostic marker for breast cancer


Asunto(s)
Humanos , Femenino , Neoplasias de la Mama/enzimología , Telomerasa/genética , Selenio/farmacología , Zinc/farmacología , Cobre/farmacología , Línea Celular , Extractos de Tejidos , Células Tumorales Cultivadas , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
19.
GJO-Gulf Journal of Oncology [The]. 2011; July (10): 18-26
en Inglés | IMEMR | ID: emr-146109

RESUMEN

Cervical cancer is the second most common cancer in women worldwide after breast cancer. Cervical cancer is a preventable disease. The implementation of cervical cancer screening programs has greatly decreased the morbidity and mortality, as precancerous lesions and early invasive cervical cancer could be detected and treated effectively. The detection of hTERC gene amplification was suggested as a possible diagnostic marker for use in routine cytological screening. The present study was designed to detect genomic gains of the hTERC and C-MYC genes using FISH technique and to investigate the relationship between genes amplification and the clinical data of the patients. The current study was carried out on twelve cases with cervical cancer at different grades [three cases were grade I, six cases were grade II and three cases were grade III]. Interphase FISH analysis using LSI probe, Cervical Cancer probe hTERC [3q26] and C-MYC [8q24], was successfully performed on 12 patients with cancer cervix. Interphase FISH analysis revealed positive hTERC gene amplification in all cases of cancer cervix [100%]. However C-MYC gene amplification was detected in four cases only [33.3%]. Statistical analysis of the data revealed significant correlation between hTERC amplification and grating. Also, there was significant correlation between C-MYC amplification and grading and highly significant correlation between C-MYC amplification and hTERC amplification. On the other hand hTERC and C-MYC genes amplification showed an inverse correlation with the ages of the patients. The present study highlights the importance of using hTERC and C-MYC genes FISH probes for cases with cancer cervix or pre-malignant lesions as a sensitive technique. This method provides an easy and effective applicable approach which helps in the diagnosis and prognosis, as an increased copy number is associated with a more advanced grade that could be detected in the early stages of the disease


Asunto(s)
Humanos , Femenino , Genes myc , Bandeo Cromosómico , Hibridación Fluorescente in Situ , Clasificación del Tumor , Telomerasa/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología
20.
Artículo en Inglés | IMSEAR | ID: sea-139846

RESUMEN

Background : Human telomerase is a multi subunit ribonucleoprotein enzyme concerned with telomeric lengthening and homeostasis in man. This enzyme has been found to be elevated in inflammatory conditions like rheumatoid arthritis and silica injury lung. Since chronic periodontitis is also an inflammatory condition where immune cells and cytokines mediate tissue destruction, we set out to evaluate telomerase in gingival tissue samples from healthy subjects and chronic periodontitis patients by reverse transcriptase polymerase chain reaction. Materials and Methods : Gingival biopsies were obtained from eight healthy subjects and eight chronic periodontitis patients. Reverse transcriptase polymerase chain reaction (RTPCR) was carried out to evaluate telomerase gene expression in the samples. Results : None of the healthy gingival tissue samples expressed the telomerase gene while all the chronic periodontitis samples expressed it. The severe chronic periodontitis samples expressed the gene more intensely than the moderate chronic periodontitis samples. Conclusion : Various mechanisms have been explained to account for telomerase elevation in chronic periodontitis .This study helps us understand the role of telomerase in the pathogenesis of periodontal disease. It could be concluded that telomerase could be used as a marker to assess the severity of inflammation in chronic periodontitis.


Asunto(s)
Biomarcadores , Estudios de Casos y Controles , Periodontitis Crónica/enzimología , Periodontitis Crónica/genética , Femenino , Expresión Génica , Humanos , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Telomerasa/biosíntesis , Telomerasa/genética
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