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Breast cancer is the second cause of cancer death in women worldwide. The search for therapeutic and preventive alternatives has increased in recent years. One synthetic drug for patients with hormone receptor-positive tumours is tamoxifen citrate (TMX). Curcumin (Cur) is a natural compound that is being tested. Both were coupled with nanoscale-controlled and sustained release systems to increase the effectiveness of the treatment and reduce adverse effects. We produced a controlled release system based on uniaxial and coaxial polymeric nanofibers of polycaprolactone (PCL), alginate (Alg) and gelatine (Gel) for the transport and release of TMX and Cur, as a new alternative to breast cancer treatment. Nanofibers combining PCL-Alg and PCL-Gel were fabricated by the electrospinning technique and physicochemically characterised by thermal analysis, absorption spectroscopy in the infrared region and X-ray diffraction. Morphology and size were studied by scanning electron microscopy. Additionally, the release profile of TMX and Cur was obtained by UV-Vis spectroscopy. Additionally, the cytotoxic effect on breast cancer cell line MCF7 and peripheral-blood mononuclear cells (PBMCs) from a healthy donor were evaluated by a Resazurin reduction assay. These assays showed that PCL-TMX nanofiber was highly toxic to both cell types, while PCL-Cur was less toxic.

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Breast cancer is the second leading cause of death in women, and tamoxifen citrate (TMX) is accepted widely for the treatment of hormone receptor-positive breast cancers. Several local drug-delivery systems, including nanofibers, have been developed for antitumor treatment. Nanofibers are biomaterials that mimic the natural extracellular matrix, and they have been used as controlled release devices because they enable highly efficient drug loading. The purpose of the present study was to develop polycaprolactone (PCL) nanofibers incorporating TMX for use in the treatment of breast tumors. Pristine PCL and PCL-TMX nanofibers were produced by electrospinning and characterized physiochemically using different techniques. In addition, an in vitro study of TMX release from the nanofibers was performed. The PCL-TMX nanofibers showed sustained TMX release up to 14 h, releasing 100% of the TMX. The Resazurin reduction assay was used to evaluate the TMX cytotoxicity on MCF-7 breast cancer cell line and PBMCs human. The PCL-TMX nanofiber was cytotoxic toPBMCs and MCF-7. Based on these results, the PCL-TMX nanofibers developed have potential as an alternative for local chronic TMX use for breast cancer treatment, however tissue tests must be done.

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AIM: This study aims to investigate similarities and differences using lncRNA and mRNA coexpression network analysis in African ancestry (AA) and European ancestry (EA) among prostate cancer (PCa) patients. METHODS: We performed weighted gene coexpression network analysis of the expression from 49 of AA and 49 of EA to identify lncRNAs-mRNAs. RESULTS: 27 lncRNAs and 36 mRNAs were highly expressed in patients of AA. Two mRNAs and their antisense lncRNAs were expressed. Additionally, seven mRNAs were DE or coexpressed and had an impact on survival. CONCLUSION: We present a list of lncRNAs and mRNAs that were DE and coexpressed when comparing patients of AA and EA, and these data are a resource for future studies to understand the role of lncRNAs.

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Background and Objective Prostate cancer is a multifactorial disease and is among the top five causes of death in men worldwide. The Colombian Ministry of Health has adopted the Integrated Information System on Social Protection (Sistema Integrado de Información de la Protección Social, SISPRO, by its Spanish acronym) registry to collect comprehensive information from the Colombian health system. The system provides close to universal coverage (around 95%). We aimed to establish the prevalence of prostate cancer in Colombia and to describe its demographics, based on data provided by SISPRO, openly available for scientific analysis. Methods Using the SISPRO data from 2015 through 2019, we analyzed the prevalence and demographic characteristics of patients diagnosed with prostate cancer. Results We identified a total of 43,862 patients with prostate cancer in the 5-year period and estimated a prevalence of 4.54 cases per 1,000 habitants, using as denominator males over 35 years old. We calculated a prevalence of early-onset prostate cancer (i.e., 35­54 years) of 0.14 per 1,000 habitants (791 cases in 5 years). The highest prevalence was observed in patients>80 years (33.45 per 1,000 habitants). The departments with the highest prevalence were Bogotá, Valle del Cauca, Risaralda, and Boyacá, and the region with the lowest prevalence was Amazonas.

Antecedentes y Objetivo El cáncer de próstata es una enfermedad multifactorial, y se encuentra entre las cinco principales causas de muerte en hombres a nivel mundial. El Ministerio de Salud de Colombia ha adoptado el Sistema Integrado de Información de la Protección Social (SISPRO) para la recopilación de la información integral del sistema de salud colombiano. El sistema proporciona una cobertura casi universal (alrededor del 95%). El objetivo de este estudio fue establecer la prevalencia del cáncer de próstata en Colombia y describir su demografía, con base en los datos proporcionados por el SISPRO, disponibles de forma abierta para el análisis científico. Métodos Utilizando los datos del SISPRO de 2015 a 2019, se analizaron la prevalencia y las características demográficas de los pacientes diagnosticados con cáncer de próstata. Resultados Se identificó un total de 43,862 pacientes con cáncer de próstata en el período de 5 años, con una prevalencia de 4,54 casos por cada mil habitantes, utilizando como denominador hombres mayores de 35 años. La prevalencia de cáncer de próstata de inicio temprano (es decir, paciente de 35 a 54 años) fue de 0.14 por mil habitantes (791 casos en 5 años). La mayor prevalencia se observó en pacientes > 80 años (33,45 por mil habitantes). Los departamentos con mayor prevalencia fueron Bogotá, Valle del Cauca, Risaralda, y Boyacá. Y la región con menor prevalencia fue Amazonas. Conclusión Describimos la prevalencia y la demografía del cáncer de próstata y el cáncer de próstata de inicio temprano en Colombia utilizando la base de datos del sistema nacional de salud. Observamos una distribución desigual de la prevalencia entre las regiones, que puede estar relacionada con factores raciales, ambientales, o de acceso, que justifican más estudios.

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The incidence of patients under 55 years old diagnosed with Prostate Cancer (EO-PCa) has increased during recent years. The molecular biology of PCa cancer in this group of patients remains unclear. Here, we applied weighted gene coexpression network analysis of the expression of miRNAs from 24 EO-PCa patients (38-45 years) and 25 late-onset PCa patients (LO-PCa, 71-74 years) to identify key miRNAs in EO-PCa patients. In total, 69 differentially expressed miRNAs were identified. Specifically, 26 and 14 miRNAs were exclusively deregulated in young and elderly patients, respectively, and 29 miRNAs were shared. We identified 20 hub miRNAs for the network built for EO-PCa. Six of these hub miRNAs exhibited prognostic significance in relapse-free or overall survival. Additionally, two of the hub miRNAs were coexpressed with mRNAs of genes previously identified as deregulated in EO-PCa and in the most aggressive forms of PCa in African-American patients compared with Caucasian patients. These genes are involved in activation of immune response pathways, increased rates of metastasis and poor prognosis in PCa patients. In conclusion, our analysis identified miRNAs that are potentially important in the molecular pathology of EO-PCa. These genes may serve as biomarkers in EO-PCa and as possible therapeutic targets.

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Abstract Introduction : Aging is the main risk factor for the development of chronic diseases such as cancer, diabetes, Parkinson's disease, and Alzheimer's disease. The central nervous system is particularly susceptible to progressive functional deterioration associated with age, among the brain regions the prefrontal cortex (PFC) has one of the highest involvements. Transcriptomics studies of this brain region have identified the decrease in synaptic function and activation of neuroglia cells as fundamental characteristics of the aging process. The aim of this study was to identify hub genes in the transcriptomic deregulation in the PFC aging to advance in the knowledge of this process. Materials and methods : A gene co-expression analysis was carried out for 45 people 60 to 80 years old compared with 38 people 20 to 40 years old. The networks were visualized and analyzed using Cytoscape; citoHubba was used to determine which genes had the best topological characteristics in the co-expression networks. Results : Five genes with high topological characteristics were identified. Four of them -HPCA, CACNG3, CA10, PLPPR4- were repressed and one was over-expressed -CRYAB-. Conclusion: The four repressed genes are expressed preferentially in neurons and regulate the synaptic function and the neuronal plasticity, while the overexpressed gene is typical of glial cells and is expressed as a response to neuronal damage, facilitating myelination and neuronal regeneration.

Resumen Introducción : el envejecimiento es el principal factor de riesgo para el desarrollo de enfermedades crónicas como el cáncer, la diabetes, el Parkinson y el Alzheimer. El sistema nervioso central es particularmente susceptible al deterioro funcional progresivo asociado con la edad, entre las regiones cerebrales con mayor compromiso se encuentra la corteza prefrontal (CPF). Estudios de transcriptómica de esta región han identificado como características fundamentales del proceso de envejecimiento la disminución de la función sináptica y la activación de las células de la neuroglia. No es claro cuáles son las causas iniciales, ni los mecanismos moleculares subyacentes a estas alteraciones. El objetivo de este estudio fue identificar genes clave en la desregulación transcriptómica en el envejecimiento de la CPF para avanzar en el conocimiento de este proceso. Materiales y métodos : se hizo un análisis de coexpresión de genes de los transcriptomas de 45 personas entre 60 y 80 años con el de 38 personas entre 20 y 40 años. Las redes fueron visualizadas y analizadas usando Cytoscape, se usó citoHubba para determinar qué genes tenían las mejores características topológicas en las redes de coexpresión. Resultados : se identificaron cinco genes con características topológicas altas. Cuatro de ellos -HPCA, CACNG3, CA10, PLPPR4- reprimidos y uno sobreexpresado -CRYAB-. Conclusión : los cuatro genes reprimidos se expresan preferencialmente en neuronas y regulan la función sináptica y la plasticidad neuronal, mientras el gen sobreexpresado es típico de células de la glía y se expresa como respuesta a daño neuronal facilitando la mielinización y la regeneración neuronal.

Resumo Introdução : o envelhecimento é o principal fator de risco pra o desenvolvimento de doenças crónicas como o câncer, a diabetes, o Parkinson e o Alzheimer. O sistema nervoso central é particularmente susceptível ao deterioro funcional progressivo associado à idade, uma das regiões do cérebro com maior compromisso é o pré-frontal (CPF). Estudos de transcritoma desta região têm identificado como características fundamentais do processo de envelhecimento a diminuição da função sináptica e ativação das células da neuroglia. Não é claro quais são as causas iniciais, nem os mecanismos moleculares subjacentes a estas alterações. O objetivo deste estudo foi identificar genes chave na desregulação transcritoma no envelhecimento da CPF para avançar no conhecimento deste processo. Materiais e métodos : se fez uma análise de co-expressão de genes dos transcritomas de 45 pessoas entre 60 e 80 anos com o de 38 pessoas entre 20 e 40 anos. As redes foram visualizadas e analisadas usando Cytoscape, usou-se citoHubba para determinar que genes tinham as melhores características topológicas nas redes de co-expressão. Resultados : identificaram-se cinco genes com características topológicas altas. Quatro deles -HPCA, CACNG3, CA10, PLPPR4- reprimidos e um superexpresso -CRYAB-. Conclusão : os quatro genes reprimidos se expressam preferencialmente em neurônios e regulam a função sináptica e plasticidade neuronal, enquanto o gene superexpresso é típico de células da glia e se expressa como resposta ao dano neuronal facilitado a mielinização e a regeneração neuronal.

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BACKGROUND: This meta-analysis presents evidence regarding the diagnostic accuracy of mammaglobin detected using the RT-PCR technique, related to the presence of sentinel node metastasis in breast cancer patients. METHODS: The following databases were consulted: Cochrane, Lilacs, Scielo, Hinary, PubMed, Elsevier, Embase, ProQuest, the Universidad del Rosario´s Centro de Recursos Para el Aprendizaje y la Investigación (CRAI-UR) [Resource Center for Learning and Research], and the Google Scholar search engine. The quality of the studies was assessed using the QUADAS-2 and CASpe tools. The selected studies presented the necessary data to calculate diagnostic validity index of mammaglobin detection using RT-PCR, compared with the reference standard test. Global values for the sensitivity, specificity, positive predictive value, negative predictive value, probability ratios, diagnostic ORs, and summary ROC curves of this meta-analysis were obtained using the Meta-DiSc 1.4 program. RESULTS: Initially, 731 articles were obtained; but only 25 were included in the meta-analysis. Sensitivity was 84% (95% CI: 83% - 86%), and specificity was 92% (95% CI: 91% - 93%). Positive and negative predictive values were 9.26 (95% CI: 6.47-13.26) and 0.17 (95% CI: 0.13-0.23), respectively. The diagnostic OR was 66.34 (95% CI: 42.52-103.52). The predictive area under the sROC curve was 94.78 (Q = 0.8876). CONCLUSIONS: The evaluated diagnostic index showed that the expression of the mammaglobin biomarker has diagnostic prediction for detecting lymph node metastasis in breast cancer patients, when analyzed using RT-PCR, although more than 50% heterogeneity was found.

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The prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the cognitive decline and mood changes during aging are not completely understood. To improve our knowledge, we integrated transcriptomic data of four studies of human PFC from elderly people (58⁻80 years old) compared with younger people (20⁻40 years old) using a meta-analytic approximation combined with molecular signature analysis. We identified 1817 differentially expressed genes, 561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of sonic hedgehog (SHH) pathway and up-regulation of metallothioneins I and genes of the family ERM (ezrin, radixin, and moesin). The main conclusions of our study are the confirmation of a global dysfunction of the synapses in the aged PFC and the evidence of opposite phenotypes of astrogliosis in the aging brain, which we report for the first time in the present article.

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Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the family of non-inhibitory serpins. The broad spectrum of PEDF biological activity is evident when considering its effects in promoting cell survival and proliferation, as well as its antiangiogenic, antitumor, and anti-metastatic properties. Although the structural domains of the PEDF gene that mediate such diverse effects and their mechanisms of action have not been completely elucidated, there is a large body of evidence describing their diverse range of activities; this evidence combined with the regulation of PEDF expression by sex steroids and their receptors have led to the idea that PEDF is not only a diagnostic and prognostic marker for certain diseases such as cancer, but is also a potential therapeutic target. In this manner, this paper aims to generally review the regulation of PEDF expression and PEDF interactions, as well as the findings that relate PEDF to the role of estrogens and estrogen receptors. In addition, this manuscript will review major advances toward potential therapeutic applications of PEDF.

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Non-coding RNAs are a complex class of nucleic acids, with growing evidence supporting regulatory roles in gene expression. Here we identify a non-coding RNA located head-to-head with the gene encoding the Glioma-associated oncogene 1 (GLI1), a transcriptional effector of multiple cancer-associated signaling pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated GLI1 and increased cellular proliferation and tumor growth in a xenograft model system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1 transcription factor. Activation of TGFß and Hedgehog signaling, two known regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the interplay between GLI1 and GLI1AS indicates that the non-coding RNA elicits a local alteration of chromatin structure by increasing the silencing mark H3K27me3 and decreasing the recruitment of RNA polymerase II to this locus. Taken together, the data demonstrate the existence of a novel non-coding RNA-based negative feedback loop controlling GLI1 levels, thus expanding the repertoire of mechanisms regulating the expression of this oncogenic transcription factor.

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Among the different types of tests used for cancer diagnosis, molecular tests have been increrasingly incorporated because of their ability to detect either expression or functional changes in the molecules associated with the disease. Mammaglobin is a protein found in mammary tissue and can be detected in serum. This protein has been proposed as a biomarker to diagnose breast cancer, given that patients exhibit an increased amount of the protein in serum and tumor tissue, in comparison to healthy individuals. The ELISA test was used in the present study to detect mammaglobin in blood samples from 51 breast cancer patients and 51 control individuals. Antibodies against mamaglobin were generated in rabbits by using the following synthetic peptides: A (amino acids 13 to 21), B (amino acids 31 to 39), C (amino acids 56 to 64) and a D peptide, corresponding to the protein isoform without three amino acids (59, 60 and 61 amino acids) from peptide C. All peptides were immunogenic and allowed generation of antibodies that were able to discriminate patients from controls. The best results were obtained for antiserum B, achieving the best sensitivity (86.3%) and specificity (96%).

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Introducción: El estudio del papel de polimorfismos en genes de las vías metabólicas de la homocisteína-metionina y el ácido fólico en anomalías congénitas, es cada vezmás importante debido a que sus efectos podrían ser modulados.Objetivo: Determinar si la presencia del polimorfismo C677T en el gen de lametilentetrahidrofolato reductasa (MTHFR) se asocia con el desarrollo de cardiopatías congénitas aisladas.Métodos: Se compararon las frecuencias alélicas y genotípicas del polimorfismo en 34 recién nacidos con cardiopatías congénitas aisladas y en 102 individuos sanos. La genotipificación se hizo mediante la reacción en cadena de la polimerasa (PCR) y se determinó el genotipo por medio de la técnica de polimorfismo de longitud de los fragmentos de restricción (RFLP). Resultados: No se encontraron diferencias estadísticamente significativas en lasfrecuencias alélicas ni genotípicas entre los grupos de casos y controles. Sin embargo, se observó una tendencia estadística para un posible efecto protector del genotipo TT...

The research of the role of gene polymorphisms in the metabolic pathways of homocysteine-methionineand folic acid in congenital malformations is very important because its effect could be modulated.Objetive: The aim of this study was to determine whether the C677T polymorphism in the gene ofthe enzyme methylenetetrahydrofolate reductase(MTHFR) was associated with the development of isolated congenital heart disease. Methodology: We compared the allele and genotypefrequencies of this polymorphism in 34infants with isolated congenital heart defects and 102 healthy individuals. Genotyping was performedby Polymerase Chain Reaction (PCR)and with the technique Restriction Fragment Length Polymorphism (RFLP). Results: There were no statistically significant differences in allele or genotype frequencies between case and control groups. Although our results show no statistically significant differencesbetween the groups assessed there was a statistical trend for a possible protective effect of TT genotype against the development of congenitalheart disease...

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Introducción: Un campo de investigación creciente de la biología es la senescencia celular, mecanismo que ha sido asociado -bajo determinadas circunstancias- con la transformación maligna. Teniendo en cuenta la elevada incidencia de cáncer ovárico y su génesis preferencial a partir del epitelio superficial del ovario, así como la posibilidad de ocurrencia de una transición epitelio-mesenquimática, se evaluó, tanto el crecimiento in vitro de los fibroblastos del estroma cortical, como la actividad a pH 6 de la β-galactosidasa, enzima cuya expresión ha sido clásicamente considerada como marcador de senescencia replicativa. Metodología: 48 muestras de fibroblastos de la corteza ovárica provenientes de donantes sin antecedentes de cáncer fueron cultivadas en forma seriada hasta el final de su vida replicativa. Mediante el método quimioluminiscente, en cada pase fue cuantificada la actividad β-galactosidasa a pH 6. Como control se utilizaron cultivos de células del epitelio superficial ovárico de las mismas donantes. La actividad enzimática fue también evaluada en fibroblastos previamente inducidos a senescencia con peróxido de hidrógeno. Resultados: Las lecturas de actividad enzimática, analizadas en conjunto con la capacidad replicativa, indican que los cultivos de fibroblastos alcanzaron el estado senescente hacia los pases 4-5, lo que también ocurrió con las células epiteliales. Los fibroblastos inducidos a senescencia mostraron valores variables de actividad enzimática. Conclusiones: La semejanza entre los fibroblastos y las células epiteliales en cuanto al inicio de la senescencia podría estar relacionado con la transición epitelio-mesenquimática que ha sido descrita como factor de riesgo de cáncer derivado del epitelio superficial ovárico. Valores bajos de actividad β-galactosidasa podrían sugerir que, en algunos casos, ocurrió inactivación de las vías de respuesta al estrés oxidativo.

Introduction: A growing biological research field is the cellular senescence, a mechanism that has been associated, under certain circumstances, with malignant transformation. Given the high incidence of ovarian cancer and its main origin from the ovarian surface epithelium, as well as the possibility that an epithelial-mesenchymal transition occurs, we evaluated both the in vitro growth of stromal fibroblasts from the ovarian cortex and their β-galactosidase activity at pH 6, enzyme whose expression is considered as a marker of replicative senescence. Methods: 48 samples of ovarian cortical fibroblasts from donors without a history of cancer were serially cultured until the end of their replicative life. β-galactosidase activity at pH 6 was quantified in each passage by the chemiluminiscent method. As control, we used ovarian epithelial cell cultures from the same donors. The enzyme activity was also evaluated in fibroblasts previously induced to senescence by exposure to hydrogen peroxide. Results: The analysis of the enzyme activity and the replicative capacity taken together showed that the fibroblast cultures reached the senescent state at passages 4-5, as what happened with the control epithelial cells. Fibroblasts induced to senescence showed high variability in the values of enzymatic activity. Conclusions: The similarity between both types of cells in reaching the senescent state deserves to be taken into account in relation to the epithelial-mesenchymal transition that has been proposed to explain their behavior in the genesis of cancer arising from ovarian surface epithelium. Low β-galactosidase activity values at pH 6 would suggest possible inactivation of the response pathways to oxidative stress.

Introdução: um campo de pesquisa crescente da biologia é a senescência celular, mecanismo que tem sido associado, sob determinadas circunstancias, com a transformação maligna. Tendo em conta a elevada incidência de câncer ovariano e sua gênese preferencial a partir do epitélio superficial do ovário, assim como a possibilidade de ocorrência de uma transição epitélio-mesenquimática, se avaliou, tanto o crescimento in vitro dos fibroblastos do estroma cortical, como a atividade a pH 6 da β-galactosidase, enzima cuja expressão tem sido classicamente considerada como marcador de senescência replicativa. Metodologia: 48 amostras de fibroblastos do córtex ovariano provenientes de doadores sem antecedentes de câncer foram cultivadas em forma seriada até o final de sua vida replicativa. Mediante o método quimioluminescente, em cada passe foi quantificada a atividade β-galactosidase a pH 6. Como controle utilizou-se cultivos de células do epitélio superficial ovariano das mesmas doadoras. A atividade enzimática foi também avaliada em fibroblastos previamente induzidos a senescência com peróxido de hidrogeno. Resultados: as leituras da atividade enzimática, analisada em conjunto com a capacidade replicativa, indicam que os cultivos de fibroblastos alcançaram o estado senescente para os passes 4-5, o que também ocorreu com as células epiteliais. Os fibroblastos induzidos a senescência mostraram valores variáveis de atividade enzimática. Conclusões:as semelhanças entre os fibroblastos e as células epiteliais em quanto ao inicio da senescência poderia estar relacionado com a transição epitélio-mesenquimática que tem sido descrita como fator de risco de câncer derivado do epitélio superficial ovariano. Valores baixos de atividade β-galactosidase poderiam sugerir que, em alguns casos, ocorreu inativação das vias de resposta ao estresse oxidativo.

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Our objective was to determine the presence of chromosomal abnormalities in primary cultures of ovarian surface epithelial cells in women of different ages with no history of cancer. Throughout conventional cytogenetic techniques, we analyzed chromosome spreads of cultured ovarian epithelial cells from 10 donors who were 50 or more years old (B) and 16 controls between 20 and 49 years old (A), belonging to the mestizo population in Bogota DC, Colombia. Of the 26 cultures that were analyzed in passage 1, 61.5% had an abnormal chromosome complement (62.5% in A, and 60% in B). Abnormalities included polyploidies, endoduplications and monosomies. Deletions in chromosomes 3 and 11 were found in just one metaphase. None of the samples showed weaknesses or breakpoints. After transforming and applying the exact student’s t-test for variance heterogeneity, we found significant differences in the frequency of metaphases, that were higher in A than in B (p=0.05), and in the frequency of polyploidies, which were higher in B than in A (p=0.044). Through the application of the Mann-Whitney test, we determined that the frequency of endoduplications was higher in A than in B (p=0.126), without reaching significant differences. There were no significant differences in the frequency of monosomies. The level of significance was set at p £ 0.05. Taking into account that polyploidization is a marker of chromosomal instability and that the risk of cancer arising from the ovarian surface epithelium augments substantially after menopause, the increase in the frequency of age-associated polyploidies could be used as a predictor of ovarian cancer in women from an ethnically homogeneous population as the mestizo one in Bogota DC.

El objetivo del presente trabajo fue determinar la presencia de anormalidades cromosómicas en cultivos primarios de células del epitelio superficial ovárico en mujeres de diferentes edades, sin antecedentes de cáncer. Mediante técnicas de citogenética convencional fueron analizados extendidos de células epiteliales ováricas histológicamente normales, provenientes de cultivos primarios de 10 donantes de 50 o más años (B) y de 16 donantes entre 20 y 49 años que se utilizaron como grupo control (A), pertenecientes a la población mestiza de Bogotá DC, Colombia. De 26 cultivos examinados en pase 1, 61,5% presentó complemento cromosómico anormal, 62,5% en A y 60% en B. Las anomalías numéricas halladas, todas en mosaico, incluyeron poliploidías, endoduplicaciones y monosomías. En una única célula en metafase de un cultivo, se presentaron deleciones en los cromosomas 3 y 11. Ninguna muestra presentó fragilidades o roturas. Previa aplicación de transformaciones, con la prueba exacta t-student para varianzas heterogéneas, se encontraron diferencias significativas en la frecuencia de células con metafase normal, mayor en A que en B (p=0,05) y en la de poliploidías, mayor en B que en A (p=0,044). Con la prueba exacta de Mann-Whitney se determinó que la frecuencia de endoduplicaciones en A fue mayor que en B (p=0,126), sin alcanzar diferencias significativas y que no hubo diferencias significativas en la frecuencia de monosomías. El nivel de significación fue p £ 0,05. Si se tiene en cuenta que la poliploidización es un marcador de inestabilidad cromosómica y, que además, el riesgo de aparición de cáncer derivado del epitelio superficial del ovario aumenta sustancialmente después de la menopausia, el incremento en la frecuencia de poliploidías asociado con la edad podría ser utilizado como predictor de cáncer ovárico en mujeres de una población étnicamente homogénea como la población mestiza de Bogotá DC.

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La actividad de la ß-galactosidasa refleja la tasa de envejecimiento celular in vitro. Mediante quimioluminiscencia se cuantificó dicha actividad a pH 6 en células epiteliales ováricas provenientes de 28 donantes sin antecedentes de cáncer. Las células fueron cultivadas en forma seriada hasta alcanzar el estado de detención permanente de crecimiento. Durante la fase de crecimiento exponencial, todos los cultivos mostraron un patrón semejante de crecimiento y una baja actividad ß-galactosidasa. Sin embargo, el inicio de la disminución de la capacidad replicativa que caracteriza el final de dicha fase, así como el inicio de la fase estacionaria o senescente presentaron un aumento significativo en la actividad enzimática. Nuestros resultados mostraron que la actividad ß-galactosidasa puede ser considerada como marcador de senescencia replicativa del epitelio superficial del ovario a pH 6.

ß-galactosidase activity reflects the rate of cellular aging in vitro. Such activity was quantified at pH 6 in ovarian epithelial cells from 28 donors without a history of cancer, by the chemoluminiscent method. The cells were serially cultured until they achieved the state of permanent growth arrest. During the exponential growth phase, all cultures showed a similar pattern of growth and low ß-galactosidase activity. However, both in the onset of decrease replicative activity, as well as in the onset of the stationary phase, there was a significant rise in the enzyme activity. Our results showed that ß-galactosidase activity can be considered as a replicative senescence marker of the ovarian surface epithelium at pH 6.

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Senescence was rendered a tumor suppressor mechanism based on the observation of its protective effect against cancer in young organisms under conditions of oncogene activation or inactivation of tumor suppressor genes. In addition to this beneficial effect, senescence has been deemed to have age-associated deleterious effects because, apparently, senescence not only recapitulates aging and therefore loss of function and tissue regeneration capacity, but can also induce preneoplastic changes in adjacent stromal cells, provoke degenerative diseases or induce the production of tumor cell growth promoting factors. For that reason, senescence has become an attractive therapeutic target against cancer. This paper reviews some of the latest findings on the role of senescence in the malignant progression and analyzes them in relation to the concept of antagonistic pleiotropism, as well as its possible use as a therapeutic target against cancer.

La relación entre senescencia y transformación maligna ha sido objeto de particular atención, debido a una aparente dualidad de funciones, en la que la senescencia participaría tanto en la inducción como en la inhibición de la malignidad. El objetivo del trabajo fue revisar algunos de los hallazgos más recientes sobre el papel de la senescencia en la progresión maligna y analizarlos a la luz del concepto de la pleiotropía antagónica y de su posible utilización como blanco terapéutico contra el cáncer. Se considera a la senescencia como un mecanismo supresor tumoral, debido al efecto protector contra el cáncer que ejerce en organismos jóvenes, en caso de activación de oncogenes o de inactivación de genes supresores tumorales. Además de este efecto beneficioso, se le han adjudicado efectos deletéreos asociados con la edad pues, en apariencia, la senescencia no sólo recapitula el envejecimiento y por tanto la pérdida de función y capacidad de regeneración tisular, sino también puede inducir cambios preneoplásicos en las células del estroma adyacente, provocar enfermedades degenerativas o inducir la secreción de factores promotores del crecimiento de células tumorales. La aparición de defectos en el programa de senescencia puede contribuir a la transformación tumoral, lo que la ha convertido en un atractivo blanco terapéutico contra el cáncer. El avance en el estudio de los aspectos biológicos de la senescencia proporcionará valiosa información para el desarrollo de nuevas estrategias terapéuticas que detengan la progresión tumoral.

Assuntos

RESUMO

Our objective was to determine the presence of chromosomal abnormalities in primary cultures of ovarian surface epithelial cells in women of different ages with no history of cancer. Throughout conventional cytogenetic techniques, we analyzed chromosome spreads of cultured ovarian epithelial cells from 10 donors who were 50 or more years old (B) and 16 controls between 20 and 49 years old (A), belonging to the mestizo population in Bogota DC, Colombia. Of the 26 cultures that were analyzed in passage 1, 61.5% had an abnormal chromosome complement (62.5% in A, and 60% in B). Abnormalities included polyploidies, endoduplications and monosomies. Deletions in chromosomes 3 and 11 were found in just one metaphase. None of the samples showed weaknesses or breakpoints. After transforming and applying the exact student's t-test for variance heterogeneity, we found significant differences in the frequency of metaphases, that were higher in A than in B (p=0.05), and in the frequency of polyploidies, which were higher in B than in A (p=0.044). Through the application of the Mann-Whitney test, we determined that the frequency of endoduplications was higher in A than in B (p=0.126), without reaching significant differences. There were no significant differences in the frequency of monosomies. The level of significance was set at p < or = 0.05. Taking into account that polyploidization is a marker of chromosomal instability and that the risk of cancer arising from the ovarian surface epithelium augments substantially after menopause, the increase in the frequency of age-associated polyploidies could be used as a predictor of ovarian cancer in women from an ethnically homogeneous population as the mestizo one in Bogota DC.

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RESUMO

Beta-galactosidase activity reflects the rate of cellular aging in vitro. Such activity was quantified at pH 6 in ovarian epithelial cells from 28 donors without a history of cancer, by the chemoluminiscent method. The cells were serially cultured until they achieved the state of permanent growth arrest. During the exponential growth phase, all cultures showed a similar pattern of growth and low beta-galactosidase activity. However, both in the onset of decrease replicative activity, as well as in the onset of the stationary phase, there was a significant rise in the enzyme activity. Our results showed that beta-galactosidase activity can be considered as a replicative senescence marker of the ovarian surface epithelium at pH 6.

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RESUMO

El epitelio superficial del ovario (ESO), tejido formado por una sola capa de células, está sujeto a una elevada tasa de renovación en el sitio de la ruptura provocada por la ovulación, lo que ha sido asociado con un mayor riesgo de desarrollar cáncer como consecuencia de la transformación maligna de sus células. El hallazgo de un 90% de tumores ováricos derivados del epitelio superficial, así como de mutaciones del gen p53 en la gran mayoría de ellos, constituyen la justificación para revisar la estructura y la histogénesis de dicho tejido con referencia a p53. Igualmente se consideran algunos aspectos relacionados con la estabilización de la proteína, su regulación, su participación en eventos claves como detención del ciclo celular, inducción de apoptosis, la etiología y patogénesis del cáncer ovárico epitelial y por último, algunos de los más recientes avances farmacogenéticos que utilizan a p53 como blanco terapéutico contra el cáncer.

Assuntos

RESUMO

El cáncer es el resultado de la acumulación de alteraciones en moléculas con importante función en procesos celulares como proliferación, apoptosis, muerte celular y reparación génica. Las moléculas, sustancias o procesos alterados pueden constituirse en marcadores o biomarcadores tumorales de gran utilidad clínica en el seguimiento de pacientes oncológicos ya que han demostrado ser idóneos para la valoración del tratamiento y su eficiencia. La determinación de biomarcadores tumorales no ha sido muy exitosa debido a la baja sensibilidad y especificidad de las técnicas usadas y al requerimiento de muestras biológicas en volúmenes grandes o de métodos invasivos para su recolección. Los marcadores tumorales séricos surgen, entonces, como una herramienta útil en la obtención de información sobre el estado de la enfermedad y constituye un reto científico mejorar su aplicabilidad en el diagnóstico temprano, pronóstico, seguimiento de la enfermedad y evaluación de la eficacia terapéutica.

Cancer is the result of the accumulation of changes in molecules with important functions in processes such as cell proliferation, apoptosis, cell death and gene repair. Molecules, substances or altered pathways constitute tumor markers or biomarkers useful in clinical monitoring of cancer patients, because they have demonstrated to be suitable for the valuation of the patient's treatment and it efficiency. Determination of tumor markers has not been very successful due to the low sensitivity and specificity of the techniques used and the requirement of large volumes of biological samples or the use of invasive methods for collecting them. The serum tumor markers arise, as a useful tool to obtain information about the disease progress and constitute as a scientific challenge to improve its applicability in early diagnosis, prognosis, monitoring of the disease and evaluation of therapeutic efficacy.

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