Modulación de la expresión del gen hmam en líneas celulares de cáncer de mama sometidas a tamoxifen y 17β-estradiol

La función de la proteína mamoglobina (MAM) no se conoce con claridad a la fecha, se cree que juega un papel en el metabolismo esteroideo debido a que forma un complejo hidrofóbico en forma de bolsillo con otra uteroglobulina la lipofilina B (LIPB), este complejo podría estar implicado en el trasporte de hormonas esteroideas como el estradiol y en este sentido estar asociado al análogo del estrógeno el Tamoxifen. Mediante ensayos in vitro utilizando líneas celulares de cáncer de mama (MCF-7, T47D, ZR75-1, BT474, JIMT-1) sometidas a tratamientos en tres tiempos con tamoxifen y 17B estradiol se investigó la posible modulación de la expresión de mamoglobina A y lipofilina B por estas sustancias. Nuestros hallazgos fueron que el tamoxifen ejerce una modulación negativa en líneas celulares RE+ HER- de los genes hMAM y LIPB y una regulación positiva en BT474 (RE+ HER+) de hMAM. Opuesto al tamoxifen el 17 B estradiol modula de forma positiva la expresión de hMAM en las líneas celulares con presencia de RE y HER2. Esto confirma que estos genes están regulados por las vías de señalización de los estrógenos y que estos genes varían su expresión en función de los RE y HER2.Abstract. The fuction of the mammaglobin protein (MAM) is not clearly know nowadays, it is thought that it plays a role in the esteroid metabolism because it forms a hydrophobic complex shaped as a pocket whit another uteroglobulin the lipophilin B (LIPB), this complex could be involved in the esteroid hormone transportation as the estradiol and in this way it is associated to the estrogen analogue, the Tamoxifen. By test in vitro, using cellular cell lines of breast cancer (MCF-7, T47D, ZR75-1, BT474 and JIMT-1) it was subject to treatments done three times with Tamoxifen an 17β estradiol. It was investigated the possible modulation of the expression of mammaglobin and Lipophilin B by this substances. Our findings were that the Tamoxifen has negative modulation cell lines ER+ HER- from the genes hMAM and LIPB and a positive regulation in BT474 (ER+ HER+) from hMAM. Opposite to Tamoxifen the 17β estradiol modulates in a positive way the expression of hMAM in the cell lines whit the presence of ER and HER. It supports that these genes are regulated by the signal pathways of estrogen and that these genes vary their expression in fuction of the ER and HER.Maestrí

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Regulation of Antitumor Immune Responses by Exosomes Derived from Tumor and Immune Cells

Exosomes are lipid membrane-enclosed vesicles released by all cell types that act at the paracrine or endocrine level to favor cell differentiation, tissue homeostasis, organ remodeling and immune regulation. Their biosynthesis begins with a cell membrane invagination which generates an early endosome that matures to a late endosome. By inward budding of the late endosome membrane, a multivesicular body (MVB) with intraluminal vesicles (ILVs) is generated. The fusion of MVBs with the plasma membrane releases ILVs into the extracellular space as exosomes, ranging in size from 30 to 100 nm in diameter. The bilipid exosome membrane is rich in cholesterol, ceramides and phosphatidylserine and can be loaded with DNA, RNA, microRNAs, proteins and lipids. It has been demonstrated that exosome secretion is a common mechanism used by the tumor to generate an immunosuppressive microenvironment that favors cancer development and progression, allowing tumor escape from immune control. Due to their ability to transport proteins, lipids and nucleic acids from the cell that gave rise to them, exosomes can be used as a source of biomarkers with great potential for clinical applications in diagnostic, prognostic or therapeutic areas. This article will review the latest research findings on exosomes and their contribution to cancer development

Characterizing the content of exosomes associated with tumors in a population of gastric cancer patients.

ilustraciones (algunas a color), diagramas, fotografíasA nivel mundial, uno de los tipos de cáncer con mayor incidencia y mortalidad es el cáncer gástrico, que ocupa el quinto lugar en incidencia con más de 1. 000.000 de casos nuevos en 2020, lo que correspondió al 5.6% del total de casos de cáncer a nivel mundial, y con una mortalidad que supera los 750.000 decesos, de acuerdo con lo reportado en Globocan 2020. El cáncer gástrico es 50% más común en hombres que en mujeres. Según Cancer Today de la Agencia Internacional para la investigación en cáncer (IARC), el cáncer gástrico es la principal causa de muerte por cáncer en hombres en Colombia, con aproximadamente 3.963 muertes y la quinta causa de muerte en mujeres con más de 2.488 muertes, por lo cual es considerado como un problema de salud pública. Su alta mortalidad es debida en parte, a la dificultad para realizar un diagnóstico oportuno, y aunque la prueba de oro para el diagnóstico de este cáncer es la endoscopia-biopsia, esta prueba no es costo-efectiva para ser implementada como prueba de tamizaje en países que están en vías de desarrollo. Los exosomas son vesículas de entre 30 y 100nm de diámetro, secretadas por las células cuya síntesis, en el sistema endosomal, es mediada por la formación de cuerpos multivesiculares (MVB) que se fusionan con la membrana celular para liberarlas al ambiente extracelular. Poseen una membrana bi-lipídica rica en colesterol, ceramidas, y residuos de fosfatidilserina; y transportan una amplia variedad de DNA, RNA, proteínas y lípidos que les confieren una gran variedad de funciones en diferentes escenarios, que abarcan desde el transporte de moléculas y la comunicación célula-célula a nivel local o sistémico, hasta la regulación inmunológica. Los exosomas derivados de células tumorales juegan un papel fundamental en el microambiente tumoral al favorecer la comunicación entre las células tumorales, o entre éstas y las células del sistema inmune. Se considera que su secreción es un mecanismo mediante el cual el tumor es capaz de favorecer su propio desarrollo al transportar moléculas moduladoras del sistema inmune tales como HLA-G, PD1, PD-L1, CTLA-4, oncoproteínas y factores de crecimiento. También se ha descrito su papel en la transferencia horizontal de diversos tipos de RNA capaces de incrementar la agresividad de las células tumorales. Dada la importancia de los exosomas en el desarrollo y progresión del cáncer gástrico, este estudio tuvo como objetivo identificar y caracterizar los contenidos biológicos de los exosomas asociados a tumor, con el fin de obtener información relevante acerca del papel de los exosomas en el desarrollo y establecimiento de la enfermedad. La investigación fue desarrollada en dos fases: inicialmente se realizó un estudio in-silico en el cual se ejecutó un metaanálisis con 7 bases de datos de miRNAs provenientes de exosomas aislados de diferentes tipos de cáncer, en búsqueda de un patrón molecular común a todos ellos. Posteriormente se desarrolló la fase experimental, en la cual se incluyeron exosomas aislados del plasma de 30 pacientes: 20 con cáncer gástrico y 10 con enfermedades gástricas benignas. La metodología empleada para desarrollar la etapa experimental incluyó un protocolo ajustado para la obtención de los exosomas a partir de plasma humano, su caracterización por microscopía electrónica de barrido, análisis de nano-partículas y detección de la expresión de proteínas propias de los exosomas. Una vez caracterizados los exosomas, se realizó la extracción de los miRNAs y las proteínas, y luego, mediante el uso de técnicas de nueva generación como RNA-seq y espectrometría de masas, se determinó su composición en cuanto a miRNAs y proteínas. Se identificó una firma de 9 miRNAs y 35 proteínas con expresión diferencial entre los pacientes con cáncer gástrico y aquellos con enfermedades gástricas benignas, asociadas con procesos biológicos y rutas metabólicas involucradas en la carcinogénesis. En cuanto a la caracterización a nivel de proteínas, se identificaron más de 700 proteínas en los exosomas de pacientes con cáncer gástrico y con enfermedades gástricas benignas. Se determino 5 proteínas con implicaciones en el desarrollo del cáncer y que pueden ser estudiadas con el fin de establecer su utilidad como biomarcadores. Los resultados aquí presentados pueden ser tomados como punto de partida para el descubrimiento de nuevos biomarcadores para el diagnóstico y seguimiento del cáncer gástrico a partir de exosomas aislados en biopsia liquida. (Texto tomado de la fuente)Gastric cancer is a prevalent and deadly type of cancer worldwide, ranking fifth in terms of incidence with over 1,000,000 new cases in 2020, accounting for 5.6% of total cancer cases globally. Furthermore, according to the Globocan 2020 report, the number of deaths resulting from the issue surpasses 750,000. Men are 50% more likely to develop gastric cancer than women. In Colombia, gastric cancer is the leading cause of cancer-related death among men, with approximately 3,963 deaths, and the fifth leading cause of death among women, with over 2,488 deaths. Consequently, it poses a significant public health concern. The high mortality is partly attributed to challenges in achieving timely diagnosis, with endoscopy-biopsy being the gold standard but not cost-effective for screening in developing countries. Exosomes, small vesicles ranging from 30 to 100 nm in diameter, are secreted by cells through the endosomal system. They are formed through the fusion of multivesicular bodies (MVBs) with the cell membrane, releasing them into the extracellular environment. Exosomes possess a cholesterol-rich bilipid membrane containing ceramides and phosphatidylserine residues. They serve as vehicles for transporting a diverse range of DNA, RNA, proteins, and lipids, enabling various functions in different contexts. These functions include molecular transportation, local or systemic cell-to-cell communication, and immunoregulation. Exosomes derived from tumor cells play a crucial role in the tumor microenvironment by facilitating communication among tumor cells and between tumor cells and immune cells. Their secretion serves as a mechanism through which tumors promote their own development by transporting immune system-modulating molecules, such as HLA-G, PD1, PD-L1, CTLA-4, oncoproteins, and growth factors. Additionally, they have been implicated in the horizontal transfer of various types of RNA, which can enhance the aggressiveness of tumor cells. Given the significance of exosomes in the development and progression of gastric cancer, this study aimed to identify and characterize the biological contents of tumor-associated exosomes to gain relevant insights into their role in disease development and establishment. The research comprised two phases. Firstly, an in-silico study involved a meta-analysis of miRNAs from exosomes isolated from different types of cancer using seven databases to identify common molecular patterns. Subsequently, the experimental phase encompassed the isolation of exosomes from the plasma of 30 patients, including 20 with gastric cancer and 10 with benign gastric diseases. The experimental methodology entailed a customized protocol for exosome isolation from human plasma, followed by their characterization using scanning electron microscopy, nanoparticle analysis, and detection of exosome-specific protein expression. After characterizing the exosomes, miRNAs and proteins were extracted, and their composition was determined using advanced techniques such as RNA-seq and mass spectrometry. The protein characterization identified over 700 proteins in the exosomes, 35 of them exhibiting differential expression between patients with gastric cancer and those with benign gastric. Five proteins with implications in cancer development were identified, warranting further investigation to evaluate their potential as biomarkers. These molecules are associated with biological processes and metabolic pathways involved in carcinogenesis. On the other hand, 156 miRNAs were identified in the exosomes, 9 of them differentially expressed between gastric cancer patients and controls. The findings presented in this study serve as a promising foundation for the discovery of novel biomarkers for the diagnosis and monitoring of gastric cancer using exosomes isolated from liquid biopsies.DoctoradoDoctor en Oncologí

Study on the relationship between good project management practices recommended by the Project Management Institute (PMI) and infrastructure development in Latin America

Este estudio tuvo como objetivo identificar la relación entre el nivel de implementación de buenas prácticas de gestión de proyectos recomendadas por el PMI utilizadas en cada país de AL y los resultados de los indicadores de desarrollo publicados en el informe del año 2019 del Infrascope para AL. En este caso se buscó realizar un análisis de la influencia que tenía la implementación de estas buenas prácticas sobre la calificación obtenida para cada uno de los países que hicieron parte del presente estudio. Partiendo de un análisis literario y de la aplicación de encuestas piloto estructuramos un cuestionario que nos permitiera contrastar los resultados con los indicadores de desarrollo del Infrascope, se divulgó este en los Capítulos del PMI ubicados en AL. Aplicando métodos estadísticos a los resultados obtenidos pudimos establecer esta relación. Lo anterior, sirvió de base para elaborar diferentes modelos explicativos de regresión múltiple y confirmar los resultados obtenidos en las matrices de relación, comparando y comprobando la influencia de cada una de las variables independientes (Buenas prácticas) y como estas influían sobre el comportamiento de las variables dependientes (Indicadores del Infrascope). Finalmente, se concluyó que el conocimiento en buenas prácticas es general, pero al analizar su implantación se encuentran vacíos debido al desinterés estatal como privado en su adopción. Existe ausencia de las organizaciones gubernamentales en el fomento de la implementación de buenas, la cultura y madurez de las organizaciones ha dificultado la capacitación de sus colaboradores ya que no lo consideran relevante.This study’s main objective was to identify the relationship between the level of implementation of good project management practices recommended by the PMI used in each Latin American country and the results of the development indicators published in the 2019 Infrascope report for LA. In this case, an analysis of the influence that the implementation of these good practices was done, it was about the qualification obtained for each of the countries that were part of this study. Furthermore, starting from a literary analysis and the application of surveys, we structured a questionnaire that would allow us to compare the results with the development indicators of the Infrascope, this was disclosed in the PMI Chapters located in AL. Applying statistical methods to the results obtained, we were able to establish this relationship. It worked as the basis for developing different explanatory models of multiple regression and confirming the results obtained in the relationship matrices, comparing and verifying the influence of each of the independent variables (Good practices) and how these influenced the behavior of the dependent variables (Infrascope Indicators). Finally, it was concluded that the knowledge in good practices is general, but when analyzing its implementation, there are voids due to state and private disinterest in its adoption. There is an absence of government organizations in promoting the implementation of good practices, the culture and maturity of the organizations have made it difficult to train their collaborators since they do not consider it relevant.Magíster en Ingeniería CivilMaestrí

Regulation of Antitumor Immune Responses by Exosomes Derived from Tumor and Immune Cells

Exosomes are lipid membrane-enclosed vesicles released by all cell types that act at the paracrine or endocrine level to favor cell differentiation, tissue homeostasis, organ remodeling and immune regulation. Their biosynthesis begins with a cell membrane invagination which generates an early endosome that matures to a late endosome. By inward budding of the late endosome membrane, a multivesicular body (MVB) with intraluminal vesicles (ILVs) is generated. The fusion of MVBs with the plasma membrane releases ILVs into the extracellular space as exosomes, ranging in size from 30 to 100 nm in diameter. The bilipid exosome membrane is rich in cholesterol, ceramides and phosphatidylserine and can be loaded with DNA, RNA, microRNAs, proteins and lipids. It has been demonstrated that exosome secretion is a common mechanism used by the tumor to generate an immunosuppressive microenvironment that favors cancer development and progression, allowing tumor escape from immune control. Due to their ability to transport proteins, lipids and nucleic acids from the cell that gave rise to them, exosomes can be used as a source of biomarkers with great potential for clinical applications in diagnostic, prognostic or therapeutic areas. This article will review the latest research findings on exosomes and their contribution to cancer development

Identification of Two Exosomal miRNAs in Circulating Blood of Cancer Patients by Using Integrative Transcriptome and Network Analysis

Exosomes carry molecules of great biological and clinical interest, such as miRNAs. The contents of exosomes vary between healthy controls and cancer patients. Therefore, miRNAs and other molecules transported in exosomes are considered a potential source of diagnostic and prognostic biomarkers in cancer. Many miRNAs have been detected in recent years. Consequently, a substantial amount of miRNA-related data comparing patients and healthy individuals is available, which contributes to a better understanding of the initiation, development, malignancy, and metastasis of cancer using non-invasive sampling procedures. However, a re-analysis of available ncRNA data is rare. This study used available data about miRNAs in exosomes comparing healthy individuals and cancer patients to identify possible global changes related to the presence of cancer. A robust transcriptomic analysis identified two common miRNAs (miR-495-3p and miR-543) deregulated in five cancer datasets. They had already been implicated in different cancers but not reported in exosomes circulating in blood. The study also examined their target genes and the implications of these genes for functional processes

Positioning and Web Traffic of Colombian Banking Establishments

The use of digital technologies has become one factor that significantly impacts business results in the financial industry. This study seeks to characterize the positioning and web traffic of Colombian banking establishments through analysis of the classification of their website, taking as reference the metrics related to web traffic and the attractiveness of the content and relevance for users as the bounce rate. The study presents a quantitative approach, non-experimental design, and descriptive scope. With a sample of 28 banking establishments, it is intended to contribute to the body of literature on bank marketing based on a systematic analysis of indicators. The findings of the study made it possible to elucidate that a good part of the websites of the banking establishments is well positioned, in addition to presenting low bounce rates. It is also possible to show that a significant portion of this traffic comes from individuals between 18 and 34 years of age and of the female gender. Likewise, traffic to the website is derived to a greater extent from direct access to the establishment’s portal or search engines

Sentiment Analysis on Twitter-Based Teleworking in a Post-Pandemic COVID-19 Context

The implementation of the telework model has become popular globally due to the COVID-19 pandemic. However, this new model of work organization generates conflicting opinions regarding the positive and negative effects that its implementation can bring to organizations. In this study, sentiment analysis of Twitter-based teleworking in a post-pandemic COVID-19 context was conducted. A set of Twitter conversations is examined by applying text mining and opinion analysis techniques. The results show the prevalence of positive sentiments regarding telework. In addition, opinions are generally associated with confidence, anticipation, and joy. According to the results, it is recommended to consider telework as an opportunity to improve worker well-being. However, it is important to consider some factors, such as the sector to which the company belongs, the characteristics of the job, and the working conditions

Primary Breast Angiosarcoma: Comparative Transcriptome Analysis

Primary breast angiosarcoma, with de novo appearance and not associated with exposure to radiation or lymphedema, is a rare pathology representing less than 0.05% of the neoplasms related to this organ. The pathology is characterized by its aggressiveness, poor prognosis, and difficulties in its differential diagnosis. This article reports the case of a 55-year-old white woman with no family history of cancer, with a rapidly growing mass in the left mammary gland that ulcerates and bleeds. It is confirmed as primary breast angiosarcoma by immunostaining in the tumor tissue for CD31, CD34, and FLI-1. In addition, a sample of neoplastic and healthy tissues is collected from the patient for RNA sequencing; the results are contrasted with a tissue sample from a patient with Luminal A subtype of breast cancer, as well as data from other cases of angiosarcoma available in public databases. These findings revealed a genetic profile associated with the immune and inflammatory response in the patient’s sample when compared to available angiosarcoma data; these molecular patterns are consistent with other recent studies. Due to the rarity of the disease, the studies carried out on each patient contribute to the expanding knowledge of the etiology and molecular pathways that are still partially known and continue to be the subject of research. Aside from a comparative transcriptome study, this article aims to provide an update on the state of knowledge about this disease