Browsing by Author "Morales, Fernanda"

Now showing 1 - 5 of 5
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    Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis
    (2024) Tapia, Camilo; Valenzuela, Guillermo; González, Evelin; Maureira, Ignacio; Toro, Jessica; Freire, Matías; Sepúlveda, Gonzalo; Ampuero, Diego; Blanco, Alejandro; Gallegos, Iván; Morales, Fernanda; Erices, José; Barajas, Olga; Ahumada, Mónica; Contreras, Héctor; González, Jaime; Armisén, Ricardo; Marcelain, Katherine
    Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.
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    Immune-related IncRNA LINC00944 responds to variations in ADAR1 levels and it is associated with breast cancer prognosis
    (Elsevier Inc., 2020) Blanco, Alejandro; Morales, Fernanda; Marcelain, Katherine; Harismendy, Olivier; Sjöberg, Marcela; Armisén, Ricardo; de Santiago, Pamela
    Aims: Breast cancer is one of the leading causes of woman deaths worldwide, being a major public health problem. It has been reported that the expression of the RNA-editing enzyme Adenosine Deaminase Acting on RNAs 1 (ADAR1) is upregulated in breast cancer, predicting poor prognosis in patients. A few reports in literature examine ADAR1 and long non-coding RNAs (lncRNAs) interplay in cancer and suggest key roles in cancer-related pathways. This study aimed to investigate whether ADAR1 could alter the expression levels of lncRNAs and explore how those changes are related to breast cancer biology. Main methods: ADAR1 overexpression and knockdown studies were performed in breast cancer cell lines to analyze the effects over lncRNAs expression. Guilt-by-Association correlation analysis of the TCGA-BRCA cohort was performed to predict the function of the lncRNA LINC00944. Key findings: Here, we show that LINC00944 is responsive to ADAR1 up- and downregulation in breast cancer cells. We found that LINC00944 expression has a strong relationship with immune signaling pathways. Further assessment of the TCGA-BRCA cohort showed that LINC00944 expression was positively correlated to tumor-infiltrating T lymphocytes and pro-apoptotic markers. Moreover, we found that LINC00944 expression was correlated to the age at diagnosis, tumor size, and estrogen and progesterone receptor expression. Finally, we showed that the low expression of LINC00944 is correlated to poor prognosis in breast cancer patients. Significance: Our study provides further evidence of the effect of ADAR1 over lncRNA expression levels, and on the participation of LINC00944 in breast cancer, suggesting to further investigate its potential role as prognostic biomarker.
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    Increase in ADAR1p110 activates the canonical Wnt signaling pathway associated with aggressive phenotype in triple negative breast cancer cells
    (2022) Morales, Fernanda; Pérez, Paola; Tapia, Julio; Lobos-González, Lorena; Herranz, José Manuel; Guevara, Francisca; Rojas, Pamela; Palacios, Esteban; Andaur, Rodrigo; Sagredo, Eduardo; Marcelain, Katherine; Armisén, Ricardo
    Triple-negative breast cancer (TNBC) represents a challenge in the search for new therapeutic targets. TNBCs are aggressive and generate resistance to chemotherapy. Tumors of TNBC patients with poor prognosis present a high level of adenosine deaminase acting on RNA1 (ADAR1). We explore the connection of ADAR1 with the canonical Wnt signaling pathway and the effect of modulation of its expression in TNBC. Expression data from cell line sequencing (DepMap) and TCGA samples were downloaded and analyzed. We lentivirally generated an MDA-MB-231 breast cancer cell line that overexpress (OE) ADAR1p110 or an ADAR knockdown. Abundance of different proteins related to Wnt/β-catenin pathway and activity of nuclear β-catenin were analyzed by Western blot and luciferase TOP/FOP reporter assay, respectively. Cell invasion was analyzed by matrigel assay. In mice, we study the behavior of tumors generated from ADAR1p110 (OE) cells and tumor vascularization immunostaining were analyzed. ADAR1 connects to the canonical Wnt pathway in TNBC. ADAR1p110 overexpression decreased GSK-3β, while increasing active β-catenin. It also increased the activity of nuclear β-catenin and increased its target levels. ADAR1 knockdown has the opposite effect. MDA-MB-231 ADAR1 (OE) cells showed increased capacity of invasion. Subsequently, we observed that tumors derived from ADAR1p110 (OE) cells showed increased invasion towards the epithelium, and increased levels of Survivin and CD-31 expressed in vascular endothelial cells. These results indicate that ADAR1 overexpression alters the expression of some key components of the canonical Wnt pathway, favoring invasion and neovascularization, possibly through activation of the β-catenin, which suggests an unknown role of ADAR1p110 in aggressiveness of TNBC tumors.
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    La salud mental, dependencia y adicción en jóvenes con videojuegos en América
    (Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, 2020) Morales, Fernanda
    El ser humano lleva a cabo muchas actividades al día,y diversas herramientas digitales ayudan en estas tareas. Dentro de estas funcionalidades, los videojuegos eventualmente son capaces de retrasar las actividades hasta el punto de generar un olvido de las responsabilidades diarias, lo que, en algunos casos, se produce al padecer algún grado de dependencia o adicción al juego. A pesar de que el individuo incurra en un uso excesivo, este no siempre es causado por iniciativa propia, sino que el entorno en el que se desenvuelve,también repercute en dicha decisión. Es por esto que la presente reflexión tiene por objetivo analizar los factores sociales que inciden en la adicción a los videojuegos.
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    Percepción de los adultos mayores del Hogar Italiano sobre su proceso de envejecimiento
    (Universidad del Desarrollo. Facultad de Medicina. Escuela de Enfermería, 2018) Díaz, Catalina; Henríquez, Valentina; Morales, Fernanda; Navarrete, Cecilia; Rousseau, Pía; Díaz, Catalina; Henríquez, Valentina; Morales, Fernanda; Navarrete, Cecilia; Rousseau, Pía; Astorga, Sofía; Astorga, Sofía
    El resultado principal del estudio es que la percepción de los adultos mayores participantes sobre su proceso de envejecimiento tiende a ser positiva, ya que concuerdan en que la palabra “envejecer” es un proceso propio del ser humano y de su ciclo vital, sin darle una connotación negativa. Considerando la escasa información que existe en el país con respecto a la vivencia del adulto mayor sobre su proceso de envejecimiento en un ELEAM, es que con la información obtenida, en conjunto con los objetivos sanitarios, se busca aportar a los cuidados integrales de esta población, con el propósito de contribuir plenamente al desarrollo de un envejecimiento activo a través de la entrega de información para facilitar la creación de estrategias de cuidados específicos y fomento de la formación y/o mantención de redes de apoyo. El presente documento se organiza en base a un marco teórico, donde se presentan los principales contenidos de la investigación basados en búsquedas bibliográficas realizadas en base de datos científicas (ver Anexo 1) y los modelos teóricos, seguidos de la metodología del estudio y posterior presentación y análisis de los resultados obtenidos, que permiten finalmente elaborar la discusión y conclusiones

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