Browsing by Author "Fernández, Elmer A."
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- ItemCyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer(2023) Gómez-Valenzuela, Fernán; Wichmann Pérez, Ignacio Alberto; Suárez, Felipe; Kato Cardemil, Sumie Rode; Ossandón, Enrique; Hermoso, Marcela; Fernández, Elmer A.; Cuello, Mauricio A.Chronic inflammation influences the tumor immune microenvironment (TIME) in high-grade serous ovarian cancer (HGSOC). Specifically, cyclooxygenase-2 (COX-2) overexpression promotes cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) expression. Notably, elevated COX-2 levels in the TIME have been associated with reduced response to anti-CTLA-4 immunotherapy. However, the precise impact of COX-2, encoded by PTGS2, on the immune profile remains unknown. To address this, we performed an integrated bioinformatics analysis using data from the HGSOC cohorts (TCGA-OV, n = 368; Australian cohort AOCS, n = 80; GSE26193, n = 62; and GSE30161, n = 45). Employing Gene Set Variation Analysis (GSVA), MIXTURE and Ecotyper cell deconvolution algorithms, we concluded that COX-2 was linked to immune cell ecosystems associated with shorter survival, cell dysfunction and lower NK cell effector cytotoxicity capacity. Next, we validated these results by characterizing circulating NK cells from HGSOC patients through flow cytometry and cytotoxic assays while undergoing COX-2 and CTLA-4 blockade. The blockade of COX-2 improved the cytotoxic capacity of NK cells against HGSOC cell lines. Our findings underscore the relevance of COX-2 in shaping the TIME and suggest its potential as a prognostic indicator and therapeutic target. Increased COX-2 expression may hamper the effectivity of immunotherapies that require NK cell effector function. These results provide a foundation for experimental validation and clinical trials investigating combined therapies targeting COX-2 and CTLA-4 in HGSOC.
- ItemIdentification of long noncoding RNAs in competing endogenous RNA networks through out the gastric precancerous cascade(2020) Wichmann Pérez, Ignacio Alberto; Corvalán R., Alejandro; Fernández, Elmer A.; Pontificia Universidad Católica de Chile. Escuela de MedicinaEl cáncer gástrico es una de las causas principales de muerte por cáncer en Chile y el mundo, debido principalmente a la ausencia de test de tamizaje capaces de detectar a pacientes en cáncer incipiente o en riesgo de desarrollar la enfermedad. En este contexto, es particularmente importante comprender la biología que antecede a la aparición de cáncer invasor ya que puede proveer información biológica relevante para la detección temprana de la enfermedad. Mediante la integración de múltiples estrategias bioinformáticas y el empleo de datos públicos, identificamos un grupo de RNAs largos no codificantes que aumentan en estadios previos a la aparición de cáncer gástrico y que contribuyen a la progresión de esta enfermedad mediante un mecanismo conocido como redes de competencia endógena de RNAs.
- ItemInverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer(2018) Cerda, Paulina.; Wichmann Pérez, Ignacio Alberto; Rodríguez, Andrés.; Contreras-Reyes, Daniel.; Corvalán R., Alejandro; Valenzuela Valderrama, Manuel Alejandro.; Fernández, Elmer A.; Carrasco-Avino, Gonzalo.; Quest, Andrew.