Browsing by Author "Wichmann Pérez, Ignacio Alberto"

Now showing 1 - 15 of 15
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    Cyclooxygenase-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.
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    Differentially Expressed Oncogenic Pathways Are Associated With Ethnicity Differences in Gastric Cancer
    (2016) Corvalán R., Alejandro; Wichmann Pérez, Ignacio Alberto; Artigas, Rocío.
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    Evaluation of the chemopreventive potentials of ezetimibe and aspirin in a novel mouse model of gallbladder preneoplasia
    (2020) Rosa, L.; Muñoz Durango, Natalia; García Cañete, Patricia; Bizama, Carolina; González Briones, Ximena María; Wichmann Pérez, Ignacio Alberto; Arrese, Marco; Ferreccio Readi, Catterina; Kalergis Parra, Alexis Mikes; Miquel P., Juan Francisco; Roa Strauch, Juan Carlos Enrique; Lobos-Gonzalez, L.; Gomez, N.; Saavedra, N.; Guevara, F.; Villegas, J.; Espinoza, J. A.
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    Evolutionary history of the reprimo tumor suppressor gene family in vertebrates with a description of a new reprimo gene lineage
    (2016) Wichmann Pérez, Ignacio Alberto; Corvalán R., Alejandro; Amigo Donoso, Julio; Owen, Gareth Ivor; Zavala, Kattina.; Hoffmann, Federico G.; Vandewege, Michael W.; Opazo, Juan C.
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    Expression of RPRM/rprm in the olfactory system of embryonic zebrafish (Danio rerio)
    (2018) Stanic, Karen; Quiroz Vallverdu, Alonso Ingmar; Lemus, Carmen G.; Wichmann Pérez, Ignacio Alberto; Corvalán R., Alejandro; Owen, Gareth Ivor; Opazo, Juan C.; Concha, Miguel L.; Amigo Donoso, Julio
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    Identification 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 Medicina
    El 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.
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    Inverse 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.
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    Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities
    (2024) Durán-Jara, Eduardo; Campo, Matías del ; Gutiérrez, Valentina; Wichmann Pérez, Ignacio Alberto; Trigo, César; Ezquer, Marcelo; Lobos-González, Lorena
    Background: Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted glycoprotein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. Results: We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV-MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. Conclusions: As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.
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    Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers
    (2015) Sandoval-Bórquez, Alejandra.; Wichmann Pérez, Ignacio Alberto; Saavedra, Kathleen.; García Bloj, Benjamín.; Fry, Jacqueline.; Corvalán R., Alejandro; Carrasco-Avino, Gonzalo.
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    Reprimo tissue-specific expression pattern is conserved between zebrafish and human
    (2017) Figueroa, Ricardo J.; Wichmann Pérez, Ignacio Alberto; Owen, Gareth Ivor; Corvalán R., Alejandro; Amigo Donoso, Julio; Carrasco-Avino, Gonzalo.; Lange, Martin.; Siekmann, Arndt F.; Opazo, Juan C.
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    Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers
    (2018) Polakovicova, I.; Jerez, S.; Wichmann Pérez, Ignacio Alberto; Sandoval Borquez, A.; Carrascow, N.; Corvalán R., Alejandro
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    Survivin and Reprimo Expression Are Mutually Exclusive in Gastric Cancer
    (2016) Corvalán R., Alejandro; Wichmann Pérez, Ignacio Alberto; Cerda, Paulina.; Rodríguez, Andrés.; Quest, Andrew.
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    The Reprimo gene family member, reprimo-like (rprml), is required for blood development in embryonic zebrafish
    (2019) Stanic, Karen; Reig, German; Figueroa, Ricardo J.; Retamal, PedroA.; Wichmann Pérez, Ignacio Alberto; Opazo, JuanC.; Owen, Gareth Ivor; Corvalán R., Alejandro; Concha, Miguel L.; Amigo, Julio
    The Reprimo gene family comprises a group of sing le-exon genes for which their physiological function remains poorly understood. Heretofore, mammalian Reprimo (RPRM) has been described as a putative p53-dependent tumor suppressor gene that functions at the G2/M cell cycle checkpoint. Another family member, Reprimo-like (RPRML), has not yet an established role in physiology or pathology. Importantly, RPRML expression pattern is conserved between zebrafish and human species. Here, using CRISPR-Cas9 and antisense morpholino oligonucleotides, we disrupt the expression of rprml in zebrafish and demonstrate that its loss leads to impaired definitive hematopoiesis. The formation of hemangioblasts and the primitive wave of hematopoiesis occur normally in absence of rprml Later in development there is a significant reduction in erythroid-myeloid precursors (EMP) at the posterior blood island (PBI) and a significant decline of definitive hematopoietic stem/progenitor cells (HSPCs). Furthermore, loss of rprml also increases the activity of caspase-3 in endothelial cells within the caudal hematopoietic tissue (CHT), the first perivascular niche where HSPCs reside during zebrafish embryonic development. Herein, we report an essential role for rprml during hematovascular development in zebrafish embryos, specifically during the definitive waves of hematopoiesis, indicating for the first time a physiological role for the rprml gene.
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    The Reprimo Gene Family: A Novel Gene Lineage in Gastric Cancer with Tumor Suppressive Properties
    (2018) Amigo Donoso, Julio; Wichmann Pérez, Ignacio Alberto; Jorquera Cifuentes, Roddy Alberto.; García Bloj, Benjamín.; Alarcón Alarcón, María Alejandra; Owen, Gareth Ivor; Corvalán R., Alejandro; Opazo, Juan C.
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    The reprimo-like gene is an epigenetic-mediated tumor suppressor and a candidate biomarker for the non-invasive detection of gastric cancer
    (2020) Alarcón Alarcón, María Alejandra; Olivares, W.; Córdova Delgado, M.; Wichmann Pérez, Ignacio Alberto; Amigo, Julio; Norero Muñoz, Enrique; Riquelme Pérez, Arnoldo; Garrido S., Marcelo; Owen, Gareth Ivor; Corvalán R., Alejandro; Muñoz-Medel, M.; Mayo, T. de; Carrasco-Aviño, G.; Landeros, N.; Villarroel Espíndola, F.