Browsing by Author "Vergara, Luis"
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Publication A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance(2023) Vergara, Luis; Bizama, Carolina; Zhong, Jun; Buchegger, Kurt; Suárez, Felipe; Rosa, Lorena; Ili, Carmen; Weber, Helga; Obreque, Javiera; Espinoza, Karena; Repetto, Gabriela; Roa, Juan; Leal, Pamela; García, PatriciaTreatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but the effectiveness of any regimen is limited and recurrence rates are high. Here, we investigated the molecular mechanisms of acquired resistance in GBC through the development and characterization of two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR). Morphological changes, cross-resistance, and migratory/invasive capabilities were evaluated. Then, microarray-based transcriptome profiling and quantitative SILAC-based phosphotyrosine proteomic analyses were performed to identify biological processes and signaling pathways dysregulated in gemcitabine-resistant GBC cells. The transcriptome profiling of parental and gemcitabine-resistant cells revealed the dysregulation of protein-coding genes that promote the enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, the phosphoproteomics analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as ABL1, PDGFRA, and LYN, which could be novel therapeutic targets in GBC. Accordingly, NOZ GemR showed increased sensitivity toward the multikinase inhibitor dasatinib compared to parental cells. Our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant GBC cells, which greatly expands our understanding of the underlying mechanisms of acquired drug resistance in GBC.Publication LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells(2024) Perez Moreno, Pablo; Riquelme, Ismael; Bizama, Carolina; Vergara, Luis; Tapia, Julio; Brebi, Priscilla; García, Patricia; Roa, JuanPublication Novel sponge formulation of mesenchymal stem cell secretome and hyaluronic acid: a safe and effective topical therapy for Psoriasis vulgaris(2025) Elgueta, Estefanía; Prieto, Catalina P.; Hartmann, Dan; Carrillo, Daniela; Edwards, Natalie; Martínez, Constanza; Pérez, Dan; Casas, Bárbara; Vergara, Luis; Valenzuela, Fernando; Catalán, Verónica; Lattus, José; Oyarzun-Ampuero, Felipe; Palma, VerónicaBackground Psoriasis vulgaris is the most common form of psoriasis, yet current treatments often lead to significant side effects, resulting in a high rate of therapy desertion. Here, we explored a novel therapeutic approach using the secretome from Wharton Jelly-derived mesenchymal stem cells, biologically stabilized and enhanced with hyaluronic acid (HA), its presentation is an easy-to-apply topical sponge. This formulation had previously demonstrated efficacy in vitro and in experimental psoriasis mouse models. Methods In vitro characterization studies included dynamic light scattering, nanoparticle tracking analysis, optical/electronic microscopy, microbiological experiments, and angiogenic capacity (HUVEC cells). In vivo studies included angiogenic capacity in chicken embryo chorioallantoic membrane (CAM), safety (hypersensitive and healthy volunteers), and efficacy (double-blinded and randomized patients). Results We demonstrated the presence of spherical exosomes (164 ± 87 nm, PDI of 0.38, and 1.5 × 10⁷ particles/mL) within the selected secretomes, which exhibited significant proangiogenic activity in HUVEC cells and in a CAM assay. The secretome-containing sponges displayed distinct physicochemical properties, such as the absence of nitrogen and reduced carbon and oxygen content, resulting in a more cross-linked material with thinner fibers. These characteristics extended the dispersion time in aqueous media. Microbiological testing confirmed sterility in the packed, ready-to-use secretome-HA sponges after 3 months of storage. To assess safety, we selected doses (based on total protein content) that were applied to three patients with atopic dermatitis (42 μg of protein, patch test, 5 days) and four healthy volunteers (210 μg, 15 days) with no observed adverse topical or systemic effects. In a 30-day.