Browsing by Author "Weber, Helga"

Now showing 1 - 7 of 7
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    A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance
    (2023) Vergara-Gómez, Luis; Bizama, Carolina; Zhong, Jun; Buchegger, Kurt; Suárez Vega, Felipe Ignacio; Rosa, Lorena; Ili, Carmen; Weber, Helga; Obreque, Javiera; Espinoza, Karena; Repetto, Gabriela; Roa, Juan C.; Leal, Pamela; García, PatriciaVergara-Gómez, Luis; Bizama, Carolina; Zhong, Jun; Buchegger, Kurt; Suárez Vega, Felipe Ignacio; Rosa, Lorena; Ili, Carmen; Weber, Helga; Obreque, Javiera; Espinoza, Karena; Repetto, Gabriela; Roa, Juan C.; Leal, Pamela; García, Patricia
    Treatment 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.
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    Advances towards the use of gastrointestinal tumor patient-derived organoids as a therapeutic decision-making tool
    (2023) Obreque Castro, Javiera Constanza; Vergara Gómez, Luis; Venegas Labra, Nicolás; Weber, Helga; Owen, Gareth Ivor; Pérez Moreno, Pablo; Leal, Pamela; Roa Strauch, Juan Carlos Enrique; Bizama, Carolina
    In December 2022 the US Food and Drug Administration (FDA) removed the requirement that drugs in development must undergo animal testing before clinical evaluation, a declaration that now demands the establishment and verification of ex vivo preclinical models that closely represent tumor complexity and that can predict therapeutic response. Fortunately, the emergence of patient-derived organoid (PDOs) culture has enabled the ex vivo mimicking of the pathophysiology of human tumors with the reassembly of tissue-specific features. These features include histopathological variability, molecular expression profiles, genetic and cellular heterogeneity of parental tissue, and furthermore growing evidence suggests the ability to predict patient therapeutic response. Concentrating on the highly lethal and heterogeneous gastrointestinal (GI) tumors, herein we present the state-of-the-art and the current methodology of PDOs. We highlight the potential additions, improvements and testing required to allow the ex vivo of study the tumor microenvironment, as well as offering commentary on the predictive value of clinical response to treatments such as chemotherapy and immunotherapy.
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    AKT/mTOR substrate p70S6k is frequently phosphorylated in gallbladder cancer tissue and cell lines
    (2013) Leal, Pamela; García Cañete, Patricia; Sandoval, Alejandra; Buchegger, Kurt; Weber, Helga; Tapia, Oscar; Roa Strauch, Juan Carlos Enrique
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    Effects of c-FLIPL Knockdown in Cervical Uterine Carcinoma Cell Lines
    (2015) Ili, Caremen G.; Brebi, Priscilla; García Cañete, Patricia; Leal, Pamela; Lopez, Jaime; Tapia, Oscar; Letelier, Pablo; Weber, Helga; Castillo, Jonathan; Roa Strauch, Juan Carlos Enrique
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    Rapamycin and WYE-354 suppress human gallbladder cancer xenografts in mice
    (2015) Weber, Helga; Leal, Pamela; Stein, Stefan; Kunkel, Hana; García Cañete, Patricia; Bizama, Carolina; Espinoza, Jaime A.; Riquelme, Ismael; Nervi Nattero, Bruno; Araya, Juan C.; Grez, Manuel; Roa Strauch, Juan Carlos Enrique
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    Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer
    (2017) Weber, Helga; Valbuena Mora, José Rafael; Barbhuiya, Mustafa A.; Stein, Stefan; Kunkel, Hana; García Muñoz, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime A.; Kurtz, Stephen E.; Tyner, Jeffrey W.; Calderon, Juan Francisco; Corvalán R., Alejandro; Grez, Manuel; Pandey, Akhilesh; Leal Rojas, Pamela; Roa Strauch, Juan Carlos Enrique
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    The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance
    (2014) Tapia, Oscar; Riquelme, Oscar Ismael; Leal, Pamela; Sandoval, Alejandra; Aedo, Susana; Weber, Helga; Letelier, Pablo; Bellolio, Enrique; Villaseca, Miguel; García Cañete, Patricia; Roa Strauch, Juan Carlos Enrique