Browsing by Author "Leal, Pamela"

Now showing 1 - 12 of 12
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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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    Cellular FLICE-like Inhibitory Protein Long Form (c-FLIPL) Overexpression is Related to Cervical Cancer Progression
    (2013) Ili, Carmen Gloria; Brebi, Priscilla; Tapia, Oscar; Sandoval, Alejandra; López, Jaime; García Muñoz, Patricia; Leal, Pamela; Sidransky, David; Guerrero Preston, Rafael; Roa Strauch, Juan Carlos Enrique
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    Connective Tissue Growth Factor Immunohistochemical Expression Is Associated With Gallbladder Cancer Progression
    (2013) García Cañete, Patricia; Leal, Pamela; Álvarez, Héctor; Brebi, Priscilla; Ili, Carmen Gloria; Tapia, Oscar; Roa Strauch, Juan Carlos Enrique
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    Effects of c-FLIPL Knockdown in Cervical Uterine Carcinoma Cell Lines
    (2015) Ili, Carmen G.; Brebi, Priscilla; Garcia, Patricia; Leal, Pamela; Lopez, Jaime; Tapia, Oscar; Letelier, Pablo; Weber, Helga; Castillo, Jonathan; Roa, Juan C.
    Overexpression of Short and Raji variants of Cellular FLICE-like inhibitory protein (c-FLIP) is capable of inhibiting apoptosis, while the function of the Long isoform depends of c-FLIPL concentration in cells. The aim of this study was to determine the effects of c-FLIPL knockdown in cervical cell lines. SiHa, C-4I and C-33A cervical cancer cell lines were analyzed. c-FLIPL level expression was determined by quantitative real-time PCR and western blotting. c-FLIPL was transiently downregulated by siRNA. The effects of knockdown of c-FLIPL on cell viability, proliferation and apoptosis were assessed by comparing with scrambled siRNA-transfected cells. SiHa and C-4I c-FLIPL knockdown cells showed increased viability compared with scrambled siRNA-transfected cells (P<0.05), while C-33A cells did not show significant differences. Ki-67 and PCNA immunocytochemistry was performed to evaluate proliferation on these cervical cancer cell lines. SiHa cells with c-FLIPL knockdown showed elevated expression of Ki-67 protein compared with their scrambled counterparts (P<0.0001), while C-33A c-FLIPL knockdown cells showed a significantly lower in PCNA expression (P<0.01) compared with control. All three c-FLIP-transfected cell lines showed a higher level of apoptosis compared with their scrambled controls. Our results suggest that c-FLIPL could have effects in proliferation and apoptosis in cervical cancer cell lines.
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    Effects of c-FLIPL Knockdown in Cervical Uterine Carcinoma Cell Lines
    (2015) Ili, Carmen 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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    Immunohistochemical Expression of Vascular Endothelial Growth Factor A in Advanced Gallbladder Carcinoma
    (2014) Letelier, Pablo; García Cañete, Patricia; Leal, Pamela; Ili, Carmen; Buchegger, Kurt; Riquelme, Ismael; Sandoval, Alejandra; Tapia, Oscar; 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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    The ERK/MAPK pathway is overexpressed and activated in gallbladder cancer
    (2017) Buchegger, Kurt; Silva, Ramón; López, Jaime; Lli, Carmen; Araya, Juan Carlos; Leal, Pamela; Brebi, Priscilla; Riquelme, Ismael; Roa Strauch, Juan Carlos Enrique
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    The Gene Expression Status of the PI3K/AKT/mTOR Pathway in Gastric Cancer Tissues and Cell Lines
    (2016) Riquelme, Ismael; Tapia, Óscar; Espinoza, Jaime A.; Leal, Pamela; Buchegger, Kurt; Sandoval, Alejandra; Bizama, Carolina; Araya, Juan Carlos; Peek, Richard M.; 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