Browsing by Author "Buchegger, Kurt"
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- ItemA 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, 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.
- ItemAKT/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
- ItemEvaluation of DNA methylation in promoter regions of SFRP4 and ZAR1 in urine and plasma of women with cervical lesions(2017) Hoffstetter, Rene; Riquelme, Ismael; Andana, Alejandra; Ili, Carmen G.; Buchegger, Kurt; Vargas, Hernan; Brebi, Priscilla; Roa Strauch, Juan Carlos Enrique
- ItemExploring the Genetic Diversity of Epstein–Barr Virus among Patients with Gastric Cancer in Southern Chile(2023) Reyes, María Elena; Zanella, Louise; Riquelme, Ismael; Buchegger, Kurt; Mora-Lagos, Bárbara; Guzmán, Pablo; García Cañete, Patricia; Roa Strauch, Juan Carlos Enrique; Gloria Ili, Carmen; Brebi, PriscillaThe Epstein–Barr virus (EBV) has been associated with gastric cancer (GC), one of the deadliest malignancies in Chile and the world. Little is known about Chilean EBV strains. This study aims to investigate the frequency and genetic diversity of EBV in GC in patients in southern Chile. To evaluate the prevalence of EBV in GC patients from the Chilean population, we studied 54 GC samples using the gold standard detection method of EBV-encoded small RNA (EBER). The EBV-positive samples were subjected to amplification and sequencing of the Epstein–Barr virus nuclear protein 3A (EBNA3A) gene to evaluate the genetic diversity of EBV strains circulating in southern Chile. In total, 22.2% of the GC samples were EBV-positive and significantly associated with diffuse-type histology (p = 0.003). Phylogenetic analyses identified EBV-1 and EBV-2 in the GC samples, showing genetic diversity among Chilean isolates. This work provides important information for an epidemiological follow-up of the different EBV subtypes that may cause GC in southern Chile.
- ItemImmunohistochemical 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
- ItemReprimo, a Potential p53-Dependent Tumor Suppressor Gene, Is Frequently Hypermethylated in Estrogen Receptor Alpha-Positive Breast Cancer(2017) Buchegger, Kurt; Riquelme, Ismael; Viscarra, Tamara; Ili, Carmen; Brebi, Priscilla; Hui-Ming Huang, Tim; Roa Strauch, Juan Carlos Enrique
- ItemThe 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
- ItemThe 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