Browsing by Author "Ili, Carmen"

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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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    Detection and genotyping of human papillomavirus virus (HPV): a comparative analysis of clinical performance in cervical and urine samples in Chilean women
    (2018) Buchegger, Kurt; Viscarra, Tamara; Andana, Alejandra; Ili, Carmen; Lopez, Jaime; Zanella, Louise; Ines Carmona-Lopez, Maria; Jose Fernandez, Juan; Cartas Espinel, Irene; Sanchez, Raul; Carlos Roa, Juan; Brebi, Priscilla
    Human papillomavirus (HPV) is the most common sexually transmitted infectious agent and is the main cause of cervical cancer (CC). In Chile, CC is the second leading cause of death by cancer in women aged 20-44 years, four times higher than in developed countries. Currently, the detection of HPV infection using a cervical brush is recommended; however, this is an invasive procedure that many women try to avoid. The aim of this study was to evaluate the clinical performance of a self-collected, urine-based HPV detection method using conventional PCR followed by a reverse line blot. A PCR-based HPV genotyping was performed on 190 paired cervical and urine samples from gynecological exams at public health centers in the Araucania Region, Chile. HPV DNA detection and genotyping were performed by PCR and reverse line blot assay. Carcinogenic HPV types were present in 64.7% and 65.8% of the cervical and urine samples; the infection rates of HPV16 were 34.7% and 33.2%, respectively. The overall percent agreement between carcinogenic HPV detection in cervical and urine samples was 73.7%, with a moderate concordance rate of carcinogenic HPV detection (kappa = 0.42). Clinical sensitivities for cervical and urine-based sampling methods to diagnose cervical intraepithelial neoplasia 2/3 (CIN2/3) by histology were 93.4% and 90.2%, respectively. These results suggest that both cervical brush and urine-based sampling show a good clinical performance in the detection of HPV infection. The urine-based sampling method represents a valuable alternative with a great impact on public health, allowing increased cervical cancer screening coverage among women who do not undergo pelvic examinations.
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    Epigallocatechin Gallate Enhances MAL-PDT Cytotoxic Effect on PDT-Resistant Skin Cancer Squamous Cells
    (2020) Leon, Daniela; Buchegger, Kurt; Silva, Ramon; Riquelme, Ismael; Viscarra, Tamara; Mora-Lagos, Barbara; Zanella, Louise; Schafer, Fabiola; Kurachi, Cristina; Roa, Juan Carlos; Ili, Carmen; Brebi, Priscilla
    Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.
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    Frecuencia de la infección por Chlamydia trachomatis en un grupo de mujeres de la Región de la Araucanía, Chile
    (2013) Silva, Ramón; León, Daniela; Viscarra, Támara; Ili, Carmen; Roa Strauch, Juan Carlos Enrique; Sánchez, Raúl; Guzmán, Pablo; Brebi, Priscilla
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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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    Reprimo, a Potential p53-Dependent Tumor Suppressor Gene, Is Frequently Hypermethylated in Estrogen Receptor α-Positive Breast Cancer
    (2017) Buchegger, Kurt; Riquelme, Ismael; Viscarra, Tamara; Ili, Carmen; Brebi, Priscilla; Hui-Ming Huang, Tim; Roa Strauch, Juan Carlos Enrique