Browsing by Author "Roa, Juan C."

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    A snapshot of cancer in Chile II: an update on research, strategies and analytical frameworks for equity, innovation and national development
    (2024) Vacarezza, Cristóbal; Araneda, Julieta; González Hevia, Pamela Andrea; Arteaga, Oscar; Marcelain, Katherine; Castellon, Enrique A.; Periera, Ana; Khoury, Maroun; Müller, Bettina; Lecaros, Juan A.; Salas, Sofia P.; Riquelme Pérez, Arnoldo; Corvalán R., Alejandro; de la Jara, Jorge J.; Ferreccio, Catterina; Goic B., Carolina; Nervi Nattero, Bruno; Roa, Juan C.; Owen, Gareth Ivor
    Abstract Introduction Chile has achieved developed nation status and boasts a life expectancy of 81 + years; however, the healthcare and research systems are unprepared for the social and economic burden of cancer. One decade ago, the authors put forward a comprehensive analysis of cancer infrastructure, together with a series of suggestions on research orientated political policy. Objectives Provide an update and comment on policy, infrastructure, gender equality, stakeholder participation and new challenges in national oncology. Assess the funding and distribution of cancer investigation. Present actions for the development of oncology research, innovation and patient care. Methods Triangulating objective system metrics of economic, epidemiological, private and public sector resources together with policy analysis, we assessed cancer burden, infrastructure, and investigation. We analyzed governmental and private-sector cancer databases, complemented by interviews with cancer stakeholders. Results Governmental policy and patient advocacy have led to the recognition of cancer burden, a cancer law, and a national cancer plan. Cancer has become the leading cause of death in Chile (59,876 cases and 31,440 cancer deaths in 2022), yet only 0.36% gross domestic product (GDP) is directed to research and development. Inequalities in treatment regimens persist. Prevention policy has lowered tobacco consumption, sugar intake via soft drinks and offered a high coverage of HPV vaccines. A high-quality cancer research community is expanding, and internationally sponsored clinical oncology trials are increasing. Conclusions The cancer law has facilitated advancement in policy. Prevention policies have impacted tobacco and sugar intake, while gender equality and care inequality have entered the public forum. Cancer research is stagnated by the lack of investment. Implementation of a cancer registry and biobanking, reinforcement of prevention strategies, development of human resources, promotion of clinical trial infrastructure and investment in new technologies must be placed as a priority to permit advancements in innovation and equitable cancer care.
  • No Thumbnail Available
    Item
    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.
  • No Thumbnail Available
    Item
    Female offspring gestated in hypothyroxinemia and infected with human Metapneumovirus (hMPV) suffer a more severe infection and have a higher number of activated CD8+ T lymphocytes
    (2022) Funes, Samanta C.; Rios, Mariana; Fernandez-Fierro, Ayleen; Rivera-Perez, Daniela; Soto, Jorge A.; Valbuena, Jose R.; Altamirano-Lagos, Maria J.; Gomez-Santander, Felipe; Jara, Evelyn L.; Zoroquiain, Pablo; Roa, Juan C.; Kalergis, Alexis M.; Riedel, Claudia A.
    Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71(+) and FasL(+)) CD8(+) T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T-4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.
  • No Thumbnail Available
    Item
    Gallbladder cancer
    (2022) Roa, Juan C.; Garcia, Patricia; Kapoor, Vinay K.; Maithel, Shishir K.; Javle, Milind; Koshiol, Jill
    Gallbladder cancer is the most common cancer of the biliary tract and often has a very poor prognosis. This Primer by Roa and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of gallbladder cancer, and discusses patient quality of life and open research questions for this disease.
  • Thumbnail Image
    Item
    Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer
    (AMER ASSOC CANCER RESEARCH, 2008) Alvarez, Hector; Corvalan, Alejandro; Roa, Juan C.; Argani, Pedram; Murillo, Francisco; Edwards, Jennifer; Beaty, Robert; Feldmann, Georg; Hong, Seung Mo; Mullendore, Michael; Roa, Ivan; Ibanez, Luis; Pimente, Fernando; Diaz, Alfonso; Riggins, Gregory J.; Maitra, Anirban
    Background: Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist.