Browsing by Author "Colombo, Alicia"

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    ALS-linked protein disulfide isomerase variants cause motor dysfunction
    (2016) Woehlbier, Ute; Colombo, Alicia; Saaranen, Mirva J.; Pérez, Viviana; Fernandez, Sara; Henny V., Pablo
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    Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome
    (FRONTIERS MEDIA SA, 2023) Sanhueza, Sergio; Vidal, Mabel A.; Hernandez, Mauricio A.; Henriquez-Beltran, Mario E.; Cabrera, Camilo; Quiroga, Romina; Antilef, Barbara E.; Aguilar, Kevin P.; Castillo, Daniela A.; Llerena, Faryd J.; Figueroa, Marco Fraga; Nazal, Mauricio; Castro, Eritson; Lagos, Paola; Moreno, Alexa; Lastra, Jaime J.; Gajardo, Jorge; Garces, Pamela; Riffo, Benilde; Buchert, Jorge; Sanhueza, Rocio; Ormazaba, Valeska; Saldivia, Pablo; Vargas, Cristian; Nourdin, Guillermo; Koch, Elard; Zuniga, Felipe A.; Lamperti, Liliana; Bustos, Paula; Guzman-Gutierrez, Enrique; Tapia, Claudio A.; Ferrada, Luciano; Cerda, Gustavo; Woehlbier, Ute; Riquelme, Marcelo; Yuseff, Maria Isabel; Ramirez, Braulio A. Munoz; Lombardi, Giovanna; De Gonzalo-Calvo, David; Salomon, Carlos; Verdugo, Ricardo A.; Quinones, Luis A.; Colombo, Alicia; Barria, Maria I.; Labarca, Gonzalo; Nova-Lamperti, Estefania
    Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced Fc gamma RIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced Fc gamma RIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.
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    Daam1a mediates asymmetric habenular morphogenesis by regulating dendritic and axonal outgrowth
    (2013) Colombo, Alicia; Palma, Karina; Armijo, Lorena; Mione, Marina; Signore, Iskra A.; Morales, Camila; Guerrero, Néstor; Meynard, Margarita M.; Pérez, Ramón; Suazo, José; Marcelain, Katherine; Briones, Luis; Häertel, Steffen; Wilson, Stephen W.; Concha, Miguel L.
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    Gene-gene interaction for nonsyndromic cleft lip with or without cleft palate in chilean case-parent trios
    (2018) Suazo, José; Santos Martín, José Luis; Colombo, Alicia; Pardo, Rosa
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    Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women
    (2022) de Almeida, Liz Maria; Cortés Arancibia, Sandra; Vilensky, Marta; Valenzuela, Olivia; Cortes-Sanabria, Laura; de Souza, Mirian; Alonso Barbeito, Rafael; Abdelhay, Eliana; Artagaveytia, Nora; Daneri-Navarro, Adrian; Llera, Andrea S.; Muller, Bettina; Podhajcer, Osvaldo L.; Velazquez, Carlos; Alcoba, Elsa; Alonso, Isabel; Bravo, Alicia, I; Camejo, Natalia; Maria Carraro, Dirce; Castro, Monica; Cataldi, Sandra; Cayota, Alfonso; Cerda, Mauricio; Colombo, Alicia; Crocamo, Susanne; Del Toro-Arreola, Alicia; Delgadillo-Cristerna, Raul; Delgado, Lucia; Breitenbach, Marisa Dreyer; Fernandez, Elmer; Fernandez, Jorge; Fernandez, Wanda; Franco-Topete, Ramon A.; Gaete, Fancy; Gomez, Jorge; Gonzalez-Ramirez, Leivy P.; Guerrero, Marisol; Gutierrez-Rubio, Susan A.; Jalfin, Beatriz; Lopez-Vazquez, Alejandra; Loria, Dora; Miguez, Silvia; Moran-Mendoza, Andres de J.; Morgan-Villela, Gilberto; Mussetti, Carina; Nagai, Maria Aparecida; Oceguera-Villanueva, Antonio; Reis, Rui M.; Retamales, Javier; Rodriguez, Robinson; Rosales, Cristina; Salas-Gonzalez, Efrain; Segovia, Laura; Sendoya, Juan M.; Silva-Garcia, Aida A.; Vina, Stella; Zagame, Livia; Jones, Beth; Szklo, Moyses
    Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status not less than or equal to 1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (>= 60 years) (1.84) compared with younger (<= 40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.
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    The Ski Protein is Involved in the Transformation Pathway of Aurora Kinase A
    (WILEY, 2016) Rivas, Solange; Armisen, Ricardo; Rojas, Diego A.; Maldonado, Edio; Huerta, Hernan; Tapia, Julio C.; Espinoza, Jaime; Colombo, Alicia; Michea, Luis; Hayman, Michael J.; Marcelain, Katherine
    Oncogenic kinase Aurora A (AURKA) has been found to be overexpresed in several tumors including colorectal, breast, and hematological cancers. Overexpression of AURKA induces centrosome amplification and aneuploidy and it is related with cancer progression and poor prognosis. Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life. Reduced levels of Ski resulted in centrosomes amplification and multipolar spindles formation, same as AURKA overexpressing cells. Importantly, overexpression of Ski wild type, but not S326D and S383D mutants inhibited centrosome amplification and cellular transformation induced by AURKA. Altogether, these results suggest that the Ski protein is a target in the transformation pathway mediated by the AURKA oncogene. (C) 2015 Wiley Periodicals, Inc.
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    Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America
    (2021) Salvo, Mauricio; Gonzalez-Feliu, Evelin; Toro, Jessica; Gallegos, Ivan; Maureira, Ignacio; Miranda-Gonzalez, Nicolas; Barajas, Olga; Bustamante, Eva; Ahumada, Monica; Colombo, Alicia; Armisen, Ricardo; Villaman, Camilo; Ibanez, Carolina; Bravo, Maria Loreto; Sanhueza, Veronica; Spencer, M. Loreto; de Toro, Gonzalo; Morales, Erik; Bizama, Carolina; Garcia, Patricia; Carrasco, Ana Maria; Gutierrez, Lorena; Bermejo, Justo Lorenzo; Verdugo, Ricardo A.; Marcelain, Katherine
    Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.