Browsing by Author "Owen, Gareth Ivor"
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- Item2-Methoxyestradiol and Disorders of Female Reproductive Tissues(2014) Pinto, M.; Medina, R.; Owen, Gareth Ivor
- Item2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells(2010) Quezada, M.; Diaz, J.; Henriquez, S.; Bravo Castillo, María Loreto; Aranda, E.; Oliva, B.; Villalón, Manuel J.; Kato Cardemil, Sumie Rode; Cuello F., Mauricio; Brosens, J. J.; Lange, C. A.; Owen, Gareth Ivor2-Methoxyestradiol (2ME) is an endogenous metabolite of 17β-estradiol with antiangiogenic and antitumor properties, although its mechanisms of action remain unclear. Progestins in hormone replacement therapy increase the risk of breast cancer. Progesteron
- Item2-Methoxyestradiol mediates apoptosis through caspase-dependent and independent mechanisms in ovarian cancer cells but not in normal counterparts(2008) Kato Cardemil, Sumie Rode; Sadarangani, Anil; Lange Smith, María Soledad; Delpiano, Ana M.; Vargas, Macarena; Brañes, Jorge; Carvajal Cabrera, Jorge Andrés; Lipkowitz, Stanley; Owen, Gareth Ivor; Cuello Fredes, Mauricio Arturo
- ItemA case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer(2021) Cordova-Delgado, Miguel; Bravo Castillo, María Loreto; Cumsille, Elisa; Hill Machado, Charlotte Nicole; Pinto, Mauricio P.; Miquel P., Juan Francisco; Rodríguez-Fernández, María; Corvalán R., Alejandro; Garrido S., Marcelo; Owen, Gareth IvorBackground: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3–4 toxicity. Methods: Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. Results; Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. Conclusion: Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.
- ItemA Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability(2020) Pinto Paganini, Mauricio Arturo; Bravo Castillo, Maria Loreto; Sánchez Rojel, César Giovanni; Acevedo, Francisco; Mondaca Contreras, Sebastián Patricio; Ibañez, Carolina; Galindo A., Héctor; Madrid Arenas, Jorge; Nervi Nattero, Bruno; Peña Durán, José Esteban; Torres Montes, Paula Javiera; Owen, Gareth Ivor; Corvalán R., Alejandro; Garrido S., Marcelo; Córdova Delgado, M.; Retamal, I. N.; Muñoz Medel, M.; Durán, D.; Villanueva, F.; Koch, E.; Armisen, R.
- ItemA semi-quantitative assay to screen for angiogenic compounds and compounds with angiogenic potential using the EA.hy926 endothelial cell line(2009) Aranda Jaque, Evelyn Jacqueline.; Owen, Gareth Ivor
- ItemAdvances 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, CarolinaIn 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.
- ItemAngiogenesis inhibitors in early development for gastric cancer(2017) Pinto, Mauricio P.; Owen, Gareth Ivor; Retamal, Ignacio; Garrido Salvo, Marcelo
- ItemAntiangiogenic, antimigratory and antiinflammatory effects of 2-methoxyestradiol in zebrafish larvae(2013) Quezada, Marisol; Alvarez, Marjorie; Peña, Oscar A.; Henríquez, Soledad; D' Alencon, Claudia A.; Lange, Soledad; Oliva, Barbara; Owen, Gareth Ivor; Allende, Miguel L.
- ItemBreaking through an epigenetic wall Re-activation of Oct4 by KRAB-containing designer zinc finger transcription factors(2013) Juárez Moreno, Karla; Erices, Rafaela; Beltrán, Adriana S.; Stolzenburg, Sabine; Cuello F., Mauricio; Owen, Gareth Ivor; Qian, Haili; Blancafort, Pilar
- ItemCancer's new Achilles'hell(2017) Owen, Gareth Ivor
- ItemCharacterization and phenotypic variation with passage number of cultured human endometrial adenocarcinoma cells(2008) Kato Cardemil, Sumie Rode; Villalón, Manuel J.; Cuello F., Mauricio; Owen, Gareth Ivor; Espinoza, Natalia; Lange, Soledad
- ItemChilean Gastric Cancer Task Force : a study protocol to obtain a clinical and molecular classification of a cohort of gastric cancer patients(2018) Owen, Gareth Ivor; Pinto, Mauricio P.; Retamal, Ignacio N.; Fernández, María F.; Cisternas, Betzabe; Mondaca Contreras, Sebastián Patricio; Sánchez Rojel, César Giovanni; Galindo A., Héctor; Nervi, Bruno; Ibáñez Cáceres, Carolina; Acevedo Claros, Francisco Nicolás; Madrid Arenas, Jorge; Peña, José; Bravo Castillo, María Loreto; Maturana, María, José; Córdova Delgado, Miguel; Romero, Diego; De la Jara, Nathaly; Torres Montes, Paula Javiera; Rodríguez Fernández, María; Espinoza Sepúlveda, Manuel Antonio; Balmaceda, Carlos; Freire, Matías; Gárate Calderón, Valentina; Crovari Eulufi, Fernando; Jiménez Fonseca, Paula; Carmona Bayonas, Alberto; Zwenger, Ariel; Armisen, Ricardo; Corválan, Alejandro H.; Garrido Salvo, Marcelo; Owen, Gareth Ivor; Pinto, Mauricio P.; Retamal, Ignacio N.; Fernández, María F.; Cisternas, Betzabe; Mondaca, Sebastián; Sánchez Rojel, César Giovanni; Galindo Aranibar, Héctor Gonzalo; Nervi, Bruno; Ibáñez Cáceres, Carolina; Acevedo Claros, Francisco Nicolás; Madrid, Jorge; Peña, José; Bravo, María, Loreto; Maturana, María, José; Córdova Delgado, Miguel; Romero, Diego; De la Jara, Nathaly; Torres, Javiera; Rodríguez Fernández, María; Espinoza Sepúlveda, Manuel Antonio; Balmaceda, Carlos; Freire, Matías; Gárate Calderón, Valentina; Crovari Eulufi, Fernando; Jiménez Fonseca, Paula; Carmona Bayonas, Alberto; Zwenger, Ariel; Armisen, Ricardo; Corválan, Alejandro H.; Garrido, Marcelo
- ItemChilean Registry for Neuroendocrine Tumors: A Latin American Perspective(2019) Pinto, Mauricio P.; Muñoz Medel, Matías; Carrillo, Diego; Retamal, Ignacio N.; Bravo Castillo, María Loreto; Nervi Nattero, Bruno; Sánchez Rojel, César Giovanni; Galindo A., Héctor; Ibáñez Cáceres, Carolina; Peña Durán, José Esteban; Madrid Arenas, Jorge; Valenzuela, Yasna; Balmaceda, Carlos; Briones, Juan; Torres Montes, Paula Javiera; Nilo, Flavia; Guarda Vega, Francisco; Quintana, Juan Carlos; Orellana, Pilar; Mondaca Contreras, Sebastián Patricio; Acevedo Claros, Francisco Nicolás; Vicentini, Daniel; Córdova Delgado, Miguel; Owen, Gareth Ivor; Garrido Salvo, Marcelo
- ItemCoagulation factor Xa promotes metastasis through endothelial cell activation(2019) Arce Arata, Maximiliano Amadeo; Owen, Gareth Ivor; Pontificia Universidad Católica de Chile. Facultad de Ciencias BiológicasDiversos estudios han demostrado una alta asociación entre hipercoagulabilidad sanguínea y la progresión del cáncer. La principal consecuencia de esta asociación es el desarrollo de cuadros de trombosis venosa, la cual es la segunda causa de muerte en pacientes oncológicos. Sin embargo, se desconocen ciertos mecanismos asociados al efecto de la vía de coagulación en diversos aspectos relacionados a la progresión del cáncer. Por lo tanto, analizamos el efecto del factor de coagulación Xa (FXa), una proteína central de la vía de coagulación, sobre el crecimiento tumoral y en la metástasis experimental de células de cáncer. El tratamiento intravenoso con FXa aumentó el crecimiento tumoral y la metástasis de células de melanoma murino (B16F10) al hígado, riñón y ganglios linfáticos. Tras la administración concomitante del anticoagulante anti-FXa Dalteparina, la metástasis pulmonar se redujo significativamente y no se observó metástasis en otros órganos. FXa no alteró directamente la proliferación, migración o invasión de células cancerosas in vitro. Por otro lado, FXa aumentó la formación de fibras de estrés, promoviendo así la disrupción de la VEcadherina en la membrana y en consecuencia un aumento en la permeabilidad endotelial. Adicionalmente, células endoteliales tratadas con FXa mostraron un aumento en las moléculas de adhesión ICAM-1 y VCAM-1, lo cual promovió la adhesión de células B16F10. Un análisis realizado mediante un Microarray demostró que células endoteliales tratadas con FXa expresaron mayores niveles de transcritos inflamatorios en comparación al control, lo cual se relacionó con un incremento en la infiltración de células inmunes en los pulmones de ratones tratados con FXa. En conjunto, nuestros resultados sugieren que FXa incrementa la metástasis de células B16F10 a través de la activación de células endoteliales, lo cual apoya el concepto de que el sistema de coagulación no es simplemente un espectador en el proceso de metástasis del cáncer.
- ItemConcanavalin-A Induces Granulosa Cell Death and Inhibits FSH-Mediated Follicular Growth and Ovarian Maturation in Female Rats(2013) Velásquez Opazo, Ethel Virginia; Ríos Raggio, Mariana; Ortíz Scarlazetta, María Elena; Lizama, Carlos; Orge, Felipe; Oliva, Barbara; Orellana Walden, Renán Felipe; Villalón, Manuel J.; Moreno Mauro, Ricardo D.; Owen, Gareth Ivor; Núñez, Elizabeth; Abramovich, Dalhia; Tesone, Marta, Rokka, Anne; Corthals, Garry; Croxatto A., Horacio; Parborell, Fernanda
- ItemConflicts of CpG density and DNA methylation are proximally and distally involved in gene regulation in human and mouse tissues(2018) Li, Zhiguang; Chen, Fushun; Zhang, Qingzheng; Deng, Xiaodi; Zhang, Xia; Chen, Chengjun; Lv, Dekang; Li, Yulong; Li, Dan; Owen, Gareth Ivor; Zhang, Yu; Li, Peiying; Diao, Yunpeng; Kang, Lan; Chen, Jun; Li, Zhiguang
- ItemCorrection to : MicroRNA‑335‑5p is a potential suppressor of metastasis and invasion in gastric cancer(2021) Sandoval Bórquez, Alejandra; Polakovicova, Iva; Carrasco Véliz, Nicolás; Lobos González, Lorena; Riquelme, Ismael; Carrasco Avino, Gonzalo; Bizama, Carolina; Norero Muñoz, Enrique; Owen, Gareth Ivor; Roa Strauch, Juan Carlos Enrique; Corvalán R., AlejandroAn amendment to this paper has been published and can be accessed via the original article.
- ItemDifferent effects of progesterone and estradiol on chimeric and wild type aldosterone synthase in vitro(2013) Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Allende, Fidel; Campino Johnson, María del Carmen; Valdivia, Carolina.; Tapia Castillo, Alejandra.; Owen, Gareth Ivor; Solari Gajardo, Sandra; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos; Ogishima, Tadashi.; Mukai, Kuniaki.Abstract Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone action, which could be involved in protecting pregnant women with FH-1 against hypertension. In vitro, both enzymes showed comparable kinetic parameters, but ASWT was more strongly inhibited than ASCE. This study implicates a new role for progesterone in the regulation of aldosterone levels that could contribute, along with other factors, to the maintenance of an adequate aldosterone-progesterone balance in pregnancy.Abstract Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone action, which could be involved in protecting pregnant women with FH-1 against hypertension. In vitro, both enzymes showed comparable kinetic parameters, but ASWT was more strongly inhibited than ASCE. This study implicates a new role for progesterone in the regulation of aldosterone levels that could contribute, along with other factors, to the maintenance of an adequate aldosterone-progesterone balance in pregnancy.
- ItemDifferential Regulation of Glucose Transporter Expression by Estrogen and Progesterone in Ishikawa Endometrial Cancer Cells(2004) Medina, R.; Owen, Gareth Ivor