Browsing by Author "Corvalán R., Alejandro"
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- 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 Novel Role for Helicobacter pylori Gamma-Glutamyltranspeptidase in Regulating Autophagy and Bacterial Internalization in Human Gastric Cells(2019) Bravo, J.; Diaz, P.; Corvalán R., Alejandro; Quest, A.F.G.
- ItemA 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 IvorAbstract 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.
- ItemA snapshot of cancer in Chile: analytical frameworks for developing a cancer policy(2015) Jiménez de la Jara, Jorge; Bastías, Gabriel; Ferreccio Readi, Catterina; Moscoso, Cristián; Sagués, Sofía; Cid Pedraza, Camilo; Bronstein, Eduardo; Herrera Riquelme, Cristian Alberto; Nervi, Bruno; Corvalán R., Alejandro; Jiménez de la Jara, Jorge; Bastías, Gabriel; Ferreccio Readi, Catterina; Moscoso, Cristián; Sagués, Sofía; Cid Pedraza, Camilo; Bronstein, Eduardo; Herrera Riquelme, Cristian Alberto; Nervi, Bruno; Corvalán R., Alejandro
- ItemAngiotensin-(1-9) prevents cardiomyocyte hypertrophy by controlling mitochondrial dynamics via miR-129-3p/PKIA pathway(2020) Sotomayor-Flores, C.; Rivera-Mejias, P.; Vasquez-Trincado, C.; Lopez-Crisosto, C.; Morales, P. E.; Pennanen, C.; Polakovicova, Iva; Roa Strauch, Juan Carlos Enrique; Ocaranza, María Paz; Corvalán R., Alejandro; Aliaga-Tobar, V.; Garcia, L.; Rothermel, B. A.; Maracaja-Coutinho, V.; Ho-Xuan, H.; Meister, G.; Chiong, M.; Parra, V.; Lavandero, S.
- ItemBaseline assessment of prevalence and geographical distribution of HPV types in Chile using self-collected vaginal samples(2008) Ferreccio Readi, Catterina; Corvalán R., Alejandro; Margozzini Maira, Paula; Viviani García, Paola; González, Claudia; Aguilera, Ximena; Gravitt, Patti EAbstract Background Chile has broad variations in weather, economics and population from the far desert north (Region 1) to the cold, icy south (Region 12). A home-based self-collected vaginal sampling was nested in the 2003 Chilean population-based health survey in order to explore the possibility of a type-specific geographical variation for human papillomavirus Methods The population was a national probability sample of people 17 years of age and over. Consenting women provided self-collected cervicovaginal swabs in universal collection media (UCM). DNA was extracted and typed to 37 HPV genotypes using PGMY consensus PCR and line blot assay. Weighted prevalence rates and adjusted OR were calculated. Results Of the 1,883 women participating in the health survey, 1,219 (64.7%) provided a cervicovaginal sample and in 1,110 (56.2% of participants and 66.5% of those eligible) the samples were adequate for analysis. Refusal rate was 16.9%. HPV prevalence was 29.2% (15.1% high-risk HPV and 14.1% low-risk HPV). Predominant high-risk types were HPV 16, 52, 51, 56 and 58. Predominant low-risk HPVs were HPV 84, CP6108, 62, 53 and 61. High-risk and low-risk HPV rates were inversely correlated between the regions. High-risk HPV prevalence was highest among the youngest women, whereas low-risk HPV increased slightly with age. Conclusion Self-obtained vaginal sampling is adequate for monitoring HPV in the community, for identifying high-risk areas, and for surveying the long term impact of interventions.
- 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 Array CGH profiles within hereditary breast cancer tumors associated to BRCA1 expression and overall survival(2016) Álvarez Aguilera, Carolina Soledad.; Tapia Espinoza, Teresa Marloren; Solís, Luisa.; Corvalán R., Alejandro; Camus Appuhn, Mauricio Gonzalo; Carvallo de Saint Quentin, Pilar; Aravena, Andrés.; Rozenblum, Ester.; Álvarez, Manuel.; Munroe, David.; Maass, Alejandro.Abstract Background Array CGH analysis of breast tumors has contributed to the identification of different genomic profiles in these tumors. Loss of DNA repair by BRCA1 functional deficiency in breast cancer has been proposed as a relevant contribution to breast cancer progression for tumors with no germline mutation. Identifying the genomic alterations taking place in BRCA1 not expressing tumors will lead us to a better understanding of the cellular functions affected in this heterogeneous disease. Moreover, specific genomic alterations may contribute to the identification of potential therapeutic targets and offer a more personalized treatment to breast cancer patients. Methods Forty seven tumors from hereditary breast cancer cases, previously analyzed for BRCA1 expression, and screened for germline BRCA1 and 2 mutations, were analyzed by Array based Comparative Genomic Hybridization (aCGH) using Agilent 4x44K arrays. Overall survival was established for tumors in different clusters using Log-rank (Mantel-Cox) Test. Gene lists obtained from aCGH analysis were analyzed for Gene Ontology enrichment using GOrilla and DAVID tools. Results Genomic profiling of the tumors showed specific alterations associated to BRCA1 or 2 mutation status, and BRCA1 expression in the tumors, affecting relevant cellular processes. Similar cellular functions were found affected in BRCA1 not expressing and BRCA1 or 2 mutated tumors. Hierarchical clustering classified hereditary breast tumors in four major, groups according to the type and amount of genomic alterations, showing one group with a significantly poor overall survival (p = 0.0221). Within this cluster, deletion of PLEKHO1, GDF11, DARC, DAG1 and CD63 may be associated to the worse outcome of the patients. Conclusions These results support the fact that BRCA1 lack of expression in tumors should be used as a marker for BRCAness and to select these patients for synthetic lethality approaches such as treatment with PARP inhibitors. In addition, the identification of specific alterations in breast tumors associated with poor survival, immune response or with a BRCAness phenotype will allow the use of a more personalized treatment in these patients.
- ItemDifferentially Expressed Oncogenic Pathways Are Associated With Ethnicity Differences in Gastric Cancer(2016) Corvalán R., Alejandro; Wichmann Pérez, Ignacio Alberto; Artigas, Rocío.
- ItemEffects of preparation on catalytic, magnetic and hybrid micromotors on their functional features and application in gastric cancer biomarker detection(2020) Baez, D. F.; Ramos, G.; Corvalán R., Alejandro; Cordero, M. L.; Bollo, S.; Kogan, M. J.
- ItemEpigenetic regulation of AURKA by miR-4715-3p in upper gastrointestinal cancers(2019) Gomaa, Ahmed; Peng, DunFa; Chen, Zhen; Soutto, Mohammed; Abouelezz, Khaled; Corvalán R., Alejandro; El-Rifai, Wael
- ItemEscaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells(2016) Pinto, M.; Sotomayor, P.; Carrasco, G.; Corvalán R., Alejandro; Owen, Gareth Ivor
- ItemExpression of RPRM/rprm in the olfactory system of embryonic zebrafish (Danio rerio)(2018) Stanic, Karen; Quiroz Vallverdu, Alonso Ingmar; Lemus, Carmen G.; Wichmann Pérez, Ignacio Alberto; Corvalán R., Alejandro; Owen, Gareth Ivor; Opazo, Juan C.; Concha, Miguel L.; Amigo Donoso, Julio
- ItemGermline Mutations in PALB2 , BRCA1 , and RAD51C , Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer(2017) Corvalán R., Alejandro; Norero Muñoz, Enrique; Álvarez Aguilera, Carolina Soledad; Tapia Espinoza, Teresa Marloren; Carvallo de Saint Quentin, Pilar; Sahasrabudhe, R.; Lott, P.; Bohorquez, M.; Toal, T.; Estrada, A.; Suarez, J.; Brea, A.; Cameselle, J.; Pinto, C.; Ramos, I.; Mantilla, A.; Prieto, R.
- ItemGold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors(2020) Lara, Pablo.; Polakovicova, Iva; Corvalán R., Alejandro; Palma‑Florez, Sujey.; Salas-Huenuleo, Edison.; Guerrero, Simón.; Lobos González, Lorena.; Campos, América.; Muñoz Anrique, Luis.; Jorquera‑Cordero, Carla.Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.
- ItemHelicobacter pylori -induced chronic gastritis and assessing risks for gastric cancer(2013) Carrasco, Gonzalo; Corvalán R., AlejandroChronic gastritis is an inflammation of the gastric mucosa and has multiple etiologies. Here we discuss the pathological alterations induced by Helicobacter pylori (HP) leading to chronic gastritis and the epigenetic bases underlying these changes. We review the histology of the normal gastric mucosa and overview the role of HP in the multistep cascade of GC. We attempt to define the role of the Operative Link for Gastritis Assessment (OLGA) staging system in assessing the risk of GC. The epigenetic bases of chronic gastritis, mainly DNA methylation, are presented through examples such as (i) the methylation of the promoter region of E-cadherin in HP-induced chronic gastritis and its reversion after HP eradication and (ii) the association of methylation of the promoter region of Reprimo, a p53-mediated cell cycle arrest gene, with aggressive HP strains in high risk areas for GC. In addition, we discuss the finding of RPRM as a circulating cell-free DNA, offering the opportunity for noninvasive risk assessment of GC. Finally, the integration of OLGA and tissue biomarkers, by systems pathology approach, suggests that severe atrophy has a greater risk for GC development if, in addition, overexpressed p73. This trial is registered with ClinicalTrials.gov NCT01774266.
- ItemHigh frequency of p 16 promoter methylation in non-small cell lung carcinomas from Chile(2007) Guzman, Leda M.; Koriyama, Chihaya; Akiba, Suminori; Eizuru, Yoshito; Castillo, Darwins; Corvalán R., Alejandro; Aguayo González, FranciscoThe inactivation of tumour suppressor genes by aberrant methylation of promoter regions has been described as a frequent event in neoplasia development, including lung cancer. The p16 gene is a tumour suppressor gene involved in the regulation of cell cycle progression that has been reported to be inactivated by promoter methylation in lung carcinomas at variable frequencies around the world in a smoking habit dependent manner. The purpose of this study was to investigate the methylation status of the promoter region of the p16 gene in 74 non-small cell lung carcinomas from Chile. The frequency of p16 gene inactivation by promoter methylation was determined as 79.7% (59/74). When we considered histological type, we observed that p16 promoter methylation was significantly higher in squamous cell carcinomas (30/33, 91%) compared with adenocarcinomas (21/30, 70%) (p=0.029). In addition, no association between p16 promoter methylation and gender, age or smoking habit was found (p=0.202, 0.202 and 0.147 respectively). Our results suggest that p16 promoter hypermethylation is a very frequent event in non-small cell lung carcinomas from Chile and could be smoking habit-independent.
- ItemHigh-risk HPV infection after five years in a population-based cohort of Chilean women(2011) Ferreccio Readi, Catterina; Van De Wyngard, Vanessa; Domínguez, M. A.; Puschel Illanes, Klaus; Corvalán R., Alejandro; Olcay, Fabiola; Franceschi, Silvia; Snijders, Peter J.; Ferreccio Readi, Catterina; Van De Wyngard, Vanessa; Domínguez, M. A.; Puschel Illanes, Klaus; Corvalán R., Alejandro; Olcay, Fabiola; Franceschi, Silvia; Snijders, Peter J.Abstract Background The need to review cervical cancer prevention strategies has been triggered by the availability of new prevention tools linked to human papillomavirus (HPV): vaccines and screening tests. To consider these innovations, information on HPV type distribution and natural history is necessary. This is a five-year follow-up study of gynecological high-risk (HR) HPV infection among a Chilean population-based cohort of women. Findings A population-based random sample of 969 women from Santiago, Chile aged 17 years or older was enrolled in 2001 and revisited in 2006. At both visits they answered a survey on demographics and sexual history and provided a cervical sample for HPV DNA detection (GP5+/6+ primer-mediated PCR and Reverse line blot genotyping). Follow-up was completed by 576 (59.4%) women; 45 (4.6%) refused participation; most losses to follow-up were women who were unreachable, no longer eligible or had missing samples. HR-HPV prevalence increased by 43%. Incidence was highest in women < 20 years of age (19.4%) and lowest in women > 70 (0%); it was three times higher among women HR-HPV positive versus HPV negative at baseline (25.5% and 8.3%; OR 3.8, 95% CI 1.8-8.0). Type-specific persistence was 35.3%; it increased with age, from 0% in women < 30 years of age to 100% in women > 70. An enrollment Pap result ASCUS or worse was the only risk factor for being HR-HPV positive at both visits. Conclusions HR-HPV prevalence increased in the study population. All HR-HPV infections in women < 30 years old cleared, supporting the current recommendation of HR-HPV screening for women > 30 years.
- ItemHuman Papillomavirus 16 E7 Promotes EGFR/PI3K/AKT1/NRF2 Signaling Pathway Contributing to PIR/NF-kappa B Activation in Oral Cancer Cells(2020) Carrillo Beltrán, D.; Muñoz, J. P.; Guerrero Vásquez, N.; Blanco, R.; León, O.; Lino, V. D.; Tapia, J. C.; Maldonado, E.; Corvalán R., Alejandro; Aguayo González, Francisco; Dubois Camacho, K.; Hermoso, M. A.; Calaf, G. M.; Boccardo, E.
- ItemHuman papillomavirus and Epstein-Barr virus infections in breast cancer from chile(2011) Padilla, Oslando; Solís, Luisa.; Corvalán R., Alejandro; Aguayo González, Francisco; Khan, Noureen.; Koriyama, Chihaya.; González, Carolina; Ampuero, Sandra.; Eizuru, Yoshito.; Akiba, Suminori.Abstract Background Human papillomavirus (HPV) and Epstein Barr virus (EBV) have been found in breast carcinomas (BCs) around the world. In this study, fifty-five BCs from Chile were analyzed for HPV and EBV presence. In addition, HPV-16 viral load/physical status and E6/E7 expressions were determined. Results The amplification of a housekeeping gene showed that 46/55 samples (84%) had amplifiable DNA. HPV-16 was detected in 4/46 BCs (8.7%) and EBV was detected in 3/46 (6.5%) BCs. The analysis of HPV-16 physical status showed that this virus was integrated in all of the tumors with a relatively low viral load (range: 0.14 to 33.8 copies/cell). E6 and E7 transcripts, however, were not detected in any HPV-16 positive specimens. Using a Cox-regression model, we found a statistically significant association between EBV presence and poor survival (p = 0.013). Conclusions The findings in this study suggest that it is unlikely that HPV and/or EBV play a direct role in the etiology of BC.Abstract Background Human papillomavirus (HPV) and Epstein Barr virus (EBV) have been found in breast carcinomas (BCs) around the world. In this study, fifty-five BCs from Chile were analyzed for HPV and EBV presence. In addition, HPV-16 viral load/physical status and E6/E7 expressions were determined. Results The amplification of a housekeeping gene showed that 46/55 samples (84%) had amplifiable DNA. HPV-16 was detected in 4/46 BCs (8.7%) and EBV was detected in 3/46 (6.5%) BCs. The analysis of HPV-16 physical status showed that this virus was integrated in all of the tumors with a relatively low viral load (range: 0.14 to 33.8 copies/cell). E6 and E7 transcripts, however, were not detected in any HPV-16 positive specimens. Using a Cox-regression model, we found a statistically significant association between EBV presence and poor survival (p = 0.013). Conclusions The findings in this study suggest that it is unlikely that HPV and/or EBV play a direct role in the etiology of BC.
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