DSpace Angular :: Browsing by Author "Aguayo, Francisco"

Browsing by Author "Aguayo, Francisco"

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Adolescence and Suicide: Subjective Construction of the Suicidal Process in Young Gay and Lesbian Chileans
(2021) Tomicic, Alemka; Martinez, Claudio; Rosenbaum, Catalina; Aguayo, Francisco; Leyton, Fanny; Rodriguez, Juliana; Galvez, Constanza; Lagazzi, Iside
The association between suicide risk and sexual minority status can be understood from the perspective of the social determinants of health, an approach that requires the development of culturally sensitive knowledge. The aim of this study was to characterize young gay and lesbian people's subjective construction of their experience of having lived and survived a suicidal process. Qualitative interviews were conducted and analyzed as products based on life events. In the participants' accounts, we identified hostile contexts associated with suicide, trajectories associated with gay/lesbian identification processes, and milestones related to victimization experiences as part of the intentionality and rationality of suicide.
Analytical detection of immunoglobulin heavy chain gene rearrangements in gastric lymphoid infiltrates by peak area analysis of the melting curve in the LightCycler System
(ELSEVIER SCIENCE INC, 2007) Retamales, Eduardo; Rodriguez, Luis; Guzman, Leda; Aguayo, Francisco; Palma, Mariana; Backhouse, Claudia; Argandona, Jorge; Riquelme, Erick; Corvalan, Alejandro
Because it is difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from chronic gastritis in gastric lymphoid infiltrates, molecular detection of monoclonality through immunoglobulin heavy chain (IgH) gene rearrangements is commonly performed. However, heterogeneity in the performance and results obtained from IgH gene rearrangements has been reported. To improve the accuracy in the diagnosis of gastric lymphoid infiltrates, we developed an analytical approach based on one-peak area analysis of the melting curve in the LightCycler System. Using a training-testing approach, the likelihood ratio method was selected to find a discriminative function of 4.64 in the training set (10 gastric MALT lymphomas and 10 chronic gastritis cases). This discriminative function was validated in the testing set (five gastric MALT lymphomas, six abnormal lymphocytic infiltrates with subsequently demonstrated gastric MALT lymphomas, and six cases of chronic gastritis). All but one case of gastric MALT lymphoma, as well as abnormal lymphocytic infiltrates, clustered under 4.64, and all chronic gastritis cases clustered above 4.64. These results were validated by conventional electrophoreses confirming one or two sharp bands in cases of gastric MALT lymphomas and a smear of multiple bands in cases of chronic gastritis. Analytical detection of IgH gene rearrangement in gastric lymphoid infiltrates by one-peak area analysis correctly distinguishes gastric MALT lymphomas from chronic gastritis, even in cases with diagnosis of abnormal lymphocytic infiltrates.
Cancer Stem Cell and Aggressiveness Traits Are Promoted by Stable Endothelin-Converting Enzyme-1c in Glioblastoma Cells
(2023) Niechi, Ignacio; Erices, Jose I.; Carrillo-Beltran, Diego; Uribe-Ojeda, Atenea; Torres, Angelo; Rocha, Jose Dellis; Uribe, Daniel; Toro, Maria A.; Villalobos-Nova, Karla; Gaete-Ramirez, Belen; Mingo, Gabriel; Owen, Gareth I. I.; Varas-Godoy, Manuel; Jara, Lilian; Aguayo, Francisco; Burzio, Veronica A.; Quezada-Monras, Claudia; Tapia, Julio C. C.
Glioblastoma (GBM) is the most common and aggressive type of brain tumor due to its elevated recurrence following treatments. This is mainly mediated by a subpopulation of cells with stemness traits termed glioblastoma stem-like cells (GSCs), which are extremely resistant to anti-neoplastic drugs. Thus, an advancement in the understanding of the molecular processes underlying GSC occurrence should contribute significantly towards progress in reducing aggressiveness. High levels of endothelin-converting enzyme-1 (ECE1), key for endothelin-1 (ET-1) peptide activation, have been linked to the malignant progression of GBM. There are four known isoforms of ECE1 that activate ET-1, which only differ in their cytoplasmic N-terminal sequences. Isoform ECE1c is phosphorylated at Ser-18 and Ser-20 by protein kinase CK2, which increases its stability and hence promotes aggressiveness traits in colon cancer cells. In order to study whether ECE1c exerts a malignant effect in GBM, we designed an ECE1c mutant by switching a putative ubiquitination lysine proximal to the phospho-serines Lys-6-to-Arg (i.e., K6R). This ECE1c(K6R) mutant was stably expressed in U87MG, T98G, and U251 GBM cells, and their behavior was compared to either mock or wild-type ECE1c-expressing clone cells. ECE1c(K6R) behaved as a highly stable protein in all cell lines, and its expression promoted self-renewal and the enrichment of a stem-like population characterized by enhanced neurospheroid formation, as well as increased expression of stem-like surface markers. These ECE1c(K6R)-derived GSC-like cells also displayed enhanced resistance to the GBM-related chemotherapy drugs temozolomide and gemcitabine and increased expression of the ABCG2 efflux pump. In addition, ECE1c(K6R) cells displayed enhanced metastasis-associated traits, such as the modulation of adhesion and the enhancement of cell migration and invasion. In conclusion, the acquisition of a GSC-like phenotype, together with heightened chemoresistance and invasiveness traits, allows us to suggest phospho-ECE1c as a novel marker for poor prognosis as well as a potential therapeutic target for GBM.
DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA 1 promoter region in early-onset gastric carcinogenesis
(SOC BIOLGIA CHILE, 2008) Bernal, Carolina; Vargas, Macarena; Ossandon, Francisco; Santibanez, Eudocia; Urrutia, Julio; Luengo, Victor; Zavala, Luis F.; Backhouse, Claudia; Palma, Mariana; Argandona, Jorge; Aguayo, Francisco; Corvalan, Alejandro
Diffuse type gastric carcinoma is the most aggressive type of gastric cancer. This type Of tumor is not preceded by precancerous changes and is associated with carly-onset and hereditary syndromes. To test the hypothesis that DNA methylation profile Would be useful for molecular classification of the diffuse type gastric carcinoma, DNA methylation patterns of the CpG Island of 17 genes were studied in 104 cases and 47 normal adjacent gastric mucosa by Methylation-specific PCR, Immunohistochemistry and Hierarchical Clustering analysis. The most frequent methylated genes were FHIT, E-cadherin, BRCA1 and APC (>50%), followed by p14, p16, p15, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveals four groups with different clinical features. The first was characterized by hypermethylation of BRCA 1 and younger age (<45 years old), and the second by hypermethylation of p14 and p 16 genes, male. predominance and Epstein-Barr virus infection. The third group was characterized by hypermethylation of FHIT and antrum located tumors and the fourth was not associated with any clinical variables. In normal adjacent mucosa only the p73 gene was significantly less methylated in comparison to tumor mucosa. DNA methylation identified subgroups of diffuse type gastric cancer. Hypermethylation of BRCA I associated with Young age suggests a role in early-onset gastric carcinoma.
Epstein-Barr Virus BARF1 Is Expressed in Lung Cancer and Is Associated with Cancer Progression
(2024) Osorio, Julio C.; Armijo, Alvaro; Carvajal, Francisco J.; Corvalan, Alejandro H.; Castillo, Andres; Fuentes-Panana, Ezequiel M.; Moreno-Leon, Carolina; Romero, Carmen; Aguayo, Francisco
Background: Epstein-Barr virus (EBV) is involved in the development of lymphomas, nasopharyngeal carcinomas (NPC), and a subgroup of gastric carcinomas (GC), and has also been detected in lung carcinomas, even though the role of the virus in this malignancy has not yet been established. BamH1-A Rightward Frame 1 (BARF1), a suggested exclusive epithelial EBV oncoprotein, is detected in both EBV-associated GCs (EBVaGC) and NPC. The expression and role of BARF1 in lung cancer is unknown. Methods: A total of 158 lung carcinomas including 80 adenocarcinomas (AdCs) and 78 squamous cell carcinomas (SQCs) from Chilean patients were analyzed for EBV presence via polymerase chain reaction (PCR), Immunohistochemistry (IHC), or chromogenic in situ hybridization (CISH). The expression of BARF1 was evaluated using Reverse Transcription Real-Time PCR (RT-qPCR). Additionally, A549 and BEAS-2B lung epithelial cells were transfected with a construct for ectopic BARF1 expression. Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were evaluated. Results: We found that EBV was present in 37 out of 158 (23%) lung carcinomas using PCR. Considering EBV-positive specimens using PCR, IHC for Epstein-Barr nuclear antigen 1 (EBNA1) detected EBV in 24 out of 30 (80%) cases, while EBERs were detected using CISH in 13 out of 16 (81%) cases. Overall, 13 out of 158 (8%) lung carcinomas were shown to be EBV-positive using PCR/IHC/CISH. BARF1 transcripts were detected in 6 out of 13 (46%) EBV-positive lung carcinomas using RT qPCR. Finally, lung cells ectopically expressing BARF1 showed increased migration, invasion, and EMT. Conclusions. EBV is frequently found in lung carcinomas from Chile with the expression of BARF1 in a significant subset of cases, suggesting that this viral protein may be involved in EBV-associated lung cancer progression.
Epstein–Barr Virus Infection in Lung Cancer: Insights and Perspectives
(MDPI, 2022) Osorio, Julio C.; Blanco, Rancés; Corvalan, Alejandro H.; Muñoz, Juan P.; Calaf, Gloria M.; Aguayo, Francisco
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.Lung cancer (LC) is the leading cause of cancer death worldwide. Tobacco smoke is the most frequent risk factor etiologically associated with LC, although exposures to other environmental factors such as arsenic, radon or asbestos are also involved. Additionally, the involvement of some viral infections such as high-risk human papillomaviruses (HR-HPVs), Merkel cell polyomavirus (MCPyV), Jaagsiekte Sheep Retrovirus (JSRV), John Cunningham Virus (JCV), and Epstein– Barr virus (EBV) has been suggested in LC, though an etiological relationship has not yet been established. EBV is a ubiquitous gamma herpesvirus causing persistent infections and some lymphoid and epithelial tumors. Since EBV is heterogeneously detected in LCs from different parts of the world, in this review we address the epidemiological and experimental evidence of a potential role of EBV. Considering this evidence, we propose mechanisms potentially involved in EBV-associated lung carcinogenesis. Additional studies are warranted to dissect the role of EBV in this very frequent malignancy.
Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells
(PUBLIC LIBRARY SCIENCE, 2012) Pablo Munoz, Juan; Gonzalez, Carolina; Parra, Barbara; Corvalan, Alejandro H.; Tornesello, Maria Lina; Eizuru, Yoshito; Aguayo, Francisco
The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction between HPV infection and smoke carcinogens, however, remains unclear. In this study we address a potential cooperation between tobacco smoke and HPV16 E6 and E7 oncoproteins for alterations in proliferative and tumorigenic properties of lung epithelial cells. A549 (alveolar, tumoral) and BEAS-2B (bronchial, non-tumoral) cell lines were stably transfected with recombinant pLXSN vectors expressing HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC) at different concentrations. HPV16 E6 and E7 expression was associated with loss of p53 stability, telomerase (hTERT) and p16(INK4A) overexpression in BEAS-2B cells as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). In A549 cells we observed downregulation of p53 but not a significant increase of hTERT transcripts. In addition, the HPV16 E6/E7 transfected cell lines showed an increased proliferation rate and anchorage-independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover, both HPV16 E6/E7 and mock transfected cells showed an increased proliferation rate and anchorage-independent growth in the presence of 0.1 and 10 mu g/mL CSC. However, this increase was significantly greater in HPV16 E6/E7 transfected cells (p<0.001). Data were confirmed by FCSE proliferation assay. The results obtained in this study are suggestive of a functional interaction between tobacco smoke and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of lung epithelial cells. More studies are warranted in order to dissect the molecular mechanisms involved in this cooperation.
High-Risk Human Papillomavirus and Epstein-Barr Virus Coinfection: A Potential Role in Head and Neck Carcinogenesis
(2021) Blanco, Rances; Carrillo-Beltran, Diego; Corvalan, Alejandro H.; Aguayo, Francisco
Simple Summary A subset of carcinomas that arise in the head and neck region show a viral etiology. In fact, a subgroup of oropharyngeal cancers are caused by some types of human papillomavirus (HPV), so-called high-risk (HR)-HPVs, whereas undifferentiated nasopharyngeal carcinomas are etiologically related to Epstein-Barr virus (EBV). However, studies have reported the presence of both HR-HPV and EBV in some types of head and neck cancers. In this review, we discuss the potential contribution and role of HR-HPV/EBV coinfection in head and neck carcinogenesis, as well as the mechanisms that are potentially involved. In addition, HR-HPV/EBV interaction models are proposed. High-risk human papillomaviruses (HR-HPVs) and Epstein-Barr virus (EBV) are recognized oncogenic viruses involved in the development of a subset of head and neck cancers (HNCs). HR-HPVs are etiologically associated with a subset of oropharyngeal carcinomas (OPCs), whereas EBV is a recognized etiological agent of undifferentiated nasopharyngeal carcinomas (NPCs). In this review, we address epidemiological and mechanistic evidence regarding a potential cooperation between HR-HPV and EBV for HNC development. Considering that: (1) both HR-HPV and EBV infections require cofactors for carcinogenesis; and (2) both oropharyngeal and oral epithelium can be directly exposed to carcinogens, such as alcohol or tobacco smoke, we hypothesize possible interaction mechanisms. The epidemiological and experimental evidence suggests that HR-HPV/EBV cooperation for developing a subset of HNCs is plausible and warrants further investigation.
Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile
(W J G PRESS, 2006) Castillo, Andres; Aguayo, Francisco; Koriyama, Chihaya; Torres, Miyerlandi; Carrascal, Edwin; Corvalan, Alejandro; Roblero, Juan P.; Naquira, Cecilia; Palma, Mariana; Backhouse, Claudia; Argandona, Jorge; Itoh, Tetsuhiko; Shuyama, Karem; Eizuru, Yoshito; Akiba, Suminori
AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.
Merkel cell polyomavirus in non-small cell lung carcinomas from Chile
(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2012) Gheit, Tarik; Pablo Munoz, Juan; Levican, Jorge; Gonzalez, Carolina; Ampuero, Sandra; Parra, Barbara; Gaggero, Aldo; Corvalan, Alejandro H.; Meneses, Manuel; Tommasino, Massimo; Aguayo, Francisco
Lung cancer is a leading pathology strongly associated with the smoking habit. However, a viral etiology for a subset of patients developing lung cancer has been suggested. Polyomaviruses (PyVs) are small double stranded DNA viruses associated with the development of some human diseases. However, a causal role of these viruses in human cancer has been difficult to demonstrate. In this study, eighty-six non-small cell lung carcinomas (NSCLCs), including adenocarcinomas (AdCs) and squamous cell lung carcinomas (SQCs) from Chile were analyzed for the presence of PyVs using polymerase chain reaction (PCR). All of the specimens were positive for a fragment of the betaglobin gene. We found that 4/86 (4.7%) of lung carcinomas were positive for PyVs. After sequencing and BlastN alignment, all four cases were identified as Merkel cell polyomaviruses (MCV) that corresponded to two AdCs and two SQCs. A non-significant statistical association was found between the presence of MCV and clinic-pathological features of the patients and tumors. In addition, 1/4 (25%) of the carcinomas were actively expressing large T antigen (LT) transcripts, as demonstrated by reverse-transcriptase PCR (RT-PCR). Thus a possible role of MCV in a very small subset of patients with lung cancer cannot be ruled out and warrants more investigation. (C) 2012 Elsevier Inc. All rights reserved.
Reprimo as a Potential Biomarker for Early Detection in Gastric Cancer
(AMER ASSOC CANCER RESEARCH, 2008) Bernal, Carolina; Aguayo, Francisco; Villarroel, Cynthia; Vargas, Macarena; Diaz, Ignacio; Ossandon, Francisco J.; Santibanez, Eudocia; Palma, Mariana; Aravena, Edmundo; Barrientos, Carlos; Corvalan, Alejandro H.
Purpose: Gastric cancer is a curable disease if diagnosed at early stage. However, most cases are diagnosed at advanced stage because of the lack of screening programs. Therefore, the identification of plasma biomarkers for early detection is necessary.
Suicidio en poblaciones lesbiana, gay, bisexual y trans : revisión sistemática de una década de investigación (2004-2014)
(2016) Tomicic S., Alemka; Gálvez, Constanza; Quiroz, Constanza; Martínez, Claudio; Fontbona, Jaime; Rodríguez, Juliana; Aguayo, Francisco; Rosenbaum, Catalina; Leyton Álvarez, Fanny Lorena; Lagazzi, Iside
The Phylogeographic Diversity of EBV and Admixed Ancestry in the Americas-Another Model of Disrupted Human-Pathogen Co-Evolution
(2019) Corvalán Rodríguez, Alejandro; Ruedlinger, Jenny; Mayo, Tomás de; Polakovicova, Iva; González-Hormázabal, Patricio; Aguayo, Francisco
Epstein-Barr virus (EBV) is an etiological agent for gastric cancer with significant worldwide variations. Molecular characterizations of EBV have shown phylogeographical variations among healthy populations and in EBV-associated diseases, articularly the cosegregated BamHI-I fragment and XhoI restriction site of exon 1 of the LMP-1 gene. In the Americas, both cosegregated variants are present in EBV carriers, which aligns with the history of Asian and European human migration to this continent. Furthermore, novel recombinant variants have been found, reflecting the genetic makeup of this continent. However, in the case of EBV-associated gastric cancer (EBV-associated GC), the cosegregated European BamHI-“i” fragment and XhoI restriction site strain prevails. Thus, we propose that a disrupted coevolution between viral phylogeographical strains and mixed human ancestry in the Americas might explain the high prevalence of this particular gastric cancer subtype. This cosegregated region contains two relevant transcripts for EBV-associated GC, the BARF-1 and miR-BARTs. Thus, genome-wide association studies (GWAS) or targeted sequencing of both transcripts may be required to clarify their role as a potential source of this disrupted coevolution.
UL146 variability among clinical isolates of Human Cytomegalovirus from Japan
(SOC BIOLGIA CHILE, 2010) Aguayo, Francisco; Murayama, Tsugiya; Eizuru, Yoshito
Human Cytomegalovirus (HCMV) is a herpesvirus associated with serious diseases in immunocompromised subjects. The region between ORF UL133 and UL151 from HCMV, named ULb' is frequently deleted in attenuated AD169 and in highly passaged laboratory strains. However, this region is conserved in low-passaged and more virulent HCMV, like the Toledo strain. The UL146 gene, which is located in the ULb' region, encodes a CXC-chemokine analogue. The diversity of UL146 gene was evaluated among fifty-six clinical isolates of HCMV from Japan. Results show that UL146 gene was successfully amplified by the polymerase chain reaction (PCR) in only 17/56 strains (30%), while the success rate for UL145/UL147 gene was 18/56 strains (32%). After DNA sequencing, the 35 amplified strains were classified into 8 groups. When compared, variability of UL146 ranged from 25.1% to 52.9% at the DNA level and from 34.5% to 67% at the amino acid level. Seven groups had the interleukin-8 (IL-8) motif ERL (Glu-Leu-Arg) CXC and one group had only the CXC motif, suggesting the absence of the IL-8 function of UL146. In conclusion, we found that UL146 gene of HCMV is hypervariable in clinical strains from Japan suggesting the possibility of a different function in each sequence group.

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