Browsing by Author "Corvalan, Alejandro H."
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- ItemEpstein–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.
- ItemFunctional 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, FranciscoThe 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.
- ItemHelicobacter pylori-Induced Loss of the Inhibitor-of-Apoptosis Protein Survivin Is Linked to Gastritis and Death of Human Gastric Cells(OXFORD UNIV PRESS INC, 2010) Valenzuela, Manuel; Perez Perez, Guillermo; Corvalan, Alejandro H.; Carrasco, Gonzalo; Urra, Hery; Bravo, Denisse; Toledo, Hector; Quest, Andrew F. G.Helicobacter pylori infects the human stomach and modifies signaling pathways that affect gastric epithelial cell proliferation and viability. Chronic exposure to this pathogen contributes to the onset of gastric atrophy, an early event in the genesis of gastric cancer associated with H. pylori infection. Susceptibility to H. pylori-induced cell death ultimately depends on the presence of protective host cell factors. Although expression of the inhibitor-of-apoptosis protein survivin in adults is frequently linked to the development of cancer, evidence indicating that the protein is present in normal gastric mucosa is also available. Thus, we investigated in human gastric tissue samples and cell lines whether H. pylori infection is linked to loss of survivin and increased cell death. Our results show that infection with H. pylori decreased survivin protein levels in the mucosa of patients with gastritis. Furthermore, survivin down-regulation correlated with apoptosis and loss of cell viability in gastrointestinal cells cocultured with different H. pylori strains. Finally, overexpression of survivin in human gastric cells was sufficient to reduce cell death after infection. Taken together, these findings implicate survivin as an important survival factor in the gastric mucosa of humans.
- ItemIdentification of The Distinctive Type i/XhoI plus Strain of Epstein-Barr Virus in Gastric Carcinoma in Peru(INT INST ANTICANCER RESEARCH, 2011) Ordonez, Paula; Koriyama, Chihaya; Ding, Shan; Yoshiwara, Elena; Corvalan, Alejandro H.; Takano, Juan; Chirinos, Jesus L.; Watanabe, Jose; Miyagui, Juan; Hidalgo, Heriberto; Chacon, Pedro; Linares, Victor; Eizuru, Yoshito; Akiba, SuminoriAim: To clarify the reason for the low frequency of Epstein-Barr virus-associated gastric carcinoma (EBVaGC) in Peru, despite the high frequency reported in neighboring countries, the distribution of the distinctive EBV (type i/XhoI+) strain in EBVaGC and a healthy population was examined. Materials and Methods: EBV polymorphisms in BamHI W1/I1 and XhoI restriction site of the latent membrane protein 1 gene (LMP1) were examined among 11 EBVaGCs and 172 healthy controls from Peru, and these frequencies were compared with those in a previous study of Chile and Colombia (n=303). Results: The frequency of the distinctive EBV strain in EBVaGCs (55%) was significantly higher than that in controls (7%). Furthermore, the frequency of this EBV type in Peruvian controls was significantly lower than that in controls from Chile and Colombia (27%, p<0.001). Conclusion: The low frequency of the distinctive EBV strain among the Peruvian population might be a reason for the lower incidence of EBVaGC in Peru, as compared with neighboring countries.
- ItemMerkel 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, FranciscoLung 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.
- ItemOverexpression of p73 as a Tissue Marker for High-Risk Gastritis(AMER ASSOC CANCER RESEARCH, 2010) Carrasco, Gonzalo; Diaz, Jose; Valbuena, Jose R.; Ibanez, Paulina; Rodriguez, Paz; Araya, Gabriela; Rodriguez, Carolina; Torres, Javiera; Duarte, Ignacio; Aravena, Edmundo; Mena, Fernando; Barrientos, Carlos; Corvalan, Alejandro H.Purpose: Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment.
- ItemProspective follow-up of chronic atrophic gastritis in a high-risk population for gastric cancer in latin america(2022) Latorre, Gonzalo; Silva, Felipe; Montero, Isabella; Bustamante, Miguel; Dukes, Eitan; Gandara, Vicente; Robles, Camila; Uribe, Javier; Corsi, Oscar; Crispi, Francisca; Espinoza Sepúlveda, Manuel Antonio; Cuadrado, Cristobal; Fuentes-Lopez, Eduardo; Shah, Shailja; Camargo, M. Constanza; Torres, Javiera; Roa, Juan Carlos; Corvalan, Alejandro H.; Candia, Roberto; Aguero, Carlos; Gonzalez, Robinson G.; Vargas Domínguez, José Ignacio; Espino, Alberto; Riquelme, ArnoldoBackground. Gastric adenocarcinoma (GA) is preceded by premalignant conditions such as chronic atrophic gastritis (CAG) with or without gastric intestinal metaplasia (GIM). Endoscopic follow-up of these conditions has been proposed as a strategy for the detection of early-stage GA. Aim. To describe the risk of progression to gastric dysplasia (GD) and early-stage GA of patients who underwent esophagogastroduodenoscopy (EGD) with gastric biopsies obtained following the updated Sydney System biopsy protocol (USSBP). Methods. We conducted a real-world, multicenter, prospective cohort study. Patients undergoing EGD surveillance with USSBP were enrolled between 2015 and 2021 from three endoscopy units at Santiago, Chile. Patients with prior history of GA or gastric resection were excluded. Follow-up surveillance schedule was determined by gastroenterologist in accordance with the Chilean Digestive Endoscopy Association Guidelines. CAG was confirmed by two expert GI pathologists and categorized by the Operative Link on Gastritis Assessment as stage 0 (normal) through stage IV (advanced stage). The primary endpoint was a composite of GD (low-grade, LGD or high-grade, HGD) or GA, while secondary endpoints were progression in OLGA and separate outcomes of LGD, HGD or GA. Multivariable Cox regression analysis was used to estimate the association between CAG +/- GIM and the outcomes, adjusted for age, sex and Helicobacter pylori (Hp) infection. Results. 600 patients were included in the cohort (64% female; mean age 58 years). At baseline 32.3% (n=194) had active Hp infection. OLGA stage was: 31% (n=184) OLGA 0, 48% (n=291) OLGA I-II and 21% (125) OLGA III-IV. GIM was identified in 52% (n=312) and autoimmune gastritis in 6.2% (n=37). Median follow-up was 28 months (IQR 17-42). During follow-up, 6 early-stage GA, 3 HGD and 6 LGD were observed. No advanced-stage GA was diagnosed. Only 19% (n=35) of baseline OLGA 0 patients progressed to OLGA I-IV, with <2% progressing to OLGA III/IV (Figure 1). Persistence of Hp infection (aOR 2.1; 95%CI 1.1-4.0) was independently associated with increase of at least 1 point in the OLGA scale during follow-up. GA/GD free survival at 3- years for OLGA 0, I-II and III-IV was 99.4%, 97.1% and 91.7%, respectively (p=0.0015) (Figure 2). Based on multivariable Cox regression, OLGA III-IV (vs. OLGA 0) was associated with a 12.1-fold (95%CI 1.5-97.4) higher risk of GA, while GIM was associated with a 13.0-fold (95%CI 1.7-101.2) higher risk, although the CI was wide; this was particularly between 2 and 3 years of follow-up. Discussion: These findings, including the observation that all GAs were early-stage, support endoscopic/histologic surveillance for patients with advanced OLGA stages or GIM, which is a common finding in patients with advanced CAG. Further studies are needed to determine the optimal time interval for surveillance.
- ItemReprimo 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.