Browsing by Author "Bernal, Giuliano"
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Publication Annona cherimola Seed Extracts Trigger an Early Apoptosis Response and Selective Anticlonogenic Activity against the Human Gastric Carcinoma Cell Line SNU-1(2023) Macuer, Johan; Giovagnoli, Claudia; Bernal, Giuliano; Lobos-González, Lorena; De la Fuente, Erwin; Araya, Michael; Ibáñez, CristianThe aim of this study was to evaluate, for the first time, the antiproliferative, apoptotic and diminishing effects of the anchored growth-independent capacity of an ethanol macerate extract from the Annona cherimola seed (EMCHS) in the human gastric cancer cell line SNU-1. The cells treated with EMCHS (20 μg/mL) significantly reduced the capacity to form clones of the tumor cell. Moreover, 50 μg/mL of EMCHS extract induced apoptosis, as was shown by the Annexin-V assay. UHPLC-MS/MS analysis detected two acetogenins (Annonacinone and Annonacin) in the EMCHS, which could be largely responsible for its selective antiproliferative effect. The identification of fatty acids by GC-FID showed the presence of eight fatty acids, among which was, oleic acid, which has recognized activity as an adjuvant in antitumor treatments. Taken together, our results indicate that the EMCHS seems promising for use as a natural therapy against gastric cancer disease.Publication Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers(2024) Garrido, Javiera; Bernal, Yanara; González, Evelin; Blanco, Alejandro; Sepúlveda, Gonzalo; Freire, Matías; Oróstica, Karen; Rivas, Solange; Marcelain, Katherine; Owen, Gareth; Ibañez, Carolina; Corvalan, Alejandro; Garrido, Marcelo; Assar, Rodrigo; Lizana, Rodrigo; Cáceres, Javier; Ampuero, Diego; Ramos, Liliana; Pérez, Paola; Aren, Osvaldo; Chernilo, Sara; Fernández, Cristina; Spencer, María; Flores, Jacqueline; Bernal, Giuliano; Ahumada, Mónica; Rasse, Germán; Sánchez, Carolina; De Amorim, Maria; Bartelli, Thais; Noronha, Diana; Dias, Emmanuel; Freitas, Helano; Armisén, RicardoBackground: Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10-20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. Methods: We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. Results: Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. Conclusions: We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.Item Concordance analysis of ALK gene fusion detection methods in patients with Non– Small-Cell Lung Cancer from Chile, Brazil, and Peru(2021-06) Sepúlveda-Hermosilla, Gonzalo; Freire, Matías; Blanco, Alejandro; Cáceres, Javier; Lizana, Rodrigo; Ramos, Liliana; Assar, Rodrigo; Ampuero, Diego; Aren, Osvaldo; Chernilo, Sara; Spencer, María Loreto; Bernal, Giuliano; Flores, Jacqueline; Rasse, Germán; Sánchez, Carolina; Marcelain, Katherine; Rivas, Solange; Pereira Branco, Gabriela; Galli de Amorim, María; Noronha Nunes, Diana; Dias-Neto, Emmanuel; Freitas, Helano C.; Fernández, Cristina; Pérez, Paola; NIRVANA team; Armisén, RicardoAbout 4 to 7 % of the Non-small cell lung cancer patients have ALK rearrangements and specific target therapies improve patients’ outcomes significantly. ALK gene fusions are detected by immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH) as gold standards in South America. Next Generation Sequencing (NGS) based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4,240 Non-small cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru; where ALK rearrangements were determined as part of their standard of care (SofC) using either IHC or FISH. A subset of 1450 samples was sequenced with the Oncomine Focus Assay (OFA), and the concordance with the SofC tests was measured. An orthogonal analysis was performed using a qPCR EML4-ALK fusion detection kit. ALK fusion prevalence is very similar for Chile (3.67%, N=2142), Brazil (4.05%, N=1013) and Peru (4.59%, N=675). Whereas a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALK gene rearrangements.Item Corrigendum to "The Ω-3 fatty acid docosahexaenoic acid selectively induces apoptosis in tumor-derived cells and suppress tumor growth in gastric cancer"(2021) Ortega, Lorena; Reyna, Mauricio; Erwin, de la Fuente; Castro, Patricio; Lobos-González, Lorena; Bernal, Giuliano; Coddou, Claudio; Cerda, DanielaDespite current achievements and innovations in cancer treatment, conventional chemotherapy has several limitations, such as unsatisfactory long-term survival, cancer drug resistance and toxicity against non-tumoral cells. In the search for safer therapeutic alternatives, docosahexaenoic acid (DHA) has shown promising effects inhibiting tumor growth without significant side effects in several types of cancer, but in gastric cancer (GC) its effects have not been completely described. In this study, we characterized the effects of DHA in GC using in vivo and in vitro models. Among all of the evaluated Ω-3 and Ω-6 fatty acids, DHA showed the highest antiproliferative potency and selectivity against the GC-derived cell line AGS. 10–100 μM DHA decreased AGS cell viability in a concentration-dependent manner but had no effect on non-tumoral GES-1 cells. To evaluate if the effects of DHA were due to apoptosis induction, cells were stained with Annexin V-PI, observing that 75 and 100 μM DHA increased apoptosis in AGS, but not in GES-1 cells. Additionally, levels of several proapoptotic and antiapoptotic regulators were assessed by qPCR, western blot and activity assays, showing similar results. In order to evaluate DHA efficacy in vivo, xenografts in an immunodeficient mouse model (BALB/cNOD-SCID) were used. In these experiments, DHA treatment for six weeks consistently reduced subcutaneous tumor size, ascitic fluid volume and liver metastasis. In summary, we found that DHA has a selective antiproliferative effect on GC, being this effect driven by apoptosis induction. Our investigation provides promising features for DHA as potential therapeutic agent in GCItem The Ω-3 fatty acid docosahexaenoic acid selectively induces apoptosis in tumor-derived cells and suppress tumor growth in gastric cancer(2021) Ortega, Lorena; Lobos-González, Lorena; Reyna-Jeldes, Mauricio; Cerda, Daniela; De la Fuente-Ortega, Erwin; Castro, Patricio; Bernal, Giuliano; Coddou, ClaudioDespite current achievements and innovations in cancer treatment, conventional chemotherapy has several limitations, such as unsatisfactory long-term survival, cancer drug resistance and toxicity against non-tumoral cells. In the search for safer therapeutic alternatives, docosahexaenoic acid (DHA) has shown promising effects inhibiting tumor growth without significant side effects in several types of cancer, but in gastric cancer (GC) its effects have not been completely described. In this study, we characterized the effects of DHA in GC using in vivo and in vitro models. Among all of the evaluated Ω-3 and Ω-6 fatty acids, DHA showed the highest antiproliferative potency and selectivity against the GC-derived cell line AGS. 10-100 μM DHA decreased AGS cell viability in a concentration-dependent manner but had no effect on non-tumoral GES-1 cells. To evaluate if the effects of DHA were due to apoptosis induction, cells were stained with Annexin V-PI, observing that 75 and 100 μM DHA increased apoptosis in AGS, but not in GES-1 cells. Additionally, levels of several proapoptotic and antiapoptotic regulators were assessed by qPCR, western blot and activity assays, showing similar results. In order to evaluate DHA efficacy in vivo, xenografts in an immunodeficient mouse model (BALB/cNOD-SCID) were used. In these experiments, DHA treatment for six weeks consistently reduced subcutaneous tumor size, ascitic fluid volume and liver metastasis. In summary, we found that DHA has a selective antiproliferative effect on GC, being this effect driven by apoptosis induction. Our investigation provides promising features for DHA as potential therapeutic agent in GC.