Browsing by Author "Pinto, Mauricio"

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    A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability
    (MDPI, Basel Sz., 2020) Pinto, Mauricio; Córdova-Delgado, Miguel; Retamal, Ignacio; Muñoz-Medel, Matías; Bravo, Loreto; Durán, Doris; Villanueva, Francisco; Sánchez, César; Acevedo, Francisco; Mondaca, Sebastián; Érica, Koch; Ibáñez, Carolina; Galindo, Héctor; Madrid, Jorge; Nervi, Bruno; Peña, José; Torres, Javiera; Garrido, Marcelo; Owen, Gareth I.; Corvalán, Alejandro H.; Armisén, Ricardo
    Gastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein–Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53−). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinic
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    Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation
    (Multidisciplinary Digital Publishing Institute (MDPI), 2019) Arce, Maximiliano; Pinto, Mauricio; Galleguillos, Macarena; Muñoz, Catalina; Lange, Soledad; Ramirez, Carolina; Erices, Rafaela; González, Pamela; Velásquez, Ethel; Tempio, Fabián; López, Mercedes; Salazar-Onfray, Flavio; Cautivo, Kelly; Kalergis, Alexis; Cruz, Sebastián; Lobos-González, Lorena; Lladser, Álvaro; Valenzuela, Guillermo; Olivares, Nixa; Sáez, Claudia; Koning, Tania; Sánchez, Fabiola; Fuenzalida, Patricia; Godoy, Alejandro; Contreras, Pamela; Leyton, Lisette; Lugano, Roberta; Dimberg, Anna; Quest, Andrew; Owen, Gareth
    Hypercoagulable state is linked to cancer progression; however, the precise role of the coagulation cascade is poorly described. Herein, we examined the contribution of a hypercoagulative state through the administration of intravenous Coagulation Factor Xa (FXa), on the growth of solid human tumors and the experimental metastasis of the B16F10 melanoma in mouse models. FXa increased solid tumor volume and lung, liver, kidney and lymph node metastasis of tail-vein injected B16F10 cells. Concentrating on the metastasis model, upon coadministration of the anticoagulant Dalteparin, lung metastasis was significantly reduced, and no metastasis was observed in other organs. FXa did not directly alter proliferation, migration or invasion of cancer cells in vitro. Alternatively, FXa upon endothelial cells promoted cytoskeleton contraction, disrupted membrane VE-Cadherin pattern, heightened endothelial-hyperpermeability, increased inflammatory adhesion molecules and enhanced B16F10 adhesion under flow conditions. Microarray analysis of endothelial cells treated with FXa demonstrated elevated expression of inflammatory transcripts. Accordingly, FXa treatment increased immune cell infiltration in mouse lungs, an effect reduced by dalteparin. Taken together, our results suggest that FXa increases B16F10 metastasis via endothelial cell activation and enhanced cancer cell-endothelium adhesion advocating that the coagulation system is not merely a bystander in the process of cancer metastasis.

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