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• W2201245685 abstract "// Helga Weber 1, * , Pamela Leal 1, * , Stefan Stein 2 , Hana Kunkel 2 , Patricia García 3 , Carolina Bizama 3 , Jaime A. Espinoza 3 , Ismael Riquelme 1 , Bruno Nervi 4 , Juan C. Araya 1 , Manuel Grez 2, * , Juan C. Roa 3, * 1 Department of Pathology, Center of Genetic and Immunological Studies (CEGIN) and Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile 2 Gene Therapy Unit, Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt, Germany 3 Department of Pathology, UC-Center for Investigational Oncology (CITO), Advanced Center for Chronic Diseases (ACCDiS), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile 4 Department of Hematology Oncology, UC-Center for Investigation in Translational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile * These authors have contributed equally to this work Correspondence to: Juan C. Roa, e-mail: jcroas@gmail.com Manuel Grez, e-mail: grez@em.uni-frankfurt.de Keywords: gallbladder cancer, mTOR inhibitors, gallbladder cancer xenografts, rapamycin, WYE-354 Received: May 12, 2015      Accepted: September 01, 2015      Published: September 11, 2015 ABSTRACT Gallbladder cancer (GBC) is a highly malignant tumor characterized by a poor response to chemotherapy and radiotherapy. We evaluated the in vitro and in vivo antitumor efficacy of mTOR inhibitors, rapamycin and WYE-354. In vitro assays showed WYE-354 significantly reduced cell viability, migration and invasion and phospho-P70S6K expression in GBC cells. Mice harboring subcutaneous gallbladder tumors, treated with WYE-354 or rapamycin, exhibited a significant reduction in tumor mass. A short-term treatment with a higher dose of WYE-354 decreased the tumor size by 68.6% and 52.4%, in mice harboring G-415 or TGBC-2TKB tumors, respectively, compared to the control group. By contrast, treatment with a prolonged-low-dose regime of rapamycin almost abrogated tumor growth, exhibiting 92.7% and 97.1% reduction in tumor size, respectively, compared to control mice. These results were accompanied by a greater decrease in the phosphorylation status of P70S6K and a lower cell proliferation Ki67 index, compared to WYE-354 treated mice, suggesting a more effective mTOR pathway inhibition. These findings provide a proof of concept for the use of rapamycin or WYE-354 as potentially good candidates to be studied in clinical trials in GBC patients." @default.
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• W2201245685 date "2015-09-11" @default.
• W2201245685 modified "2023-10-06" @default.
• W2201245685 title "Rapamycin and WYE-354 suppress human gallbladder cancer xenografts in mice" @default.
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• W2201245685 doi "https://doi.org/10.18632/oncotarget.5047" @default.
• W2201245685 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4741647" @default.
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• W2201245685 hasPublicationYear "2015" @default.
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