Browsing by Author "Riquelme, Ismael"
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Publication LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells(2024) Perez Moreno, Pablo; Riquelme, Ismael; Bizama, Carolina; Vergara, Luis; Tapia, Julio; Brebi, Priscilla; García, Patricia; Roa, JuanPublication Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival(2025) Mora, Bárbara; Reyes, María; Lobos, Lorena; Del Campo, Matías; Buchegger, Kurt; Zanella, Louise; Riquelme, Ismael; Ili, Carmen; Brebi, PriscillaBackground: Gastric cancer (GC) is a significant cancer-related cause of death worldwide. GC's most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor type 5 (CCR5) have been proposed as a pivotal factor in cancer progression since its blockade has been linked with antineoplastic effects on tumor cell proliferation; nevertheless, its role in the chemoresistance of GC has not been elucidated. This study aimed to determine the effects induced by the CCR5 using Maraviroc (MVC), a highly selective CCR5 antagonist, on CDDP-resistant AGS cells (AGS R-CDDP), tumoroids (3D tumor spheroids), and animal models. Results: The combined CDDP and MVC treatment reduced cell viability and inhibited tumoroid formation in AGS R-CDDP cells. The effects of the MVC/CDDP combination on apoptosis and cell cycle progression were correlated with the increase in CDDP (dose-dependent). The mRNA levels of C-C Motif Chemokine Ligand 5 (CCL5), the main ligand for CCR5, decreased significantly in cells treated with the MVC/CDDP combination. MVC in the MVC/CDDP combination improved the survival rate and biochemical parameters of CDDP-treated mice by reducing the side effects of CDDP alone. Conclusions: This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.Item Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer(Impact Journals, 2017) Weber, Helga; Valbuena, Jose R.; Barbhuiya, Mustafa A; Stein, Stefan; Kunkel, Hana; Garcia, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime; Kurtz, Stephen; Tyner, Jeffrey; Calderón, Juan Francisco; Corvalan, Alejandro; Grez, Manuel; Pandey, Akhilesh; Leal-Rojas, Pamela; Roa, Juan C.Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.