Person:
Anguita Mandly, Eduardo Luis

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First Name
Eduardo Luis
Last Name
Anguita Mandly
URI
https://hdl.handle.net/20.500.14352/79480
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Medicina
Area
Medicina
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2023 - 20242
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    Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production
    (International journal of molecular sciences, 2024) Ramos Acosta, Carlos; Huerta Pantoja, Laura; Salazar Hidalgo, Milton Eduardo; Mayol, Elsa; Jiménez Vega, Selene; García Peña, Pablo; Jordi Cruz, Jenifeer; Baquero, Cristina; Porras Gallo, María Almudena; Íñigo Rodríguez, Belén; Benavente Cuesta, Celina; Candel González, Francisco Javier; Anguita Mandly, Eduardo Luis
    Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.
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    Specific Cellular and Humoral Immune Responses to the Neoantigen RBD of SARS-CoV-2 in Patients with Primary and Secondary Immunodeficiency and Healthy Donors
    (Biomedicines, 2023) Mohamed, Kauzar Mohamed; Guevara Hoyer, Kissy; Jiménez García, Carlos; García Bravo, Laura; Rodríguez de la Peña, Antonia; Mediero Valeros, Beatriz; Cañizares Velázquez, Cristina; Culebras López, Esther; Cabello, Noemí; Estrada Pérez, Vicente; Fernández Arquero, Miguel; Ocaña, Alberto; Delgado-Iribarren García-Campero, Albert; Martínez-Novillo González, Mercedes; Bolaños, Estefanía; Anguita Mandly, Eduardo Luis; Peña Cortijo, Ascensión; Benavente Cuesta, Celina; Benítez Fuentes, Javier David; Pérez Segura, Pedro; Sánchez Ramón, Silvia María
    Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.