Person: Fernández Aceñero, María Jesús
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First Name
María Jesús
Last Name
Fernández Aceñero
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Area
Anatomía Patológica
Identifiers
10 results
Search Results
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Item Multiplexed biosensing diagnostic platforms detecting autoantibodies to tumor-associated antigens from exosomes released by CRC cells and tissue samples showed high diagnostic ability for colorectal cancer(Engineering, 2021) Montero Calle, Ana; Aranguren Abeigon, Itziar; Garranzo Asensio, María; Povés Francés, Carmen; Fernández Aceñero, María Jesús; Martínez Useros, Javier; Sanz, Rodrigo; Dziaková, Jana; Rodríguez Cobos, Javier; Solís Fernández, Guillermo; Povedano, Eloy; Gamella Carballo, Maria; Torrente Rodríguez, Rebeca Magnolia; Alonso Navarro, Miren; Ríos, Vivian de los; Casal, J. Ignacio; Domínguez Muñóz, Gemma; Guzmán Aránguez, Ana Isabel; Peláez García, Alberto, Alberto; Pingarrón Carrazón, José Manuel; Campuzano Ruiz, Susana; Barderas Manchado, RodrigoColorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. The 5-year survival rate of CRC patients depends on the stage at diagnosis, being higher than 80% when CRC is diagnosed in the early stages but lower than 10% when CRC is diagnosed in advanced stages. Autoantibodies against specific CRC autoantigens (tumor-associated antigens (TAAs)) in the sera of patients have been widely demonstrated to aid in early diagnosis. Thus, we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy. To that end, we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis. A total of 103 proteins were identified as potential autoantigens specific to CRC. After bioinformatics and meta-analysis, we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot (WB) and immunohistochemistry (IHC). We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients, along with an association of nine of these proteins with CRC prognosis. After validation, all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals, either by luminescence Halotag-based beads, or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection. Taken together, our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases; they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care (POC) device for CRC detection with high diagnostic ability.Item p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins(Cancers, 2023) Montero Calle, Ana; Garranzo Asensio, María; Torrente Rodríguez, Rebeca Magnolia; Ruiz Valdepeñas Montiel, Víctor; Poves, Carmen; Dziakova, Jana; Sanz, Rodrigo; Díaz Del Arco, Cristina; Pingarrón Carrazón, José Manuel; Fernández Aceñero, María Jesús; Campuzano Ruiz, Susana; Barderas Manchado, RodrigoColorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by liquid biopsy. However, new studies related to the humoral immune response in cancer are needed to enable blood-based diagnosis of the disease. Here, our aim was to characterize the humoral immune response associated with the different p53 and p63 proteoforms derived from alternative splicing and previously described as aberrantly expressed in CRC. Thus, here we investigated the diagnostic ability of the twelve p53 proteoforms and the eight p63 proteoforms described to date, and their specific N-terminal and C-terminal end peptides, by means of luminescence HaloTag beads immunoassays. Full-length proteoforms or specific peptides were cloned as HaloTag fusion proteins and their seroreactivity analyzed using plasma from CRC patients at stages I-IV (n = 31), individuals with premalignant lesions (n = 31), and healthy individuals (n = 48). p53γ, Δ40p53β, Δ40p53γ, Δ133p53γ, Δ160p53γ, TAp63α, TAp63δ, ΔNp63α, and ΔNp63δ, together with the specific C-terminal end α and δ p63 peptides, were found to be more seroreactive against plasma from CRC patients and/or individuals with premalignant lesions than from healthy individuals. In addition, ROC (receiver operating characteristic) curves revealed a high diagnostic ability of those p53 and p63 proteoforms to detect CRC and premalignant individuals (AUC higher than 85%). Finally, electrochemical biosensing platforms were employed in POC-like devices to investigate their usefulness for CRC detection using selected p53 and p63 proteoforms. Our results demonstrate not only the potential of these biosensors for the simultaneous analysis of proteoforms’ seroreactivity, but also their convenience and versatility for the clinical detection of CRC by liquid biopsy. In conclusion, we here show that p53 and p63 proteoforms possess differential seroreactivity in CRC patients in comparison to controls, distinctive from canonical proteins, which should improve the diagnostic panels for obtaining a blood-based biomarker signature for CRC detection.Item Multiplexed monitoring of a novel autoantibody diagnostic signature of colorectal cancer using HaloTag technology-based electrochemical immunosensing platform(Theranostics, 2020) Garranzo Asensio, María; Guzmán Aránguez, Ana Isabel; Povedano, Eloy; Ruiz Valdepeñas Montiel, Víctor; Povés Francés, Carmen; Fernández Aceñero, María Jesús; Montero Calle, Ana; Solís Fernández, Guillermo; Fernández Díez, Servando; Camps, Jordi; Arenas, Meritxell; Rodríguez Tomás, Elisabeth; Joven, Jorge; Sánchez Martínez, Maricruz; Rodrígez, Nuria; Domínguez Muñóz, Gemma; Yáñez Sedeño, Paloma; Pingarrón Carrazón, José Manuel; Campuzano Ruiz, Susana; Barderas Manchado, RodrigoBackground and Purpose: The humoral immune response in cancer patients can be used for early detection of the disease. Autoantibodies raised against tumor-associated antigens (TAAs) are promising clinical biomarkers for reliable cancer diagnosis, prognosis, and therapy monitoring. In this study, an electrochemical disposable multiplexed immunosensing platform able to integrate difficult- and easy-to-express colorectal cancer (CRC) TAAs is reported for the sensitive determination of eight CRC-specific autoantibodies. Methods: The electrochemical immunosensing approach involves the use of magnetic microcarriers (MBs) as solid supports modified with covalently immobilized HaloTag fusion proteins for the selective capture of specific autoantibodies. After magnetic capture of the modified MBs onto screen-printed carbon working electrodes, the amperometric responses measured using the hydroquinone (HQ)/H2O2 system were related to the levels of autoantibodies in plasma. Results: The biosensing platform was applied to the analysis of autoantibodies against 8 TAAs described for the first time in this work in plasma samples from healthy asymptomatic individuals (n=3), and patients with high-risk of developing CRC (n=3), and from patients already diagnosed with colorectal (n=3), lung (n=2) or breast (n=2) cancer. The developed bioplatform demonstrated an improved discrimination between CRC patients and controls (asymptomatic healthy individuals and breast and lung cancer patients) compared to an ELISA-like luminescence test. Conclusions: The proposed methodology uses a just-in-time produced protein in a simpler protocol, with low sample volume, and involves cost-effective instrumentation, which could be used in a high-throughput manner for reliable population screening to facilitate the detection of early CRC patients at affordable cost.Item Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus(Acta Biomaterialia, 2022) Aguilera Correa, John Jairo; Gisbert Garzarán, Miguel; Mediero, A.; Pablo Velasco, David de; Fernández Aceñero, María Jesús; Lozano Borregón, Daniel; Esteban, J.; Vallet Regí, María Dulce NombreOsteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis. Statement of significance In this work, we propose the use of bone-targeted mesoporous silica nanoparticles to address S. aureus-caused osteomyelitis that render synergistic therapeutic effect via multidrug delivery. Because the bacterial biofilm is responsible for an aggressive surgical approach and prolonged antibiotic treatment, the nanoparticles have been functionalized with a functional coating able to both disaggregate the biofilm, hamper premature antibiotic release and protect the intact bone. These engineered nanoparticles are able to effectively target bone tissue both in vitro and in vivo, showing high biocompatibility and elevated antibacterial effect.- Project number: 342
Item Uso de los modelos 3D de los corazones fetales en la docencia multidisciplinar del diagnóstico tratamiento y pronóstico de las cardiopatías congénitas complejas(2022) Leon Luis, Juan; Bravo Arribas, Coral; Álvarez Martín, Teresa; Marín Rodriguez, Carlos; Fernández Aceñero, María Jesús; Ortega Núñez, Miguel Angel; Gamez Alderete, Francisco de Asis; Felter, Marta; Fernández Muñóz, María; Fraile, Andrea; Gonzalez Martín, Agustina Eliana; Gutiérrez Rio, Beatriz; Pérez Caballero, Ramón; Reyes Angullo, Zurine RaquelComo continuidad a un proyecto de innovación docente previo basado en el desarrollo de los modelos 3D del corazón fetal, normal y patológico, en estos momentos somos más conscientes como esta tecnología La tecnología 3D supone un cambio de paradigma en docencia en la que pueden participar, obstetras, pediatras, cirujanos cardiacos infantiles y además anatomopatólogos. Como hemos destacado los modelos 3d son un tipo de manufactura aditiva que permite transformar un modelo digital en un objeto tridimensional real y tangible. Esto permite una docencia teórico-práctica innovadora que se enmarca en el contexto moderno de una atención médica personalizada (medicina de precisión centrada en el paciente, visible y comprensible por el estudiante, comprensión en el proceso de comunicación médica con el paciente y con el resto de profesionales médicos que atienden a los pacientes, ayuda en la toma de decisiones ante el diagnostico de entidades patológicas, entre otras cuestiones). Item Antibiotic delivery from bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus(2022) Aguilera Correa, John Jairo; Gisbert Garzarán, Miguel; Mediero Pérez, María Carmen; Fernández Aceñero, María Jesús; Pablo-Velasco, D. de; Lozano Borregón, Daniel; J. Esteban; Vallet Regí, María Dulce NombreOsteomyelitis is a hard-to-treat infection of the bone and bone marrow that is mainly caused by Staphylococcus aureus, with an increasing incidence of methicillin-resistant S. aureus (MRSA). Owing to the aggressiveness of these bacteria in colonizing and destroying the bone, systemic antibiotic treatments fail to eradicate the infection. Instead, it normally entails surgery to remove the dead or infected bone. In this work, we report bone-targeted mesoporous silica nanoparticles for the treatment of osteomyelitis. The nanoparticles have been engineered with a functional gelatine/colistin coating able to hamper premature release from the mesopores while effectively disaggregating the bacterial biofilm. Because antibiotic resistance is a global emergency, we have designed two sets of identical nanoparticles, carrying each of them a clinically relevant antibiotic, that have demonstrated to have synergistic effect. The bone-targeted nanoparticles have been thoroughly evaluated in vitro and in vivo, obtaining a notable reduction of the amount of bacteria in the bone in just 24 h after only one dose, and paving the way for localized, nanoparticle-mediated treatment of MRSA-caused osteomyelitis.Item Impact of Age at Diagnosis on Clinicopathological Features, Prognosis, and Management of Gastric Cancer: A Retrospective Single-Center Experience from Spain(Cancers, 2023) Estrada Muñoz, Lourdes; Molina Roldán, Elena; García Gómez de las Heras, Soledad; Díaz Del Arco, Cristina; Ortega Medina, Luis; Fernández Aceñero, María JesúsThe incidence of renal mass detection has increased during recent decades, with an increased diagnosis of small renal masses, and a final benign diagnosis in some cases. To avoid unnecessary surgeries, there is an increasing interest in using radiomics tools to predict histological results, using radiological features. We performed a narrative review to evaluate the use of radiomics in renal mass characterization. Conventional images, such as computed tomography (CT) and magnetic resonance (MR), are the most common diagnostic tools in renal mass characterization. Distinguishing between benign and malignant tumors in small renal masses can be challenging using conventional methods. To improve subjective evaluation, the interest in using radiomics to obtain quantitative parameters from medical images has increased. Several studies have assessed this novel tool for renal mass characterization, comparing its ability to distinguish benign to malign tumors, the results in differentiating renal cell carcinoma subtypes, or the correlation with prognostic features, with other methods. In several studies, radiomic tools have shown a good accuracy in characterizing renal mass lesions. However, due to the heterogeneity in the radiomic model building, prospective and external validated studies are needed.- Project number: 66
Item Uso de los modelos 3D de los corazones fetales en la docencia multidisciplinar del diagnóstico tratamiento y pronóstico de las cardiopatías congénitas(2022) León Luis, Juan Antonio; Bravo Arribas, Coral; Álvarez Martín, Teresa; Perez Caballero, Ramón; Fernández Aceñero, María Jesús; Calvo Haro, José Antonio; Perez Mañanes, Ruben; Gonzalez Martín, Agustina Eliana; Caamiña Alvarez, Sara; Rodeño Fernández, Haizea; Gamez Alderete, Francisco de Asis Item Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis(Journal of proteomics, 2020) Garranzo Asensio, María; San Segundo Acosta, Pablo; Povés Francés, Carmen; Fernández Aceñero, María Jesús; Martínez Useros, Javier; Montero Calle, Ana; Solís Fernández, Guillermo; Sánchez Martínez, Mari Cruz; Rodríguez, Nuria; Cerón, María Ángeles; Fernández Díez, Servando; Domínguez Muñóz, Gemma; Ríos, Vivian de los; Peláez García, Alberto, Alberto; Guzmán Aránguez, Ana Isabel; Barderas, RodrigoColorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related death worldwide. Its diagnosis at early stages would significantly improve the survival of CRC patients. The humoral immune response has been demonstrated useful for cancer diagnosis, predating clinical symptoms up to 3 years. Here, we employed an in-depth seroproteomic approach to identify proteins that elicit a humoral immune response in CRC patients. The seroproteomic approach relied on the immunoprecipitation with patient-derived autoantibodies of proteins from CRC cell lines with different metastatic properties followed by LC-MS/MS. After bioinformatics, we focused on 31 targets of CRC autoantibodies. After WB and IHC validation, ERP44 and TALDO1 showed potential to discriminate disease-free and metastatic CRC patients, and time to recurrence of CRC patients in stage II. Using plasma samples of 30 healthy individuals, 28 premalignant individuals, and 32 CRC patients, nine out of 13 selected targets for seroreactive analysis showed significant diagnostic ability to discriminate either CRC patients or premalignant subjects from controls. Our results suggest that the here defined panel of CRC autoantibodies and their target proteins should be included in CRC blood-based biomarker panels to get a clinically useful blood-based diagnostic signature for CRC detection. Significance: Colorectal cancer is one of the deadliest cancer types mainly due to its late diagnosis. Its early diagnosis, therefore, is of great importance since it would significantly improve the survival of CRC patients. In our work, the in-depth seroproteomic analysis of colorectal cancer using isolated IgGs from colorectal cancer patients and controls and protein extract of colorectal cancer cells provide the identification of valuable biomarkers with diagnostic and prognostic ability of the disease.Item Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis(Journal of proteomics, 2020) Garranzo Asensio, María; San Segundo Acosta, Pablo; Povés Francés, Carmen; Fernández Aceñero, María Jesús; Martínez Useros, Javier; Montero Calle, Ana; Solís Fernández, Guillermo; Sánchez Martínez, Maricruz; Rodríguez Salas, Nuria; Cerón, María Ángeles; Fernández Díez, Servando; Domínguez Muñóz, Gemma; Ríos, Vivian de los; Peláez García, Alberto, Alberto; Guzmán Aránguez, Ana Isabel; Barderas Manchado, RodrigoColorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related death worldwide. Its diagnosis at early stages would significantly improve the survival of CRC patients. The humoral immune response has been demonstrated useful for cancer diagnosis, predating clinical symptoms up to 3 years. Here, we employed an in-depth seroproteomic approach to identify proteins that elicit a humoral immune response in CRC patients. The seroproteomic approach relied on the immunoprecipitation with patient-derived autoantibodies of proteins from CRC cell lines with different metastatic properties followed by LC-MS/MS. After bioinformatics, we focused on 31 targets of CRC autoantibodies. After WB and IHC validation, ERP44 and TALDO1 showed potential to discriminate disease-free and metastatic CRC patients, and time to recurrence of CRC patients in stage II. Using plasma samples of 30 healthy individuals, 28 premalignant individuals, and 32 CRC patients, nine out of 13 selected targets for seroreactive analysis showed significant diagnostic ability to discriminate either CRC patients or premalignant subjects from controls. Our results suggest that the here defined panel of CRC autoantibodies and their target proteins should be included in CRC blood-based biomarker panels to get a clinically useful blood-based diagnostic signature for CRC detection. Significance: Colorectal cancer is one of the deadliest cancer types mainly due to its late diagnosis. Its early diagnosis, therefore, is of great importance since it would significantly improve the survival of CRC patients. In our work, the in-depth seroproteomic analysis of colorectal cancer using isolated IgGs from colorectal cancer patients and controls and protein extract of colorectal cancer cells provide the identification of valuable biomarkers with diagnostic and prognostic ability of the disease.