Provencio, M. (Mariano)

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    Immunotherapy moves to the early-stage setting in non-small cell lung cancer: emerging evidence and the role of biomarkers
    (MDPI AG, 2018) Berraondo, P. (Pedro); Couñago, F. (Felipe); Hernando-Trancho, F. (Florentino); Calvo, V. (Virginia); Mielgo-Rubio, X. (Xabier); Conde, E. (Esther); Martín, M. (Margarita); De-Castro, J. (Javier); López-Ríos, F. (Fernando); Provencio, M. (Mariano); Luna, J. (Javier); Remon, J. (Jordi); Higuera, O. (Oliver); Jarabo, J.R. (José Ramón)
    Despite numerous advances in targeted therapy and immunotherapy in the last decade, lung cancer continues to present the highest mortality rate of all cancers. Targeted therapy based on specific genomic alterations, together with PD-1 and CTLA-4 axis blocking-based immunotherapy, have significantly improved survival in advanced non-small cell lung cancer (NSCLC) and both therapies are now well-established in this clinical setting. However, it is time for immunotherapy to be applied in patients with early-stage disease, which would be an important qualitative leap in the treatment of lung cancer patients with curative intent. Preliminary data from a multitude of studies are highly promising, but therapeutic decision-making should be guided by an understanding of the molecular features of the tumour and host. In the present review, we discuss the most recently published studies and ongoing clinical trials, controversies, future challenges and the role of biomarkers in the selection of best therapeutic options.
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    SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry
    (2023) López-Criado, P. (Pilar); Fernández-Morales, L.A. (Luis Antonio); Boada, A. (Aram); Feito-Rodríguez, M. (Marta); Carrera, C. (Cristina); Yelamos, O. (Oriol); Gonzalez-Cao, M. (María); Luna-Fra, P. (Pablo); Soria, A. (Ainara); Valles, L. (Lara); Antoñanzas-Basa, M. (Mónica); Martin-Algarra, S. (Salvador); Sequero, S. (Silvia); Martin-Liberal, J. (Juan); Villalobos, L. (Laura); Aguayo-Zamora, C. (Cristina); Cruz, R. (Raquel); Marquez-Rodas, I. (Iván); Maldonado-Seral, C. (Cayetana); Manzano, J.L. (José Luis); García-Castaño, A. (Almudena); Puig, S. (Susana); González-Barrallo, I. (Inés); López-Castro, R. (Rafael); Cerezuela, P. (Pablo); Muñoz, E. (Eva); Gardeazabal, J. (Jesús); Rubio, B. (Belén); Feltes-Ochoa, R. (Rosa); Puertolas, T. (Teresa); Drozdowskyj, A. (Ana); Rodrigo, A. (Alberto); Rodríguez-Jiménez, P. (Pedro); Provencio, M. (Mariano); Martínez-Vila, C. (Clara); Berrocal, A. (Alfonso); Crespo, G. (Guillermo); Rodríguez-Moreno, J.F. (Juan Francisco); Mujica, K. (Karmele); Ayala-De-Miguel, P. (Pablo)
    Background The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ( GRAVID ).Methods The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021.Results One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality.Conclusion Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection.
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    A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non‑processed plasma
    (2022) Beneitez, A. (Alexandra); Sánchez-Herrero, E. (Estela); Valés-Gómez, M. (Mar); Gonzalez-Hernandez, A. (Alvaro); Romero, A. (A.); Provencio, M. (Mariano); Jara-Acevedo, R. (Ricardo); Yáñez-Mó, M. (María); Campos-Silva, C. (Carmen)
    Background: Extracellular vesicles (EVs), released by most cell types, provide an excellent source of biomarkers in biological fluids. However, in order to perform validation studies and screenings of patient samples, it is still necessary to develop general techniques permitting rapid handling of small amounts of biological samples from large numbers of donors. Results: Here we describe a method that, using just a few microliters of patient’s plasma, identifies tumour markers exposed on EVs. Studying physico-chemical properties of EVs in solution, we demonstrate that they behave as stable colloidal suspensions and therefore, in immunocapture assays, many of them are unable to interact with a stationary functionalised surface. Using flocculation methods, like those used to destabilize colloids, we demonstrate that cationic polymers increase EV ζ-potential, diameter, and sedimentation coefficient and thus, allow a more efficient capture on antibody-coated surfaces by both ELISA and bead-assisted flow cytometry. These findings led to optimization of a protocol in microtiter plates allowing effective immunocapture of EVs, directly in plasma without previous ultracentrifugation or other EV enrichment. The method, easily adaptable to any laboratory, has been validated using plasma from lung cancer patients in which the epithelial cell marker EpCAM has been detected on EVs. Conclusions: This optimized high throughput, easy to automate, technology allows screening of large numbers of patients to phenotype tumour markers in circulating EVs, breaking barriers for the validation of proposed EV biomarkers and the discovery of new ones.