The Conversation: un escaparate del conocimiento para todos los públicos

Artículo de divulgación publicado en The Conversation España el día 26/06/2023.La edición en español de The Conversation celebra hoy su quinto aniversario en un evento abierto al público en Fundación Telefónica. En este tiempo esta plataforma divulgativa ha editado, publicado y diseminado cerca de 10 000 artículos de casi 8 000 autores y autoras vinculados a instituciones académicas y científicas del ámbito hispanohablante, que han sido republicados por 700 medios de todo el mundo y leídos más de 300 millones de veces. Con motivo de este aniversario, hemos pedido a miembros del comité asesor , encargado de velar por el rigor y solvencia de esta plataforma, que emitan su valoración sobre la evidencia y calidad del contenido publicado cada día.N

Engineering Iron Oxide Nanoparticles for Clinical Settings

Iron oxide nanoparticles (IONPs) occupy a privileged position among magnetic nanomaterials with potential applications in medicine and biology. They have been widely used in preclinical experiments for imaging contrast enhancement, magnetic resonance, immunoassays, cell tracking, tissue repair, magnetic hyperthermia and drug delivery. Despite these promising results, their successful translation into a clinical setting is strongly dependent upon their physicochemical properties, toxicity and functionalization possibilities. Currently, IONPs-based medical applications are limited to the use of non-functionalized IONPs smaller than 100 nm, with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. However, the main entry of IONPs into the scene of medical application will surely arise from their functionalization possibilities that will provide them with the capacity to target specific cells within the body, and hence to play a role in the development of specific therapies. In this review, we offer an overview of their basic physicochemical design parameters, giving an account of the progress made in their functionalization and current clinical applications. We place special emphasis on past and present clinical trials

A New Natural Antimycotic Agent is Effective Against Oropharyngeal Candidiasis: The VIPROCAN Study.

Background: The incidence of community and nosocomial candidiasis has dramatically increased in the last two decades. There are multiple treatments for this infection, but the toxicity of some and the induction of resistant strains require the development of new compounds. Objectives: With the aim of reducing the Candida population in the oropharyngeal cavity, we have formulated a toothpaste with VG-01 agent, composed of a mixture of carnosic acid (CA) and propolis (PP). Methods: We investigated the ability of VG-01 toothpaste to minimize and stabilize fungal presence in 21 patients diagnosed with clinical oropharyngeal candidiasis. Results: Our data indicate that VG-01 toothpaste showed an effect not only against the most frequent species of Candida, C. albicans, but also in the other species analyzed. 82% of patients stated that they would continue using it outside the study. Conclusion: Our data demonstrate that VG-01, composed of CA and PP is a potential antimycotic agent effective against the most common species that cause oropharyngeal candidiasis present in clinical practicepost-print988 K

Original Article Biomarkers of erlotinib response in non-small cell lung cancer tumors that do not harbor the more common epidermal growth factor receptor mutations

Abstract: Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancers, which are the leading cause of cancer-related deaths in the world. Tyrosine kinase inhibitors such as erlotinib represent one therapeutic options presently recommended for tumors produced by activating mutations in the gene coding of epidermal growth factor receptor (EGFR). The aim of this study is the identification of possible biomarkers for tumor sensitivity to erlotinib in the absence of the main EGFR mutations. The erlotinib sensitivity of cells isolated from 41 untreated NSCLC patients was determined and compared with the presence of the more frequent EGFR mutations. Several patients had tumor cells highly sensitive to erlitinib in the absence of the EGFR mutations analyzed. The gene expression profile of 3 erlotinib-sensitive tumors was compared with that of 4 resistant tumors by DNA microarray hybridization. Sixteen genes were expressed at significantly higher levels in the resistant tumors than in the sensitive tumors. The possible correlation between erlotinib sensitivity and the expression of these genes was further analyzed using the data for the NSCLC, breast cancer and colon cancer cell lines of the NCI60 collection. The expression of these genes was correlated with the overall survival of 5 patients treated with erlotinib, according to The Cancer Genome Atlas (TCGA) database. Overlapping groups of 7, 5 and 3 genes, including UGT1A6, TRIB3, MET, MMP7, COL17A1, LCN2 and PTPRZ1, whose expression correlated with erlotinib activity was identified. In particular, low MET expression levels showed the strongest correlation

SOX2(+) Cell Population from Normal Human Brain White Matter Is Able to Generate Mature Oligodendrocytes

Peer reviewe

Cancer stem cells from human glioblastoma resemble but do not mimic original tumors after in vitro passaging in serum-free media

Human gliomas harbour cancer stem cells (CSCs) that evolve along the course of the disease, forming highly heterogeneous subpopulations within the tumour mass. These cells possess self-renewal properties and appear to contribute to tumour initiation, metastasis and resistance to therapy. CSC cultures isolated from surgical samples are considered the best preclinical in vitro model for primary human gliomas. However, it is not yet well characterized to which extent their biological and functional properties change during in vitro passaging in the serum-free culture conditions. Here, we demonstrate that our CSC-enriched cultures harboured from one to several CSC clones from the human glioma sample. When xenotransplanted into mouse brain, these cells generated tumours that reproduced at least three different dissemination patterns found in original tumours. Along the passages in culture, CSCs displayed increased expression of stem cell markers, different ratios of chromosomal instability events, and a varied response to drug treatment. Our findings highlight the need for better characterization of CSC-enriched cultures in the context of their evolution in vitro, in order to uncover their full potential as preclinical models in the studies aimed at identifying molecular biomarkers and developing new therapeutic approaches of human gliomas.Peer reviewe

Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study

Purpose: FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ~8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study of a selective FGFR1–3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas. Patients and Methods: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology criteria. Comprehensive genomic profiling was performed on available pretreatment archival tissue to explore additional molecular correlations with efficacy. Results: Among 26 patients, the 6-month PFS rate was 16.0% [95% confidence interval (CI), 5.0–32.5], median PFS was 1.7 months (95% CI, 1.1–2.8), and objective response rate was 3.8%. However, 4 patients had durable disease control lasting longer than 1 year. Among these, 3 had tumors harboring activating point mutations at analogous positions of FGFR1 (K656E; n = 2) or FGFR3 (K650E; n = 1) in pretreatment tissue; an FGFR3-TACC3 fusion was detected in the other. Hyperphosphatemia was the most frequently reported treatment-related adverse event (all-grade, 76.9%; grade 3, 3.8%) and is a known on-target toxicity of FGFR inhibitors. Conclusions: FGFR inhibitor monotherapy with infigratinib had limited efficacy in a population of patients with recurrent gliomas and different FGFR genetic alterations, but durable disease control lasting more than 1 year was observed in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3-TACC3 fusions. A follow-up study with refined biomarker inclusion criteria and centralized FGFR testing is warranted

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

Background: The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods: Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings: In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49-5956·71) in the IG and 7298·22 BAU/mL (6739·41-7903·37) in the CG (p 1:100 at day 180 (19% and 22%, respectively). Interpretation: Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180.Funded by Instituto de Salud Carlos III (ISCIII). AMB, AJC, JO, and JF are members of the VACCELERATE (European Corona Vaccine Trial Accelerator Platform) Network, which aims to facilitate and accelerate the design and implementation of COVID-19 phase 2 and 3 vaccine trials. JO is a member of the INsTRuCT (Innovative Training in Myeloid Regulatory Cell Therapy) Consortium, a network of European scientists from academia and industry focused on developing innovative immunotherapies. This work is funded by Instituto de Salud Carlos III, a Spanish public body assigned to the Ministry of Science and Innovation that manages and promotes public clinical research related to public health. The Spanish Clinical Trials Platform is a public network funded by the Instituto de Salud Carlos III (grant numbers PTC20/00018 and PT17/0017), the State Plan for Research, Development, and Innovation 2013−16, the State Plan for Scientific and Technical Research and Innovation 2017−20, and the Subdirectorate General for Evaluation and Promotion of Research, Instituto de Salud Carlos III, cofinanced with FEDER funds. CombiVacS was designed under the umbrella of the VACCELERATE project. VACCELER ATE and INsTRuCT received funding from the EU’s Horizon 2020 Research and Innovation Programme (grant agreement numbers 101037867 and 860003). The Instituto de Salud Carlos III is the Spanish partner in the VACCELERATE project. This work is partially funded by Institute of Health Carlos III (Instituto de Salud Carlos III − ISCIII −), (grants PI19CIII/00004 to JA and PI21CIII/00025 to MPO and JGP), and COVID-19 FUND (grants COV20/00679 and COV20/00072 to MPO and JA) and CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”. The authors thank all trial participants, the international data safety monitoring board (Appendix 1 p 23), and the trial steering committee (Appendix 1 pp 24−25). The authors thank Esther Prieto for editorial assistance and writing support (employed by Hospital Universitario La Paz; funded by the Instituto de Salud Carlos III, grant number PCT20/00018) and María Castillo-de la Osa (PEJ2018-004557-A) for excellent technical assistance.S

Financiación extraordinaria de proyectos de investigación sobre el SARS-Cov-2 y la enfermedad Covid-19

Sesión 4. La importancia del fomento y coordinación de la investigación en el control de la pandemia COVID-19Descripción de la financiación de proyectos de investigación sobre el SARS-COV-2 y la enfermedad COVID19, de acuerdo con los principios de necesidad social, emergencia y eficacia dado el interés general, con cargo al FONDO – COVID19 para contribuir a un mejor diagnóstico y tratamiento clínico de pacientes del SNS infectados por SARS-CoV-19 así como a la preparación y respuesta de salud pública en el contexto de la pandemia en curso de SARS-CoV-2N

Programa académico. SEMINARIO COVID-19: la epidemiología, la microbiología y la investigación en las estrategias de vigilancia y control de la pandemia. Universidad Internacional Menéndez Pelayo del 27 y 28 agosto de 2020

La pandemia por COVID-19 está provocando millones de casos en el todo el mundo, con una mortalidad relevante. El impacto de la infección ha sido devastador y podrían producirse nuevas ondas epidémicas. Para detectar precozmente estas nuevas ondas y controlar eficazmente sus efectos, deben desarrollarse e implementarse sistemas epidemiológicos y biológicos de vigilancia, y que estos sistemas puedan incorporar los hallazgos de las numerosas iniciativas investigadoras que existen por todo el mundo. El seminario va dirigido a profesionales sanitarios en general, con especial orientación a trabajadores de la salud pública: epidemiólogos, microbiólogos, infectólogos y otras especialidades sanitarias directamente implicadas en el control de la pandemia. También debería interesar a investigadores y científicos con proyectos en este campo de conocimiento, sociedades científicas, organizaciones y público en general que puedan estar implicados en los diferentes aspectos de COVID-19.N