Demostren l'efectivitat d'un fàrmac contra les cèl·lules que inicien els tumors

Un estudi dirigit pel professor de la UAB Joan Seoane, investigador principal del grup de recerca Expressió Gènica i Càncer del Vall d'Hebron Institut d'Oncologia (VHIO), ha identificat marcadors que assenyalen quines són les cèl·lules responsables de l'inici i recurrència d'un tumor. Els científics han demostrar l'efectivitat d'un conjunt de fàrmacs per a eliminar aquestes cèl·lules.Un estudio dirigido por el profesor de la UAB Joan Seoane, investigador principal del grupo de investigación Expresión Génica y Cáncer del Vall d'Hebron Institut d'Oncologia (VHIO), ha identificado marcadores que señalan cuáles son las células responsables del inicio y recurrencia de un tumor. Los científicos han demostrado la efectividad de un conjunto de fármacos para eliminar estas células.A research carried out by Joan Seoane, head researcher of the Gene Expression and Cancer group at Vall d'Hebron Institute of Oncology (VHIO), identified markers indicating the cells responsible for the onset and recurrence of tumours. Scientists have demonstrated that a combination of drugs can be effective in eliminating these cells

Identificación de marcadores de superficie celular en célulasin iniciadoras del cáncer procedentes de pacientes con glioma

Comunicaciones a congreso

On the nomenclatural types of "Gelidiella tinerfensis" Seoane-Camba, "Gelidium cantabricum" Seoane-Camba and "Gelidiocolax deformans" Seoane-Camba

Sobre els tipus nomenclaturals de Gelidiella tinerfensis Seoane-Camba, Gelidium cantabricum Seoane-Camba i Gelidiocolax deformans Seoane-Camba

Functional screening of amplification outlier oncogenes in organoid models of early tumorigenesis

Genomics; Organoid; Squamous cancerGenómica funcional; Organoide; Cáncer escamosoGenòmica funcional; Organoide; Càncer escamósSomatic copy number gains are pervasive across cancer types, yet their roles in oncogenesis are insufficiently evaluated. This inadequacy is partly due to copy gains spanning large chromosomal regions, obscuring causal loci. Here, we employed organoid modeling to evaluate candidate oncogenic loci identified via integrative computational analysis of extreme copy gains overlapping with extreme expression dysregulation in The Cancer Genome Atlas. Subsets of “outlier” candidates were contextually screened as tissue-specific cDNA lentiviral libraries within cognate esophagus, oral cavity, colon, stomach, pancreas, and lung organoids bearing initial oncogenic mutations. Iterative analysis nominated the kinase DYRK2 at 12q15 as an amplified head and neck squamous carcinoma oncogene in p53−/− oral mucosal organoids. Similarly, FGF3, amplified at 11q13 in 41% of esophageal squamous carcinomas, promoted p53−/− esophageal organoid growth reversible by small molecule and soluble receptor antagonism of FGFRs. Our studies establish organoid-based contextual screening of candidate genomic drivers, enabling functional evaluation during early tumorigenesis.This work was supported by the NCI Cancer Target Discovery and Development (CTD∧2) Network (U01CA217851, C.J.K and C.C.; U01CA176058, W.C.H.). Support was also provided by NIH K08DE027730 and D.R. discretionary funds to A.A.S., AEI RYC2019- 026576-I, “LaCaixa” Foundation LCF/PR/PR17/51120011 to J.A.S., and NIH U54CA224081, NIH U01CA199241, Emerson Collective, Ludwig Cancer Research, and Stand Up To Cancer to C.J.K. This manuscript is dedicated to the memories of Dr. Daniela Gerhard and Dr. Kenneth Scott

Dual inhibition of TGF-β and PD-L1: a novel approach to cancer treatment

Immune checkpoint inhibitor; Tumor microenvironmentInhibidor del punto de control inmunitario; Microambiente tumoralInhibidor del punt de control immunitari; Microambient tumoralTransforming growth factor-β (TGF-β) and programmed death ligand 1 (PD-L1) initiate signaling pathways with complementary, nonredundant immunosuppressive functions in the tumor microenvironment (TME). In the TME, dysregulated TGF-β signaling suppresses antitumor immunity and promotes cancer fibrosis, epithelial-to-mesenchymal transition, and angiogenesis. Meanwhile, PD-L1 expression inactivates cytotoxic T cells and restricts immunosurveillance in the TME. Anti-PD-L1 therapies have been approved for the treatment of various cancers, but TGF-β signaling in the TME is associated with resistance to these therapies. In this review, we discuss the importance of the TGF-β and PD-L1 pathways in cancer, as well as clinical strategies using combination therapies that block these pathways separately or approaches with dual-targeting agents (bispecific and bifunctional immunotherapies) that may block them simultaneously. Currently, the furthest developed dual-targeting agent is bintrafusp alfa. This drug is a first-in-class bifunctional fusion protein that consists of the extracellular domain of the TGF-βRII receptor (a TGF-β ‘trap’) fused to a human immunoglobulin G1 (IgG1) monoclonal antibody blocking PD-L1. Given the immunosuppressive effects of the TGF-β and PD-L1 pathways within the TME, colocalized and simultaneous inhibition of these pathways may potentially improve clinical activity and reduce toxicity.This manuscript was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945), and was previously part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline. Medical writing support was provided by Spencer Hughes of ClinicalThinking, Inc., which was also funded by the healthcare business of Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3). This manuscript was funded in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, and by a Cooperative Research and Development Agreement between the National Cancer Institute and EMD Serono, Billerica, MA, USA (CrossRef Funder ID:10.13039/100004755)

Effects of Cognitive Reserve on Cognitive Performance in a Follow-Up Study in Older Adults With Subjective Cognitive Complaints. The Role of Working Memory

Objective: Analyze the effects of CR on cognitive performance in adults with subjective cognitive complaints at follow-up. Method: We analyzed the factorial structure of the three constructs defined in cognitive performance (Episodic memory, Working memory, and General cognitive performance) separately to search for evidence of the invariance of the measurement model. We then developed four structural nested models to analyze the relationship between CR and cognitive performance, measured at baseline and after approximately 18 months, in 266 participants older than 50 years with subjective cognitive complaints. Results: The nested models revealed the following main results: direct effects of CR on all cognitive constructs at baseline and also indirect effects on the same constructs at follow-up, and indirect effects of CR on other cognitive constructs at follow-up via working memory at follow-up. Conclusion: The findings show that the proposed model is useful for measuring the influence of CR on cognitive performance in follow-up studies and that CR has a positive influence on cognitive performance at follow-up via working memory. CR may enhance mechanisms of information processing, favoring performance of tasks involving other cognitive constructs in older adults with subjective cognitive complaintsThis work was financially supported by the Spanish Directorate General of Scientific and Technical Research (Project PSI2014- 55316-C3-1-R) and by the Galician Government (Consellería de Cultura, Educación e Ordenación Universitaria; axudas para a consolidación e estruturación de unidades de investigación competitivas do Sistema Universitario de Galicia; GRC (GI-1807-USC); Ref: ED431-2017/27) through FEDER foundsS

Using an overlapping time interval strategy to study diagnostic instability in mild cognitive impairment subtypes.

(1) Background: Mild cognitive impairment (MCI) is a diagnostic label in which stability is typically low. The aim of this study was to examine temporal changes in the diagnosis of MCI subtypes by using an overlapping-time strategy; (2) Methods: The study included 435 participants aged over 50 years with subjective cognitive complaints and who completed at least one follow-up evaluation. The probability of transition was estimated using Bayesian odds ratios; (3) Results: Within the different time intervals, the controls with subjective cognitive complaints represented the largest proportion of participants, followed by sda-MCI at baseline and in the first five intervals of the follow-up, but not in the last eight intervals. The odds ratios indicated higher odds of conversion to dementia in sda-MCI and mda-MCI groups relative to na-MCI (e.g., interval 9-15 months-sda-MCI OR = 9 and mda-MCI OR = 3.36; interval 27-33-sda-MCI OR = 16 and mda-MCI = 5.06; interval 42-48-sda-MCI OR = 8.16 and mda-MCI = 3.45; interval 45-51-sda-MCI OR = 3.31 and mda-MCI = 1); (4) Conclusions: Notable patterns of instability consistent with the current literature were observed. The limitations of a prospective approach in the study of MCI transitions are discussed

Validación por SRM de marcadores de la actividad TGF-β en CSF de pacientes con glioma

Comunicaciones a congreso

Leptomeningeal metastasis from solid tumours: EANO–ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Central nervous system; Clinical practice guideline; NeurologicalSistema nerviós central; Guia de pràctica clínica; NeurològicSistema nervioso central; Guía de práctica clínica; NeurológicoThis Clinical Practice Guideline provides recommendations for managing leptomeningeal metastases from solid tumours