Research publications

Found 1424 publicacions matching the indicated search criteria.
Comes M, Batlle M, Ribera JM

Treatment adapted to pregnancy in a patient with Burkitt lymphoma.

Med Clin (Barc) 12 Jun 2020, 154 (11) 470-471. Epub 20 Jul 2019More information
Casas E, Vavouri T

Mechanisms of epigenetic inheritance of variable traits through the germline.

Reproduction Jun 2020, 159 (6) R251-R263. Epub 22 Apr 2020
During the past half century, evidence for inheritance of variable traits has accumulated from experiments in plants and animals and epidemiological studies in humans. Here, we summarize some of the reported cases of epigenetic inheritance and the proposed mechanisms involved in the transmission of non-genetic information between generations in plants, nematodes, flies and mammals. It has long been accepted that information is epigenetically inherited in plants. Although many questions regarding the underlying mechanisms remain to be answered, it is now evident that epigenetic mechanisms are also responsible for the transmission of phenotypes in animals. We highlight similarities and differences between models and species.
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Blasco M, Martínez-Roca A, Rodríguez-Lobato LG, Garcia-Herrera A, Rosiñol L, Castro P, Fernández S, Quintana LF, Cibeira MT, Bladé J, Fernández de Larrea C, Tovar N, Jimenez R, Poch E, Guillen E, Campistol JM, Carreras E, Diaz-Ricart M, Palomo M

Complement as the enabler of carfilzomib-induced thrombotic microangiopathy.

Br. J. Haematol. 29 May 2020, . Epub 29 May 2020
Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.
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Cossío FP, Esteller M, Berdasco M

Towards a more precise therapy in cancer: Exploring epigenetic complexity.

Curr Opin Chem Biol 29 May 2020, 57 41-49. Epub 29 May 2020
A plethora of preclinical evidences suggests that pharmacological targeting of epigenetic dysregulation is a potent strategy to combat human diseases. Nevertheless, the implementation of epidrugs in clinical practice is very scarce and mainly limited to haematological malignancies. In this review, we discuss cutting-edge strategies to foster the chemical design, the biological rationale and the clinical trial development of epidrugs. Specifically, we focus on the development of dual hybrids to exploit multitargeting of key epigenetic molecules deregulated in cancer; the study of epigenetic-synthetic lethality interactions as a mechanism to address loss-of-function mutations, and the combination of epidrugs with other therapies such as immunotherapy to avoid acquired chemoresistance and increase therapy sensitivity. By exploring these challenges, among others, the field of epigenetic chemical biology will increase its potential for clinical benefit, and more effective strategies targeting the aberrant epigenome in cancer are likely to be developed both in haematological and solid tumours.
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Colli ML, Ramos-Rodríguez M, Nakayasu ES, Alvelos MI, Lopes M, Hill JLE, Turatsinze JV, Coomans de Brachène A, Russell MA, Raurell-Vila H, Castela A, Juan-Mateu J, Webb-Robertson BM, Krogvold L, Dahl-Jorgensen K, Marselli L, Marchetti P, Richardson SJ, Morgan NG, Metz TO, Pasquali L, Eizirik DL

An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells.

Nat Commun 22 May 2020, 11 (1) 2584. Epub 22 May 2020
Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells.
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Laporte-Amargos J, Gudiol C, Arnan M, Puerta-Alcalde P, Carmona-Torre F, Huguet M, Albasanz-Puig A, Parody R, Garcia-Vidal C, Del Pozo JL, Batlle M, Tebé C, Rigo-Bonnin R, Muñoz C, Padullés A, Tubau F, Videla S, Sureda A, Carratalà J

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE).

Trials 18 May 2020, 21 (1) 412. Epub 18 May 2020
Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN.
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Im A, Rashidi A, Wang T, Hemmer M, MacMillan ML, Pidala J, Jagasia M, Pavletic S, Majhail NS, Weisdorf D, Abdel-Azim H, Agrawal V, Al-Homsi AS, Aljurf M, Askar M, Auletta JJ, Bashey A, Beitinjaneh A, Bhatt VR, Byrne M, Cahn JY, Cairo M, Castillo P, Cerny J, Chhabra S, Choe H, Ciurea S, Daly A, Perez MAD, Farhadfar N, Gadalla SM, Gale R, Ganguly S, Gergis U, Hanna R, Hematti P, Herzig R, Hildebrandt GC, Lad DP, Lee C, Lehmann L, Lekakis L, Kamble RT, Kharfan-Dabaja MA, Khandelwal P, Martino R, Murthy HS, Nishihori T, O'Brien TA, Olsson RF, Patel SS, Perales MA, Prestidge T, Qayed M, Romee R, Schoemans H, Seo S, Sharma A, Solh M, Strair R, Teshima T, Urbano-Ispizua A, Van der Poel M, Vij R, Wagner JL, William B, Wirk B, Yared JA, Spellman SR, Arora M, Hamilton BK

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.

Biol. Blood Marrow Transplant. 17 May 2020, . Epub 17 May 2020
Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with relatively low incidence of GVHD. Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haploHCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with AML, ALL, MDS, or CML who underwent PTCy-based haploHCT (2013-2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced intensity (RIC) conditioning and bone marrow (BM) or peripheral blood (PB) graft source. 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2-4 aGVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (p=0.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (p<0.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2-4 acute GVHD; however, older donor age (30-49 versus <29 years) was significantly associated with higher rates of grade 2-4 acute GVHD (HR 1.53, 95% CI 1.11-2.12, p=0.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR 1.70, 95% CI 1.11-2.62, p=0.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haploHCT.  Our results indicate that in RIC haploHCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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García-Alfonso P, García-Carbonero R, García-Foncillas J, Pérez-Segura P, Salazar R, Vera R, Ramón Y Cajal S, Hernández-Losa J, Landolfi S, Musulén E, Cuatrecasas M, Navarro S

Update of the recommendations for the determination of biomarkers in colorectal carcinoma: National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

Clin Transl Oncol 16 May 2020, . Epub 16 May 2020
In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future.
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Martinez-Sanchez J, Palomo M, Torramade-Moix S, Moreno-Castaño AB, Rovira M, Gutiérrez-García G, Fernández-Avilés F, Escolar G, Penack O, Rosiñol L, Carreras E, Diaz-Ricart M

The induction strategies administered in the treatment of multiple myeloma exhibit a deleterious effect on the endothelium.

Bone Marrow Transplant. 13 May 2020, . Epub 13 May 2020
Multiple myeloma induction treatment includes proteasome inhibitors (PI) and immunomodulatory agents at present. The incidence of engraftment syndrome, a transplant complication potentially related to endothelium, has increased in the last years. Our aim was to investigate whether bortezomib (Velcade, V), thalidomide (T), and dexamethasone (D) affect the endothelium, and explore defibrotide (DF) as protective agent. Endothelial cells (ECs) in culture were exposed to the compounds separately or in combination, without (VTD) and with DF (VTD + DF). Changes in markers of: (i) inflammation (ICAM-1 expression and leukocyte adhesion), (ii) VWF production, (iii) cell permeability (VE-cadherin expression and cell monolayer integrity), and (iv) oxidative stress (ROS production and eNOS expression) were measured. ICAM-1 and VWF expression increased significantly in VTD but were similar to controls in VTD + DF. Separately, bortezomib was the main deleterious agent whereas dexamethasone showed no harmful effect. Leukocyte adhesion showed similar trends. VE-cadherin expression was lower in VTD and normalized in VTD + DF. EC permeability increased only with bortezomib. No changes were observed in oxidative stress markers. Our results demonstrate that bortezomib damages the endothelium, and DF prevents this effect. A better knowledge of the induction drugs impact will allow the design of measures to protect the endothelium.
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Eizirik DL, Pasquali L, Cnop M

Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure.

Nat Rev Endocrinol 12 May 2020, . Epub 12 May 2020
Loss of functional β-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind β-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms. These mechanisms differentially affect early β-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on β-cells in human disease. These advances include studies of islet morphology and human β-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the β-cell level and the endoplasmic reticulum stress signalling that contributes to β-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2α dependent). Here, we review these new findings, focusing on studies performed on human β-cells or on samples obtained from patients with diabetes mellitus.
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