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 informationCasas E, Vavouri T
Mechanisms of epigenetic inheritance of variable traits through the germline.
Reproduction Jun 2020, 159 (6) R251-R263. Epub 22 Apr 2020During 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.
More informationBlasco 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 2020Carfilzomib 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.
More informationCossío 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 2020A 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.
More informationColli 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 2020Interferon-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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