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  1. Article ; Online: RROL lncRNA role in multiple myeloma.

    Agirre, Xabier

    Blood

    2023  Volume 141, Issue 4, Page(s) 328–330

    MeSH term(s) Humans ; RNA, Long Noncoding/genetics ; Multiple Myeloma/genetics ; Multiple Myeloma/metabolism ; Chromatin ; MicroRNAs/metabolism ; Cell Communication
    Chemical Substances RNA, Long Noncoding ; Chromatin ; MicroRNAs
    Language English
    Publishing date 2023-01-26
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2022018471
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Aptamers, a New Therapeutic Opportunity for the Treatment of Multiple Myeloma.

    Amundarain, Ane / Pastor, Fernando / Prósper, Felipe / Agirre, Xabier

    Cancers

    2022  Volume 14, Issue 21

    Abstract: Multiple Myeloma (MM) remains an incurable disease due to high relapse rates and fast development of drug resistances. The introduction of monoclonal antibodies (mAb) has caused a paradigm shift in MM treatment, paving the way for targeted approaches ... ...

    Abstract Multiple Myeloma (MM) remains an incurable disease due to high relapse rates and fast development of drug resistances. The introduction of monoclonal antibodies (mAb) has caused a paradigm shift in MM treatment, paving the way for targeted approaches with increased efficacy and reduced toxicities. Nevertheless, antibody-based therapies face several difficulties such as high immunogenicity, high production costs and limited conjugation capacity, which we believe could be overcome by the introduction of nucleic acid aptamers. Similar to antibodies, aptamers can bind to their targets with great affinity and specificity. However, their chemical nature reduces their immunogenicity and production costs, while it enables their conjugation to a wide variety of cargoes for their use as delivery agents. In this review, we summarize several aptamers that have been tested against MM specific targets with promising results, establishing the rationale for the further development of aptamer-based strategies against MM. In this direction, we believe that the study of novel plasma cell surface markers, the development of intracellular aptamers and further research on aptamers as building blocks for complex nanomedicines will lead to the generation of next-generation targeted approaches that will undoubtedly contribute to improve the management and life quality of MM patients.
    Language English
    Publishing date 2022-11-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14215471
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  3. Article ; Online: Lipid nanoparticles for siRNA delivery in cancer treatment

    El Moukhtari, Souhaila H. / Garbayo, Elisa / Amundarain, Ane / Pascual-Gil, Simón / Carrasco-León, Arantxa / Prosper, Felipe / Agirre, Xabier / Blanco-Prieto, María J.

    Journal of Controlled Release. 2023 Sept., v. 361 p.130-146

    2023  

    Abstract: RNA-based therapies, and siRNAs in particular, have attractive therapeutic potential for cancer treatment due to their ability to silence genes that are imperative for tumor progression. To be effective and solve issues related to their poor half-life ... ...

    Abstract RNA-based therapies, and siRNAs in particular, have attractive therapeutic potential for cancer treatment due to their ability to silence genes that are imperative for tumor progression. To be effective and solve issues related to their poor half-life and poor pharmacokinetic properties, siRNAs require adequate drug delivery systems that protect them from degradation and allow intracellular delivery. Among the various delivery vehicles available, lipid nanoparticles have emerged as the leading choice. These nanoparticles consist of cholesterol, phospholipids, PEG-lipids and most importantly ionizable cationic lipids. These ionizable lipids enable the binding of negatively charged siRNA, resulting in the formation of stable and neutral lipid nanoparticles with exceptionally high encapsulation efficiency. Lipid nanoparticles have demonstrated their effectiveness and versatility in delivering not only siRNAs but also multiple RNA molecules, contributing to their remarkable success. Furthermore, the advancement of efficient manufacturing techniques such as microfluidics, enables the rapid mixing of two miscible solvents without the need for shear forces. This facilitates the reproducible production of lipid nanoparticles and holds enormous potential for scalability. This is shown by the increasing number of preclinical and clinical trials evaluating the potential use of siRNA-LNPs for the treatment of solid and hematological tumors as well as in cancer immunotherapy. In this review, we provide an overview of the progress made on siRNA-LNP development for cancer treatment and outline the current preclinical and clinical landscape in this area. Finally, the translational challenges required to bring siRNA-LNPs further into the clinic are also discussed.
    Keywords RNA ; cancer therapy ; cholesterol ; drugs ; encapsulation ; half life ; immunotherapy ; landscapes ; microfluidic technology ; nanoparticles ; neoplasm progression ; pharmacokinetics ; phospholipids ; Small interfering RNAs (siRNAs) ; Gene inhibition ; Lipid nanoparticles ; Microfluidics ; cancer ; Endosomal escape ; AML ; ASOs ; CML ; DODAP ; DODMA ; DOTAP ; DSPC ; FFR ; HCC ; HFF ; LNC ; LNP ; MDK ; mRNA ; RES ; NP ; RISC ; RNAi ; RRM2 ; SHMs ; siRNA ; SLN ; TFR ; TME ; TrM
    Language English
    Dates of publication 2023-09
    Size p. 130-146.
    Publishing place Elsevier B.V.
    Document type Article ; Online
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2023.07.054
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2055: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: HDACi vorinostat protects muscle from degeneration after acute rotator cuff injury in mice.

    Gil-Melgosa, Lara / Llombart-Blanco, Rafael / Extramiana, Leire / Lacave, Isabel / Abizanda, Gloria / Miranda, Estibaliz / Agirre, Xabier / Prósper, Felipe / Pineda-Lucena, Antonio / Pons-Villanueva, Juan / Pérez-Ruiz, Ana

    Bone & joint research

    2024  Volume 13, Issue 4, Page(s) 169–183

    Abstract: Aims: Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors ( ... ...

    Abstract Aims: Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.
    Methods: HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.
    Results: Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy.
    Conclusion: The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury.
    Language English
    Publishing date 2024-04-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2669244-2
    ISSN 2046-3758
    ISSN 2046-3758
    DOI 10.1302/2046-3758.134.BJR-2023-0292.R1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Correction: Ordoñez, et al.; DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters? Cancers 2019, 11, 1424.

    Ordoñez, Raquel / Martínez-Calle, Nicolás / Agirre, Xabier / Prosper, Felipe

    Cancers

    2020  Volume 12, Issue 7

    Abstract: The authors would like to make a correction to their published paper [ ... ]. ...

    Abstract The authors would like to make a correction to their published paper [...].
    Language English
    Publishing date 2020-07-13
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12071885
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  6. Article: The Role of lncRNAs in the Pathobiology and Clinical Behavior of Multiple Myeloma.

    Carrasco-León, Arantxa / Amundarain, Ane / Gómez-Echarte, Nahia / Prósper, Felipe / Agirre, Xabier

    Cancers

    2021  Volume 13, Issue 8

    Abstract: MM is a hematological neoplasm that is still considered an incurable disease. Besides established genetic alterations, recent studies have shown that MM pathogenesis is also characterized by epigenetic aberrations, such as the gain of de novo active ... ...

    Abstract MM is a hematological neoplasm that is still considered an incurable disease. Besides established genetic alterations, recent studies have shown that MM pathogenesis is also characterized by epigenetic aberrations, such as the gain of de novo active chromatin marks in promoter and enhancer regions and extensive DNA hypomethylation of intergenic regions, highlighting the relevance of these non-coding genomic regions. A recent study described how long non-coding RNAs (lncRNAs) correspond to 82% of the MM transcriptome and an increasing number of studies have demonstrated the importance of deregulation of lncRNAs in MM. In this review we focus on the deregulated lncRNAs in MM, including their biological or functional mechanisms, their role as biomarkers to improve the prognosis and monitoring of MM patients, and their participation in drug resistance. Furthermore, we also discuss the evidence supporting the role of lncRNAs as therapeutic targets through different novel RNA-based strategies.
    Language English
    Publishing date 2021-04-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13081976
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  7. Article ; Online: BOSO: A novel feature selection algorithm for linear regression with high-dimensional data.

    Valcárcel, Luis V / San José-Enériz, Edurne / Cendoya, Xabier / Rubio, Ángel / Agirre, Xabier / Prósper, Felipe / Planes, Francisco J

    PLoS computational biology

    2022  Volume 18, Issue 5, Page(s) e1010180

    Abstract: With the frenetic growth of high-dimensional datasets in different biomedical domains, there is an urgent need to develop predictive methods able to deal with this complexity. Feature selection is a relevant strategy in machine learning to address this ... ...

    Abstract With the frenetic growth of high-dimensional datasets in different biomedical domains, there is an urgent need to develop predictive methods able to deal with this complexity. Feature selection is a relevant strategy in machine learning to address this challenge. We introduce a novel feature selection algorithm for linear regression called BOSO (Bilevel Optimization Selector Operator). We conducted a benchmark of BOSO with key algorithms in the literature, finding a superior accuracy for feature selection in high-dimensional datasets. Proof-of-concept of BOSO for predicting drug sensitivity in cancer is presented. A detailed analysis is carried out for methotrexate, a well-studied drug targeting cancer metabolism.
    MeSH term(s) Algorithms ; Humans ; Linear Models ; Machine Learning ; Neoplasms/drug therapy ; Neoplasms/metabolism
    Language English
    Publishing date 2022-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1010180
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  8. Article ; Online: Explainable artificial intelligence for precision medicine in acute myeloid leukemia.

    Gimeno, Marian / San José-Enériz, Edurne / Villar, Sara / Agirre, Xabier / Prosper, Felipe / Rubio, Angel / Carazo, Fernando

    Frontiers in immunology

    2022  Volume 13, Page(s) 977358

    Abstract: Artificial intelligence (AI) can unveil novel personalized treatments based on drug screening and whole-exome sequencing experiments (WES). However, the concept of "black box" in AI limits the potential of this approach to be translated into the clinical ...

    Abstract Artificial intelligence (AI) can unveil novel personalized treatments based on drug screening and whole-exome sequencing experiments (WES). However, the concept of "black box" in AI limits the potential of this approach to be translated into the clinical practice. In contrast, explainable AI (XAI) focuses on making AI results understandable to humans. Here, we present a novel XAI method -called multi-dimensional module optimization (MOM)- that associates drug screening with genetic events, while guaranteeing that predictions are interpretable and robust. We applied MOM to an acute myeloid leukemia (AML) cohort of 319
    MeSH term(s) Artificial Intelligence ; Crizotinib/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Precision Medicine/methods
    Chemical Substances Crizotinib (53AH36668S)
    Language English
    Publishing date 2022-09-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.977358
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A network-based approach to integrate nutrient microenvironment in the prediction of synthetic lethality in cancer metabolism.

    Apaolaza, Iñigo / San José-Enériz, Edurne / Valcarcel, Luis V / Agirre, Xabier / Prosper, Felipe / Planes, Francisco J

    PLoS computational biology

    2022  Volume 18, Issue 3, Page(s) e1009395

    Abstract: Synthetic Lethality (SL) is currently defined as a type of genetic interaction in which the loss of function of either of two genes individually has limited effect in cell viability but inactivation of both genes simultaneously leads to cell death. Given ...

    Abstract Synthetic Lethality (SL) is currently defined as a type of genetic interaction in which the loss of function of either of two genes individually has limited effect in cell viability but inactivation of both genes simultaneously leads to cell death. Given the profound genomic aberrations acquired by tumor cells, which can be systematically identified with -omics data, SL is a promising concept in cancer research. In particular, SL has received much attention in the area of cancer metabolism, due to the fact that relevant functional alterations concentrate on key metabolic pathways that promote cellular proliferation. With the extensive prior knowledge about human metabolic networks, a number of computational methods have been developed to predict SL in cancer metabolism, including the genetic Minimal Cut Sets (gMCSs) approach. A major challenge in the application of SL approaches to cancer metabolism is to systematically integrate tumor microenvironment, given that genetic interactions and nutritional availability are interconnected to support proliferation. Here, we propose a more general definition of SL for cancer metabolism that combines genetic and environmental interactions, namely loss of gene functions and absence of nutrients in the environment. We extend our gMCSs approach to determine this new family of metabolic synthetic lethal interactions. A computational and experimental proof-of-concept is presented for predicting the lethality of dihydrofolate reductase (DHFR) inhibition in different environments. Finally, our approach is applied to identify extracellular nutrient dependences of tumor cells, elucidating cholesterol and myo-inositol depletion as potential vulnerabilities in different malignancies.
    MeSH term(s) Cell Line, Tumor ; Genomics ; Humans ; Metabolic Networks and Pathways/genetics ; Neoplasms/genetics ; Neoplasms/metabolism ; Nutrients ; Synthetic Lethal Mutations/genetics ; Tumor Microenvironment
    Language English
    Publishing date 2022-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1009395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Identifying Lethal Dependencies with HUGE Predictive Power.

    Gimeno, Marian / San José-Enériz, Edurne / Rubio, Angel / Garate, Leire / Miranda, Estíbaliz / Castilla, Carlos / Agirre, Xabier / Prosper, Felipe / Carazo, Fernando

    Cancers

    2022  Volume 14, Issue 13

    Abstract: Recent functional genomic screens—such as CRISPR-Cas9 or RNAi screening—have fostered a new wave of targeted treatments based on the concept of synthetic lethality. These approaches identified LEthal Dependencies (LEDs) by estimating the effect of ... ...

    Abstract Recent functional genomic screens—such as CRISPR-Cas9 or RNAi screening—have fostered a new wave of targeted treatments based on the concept of synthetic lethality. These approaches identified LEthal Dependencies (LEDs) by estimating the effect of genetic events on cell viability. The multiple-hypothesis problem is related to a large number of gene knockouts limiting the statistical power of these studies. Here, we show that predictions of LEDs from functional screens can be dramatically improved by incorporating the “HUb effect in Genetic Essentiality” (HUGE) of gene alterations. We analyze three recent genome-wide loss-of-function screens—Project Score, CERES score and DEMETER score—identifying LEDs with 75 times larger statistical power than using state-of-the-art methods. Using acute myeloid leukemia, breast cancer, lung adenocarcinoma and colon adenocarcinoma as disease models, we validate that our predictions are enriched in a recent harmonized knowledge base of clinical interpretations of somatic genomic variants in cancer (AUROC > 0.87). Our approach is effective even in tumors with large genetic heterogeneity such as acute myeloid leukemia, where we identified LEDs not recalled by previous pipelines, including FLT3-mutant genotypes sensitive to FLT3 inhibitors. Interestingly, in-vitro validations confirm lethal dependencies of either NRAS or PTPN11 depending on the NRAS mutational status. HUGE will hopefully help discover novel genetic dependencies amenable for precision-targeted therapies in cancer. All the graphs showing lethal dependencies for the 19 tumor types analyzed can be visualized in an interactive tool.
    Language English
    Publishing date 2022-07-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14133251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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