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  1. Article: ClustMMRA v2: A Scalable Computational Pipeline for the Identification of MicroRNA Clusters Acting Cooperatively on Tumor Molecular Subgroups.

    Hernandez, Céline / Cancila, Gabriele / Ayrault, Olivier / Zinovyev, Andrei / Martignetti, Loredana

    Advances in experimental medicine and biology

    2022  Volume 1385, Page(s) 259–279

    Abstract: In recent cancer genomics programs, large-scale profiling of microRNAs has been routinely used in order to better understand the role of microRNAs in gene regulation and disease. To support the analysis of such amount of data, scalability of ... ...

    Abstract In recent cancer genomics programs, large-scale profiling of microRNAs has been routinely used in order to better understand the role of microRNAs in gene regulation and disease. To support the analysis of such amount of data, scalability of bioinformatics pipelines is increasingly important to handle larger datasets.Here, we describe a scalable implementation of the clustered miRNA Master Regulator Analysis (clustMMRA) pipeline, developed to search for genomic clusters of microRNAs potentially driving cancer molecular subtyping. Genomically clustered microRNAs can be simultaneously expressed to work in a combined manner and jointly regulate cell phenotypes. However, the majority of computational approaches for the identification of microRNA master regulators are typically designed to detect the regulatory effect of a single microRNA.We have applied the clustMMRA pipeline to multiple pediatric tumor datasets, up to a hundred samples in size, demonstrating very satisfying performances of the software on large datasets. Results have highlighted genomic clusters of microRNAs potentially involved in several subgroups of the different pediatric cancers or specifically involved in the phenotype of a subgroup. In particular, we confirmed the cluster of microRNAs at the 14q32 locus to be involved in multiple pediatric cancers, showing its specific downregulation in tumor subgroups with aggressive phenotype.
    MeSH term(s) Humans ; MicroRNAs/genetics ; Gene Expression Profiling/methods ; Neoplasms/genetics ; Cluster Analysis ; Gene Expression Regulation ; Computational Biology ; Gene Expression Regulation, Neoplastic
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2022-11-09
    Publishing country United States
    Document type Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-031-08356-3_10
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: LEF-1 immunohistochemistry, a better diagnostic biomarker than β-catenin for medulloblastoma, WNT-activated subtyping.

    Aboubakr, Oumaima / Métais, Alice / Doz, François / Saffroy, Raphaël / Masliah-Planchon, Julien / Hasty, Lauren / Beccaria, Kevin / Ayrault, Olivier / Dufour, Christelle / Varlet, Pascale / Tauziède-Espariat, Arnault

    Journal of neuropathology and experimental neurology

    2024  Volume 83, Issue 2, Page(s) 136–138

    MeSH term(s) Humans ; beta Catenin ; Biomarkers ; Cerebellar Neoplasms/diagnosis ; Immunohistochemistry ; Medulloblastoma/diagnosis
    Chemical Substances beta Catenin ; Biomarkers
    Language English
    Publishing date 2024-01-18
    Publishing country England
    Document type Letter
    ZDB-ID 3088-0
    ISSN 1554-6578 ; 0022-3069
    ISSN (online) 1554-6578
    ISSN 0022-3069
    DOI 10.1093/jnen/nlad104
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Introduction. Pediatric brain tumor.

    Cheshier, Samuel / Taylor, Michael D / Ayrault, Olivier / Mueller, Sabine

    Neurosurgical focus

    2020  Volume 48, Issue 1, Page(s) E1

    MeSH term(s) Brain Neoplasms/diagnosis ; Brain Neoplasms/pathology ; Brain Neoplasms/therapy ; Craniopharyngioma/diagnosis ; Craniopharyngioma/therapy ; Glioblastoma/diagnosis ; Glioblastoma/pathology ; Glioblastoma/therapy ; Humans ; Pediatrics
    Language English
    Publishing date 2020-01-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2026589-X
    ISSN 1092-0684 ; 1092-0684
    ISSN (online) 1092-0684
    ISSN 1092-0684
    DOI 10.3171/2019.10.FOCUS19799
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Insights into cerebellar development and medulloblastoma.

    Bihannic, Laure / Ayrault, Olivier

    Bulletin du cancer

    2016  Volume 103, Issue 1, Page(s) 30–40

    Abstract: Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous ... ...

    Abstract Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous diseases such as medulloblastoma, the most common pediatric malignant brain tumor. One third of the patients with medulloblastoma are incurable and survivors have a poor quality of life due to the aggressiveness of the broad-spectrum treatments. Within the past few years, it has been highlighted that medulloblastoma is a heterogeneous disease that is divided in four molecular subgroups. This recent advance in the field, combined with the development of associated preclinical models for each subgroup, should enable, in the future, the discovery and use of targeted therapy in clinical treatments for each subtype of medulloblastoma. In this review, we first aim to show how deregulation of cerebellar development can lead to medulloblastoma formation and then to present the advances in the molecular subgrouping of medulloblastoma and the associated preclinical models.
    MeSH term(s) Animals ; Cerebellar Neoplasms/classification ; Cerebellar Neoplasms/diagnosis ; Cerebellar Neoplasms/etiology ; Cerebellar Neoplasms/therapy ; Cerebellum/anatomy & histology ; Cerebellum/embryology ; Cerebellum/growth & development ; Child ; Disease Models, Animal ; Hedgehog Proteins/antagonists & inhibitors ; Hedgehog Proteins/physiology ; Humans ; Medical Illustration ; Medulloblastoma/classification ; Medulloblastoma/diagnosis ; Medulloblastoma/etiology ; Medulloblastoma/therapy ; Mice ; Mutation ; Prognosis ; Quality of Life
    Chemical Substances Hedgehog Proteins
    Language English
    Publishing date 2016-01
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 213270-9
    ISSN 1769-6917 ; 0007-4551
    ISSN (online) 1769-6917
    ISSN 0007-4551
    DOI 10.1016/j.bulcan.2015.11.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Medulloblastomics revisited: biological and clinical insights from thousands of patients.

    Hovestadt, Volker / Ayrault, Olivier / Swartling, Fredrik J / Robinson, Giles W / Pfister, Stefan M / Northcott, Paul A

    Nature reviews. Cancer

    2019  Volume 20, Issue 1, Page(s) 42–56

    Abstract: Medulloblastoma, a malignant brain tumour primarily diagnosed during childhood, has recently been the focus of intensive molecular profiling efforts, profoundly advancing our understanding of biologically and clinically heterogeneous disease subgroups. ... ...

    Abstract Medulloblastoma, a malignant brain tumour primarily diagnosed during childhood, has recently been the focus of intensive molecular profiling efforts, profoundly advancing our understanding of biologically and clinically heterogeneous disease subgroups. Genomic, epigenomic, transcriptomic and proteomic landscapes have now been mapped for an unprecedented number of bulk samples from patients with medulloblastoma and, more recently, for single medulloblastoma cells. These efforts have provided pivotal new insights into the diverse molecular mechanisms presumed to drive tumour initiation, maintenance and recurrence across individual subgroups and subtypes. Translational opportunities stemming from this knowledge are continuing to evolve, providing a framework for improved diagnostic and therapeutic interventions. In this Review, we summarize recent advances derived from this continued molecular characterization of medulloblastoma and contextualize this progress towards the deployment of more effective, molecularly informed treatments for affected patients.
    MeSH term(s) Animals ; Biomarkers, Tumor ; Combined Modality Therapy ; Disease Management ; Disease Susceptibility ; Epigenomics/methods ; Genetic Association Studies ; Genomics/methods ; Humans ; Medulloblastoma/diagnosis ; Medulloblastoma/etiology ; Medulloblastoma/metabolism ; Medulloblastoma/therapy ; Molecular Diagnostic Techniques ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Proteomics/methods ; Recurrence ; Treatment Outcome ; Tumor Microenvironment
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2019-12-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/s41568-019-0223-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Proteogenomic profiling uncovers differential therapeutic vulnerabilities between TCF3::PBX1 and TCF3::HLF translocated B-cell acute lymphoblastic leukemia.

    Blumel, Lena / Bernardi, Flavia / Picard, Daniel / Diaz, Jacob Torrejon / Jepsen, Vera H / Hasselmann, Rebecca / Schliehe-Diecks, Julian / Bartl, Jasmin / Qin, Nan / Bornhauser, Beat / Bhatia, Sanil / Marovka, Blerim / Marsaud, Veronique / Dingli, Florent / Loew, Damarys / Stanulla, Martin / Bourqin, Jean-Pierre / Borkhardt, Arndt / Remke, Marc /
    Ayrault, Olivier / Fischer, Ute

    Haematologica

    2024  

    Abstract: Not available. ...

    Abstract Not available.
    Language English
    Publishing date 2024-02-29
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2023.283928
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Longitudinal characterization of primary osteosarcoma and derived subcutaneous and orthotopic relapsed patient-derived xenograft models.

    da Costa, Maria Eugenia Marques / Droit, Robin / Khneisser, Pierre / Gomez-Brouchet, Anne / Adam-de-Beaumais, Tiphaine / Nolla, Marie / Signolles, Nicolas / Torrejon, Jacob / Lombard, Bérangère / Loew, Damarys / Ayrault, Olivier / Scoazec, Jean-Yves / Geoerger, Birgit / Vassal, Gilles / Marchais, Antonin / Gaspar, Nathalie

    Frontiers in oncology

    2023  Volume 13, Page(s) 1166063

    Abstract: Osteosarcoma is a rare bone cancer in adolescents and young adults with a dismal prognosis because of metastatic disease and chemoresistance. Despite multiple clinical trials, no improvement in outcome has occurred in decades. There is an urgent need to ... ...

    Abstract Osteosarcoma is a rare bone cancer in adolescents and young adults with a dismal prognosis because of metastatic disease and chemoresistance. Despite multiple clinical trials, no improvement in outcome has occurred in decades. There is an urgent need to better understand resistant and metastatic disease and to generate
    Language English
    Publishing date 2023-06-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1166063
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  8. Article ; Online: Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtypes.

    Cadilhac, Christelle / Bachy, Isabelle / Forget, Antoine / Hodson, David J / Jahannault-Talignani, Céline / Furley, Andrew J / Ayrault, Olivier / Mollard, Patrice / Sotelo, Constantino / Ango, Fabrice

    Cell reports

    2022  Volume 34, Issue 13, Page(s) 108904

    Abstract: GABAergic interneurons migrate long distances through stereotyped migration programs toward specific laminar positions. During their migration, GABAergic interneurons are morphologically alike but then differentiate into a rich array of interneuron ... ...

    Abstract GABAergic interneurons migrate long distances through stereotyped migration programs toward specific laminar positions. During their migration, GABAergic interneurons are morphologically alike but then differentiate into a rich array of interneuron subtypes critical for brain function. How interneuron subtypes acquire their final phenotypic traits remains largely unknown. Here, we show that cerebellar molecular layer GABAergic interneurons, derived from the same progenitor pool, use separate migration paths to reach their laminar position and differentiate into distinct basket cell (BC) and stellate cell (SC) GABAergic interneuron subtypes. Using two-photon live imaging, we find that SC final laminar position requires an extra step of tangential migration supported by a subpopulation of glutamatergic granule cells (GCs). Conditional depletion of GCs affects SC differentiation but does not affect BCs. Our results reveal how timely feedforward control of inhibitory interneuron migration path regulates their terminal differentiation and, thus, establishment of the local inhibitory circuit assembly.
    MeSH term(s) Animals ; Axons/metabolism ; Cell Differentiation ; Cell Movement ; Cytoplasmic Granules/metabolism ; GABAergic Neurons/cytology ; Interneurons/cytology ; Interneurons/metabolism ; Mice, Transgenic
    Language English
    Publishing date 2022-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.108904
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Beta-blockers disrupt mitochondrial bioenergetics and increase radiotherapy efficacy independently of beta-adrenergic receptors in medulloblastoma.

    Rossi, Maïlys / Talbot, Julie / Piris, Patricia / Grand, Marion Le / Montero, Marie-Pierre / Matteudi, Mélanie / Agavnian-Couquiaud, Emilie / Appay, Romain / Keime, Céline / Williamson, Daniel / Buric, Duje / Bourgarel, Véronique / Padovani, Laetitia / Clifford, Steven C / Ayrault, Olivier / Pasquier, Eddy / André, Nicolas / Carré, Manon

    EBioMedicine

    2022  Volume 82, Page(s) 104149

    Abstract: Background: Medulloblastoma is the most frequent brain malignancy of childhood. The current multimodal treatment comes at the expense of serious and often long-lasting side effects. Drug repurposing is a strategy to fast-track anti-cancer therapy with ... ...

    Abstract Background: Medulloblastoma is the most frequent brain malignancy of childhood. The current multimodal treatment comes at the expense of serious and often long-lasting side effects. Drug repurposing is a strategy to fast-track anti-cancer therapy with low toxicity. Here, we showed the ability of β-blockers to potentiate radiotherapy in medulloblastoma with bad prognosis.
    Methods: Medulloblastoma cell lines, patient-derived xenograft cells, 3D spheroids and an innovative cerebellar organotypic model were used to identify synergistic interactions between β-blockers and ionising radiations. Gene expression profiles of β-adrenergic receptors were analysed in medulloblastoma samples from 240 patients. Signaling pathways were explored by RT-qPCR, RNA interference, western blotting and RNA sequencing. Medulloblastoma cell bioenergetics were evaluated by measuring the oxygen consumption rate, the extracellular acidification rate and superoxide production.
    Findings: Low concentrations of β-blockers significantly potentiated clinically relevant radiation protocols. Although patient biopsies showed detectable expression of β-adrenergic receptors, the ability of the repurposed drugs to potentiate ionising radiations did not result from the inhibition of the canonical signaling pathway. We highlighted that the efficacy of the combinatorial treatment relied on a metabolic catastrophe that deprives medulloblastoma cells of their adaptive bioenergetics capacities. This led to an overproduction of superoxide radicals and ultimately to an increase in ionising radiations-mediated DNA damages.
    Interpretation: These data provide the evidence of the efficacy of β-blockers as potentiators of radiotherapy in medulloblastoma, which may help improve the treatment and quality of life of children with high-risk brain tumours.
    Funding: This study was funded by institutional grants and charities.
    MeSH term(s) Cerebellar Neoplasms ; Child ; Energy Metabolism ; Humans ; Medulloblastoma/drug therapy ; Medulloblastoma/genetics ; Medulloblastoma/radiotherapy ; Quality of Life ; Receptors, Adrenergic, beta/metabolism ; Receptors, Adrenergic, beta/therapeutic use ; Superoxides
    Chemical Substances Receptors, Adrenergic, beta ; Superoxides (11062-77-4)
    Language English
    Publishing date 2022-07-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104149
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Immunohistochemistry as a tool to identify ELP1-associated medulloblastoma.

    Tauziède-Espariat, Arnault / Guerrini-Rousseau, Léa / Perrier, Alexandre / Torrejon, Jacob / Bernardi, Flavia / Varlet, Pascale / Hasty, Lauren / Delattre, Olivier / Beccaria, Kévin / Métais, Alice / Ayrault, Olivier / Chrétien, Fabrice / Bourdeaut, Franck / Dufour, Christelle / Masliah-Planchon, Julien

    Acta neuropathologica

    2022  Volume 143, Issue 4, Page(s) 523–525

    MeSH term(s) Carrier Proteins ; Cerebellar Neoplasms/genetics ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins ; Medulloblastoma/genetics
    Chemical Substances Carrier Proteins ; Intracellular Signaling Peptides and Proteins
    Language English
    Publishing date 2022-02-23
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-022-02409-4
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