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Cancer Research Center of Marseille (CRCM)
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  • [Show abstract] [Hide abstract]
    ABSTRACT: Mastocytosis is an incurable and sometimes fatal haematological disorder grossly described as the accumulation of abnormal mast cells in the bone marrow and other organs causing tissue and organ damage. The clinical manifestations of this disease are extremely variable; disease phenotypes range from indolent to aggressive, and often present with associated non-mast cell haematological disorders (AHNMD), mainly myeloproliferative neoplasm and myelodysplastic syndromes. Recent efforts to genetically dissect the mechanisms that define aggressive and non-aggressive mastocytosis have generated a list of recurrent somatic mutations in mastocytosis patients that are associated with and may predict the evolution towards aggressive disease phenotypes. Here we review these mutations and discuss the molecular mechanisms associated with these mutations in an effort to better understand the biology of this disease and to predict its onset and evolution, with the ultimate goal of devising new and improved treatment strategies.
    Molecular Immunology 04/2014;
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    ABSTRACT: Breast cancer is the first cause of cancer in women worldwide. Recent molecular analyses have shown that it is not a single disease but a mixture of several diseases with different biological behaviors, which should lead to treatment customization for each patient. Personalized medicine is based on tumor and/or patient molecular profiles. This new way to think oncology is currently applied at different stages of breast cancer management, including prognosis, prediction of treatment efficacy, and development of new therapies via new kinds of clinical trials. These trials are not only based on tumor site but also on tumor genetic characterization using genomic tools such as gene expression profiling, array-CGH or next-generation sequencing technologies. The aim of personalized medicine is to tailor treatment according to the specificities of a single disease in a given patient. In this review, we present the advances in treatment personalization which are currently used in daily practice as well as the technologies and therapies under investigation in various clinical trials.
    Critical reviews in oncology/hematology 01/2014;
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    ABSTRACT: Over the last 10 years, protein-protein interactions (PPIs) have shown increasing potential as new therapeutic targets. As a consequence, PPIs are today the most screened target class in high-throughput screening (HTS). The development of broad chemical libraries dedicated to these particular targets is essential; however, the chemical space associated with this 'high-hanging fruit' is still under debate. Here, we analyse the properties of 40 non-redundant small molecules present in the 2P2I database (http://2p2idb.cnrs-mrs.fr/) to define a general profile of orthosteric inhibitors and propose an original protocol to filter general screening libraries using a support vector machine (SVM) with 11 standard Dragon molecular descriptors. The filtering protocol has been validated using external datasets from PubChem BioAssay and results from in-house screening campaigns. This external blind validation demonstrated the ability of the SVM model to reduce the size of the filtered chemical library by eliminating up to 96% of the compounds as well as enhancing the proportion of active compounds by up to a factor of 8. We believe that the resulting chemical space identified in this paper will provide the scientific community with a concrete support to search for PPI inhibitors during HTS campaigns.
    Journal of The Royal Society Interface 01/2014; 11(90):20130860.

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    Marseille, France
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