High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response

Abstract The elucidation of mechanisms involved in resistance to therapies is essential to improve the survival of patients with malignant gliomas. A major feature possessed by glioma cells that may aid their ability to survive therapy and reconstitute tumors is the capacity for self-renewal. We show here that glioma stem cells (GSCs) express low levels of MKP1, a dual-specificity phosphatase, which acts as a negative inhibitor of JNK, ERK1/2, and p38 MAPK, while induction of high levels of MKP1 expression are associated with differentiation of GSC. Notably, we find that high levels of MKP1 correlate with a subset of glioblastoma patients with better prognosis and overall increased survival. Gain of expression studies demonstrated that elevated MKP1 impairs self-renewal and induces differentiation of GSCs while reducing tumorigenesis in vivo. Moreover, we identified that MKP1 is epigenetically regulated and that it mediates the anti-tumor activity of histone deacetylase inhibitors (HDACIs) alone or in combination with temozolomide. In summary, this study identifies MKP1 as a key modulator of the interplay between GSC self-renewal and differentiation and provides evidence that the activation of MKP1, through epigenetic regulation, might be a novel therapeutic strategy to overcome therapy resistance in glioblastoma

Translating the foundational model of anatomy into french using knowledge-based and lexical methods

<p>Abstract</p> <p>Background</p> <p>The Foundational Model of Anatomy (FMA) is the reference ontology regarding human anatomy. FMA vocabulary was integrated into the Health Multi Terminological Portal (HMTP) developed by CISMeF based on the CISMeF Information System which also includes 26 other terminologies and controlled vocabularies, mainly in French. However, FMA is primarily in English. In this context, the translation of FMA English terms into French could also be useful for searching and indexing French anatomy resources. Various studies have investigated automatic methods to assist the translation of medical terminologies or create multilingual medical vocabularies. The goal of this study was to facilitate the translation of FMA vocabulary into French.</p> <p>Methods</p> <p>We compare two types of approaches to translate the FMA terms into French. The first one is UMLS-based on the conceptual information of the UMLS metathesaurus. The second method is lexically-based on several Natural Language Processing (NLP) tools.</p> <p>Results</p> <p>The UMLS-based approach produced a translation of 3,661 FMA terms into French whereas the lexical approach produced a translation of 3,129 FMA terms into French. A qualitative evaluation was made on 100 FMA terms translated by each method. For the UMLS-based approach, among the 100 translations, 52% were manually rated as "very good" and only 7% translations as "bad". For the lexical approach, among the 100 translations, 47% were rated as "very good" and 20% translations as "bad".</p> <p>Conclusions</p> <p>Overall, a low rate of translations were demonstrated by the two methods. The two approaches permitted us to semi-automatically translate 3,776 FMA terms from English into French, this was to added to the existing 10,844 French FMA terms in the HMTP (4,436 FMA French terms and 6,408 FMA terms manually translated).</p