Xipell, E. (Enric)

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2016 - 20172

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    Analysis of SOX2-regulated transcriptome in glioma stem cells
    (2016-09-16) Acanda-de-la-Rocha, A.M. (Arlet María); Alonso-Roldán, M.M. (Marta María); Gomez-Manzano, C. (Candelaria); Martinez-Velez, N. (Naiara); Gonzalez-Huarriz, M. (Marisol); Xipell, E. (Enric); Guruceaga, E. (Elizabeth); Fueyo, J. (Juan); Lopez-Bertoni, H. (Hernando)
    Introduction Glioblastoma is the most malignant brain tumor in adults and is associated with poor sur- vival despite multimodal treatments. Glioma stem-like cells (GSCs) are cells functionally defined by their self-renewal potential and the ability to reconstitute the original tumor upon orthotopic implantation. They have been postulated to be the culprit of glioma chemo- and radio-resistance ultimately leading to relapse. Understanding the molecular circuits govern- ing the GSC compartment is essential. SOX2, a critical transcription regulator of embryonic and neural stem cell function, is deregulated in GSCs however; the precise molecular path- ways regulated by this gene in GSCs remain poorly understood. Results We performed a genome-wide analysis of SOX2-regulated transcripts in GSCs, using a microarray. We identified a total of 2048 differentially expressed coding transcripts and 261 non-coding transcripts. Cell adhesion and cell-cell signaling are among the most enriched terms using Gene Ontology (GO) classification. The pathways altered after SOX2 down- modulation includes multiple cellular processes such as amino-acid metabolism and inter- cellular signaling cascades. We also defined and classified the set of non-coding transcripts differentially expressed regulated by SOX2 in GSCs, and validated two of them. Conclusions We present a comprehensive analysis of the transcriptome controlled by SOX2 in GSCs, gaining insights in the understanding of the potential roles of SOX2 in glioblastoma.
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    Development of a DIPG Orthotopic Model in Mice Using an Implantable Guide-Screw System
    (Public Library of Science - Green Policies in RoMEO, 2017) Patiño-García, A. (Ana); Alonso-Roldán, M.M. (Marta María); El-Habr, E. (Elías); Chneiweiss, H. (Hervé); Martinez-Velez, N. (Naiara); Marigil, M. (Miguel); Domínguez-Echávarri, P.D. (Pablo Daniel); Garcia-Maure, M. (Marc); Gonzalez-Huarriz, M. (Marisol); Tejada-Solis, S. (Sonia); Xipell, E. (Enric); Diez-Valle, R. (Ricardo); Junier, M.P. (Marie Pierre); Idoate, M.A. (Miguel Ángel)
    Objective In this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG) model based in the implantation of a guide-screw system. Methods It consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies. Results The guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model. Conclusion Here we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons.