title: Development of a DIPG Orthotopic Model in Mice Using an Implantable Guide-Screw System.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Neurosurgery, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marigil
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Naiara
authors.initials: N
authors.lastname: Martinez-Velez
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Radiology, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Domínguez
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Pathology, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Idoate
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Xipell
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Patiño-García
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Gonzalez-Huarriz
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: García-Moure
authors.affiliation: CNRS UMR8246, Inserm U1130, UPMC, Neuroscience Paris Seine - IBPS, Sorbonne Universities, Paris, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Junier
authors.affiliation: CNRS UMR8246, Inserm U1130, UPMC, Neuroscience Paris Seine - IBPS, Sorbonne Universities, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Chneiweiss
authors.affiliation: CNRS UMR8246, Inserm U1130, UPMC, Neuroscience Paris Seine - IBPS, Sorbonne Universities, Paris, France.
authors.forename: Elías
authors.initials: E
authors.lastname: El-Habr
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Neurosurgery, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Diez-Valle
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Neurosurgery, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Tejada-Solís
authors.affiliation: The Health Research Institute of Navarra (IDISNA), Pamplona, Spain.|Program in Solid Tumors and Biomarkers, Foundation for the Applied Medical Research, Pamplona, Spain.|Dpt of Pediatrics, University Hospital of Navarra, Pamplona, Spain.
authors.forename: Marta M
authors.identifier: http://orcid.org/0000-0002-7520-7351
authors.initials: MM
authors.lastname: Alonso
mesh_terms: D000818:Animals; D001933:Brain Stem; D020295:Brain Stem Neoplasms / Q000209:etiology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005910:Glioma / Q000209:etiology*; D051379:Mice; D008819:Mice, Nude; D009339:Needles; D009368:Neoplasm Transplantation / Q000379:methods*; D009374:Neoplasms, Experimental