0000000000182456
AUTHOR
Andrey Korshunov
A Set of Cell Lines Derived from a Genetic Murine Glioblastoma Model Recapitulates Molecular and Morphological Characteristics of Human Tumors
Simple Summary Glioblastoma (GBM) is a highly aggressive and almost inevitably lethal brain tumor. Animal models for GBM are crucial to study how the tumor evolves in vivo and to test novel treatment options. Most currently available models are based on the transplantation of human GBM cells into mice with a defective immune system. However, this approach does not allow to study the contribution of immune cells to GBM growth and to test immunotherapies. Transplantation of murine GBM cells overcomes this limitation, however, up to now, only a limited number, which mostly do not mimic important characteristics of human GBM, have been available. Via in vivo passaging, we established a set of m…
A novel neural stem cell-derived immunocompetent mouse model of glioblastoma for preclinical studies
AbstractGlioblastomas are the most lethal tumors affecting the central nervous system in adults. Simple and inexpensive syngeneicin vivomodels that closely mirror human glioblastoma, including interactions between tumor and immune cells, are urgently needed for deciphering glioma biology and developing more effective treatments. Here, we generated glioblastoma cell lines by repeatedin-vivopassaging of cells isolated from a neural stem cell-specific Pten/p53 double-knockout genetic mouse brain tumor model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts…
Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort
PURPOSE The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy. PATIENTS AND METHODS From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided i…
MBCL-07. NON-METASTATIC MEDULLOBLASTOMA OF EARLY CHILDHOOD: RESULTS FROM THE PROSPECTIVE CLINICAL TRIAL HIT-2000 AND AN EXTENDED VALIDATION COHORT
Abstract OBJECTIVE To avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy. PATIENTS AND METHODS Eighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for non-response or progression. After 2006, local radiotherapy was introduced for non-responders or classic (CMB), anaplastic or large-cell medulloblastoma (LCA). Infantile SHH-activated medulloblastomas (SHH_INF) were subdivided by DNA-methylation profiling. Survival in SHH_INF subtypes were also assessed in a validation cohort (n=71). RESULT…