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Publication : Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype.

First Author  Phoenix TN Year  2016
Journal  Cancer Cell Volume  29
Issue  4 Pages  508-522
PubMed ID  27050100 Mgi Jnum  J:231825
Mgi Id  MGI:5775228 Doi  10.1016/j.ccell.2016.03.002
Citation  Phoenix TN, et al. (2016) Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype. Cancer Cell 29(4):508-22
abstractText  The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant beta-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors.
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