Abstract:
:The Hedgehog (Hh) signaling pathway has been implicated in the most common childhood brain tumor, medulloblastoma (MB). Given the toxicity of post-surgical treatments for MB, continued need exists for new, targeted therapies. Based upon our finding that Neuropilin (Nrp) transmembrane proteins are required for Hh signal transduction, we investigated the role of Nrp in MB cells. Cultured cells derived from a mouse Ptch (+/-) ;LacZ MB (Med1-MB), effectively modeled the Hh pathway-related subcategory of human MBs in vitro. Med1-MB cells maintained constitutively active Hh target gene transcription, and consistently formed tumors within one month after injection into mouse cerebella. The proliferation rate of Med1-MBs in culture was dependent upon Nrp2, while reducing Nrp1 function had little effect. Knockdown of Nrp2 prior to cell implantation significantly increased mouse survival, compared to transfection with a non-targeting siRNA. Knocking down Nrp2 specifically in MB cells avoided any direct effect on tumor vascularization. Nrp2 should be further investigated as a potential target for adjuvant therapy in patients with MB.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Hayden Gephart MG,Su YS,Bandara S,Tsai FC,Hong J,Conley N,Rayburn H,Milenkovic L,Meyer T,Scott MPdoi
10.1007/s11060-013-1216-1subject
Has Abstractpub_date
2013-11-01 00:00:00pages
161-8issue
2eissn
0167-594Xissn
1573-7373journal_volume
115pub_type
杂志文章abstract::After the second recurrence of spinal seeding in hemangioblastoma not associated to von-Hippel-Lindau disease, we treated an adult female patient with thalidomide 200 mg orally/day at night for longer than 1 year. The patient reported subjective relief of symptoms after 1 month. Magnetic resonance imaging (MRI) contro...
journal_title:Journal of neuro-oncology
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journal_title:Journal of neuro-oncology
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journal_title:Journal of neuro-oncology
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journal_title:Journal of neuro-oncology
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