{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T16:27:44Z","timestamp":1756571264178,"version":"3.41.2"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":115,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Prayers From Maria Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Leptomeningeal disease and hydrocephalus are present in up to 30% of patients with diffuse intrinsic pontine glioma (DIPG), however there are no animal models of cerebrospinal fluid (CSF) dissemination. As the tumor\u2013CSF\u2013ependymal microenvironment may play an important role in tumor pathogenesis, we identified characteristics of the Nestin-tumor virus A (Nestin-Tva) genetically engineered mouse model that make it ideal to study the interaction of tumor cells with the CSF and its associated pathways with implications for the development of treatment approaches to address CSF dissemination in DIPG.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A Nestin-Tva model of DIPG utilizing the 3 most common DIPG genetic alterations (H3.3K27M, PDGF-B, and p53) was used for this study. All mice underwent MR imaging and a subset underwent histopathologic analysis with H&amp;E and immunostaining.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Tumor dissemination within the CSF pathways (ventricles, leptomeninges) from the subependyma was present in 76% (25\/33) of mice, with invasion of the choroid plexus, disruption of the ciliated ependyma and regional subependymal fluid accumulation. Ventricular enlargement consistent with hydrocephalus was present in 94% (31\/33). Ventricle volume correlated with region-specific transependymal CSF flow (periventricular T2 signal), localized anterior to the lateral ventricles.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This is the first study to report CSF pathway tumor dissemination associated with subependymal tumor in an animal model of DIPG and is representative of CSF dissemination seen clinically. Understanding the CSF\u2013tumor\u2013ependymal microenvironment has significant implications for treatment of DIPG through targeting mechanisms of tumor spread within the CSF pathways.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdac059","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T01:19:07Z","timestamp":1651022347000},"source":"Crossref","is-referenced-by-count":3,"title":["Leptomeningeal disease and tumor dissemination in a murine diffuse intrinsic pontine glioma model: implications for the study of the tumor-cerebrospinal fluid-ependymal microenvironment"],"prefix":"10.1093","volume":"4","author":[{"given":"Shelei","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Washington University School of Medicine , Saint Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhuang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of 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