Matches in SemOpenAlex for { <https://semopenalex.org/work/W2620266114> ?p ?o ?g. }
Showing items 1 to 95 of
95
with 100 items per page.
- W2620266114 endingPage "iv17" @default.
- W2620266114 startingPage "iv17" @default.
- W2620266114 abstract "Reproducibly effective chemotherapy has yet to be identified for ependymoma (EPN), partly due to a lack of models for preclinical drug screening. Treatment of EPN has therefore changed little over the last 40 years and is essentially limited to surgery and radiation. Recurrence risk is high, particularly in those EPN harboring chromosome 1q gain. To address this, we have established 2 posterior fossa 1q+ EPN cell lines and we have utilized these in a high-throughput drug screen of FDA-approved oncology drugs. Treatment effect was measured using a tritiated-thymidine incorporation proliferation assay and EPN-selective sensitivity was determined by comparison to a panel of other pediatric brain tumor types (medulloblastoma, glioblastoma, DIPG and AT/RT). Using this approach, we identified a group of 3 small molecule tyrosine kinase inhibitors (TKIs) that showed greater potency in EPN than control cell lines. These TKIs – namely axitinib, imatinib and pazopanib – commonly target VEGFR, PDGFR and c-kit. Of note, axitinib has been proposed for an upcoming phase 1 trial for recurrent pediatric brain tumors including EPN. Studies of axitinib in other tumors demonstrated a beneficial immunomodulatory effect, of particular relevance in EPN given the key role of immunity in this tumor. Axitinib may therefore have a dual mechanism of tumor control in EPN. We selected this drug for further evaluation in our preclinical model of EPN. Dose curve analysis confirmed that axitinib more is potent in EPN than other cell types. Transcriptomic analysis of axitinib treated EPN revealed a decrease in mitosis-related gene expression and in increase in type-I interferon-associated gene expression. Further screening studies identified treatments that showed synergistic effects in EPN, most notably cisplatin. Collectively these data support clinical evaluation of axitinib for treatment EPN and provide information of potentially synergistic treatment combinations that might overcome single agent resistance." @default.
- W2620266114 created "2017-06-05" @default.
- W2620266114 creator A5008401630 @default.
- W2620266114 creator A5022692329 @default.
- W2620266114 creator A5037391462 @default.
- W2620266114 creator A5039734669 @default.
- W2620266114 creator A5048087068 @default.
- W2620266114 creator A5060449174 @default.
- W2620266114 creator A5074526101 @default.
- W2620266114 creator A5075671062 @default.
- W2620266114 creator A5079931088 @default.
- W2620266114 creator A5083090050 @default.
- W2620266114 creator A5090776132 @default.
- W2620266114 date "2017-05-31" @default.
- W2620266114 modified "2023-10-07" @default.
- W2620266114 title "EPND-12. TYROSINE KINASE INHIBITORS AXITINIB, IMATINIB AND PAZOPANIB ARE SELECTIVELY POTENT IN EPENDYMOMA" @default.
- W2620266114 doi "https://doi.org/10.1093/neuonc/nox083.070" @default.
- W2620266114 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5475033" @default.
- W2620266114 hasPublicationYear "2017" @default.
- W2620266114 type Work @default.
- W2620266114 sameAs 2620266114 @default.
- W2620266114 citedByCount "1" @default.
- W2620266114 countsByYear W26202661142021 @default.
- W2620266114 crossrefType "journal-article" @default.
- W2620266114 hasAuthorship W2620266114A5008401630 @default.
- W2620266114 hasAuthorship W2620266114A5022692329 @default.
- W2620266114 hasAuthorship W2620266114A5037391462 @default.
- W2620266114 hasAuthorship W2620266114A5039734669 @default.
- W2620266114 hasAuthorship W2620266114A5048087068 @default.
- W2620266114 hasAuthorship W2620266114A5060449174 @default.
- W2620266114 hasAuthorship W2620266114A5074526101 @default.
- W2620266114 hasAuthorship W2620266114A5075671062 @default.
- W2620266114 hasAuthorship W2620266114A5079931088 @default.
- W2620266114 hasAuthorship W2620266114A5083090050 @default.
- W2620266114 hasAuthorship W2620266114A5090776132 @default.
- W2620266114 hasBestOaLocation W26202661141 @default.
- W2620266114 hasConcept C101544691 @default.
- W2620266114 hasConcept C121608353 @default.
- W2620266114 hasConcept C126322002 @default.
- W2620266114 hasConcept C142724271 @default.
- W2620266114 hasConcept C143998085 @default.
- W2620266114 hasConcept C170493617 @default.
- W2620266114 hasConcept C2776539811 @default.
- W2620266114 hasConcept C2777583451 @default.
- W2620266114 hasConcept C2778439243 @default.
- W2620266114 hasConcept C2778729363 @default.
- W2620266114 hasConcept C2778820342 @default.
- W2620266114 hasConcept C2779490328 @default.
- W2620266114 hasConcept C2780035454 @default.
- W2620266114 hasConcept C2781432949 @default.
- W2620266114 hasConcept C42362537 @default.
- W2620266114 hasConcept C502942594 @default.
- W2620266114 hasConcept C71924100 @default.
- W2620266114 hasConcept C98274493 @default.
- W2620266114 hasConceptScore W2620266114C101544691 @default.
- W2620266114 hasConceptScore W2620266114C121608353 @default.
- W2620266114 hasConceptScore W2620266114C126322002 @default.
- W2620266114 hasConceptScore W2620266114C142724271 @default.
- W2620266114 hasConceptScore W2620266114C143998085 @default.
- W2620266114 hasConceptScore W2620266114C170493617 @default.
- W2620266114 hasConceptScore W2620266114C2776539811 @default.
- W2620266114 hasConceptScore W2620266114C2777583451 @default.
- W2620266114 hasConceptScore W2620266114C2778439243 @default.
- W2620266114 hasConceptScore W2620266114C2778729363 @default.
- W2620266114 hasConceptScore W2620266114C2778820342 @default.
- W2620266114 hasConceptScore W2620266114C2779490328 @default.
- W2620266114 hasConceptScore W2620266114C2780035454 @default.
- W2620266114 hasConceptScore W2620266114C2781432949 @default.
- W2620266114 hasConceptScore W2620266114C42362537 @default.
- W2620266114 hasConceptScore W2620266114C502942594 @default.
- W2620266114 hasConceptScore W2620266114C71924100 @default.
- W2620266114 hasConceptScore W2620266114C98274493 @default.
- W2620266114 hasIssue "suppl_4" @default.
- W2620266114 hasLocation W26202661141 @default.
- W2620266114 hasLocation W26202661142 @default.
- W2620266114 hasLocation W26202661143 @default.
- W2620266114 hasOpenAccess W2620266114 @default.
- W2620266114 hasPrimaryLocation W26202661141 @default.
- W2620266114 hasRelatedWork W1991113818 @default.
- W2620266114 hasRelatedWork W2066018157 @default.
- W2620266114 hasRelatedWork W2414149210 @default.
- W2620266114 hasRelatedWork W2416569285 @default.
- W2620266114 hasRelatedWork W2620266114 @default.
- W2620266114 hasRelatedWork W2622751763 @default.
- W2620266114 hasRelatedWork W2751395222 @default.
- W2620266114 hasRelatedWork W2902072959 @default.
- W2620266114 hasRelatedWork W2903363945 @default.
- W2620266114 hasRelatedWork W32471882 @default.
- W2620266114 hasVolume "19" @default.
- W2620266114 isParatext "false" @default.
- W2620266114 isRetracted "false" @default.
- W2620266114 magId "2620266114" @default.
- W2620266114 workType "article" @default.