FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2073480888> ?p ?o ?g. }

• W2073480888 endingPage "1424" @default.
• W2073480888 startingPage "1424" @default.
• W2073480888 abstract "Abstract Medulloblastoma comprises the most common malignant brain tumor in childhood. Recently, integrated genomic approaches revealed four major biological disease variants: WNT (wingless), SHH (sonic hedgehog), group 3, and group 4. Treatment failure mainly occurs in children harboring metastatic tumors, which typically carry an isochromosome 17 or gain of 17q, a common hallmark of intermediate and high-risk non-WNT/non-SHH medulloblastoma. Thus, novel therapeutic options for these patients are urgently warranted. Through mRNA expression profiling of 64 primary tumor samples, we identified potassium inwardly-rectifying channel J2 (KCNJ2) as one of the most upregulated genes on chromosome 17q in tumors with 17q gain. Notably, recent reports have linked deregulation of voltage-dependent ion channels to the development of other types of cancer. We first validated our microarray findings on KCNJ2 transcript levels using quantitative real-time PCR. High KCNJ2 transcript levels were significantly associated with non-WNT/non-SHH grouping, anaplastic histology, metastatic dissemination, and poor clinical outcome. KCNJ2 protein expression was analyzed by immunohistochemistry in a large cohort of patients (n=199), and high protein expression levels were found to be strongly correlated with 17q gain, metastatic dissemination, and inferior overall and progression-free survival (p&lt;0.0001). To functionally validate the potential role of KCNJ2 in medulloblastoma biology, we performed knockdown experiments by small interfering RNA-mediated silencing in two well characterized medulloblastoma cell lines. Knockdown of KCNJ2 resulted in a reduced proliferation rate and induction of apoptosis. Furthermore, treatment of the medulloblastoma cell lines with Amiodarone and SR 59230A, two inhibitors of this class of Kir channels, phenocopied these promising anti-proliferative and pro-apoptotic effects in a time- and dose-dependent manner. Whole cell patch clamp results revealed a remarkable current reduction upon inhibitor treatment with SR 59230A. In summary, we could delineate KCNJ2 immunopositivity as an independent biomarker for medulloblastoma with dismal prognosis. Thus, pharmacological inhibition of this candidate gene may constitute a new therapeutic option for patients with high-risk medulloblastomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1424. doi:1538-7445.AM2012-1424" @default.
• W2073480888 created "2016-06-24" @default.
• W2073480888 creator A5008689989 @default.
• W2073480888 creator A5010582324 @default.
• W2073480888 creator A5011013610 @default.
• W2073480888 creator A5017575332 @default.
• W2073480888 creator A5022065845 @default.
• W2073480888 creator A5022310517 @default.
• W2073480888 creator A5024624611 @default.
• W2073480888 creator A5029575769 @default.
• W2073480888 creator A5030383987 @default.
• W2073480888 creator A5031285183 @default.
• W2073480888 creator A5031617518 @default.
• W2073480888 creator A5036577334 @default.
• W2073480888 creator A5037728827 @default.
• W2073480888 creator A5038035447 @default.
• W2073480888 creator A5041096535 @default.
• W2073480888 creator A5041675024 @default.
• W2073480888 creator A5046168756 @default.
• W2073480888 creator A5046496883 @default.
• W2073480888 creator A5047048269 @default.
• W2073480888 creator A5049262839 @default.
• W2073480888 creator A5061246638 @default.
• W2073480888 creator A5064456190 @default.
• W2073480888 creator A5066882189 @default.
• W2073480888 creator A5069883266 @default.
• W2073480888 creator A5073211182 @default.
• W2073480888 creator A5078567170 @default.
• W2073480888 creator A5087348033 @default.
• W2073480888 date "2012-04-01" @default.
• W2073480888 modified "2023-09-27" @default.
• W2073480888 title "Abstract 1424: KCNJ2 comprises a marker of poor prognosis and a therapeutic target in non-WNT/non-SHH medulloblastoma" @default.
• W2073480888 doi "https://doi.org/10.1158/1538-7445.am2012-1424" @default.
• W2073480888 hasPublicationYear "2012" @default.
• W2073480888 type Work @default.
• W2073480888 sameAs 2073480888 @default.
• W2073480888 citedByCount "1" @default.
• W2073480888 countsByYear W20734808882022 @default.
• W2073480888 crossrefType "journal-article" @default.
• W2073480888 hasAuthorship W2073480888A5008689989 @default.
• W2073480888 hasAuthorship W2073480888A5010582324 @default.
• W2073480888 hasAuthorship W2073480888A5011013610 @default.
• W2073480888 hasAuthorship W2073480888A5017575332 @default.
• W2073480888 hasAuthorship W2073480888A5022065845 @default.
• W2073480888 hasAuthorship W2073480888A5022310517 @default.
• W2073480888 hasAuthorship W2073480888A5024624611 @default.
• W2073480888 hasAuthorship W2073480888A5029575769 @default.
• W2073480888 hasAuthorship W2073480888A5030383987 @default.
• W2073480888 hasAuthorship W2073480888A5031285183 @default.
• W2073480888 hasAuthorship W2073480888A5031617518 @default.
• W2073480888 hasAuthorship W2073480888A5036577334 @default.
• W2073480888 hasAuthorship W2073480888A5037728827 @default.
• W2073480888 hasAuthorship W2073480888A5038035447 @default.
• W2073480888 hasAuthorship W2073480888A5041096535 @default.
• W2073480888 hasAuthorship W2073480888A5041675024 @default.
• W2073480888 hasAuthorship W2073480888A5046168756 @default.
• W2073480888 hasAuthorship W2073480888A5046496883 @default.
• W2073480888 hasAuthorship W2073480888A5047048269 @default.
• W2073480888 hasAuthorship W2073480888A5049262839 @default.
• W2073480888 hasAuthorship W2073480888A5061246638 @default.
• W2073480888 hasAuthorship W2073480888A5064456190 @default.
• W2073480888 hasAuthorship W2073480888A5066882189 @default.
• W2073480888 hasAuthorship W2073480888A5069883266 @default.
• W2073480888 hasAuthorship W2073480888A5073211182 @default.
• W2073480888 hasAuthorship W2073480888A5078567170 @default.
• W2073480888 hasAuthorship W2073480888A5087348033 @default.
• W2073480888 hasConcept C126322002 @default.
• W2073480888 hasConcept C137620995 @default.
• W2073480888 hasConcept C143998085 @default.
• W2073480888 hasConcept C173396325 @default.
• W2073480888 hasConcept C2780789225 @default.
• W2073480888 hasConcept C502942594 @default.
• W2073480888 hasConcept C54355233 @default.
• W2073480888 hasConcept C62478195 @default.
• W2073480888 hasConcept C71924100 @default.
• W2073480888 hasConcept C81885089 @default.
• W2073480888 hasConcept C86803240 @default.
• W2073480888 hasConceptScore W2073480888C126322002 @default.
• W2073480888 hasConceptScore W2073480888C137620995 @default.
• W2073480888 hasConceptScore W2073480888C143998085 @default.
• W2073480888 hasConceptScore W2073480888C173396325 @default.
• W2073480888 hasConceptScore W2073480888C2780789225 @default.
• W2073480888 hasConceptScore W2073480888C502942594 @default.
• W2073480888 hasConceptScore W2073480888C54355233 @default.
• W2073480888 hasConceptScore W2073480888C62478195 @default.
• W2073480888 hasConceptScore W2073480888C71924100 @default.
• W2073480888 hasConceptScore W2073480888C81885089 @default.
• W2073480888 hasConceptScore W2073480888C86803240 @default.
• W2073480888 hasIssue "8_Supplement" @default.
• W2073480888 hasLocation W20734808881 @default.
• W2073480888 hasOpenAccess W2073480888 @default.
• W2073480888 hasPrimaryLocation W20734808881 @default.
• W2073480888 hasRelatedWork W2504985512 @default.
• W2073480888 hasRelatedWork W2505177984 @default.
• W2073480888 hasRelatedWork W2538724037 @default.
• W2073480888 hasRelatedWork W2755932397 @default.
• W2073480888 hasRelatedWork W2807440658 @default.
• W2073480888 hasRelatedWork W2811430526 @default.

• next