Matches in SemOpenAlex for { <https://semopenalex.org/work/W4307114519> ?p ?o ?g. }
- W4307114519 endingPage "912" @default.
- W4307114519 startingPage "899" @default.
- W4307114519 abstract "Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma.SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo.High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells.High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin." @default.
- W4307114519 created "2022-10-27" @default.
- W4307114519 creator A5002801148 @default.
- W4307114519 creator A5003760124 @default.
- W4307114519 creator A5004383794 @default.
- W4307114519 creator A5007511463 @default.
- W4307114519 creator A5008818696 @default.
- W4307114519 creator A5009045131 @default.
- W4307114519 creator A5009873168 @default.
- W4307114519 creator A5013347997 @default.
- W4307114519 creator A5015150949 @default.
- W4307114519 creator A5016414138 @default.
- W4307114519 creator A5019028542 @default.
- W4307114519 creator A5021978917 @default.
- W4307114519 creator A5022086187 @default.
- W4307114519 creator A5023084362 @default.
- W4307114519 creator A5029931049 @default.
- W4307114519 creator A5032518739 @default.
- W4307114519 creator A5032931448 @default.
- W4307114519 creator A5033651328 @default.
- W4307114519 creator A5040132448 @default.
- W4307114519 creator A5042114293 @default.
- W4307114519 creator A5042914700 @default.
- W4307114519 creator A5044432222 @default.
- W4307114519 creator A5044720635 @default.
- W4307114519 creator A5049721824 @default.
- W4307114519 creator A5051624965 @default.
- W4307114519 creator A5052210523 @default.
- W4307114519 creator A5052328478 @default.
- W4307114519 creator A5053926716 @default.
- W4307114519 creator A5054006687 @default.
- W4307114519 creator A5059478266 @default.
- W4307114519 creator A5072520782 @default.
- W4307114519 creator A5074228660 @default.
- W4307114519 creator A5077011745 @default.
- W4307114519 creator A5077969502 @default.
- W4307114519 creator A5078203308 @default.
- W4307114519 creator A5078761978 @default.
- W4307114519 creator A5079033020 @default.
- W4307114519 creator A5081859069 @default.
- W4307114519 creator A5082495125 @default.
- W4307114519 creator A5086206547 @default.
- W4307114519 date "2022-10-23" @default.
- W4307114519 modified "2023-10-17" @default.
- W4307114519 title "Epigenetic upregulation of Schlafen11 renders 
WNT- and SHH-activated medulloblastomas sensitive to cisplatin" @default.
- W4307114519 cites W1192385391 @default.
- W4307114519 cites W1929286903 @default.
- W4307114519 cites W1971412744 @default.
- W4307114519 cites W1972623885 @default.
- W4307114519 cites W1996409634 @default.
- W4307114519 cites W2039379153 @default.
- W4307114519 cites W2043398720 @default.
- W4307114519 cites W2059832504 @default.
- W4307114519 cites W2097626332 @default.
- W4307114519 cites W2111130338 @default.
- W4307114519 cites W2113360292 @default.
- W4307114519 cites W2118124054 @default.
- W4307114519 cites W2121155221 @default.
- W4307114519 cites W2122981078 @default.
- W4307114519 cites W2140266186 @default.
- W4307114519 cites W2142673125 @default.
- W4307114519 cites W2150794759 @default.
- W4307114519 cites W2153398041 @default.
- W4307114519 cites W2156239357 @default.
- W4307114519 cites W2163780400 @default.
- W4307114519 cites W2179916275 @default.
- W4307114519 cites W2318212267 @default.
- W4307114519 cites W2338116242 @default.
- W4307114519 cites W2499631704 @default.
- W4307114519 cites W2528953057 @default.
- W4307114519 cites W2588648082 @default.
- W4307114519 cites W2626440326 @default.
- W4307114519 cites W2787281531 @default.
- W4307114519 cites W2793659837 @default.
- W4307114519 cites W2895818115 @default.
- W4307114519 cites W2899298864 @default.
- W4307114519 cites W2944930506 @default.
- W4307114519 cites W2978703154 @default.
- W4307114519 cites W3008140434 @default.
- W4307114519 cites W3013462684 @default.
- W4307114519 cites W3029013190 @default.
- W4307114519 cites W3037354617 @default.
- W4307114519 cites W3094447601 @default.
- W4307114519 cites W3103942119 @default.
- W4307114519 cites W3109354095 @default.
- W4307114519 cites W3121190469 @default.
- W4307114519 cites W3126675804 @default.
- W4307114519 cites W3170859953 @default.
- W4307114519 cites W3200135473 @default.
- W4307114519 cites W3201414411 @default.
- W4307114519 cites W3204688301 @default.
- W4307114519 cites W4225533174 @default.
- W4307114519 doi "https://doi.org/10.1093/neuonc/noac243" @default.
- W4307114519 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36273330" @default.
- W4307114519 hasPublicationYear "2022" @default.
- W4307114519 type Work @default.
- W4307114519 citedByCount "2" @default.
- W4307114519 countsByYear W43071145192023 @default.