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Sökning: onr:"swepub:oai:DiVA.org:uu-262220" > WNT activation by l...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005586naa a2201033 4500
001oai:DiVA.org:uu-262220
003SwePub
008150910s2014 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2622202 URI
0247 a https://doi.org/10.1186/s40478-014-0174-y2 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Zhukova, Nataliya4 aut
2451 0a WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
264 c 2014-12-24
264 1b Springer Science and Business Media LLC,c 2014
338 a electronic2 rdacarrier
520 a TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
7001 a Ramaswamy, Vijay4 aut
7001 a Remke, Marc4 aut
7001 a Martin, Dianna C4 aut
7001 a Castelo-Branco, Pedro4 aut
7001 a Zhang, Cindy H4 aut
7001 a Fraser, Michael4 aut
7001 a Tse, Ken4 aut
7001 a Poon, Raymond4 aut
7001 a Shih, David J H4 aut
7001 a Baskin, Berivanu Uppsala universitet,Institutionen för immunologi, genetik och patologi4 aut0 (Swepub:uu)berba972
7001 a Ray, Peter N4 aut
7001 a Bouffet, Eric4 aut
7001 a Dirks, Peter4 aut
7001 a von Bueren, Andre O4 aut
7001 a Pfaff, Elke4 aut
7001 a Korshunov, Andrey4 aut
7001 a Jones, David T W4 aut
7001 a Northcott, Paul A4 aut
7001 a Kool, Marcel4 aut
7001 a Pugh, Trevor J4 aut
7001 a Pomeroy, Scott L4 aut
7001 a Cho, Yoon-Jae4 aut
7001 a Pietsch, Torsten4 aut
7001 a Gessi, Marco4 aut
7001 a Rutkowski, Stefan4 aut
7001 a Bognar, Laszlo4 aut
7001 a Cho, Byung-Kyu4 aut
7001 a Eberhart, Charles G4 aut
7001 a Conter, Cecile Faure4 aut
7001 a Fouladi, Maryam4 aut
7001 a French, Pim J4 aut
7001 a Grajkowska, Wieslawa A4 aut
7001 a Gupta, Nalin4 aut
7001 a Hauser, Peter4 aut
7001 a Jabado, Nada4 aut
7001 a Vasiljevic, Alexandre4 aut
7001 a Jung, Shin4 aut
7001 a Kim, Seung-Ki4 aut
7001 a Klekner, Almos4 aut
7001 a Kumabe, Toshihiro4 aut
7001 a Lach, Boleslaw4 aut
7001 a Leonard, Jeffrey R4 aut
7001 a Liau, Linda M4 aut
7001 a Massimi, Luca4 aut
7001 a Pollack, Ian F4 aut
7001 a Ra, Young Shin4 aut
7001 a Rubin, Joshua B4 aut
7001 a Van Meir, Erwin G4 aut
7001 a Wang, Kyu-Chang4 aut
7001 a Weiss, William A4 aut
7001 a Zitterbart, Karel4 aut
7001 a Bristow, Robert G4 aut
7001 a Alman, Benjamin4 aut
7001 a Hawkins, Cynthia E4 aut
7001 a Malkin, David4 aut
7001 a Clifford, Steven C4 aut
7001 a Pfister, Stefan M4 aut
7001 a Taylor, Michael D4 aut
7001 a Tabori, Uri4 aut
7102 a Uppsala universitetb Institutionen för immunologi, genetik och patologi4 org
7730 t Acta neuropathologica communicationsd : Springer Science and Business Media LLCg 2q 2x 2051-5960
8564 u https://doi.org/10.1186/s40478-014-0174-yy Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:852792/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 u https://actaneurocomms.biomedcentral.com/track/pdf/10.1186/s40478-014-0174-y
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-262220
8564 8u https://doi.org/10.1186/s40478-014-0174-y

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