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Statements

Subject Item
n2:RIV%2F00216208%3A11150%2F13%3A10188911%21RIV14-MSM-11150___
rdf:type
n7:Vysledek skos:Concept
rdfs:seeAlso
http://dx.doi.org/10.1007/s00411-013-0486-5
dcterms:description
We compared the effects of inhibitors of kinases ATM (KU55933) and ATR (VE-821) (incubated for 30 min before irradiation) on the radiosensitization of human promyelocyte leukaemia cells (HL-60), lacking functional protein p53. VE-821 reduces phosphorylation of check-point kinase 1 at serine 345, and KU55933 reduces phosphorylation of check-point kinase 2 on threonine 68 as assayed 4 h after irradiation by the dose of 6 Gy. Within 24 h after gamma-irradiation with a dose of 3 Gy, the cells accumulated in the G2 phase (67 %) and the number of cells in S phase decreased. KU55933 (10 μM)) did not affect the accumulation of cells in G2 phase and did not affect the decrease in the number of cells in S phase after irradiation. VE-821 (2 and 10 μM)) reduced the number of irradiated cells in the G2 phase to the level of non-irradiated cells and increased the number of irradiated cells in S phase, compared to irradiated cells not treated with inhibitors. In the 144 h interval after irradiation with 3 Gy, there was a considerable induction of apoptosis in the VE-821 group (10 μM)). The repair of the radiation damage, as observed 72 h after irradiation, was more rapid in the group exposed solely to irradiation and in the group treated with KU55933 (80 and 77 % of cells, respectively, were free of DSBs), whereas in the group incubated with 10 mu M VE-821, there were only 61 % of cells free of DSBs. The inhibition of kinase ATR with its specific inhibitor VE-821 resulted in a more pronounced radiosensitizing effect in HL-60 cells as compared to the inhibition of kinase ATM with the inhibitor KU55933. In contrast to KU55933, the VE-821 treatment prevented HL-60 cells from undergoing G2 cell cycle arrest. Taken together, we conclude that the ATR kinase inhibition offers a new possibility of radiosensitization of tumour cells lacking functional protein p53. We compared the effects of inhibitors of kinases ATM (KU55933) and ATR (VE-821) (incubated for 30 min before irradiation) on the radiosensitization of human promyelocyte leukaemia cells (HL-60), lacking functional protein p53. VE-821 reduces phosphorylation of check-point kinase 1 at serine 345, and KU55933 reduces phosphorylation of check-point kinase 2 on threonine 68 as assayed 4 h after irradiation by the dose of 6 Gy. Within 24 h after gamma-irradiation with a dose of 3 Gy, the cells accumulated in the G2 phase (67 %) and the number of cells in S phase decreased. KU55933 (10 μM)) did not affect the accumulation of cells in G2 phase and did not affect the decrease in the number of cells in S phase after irradiation. VE-821 (2 and 10 μM)) reduced the number of irradiated cells in the G2 phase to the level of non-irradiated cells and increased the number of irradiated cells in S phase, compared to irradiated cells not treated with inhibitors. In the 144 h interval after irradiation with 3 Gy, there was a considerable induction of apoptosis in the VE-821 group (10 μM)). The repair of the radiation damage, as observed 72 h after irradiation, was more rapid in the group exposed solely to irradiation and in the group treated with KU55933 (80 and 77 % of cells, respectively, were free of DSBs), whereas in the group incubated with 10 mu M VE-821, there were only 61 % of cells free of DSBs. The inhibition of kinase ATR with its specific inhibitor VE-821 resulted in a more pronounced radiosensitizing effect in HL-60 cells as compared to the inhibition of kinase ATM with the inhibitor KU55933. In contrast to KU55933, the VE-821 treatment prevented HL-60 cells from undergoing G2 cell cycle arrest. Taken together, we conclude that the ATR kinase inhibition offers a new possibility of radiosensitization of tumour cells lacking functional protein p53.
dcterms:title
Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60) Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60)
skos:prefLabel
Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60) Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60)
skos:notation
RIV/00216208:11150/13:10188911!RIV14-MSM-11150___
n7:predkladatel
n10:orjk%3A11150
n4:aktivita
n16:I n16:S
n4:aktivity
I, S
n4:cisloPeriodika
4
n4:dodaniDat
n15:2014
n4:domaciTvurceVysledku
n6:6518672
n4:druhVysledku
n19:J
n4:duvernostUdaju
n20:S
n4:entitaPredkladatele
n18:predkladatel
n4:idSjednocenehoVysledku
80206
n4:idVysledku
RIV/00216208:11150/13:10188911
n4:jazykVysledku
n13:eng
n4:klicovaSlova
ATM and ATR inhibitors; KU55933; VE-821; Radiosensitization; Ionizing radiation
n4:klicoveSlovo
n12:VE-821 n12:Radiosensitization n12:Ionizing%20radiation n12:ATM%20and%20ATR%20inhibitors n12:KU55933
n4:kodStatuVydavatele
DE - Spolková republika Německo
n4:kontrolniKodProRIV
[A8A3E7D7A44B]
n4:nazevZdroje
Radiation and Environmental Biophysics
n4:obor
n5:BO
n4:pocetDomacichTvurcuVysledku
1
n4:pocetTvurcuVysledku
9
n4:rokUplatneniVysledku
n15:2013
n4:svazekPeriodika
52
n4:tvurceVysledku
Vávrová, Jiřina Pejchal, Jaroslav Ďurišová, Kamila Lukášová, Emilie Řezáčová, Martina Šinkorová, Zuzana Tichý, Aleš Zárybnická, Lenka Novotná, Eva
n4:wos
000326074900005
s:issn
0301-634X
s:numberOfPages
9
n3:doi
10.1007/s00411-013-0486-5
n11:organizacniJednotka
11150