Mitoxantrone in Combination with a DNA-PK Inhibitor: Possible Therapy of Promyelocytic Leukaemia Resistant Forms

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F11%3A10106825" target="_blank" >RIV/00216208:11150/11:10106825 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/11:00002579

Výsledek na webu

<a href="http://fb.cuni.cz/file/5600/FB2011A0029.pdf" target="_blank" >http://fb.cuni.cz/file/5600/FB2011A0029.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Mitoxantrone in Combination with a DNA-PK Inhibitor: Possible Therapy of Promyelocytic Leukaemia Resistant Forms

Popis výsledku v původním jazyce

The aim of the study was to sensitize cells of human promyelocytic leukaemia HL-60/MX2 (resistant to mitoxantrone and further substances interacting with topoisomerase II - TI II) to the effect of mitoxantrone (MTX). We demonstrated that the main mechanism of the HL-60/MX2 cell atypical multiple drug resistance is not only their altered activity of TI II and reduced levels of TI II ? and ?. The resistance of the HL-60/MX2 cells to MTX is associated with their increased ability to repair DSB. The HL-60/MX2 cells, compared to HL-60 cells (which are MTX-sensitive), contain large amounts of DNA-PK, which is responsible for the main pathway of the DSB repair, non-homogenous end joining (NHEJ), and they also contain large amounts of further repair proteins Rad50 and Nbs1, which are important in both NHEJ and homologous re-combination. We demonstrated that specific DNA-PK inhibitor NU7026 in HL60/MX2 prevented DSB repair through the NHEJ pathway and essentially abolished the resistance to MTX

Název v anglickém jazyce

Mitoxantrone in Combination with a DNA-PK Inhibitor: Possible Therapy of Promyelocytic Leukaemia Resistant Forms

Popis výsledku anglicky

The aim of the study was to sensitize cells of human promyelocytic leukaemia HL-60/MX2 (resistant to mitoxantrone and further substances interacting with topoisomerase II - TI II) to the effect of mitoxantrone (MTX). We demonstrated that the main mechanism of the HL-60/MX2 cell atypical multiple drug resistance is not only their altered activity of TI II and reduced levels of TI II ? and ?. The resistance of the HL-60/MX2 cells to MTX is associated with their increased ability to repair DSB. The HL-60/MX2 cells, compared to HL-60 cells (which are MTX-sensitive), contain large amounts of DNA-PK, which is responsible for the main pathway of the DSB repair, non-homogenous end joining (NHEJ), and they also contain large amounts of further repair proteins Rad50 and Nbs1, which are important in both NHEJ and homologous re-combination. We demonstrated that specific DNA-PK inhibitor NU7026 in HL60/MX2 prevented DSB repair through the NHEJ pathway and essentially abolished the resistance to MTX

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

BO - Biofyzika

OECD FORD obor

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Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2011

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Folia Biologica

ISSN

0015-5500

e-ISSN

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Svazek periodika

57

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

6

Strana od-do

200-205

Kód UT WoS článku

000297182800004

EID výsledku v databázi Scopus

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