scholarly journals Topoisomerase-II-beta Inhibitor Racemic XK469

2020 ◽  
Author(s):  
Keyword(s):  
Topoisomerase Ii ◽  
Topoisomerase Ii Beta

Topoisomerase II beta levels are a determinant of melphalan-induced DNA crosslinks and sensitivity to cell death

2006 ◽  
Vol 72 (1) ◽  
pp. 11-18 ◽  
Author(s):  
M. Emmons ◽  
D. Boulware ◽  
D.M. Sullivan ◽  
L.A. Hazlehurst
Keyword(s):  
Cell Death ◽  
Topoisomerase Ii ◽  
Dna Crosslinks ◽  
Topoisomerase Ii Beta

scholarly journals The role of topoisomerase II beta on breakage and proximity of RUNX1 to partner alleles RUNX1T1 and EVI1

2013 ◽  
Vol 53 (2) ◽  
pp. 117-128 ◽  
Author(s):  
Kayleigh A. Smith ◽  
Ian G. Cowell ◽  
Yanming Zhang ◽  
Zbyslaw Sondka ◽  
Caroline A. Austin
Keyword(s):  
Topoisomerase Ii ◽  
Topoisomerase Ii Beta

Clinically Translatable Prevention of Anthracycline Cardiotoxicity by Dexrazoxane Is Mediated by Topoisomerase II Beta and Not Metal Chelation

2021 ◽  
Author(s):  
Eduard Jirkovský ◽  
Anna Jirkovská ◽  
Hana Bavlovič-Piskáčková ◽  
Veronika Skalická ◽  
Zuzana Pokorná ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Topoisomerase Ii ◽  
Left Ventricular ◽  
Functional Markers ◽  
Metal Chelation ◽  
Anthracycline Cardiotoxicity ◽  
Ventricular Cardiomyocytes ◽  
Cardioprotective Effects ◽  
Topoisomerase Ii Beta

Background: Anthracycline-induced heart failure has been traditionally attributed to direct iron-catalyzed oxidative damage. Dexrazoxane (DEX)—the only drug approved for its prevention—has been believed to protect the heart via its iron-chelating metabolite ADR-925. However, direct evidence is lacking, and recently proposed TOP2B (topoisomerase II beta) hypothesis challenged the original concept. Methods: Pharmacokinetically guided study of the cardioprotective effects of clinically used DEX and its chelating metabolite ADR-925 (administered exogenously) was performed together with mechanistic experiments. The cardiotoxicity was induced by daunorubicin in neonatal ventricular cardiomyocytes in vitro and in a chronic rabbit model in vivo (n=50). Results: Intracellular concentrations of ADR-925 in neonatal ventricular cardiomyocytes and rabbit hearts after treatment with exogenous ADR-925 were similar or exceeded those observed after treatment with the parent DEX. However, ADR-925 did not protect neonatal ventricular cardiomyocytes against anthracycline toxicity, whereas DEX exhibited significant protective effects (10–100 µmol/L; P <0.001). Unlike DEX, ADR-925 also had no significant impact on daunorubicin-induced mortality, blood congestion, and biochemical and functional markers of cardiac dysfunction in vivo (eg, end point left ventricular fractional shortening was 32.3±14.7%, 33.5±4.8%, 42.7±1.0%, and 41.5±1.1% for the daunorubicin, ADR-925 [120 mg/kg]+daunorubicin, DEX [60 mg/kg]+daunorubicin, and control groups, respectively; P <0.05). DEX, but not ADR-925, inhibited and depleted TOP2B and prevented daunorubicin-induced genotoxic damage. TOP2B dependency of the cardioprotective effects was probed and supported by experiments with diastereomers of a new DEX derivative. Conclusions: This study strongly supports a new mechanistic paradigm that attributes clinically effective cardioprotection against anthracycline cardiotoxicity to interactions with TOP2B but not metal chelation and protection against direct oxidative damage.

scholarly journals Synthesis and analysis of novel analogues of dexrazoxane and its open-ring hydrolysis product for protection against anthracycline cardiotoxicity in vitro and in vivo

2015 ◽  
Vol 4 (4) ◽  
pp. 1098-1114 ◽  
Author(s):  
Anna Jirkovská-Vávrová ◽  
Jaroslav Roh ◽  
Olga Lenčová-Popelová ◽  
Eduard Jirkovský ◽  
Kateřina Hrušková ◽  
...  
Keyword(s):  
Topoisomerase Ii ◽  
Hydrolysis Product ◽  
Iron Chelation ◽  
Anthracycline Cardiotoxicity ◽  
Promising Target ◽  
Open Ring ◽  
Topoisomerase Ii Beta

Topoisomerase II beta, rather than (or along with) iron chelation, may be a promising target for cardioprotection.

Topoisomerase II beta expression level correlates with doxorubicin-induced apoptosis in peripheral blood cells

2006 ◽  
Vol 374 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Gisela Kersting ◽  
Mladen V. Tzvetkov ◽  
Klaus Huse ◽  
Bettina Kulle ◽  
Verena Hafner ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
Topoisomerase Ii ◽  
Expression Level ◽  
Peripheral Blood Cells ◽  
Induced Apoptosis ◽  
Topoisomerase Ii Beta
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