CardioTox In Vivo ****************************************************************************************** * ****************************************************************************************** People Publications The research is tightly coordinated with the other laboratories of the network CardioTox H Králové (see the section Cooperation). We focus on the cardiovascular toxicity of anticanc especially those inducing heart failure, and the possibilities of pharmacological cardiopr main subject is the cardiotoxicity of anthracycline cytostatics (ANTs, e.g., doxorubicin o Moreover, we have studied the toxicity of newer biologically targeted drugs, such as tyros inhibitors (sunitinib) and proteasome inhibitors (bortezomib/carfilzomib). Our goal is to quality experimental and translational research in cardio-oncology. Regarding ANT cardiotoxicity, we are studying molecular mechanisms of cardiotoxicity devel are particularly interested in the role of topoisomerase II beta (TOP2B) and its poisoning induces DNA damage and DNA damage response (DDR) signaling in the heart.   We have also studied the mechanisms of action of clinically used cardioprotectant dexrazox Our recent work shows that its cardioprotective effects are not mediated by iron chelation believed. However, DEX acts as a catalytic inhibitor of TOP2B, thereby preventing poisonin by ANTs, and thus DNA damage and DDR will not happen in the heart.   We are also investigating new pharmacological cardioprotectants targeting TOP2B. We have s derivatives, which are more potent as catalytic inhibitors of TOP2B, are also more potent ANT-induced DDR and, consequently, more effective as cardioprotectants. In this regard, we compound GK-667, a prodrug of ICRF-193, as a promising cardioprotectant in vivo providing dependent cardioprotection in lower ratios to ANTs than DEX. Besides that, we study the ca effects of other TOP2B inhibitors than DEX and related agents, including newly synthesized develop TOP2B selective, effective and safe cardioprotectants.  Our recent interest is to analyze DDR signaling induced by ANTs in the heart and tumors i its pharmacological modulation by TOP2B inhibitors and DDR inhibitors. For this purpose, w established a model of mice bearing human tumor xenografts and their treatment with doxoru ****************************************************************************************** * People ****************************************************************************************** Group Leader • Doc. PharmDr. Martin Štěrba, Ph.D. [ URL "https://is.cuni.cz/webapps/whois2/osoba/108020 lang=cs"] Postdoctoral Researchers • PharmDr. Olga Lenčová [ URL "https://is.cuni.cz/webapps/whois2/osoba/1557694066595121/?l Popelová), Ph.D. • Mgr. Petra Kollárová [ URL "https://is.cuni.cz/webapps/whois2/osoba/1663163846544546/?la Brázdová), Ph.D. • Daniel Diaz Garcia, Ph.D. Former Group Members • PharmDr. Jirkovský Eduard, Ph.D. (bývalý doktorand a postdoktorand) • Mgr. Zuzana Pokorná, Ph.D. (bývalá doktorandka) • Prof. MUDr. Vladimír Geršl, Ph.D. (bývalý vedoucí skupiny) ****************************************************************************************** * Publications ****************************************************************************************** A full list of publications can be found in the Scopus database [ URL "https://www.scopus. detail.uri?authorId=6602528504"] . Overview of last 10 years • 26 papers in journals with IF in total • AIS D1 papers – 19.2 %,  AIS Q1 papers – 73.1 % • Group Leader as the corresponding author – 53.2 % (with an one exception, all are Q1 pap Selected publications 1.Pokorná Z., Kollárová-Brázdová P., Lenčová-Popelová O., Jirkovský E., Kubeš J., Mazurová M., Holečková M., Palička V., Šimůnek T., Štěrba M. Primary prevention of chronic anthra cardiotoxicity with ACE inhibitor is temporarily effective in rabbits, but benefits wane treatment follow-up. Clinical Science (London) 2022;136(1):139-161.  IF 6.876, AIS 1.456, AIS Q1 2.Jirkovský E., Jirkovská A., Bavlovič-Piskáčková H., Skalická V., Pokorná Z., Karabanovic Brázdová P., Kubeš J., Lenčová-Popelová O., Mazurová Y., Adamcová M., Lyon A. R., Roh J. Štěrbová-Kovaříková P., Štěrba M. Clinically Translatable Prevention of Anthracycline Ca by Dexrazoxane Is Mediated by Topoisomerase II Beta and Not Metal Chelation. Circulation 2021;14(11):e008209.  IF 10.447, AIS 4.093, AIS D1 3.Kollárová-Brázdová P., Lenčová-Popelová O., Karabanovich G., Kocúrová-Lengvarská J., Kub N., Mazurová Y., Adamcová M., Jirkovská A., Holečková M., Šimůnek T., Štěrbová-Kovaříkov Štěrba M. Prodrug of ICRF-193 provides promising protective effects against chronic anth cardiotoxicity in a rabbit model in vivo. Clinical Science (London) 2021;135(15):1897-19 IF 6.876, AIS 1.456, AIS Q1 4.Pokorná Z., Jirkovský E., Hlaváčková M., Jansová H., Jirkovská A., Lenčová-Popelová O., P., Kubeš J., Sotáková-Kašparová D., Mazurová Y., Adamcová M., Vostatková L., Holzerová F., Šimůnek T., Štěrba M. In vitro and in vivo investigation of cardiotoxicity associate anticancer proteasome inhibitors and their combination with anthracycline. Clinical Scie 2019;133(16):1827-1844.  IF 5.223, AIS 1.327, AIS Q1 5.Mladěnka P., Applová L., Patočka J, Costa V.M., Remiao F., Pourová J., Mladěnka A., Karl Jahodář L., Vopršalová M., Varner K.J., Štěrba M.; TOX-OER and CARDIOTOX Hradec Králové Collaborators. Comprehensive review of cardiovascular toxicity of drugs and related agen Research Reviews 2018;38(4):1332-1403.  IF 9.791, AIS 2.096, AIS D1 6.Lenčová-Popelová O., Jirkovský E., Jansová H., Jirkovská-Vávrová A., Vostatková-Tichotov Y., Adamcová M., Chládek J., Hroch M., Pokorná Z., Geršl V., Šimůnek T., Štěrba M. Cardi effects of inorganic nitrate/nitrite in chronic anthracycline cardiotoxicity: Comparison dexrazoxane. Journal of Molecular and Cellular Cardiology 2016;91:92-103.  IF 5.055, AIS 1.470, Q1 7.Štěrba M., Popelová O., Vávrová A., Jirkovský E., Kovaříková P., Geršl V., Šimůnek T. Ox stress, redox signaling and metal chelation in anthracycline cardiotoxicity and pharmaco cardioprotection. Antioxidants & Redox Signaling 2013;18(8):899-929.  IF 5.828, AIS 1.921, AIS D1/Q1