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Anticancer regimens containing third generation taxanes SB-T-121605 and SB-T-121606 are highly effective in resistant ovarian carcinoma model
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SYSNO ASEP 0565763 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Anticancer regimens containing third generation taxanes SB-T-121605 and SB-T-121606 are highly effective in resistant ovarian carcinoma model Tvůrce(i) Šeborová, K. (CZ)
Koucká, K. (CZ)
Spalenkova, A. (CZ)
Holý, P. (CZ)
Ehrlichová, M. (CZ)
Sychra, T. (CZ)
Chen, L. (US)
Bendale, H. (US)
Ojima, I. (US)
Sandoval-Acuna, Cristian (BTO-N)
Truksa, Jaroslav (BTO-N) RID, ORCID
Souček, P. (CZ)
Václavíková, R. (CZ)Celkový počet autorů 13 Číslo článku 971905 Zdroj.dok. Frontiers in Pharmacology. - : Frontiers Media - ISSN 1663-9812
Roč. 13, NOV 9 2022 (2022)Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova ovarian carcinoma ; resistance ; paclitaxel ; SB-T taxanes ; efficacy ; in vitro ; in vivo Vědní obor RIV FR - Farmakologie a lékárnická chemie Obor OECD Pharmacology and pharmacy CEP GA21-14082S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora BTO-N - RVO:86652036 UT WOS 000890969000001 EID SCOPUS 85142425806 DOI 10.3389/fphar.2022.971905 Anotace Taxanes are widely used in the treatment of ovarian carcinomas. One of the main problems with conventional taxanes is the risk of development of multidrug resistance. New-generation synthetic experimental taxoids (Stony Brook Taxanes, SB-T) have shown promising effects against various resistant tumor models. The aim of our study was to compare the in vitro efficacy, intracellular content, and in vivo antitumor effect of clinically used paclitaxel (PTX) and SB-Ts from the previously tested second (SB-T-1214, SB-T-1216) and the newly synthesized third (SB-T-121402, SB-T-121605, and SB-T-121606) generation in PTX resistant ovarian carcinoma cells NCI/ADR-RES. The efficacy of the new SB-Ts was up to 50-times higher compared to PTX in NCI/ADR-RES cells in vitro. SB-T-121605 and SB-T-121606 induced cell cycle arrest in the G2/M phase much more effectively and their intracellular content was 10-15-times higher, when compared to PTX. Incorporation of SB-T-121605 and SB-T-121606 into therapeutic regimens containing PTX were effective in suppressing tumor growth in vivo in NCI/ADR-RES based mice xenografts at small doses (& LE,3 mg/kg), where their adverse effects were eliminated. In conclusion, new SB-T-121605 and SB-T-121606 analogs are promising candidates for the next phase of preclinical testing of their combination therapy with conventional taxanes in resistant ovarian carcinomas. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2023 Elektronická adresa https://www.frontiersin.org/articles/10.3389/fphar.2022.971905/full
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