Dose and drug changes in chronic lymphocytic leukemia cell response in vitro: A comparison of standard therapy regimens with two novel cyclin‑dependent kinase inhibitors
Jazyk angličtina Země Řecko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
30864706
PubMed Central
PMC6470834
DOI
10.3892/mmr.2019.10007
Knihovny.cz E-zdroje
- MeSH
- apoptóza účinky léků MeSH
- chronická lymfatická leukemie farmakoterapie metabolismus MeSH
- cyklin-dependentní kinasy antagonisté a inhibitory MeSH
- inhibitory proteinkinas aplikace a dávkování farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové buňky kultivované MeSH
- protinádorové látky aplikace a dávkování farmakologie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklin-dependentní kinasy MeSH
- inhibitory proteinkinas MeSH
- protinádorové látky MeSH
Chronic lymphocytic leukemia (CLL) treatment is improving; however, some patients do not respond to therapy. Due to the high heterogeneity in disease development, there is an urgent need for personalization of therapy. In the present study, the response of leukemic mononuclear cells to anticancer drugs used for CLL treatment (cladribine + mafosfamide; CM or CM combined with rituximab; RCM) was compared with the response to new cyclin‑dependent kinase (CDK) inhibitors: BP14 and BP30. Viable apoptotic and necrotic cells were quantified by flow cytometry using propidium iodide and Yo‑Pro stains. CDK inhibitors were studied in several doses to determine the reduction of necrosis and simultaneous increase of apoptosis in leukemic cell incubations with anticancer agents. The distinct cell response to applied doses/anticancer agents was observed. Results obtained in the current manuscript confirmed that modulation of doses is important. This was particularly indicated in results obtained at 24 h of cells incubation with anticancer agent. While an important time for analysis of anticancer response efficacy (monitoring of apoptosis induction potential) seems to be 48 h of cells exposition to anticancer agents. High variability in response to the drugs revealed that both the nature and the dose of the anticancer agents could be important in the final effect of the therapy. The present findings support the thesis that personalized medicine, before drug administration in the clinic, could be important to avoid the application of ineffective therapy.
Department of Experimental Hematology Medical University of Lodz 93‑510 Lodz Poland
Department of Hematology Medical University of Lodz 93‑510 Lodz Poland
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