Detailed Information on Publication Record
2015
DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines
NERADIL, Jakub, Gabriela PAVLASOVÁ, Martin ŠRÁMEK, Michal KÝR, Renata VESELSKÁ et. al.Basic information
Original name
DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines
Authors
NERADIL, Jakub (203 Czech Republic, guarantor, belonging to the institution), Gabriela PAVLASOVÁ (203 Czech Republic, belonging to the institution), Martin ŠRÁMEK (203 Czech Republic, belonging to the institution), Michal KÝR (203 Czech Republic, belonging to the institution), Renata VESELSKÁ (203 Czech Republic, belonging to the institution) and Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution)
Edition
Oncology Reports, Athens, Spandidos Publications Ltd, 2015, 1021-335X
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30200 3.2 Clinical medicine
Country of publisher
Greece
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 2.486
RIV identification code
RIV/00216224:14110/15:00087437
Organization unit
Faculty of Medicine
UT WoS
000353180900010
Keywords in English
methotrexate; leucovorin; osteosarcoma; resistance; antifolate; medulloblastoma
Tags
International impact, Reviewed
Změněno: 25/11/2015 21:03, prof. RNDr. Renata Veselská, Ph.D., M.Sc.
Abstract
V originále
Although methotrexate (MTX) is the most well-known antifolate included in many standard therapeutic regimens, substantial toxicity limits its wider use, particularly in pediatric oncology. Our study focused on a detailed analysis of MTX effects in cell lines derived from two types of pediatric solid tumors: medulloblastoma and osteosarcoma. The main aim of this study was to analyze the effects of treatment with MTX at concentrations comparable to MTX plasma levels in patients treated with high-dose or low-dose MTX. The results showed that treatment with MTX significantly decreased proliferation activity, inhibited the cell cycle at S-phase and induced apoptosis in Daoy and Saos-2 reference cell lines, which were found to be MTX-sensitive. Furthermore, no difference in these effects was observed following treatment with various doses of MTX ranging from 1 to 40 µM. These findings suggest the possibility of achieving the same outcome with the application of low-dose MTX, an extremely important result, particularly for clinical practice. Another important aspect of treatment with high-dose MTX in clinical practice is the administration of leucovorin (LV) as an antidote to reduce MTX toxicity in normal cells. For this reason, the combined application of MTX and LV was also included in our experiments; however, this application of MTX together with LV did not elicit any detectable effect. The expression analysis of genes involved in the mechanisms of resistance to MTX was a final component of our study, and the results helped us to elucidate the mechanisms of the various responses to MTX among the cell lines included in our study.
Links
| NT14327, research and development project |
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