DHFR-mediated effects of methotrexate in medulloblastoma and
osteosarcoma cells: The same outcome of treatment with
different doses in sensitive cell lines

J 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.

Základní údaje

Originální název

DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines

Autoři

NERADIL, Jakub (203 Česká republika, garant, domácí), Gabriela PAVLASOVÁ (203 Česká republika, domácí), Martin ŠRÁMEK (203 Česká republika, domácí), Michal KÝR (203 Česká republika, domácí), Renata VESELSKÁ (203 Česká republika, domácí) a Jaroslav ŠTĚRBA (203 Česká republika, domácí)

Vydání

Oncology Reports, Athens, Spandidos Publications Ltd, 2015, 1021-335X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Řecko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.486

Kód RIV

RIV/00216224:14110/15:00087437

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3892/or.2015.3819

UT WoS

000353180900010

Klíčová slova anglicky

methotrexate; leucovorin; osteosarcoma; resistance; antifolate; medulloblastoma

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 11. 2015 21:03, prof. RNDr. Renata Veselská, Ph.D., M.Sc.

Anotace

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.

Návaznosti

NT14327, projekt VaV

Název: DHFR- a non-DHFR-mediované účinky metotrexátu na buněčné úrovni: studie na liniích solidních nádorů dětského věku

Investor: Ministerstvo zdravotnictví ČR, DHFR- a non-DHFR-mediované účinky metotrexátu na buněčné úrovni: studie na liniích solidních nádorů dětského věku

Citovat

NERADIL, Jakub, Gabriela PAVLASOVÁ, Martin ŠRÁMEK, Michal KÝR, Renata VESELSKÁ a Jaroslav ŠTĚRBA. DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines. Oncology Reports. Athens: Spandidos Publications Ltd, 2015, roč. 33, č. 5, s. 2169-2175. ISSN 1021-335X. Dostupné z: https://dx.doi.org/10.3892/or.2015.3819.

@article{1298332,
   author = {Neradil, Jakub and Pavlasová, Gabriela and Šrámek, Martin and Kýr, Michal and Veselská, Renata and Štěrba, Jaroslav},
   article_location = {Athens},
   article_number = {5},
   doi = {http://dx.doi.org/10.3892/or.2015.3819},
   keywords = {methotrexate; leucovorin; osteosarcoma; resistance; antifolate; medulloblastoma},
   language = {eng},
   issn = {1021-335X},
   journal = {Oncology Reports},
   title = {DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines},
   url = {http://www.spandidos-publications.com/or/33/5/2169},
   volume = {33},
   year = {2015}
}

TY  - JOUR
ID  - 1298332
AU  - Neradil, Jakub - Pavlasová, Gabriela - Šrámek, Martin - Kýr, Michal - Veselská, Renata - Štěrba, Jaroslav
PY  - 2015
TI  - DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines
JF  - Oncology Reports
VL  - 33
IS  - 5
SP  - 2169-2175
EP  - 2169-2175
PB  - Spandidos Publications Ltd
SN  - 1021335X
KW  - methotrexate
KW  - leucovorin
KW  - osteosarcoma
KW  - resistance
KW  - antifolate
KW  - medulloblastoma
UR  - http://www.spandidos-publications.com/or/33/5/2169
L2  - http://www.spandidos-publications.com/or/33/5/2169
N2  - 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.
ER  -

NERADIL, Jakub, Gabriela PAVLASOVÁ, Martin ŠRÁMEK, Michal KÝR, Renata VESELSKÁ a Jaroslav ŠTĚRBA. DHFR-mediated effects of methotrexate in medulloblastoma and osteosarcoma cells: The same outcome of treatment with different doses in sensitive cell lines. \textit{Oncology Reports}. Athens: Spandidos Publications Ltd, 2015, roč.~33, č.~5, s.~2169-2175. ISSN~1021-335X. Dostupné z: https://dx.doi.org/10.3892/or.2015.3819.

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