ArticleLeukemia2002
Schedule-dependent synergism and antagonism between methotrexate and cytarabine against human leukemia cell lines in vitro.
Article in Leukemia, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Trial
- DeepDrugs: a mechanism-aware tri-linear attention framework for synergistic drug-combination prediction.Briefings in bioinformatics · 2026Article
- Effectiveness and safety of orelabrutinib combined with rituximab, temozolomide, methotrexate, and cytarabine in intensive chemotherapy-unfit patients with PCNSL in China.European journal of medical research · 2025Article
- MATRix and HD-MTX/IFO/DEP treatment and autologous stem cell transplantation in secondary central nervous system lymphoma: a Dutch retrospective analysis.Haematologica · 2025Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- MTX-HOPE is a low-dose salvage chemotherapy for aged patients with relapsed or refractory non-Hodgkin lymphoma.Journal of clinical and experimental hematopathology : JCEH · 2021Article
- Effects of early chemotherapeutic treatment on learning in adolescent mice: implications for cognitive impairment and remediation in childhood cancer survivors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies.British journal of pharmacology · 2013Article
- Cancer cell spheroids as a model to evaluate chemotherapy protocols.Cancer biology & therapy · 2012Article
- Treatment of advanced extranodal NK/T cell lymphoma, nasal-type and aggressive NK-cell leukemia.International journal of hematology · 2010Review
- Treatment of pediatric acute lymphoblastic leukemia: progress achieved and challenges remaining.Current hematologic malignancy reports · 2007Review
- Secondary central nervous system lymphoma.International journal of hematology · 2006Review
- The seventh international childhood acute lymphoblastic leukemia workshop report: Palermo, Italy, January 29--30, 2005.Leukemia · 2005Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methotrexate (MTX) and cytarabine have been widely used for the treatment of acute leukemias and lymphomas for over 30 years. However, the optimal schedule of this combination is yet to be determined and a variety of schedules of the combination has been used. We studied the cytotoxic effects of MTX and cytarabine in combination against human leukemia cell lines at various schedules in vitro. The effects of the combinations at the concentration of drug that produced 80% cell growth inhibition (IC(80)) were analyzed using the isobologram method of Steel and Peckham. Simultaneous exposure to MTX and cytarabine for 3 days produced antagonistic effects in human T cell leukemia, MOLT-3 and CCRF-CEM, B cell leukemia, BALL-1, Burkitt's lymphoma, Daudi, promyelocytic leukemia, HL-60 and Philadelphia chromosome-positive leukemia, K-562 cells. Simultaneous exposure to MTX and cytarabine for 24 h produced antagonistic effects, sequential exposure to MTX for 24 h followed by cytarabine for 24 h produced synergistic effects, and the reverse sequence produced additive effects in both CCRF-CEM and HL-60 cells. Sequential exposure to MTX for 24 h followed by cytarabine for 3 days also produced synergistic effects in MOLT-3 cells. Cell cycle analysis supported these observations. Our findings suggest that the simultaneous administration of MTX and cytarabine is not appropriate and the sequential administration of MTX followed by cytarabine may be the optimal schedule of this combination.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.