The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

AC1N9ZJC     (2S)-2-[[(1R)-4-[(2,4- diamino-2,3...

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of methotrexate


Psychiatry related information on methotrexate


High impact information on methotrexate


Chemical compound and disease context of methotrexate


Biological context of methotrexate

  • A HSR localized to the long arm of chromosome 10(q26) is present in clones selected at or above 2.5 microM MTX [17].
  • For example, in one MTX-resistant subline studied, approximately equal to 90% of the original DHFR gene dosage is lost in 25-30 cell doublings in the absence of MTX [18].
  • MTX stimulates transient expression in a concentration-dependent manner from a hamster DHFR promoter construct containing 150 base pairs 5' to the start of transcription [19].
  • Cells transfected with the vector alone (and resistant to 0.02 or 1.0 microM MTX) or with a poly(dG-dT) insert (and resistant to 0.05 or 1.0 microM MTX) showed little change in chromosome aberrations or sister chromatid exchange frequencies [20].
  • These 6,5-fused ring heterocyclic antifolates utilized the reduced folate/MTX transporter for uptake, based on the cross-resistance of MTX uptake-impaired CCRF-CEM cells, and were efficient substrates for this uptake system, based on inhibition of [3H]MTX uptake (IC50, 0.3-5.8 microM; aminopterin IC50, 2.6 microM) [21].

Anatomical context of methotrexate

  • In this study, we examined the basis for differences between long chain MTX polyglutamate accumulation between different leukemia cell types using both leukemia cell lines and blasts freshly isolated from blood of leukemic patients [22].
  • UCB patients, who received cyclosporine (CSA) and methylprednisolone (MP), were matched for age, diagnosis, and disease stage with BM patients, who received either methotrexate (MTX) and CSA (26 pairs) or T-cell depletion (TCD) and CSA/MP (31 pairs) [23].
  • Presymptomatic central nervous system (CNS) treatment in children with a late isolated first bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL) was based on intermediate-dose systemic and intrathecal (IT) methotrexate (MTX) in the multicenter trial, ALL-REZ BFM 85 [24].
  • In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20 [25].
  • Even with the marrow suppressive influence of methotrexate (MTX), the viability of the hematopoietic stem cells was not affected, as indicated by the normal repopulation after grafting in the evaluable patients [26].

Associations of methotrexate with other chemical compounds


Gene context of methotrexate

  • Higher expression of hmFPGS relative to hcFPGS was observed in some sublines of CCRF-CEM with acquired MTX resistance suggesting that differential expression of the hmFPGS isoform may contribute to MTX resistance caused by decreased FPGS activity [31].
  • CONCLUSION: MTX, SSZ, infliximab, and IL-4 inhibit human osteoclastogenesis by modulating the interaction of RANKL, RANK, and OPG [32].
  • Loss of BCRP expression also resulted in the following: (c) an identical MTX sensitivity in these cell lines thereby losing the approximately 28-fold MTX resistance of the MCF-7/MR cells; (d) an approximately 2-fold increase in the 4- and 24-h accumulation of [(3)H]folic acid [33].
  • Pre-treatment of Tat-DHFR with MTX blocks the nuclear translocation of the chimeric protein [34].
  • To analyse in depth the effect of this drug, we first determined the structure of mucin oligosaccharide chains synthesized by HT-29 MTX cells and the changes induced by permanent drug exposure [35].

Analytical, diagnostic and therapeutic context of methotrexate


  1. Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia. Winick, N.J., Bowman, W.P., Kamen, B.A., Roach, E.S., Rollins, N., Jacaruso, D., Buchanan, G.R. J. Natl. Cancer Inst. (1992) [Pubmed]
  2. Stable transfectants of human MCF-7 breast cancer cells with increased levels of the human folate receptor exhibit an increased sensitivity to antifolates. Chung, K.N., Saikawa, Y., Paik, T.H., Dixon, K.H., Mulligan, T., Cowan, K.H., Elwood, P.C. J. Clin. Invest. (1993) [Pubmed]
  3. Rapid development of resistance to antifolates in vitro: possible clinical implication. Sobrero, A., Aschele, C., Rosso, R., Nicolin, A., Bertino, J.R. J. Natl. Cancer Inst. (1991) [Pubmed]
  4. Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis). Stucki, A., Leisenring, W., Sandmaier, B.M., Sanders, J., Anasetti, C., Storb, R. Blood (1998) [Pubmed]
  5. The AIMS2-SF: a short form of the Arthritis Impact Measurement Scales 2. French Quality of Life in Rheumatology Group. Guillemin, F., Coste, J., Pouchot, J., Ghézail, M., Bregeon, C., Sany, J. Arthritis Rheum. (1997) [Pubmed]
  6. FK506 ameliorates spontaneous locomotor activity in collagen-induced arthritis: implication of distinct effect from suppression of inflammation. Sasakawa, T., Sasakawa, Y., Ohkubo, Y., Mutoh, S. Int. Immunopharmacol. (2005) [Pubmed]
  7. Early dihydrofolate reductase gene amplification events in CHO cells usually occur on the same chromosome arm as the original locus. Trask, B.J., Hamlin, J.L. Genes Dev. (1989) [Pubmed]
  8. A novel intermediate on the import pathway of cytochrome b2 into mitochondria: evidence for conservative sorting. Gruhler, A., Ono, H., Guiard, B., Neupert, W., Stuart, R.A. EMBO J. (1995) [Pubmed]
  9. Cloning and expression of the chromosomal immune interferon gene of the rat. Dijkema, R., van der Meide, P.H., Pouwels, P.H., Caspers, M., Dubbeld, M., Schellekens, H. EMBO J. (1985) [Pubmed]
  10. Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites. Gourley, D.G., Schüttelkopf, A.W., Leonard, G.A., Luba, J., Hardy, L.W., Beverley, S.M., Hunter, W.N. Nat. Struct. Biol. (2001) [Pubmed]
  11. Lack of functional retinoblastoma protein mediates increased resistance to antimetabolites in human sarcoma cell lines. Li, W., Fan, J., Hochhauser, D., Banerjee, D., Zielinski, Z., Almasan, A., Yin, Y., Kelly, R., Wahl, G.M., Bertino, J.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  12. Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia. Clift, R.A., Buckner, C.D., Appelbaum, F.R., Schoch, G., Petersen, F.B., Bensinger, W.I., Sanders, J., Sullivan, K.M., Storb, R., Singer, J. J. Clin. Oncol. (1992) [Pubmed]
  13. Improvement in outcome for children receiving allogeneic bone marrow transplantation in first remission of acute myeloid leukemia: a report from the Groupe d'Etude des Greffes de Moelle Osseuse. Michel, G., Gluckman, E., Blaise, D., Esperou-Bourdeau, H., Vernant, J.P., Kuentz, M., Bordigoni, P., Milpied, N., Rubie, H., Thuret, I. J. Clin. Oncol. (1992) [Pubmed]
  14. Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Hooijberg, J.H., Broxterman, H.J., Kool, M., Assaraf, Y.G., Peters, G.J., Noordhuis, P., Scheper, R.J., Borst, P., Pinedo, H.M., Jansen, G. Cancer Res. (1999) [Pubmed]
  15. Rapid responses to anakinra in patients with refractory adult-onset Still's disease. Fitzgerald, A.A., Leclercq, S.A., Yan, A., Homik, J.E., Dinarello, C.A. Arthritis Rheum. (2005) [Pubmed]
  16. Chemotherapy without radiation therapy as initial treatment for primary CNS lymphoma in older patients. Freilich, R.J., Delattre, J.Y., Monjour, A., DeAngelis, L.M. Neurology (1996) [Pubmed]
  17. Quantitative correlation of homogeneously stained regions on chromosome 10 with dihydrofolate reductase enzyme in human cells. Wolman, S.R., Craven, M.L., Grill, S.P., Domin, B.A., Cheng, Y.C. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  18. Loss of unstably amplified dihydrofolate reductase genes from mouse cells is greatly accelerated by hydroxyurea. Snapka, R.M., Varshavsky, A. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  19. Stimulation of dihydrofolate reductase promoter activity by antimetabolic drugs. Eastman, H.B., Swick, A.G., Schmitt, M.C., Azizkhan, J.C. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  20. Chromosome instability associated with human alphoid DNA transfected into the Chinese hamster genome. Heartlein, M.W., Knoll, J.H., Latt, S.A. Mol. Cell. Biol. (1988) [Pubmed]
  21. Novel 6,5-fused ring heterocyclic antifolates: biochemical and biological characterization. McGuire, J.J., Bergoltz, V.V., Heitzman, K.J., Haile, W.H., Russell, C.A., Bolanowska, W.E., Kotake, Y., Haneda, T., Nomura, H. Cancer Res. (1994) [Pubmed]
  22. Disparate affinities of antifolates for folylpolyglutamate synthetase from human leukemia cells. Longo, G.S., Gorlick, R., Tong, W.P., Ercikan, E., Bertino, J.R. Blood (1997) [Pubmed]
  23. Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Barker, J.N., Davies, S.M., DeFor, T., Ramsay, N.K., Weisdorf, D.J., Wagner, J.E. Blood (2001) [Pubmed]
  24. Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. BFM (Berlin-Frankfurt-Münster) Relapse Study Group. Bührer, C., Hartmann, R., Fengler, R., Schober, S., Arlt, I., Loewke, M., Henze, G. Blood (1994) [Pubmed]
  25. Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Nemunaitis, J., Buckner, C.D., Appelbaum, F.R., Higano, C.S., Mori, M., Bianco, J., Epstein, C., Lipani, J., Hansen, J., Storb, R. Blood (1991) [Pubmed]
  26. Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation. de Witte, T., Hoogenhout, J., de Pauw, B., Holdrinet, R., Janssen, J., Wessels, J., van Daal, W., Hustinx, T., Haanen, C. Blood (1986) [Pubmed]
  27. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection. Hale, G., Zhang, M.J., Bunjes, D., Prentice, H.G., Spence, D., Horowitz, M.M., Barrett, A.J., Waldmann, H. Blood (1998) [Pubmed]
  28. Improved outcome in adult B-cell acute lymphoblastic leukemia. Hoelzer, D., Ludwig, W.D., Thiel, E., Gassmann, W., Löffler, H., Fonatsch, C., Rieder, H., Heil, G., Heinze, B., Arnold, R., Hossfeld, D., Büchner, T., Koch, P., Freund, M., Hiddemann, W., Maschmeyer, G., Heyll, A., Aul, C., Faak, T., Kuse, R., Ittel, T.H., Gramatzki, M., Diedrich, H., Kolbe, K., Fuhr, H.G., Fischer, K., Schadeck-Gressel, C., Weiss, A., Strohscheer, I., Metzner, B., Fabry, U., Gökbuget, N., Völkers, B., Messerer, D., Uberla, K. Blood (1996) [Pubmed]
  29. Intensive, very short-term chemotherapy for advanced Burkitt's lymphoma in children. Spreafico, F., Massimino, M., Luksch, R., Casanova, M., Cefalo, G.S., Collini, P., Ferrari, A., Polastri, D., Terenziani, M., Gasparini, M., Fossati-Bellani, F. J. Clin. Oncol. (2002) [Pubmed]
  30. Multiple membrane transport systems for the uptake of folate-based thymidylate synthase inhibitors. Jansen, G., Schornagel, J.H., Westerhof, G.R., Rijksen, G., Newell, D.R., Jackman, A.L. Cancer Res. (1990) [Pubmed]
  31. Human cytosolic and mitochondrial folylpolyglutamate synthetase are electrophoretically distinct. Expression in antifolate-sensitive and -resistant human cell lines. McGuire, J.J., Russell, C.A., Balinska, M. J. Biol. Chem. (2000) [Pubmed]
  32. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappaB, osteoprotegerin, and receptor activator of nuclear factor kappaB ligand. Lee, C.K., Lee, E.Y., Chung, S.M., Mun, S.H., Yoo, B., Moon, H.B. Arthritis Rheum. (2004) [Pubmed]
  33. Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression. A role for BCRP in cellular folate homeostasis. Ifergan, I., Shafran, A., Jansen, G., Hooijberg, J.H., Scheffer, G.L., Assaraf, Y.G. J. Biol. Chem. (2004) [Pubmed]
  34. Nuclear translocation of an exogenous fusion protein containing HIV Tat requires unfolding. Bonifaci, N., Sitia, R., Rubartelli, A. AIDS (1995) [Pubmed]
  35. Permanent exposure of mucin-secreting HT-29 cells to benzyl-N-acetyl-alpha-D-galactosaminide induces abnormal O-glycosylation of mucins and inhibits constitutive and stimulated MUC5AC secretion. Hennebicq-Reig, S., Lesuffleur, T., Capon, C., De Bolos, C., Kim, I., Moreau, O., Richet, C., Hémon, B., Recchi, M.A., Maës, E., Aubert, J.P., Real, F.X., Zweibaum, A., Delannoy, P., Degand, P., Huet, G. Biochem. J. (1998) [Pubmed]
  36. Combination intrathecal therapy for meningeal leukemia: two versus three drugs. Sullivan, M.P., Moon, T.E., Trueworthy, R., Vietti, T.J., Humphrey, G.B., Komp, D. Blood (1977) [Pubmed]
  37. Equivalence of intrathecal chemotherapy and radiotherapy as central nervous system prophylaxis in children with acute lymphatic leukemia: a pediatric oncology group study. Sullivan, M.P., Chen, T., Dyment, P.G., Hvizdala, E., Steuber, C.P. Blood (1982) [Pubmed]
  38. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. Reiter, A., Schrappe, M., Ludwig, W.D., Hiddemann, W., Sauter, S., Henze, G., Zimmermann, M., Lampert, F., Havers, W., Niethammer, D. Blood (1994) [Pubmed]
WikiGenes - Universities