The three most widely studied and clinically useful folate antagonists are aminopterin, methotrexate (MTX, amethopterin), and 3′ ,5′-dichloro-MTX (Fig. 1). These compounds are all 4-amino analogs of folic acid and are powerful inhibitors of the enzyme dihydrofolate reductase (DHFR) (Fig. 2). The folate antagonists have extremely low inhibition constants (ca. 10−10 M) and they bind in a stoichiometric manner to dihydrofolate reductase at pH 6.0 (Werkheiser, 1961; Bertino et al., 1964). At a more alkaline pH, they bind less tightly and the binding is competitive with the substrate, dihydrofolate. This enzyme-inhibitor complex can be dissociated with regeneration of the enzyme and inhibitor by chromatography on DEAE-cellulose or hydroxylapatite, or by gel filtration at pH 9.0 in the presence of 0.15 M KC1 (Mathews and Huennekens, 1963; Bertino et al., 1964, 1965).


Acute Myelocytic Leukemia Acute Leukemia Mycosis Fungoides Dihydrofolate Reductase Cytosine Arabinoside 
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  1. Anderson, L.L., Collins, G. J., Ojima, Y., Sullivan, R.D.: A study of the distribution of methotrexate in human tissues and tumors. Cancer Res. 30, 1344–1348 (1970).PubMedGoogle Scholar
  2. Baker, B.R.: Active-site directed irreversible inhibitors of dihydrofolate reductase. Ann. N.Y. Acad. Sci. 186, 214–226 (1971).PubMedGoogle Scholar
  3. Baker, B.R., Ho, B.T.: Differential inhibition of dihydrofolate reductase from different species. J. pharm. Sci. 53, 1137–1138 (1964).PubMedGoogle Scholar
  4. Bertino, J. R.: The mechanism of action of the folate antagonists in man. Cancer Res. 23, 1286–1306 (1963).PubMedGoogle Scholar
  5. Bertino, J.R.: Chemical action and pharmacology of methotrexate, azathioprine, and cyclophosphamide in man. Arthritis Rheum. 16, 79–83 (1973).PubMedGoogle Scholar
  6. Bertino, J. R., Booth, B. A., Cashmore, A.R., Bieber, A. L., Sartorelli, A.C.: Studies of the inhibition of dihydrofolate reductase by the folate antagonists. J. biol. Chem. 239, 479–485 (1964).PubMedGoogle Scholar
  7. Bertino, J.R., Cashmore, A.R., Fink, M., Calabresi, P., Lefkowitz, E.: The induction of leukocyte and erythrocyte dihydrofolate reductase by methotrexate. Clin. Pharm. Therap. 6, 763–770 (1965).PubMedGoogle Scholar
  8. Bertino, J. R., Deconti, R.C., Mosher, M.: Chemotherapy of head and neck cancer. Cancer 31, 1141–1149 (1973).PubMedGoogle Scholar
  9. Bertino, J. R., Johns, D.G.: Folate antagonists. Ann. Rev. Med. 18, 27–34 (1967).PubMedGoogle Scholar
  10. Bertino, J.R., Skeel, R.T.: Resistance to chemotherapeutic agents: clinical aspects. Proc. 5th int. Congr. Pharmacol. 3, 376–392 (1973).Google Scholar
  11. Bischoff, K. B., Dedriok, R. L., Zaharko, D. S.: Preliminary model for methotrexate pharmacokinetics. J. pharm. Sci. 59, 149–153 (1970).PubMedGoogle Scholar
  12. Bors A, J., Whitmore, G.F.: Studies relating to the mode of action of methotrexate. III. Inhibition of thymidylate synthetase in tissue culture cells and in cell-free systems. Molec. Pharmacol. 5, 318–332 (1969).Google Scholar
  13. Borsa, J., Whitmore, G.F.: Cell killing studies on the mode of action of methotrexate (MTX) on L-cells in vitro. Cancer Res. 29, 737–744 (1969a).PubMedGoogle Scholar
  14. Bruce, W. R.: The action of chemotherapeutic agents at the cellular level and the effects of these agents on hematopoietic and lymphomatous tissue. In: Canadian cancer conference, Proc. 7th Canad. Cancer Res. Conf., Honey Harbour, Ontario 7, 53–64 (1967).Google Scholar
  15. Bruce, W.R., Meeker, B.E., Valeriote, F.A.: Comparison of the sensitivity of normal hematopoietic and transplanted lymphoma colony forming cells to chemotherapeutic agents administered in vivo. J. nat. Cancer Inst. 37, 233 (1966).PubMedGoogle Scholar
  16. Burchall, J.J.: Comparative biochemistry of dihydrofolate reductase. Ann. N.Y. Acad. Sci. 186, 143–152 (1971).PubMedGoogle Scholar
  17. Burchall, J. J., Hitchtngs, G. H.: Inhibitor binding analysis of dihydrofolate reductases from various species. Molec. Pharmacol. 1, 126–132 (1965).Google Scholar
  18. Bubkitt, D.P.: In: Burkitt, D.P., Burohenal, J.H. (Eds.): Treatment of Burkitt’s tumor. New York: Springer 1966.Google Scholar
  19. Burrows, J.H., Talley, R.W., Drake, E.H., San Diego, F. J., Tucker, W.G.: Infusion of fluorinated pyrimidines into hepatic artery for treatment of metastatic carcinoma of liver. Cancer 21, 1886–1892 (1967).Google Scholar
  20. Capizzi, R.L.: Schedule-dependent eradication of murine leukemia with methotrexate and asparaginase. Fifteenth Ann. Meeting, Amer. Soc. Hematol. 43 (Abstr.) (1972).Google Scholar
  21. Capizzi, R.L., Bertino, J.R.: Methotrexate therapy of Wegener’s granulomatosis. Ann. int. Med. 74, 74–79 (1971a).PubMedGoogle Scholar
  22. Capizzi, R.L., Deconti, R.C., Marsh, J.C., Bertino, J.R.: Methotrexate therapy of head and neck cancer: improvement in therapeutic index by the use of leucovorin “rescue”. Cancer Ites. 30, 1782–1788 (1970).Google Scholar
  23. Capizzi, R.L., Summers, W. P., bertino, J.R.: l-asparaginase induced alteration of amethopterin (methotrexate) activity in mouse leukemia l5178y. Ann. N.Y. Acad. Sci. 186, 302 –311 (1971).Google Scholar
  24. Charache, S., Condit, P. T., Humphreys, S.R.: Studies of the folic acid vitamins. IV. The persistence of amethopterin in mammalian tissues. Cancer 13, 236–240 (1960).PubMedGoogle Scholar
  25. Chello, P., Cashmore, A.R., Jacobs, S.A., Bertino, J.R.: Improved purification of tetra- hydrofolate dehydrogenase from L1210 leukemia by affinity chromatography. Biochim. biophys. Acta (Amst.) 268, 30–34 (1972).Google Scholar
  26. Clarysse, A.M., Cathey, W.J., Cartwright, G.E., Wintrobe, M.N.: Pulmonary disease complicating intermittent therapy with methotrexate. J. Amer. med. Ass. 209, 1861–1864 (1969).Google Scholar
  27. Cleveland, J.C., Johns, D.G., Farnham, G., Bertino, J.R.: Arterial infusion of dichloromethotrexate in cancer of the head and neck: a clinical-pharmacologic study. Curr. Topics surg. Res. 1, 113–120 (1969).Google Scholar
  28. Coe, R. O., Bull, F. E.: Cirrhosis associated with methotrexate treatment of psoriasis. J. Amer. med. Ass. 206, 1514–1520 (1968).Google Scholar
  29. Cohen, s.: on the nature of thymineless death. Ann. N.Y. Acad. Sci. 186, 292–301 (1971).Google Scholar
  30. Condit, p. T.: chemotherapy of neoplastic disease with folate antagonists. Ann. N.Y. Acad. Sci. 186, 475–485 (1971).Google Scholar
  31. Condit, P.T., Chanes, R.E., Joel, W.: The renal toxicity of methotrexate. Cancer 23, 126– 131 (1969).Google Scholar
  32. Condit, P. T., Eliel, L.: Effects of large infrequent doses of amethopterin on acute leukemia in children. J. Amer. med. Ass. 172, 451–453 (1960).Google Scholar
  33. Condit, P., Shnider, B.I., Owens, A.H., JR.: Studies in the folic acid vitamins. VII. The effects of large doses of amethopterin in patients with cancer. Cancer Res. 22, 706–712 (1962).PubMedGoogle Scholar
  34. Crusberg, T.C., Leary, R., Kisliuk, R.L.: Properties of thymidylate synthetase from di- chloromethotrexate-resistant Lactobacillus casei. J. biol. Chem. 245, 5292–5296 (1970).PubMedGoogle Scholar
  35. Davidson, J. O., Oliverio, V.T.: The physiologic disposition of dichloromethotrexate-Cl36 in man. Clin. Pharmacol. Ther. 6, 325–327 (1965).Google Scholar
  36. Djerassi, I.: Methotrexate infusions and intensive supportive care in the management of children with acute lymphocytic leukemia: follow-up report. Cancer Res. 27, 2561–2564 (1967).PubMedGoogle Scholar
  37. Djerassi, I., Rominger, C. J., Kim, J.S., Turchi, J., Suvansri, U., Hughes, D.: Phase I study of high doses of methotrexate with citrovorum factor in patients with lung cancer. Cancer 30, 22–30(1972).Google Scholar
  38. Djerassi, I., Royer, G., Treat, C., Carim, H.: Management of childhood lymphosarcoma and reticulum cell sarcoma with high dose intermittent methotrexate and citrovorum factor. Proc. Amer. Ass. Cancer Res. 9, 18 (1968).Google Scholar
  39. Elliot, J.: Treatment of bladder cancer with amethopterin. Cancer Chemother. Rep. 20, 147 (1962).Google Scholar
  40. Farber, S.L.H., Diamond, R.D., Merger, R.F., Sylvester, J.R., Wolff, J.O.: Temporary remissions in acute leukemia in children produced by folic acid antagonists, 4-aminopteroyl- glutamic acid (aminopterin). New Engl. J. Med. 238, 787–793 (1948).Google Scholar
  41. Fischer, G. A., Bertino, J.R., Welch, A. D.: Uptake of tritium labeled MTX by human leukemia leukocytes. Blood 22, 819 (1963).Google Scholar
  42. Freeman, M. V.: The fluorometric measurement of the absorption, distribution and excretion of single doses of 4-amino-10-methylpteroylglutamic acid (amethopterin) in man. J. Pharmacol. exp. Ther. 122, 164–162 (1958).Google Scholar
  43. Goldin, A., Vendetti, J.M., Humphreys, S.R., Dennis, D., Mantel, N., Greenhouse, S.W.: A quantitative comparison of the antileukemic effectiveness of two folic antagonists in mice. J. nat. Cancer Inst. 15, 1657–1664 (1955).PubMedGoogle Scholar
  44. Goldie, J., Hillcoat, B.L.: Purification of tetrahydrofolate dehydrogenase by affinity chromatography. Biochim. biophys. Acta (Amst.) 268, 35–40 (1972).Google Scholar
  45. Goldman, I. D.: The characteristics of the membrane transport of amethopterin and the naturally occurring folates. Ann. N. Y. Acad. Sci. 186, 400–422 (1971).PubMedGoogle Scholar
  46. Gottlieb, J. A., Serpick, A. A.: Prolonged intravenous methotrexate therapy in the treatment of acute leukemia and solid tumors. Cancer Res. 30, 2132–2138 (1970).PubMedGoogle Scholar
  47. Gbignani, F., Martinelli, M.F., Tonato, M., Finzi, A.F.: Folate dependent enzymes in human epidermis. Arch. Derm. 96, 577–585 (1967).Google Scholar
  48. Hakala, M.T.: On the role of drug penetration in amethopterin resistance of sarcoma–180 cells in vitro. Biochim. biophys. Acta (Amst.) 102, 198–209 (1965).Google Scholar
  49. Hellman, S., Iannotti, A., Bertino, J. R.: Determinations of the levels of serum folate in patients with carcinoma of the head and neck treated with methotrexate. Cancer Res. 24, 105–113 (1964).PubMedGoogle Scholar
  50. Henderson, E.S.: Treatment of acute leukemia. Ann. int. Med. 69, 628–632 (1968).PubMedGoogle Scholar
  51. Henderson, E.S., Adamson, R.H., Oliverio, V.T.: The metabolic fate of tritiated methotrexate. II. Absorption and excretion in man. Cancer Res. 25, 1018–1024 (1965).PubMedGoogle Scholar
  52. Hertz, R., Lewis, J., JR., Lippsett, M.B.: 5 Years experience with the Chemotherapy of metastatic choriocarcinoma and related trophoblastic tumors in women. Amer. J. obstet. and Gynec. 82, 631–640 (1961).Google Scholar
  53. Hertz, R., Ross, G.T., Lipsett, M.B.: Chemotherapy in women with trophoblastic disease; choriocarcinoma, chorioadenoma destruens, and complicated hydatidiform mole. Ann. N.Y. Acad. Sci. 114, 881–885 (1964).Google Scholar
  54. Hitchings, G.H.: Folate antagonists as antibacterial and antiprotozoal agents. Ann. N.Y. Acad. Sci. 186, 444–451 (1971).PubMedGoogle Scholar
  55. Hryniuk, W.M., Bertino, J. R.: The treatment of leukemia with large doses of methotrexate and folinie acid: clinical-biochemical correlates. J. clin. Invest. 48, 2140–2155 (1969).PubMedGoogle Scholar
  56. Hryniuk, W.M., Bertino, J. R.: Growth rate and cell kill. Ann. N. Y. Acad. Sci. 186, 330–342 (1971).PubMedGoogle Scholar
  57. Hryniuk, W.M., Fischer, G. A., Bertino, J.R.: Phase cells of rapidly growing and resting populations. Differences in response to methotrexate. Molec. Pharmacol. 5, 557–564 (1969).Google Scholar
  58. Huennekens, F.M., Dunlap, R.B., Freisheim, J.H., Gundersen, L.E., Harding, N.G.L., Levison, S.A., Mell, G.P.: Dihydrofolate reductases: structural and mechanistic aspects. Ann. N.Y. Acad. Sci. 186, 85 99 (1971).Google Scholar
  59. Jaffe, N., Farber, S., Traggis, D., Geiser, C., Das, L., Kim, B., Franenberger, G., Djeras- Si, I.: Favorable response of metastatic osteogenic sarcoma to pulse high dose metho- trexate-citrovorum-administration. Proc. Amer. Ass. Cancer Res. 13, 27 (1972).Google Scholar
  60. Johns, D.G., Hollingsworth, J.W., Cashmore, A.R., Plenderleith, I.H., Bertino, J. R.: methotrexate displacement in man. J. Clin. Invest. 43, 621–629 (1964).PubMedGoogle Scholar
  61. Johns, D.G., Iannotti, A.T., Sartorelli, A.C., Booth, B. A., Bertino, J. R.: The identity of rabbit liver methotrexate oxidase. Biochim. biophys. Acta (Amst.) 105, 380–382 (1965).Google Scholar
  62. Johns, D.G., Spencer, R.P., Chang, P.K., Bertino, J.R.: I131I-3’-Iodoaminopterin: a gam- ma-labeled active-site-directed enzyme inhibitor. J. nuclear Med. 9, 530–536 (1968).Google Scholar
  63. Johns, D.G., Valerino, D.M.: Metabolism of folate antagonists. Ann. N.Y. Acad. Sci. 186, 378–386 (1971).PubMedGoogle Scholar
  64. Kaufman, B.T., Pierce, J. V.: Purification of dihydrofolic reductase from chicken liver by affinity chromatography. Biochem. biophys. Res. Comm. 44, 608–613 (1971).Google Scholar
  65. Kessel, D., Hall, T.C., Roberts, D.: Modes of uptake of methotrexate by normal and leukemic human leukocytes in vitro and their relation to drug response. Cancer Res. 28, 564– 570 (1968).Google Scholar
  66. Kessel, D., Hall, T. C., Roberts, D., Wodinsky, I.: Uptake as a determinant of methotrexate response in mouse leukemias. Science 150, 752–754 (1965).PubMedGoogle Scholar
  67. Labow, R., Maley, G.F., Maley, F.: The effect of methotrexate on enzymes following partial hepatectomy. Cancer Res. 29, 366–372 (1969).PubMedGoogle Scholar
  68. Lane, M., Moore, J.E., III., Levin, H., Smith, F.E.: Methotrexate therapy for squamous cell carcinoma of the head and neck. J. Amer. med. Ass. 204, 561–564 (1968).Google Scholar
  69. Leary, R., Kisliuk, R. L.: Crystalline thymidylate synthetase from dichlormethotrexate resistant Lactobacillus casei. Prep. Biochem. 1, 47–54 (1971).PubMedGoogle Scholar
  70. Leone, L. A., Albala, M.M., Rege, V.B.: Treatment of carcinoma of the head and neck with intravenous methotrexate. Cancer 21, 828–837 (1968).PubMedGoogle Scholar
  71. Levitt, M., Marsh, J.C., Deconti, R.C., Mitchell, M.S., Skeel, R.T., Farber, L.R., BerTino, J. R.: Combination sequential chemotherapy in advanced reticulum cell sarcoma. Cancer 29, 630–636 (1972).PubMedGoogle Scholar
  72. Li, M.C., Nixon, N.E., Freeman, M.V.: Increase of urinary citrovorum factor activity in patients receiving methotrexate (amethopterin). Proc. Soc. exp. Biol. (N.Y.) 97, 29–32 (1958).Google Scholar
  73. Liegler, D.G., Henderson, E.S., Hahn, M.A., Oliverio, V.T.: The effect of organic acids on renal clearance of methotrexate in man. Clin. Pharmacol. Ther. 10, 849–857 (1969).PubMedGoogle Scholar
  74. Livingston, R.B., Carter, S.K.: Single agents in cancer chemotherapy. London: Plenum Press 1970.Google Scholar
  75. Mathews, C.K., Huennekens, F.M.: Further studies on dihydrofolic reductase. J. biol. Chem. 238, 3436–3442 (1963).PubMedGoogle Scholar
  76. Mcdonald, C. J., Bertino, J. R.: Parenteral methotrexate for psoriasis. Arch. Derm. 100, 655–668 (1969).PubMedGoogle Scholar
  77. McDonald, C. J., Bertino, J. R.: Unpublished Observations.Google Scholar
  78. Nahas, A., Capizzi, R.L., Bertino, J. R.: Methotrexate transport in logarithmic and plateau phase cells. Submitted for publication.Google Scholar
  79. Nahas, A., Nixon, P.F., Bertino, J. R.: Uptake and metabolism of N5-formy 1 te trahy dro- folate by L1210 leukemia cells. Cancer Res. 32, 1416–1421 (1972).PubMedGoogle Scholar
  80. Nervi, C., Arcangeli, G., Casale, C., Carrese, M., Guadagni, A., LePera, V.: A Reappraisal Of Intra-Arterial Chemotherapy. Cancer 26, 577–582 (1970).PubMedGoogle Scholar
  81. Newton, W., Sayers, M., Samuels, L.: Intrathecal methotrexate (NSC 740) therapy for brain tumors in children. Cancer Chemother. Rep. 52, 257–261 (1968).Google Scholar
  82. Niethammer, D., Huennekens, F.M.: Transport of folic acid, 5-methyltetrahydrofolic acid and methotrexate through the membrane of lymphocytes. 2nd International Symposium on Metabolism and Membrane Permeability of Erythrocytes, Thrombocytes and Leukocytes, p. 81, Vienna, June 14–16, 1972.Google Scholar
  83. Perkins, J. P., Hellcoat, B.L., Bertino, J. R.: Dihydrofolate reductase from a resistant subline of the L1210 lymphoma. J. biol. Chem. 242, 4771–4776 (1967).PubMedGoogle Scholar
  84. Perrin, J., Matter, A.: Evaluation of intravenous amethopterin therapy in acute leukemia. J. Pediat. 61, 283–284 (1963).Google Scholar
  85. Roberts, D.W., Hall, T. C., Rosenthal, D.: Coordinated changes in biochemical patterns: the effects of cytosine arabinoside and methotrexate on leukocytes from patients with acute granulocytic leukemia. Cancer Res. 29, 571–578 (1969).PubMedGoogle Scholar
  86. Roberts, D.W., Loehr, E.V.: Elevation of thymidylate synthetase activity in CCRF–CEM cells. Cancer Res. 31, 1181–1187 (1971).PubMedGoogle Scholar
  87. Roenigk, H.H., Bergfeld, W.F., St. Jacques, R., Owens, F. J., Hawk, W. A.: Hepatotoxicity of methotrexate in treatment of psoriasis. Arch. Derm. 103, 250–261 (1971).PubMedGoogle Scholar
  88. Roy, D.: Treatment of advanced or recurrent carcinoma of the cervix by cytotoxic drugs. Indian J. Cancer 4, 32 (1967).Google Scholar
  89. Rubin, R. C., Ommaya, A. K., Henderson, E. S., Bering, E. A., Rall, D. P.: Cerebrospinal fluid perfusion for central nervous system neoplasms. Neurology 16, 680–692 (1966).PubMedGoogle Scholar
  90. Schwarzenberg, L., Mathe, G., Hayat, M., DeVassal, F., Amiel, J.L., Cattan, A., Schneider, M., Schlumberger, J.R., Rosenfeld, C., Jasmin, C., Ngo/Minh/Mah: une nouvelle combinaison de methotrexate et d’acide folinique pour le traitment des cancers. La presse med. 77, 385–388 (1969).Google Scholar
  91. Selawry, O.: New treatment schedule with improved survival in childhood leukemia. Intermittent parenteral vs. daily oral administration of methotrexate for maintenance of induced remission. J. Amer. med. Ass. 194, 75–81 (1965).Google Scholar
  92. Skeel, R.T., Marsh, J. C., Deconti, R.C., Mitchell, M.S., Hubbard, S.P., Bertino, J. R.: Development of a combination chemotherapy program for adults with acute leukemia: CAM and CAM-L. Cancer 32, 76–81 (1973).PubMedGoogle Scholar
  93. Steinberg, A. D.: Efficacy of immunosuppressive drugs in rheumatic diseases. Arthr. and Rheum, (in press).Google Scholar
  94. Sullivan, M. P., Vietti, T. J., Fernbach, D. J., Griffith, K.M., Haddy, T.B., Watkins, W.L.: Clinical investigations in the treatment of meningeal leukemia: radiation therapy regimens vs. conventional intrathecal methotrexate. Blood 34, 301–319 (1969).PubMedGoogle Scholar
  95. Thiersch, J.B.: Therapeutic abortion with folic acid antagonist, 4-amino pteroylglutamic acid, administered by the oral route. Amer. J. Obst. Gynec. 63, 1298 (1962).Google Scholar
  96. Thomas, E.D., Storb, R.: The effect of amethopterin on the immune response. Ann. N.Y. Acad. Sci. 186, 467–474 (1971).PubMedGoogle Scholar
  97. Vanscott, E.S., Auerbach, R., Weinstein, G.D.: Parenteral methotrexate in psoriasis. Arch. Derm. 89, 550–556 (1964).PubMedGoogle Scholar
  98. Vogel, C.L., Adamson, R.H., Devita, V.T., Johns, D.G., Kyalwazi, S.K.: Preliminary clinical trials of dichloromethotrexate (NSC-29630) in hepatocellular carcinoma. Cancer Chemother. Rep. 56, 249–258 (1972).Google Scholar
  99. Vogler, W. R., Huguley, C., Rundles, R.: Comparison of methotrexate with 6-mercaptopuri- neprednisone in treatment of acute leukemia in adults. Cancer 20, 1221–1226 (1967).PubMedGoogle Scholar
  100. Vogler, W.R., Jacobs, J.: Toxic and therapeutic effects of methotrexate-folinic acid (leuco- vorin) in advanced cancer and leukemia. Cancer 28, 894–901 (1971).PubMedGoogle Scholar
  101. Weinstein, G. D.: Biochemical and pathophysiological rationale for amethopterin in psoriasis. Ann. N.Y. Acad. Sci. 186, 452–466 (1971).PubMedGoogle Scholar
  102. Werkheiser, W.C.: Specific binding of 4-amino folic acid analogues by folic acid reductase. J. biol. Chem. 286, 888–893 (1961).Google Scholar
  103. Werkheiser, W. C.: The relation of folic acid reductase to aminopterin toxicity. J. Pharmacol, exp. Therap. 187, 167–172 (1962).Google Scholar
  104. Werkheiser, W.C.: Mathematical simulation in chemotherapy. Ann. N.Y. Acad. Sci. 186, 343–358 (1971).PubMedGoogle Scholar
  105. Wilmanns, W.: Effects of amethopterin treatment on thymidylate synthesis in human leucocytes and bone marrow cells. Ann. N.Y. Acad. Sci. 186, 365–371 (1971).PubMedGoogle Scholar
  106. Wilson, C.B.: Medulloblastoma. Current views regarding the tumor and its treatment. Oncology 24, 273–290 (1970).PubMedGoogle Scholar
  107. Wilson, C. B., Norrell, H.: Brain tumor chemotherapy with intrathecal methotrexate. Cancer 23, 1038–1045 (1969).PubMedGoogle Scholar
  108. Wiltshaw, E.: Methotrexate in treatment of sarcomata. Brit. Med. J. 2, 142–145 (1967).PubMedGoogle Scholar
  109. Wright, J.C., Gumport, S.L., Golomb, F.M.: Remissions produced with the use of methotrexate in patients with mycosis fungoides. Cancer Chemother. Rep. 9, 11–20 (1960).Google Scholar
  110. Wyatt, J., Mcaninch, L.: A chemotherapeutic approach to advanced testicular carcinoma. Canad. J. Surg. 10, 421–426 (1967).PubMedGoogle Scholar
  111. Zaharko, D.S., Bruckner, H., Oliverio, V.T.: Antibiotics alter methotrexate metabolism and excretion. Science 166, 887–888 (1969).PubMedGoogle Scholar
  112. Zaharko, D.S., Oliverio, V.T.: Reinvestigation of methotrexate metabolism in rodents. Bio- chem. Pharmacol. 19, 2923–2925 (1970).Google Scholar

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  • Joseph R. Bertino

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