Specificity and Use of Antisera Produced Against Anticancer Drugs

  • Kunio Fujiwara
  • Tsunehiro Kitagawa
Part of the Advances in Immunity and Cancer Therapy book series (IMMUNITY, volume 2)


Anticancer drugs may possess a narrow therapeutic range that approaches the levels at which serious side effects may occur, and in general they may be used only in limited doses for the treatment of various cancers. The pharmacokinetics (absorption, distribution, metabolism, and excretion) and toxicity studies of the drugs thus necessitate inevitably highly sensitive and specific quantitative assay (1). The importance of drug monitoring has become increasingly evident for achieving optimum therapeutic effectiveness and minimizing side effects because the response to therapy is often better correlated with the concentration of the drug in the fluid than with prescribed dosage (2), and the pharmacokinetics of the drug varies, depending largely upon the individual circumstances and the clinical state of the patients. The use of the radioimmunoassay (RIA) procedure, based on the antigen-antibody reaction, revolutionized the biomedical sciences with its high sensitivity, specificity, accuracy, and rapidity (3–5). Since RIAs for methotrexate and adriamycin were developed in 1974, many reports have described the use of the immunoassay for other anticancer drugs by employing the respective antidrug antibody. Most of these reports were concerned exclusively with the RIA (6–8); however, more recently, they have focused on enzyme immunoassay (EIA)(9–11). Many other methods for assaying cancer chemotherapeutic agents exist: These include classical microbiological (12,13) and conventional chemical assays; these are not ideal, but each has its strong points.


Human Serum Albumin Anticancer Drug Anthracycline Antibiotic Enzyme Label Marks Versus 
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  1. 1.
    Marks V, Lindup WE, Balis EM: Measurement of therapeutic agents in blood. Adv Clin Chem 16: 47–109, 1973.PubMedCrossRefGoogle Scholar
  2. 2.
    Vesell ES, Passonanti QT: Utility of clinical chemical determinations of drug concentrations in biologic fluids. Clin Chem 17: 851–866, 1971.Google Scholar
  3. 3.
    Berson SA, Yalow RS: Quantitative aspects of the reaction between insulin and insulin-binding antibody. J Clin Invest 38: 1966–2016, 1959.Google Scholar
  4. 4.
    Smith TW, Butler VP, Haber E: Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay. N Engl J Med 281: 1212–1216, 1969.PubMedCrossRefGoogle Scholar
  5. 5.
    Yalow RS, Berson SA: Assay of plasma insulin in human subjects by immunological methods. Nature 184: 1648–1649, 1959.PubMedCrossRefGoogle Scholar
  6. 6.
    Bohuon C, Duprey F, Boudene C: Radioimmunoassay of methotrexate in biological fluids. Clin Chim Acta 57: 263–267, 1974.PubMedCrossRefGoogle Scholar
  7. 7.
    Levine L, Powers E: Radioimmunoassay for methotrexate. Res Commun Chem Pathol Pharmacol 9: 543–554, 1974.PubMedGoogle Scholar
  8. 8.
    Van Vunakis H, Langone A, Riceberg LJ, Levine L: Radioimmunoassay for adriamycin and daunomycin. Cancer Res 34: 2546–2552, 1974.PubMedGoogle Scholar
  9. 9.
    Fujiwara K, Yasuno M, Kitagawa T: Enzyme immunoassay for pepleomycin, a new bleomycin analog. Cancer Res 41: 4121–4126, 1981.PubMedGoogle Scholar
  10. 10.
    Fujiwara K, Yasuno M, Kitagawa T: Novel preparation method of immunogen for hydrophobic hapten, enzyme immunoassay for daunomycin and adriamycin. J Immunol Methods 45: 195–203, 1981.PubMedCrossRefGoogle Scholar
  11. 11.
    Marks V, O’Sullivan MJ, Al-Bassam MN, Bridges JW: A double antibody enzyme-immunoassay for methotrexate. In Pal SB (ed): Enzyme Labelled Immunoassay of Hormones and Drugs, pp 419–428. Berlin; New York: Walter de Gruyter, 1978.Google Scholar
  12. 12.
    Abraham EP, Gardner AD, Chain E, Heatley NG, Fletcher CM, Jennings MA, Florey HW: Further observations on penicillin. Lancet 2: 177–188, 1941.CrossRefGoogle Scholar
  13. 13.
    Fleming G: On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br J Erp Pathol 10: 226–236, 1929.Google Scholar
  14. 14.
    Landsteiner K: The specificity of serological reactions. Revised ed. Cambridge, MA: Harvard University Press, 1945. Reprint. New York: Dover Publication, 1962.Google Scholar
  15. 15.
    Beiser SM, Butler VP Jr, Erlanger BF: Hapten-protein conjugates: Methodology and application. In Miescher PA, Muller-Eberhard HJ (eds): Textbook of Immunopathology, 2nd ed., pp 15–29. New. York: Grune & Stratton, 1976.Google Scholar
  16. 16.
    Aherne GW, Piall EM, Marks V: Development and application of a radioimmunoassay for methotrexate. Br J Cancer 36: 608–617, 1977.PubMedCrossRefGoogle Scholar
  17. 17.
    Broughton A: Radioimmunoassay of bleomycin. Methods Enzymol 84: 463–470, 1982.PubMedCrossRefGoogle Scholar
  18. 18.
    Broughton A, Strong JE: Radioimmunoassay of bleomycin. Cancer Res 36: 1418–1421, 1976.PubMedGoogle Scholar
  19. 19.
    Rahmani R, Barbet J, Cano JP: A 125I-radiolabelled probe for vinbastine and vindesine radioimmunoassays: Applications to measurements of vindesine plasma levels in man after intravenous injections and long-term infusions. Clin Chim Acta 129: 57–69, 1983.PubMedCrossRefGoogle Scholar
  20. 20.
    Fujiwara K, Nakamura H, Kitagawa T, Nakamura N, Saito A, Hara K: Development and application of a sensitive enzyme immunoassay for 7-N-(p-hydroxyphenyl) mitomycin C. Cancer Res 44: 4172–4176, 1984.PubMedGoogle Scholar
  21. 21.
    Sohda M, Fujiwara K, Saikusa H, Kitagawa T, Nakamura N, Hara K, Tone H: Sensitive enzyme immunoassay for the quantification of aclacinomycin A using ß-Dgalactosidase as a label. Cancer Chemother Pharmacol 14: 53–58, 1985.PubMedCrossRefGoogle Scholar
  22. 22.
    Likhite V, Sehon A: Protein-protein conjugation. In Williams CA, Chase MW (eds): Methods in Immunology and Immunochemistry, vol 1, pp 150–167. New York: Academic Press, 1967.Google Scholar
  23. 23.
    Schick AF, Singer SJ: On the formation of covalent linkages between two protein molecules. J Biol Chem 236: 2477–2485, 1961.PubMedGoogle Scholar
  24. 24.
    Erlanger BF: Principles and methods for the preparation of drug-protein conjugates for immunological studies. Pharmacol Rev 25: 271–280, 1973.PubMedGoogle Scholar
  25. 25.
    Kennedy JH, Kricka LH, Wilding P: Protein-protein coupling and the applications of protein conjugates. Clin Chim Acta 70: 1–31, 1976.PubMedCrossRefGoogle Scholar
  26. 26.
    Matsushita H, Noguchi M, Tamaki E: Conjugate of bovine serum albumin with nicotine. Biochem Biophys Res Commun 57: 1006–1010, 1974.PubMedCrossRefGoogle Scholar
  27. 27.
    Fujiwara K, Asada H, Kitagawa T, Yamamoto K, Ito T, Tsuchiya R, Sohda M, Nakamura N, Hara K, Tomonaga Y, Ichimaru M, Takahashi S: Preparation of polyamine antibody and its use in enzyme immunoassay of spermine and spermidine with 13-D-galactosidase as a label. J Immunol Methods 61: 217–226, 1983.PubMedCrossRefGoogle Scholar
  28. 28.
    Fujiwara K, Isobe M, Saikusa H, Nakamura H, Kitagawa T, Takahashi S: Sensitive enzyme immunoassay for the quantification of bleomycin using β-D-galactosidase as a label. Cancer Treat Rep 67: 363–369, 1983.PubMedGoogle Scholar
  29. 29.
    Fujiwara K, Ogawa A, Asada H, Saikusa H, Nakamura H, Ono S, Kitagawa T: The preparation of puromycin antibody and its use in enzymeimmunoassay for the quantification using β-D-galactosidase as a label. J Biochem (Tokyo) 92: 1599–1605, 1982.Google Scholar
  30. 30.
    Fujiwara K, Ono S, Fujinaka H, Kitagawa T: Heterologous enzyme immunoassay for puromycin aminonucleoside using β-D-galactosidase as a label. J Immunol Methods 72: 109–118, 1984.PubMedCrossRefGoogle Scholar
  31. 31.
    Parker CW: Radioimmunoassay of Biologically Active Compounds. Englewood Cliffs, NJ: Prentice-Hall, 1976.Google Scholar
  32. 32.
    Vaitukaitis J, Robbins JB, Nieschlag E, Rose GT: A method for producing specific antisera with small doses of immunogen. J Clin Endocr Metab 33: 988–991, 1971PubMedCrossRefGoogle Scholar
  33. 33.
    Hurn BA, Landon J: Antisera for radioimmunoassay. In Kirkham KE, Hunter WM (eds): Radioimmunoassay Methods, pp 121–142. Edinburgh: Churchill Livingstone, 1971.Google Scholar
  34. 34.
    Court G: The production of antibodies for radioimmunoassay. Pathol Biol 23: 859–862, 1975.PubMedGoogle Scholar
  35. 35.
    Castro A, Malkus H: Radioimmunoassay of drugs of abuse in humans: A review. Res Commun Chem Pathol Pharmacol 16: 291–309, 1977.PubMedGoogle Scholar
  36. 36.
    Landon J, Moffat AC: The radioimmunoassay of drugs. Analyst 101: 225–243, 1976.PubMedCrossRefGoogle Scholar
  37. 37.
    Peskar BA, Peskar BM: Advances in hapten immunoassays. Eur J Drug Metab Pharmacol 4: 163–170, 1977.CrossRefGoogle Scholar
  38. 38.
    Cameron EHD, Scarisbrick JJ, Morris SE, Hillier SG, Read G: Some aspects of the use of 123I-labelled ligands for steroid radioimmunoassay. J Steroid Biochem 5: 749–756, 1974.CrossRefGoogle Scholar
  39. 39.
    Goodfriend TL, Ball DL: Radioimmunoassay of bradykinin: Chemical modification to enable use of radioactive iodine. J Lab Clin Med 73: 501–511, 1969.PubMedGoogle Scholar
  40. 40.
    Langone JJ, Franke J, Van Vunakis H: Nicotine and its metabolites: Radioimmunoassay for y-(3-pyridyl)-7-oxo-N-methylbutyramide. Arch Biochem Biophys 164: 536–543, 1974.PubMedCrossRefGoogle Scholar
  41. 41.
    Langone JJ, Gjika HB, Van Vunakis H: Nicotine and its metabolites: Radioimmunoassays for nicotine and cotinine. Biochemistry 12: 5025–5030, 1973.PubMedCrossRefGoogle Scholar
  42. 42.
    Oliver GC Jr, Parker BM, Brasfield DL, Parker CW: The measurement of digitoxin in human serum by radioimmunoassay. J Clin Invest 47: 1035–1042, 1968.PubMedCrossRefGoogle Scholar
  43. 43.
    Greenwood FC: Radioiodination of peptide hormones: Procedures and problems. In Odell WD, Daughaday WH (eds): Principles of Competitive Protein-Binding Assays, pp 288–302. Philadelphia, PA: JB Lippincott Company, 1971.Google Scholar
  44. 44.
    Hunter WM: The preparation and assessment of iodinated antigens. In Kirkham KE, Hunter WM (eds): Radioimmunoassay Methods, pp 3–23. Baltimore: Williams & Wilkins Company, 1971.Google Scholar
  45. 45.
    David GS, Reisfeld RA: Protein iodination with solid state lactoperoxidase. Biochemistry 13: 1014–1021, 1974.PubMedCrossRefGoogle Scholar
  46. 46.
    Marchalonis JJ: An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem J 113: 299–305, 1969.PubMedGoogle Scholar
  47. 47.
    Bolton AE, Hunter WM: The labeling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J 133: 529–539, 1973.PubMedGoogle Scholar
  48. 48.
    Rudinger J, Ruegg U: Preparation of N-succinimidyl-3-(4-hydroxyphenyl)propionate. Biochem J 133: 538–539, 1973.PubMedGoogle Scholar
  49. 49.
    Makela O: Assay of anti-hapten antibody with the aid of hapten-coupled bacteriophage. Immunology 10: 81–86, 1966.PubMedGoogle Scholar
  50. 50.
    Hales CN, Randle PJ: Immunoassay of insulin with insulin-antibody precipitate. Biochem J 88: 137–146, 1963.PubMedGoogle Scholar
  51. 51.
    Adler FL: Drug testing by hemagglutination-inhibition. In Mule S, Sunshine I, Braude M, Willette RE (eds): Immunoassays for Drugs Subject to Abuse, pp 37–43. Cleveland, OH: CRC Press Inc, 1974.Google Scholar
  52. 52.
    Leute RK, Ullman EF, Goldstein A, Herzenberg LA: Spin immunoassay technique for determination of morphine. Nature 236: 93–94, 1972.Google Scholar
  53. 53.
    Schuurs AHWM, Van Weeman BK: Enzyme-immunoassay. Clin Chim Acta 81: 1–40, 1977.PubMedCrossRefGoogle Scholar
  54. 54.
    Wannlund J, Azari J, Levine L, Deluca M: A bioluminescent immunoassay for methotrexate at the subpicomole level. Biochem Biophys Res Commun 96: 440–446, 1980.PubMedCrossRefGoogle Scholar
  55. 55.
    Ullman EF, Schwarzberg M, Rubenstein KE: Fluorescent transfer immunoassay. A general method for the determination of antigens. J Biol Chem 251: 4172–4178, 1976.PubMedGoogle Scholar
  56. 56.
    Engvall E, Perlmann P: Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry 8: 871–874, 1971.PubMedCrossRefGoogle Scholar
  57. 57.
    O’Sullivan MJ, Bridges JW, Marks V: Enzyme immunoassay: A review. Ann Clin Biochem 16: 221–240, 1979.PubMedGoogle Scholar
  58. 58.
    Wisdom GB: Enzyme-immunoassay. Clin Chem 22: 1243–1255, 1976.PubMedGoogle Scholar
  59. 59.
    Joyce BG, Turkes A, Ozoran A, Read GF, Fahmy DR: The development of a sensitive EIA for steroid hormones. In Pal SB (ed): Enzyme-Linked Immunoassay of Hormones and Drugs, pp 247–256. Berlin; New York: Walter de Gruyter, 1978.Google Scholar
  60. 60.
    Numazawa M, Haryu A, Kurosaka K, Nambara T: Picogram order enzyme immunoassay of oestradiol. FEBS Lett 79: 396–398, 1977.PubMedCrossRefGoogle Scholar
  61. 61.
    Van Weemen BK, Schuurs AHWM: Immunoassay using hapten-enzyme conjugates. FEBS Lett 24: 77–82, 1972.PubMedCrossRefGoogle Scholar
  62. 62.
    Ogihara T, Miyai K, Nishi K, Ishibashi K, Kumahara Y: Enzyme-labelled immunoassay for plasma cortisol. J Clin Endocrinol Metab 44: 91–95, 1977.PubMedCrossRefGoogle Scholar
  63. 63.
    Tateishi K, Yamamoto H, Ogihara T, Hayashi C, Kitagawa M: Enzyme immunoassay of testosterone using the testosterone-glucoamylase complex. J Biochem (Tokyo) 80: 191–194, 1975.Google Scholar
  64. 64.
    Erlanger BF, Borek G, Beiser SM, Lieberman S: Steroid-protein conjugates. II. Preparation and characterisation of conjugates of bovine serum albumin with progesterone, deoxycorticosterone and oestrone. J Biol Chem 234: 1090–1094, 1959.PubMedGoogle Scholar
  65. 65.
    Grant JD, Gross SJ, Lomax P, Wong R: Antibody detection of marihuana. Nature 236: 216–217, 1972.Google Scholar
  66. 66.
    Avrameas S: Coupling of enzyme to proteins with glutaraldehyde. Immunochemistry 6: 43–52, 1969.PubMedCrossRefGoogle Scholar
  67. 67.
    Boorsma DM, Kalsbeek GL: A comparative study of horseradish peroxidase conjugates prepared with a one-step and a two-step method. J Histochem Cytochem 23: 200–207, 1975.PubMedCrossRefGoogle Scholar
  68. 68.
    Clyne DH, Norris SH, Modesto RR, Pesce AJ, Pollack VE: Antibody-enzyme conjugates. The preparation of intermolecular conjugates of horseradish peroxidase and antibody and their use in immunohistochemistry of renal cortex. J Histochem Cytochem 21: 233–240, 1973.PubMedCrossRefGoogle Scholar
  69. 69.
    Ford DJ, Radin R, Pesce AJ: Characterization of gluytaraldehyde coupled alkaline phosphatase-antibody conjugates and lactoperoxidase-antibody conjugates. Immunochemistry 15: 237–243, 1978.PubMedCrossRefGoogle Scholar
  70. 70.
    Nakane PK, Sir Ram J, Pierce GB: Enzyme-labelled antibodies for light and electron microscope localization of antigens. J Histochem Cytochem 14: 789–791, 1966.CrossRefGoogle Scholar
  71. 71.
    Van Weemen BK, Schuurs AHWM: Immunoassay using antibody-enzyme conjugates. FEBS Lett 43: 215–218, 1974.PubMedCrossRefGoogle Scholar
  72. 72.
    Nakane PK, Kawaoi A: Peroxidase-labelled antibody. A new method of conjugation. J Histochem Cytochem 22: 1084–1091, 1974.PubMedCrossRefGoogle Scholar
  73. 73.
    Kato K, Hamaguchi Y, Fukui H, Ishikawa E: Enzyme-linked immunoassay. 1. Novel method for the synthesis of the insulin-ß-galactosidase conjugate and its applicability for insulin assay. J Biochem (Tokyo) 78: 235–237, 1975.Google Scholar
  74. 74.
    Kato K, Hamaguchi Y, Fukui H, Ishikawa E: Enzyme-linked immunoassay. Conjugation of rabbit anti-(human)immunoglobulin G assay. Eur J Biochem 62: 285–292, 1976.PubMedCrossRefGoogle Scholar
  75. 75.
    Kato K, Hamaguchi Y, Fukui H, Ishikawa E: Coupling Fab’ fragment of rabbit antihuman IgG antibody to β-D-galactosidase and a highly sensitive immunoassay of human IgG. FEBS Lett 56: 370–372, 1975.PubMedCrossRefGoogle Scholar
  76. 76.
    Kitagawa T, Aikawa T: Enzyme coupled immunoassay of insulin using a novel coupling reagent. J Biochem (Tokyo) 79: 233–236, 1976.Google Scholar
  77. 77.
    Fujiwara K, Saikusa H, Kitagawa T, Takahashi S, Konishi Y: Specificity of antisera produced against mitomycin C. Cancer Treat Rep 67: 1079–1084, 1983.PubMedGoogle Scholar
  78. 78.
    Fujiwara K, Saikusa H, Yasuno M, Kitagawa T: Enzyme immunoassay for the quantification of mitomycin C using β-galactosidase as a label. Cancer Res 42: 1487–1491, 1982.PubMedGoogle Scholar
  79. 79.
    Taut RR, Bollen A, Sun TT, Hershey JWB, Sunberg J, Pierce LR: Methyl 4-mercaptobutyrimidate as a cleavable cross-linking reagent and its application to the E. coli 30S ribosome. Biochemistry 12: 3266–3273, 1973.CrossRefGoogle Scholar
  80. 80.
    Ishikawa E, Yamada Y, Hamaguchi Y, Yoshitake S, Shiomi K, Ota T, Yamamoto Y, Tanaka K: Enzyme-labelling with maleimides and its application to the immunoassay of peptide hormones. In Pal SB (ed): Enzyme-Linked Immunoassay of Hormones and Drugs, pp 43–57. Berlin; New York: Walter de Gruyter, 1978.Google Scholar
  81. 81.
    Butler VP Jr: The immunological assays of drugs. Pharmacol Rev 29: 103–184, 1978.Google Scholar
  82. 82.
    Butler VP Jr: Assays of digitalis in the blood. Prog Cardiovasc Dis 14: 571–600, 1972.PubMedCrossRefGoogle Scholar
  83. 83.
    Bauminger S, Kohen F, Lindner HR: Steroids as haptens: Optimal design of antigens for the formation of antibodies to steroid hormones. J Steroid Biochem 5: 739–747, 1974.CrossRefGoogle Scholar
  84. 84.
    Bosch AMG, den Hollander FC, Woods GF: Specificities of antisera against testosterone linked to albumin at different positions (C3, C11, C17). Steroids 23: 699–711, 1974.PubMedGoogle Scholar
  85. 85.
    Butler VP Jr, Beiser SM: Antibodies to small molecules: Biological and clinical applications. Adv Immunol 17: 255–310, 1973.PubMedCrossRefGoogle Scholar
  86. 86.
    Scatchard G: The attractions of proteins for small molecules and ions. Ann NYAcad Sci 51: 660–672, 1949.CrossRefGoogle Scholar
  87. 87.
    Odell WD, Abraham G, Raud HR, Swerdloff RS, Fisher DA: Influence of immunization procedures on the titer, affinity, and specificity of antisera to glycopeptides. Acta Endocrinol [Suppl] (Copenhagen) 142: 54–76, 1969.Google Scholar
  88. 88.
    Thorell JI, Larson SM: Assay performance. In Radioimmunoassay and Related Techniques: Methodology and Clinical Applications, pp 59–74. Saint Louis, MO: Mosby, 1978.Google Scholar
  89. 89.
    Herbert V: Coated charcoal separation of free labelled hormone from hormone bound to antibody. Protein and polypeptide hormone. Excerpta Medica Int Cong Ser 161: 55–60, 1968.Google Scholar
  90. 90.
    Herbert V, Lau K-S, Gottlieb CW: Coated charcoal assay of vitamines, minerals, hormones, and their binders. Adv Tracer Methodol 4: 273–290, 1968.PubMedGoogle Scholar
  91. 91.
    Herbert V, Lau K-S, Gottlieb CW, Bleicher SJ: Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab 25: 1375–1384, 1965.PubMedCrossRefGoogle Scholar
  92. 92.
    Hunter WM, Ganguli PC: The separation of antibody bound from free antigen. In Kirkham KE, Hunter WM (eds): Radioimmunoassay Methods, pp 243–257. Baltimore: Williams & Wilkins Company, 1971.Google Scholar
  93. 93.
    Chard T, Martin M, Landon J: The separation of antibody bound from free peptides using ammonium sulphate and ethanol. In Kirkham KE, Hunter WM (eds): Radio-immunoassay Methods, pp 257–266. Baltimore: Williams & Wilkins Company, 1971.Google Scholar
  94. 94.
    Minden P, Fan RS: The ammonium sulphate method to measure antigen-binding capacity. In Weir DM (ed): Handbook of Experimental Immunology, 2nd ed, pp 15.1–15. 21. London: Blackwell Scientific Publications, 1973.Google Scholar
  95. 95.
    Kamel RS, Gardner J: Preparation of 125iodine-labelled methotrexate and its use in a magnetisable particle solid-phase radioimmunoassay. J Clin Chim Acta 89: 363–370, 1978.CrossRefGoogle Scholar
  96. 96.
    Kamel RS, Landon J: Preparation of 125iodine-labelled methotrexate and its use in magnetizable particle solid-phase radioimmunoassay. J Methods Enzymol 84: 422–447, 1982.CrossRefGoogle Scholar
  97. 97.
    Matsuoka K, Maeda M, Tsuji A: Fluorophotometric enzyme immunoassay of neocarzinostatin using peroxidase as a label. Chem Pharm Bull 28: 1864–1868, 1980.PubMedGoogle Scholar
  98. 98.
    Al-Bassam MN, O’Sullivan MJ, Gnemmi E, Bridges JW, Marks V: Nortriptyline enzyme-immunoassay. In Pal SB (ed): Enzyme-Labelled Immunoassay of Hormones and Drugs, pp 375–386. Berlin; New York: Walter de Gruyter, 1978.Google Scholar
  99. 99.
    Rubenstein KE, Schneider RS, Ullman EF: ‘Homogeneous’ enzyme immunoassay. A new immunological technique. Biochem Biophys Res Commun 47: 846–851, 1972.PubMedCrossRefGoogle Scholar
  100. 100.
    Sugawara R, Hata T: Mitomycin, a new antibiotic from Streptomyces. H. Description of the strain. JAntibiot (Tokyo) 9: 149–151, 1956.Google Scholar
  101. 101.
    Sugiura K: Antitumor activity of mitomycin C. Cancer Chemother Rep 13: 51–65, 1961.Google Scholar
  102. 102.
    Frank W, Osterberg AE: Mitomycin C(NRC-26980): An evaluation of Japanese reports. Cancer Chemother Rep 9: 114–119, 1960.PubMedGoogle Scholar
  103. 103.
    Godfrey TE, Wilbur DW: Clinical experience with mitomycin C in large infrequent dose. Cancer 29: 1647–1652, 1972.PubMedCrossRefGoogle Scholar
  104. 104.
    Fujita H: Comparative studies on the blood level, tissue distribution, excretion and activation of anticancer drugs. Jpn J Clin Oncol 12: 151–162, 1971.Google Scholar
  105. 105.
    Imai R, Ashizawa T, Urakawa C, Morimoto M, Nakamura N: Antitumor activity of 7-N-phenyl derivatives of mitomycin C in the leukemia P 338 system. Gann 71: 560–562, 1980.PubMedGoogle Scholar
  106. 106.
    Imai R, Morimoto M, Marumo H, Kobayashi T, Tsuruo T, Inaba M, Tsukagoshi S, Sakurai Y: Antitumor activity of 7-N-(p-hydroxyphenyl)mitomycin C in experimental tumor systems. Gann 72: 744–749, 1981.Google Scholar
  107. 107.
    Umezawa H, Maeda K, Takeuchi T: New antibiotics, bleomycin A and B. J Antibiot (Tokyo) 19: 200–209, 1966.Google Scholar
  108. 108.
    Blum RH, Carter SK, Agre KA: A clinical review of bleomycin: A new antineoplastic agent. Cancer 31: 903–914, 1973.PubMedCrossRefGoogle Scholar
  109. 109.
    Crooke ST, Bradner WT: Bleomycin-a review. J Med 7: 373–428, 1976.Google Scholar
  110. 110.
    Comis RL: Bleomycin pulmonary toxicity, an overview. In Carter SK, Umezawa H, Crooke ST (eds): Bleomycin-Current Status and New Developments, pp 279–291. New York: Academic Press, 1978.Google Scholar
  111. 111.
    Umezawa H: Studies on bleomycin: Chemistry and biological action. Biol Med 18: 459–467, 1973.Google Scholar
  112. 112.
    Fujita H, Kimura K: Blood levels, tissue distribution, excretion and inactivation of bleomycin. In Progress in Antimicobial and Anticancer Chemotherapy. Proceedings of the 6th International Congress of Chemotherapy, vol 2, pp 309–314. Baltimore: University Park Press, 1970.Google Scholar
  113. 113.
    Ohnuma T, Holland JF, Matsuda H, Waligunda JA, Goldberg GA: Microbiological assay of bleomycin: Inactivation, tissue distribution, and clearance. Cancer 33: 1230–1238, 1974.CrossRefGoogle Scholar
  114. 114.
    Broughton A, Strong JE: Radioimmunoassay of antibiotics and chemotherapeutic agents. Clin Chem 22: 726–732, 1976.PubMedGoogle Scholar
  115. 115.
    Elson MK, Oken MM, Shafer RB: A radioimmunoassay for bleomycin. J Nucl Med 18: 296–300, 1977.PubMedGoogle Scholar
  116. 116.
    Teale JD, Clough JM, Marks V: Radioimmunoassay of bleomycin in plasma and urine. Br J Cancer 35: 822–827, 1977.PubMedCrossRefGoogle Scholar
  117. 117.
    Goodfriend TL, Levin L, Fasman GD: Antibodies to bradykinin and angiotensin: A use of carbomiimides in immunology. Science 144: 1344–1346, 1964.PubMedCrossRefGoogle Scholar
  118. 118.
    Crooke ST, Luft F, Broughton A, Strong JE, Casson K, Einhorn L: Bleomycin serum pharmacokinetics as determined by a radioimmunoassay and a microbiologie assay in a patient with compromised renal function. Cancer 39: 1430–1434, 1977.PubMedCrossRefGoogle Scholar
  119. 119.
    Elson MK, Oken MM, Shafer RB, Broughton A, Strong J, Braun Cl’, Crooke ST: Comparison of two radioimmunoassays and a microbiologic assay for bleomycin. Med Pediatr Oncol 5: 213–218, 1978.PubMedCrossRefGoogle Scholar
  120. 120.
    Strong JE, Broughton A, Crooke ST: Specificity of antisera produced against bleomycin. Cancer Treat Rep 61: 1509–1512, 1977.PubMedGoogle Scholar
  121. 121.
    Umezawa H: Chemistry and mechanism of action of bleomycin. Fed Proc 33: 2296–2302, 1974.PubMedGoogle Scholar
  122. 122.
    Carter SK, Blum RH: The current status of bleomycin and adriamycin. Med J 24: 322, 1974.Google Scholar
  123. 123.
    Crooke ST, Comis RL, Einhorn LH, Strong JE, Broughton A, Prestayko AW: Effects of variations in renal functions on the clinical pharmacology of bleomycin administered as an iv bolus. Cancer Treat Rep 61: 1631, 1977.PubMedGoogle Scholar
  124. 124.
    Crooke ST, Comis RI, Einhorn LH, Strong JE, Broughton A, Prestayko AW: Studies on the clinical pharmacology of bleomycin. Recent Results Cancer Res 63: 219–229, 1978.PubMedGoogle Scholar
  125. 125.
    Alberts DS, Chen HSG, Liu R, Himmelstein KJ, Mayersohn M, Perrier D, Gross J, Moon T, Broughton A, Salmon SE: Bleomycin pharmacokinetics in man. 1. Intravenous administration. Cancer Chemother Pharmacol 1: 177–181, 1978.PubMedCrossRefGoogle Scholar
  126. 126.
    Broughton A, Strong JE, Holoye PY, Berdossian CWM: Clinical pharmacology of bleomycin following intravenous infusion as determined by radioimmunoassay. Cancer 40: 2772–2778, 1977.PubMedCrossRefGoogle Scholar
  127. 127.
    Ginsberg SJ, Crooke ST, Bloomfield CD, Peterson B, Kennedy BJ, Blom J, Ellison RR, Pajak TF, Gottlieb AJ: Cyclophosphamide, doxorubicin, vincristine, and low-dose continuous infusion bleomycin in non-Hodgkin’s lymphoma. Cancer 49: 1346–1352, 1982.PubMedCrossRefGoogle Scholar
  128. 128.
    Kramer WG, Feldman S, Broughton A, Strong JE, Hall SW, Holoye PY: The pharmacokinetics of bleomycin in man. J Clin Pharmacol 18: 346–352, 1978.PubMedGoogle Scholar
  129. 129.
    Sikic BI, Collins JM, Mimnaugh EA, Gram TE: Improved therapeutic index of bleomycin when administered by continuous infusion in mice. Cancer Treat Rep 62: 2011–2017, 1978.PubMedGoogle Scholar
  130. 130.
    Hall SW, Strong JE, Broughton A, Frazier ML, Benjamin RS: Bleomycin clinical pharmacology by radioimmunoassay. Cancer Chemother Pharmacol 9: 22–25, 1982.PubMedCrossRefGoogle Scholar
  131. 131.
    Tom W-M, Montgomery MR: Disposition of the pulmonary toxin, bleomycin. Drug Metab Dispos 7: 90–93, 1978.Google Scholar
  132. 132.
    Matsuda A, Yoshioka O, Ebihara K, Ekimoto H, Yamashita T, Umezawa H: The search for new bleomycins. In Carter SK, Crooke ST, Umezawa H (eds): Bleomycin: Current Status and New Developments, pp 299–310. New York: Academic Press, Inc, 1978.Google Scholar
  133. 133.
    Sikic BJ, Siddik ZH, Gram TE: Relative pulmonary toxicity and antitumor effects of 2 new bleomycin analogs, pepleomycin and tallysomycin A. Cancer Treat Rep 64: 659–668, 1980.PubMedGoogle Scholar
  134. 134.
    Takahashi K, Ekimoto H, Aoyagi S, Koyu A, Kuramochi H, Yoshioka O, Matsuda A, Fujii A, Umezawa H: Biological studies on the degradation products of 3-[(S)-1’-phenylethylamino]propylaminobleomycin: A novel analog (pepleomycin). J Antibiot (Tokyo) 32: 36–42, 1979.Google Scholar
  135. 135.
    Tanaka W: Development of new bleomycins with potential clinical utility. J Antibiot (Tokyo) 30 (Suppl):S-41–48, 1977.Google Scholar
  136. 136.
    Aherne GW, Saesow N, James S, Marks V: Development and application of a radio-immunoassay for pepleomycin. Cancer Treat Rep 66: 1365–1370, 1982.PubMedGoogle Scholar
  137. 137.
    Kawaguchi H, Tsukiura H, Tornita K, Konishi M, Saito K, Kobaru S, Numata K, Fujisawa K, Miyaki T, Hatori M: Tallysomycin, a new antitumor antibiotic complex related to bleomycin. 1. Production, isolation and properties. J Antibiot (Tokyo) 30: 779–788, 1977.Google Scholar
  138. 138.
    Konishi M, Saito K, Numata K, Tsuno T, Mama K, Tsukiura H, Naito T, Kawaguchi H: Tallysomycin, a new antitumor antibiotic complex related to bleomycin. II. Structure determination of tallysomycin A and B. J Antibiot (Tokyo) 30: 779–788, 1977.Google Scholar
  139. 139.
    Broughton A, Strong JE, Crooke ST, Prestayko AW, Kight J: A radioimmunoassay for tallysomycin. Cancer Treat Rep 63: 1829–1832, 1979.PubMedGoogle Scholar
  140. 140.
    Van Harken DR, Smyth RD, Lee FH, Strong JE, Hottendorf GH: Preliminary studies of the pharmacokinetics of tallysomycin in the rhesus monkey. Res Commun Chem Pathol Pharmacol 31: 403–416, 1981.PubMedGoogle Scholar
  141. 141.
    Bachur NR: Interdisciplinary session report. Current status of studies with adriamycin (NSC-123127). Cancer Chemother Rep 4: 47–50, 1973.Google Scholar
  142. 142.
    Carter SK, Di Marco A, Ghione M, Krakoff IH, Mathe G (eds): International Symposium on Adriamycin, Milan, September 9–10, 1971. Berlin: Springer-Verlag, 1972.Google Scholar
  143. 143.
    Zbinden G, Bachmann E, Holderegger C: Model systems for cardiac effects of anthracyclines. Antibiot Chemother 23: 255–270, 1978.PubMedGoogle Scholar
  144. 144.
    Bachur NR, Moore AL, Bernstein JG, Liu A: Tissue distribution and disposition of daunomycin (NSC-82151) in mice: Fluorometric and isotopic methods. Cancer Chemother Rep 54: 89–94, 1970.PubMedGoogle Scholar
  145. 145.
    Benjamin RS, Riggs CE, Bachur NR: The pharmacokinetics and metabolism of adriamycin in man. Clin Pharmacol Ther 14: 592–600, 1973.PubMedGoogle Scholar
  146. 146.
    Langone JJ, Van Vunakis H: Adriamycin and metabolites: Separation by high-pressure liquid chromatography and quantitation by radioimmunoassay. Biochem Med 12: 283–289, 1975.PubMedCrossRefGoogle Scholar
  147. 147.
    Bachur NR, Riggs CE, Green MR, Langone JJ, Van Vunakis H, Levine L: Plasma adriamycin and daunorubicin levels by fluorescence and radioimmunoassay. Clin Pharmacol 7her 21: 70–77, 1977.Google Scholar
  148. 148.
    Boston RC, Phillips DR: Evidence of possible dose-dependent doxorubicin plasma kinetics in man. Cancer Treat Rep 67: 63–69, 1983.PubMedGoogle Scholar
  149. 149.
    Ishida N, Miyazaki K, Kumagai K, Rikimaru M: Neocarzinostatin, an antitumor antibiotic of high molecular weight: Isolation, purification, physical chemical properties and biologic activities. J Antibiot (Tokyo) [A] 18: 68–76, 1965.Google Scholar
  150. 150.
    Maeda H, Kumagai K, Ishida N: Characterization of neocarzinostatin. J Antibiot (Tokyo) [A] 19: 253–259, 1966.Google Scholar
  151. 151.
    Kappen LS, Napier MA, Goldberg IH: Roles of chromophore and apo-protein in neocarzinostatin action. Proc Natl Acad Sci USA 77: 1970–1971, 1980.PubMedCrossRefGoogle Scholar
  152. 152.
    Bradner WT, Hutchison DJ: Neocarzinostatin (NSC-69985). An antitumor antibiotic effective against ascitic leukemia L 1210 in mice. Cancer Chemother Rep 50: 79–84, 1966.PubMedGoogle Scholar
  153. 153.
    Kumagai K, Miyazaki K. The effect of carzinostatin on mouse ascitic leukemia SN-36. J Antibiot (Tokyo) 16: 55, 1963.Google Scholar
  154. 154.
    Legha SS, Van Hoff DD, Rozencweig M, Abraham D, Slavik M, Muggia FM: Neocarzinostatin (NSC 157365). a new carcinostatic compound. Oncology (Basel) 33: 265–270, 1976.CrossRefGoogle Scholar
  155. 155.
    Anantha TS, Raso V: Radioimmunoassay of neocarzinostatin, an antitumor protein. Cancer Res 36: 4378–4381, 1976.Google Scholar
  156. 156.
    Comis RC, Griffin TW, Raso V, Ginsberg SJ: Pharmacokinetics of the protein antitumor antibiotic neocarzinostatin after bolus injection in humans. Cancer Res 39: 757–761, 1979.PubMedGoogle Scholar
  157. 157.
    Comis RL, Griffin T, Raso V, Ginsberg ST: Neocarzinostatin: Initial clinical and pharmacologic studies in the United States. Recent Results Cancer Res 63: 261–271, 1978.PubMedGoogle Scholar
  158. 158.
    Hall SW, Knight J, Broughton A, Benjamin RS, McKelvey E: Clinical pharmacology of the anticancer polypeptide neocarzinostatin. Cancer Chemother Pharmacol 10: 200–204, 1983.PubMedCrossRefGoogle Scholar
  159. 159.
    Kitagawa T, Tanimori H, Yoshida K: Enzyme immunoassay with high sensitivity and accuracy for specific antibody to neocarzinostatin. J Immunol Methods 72: 297–303, 1984.PubMedCrossRefGoogle Scholar
  160. 160.
    Tanimori H, Kitagawa T, Tsunoda T, Tsuchiya R: Enzyme immunoassay of neocarzinostatin using 0-galactosidase as label. J Pharm Dyn 4: 812–819, 1981.Google Scholar
  161. 161.
    Chimura H, Ishizuka M, Hamada M, Hori S, Kimura K, Iwanaga J, Takeuchi T, Umezawa H: A new antibiotic, macromomycin, exhibiting antitumor activity and antimicrobial activity. J Antibiot (Tokyo) [A] 21: 44–49, 1968.Google Scholar
  162. 162.
    Lippman MM, Laster WR, Abbott BJ, Venditti J, Baratta M: Antitumor activity of macromomycin B (NSC 170105) against murine leukemias, melanoma, and lung carcinoma. Cancer Res 35: 939–945, 1975.PubMedGoogle Scholar
  163. 163.
    Vinkelhake JL, Buckmire FLA: Radioimmune assay and characteristics of antibodies to macromomycin (NSC 170105). Cancer Res 37: 1197–1204, 1977.Google Scholar
  164. 164.
    Farber S, Roch R, Sears EM, Pinkel D: Advances in chemotherapy of cancer in man Adv Cancer Res 4: 1–71, 1956.PubMedCrossRefGoogle Scholar
  165. 165.
    Pratt WB, Ruddon RW: The Anticancer Drugs, pp 323. New York: Oxford University Press, 1979.Google Scholar
  166. 166.
    Raso V: Radioimmunoassays for methotrexate, citrovorum factor, neocarzinostatin, and actinomycin D. Cancer Treat Rep 61: 585–590, 1977.PubMedGoogle Scholar
  167. 167.
    Brothman AR, Davis TP, Duffy JJ, Lindell TJ: Development of an antibody to antinomycin D and its application for the detections of serum levels by radioimmunoassay. Cancer Res 42: 1184–1187, 1982.PubMedGoogle Scholar
  168. 168.
    Meienhofer J, Atherton E: Structure-activity relationships in the actinomycins. In Perlman D (ed): Structure-activity Relationships Among the Semisynthetic Antibiotics, pp 428–529. New York: Academic Press, 1977.Google Scholar
  169. 169.
    Meinhofer J, Maeda K, Claser CB, Kuromizu K: Primary structure of the antitumor protein neocarzinostatin. Science 178: 875–876, 1972.CrossRefGoogle Scholar
  170. 170.
    Taksuoka S, Nakazawa K, Miyake A, Kajiwara K, Aramaki Y, Shibata M, Tanabe K, Hamada Y, Hitomi H, Miyamoto M, Mizuno K, Watanabe J, Ishidate M, Yokotani H, Ishikawa I: Isolation anticancer activity and pharmacology of a new antibiotic chromomycin. Gann 49 (Suppl): 23–24, 1958.Google Scholar
  171. 171.
    Gause GF: Olivomycin, mithramycin, chromomycin: Three related cancerostatic antibiotics. Adv Chemother 2: 179–195, 1965.PubMedGoogle Scholar
  172. 172.
    Slavik M, Carter SK: Chromomycin A3, mithramycin and olivomycin antitumor antibiotics of related structure. Adv Pharmacol Chemother 12: 1, 1974.CrossRefGoogle Scholar
  173. 173.
    Falkson G, Sandison AG, Falkson HC, Fichardt T: Chromomycin A3 (toyomycin) and radiotherapy in the treatment of advanced malignancy. S Afr J Radiol 4: 38–39, 1966.Google Scholar
  174. 174.
    Oki T, Matsuzawa Y, Yoshimoto A, Numata K, Kitamura I, Hori S, Takamatsu A, Umezawa H, Ishizuka M, Naganawa H, Suda H, Hamada M, Takeuchi T: New antitumor antibiotics, aclacinomycins A and B. J Antibiot (Tokyo) 28: 830–834, 1975.Google Scholar
  175. 175.
    Hori S, Shirai M, Hirano S, Oki T, Inui T, Tsukagoshi S, Ishizuka M, Takeuchi T, Umezawa H: Antitumor activity of new anthracycline antibiotics, aclacinomycin A and its analogs, and their toxicity. Gann 68: 685–690, 1977.PubMedGoogle Scholar
  176. 176.
    Oki T, Takeuchi T, Oka S, Umezawa H: New anthracycline antibiotic aclacinomycin A: Experimental studies and correlations with clinical trials. Recent Results Cancer Res 76: 21–40, 1981.PubMedGoogle Scholar
  177. 177.
    Furue H, Komita T, Nakao I, Furukawa I, Kanko T, Yokoyama T: Clinical experiences with aclacinomycin A. Recent Results Cancer Res 63: 241–246, 1978.PubMedGoogle Scholar
  178. 178.
    Matsuzawa Y, Kiyosaki T, Oki T, Takeuchi T, Umezawa H: Radioimmunoassay for aclacinomycin A. Gann 73: 229–233, 1982.PubMedGoogle Scholar
  179. 179.
    Matsuzawa Y, Kiyosaki T, Yoshimoto A, Ishikura T, Takeuchi T, Umezawa H: Immunological cross-reactivities of various anthracycline antibiotics against aclacinomycin A antisera. J Pharm Dyn 5: 886–892, 1982.Google Scholar
  180. 180.
    Tanaka H, Yoshioka T, Shimauchi Y, Matsuzawa Y, Oki T, Inui T: Chemical modification of anthracycline antibiotics. 1. Demethoxycarbonylation, 10-epimerization and 4-O-methylation of aclacinomycin A. J Antibiot (Tokyo) 33: 1323–1330, 1980.Google Scholar
  181. 181.
    Chu MY, Fischer GA: A proposed mechanism of action of 1-β-D-arabinofuranosylcytosine as an inhibitor of the growth of leukemic cells. Biochem Pharmacol 11: 423–430, 1962.PubMedCrossRefGoogle Scholar
  182. 182.
    Goodell B, Leventhal B, Henderson E: Cytosine arabinoside in acute granulocytic leukemia. Clin Pharmacol Ther 12: 599–606, 1971.PubMedGoogle Scholar
  183. 183.
    Sinsheimer RL, Nutter RL, Hopkins GR: Infra-red absorption spectra of pyrimidine nucleotides in H2O and D2O solution. Biochim Biophys Acta 18: 13–27, 1955.PubMedCrossRefGoogle Scholar
  184. 184.
    Furth JJ, Cohen SS: Inhibition of mammalian DNA polymerase by the 5 ’-triphosphate of 1-β-D-arabinofuranosylcytosine and the 5 ’-triphosphate of 9–0D-arabinofuranosyladenine. Cancer Res 28: 2061, 1968.PubMedGoogle Scholar
  185. 185.
    Hanka LJ: Microbiological assay for cytosine arabinoside (NSC-63878) in biologic materials containing other antitumor or antibacterial drugs. Cancer Chemother Rep 55: 557–560, 1971.PubMedGoogle Scholar
  186. 186.
    Momparler RL, Labitan A, Rossi M: Enzymatic estimation and metabolism of 1-β-D-arabinofuranosylcytosine in man. Cancer Res 32: 408–412, 1972.PubMedGoogle Scholar
  187. 187.
    Okabayashi T, Mihara S, Repke DB, Moffatt JG: A radioimmunoassay for 1-β-Darabinofuranosylcyto sine. Cancer Res 37: 619–624, 1977.PubMedGoogle Scholar
  188. 188.
    Piall EM, Aherne W, Marks VM: A radioimmunoassay for cytosine arbinoside. Br J Cancer 40: 548–555, 1979.PubMedCrossRefGoogle Scholar
  189. 189.
    Ho DHW: Distribution of kinase and deaminase of 1-β-D-arabinofuranosylcytosine in tissues of man and mouse. Cancer Res 33: 2816–2820, 1973.PubMedGoogle Scholar
  190. 190.
    Okabayashi T, Mihara S, Repke DB, Moffatt JG: A radioimmunoassay for 1-β-Darabinofuranosyluracil with reference to cross-reactivity of 1–0-D-arabinofuranosylcytosine with an antibody. Cancer Res 37: 3132–3135, 1977.PubMedGoogle Scholar
  191. 191.
    Sullivan RD: Protracted arterial infusion cancer chemotherapy with special emphasis on the treatment of liver neoplasia. In Brodsky I, Kahn SB, Moyer JH (eds): Cancer Chemotherapy: Basic and Clinical Applications, pp 311–317. New York: Grune & Stratton, 1967.Google Scholar
  192. 192.
    Wirtanen GW, Bernhardt LC, Madman S, Ramirez G, Curreri AR, Ansfield FJ: Hepatic artery and celiac axis infusion for the treatment of upper abdominal malignant lesions. Ann Sorg 168: 137–141, 1968.CrossRefGoogle Scholar
  193. 193.
    Schreiber R, Raso V: Radioimmunoassay for the detection and quantitation of 5-fluorodeoxyuridine. Cancer Res 38: 1889–1892, 1978.PubMedGoogle Scholar
  194. 194.
    Hertz R, Lewis J Jr, Lipsett MB: Five years experience with the chemotherapy of metastatic choriocarcinoma and related trophoblastic tumors in women. Am J Obstet Gynecol 82: 631–640, 1961.PubMedGoogle Scholar
  195. 195.
    Li HC, Hertz R, Bergenstal DM: Therapy of choriocarcinoma and relayed trophoblastic tumors with folic acid and purine antagonists. N Engl J Med 259: 66–74, 1958.PubMedCrossRefGoogle Scholar
  196. 196.
    Porter R, Wiltshow E: Methotrexate in the Treatment of Cancer, pp 1–9. Baltimore, MD: Williams & Wilkins, 1962.Google Scholar
  197. 197.
    Capizzi RL, Bertino JR: Methotrexate therapy of Wegener’s granulomatosis. Ann Intern Med 74: 74–79, 1971.PubMedGoogle Scholar
  198. 198.
    Von Leden H, Schiff M: Antimetabolite therapy in midline lethal granulomas. Arch Ophthalmol 80: 460–468, 1964.Google Scholar
  199. 199.
    Weinstein GD, Frost P: Methotrexate for psoriasis. Arch Dermatol 103: 33–38, 1971PubMedCrossRefGoogle Scholar
  200. 200.
    Bertino JR: Rescue techniques in cancer chemotherapy: Use of leucovorin and other rescue agents after methotrexate treatment. Semin Oncol 4: 203–216, 1977.PubMedGoogle Scholar
  201. 201.
    Frei E, Jaffe N, Tattersall HNM, Pitman S, Parker L: New approaches to cancer chemotherapy with methotrexate. N Engl J Med 292: 846–851, 1975.PubMedCrossRefGoogle Scholar
  202. 202.
    Goldin A: Studies with high-dose methotrexate-historical background. Cancer Treat Rep 62: 307–312, 1978.PubMedGoogle Scholar
  203. 203.
    Jacobs SA, Stoller RG, Chabner BA, Johns DG: 7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate. J Clin Invest 57: 534–538, 1976.PubMedCrossRefGoogle Scholar
  204. 204.
    Watson E, Cohen JL, Chan KK: High pressure liquid chromatographic determination of methotrexate and its major metabolite, 7-hydroxymethotrexate, in human plasma. Cancer Treat Rep 62: 381–389, 1978.PubMedGoogle Scholar
  205. 205.
    Donehower RC, Hande KR, Drake JC, Chabner BA: Presence of 2,4-diaminoN’nmethylpteroic acid after high-dose methotrexate. Clin Pharmacol Ther 26: 63–72, 1979.PubMedGoogle Scholar
  206. 206.
    Mehta BM, Gisolfi AL, Hutchinson DJ, Nirenberg A, Kellick MG, Rosen G: Serum distribution of citrovorum factor and 5-methyltetrahydrofolate following oral and i.m. administration of calcium leucovorin in normal adults. Cancer Treat Rep 62: 345–350, 1978.PubMedGoogle Scholar
  207. 207.
    Nixon PF, Bertino JR: Effective absorption and utilization of oral formyltetrahydrofolate in man. N Engl J Med 286: 175–179, 1972.PubMedCrossRefGoogle Scholar
  208. 208.
    Perry J, Chanarin I: Intestinal absorption of reduced folate compounds in man. Br J Haematol 18: 329–339, 1970.PubMedCrossRefGoogle Scholar
  209. 209.
    Bleyer WA, Drake JC, Chabner PA: Neurotoxicity and elevated cerebrospinal fluid methotrexate concentration in meningeal leukemia. N Engl J Med 287: 770–773, 1973.CrossRefGoogle Scholar
  210. 210.
    Noble WC, White PM, Baker H: Assay of therapeutic doses of methotrexate in body fluids of patients with psoriasis. J Invest Dermatol 64: 69–76, 1975.PubMedCrossRefGoogle Scholar
  211. 211.
    Chakrabarti SG, Berstein IA: A simplified fluorometric method for determination of plasma methotrexate. Clin Chem 15: 1157–1161, 1969.PubMedGoogle Scholar
  212. 212.
    Kindade JM Jr, Vogler WR, Dayton PG: Plasma levels of methotrexate in cancer patients as studied by an improved spectrophotofluorometric method. Biochem Med 10: 337–350, 1976.Google Scholar
  213. 213.
    Falk LC, Clark DR, Kalman SM, Long TF: Enzymatic assay for methotrexate in serum and cerebrospinal fluid. Clin Chem 22: 785–788, 1976.PubMedGoogle Scholar
  214. 214.
    Nelson JA, Harris BA, Decker WJ, Farquhar D: Analysis of methotrexate in human plasma by high-pressure liquid chromatography with fluorescence detection. Cancer Res 37: 3970–3973, 1977.PubMedGoogle Scholar
  215. 215.
    Erlichman C, Donehower RC, Myer CE: Competitive protein binding assay of methotrexate. Methods Enzymol 84: 447–458, 1982.PubMedCrossRefGoogle Scholar
  216. 216.
    Langone JJ: Radioimmunoassay of methotrexate, leucovorin, and 5-methyltetrahydrofolate. Methods Enzymol 84: 409–422, 1982.PubMedCrossRefGoogle Scholar
  217. 217.
    Raso V, Schreiber R: A rapid and specific radioimmunoassay for methotrexate. Cancer Res 35: 1407–1410, 1975.PubMedGoogle Scholar
  218. 218.
    Hendel J, Sarek Li, Hvidberg EF: Rapid radioimmunoassay for methotrexate in biological fluids. Clin Chem 22: 813–816, 1976.PubMedGoogle Scholar
  219. 219.
    Loeffler LI, Blum MR, Nelson MA: A radioimmunoassay for methotrexate and its comparison with spectrofluorimetric procedures. Cancer Res 36: 3306–3311, 1976.PubMedGoogle Scholar
  220. 220.
    Aherne W, Piall E, Marks V: Radioimmunoassay of methotrexate: Use of 75Selabelled methotrexate. Ann Clin Biochem 15: 331–334, 1978.PubMedGoogle Scholar
  221. 221.
    Paxton JW, Rowell FJ: A radiosensitive and specific radioimmunoassay for methotrexate. Clin Chim Acta 80: 563–572, 1977.PubMedCrossRefGoogle Scholar
  222. 222.
    Paxton JW, Rowell FJ, Cree GM: Comparison of three radioligands, selenium-75, iodine-125, and tritium, in the radioimmunoassay of methotrexate. Clin Chem 24: 1534–1538, 1978.PubMedGoogle Scholar
  223. 223.
    Kamel R, Landon J, Forrest GC: A fully automated, continuous-flow radioimmunoassay for methotrexate. Clin Chem 26: 97–100, 1980.PubMedGoogle Scholar
  224. 224.
    Langone JJ: [125I]-protein A: A tracer for general use in immunoassay. J Immunol Methods 24:269–285, 1978.PubMedCrossRefGoogle Scholar
  225. 225.
    Tracey KJ, Mutkoski R, Lopez JA, Franzblau W, Franzblau C: Radioimmunoassay for methotrexate using hydroxylmethacrylate hydrogel. Cancer Chemother Pharmacol 10: 96–99, 1983.PubMedCrossRefGoogle Scholar
  226. 226.
    Quinton MI, Aherne W, Marks V: A radioimmunoassay for methotrexate adapted to the Centria System 2. J Immunoassay 1: 475–486, 1980.PubMedCrossRefGoogle Scholar
  227. 227.
    Langone JJ, Levine L: Immunoassay of leucovorin: Use of 125I-labelled protein A to detect immunological binding. Anal Biochem 95: 472–478, 1979.PubMedCrossRefGoogle Scholar
  228. 228.
    Langone JJ: Immunoassay of 5-methyltetrahydrofolate: Use of 125I-labelled protein A as a tracer molecule for specific antibody. Anal Biochem 104: 347–354, 1980.PubMedCrossRefGoogle Scholar
  229. 229.
    Fong KL, Ho DHW, Benjamin RS, Yang Y, Sickler J, Brown SN, Bodey GP: A radioimmunoassay for 5-methyltetrahydrohomofolate. J Pharmacol Exp Ther 218: 344–347, 1981.PubMedGoogle Scholar
  230. 230.
    Al-Bassam MN, O’Sullivan MJ, Bridges JW, Marks V: Improved double-antibody enzyme immunoassay for methotrexate. Clin Chem 25: 1448–1452, 1979.PubMedGoogle Scholar
  231. 231.
    Buice RG, Evans WE, Karas J, Nicholas CA, Sidhu P, Straughn AB, Meyer MC, Crom WR: Evaluation of enzyme immunoassay, radioassay, and radioimmunoassay of serum methotrexate, as compared with liquid chromatography. Clin Chem 26: 1902–1904, 1980.PubMedGoogle Scholar
  232. 232.
    Finley PR, Williams RJ, Griffith F, Lichti DA: Adaptation of the enzyme-multiplied immunoassay for methotrexate to the centrifugal analyzer. Clin Chem 26: 341–343, 1980.PubMedGoogle Scholar
  233. 233.
    Gushaw JB, Miller JG: Homogeneous enzyme immunoassay for methotrexate in serum. Clin Chem 24: 1032, 1978.Google Scholar
  234. 234.
    Oellerich M, Engelhardt P, Schaadt M, Diehk V: Determination of methotrexate in serum by a rapid, fully mechanized enzyme immunoassay (EMIT). J Clin Chem Clin Biochem 18: 169–174, 1980.PubMedGoogle Scholar
  235. 235.
    Oellerich M, Haeckel R, Haindl H: Evaluation of EMIT adapted to the <Cobas> biocentrifugal analyzer. J Clin Chem Clin Biochem 20:765–772, 1982.PubMedGoogle Scholar
  236. 236.
    Pesce MA, Bodourian SH: Enzyme immunoassay and enzyme inhibition assay of methotrexate, with use of the centrifugal analyzer. Clin Chem 27: 380–384, 1981.PubMedGoogle Scholar
  237. 237.
    Ferrua B, Milano G, Ly B, Guennec JY, Masseyeff R: An enzyme immunoassay design using labelled antibodies for the determination of haptens. Application to methotrexate assay. J Immunol Methods 60: 257–268, 1983.PubMedCrossRefGoogle Scholar
  238. 238.
    Hendel J, Sarek LJ: Production of methotrexate antiserum in rabbits: The significance of immunogen solubility, hapten content, and mode of administration on the antibody response. J Clin Lab Invest 37: 273–278, 1977.CrossRefGoogle Scholar
  239. 239.
    Howell SK, Wang Y-M, Sutow WW: Plasma methotrexate as determined by liquid chromatography, enzyme-inhibition assay, and radioimmunoassay after high-dose infusion. Clin Chem 26: 734–737, 1980.PubMedGoogle Scholar
  240. 240.
    Case DC Jr, Young CW, Lee BJ III: Combination chemotherapy of MOPP-resistant Hodgkin’s disease with adriamycin, bleomycin, decarbazine and vinblastine (ABDV). Cancer 39: 1382–1386, 1977.PubMedCrossRefGoogle Scholar
  241. 241.
    Durant JR, Loeb V, Dorfman R, Chan YK: 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, vincristine and prednisone (BCOP). Cancer 36: 1936–1944, 1975.PubMedCrossRefGoogle Scholar
  242. 242.
    McElwain TJ, Toy J, Smith E, Peckham MJ, Austin DE: A combination of chlorambucil, vinblastine, procarbazine and prednisolone for treatment of Hodgkin’s disease. Br J Cancer 36: 276–280, 1977.PubMedCrossRefGoogle Scholar
  243. 243.
    Gerzon K: Dimeric catharanthus alkaloids. In Cassady JK, Douros JD (eds): Anticancer Agents Based on Natural Product Models, p 271. New York: Academic Press, 1980.Google Scholar
  244. 244.
    Teale JD, Clough JM, Marks V: Radioimmunoassay of vinblastine and vincristine. Br J Clin Pharmacol 4: 169–172, 1977.PubMedGoogle Scholar
  245. 245.
    Van den Berg HW, Desai ZR, Wilson R, Kennedy G, Bridges JM, Shanks RG: The pharmacokinetics of vincristine in man: Reduced drug clearance associated with raised serum alkaline phosphatase and dose-limited elimination. Cancer Chemother Pharmacol 8: 215–219, 1982.PubMedCrossRefGoogle Scholar
  246. 246.
    Root MA, Gerzon K, Dyke RW: A radioimmunoassay for vinblastine and vincristine. In Federation of Analytical Chemistry and Spectroscopy Societies,October, 1973, p 125 (Abstract 183).Google Scholar
  247. 247.
    Creasey WA, Marsh JC: Metabolism of vinblastine (VLB) in the dog. Proc Am Assoc Cancer Res 14: 57, 1973.Google Scholar
  248. 248.
    Cullinan GJ, Gerzon K, Poore GA, Sweeney MJ: Vinblastine modifications; desacetyl-VLB amides. In Proceedings of the 9th International Congress on Chemotherapy,July 1975, Abstract SC-19.Google Scholar
  249. 249.
    Sweeney MJ, Cullinan GJ, Poore GA, Gerzon K: Experimental antitumor activity of vinblastine amides. Proc Am Assoc Cancer Res 15: 36, 1974.Google Scholar
  250. 250.
    Owellen RJ, Hartke CA, Hains FO: Pharmacokinetics and metabolism of vinblastine in humans. Cancer Res 37: 2597–2602, 1977.PubMedGoogle Scholar
  251. 251.
    Owellen RJ, Root MA, Hains FO: Pharmacokinetics of vindesine and vincristine in humans. Cancer Res 37: 2603–2607, 1977.PubMedGoogle Scholar
  252. 252.
    Owellen RJ, Blair M, Van Tosh A, Hains FC: Determination of tissue concentrations of vinca alkaloids by radioimmunoassay. Cancer Treat Rep 65: 469–475, 1981.PubMedGoogle Scholar
  253. 253.
    Sethi VS, Burton SS, Jackson DV: A sensitive radioimmunoassay for vincristine and vinblastine. Cancer Chemother Pharmacol 4: 183–187, 1980.PubMedCrossRefGoogle Scholar
  254. 254.
    Jackson DV Jr, Barringer ML, Rosenbaum DL, Long TR, Sterchi JM, Meredith W, Sethi VS, Modest FJ, Wells HB, Spun CL, Castle MC: Continuous intravenous infusion of vinca alkaloid using a subcutaneously implanted pump in a canine model. Cancer Chemother Pharmacol 10: 217–220, 1983.PubMedCrossRefGoogle Scholar
  255. 255.
    Langone JJ, D’Onofrio MR, Van Vunakis H: Radioimmunoassay for the vinca alkaloids, vinblastine and vincristine. Anal Biochem 95: 214–221, 1979.PubMedCrossRefGoogle Scholar
  256. 256.
    Kupchan SM, Brittor RW, Ziegler MF, Sigel CW: Bruceantin, a new potent anti-leukemic simaroubolide from Bruces antidysenterica. J Org Chem 38: 178–179, 1973.PubMedCrossRefGoogle Scholar
  257. 257.
    Hartwell JL: Types of anticancer agents isolated from plants. Cancer Treat Rep 60: 1031–1067, 1976.PubMedGoogle Scholar
  258. 258.
    Suling WJ, Woolley CW, Shannon WM: Disposition and metabolism of bruceantin in the mouse. Cancer Chemother Pharmacol 3: 171–176, 1979.PubMedCrossRefGoogle Scholar
  259. 259.
    Fong K-LL, Ho DHW, Carter CJK, Brown NS, Benjamin RS, Freireich EJ, Bodey GP Sr: Radioimmunoassay for the detection and quantitation of bruceantin. Anal Biochem 105: 281–286, 1980.PubMedCrossRefGoogle Scholar
  260. 260.
    Fong K-LL, Ho DHW, Benjamin RS, Brown NS, Bedikian A, Yap BS, Wiseman CL, Kramer W, Bodey GP: Clinical pharmacology of bruceantin by radioimmunoassay. Cancer Chemother Pharmacol 9: 169–172, 1982.PubMedCrossRefGoogle Scholar
  261. 261.
    Beer CT, Kajiwara K, Mueller GC: Synchronization of HeLa cells with 2,3- dihydro1H-imidazo(1,2-b)pyrazole. Biochem Pharmacol 23: 1115–1122, 1974.PubMedCrossRefGoogle Scholar
  262. 262.
    Ennis HL, Moller L, Wang JJ, Selawry OS: 2,3-Dihydro-1H-imidazo(1,2-b)pyrazole. A new inhibitor of deoxyribonucleic acid synthesis. Biochem Pharmacol 20: 2639–2646, 1971.PubMedCrossRefGoogle Scholar
  263. 263.
    Staubus AE, Kerr TA, Balcerzak SP et al.: Pharmacokinetics of pyrazolo-imidazole in humans. Proc Am Assoc Cancer Res ASCO 20: 366, 1979.Google Scholar
  264. 264.
    Yap BS, Murphy WK, Burgess MA, Valdivieso M, Bodey GP: Phase 1 clinical evaluation of 2,3-dihydro-1H-imidazo[1,2-b)pyrazole. Cancer Treat Rep 63: 1849–1851, 1979.PubMedGoogle Scholar
  265. 265.
    Malspeis L, Desouza JJV, Staubus AE, Bhat HB: Metabolism and pharmacokinetics of IMPY (NSC 51143) in the dog. Proc Am Assoc Cancer Res ASCO 20: 153, 1979.Google Scholar
  266. 266.
    Neidhart J, Sagone A, Malspeis L: IMPY and its β-ribosyl metabolite show differential in vitro effects. Proc Am Assoc Cancer Res ASCO 20: 177, 1979.Google Scholar
  267. 267.
    Allen LM: Correlation of the disposition kinetics and intracellular accumulation of imidazo-pyrazole (NSC 51149) with alterations in ribonucleotide pools and DNA distribution content of mastocytoma cells in vivo. Proc Am Assoc Cancer Res ASCO 20: 107, 1979.Google Scholar
  268. 268.
    Fong K-L, Ho DHW, Yap BS, Stewart D, Brown NS, Benjamin RS, Freireich EJ, Bodey GP: Clinical pharmacology of IMPY by radioimmunoassay. Cancer Treat Rep 64: 1253–1260, 1980.PubMedGoogle Scholar
  269. 269.
    Okabayashi T, Mihara S, Moffatt JG: A radioimmunoassay method for 1-ß-D-arabinofuranosyluracil using antibodies directed against 1–13-D-arabinofuranosylcytosine. Cancer Res 37: 625–628, 1977.PubMedGoogle Scholar
  270. 270.
    Piall E, Aherne GW, Marks V: Evaluation of a commercially available radioimmunoassay kit for measurement of doxorubicin in plasma. Clin Chem 28: 119–121, 1982.PubMedGoogle Scholar
  271. 271.
    Fujiwara K, Nakamura H, Kitagawa T: Development of enzyme immunoassay for chromomycin A3 and olivomycin using β-D-galactosidase as a label. Cancer Res 45: 5442–5446, 1985.PubMedGoogle Scholar
  272. 272.
    Sethi VS, Kimball JC: Pharmacokinetics of vincristine sulfate in children. Cancer Chemother Pharmacol 6: 111–115, 1981.PubMedCrossRefGoogle Scholar
  273. 273.
    Berlin YA, Keselva OA, Kolosov MN, Shemyakin MM, Soifer VS, Vasina IV, Yartseve IV: Aureolic acid group of antitumor antibiotics. Nature 218: 193–194, 1968.PubMedCrossRefGoogle Scholar
  274. 274.
    Pitina LR, Baranov EP, Grinchenko BI, Brikenshtein BK, Barenboim GM: Interaction of olivomycin, an antitumor antibiotic with magnesium ions. Antibiotiki (Mosc.) 26: 906–912, 1981.Google Scholar
  275. 275.
    Trofinova NB: Experience with clinical use of mithramycin in treatment of testicular cancer. Antibiotiki (Mosco.) 25: 773–777, 1980.Google Scholar
  276. 276.
    Vogelzank NJ, Raghavan D, Anderson RW, Rosai J, Levitt SH, Kennedy BP Mediastinal nonseminomatous germ cell tumor: the role of combined modality therapy. Ann Thorac Surg 33: 333–339, 1982.CrossRefGoogle Scholar
  277. 277.
    Fujiwara K, Saita T, Nakashima K, Kitagawa T: Enzyme immunoassay for the quantification of mithramycin using β-D-galactosidase as a label. Cancer Res 46: March, 1986, in press.Google Scholar
  278. 278.
    Hacker MP, Dank JR, Ershler WB: Vinblastine pharmacokinetics measured by a sensitive enzyme-linked immunosorbent assay. Cancer Res 44: 478–481, 1984.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1986

Authors and Affiliations

  • Kunio Fujiwara
  • Tsunehiro Kitagawa

There are no affiliations available

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