Catalytic inhibitors of DNA topoisomerase II

Biochimica et Biophysica Acta - Gene Structure and Expression

Volumn 1400, Issue 1-3, 1998, Pages 155-171

  Andoh, Toshiwo ^a   Ishida, Ryoji ^b  

^a SOKA UNIVERSITY   (Japan)

^b AICHI CANCER CENTER HOSPITAL   (Japan)

Author keywords

Bisdioxopiperazine; Catalytic inhibitor; Clearable complex; DNA topoisomerase; ICRF; MST 16

Indexed keywords

ACLARUBICIN; AMSACRINE; CHLOROQUINE; DNA TOPOISOMERASE; DOXORUBICIN; ETOPOSIDE; FOSTRIECIN; INTOPLICINE; MERBARONE; MITOXANTRONE; NOVOBIOCIN; PIPERAZINE; SURAMIN;

ANTINEOPLASTIC ACTIVITY; CATALYSIS; DNA CLEAVAGE; DNA PROBE; DNA REPLICATION; DRUG EFFICACY; ENZYME INHIBITOR COMPLEX; ENZYME SYNTHESIS; HEART PROTECTION; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANTINEOPLASTIC AGENTS; CATALYSIS; DNA TOPOISOMERASES, TYPE II; ENZYME INHIBITORS; HUMANS; INTERCALATING AGENTS; MOLECULAR STRUCTURE; PIPERAZINES;

EID: 0032189962     PISSN: 01674781     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0167-4781(98)00133-X     Document Type: Review

References (108)

1. Chen A.Y., Liu L.F. DNA topoisomerases: essential enzymes and lethal targets. Annu. Rev. Pharmacol. Toxicol. 34:1994;191-218.
2. Froelich-Ammon S.J., Osheroff N. Topoisomerase poisons: harnessing the dark side of enzyme mechanism. J. Biol. Chem. 270:1995;21429-21432.
3. Binaschi M., Zunino F., Capranico G. Mechanism of action of DNA topoisomerase inhibitors. Stem Cells. 13:1995;369-379.
4. Nitiss J.L., Beck W.T. Antitopoisomerase drug action and resistance. Eur. J. Cancer. 32A:1996;958-966.
5. W.T. Beck, M.K. Danks, Multidrug resistance associated with alterations in topoisomerase II, in: M. Potmesil, K. Kohn (Eds.), DNA Topoisomerases in Cancer, Oxford Univ. Press, New York, 1991, pp. 260-275.
6. Chen M., Beck W.T. Teniposide-resistant CEM cells, which express mutant DNA topoisomerase IIα, when treated with non-complex-stabilizing inhibitors of the enzyme, display no cross-resistance and reveal aberrant functions of the mutant enzyme. Cancer Res. 53:1993;5946-5953.
7. Jensen P.B., Søresen B.S., Sehested M., Demant E.J.F., Kjeldsen E., Friche E., Hansen H.H. Different modes of anthracycline interaction with topoisomerase II: separate structures critical for DNA-cleavage, and for overcoming topoisomerase II-related drug resistance. Biochem. Pharmacol. 45:1993;2025-2035.
8. Drake F.H., Hofmann G.A., Mong S.-M., Bartus J.O., Hertzberg R.P., Johnson R.K., Mattern M.R., Mirabelli C.K. In vitro and intracellular inhibition of topoisomerase II by the antitumor agent merbarone. Cancer Res. 49:1989;2578-2583.
9. Boritzki T.J., Wolfard T.S., Besserer J.A., Jackson R.C., Fry D.W. Inhibition to type II topoisomerase by fostriecin. Biochem. Pharmacol. 37:1988;4063-4068.
10. Jensen P.B., Sørenson B.S., Demant E.J.F., Sehested M., Jensen P.S., Vindelov L., Hansen H.H. Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4′-(9-acridinylamino)-methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase II-mediated DNA cleavage. Cancer Res. 50:1990;3311-3316.
11. Bojanowski K., Lelievre S., Markovits J., Coupree J., Jacquemin-Sablon A., Larsen A.K. Suramin is an inhibitor of DNA topoisomerase II in vitro and in Chinese hamster fibrosarcoma cells. Proc. Natl. Acad. Sci. USA. 89:1992;3025-3029.
12. Permana P.A., Snapka R.M., Shen L.L., Chu D.T.W., Clement J.J., Plattner J.J. Quinobenoxazines: a class of novel antitumor quinolones and potent mammalian DNA topoisomerase II catalytic inhibitors. Biochemistry. 33:1994;11333-11339.
13. Tanabe K., Ikegami Y., Ishida R., Andoh T. Inhibition of topoisomerase II by antitumor agents bis(2,6-dioxopiperazine) derivatives. Cancer Res. 51:1991;4903-4908.
14. Ishida R., Miki T., Narita T., Yui R., Sato M., Utsumi K.R., Tanabe K., Andoh T. Inhibition of intracellular topoisomerase II by antitumor bis(2,6-dioxopiperazine) derivatives: mode of cell growth inhibition distinct from that of cleavable complex-forming type inhibitors. Cancer Res. 51:1991;4909-4916.
15. Jensen P.B., Sørensen B.S., Sehested M., Grue P., Demant E.J.F., Hansen H.H. Targeting the cytotoxicity of topoisomerase II-directed epipodophyllotoxins to tumor cells in acidic environments. Cancer Res. 54:1994;2959-2963.
16. Utsumi H., Shibuya M.L., Kosaka T., Buddenbaum W.E., Elkind M.M. Abrogation by novobiocin of cytotoxicity due to the topoisomerase II inhibitor amsacrine in Chinese hamster cells. Cancer Res. 50:1990;2577-2581.
17. Osheroff N. Biochemical basis for the interactions of type I and type II topoisomerases with DNA. Pharmacol. Ther. 41:1989;223-241.
18. Watt P.M., Hickson I.D. Structure and function of type II DNA topoisomerases. Biochem. J. 303:1994;681-695.
19. Roca J. The mechanism of DNA topoisomerases. Trends Biochem. Sci. 20:1995;156-160.
20. Berger J.M., Gamblin S.J., Harrison S.C., Wang J.C. Structure and mechanism of DNA topoisomerase II. Nature. 379:1996;225-232.
21. Wang J.C. DNA topoisomerases. Annu. Rev. Biochem. 65:1996;635-692.
22. Creighton A.M., Hellmann K., Whitecross S. Antitumour activity in a series of bisdiketopiperazines. Nature. 222:1969;384-385.
23. Hellmann K., Newton K.A., Whitmore D.N., Hanham I.W.F., Bond J.V. Preliminary clinical assessment of ICRF-159 in acute leukaemia and lymphosarcoma. Br. Med. J. 1:1969;822-824.
24. Herman E.H., Witiak D.T., Hellmann K., Waravdekar V.S. Biological properties of ICRF-159 and related bis(dioxopiperazine) compounds. Adv. Pharmacol. Chemother. 19:1982;249-290.
25. Creighton A.M., Birnie G.D. The effect of bisdioxopiperazines on the synthesis of deoxyribonucleic acid, ribonucleic acid and protein in growing mouse embryo fibroblasts. Biochem. J. 114:1969;58P.
26. Sharp H.B.A., Field E.O., Hellmann K. Mode of action of the cytostatic agent 'ICRF-159'. Nature. 226:1970;524-526.
27. Hallowes R.C., West D.G., Hellmann K. Cumulative cytostatic effect of ICRF-159. Nature. 247:1974;487-491.
28. Witiak D.T., Lee H.J., Hart R.W., Gibson R.E. Study of trans-cyclopropylbis(diketopiperazine) and chelating agents related to ICRF 159. Cytotoxicity, mutagenicity, and effects on scheduled and unscheduled DNA synthesis. J. Med. Chem. 20:1977;630-635.
29. Roca J., Ishida R., Berger J.M., Andoh T., Wang J.C. Antitumor bisdioxopiperazines inhibit yeast DNA topoisomerase II by trapping the enzyme in the form of a closed protein clamp. Proc. Natl. Acad. Sci. USA. 91:1994;1781-1785.
30. Witiak D.T., Wei Y. Dioxopiperazines: chemistry and biology. Prog. Drug Res. 35:1990;249-363.
31. Ishimi Y., Ishida R., Andoh T. Effect of ICRF-193, a novel DNA topoisomerase II inhibitor, on simian virus 40 DNA and chromosome replication in vitro. Mol. Cell. Biol. 12:1992;4007-4014.
32. Ishimi Y., Ishida R., Andoh T. Synthesis of simian virus 40 C-family catenated dimers in vivo in the presence of ICRF-193. J. Mol. Biol. 247:1995;835-839.
33. Ishida R., Hamatake M., Wasserman R.A., Nitiss J.L., Wang J.C., Andoh T. DNA topoisomerase II is the molecular target of bisdioxopiperazine derivatives ICRF-159 and ICRF-193 in Saccharomyces cerevisiae. Cancer Res. 55:1995;2299-2303.
34. Sato M., Ishida R., Ohsumi K., Narita T., Andoh T. DNA topoisomerase II as the cellular target of a novel antitumor agent ICRF-193, a bisdioxopiperazine derivative, in Xenopus egg extract. Biochem. Biophys. Res. Commun. 235:1997;571-575.
35. Beere H.M., Chresta C.M., Hickman J.A. Selective inhibition of topoisomerase II by ICRF-193 does not support a role for topoisomerase II activity in the fragmentation of chromatin during apoptosis of human leukemia cells. Mol. Pharmacol. 49:1996;842-851.
36. Adams D.E., Shekhetman E.M., Zechiedrich E.L., Schmid M.B., Cozzarelli N.R. The role of topoisomerase IV in partitioning bacterial replicons and the structure of catenated intermediates in DNA replication. Cell. 71:1992;277-288.
37. DiNardo S., Voelkel K., Sternglanz R. DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc. Natl. Acad. Sci. USA. 81:1984;2616-2620.
38. Caron P.R., Watt P., Wang J.C. The C-terminal domain of Saccharomyces cerevisiae DNA topoisomerase II. Mol. Cell. Biol. 14:1994;3197-3207.
39. Snapka R.M., Permana P.A. SV40 DNA replication intermediates: analysis of drugs which target mammalian DNA replication. BioEssays. 15:1993;121-127.
40. Permana P.A., Ferrer C.A., Snapka R.M. Inverse relationship between catenation and superhelicity in newly replicated simian virus 40 daughter chromosomes. Biochem. Biophys. Res. Commun. 201:1994;1510-1517.
41. Ishimi Y., Sugasawa K., Hanaoka F., Eki T., Hurwitz J. Topoisomerase II plays an essential role as a swivelase in the late stage of SV40 chromosome replication in vitro. J. Biol. Chem. 267:1992;462-466.
42. Sato M., Ishida R., Narita T., Kato J.-I., Ikeda H., Andoh T. Interaction of DNA topoisomerase II catalytic inhibitor ICRF-193, a bisdioxopiperazine derivative, with conserved region(s) of eukaryotic but not prokaryotic enzyme. Biochem. Pharmacol. 54:1997;545-550.
43. Hasinoff B.B., Kuschak T.I., Yalowich J.C., Creighton A.M. A qsar study comparing the cytotoxicity and DNA topoisomerase II inhibitory effects of bisdioxopiperazine analogs of ICRF-187 (dexrazoxane). Biochem. Pharmacol. 50:1995;953-958.
44. Fattman C.l., Allan W.P., Hashinoff B.B., Yalowich J.C. Collateral sensitivity to the bisdioxopiperazine dexrazoxane (ICRF-187) in etoposide (VP-16)-resistant human leukemia K562 cells. Biochem. Pharmacol. 52:1996;635-642.
45. Davies S.L., Bergh J., Harris A.L., Hickson I.D. Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors. Br. J. Cancer. 75:1997;816-821.
46. Hasinoff B.B., Kuschak T.I., Creighton A.M., Fattman C.L., Allan W.P., Thampatty P., Yalowich J.C. Characterization of a Chinese hamster ovary cell line with acquired resistance to the bisdioxopiperazine dexrazoxane (ICR-187) catalytic inhibitor of topoisomerase II. Biochem. Pharmacol. 53:1997;1843-1853.
47. Sehested M., Wessel I., Jensen L.H., Holm B., Oliveri R., Kenwrick S., Creighton A., Nitiss J.L., Jensen P.B. Chinese hamster ovary cells resistant to the topoisomerase II catalytic inhibitor ICRF-159: a Tyr49Phe mutation confers high-level resistance to bisdioxopiperazines. Cancer Res. 58:1998;1460-1468.
48. Wessel I., Jensen L.H., Jensen P.B., Falck J., Roerth M., Nitiss J.L., Sehested M. Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II (topo II) catalytic inhibitor ICRF-187 (NYH/187) demonstrate a functional Arg162Gln mutation in the Walker A consensus ATP binding site of the α isoform. Proc. Am. Assoc. Cancer Res. 39:1998;2552.
49. Vassetzky Y.S., Alghisi G.-C., Gasser S.M. DNA topoisomerase II mutations and resistance to anti-tumor drugs. BioEssays. 17:1995;767-774.
50. Jensen P.B., Jensen P.S., Demant E.J.F., Friche E., Sørensen B.S., Sehested M., Wassermann K., Vindeloev L., Westergaard O., Hansen H.H. Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II. Cancer Res. 51:1991;5093-5099.
51. Holm B., Jensen P.B., Sehested M., Hansen H.H. In vivo inhibition of etoposide-mediated apoptosis, toxicity, and antitumor effect by the topoisomerase II-uncoupling anthracycline aclarubicin. Cancer Chemother. Pharmacol. 34:1994;503-508.
52. Roberge M., Tudan C., Hung S.M.F., Harder K.W., Jirik F.R., Anderson H. Antitumor drug fostriecin inhibits the mitotic entry checkpoint and protein phosphatase 1 and 2A. Cancer Res. 54:1994;6115-6121.
53. Kim R.A., Wang J.C. Function of DNA topoisomerases as replication swivels in Saccharomyces cerevisiae. J. Mol. Biol. 208:1989;257-267.
54. Yang L., Wold M.S., Li J.J., Kelly T.J., Liu L.F. Roles of DNA topoisomerases in simian virus 40 DNA replication in vitro. Proc. Natl. Acad. Sci. USA. 84:1987;950-954.
55. Aveman K., Knippers R., Koller T., Sogo J.M. Camptothecin, a specific inhibitor of type 1 DNA topoisomerase, induces DNA breaks at replication forks. Mol. Cell. Biol. 8:1988;3026-3034.
56. Sundin O., Varshavsky A. Terminal stages of SV40 DNA replication proceed via multiply intertwined catenated dimers. Cell. 21:1980;103-114.
57. Brush G.S., Kelly T.J., Stillman B. Identification of eukaryotic DNA replication proteins using simian virus 40 replication system. Methods Enzymol. 262:1995;522-548.
58. Takasuga Y., Andoh T., Yamashita J., Yagura T. ICRF-193, an inhibitor of topoisomerase II, demonstrates that DNA replication in sperm nuclei reconstituted in Xenopus egg extracts does not require chromatin decondensation. Exp. Cell Res. 217:1995;378-384.
59. Holm C., Goto T., Wang J.C., Botstein D. DNA topoisomerase II is required at the time of mitosis in yeast. Cell. 41:1985;553-563.
60. Uemura T., Yanagida M. Mitotic spindle pulls but fails to separate chromosomes in type II DNA topoisomerase mutants: uncoordinated mitosis. EMBO J. 5:1986;1003-1010.
61. Ishida R., Sato M., Narita T., Utsumi K.R., Nishimoto T., Morita T., Nagata H., Andoh T. Inhibition of DNA topoisomerase II by ICRF-193 induces polyploidization by uncoupling chromosome dynamics from other cell cycle events. J. Cell Biol. 126:1994;1341-1351.
62. Anderson H.J., Roberge M. DNA topoisomerase II: a review of its involvement in chromosome structure, DNA replication, transcription and mitosis. Cell Biol. Int. Rep. 16:1992;717-724.
63. Andoh T., Sato M., Narita T., Ishida R. Role of DNA topoisomerase II in chromosome dynamics in mammalian cells. Biotechnol. Appl. Biochem. 18:1993;165-174.
64. Uemura T., Ohkura H., Adachi Y., Morino K., Shiozaki K., Yanagida M. DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe. Cell. 50:1987;917-925.
65. Giménez-Abián J.F., Clarke D.J., Mullinger A.M., Downes C.S., Johnson R.T. A postprophase topoisomerase II-dependent chromatid core separation step in the formation of metaphase chromosomes. J. Cell Biol. 131:1995;7-17.
66. Anderson H.J., Roberge M. Topoisomerase II inhibitors affect entry into mitosis and chromosome condensation in BHK cells. Cell Growth Differ. 7:1996;83-90.
67. Inazawa J., Ariyama T., Tokino T., Tanigami A., Nakamura Y., Abe T. High resolution ordering of DNA markers by multi-color fluorescent in situ hybridization of prophase chromosomes. Cytogenet. Cell Genet. 65:1994;130-135.
68. Ariyama T., Kimura T., Yamakawa K., Nakamura Y., Abe T., Inazawa J. Precise ordering of 26 cosmid markers on chromosome region 3p23-p21.3 by two-color FISH on human prophase chromosomes and stretched DNAs. Cytogenet. Cell Genet. 70:1995;129-133.
69. Clarke D.J., Johnson R.T., Downes C.S. Topoisomerase II inhibition prevents anaphase chromatid segregation in mammalian cells independently of the generation of DNA strand breaks. J. Cell Sci. 105:1993;563-569.
70. Gorbsky G.J. Cell cycle progression and chromosome segregation in mammalian cells cultured in the presence of the topoisomerase II inhibitors ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane; ADR-529] and ICRF-159 (razoxane). Cancer Res. 54:1994;1042-1048.
71. Hartwell L.H., Weinert T.A. Checkpoints: controls that ensure the order of cell cycle events. Science. 246:1989;629-634.
72. Downes C.s., Clarke D.J., Mullinger A.M., Gimenez-Ablan J.F., Greighton A.M., Johnson R.T. A topoisomerase II-dependent G2 cycle checkpoint in mammalian cells. Nature. 372:1994;467-470.
73. Iwai M., Hara A., Andoh T., Ishida R. ICRF-193, a catalytic inhibitor of DNA topoisomerase II, delays the cell cycle progression from metaphase, but not from anaphase to the G1 phase in mammalian cells. FEBS Lett. 406:1997;267-270.
74. Rieder C.L., Schultz A., Cole R., Sluder G. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attached to the spindle. J. Cell Biol. 127:1994;1301-1310.
75. Li X., Nicklas R.B. Mitotic forces control a cell-cycle checkpoint. Nature. 373:1995;630-632.
76. Sørensen B.S., Sinding J., Andersen A.H., Alsner J., Jensen P.B., Westergaard O. Mode of action of topoisomerase II-targeting agents at a specific DNA sequence: uncoupling the DNA binding, cleavage and religation events. J. Mol. Biol. 228:1992;778-786.
77. Woynarowski J.M., Sigmund R.D., Beerman T.A. DNA minor groove binding agents interfere with topoisomerase II mediated lesions induced by epipodophyllotoxin derivative VM-26 and acridine derivative m-AMSA in nuclei from L1210 cells. Biochemistry. 28:1989;3850-3855.
78. Sehested M., Jensen P.B. Mapping of DNA topoisomerase II poisons (etoposide, clerocidin) and catalytic inhibitors (aclarubicin, ICRF-187) to four distinct steps in the topoisomerase II catalytic cycle. Biochem. Pharmacol. 51:1996;879-886.
79. Kawada S.-Z., Yamashita Y., Fujii N., Nakano H. Induction of a heat-stable topoisomerase II-DNA cleavable complex by nonintercalative terpenoides, terpentecin and clerocidin. Cancer Res. 51:1991;2922-2925.
80. Kano Y., Narita T., Suzuki K., Akutsu M., Suda K., Sakamoto S., Miura Y. The effects of ICRF-154 in combination with other anticancer agents in vitro. Br. J. Cancer. 66:1992;281-286.
81. Ishida R., Iwai M., Hara A., Andoh T. The combination of different types of antitumor topoisomerase II inhibitors, ICRF-193 and VP-16, has synergistic and antagonistic effects on cell survival, depending on treatment schedule. Anticancer Res. 16:1996;2735-2740.
82. Rhomberg W.U. Radiotherapy combined with ICRF 159 (NSC 129943). Int. J. Rad. Oncol. Biol. Phys. 4:1978;121-126.
83. Taylor I.W., Bleehen N.M. Interaction of ICRF 159 with radiation, and its effect on sub-lethal and potentially lethal radiation damage in vitro. Br. J. Cancer. 36:1977;493-500.
84. Keizer H.G., Pinedo H.M., Schuurhuis G.J., Joenje H. Doxorubicin (adriamycin): a critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacol. Ther. 47:1990;219-231.
85. Myers C.E., Gianni L., Simone C.B., Klecker R., Green R. Oxidative destruction of erythrocyte ghost membranes catalyzed by the doxorubicin-iron complex. Biochemistry. 21:1982;1707-1713.
86. Bastra J., Wolf C.R., Brown J.R., Patterson L.H. Evidence for human liver mediated free-radical formation by doxorubicin and mitoxantrone. Anti-Cancer Drug Des. 1:1985;45-52.
87. Novak R.F., Kharasch E.D. Mitoxantrone: propensity for free radical formation and lipid peroxidation-implications for cardiotoxicity. Invest. New Drugs. 3:1985;95-99.
88. Rajagopalan S., Politi P.M., Sinha B.K., Myers C.E. Adriamycin-induced free radical formation in the perfused rat heart: implications for cardiotoxicity. Cancer Res. 48:1988;4766-4769.
89. Herman E.H., Ferrans V.J. Amelioration of chronic anthracycline cardiotoxicity by ICRF-187 and other compounds. Cancer Treat. Rep. 14:1987;225-229.
90. Woodman R.J., Cysyk R.L., Kline K., Gang M., Venditti J.M. Enhancement of the effectiveness of daunorubicin (NSC-82151) or adriamycin (NSC-129943). Cancer Chemother. Rep. 59:1975;689-695.
91. Shipp N.G., Dorr R.T., Alberts D.S., Dawson B.V., Hendrix M. Characterization of experimental mitoxantrone cardiotoxicity and its partial inhibition by ICRF-187 in cultured neonatal rat heart cells. Cancer Res. 53:1993;550-556.
92. Holm B., Jensen P.B., Sehested M. ICRF-187 rescue in etoposide treatment in vivo. A model targeting high-dose topoisomerase II poisons to CNS tumors. Cancer Chemother. Pharmacol. 38:1996;203-209.
93. Speyer J.L., Green M.D., Zelenius-Jacquotte A., Wernz J.C., Rey M., Sanger J., Kramer K., Ferrans V., Hochster H., Meyers M., Blum R.H., Feit F., Attubato M., Burrows M., Muggia F.M. ICRF-187 permits longer treatment with doxorubicin in woman with breast cancer. J. Clin. Oncol. 10:1992;117-127.
94. Green M.D., Alderton P., Gross J., Muggia F.M., Speyer J.L. Evidence of the selective alteration of anthracycline activity due to modulation by ICRF-187 (ADR-529). Pharmacol. Ther. 48:1990;61-69.
95. Salsbury A.J., Burrage K., Hellmann K. Inhibition of metastatic spread by ICRF 159: selective deletion of a malignant characteristic. Br. Med. J. 4:1970;344-346.
96. Witiak D.T., Lee H.J., Goldman H.D., Zwilling B.S. Stereoselective effects of cis- and trans-cyclopropylbis(dioxopiperazines) related to ICRF-159 on metastases of a hamster lung adenocarcinoma. J. Med. Chem. 21:1978;1194-1197.
97. Hellmann K., Gilbert J., Evans M., Cassell P., Taylor R. Effect of razoxane on metastases from colorectal cancer. Clin. Exp. Metastasis. 5:1987;3-8.
98. Jensen P.B., Vindelov L., Roed H., Demant E.J.R., Sehested M., Skovsgaard T., Hansen H.H. In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL). Br. J. Cancer. 60:1989;838-844.
99. Cai J.C., Shu H.L., Tang C.F., Komatsu T., Matsuno T., Narita T., Yamaguchi S., Koide Y., Takase M. Synthesis and antitumor properties of N1-acyloxymethyl derivatives of bis(2,6-dioxopiperazines). Chem. Pharm. Bull. 37:1989;2976-2983.
100. Narita T., Yaguchi S., Komatsu T., Takase M., Hishino A., Inaba M., Tsukagoshi S. Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models. Cancer Chemother. Pharmacol. 26:1990;193-197.
101. Narita T., Koide Y., Yaguchi S., Kimura S., Izumisawa Y., Takase M., Inaba M., Tsukagoshi S. Antitumor activities and schedule dependence of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine). Cancer Chemother. Pharmacol. 28:1991;235-240.
102. Hellmann K., Field E.O. Effect of ICRF 159 on the mammalian cell cycle: significance for its use in cancer chemotherapy. J. Natl. Cancer Inst. 44:1970;539-543.
103. Furue H., Niitani H., Nakao I., Hoshino A., Hasegawa K., Tsukagoshi S., Fujita H. Phase I study of MST-16 (Sobuzoxane). Cancer and Chemother. (Japanese). 17:1990;1287-1294.
104. Ohno R., Yamada K., Hirano M., Shirakawa S., Tanaka M., Oguri T., Kodera Y., Mitomo Y., Ikeda Y., Yokomaku S., Kamiya O., Kobayashi M., Saito H., Kimura K. The Tokai Blood Cancer Study Group: phase II study: treatment of non-Hodgkin's lymphoma with an oral antitumor derivative of bis(2,6-dioxopiperazine). J. Natl. Cancer Inst. 84:1992;435-438.
105. Flannery E.P., Corder M.P., Sheehan W.W., Pajak T.F., Bateman J.R. Phase II study of ICRF-159 in non-Hodgkin's lymphomas. Cancer Treat. Rep. 62:1978;465-467.
106. Ohno R., Masaoka T., Shirakawa S., Sakamoto S., Hirano M., Hanada S., Yasunaga K., Yokomaku S., Mitomo Y., Nagi K., Yamada K., Furue H. for the MST-16 Study Group, Treatment of adult T-cell leukemia/lymphoma with MST-16, a new oral antitumor drug and a derivative of bis(2,6-dioxopiperazine). Cancer. 71:1993;2217-2221.
107. Jensen P.B., Sehested M. DNA topoisomerase II rescue by catalytic inhibitors: a new strategy to improve the antitumor selectivity of etoposide. Biochem. Pharmacol. 54:1997;755-759.
108. Kagami Y., Ariyoshi Y., Horiuchi A., Kanamaru A., Kano Y., Naoe T., Oguro M., Ohno R., Sampi K., Shirakawa S., Masaoka T., Furue H. for the MST-16 Study Group, Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. Int. J. Hematol. 64:1996;221-229.