Flavones and Xanthenones as Vascular-disrupting Agents

Vascular-Targeted Therapies in Oncology

Volumn , Issue , 2006, Pages 159-178

  Siim, Bronwyn G ^a   Baguley, Bruce C ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

Antivascular activity of FAA and DMXAA; Combination treatments; DMXAA and FAA vascular shutdown; DMXAA and photodynamic therapy; DMXAA and radioimmunotherapy; Flavones and xanthenones as vascular disrupting agents; Molecular target; Serotonin and DMXAA dose

Indexed keywords

EID: 33846869795     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/0470035439.ch9     Document Type: Chapter

References (89)

1. Aitken, R.A., Bibby, M.C., Cooper, P.A., Double, J.A., Laws, A.L., Ritchie, R.B. and Wilson, D.W. (2000). Synthesis and antitumor activity of new derivatives of flavone-8-acetic acid (FAA. Part 4: Variation of the basic structure. Arch Pharm (Weinheim) 333 (6), 181-188.
2. Atassi, G., Briet, P., Berthelon, J.J. and Collonges, F. (1985). Synthesis and antitumor activity of some 8-substituted 4-oxo-4H-1-benzopyrans. Eur J Medicinal Chem 5, 393-402.
3. Baguley, B.C. (2003). Antivascular therapy of cancer: DMXAA. Lancet Oncol 4, 141-148.
4. Baguley, B.C. and Ching, L.M. (1997). Immunomodulatory actions of xanthenone anticancer drugs. BioDrugs 8, 119-127.
5. Baguley, B.C., Cole, G., Thomsen, L.L. and Li, Z. (1993). Serotonin involvement in the antitumor and host effects of flavone-8-acetic acid and 5,6-dimethylxanthenone-4-acetic acid. Cancer Chemother Pharmacol 33 (1), 77-81.
6. Baguley, B.C., Wang, L.C., Ching, L.M., Paxton, J., Ding, Q. and Kestell, P. (2004). Enhancement of the action of the antivascular drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by co-administration of non-steroidal anti-inflammatory drugs. Eur J Cancer, Supplement 2, 44.
7. Baguley, B.C. and Wilson, W.R. (2002). Potential of DMXAA combination therapy for solid tumors. Exp Rev Anticancer Ther 2 (5), 593-603.
8. Baguley, B.C., Zhuang, L. and Kestell, P. (1997). Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6-dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: relation to vascular effects. Oncol Res 9 (2), 55-60.
9. Bellnier, D.A. (1991). Potentiation of photodynamic therapy in mice with recombinant human tumor necrosis factor-alpha. J Photochem Photobiol B 8 (2), 203-210.
10. Bellnier, D.A., Gollnick, S.O., Camacho, S.H., Greco, W.R. and Cheney, R.T. (2003). Treatment with the tumor necrosis factor-alpha-inducing drug 5,6-dimethylxanthenone-4-acetic acid enhances the antitumor activity of the photodynamic therapy of RIF-1 mouse tumors. Cancer Res 63 (22), 7584-7590.
11. Bowler, K. and Pearson, J.A. (1992). Long-term effects of flavone acetic acid on the growth of a rat tumor. Anticancer Res 12 (4), 1275-1279.
12. Brown, J.M. (2002). Tumor microenvironment and the response to anticancer therapy. Cancer Biol Ther 1 (5), 453-458.
13. Cao, Z., Baguley, B.C. and Ching, L.M. (2001). Interferon-inducible protein 10 induction and inhibition of angiogenesis in vivo by the antitumor agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Cancer Res 61 (4), 1517-1521.
14. Cao, Z., Joseph, W.R., Browne, W.L., Mountjoy, K.G., Palmer, B.D., Baguley, B.C. and Ching, L.M. (1999). Thalidomide increases both intra-tumoral tumor necrosis factor-alpha production and anti-tumor activity in response to 5,6-dimethylxanthenone-4-acetic acid. Br J Cancer 80, (5/6), 716-723.
15. Chaplin, D.J., Pettit, G.R., Parkins, C.S. and Hill, S.A. (1996). Antivascular approaches to solid tumor therapy: evaluation of tubulin binding agents. Br J Cancer 74 (Suppl. 27), S86-S88.
16. Ching, L.M. and Baguley, B.C. (1987). Induction of natural killer cell activity by the antitumor compound flavone acetic acid (NSC 347 512). Eur J Cancer Clin Oncol 23 (7), 1047-1050.
17. Ching, L.M., Cao, Z., Kieda, C., Zwain, S., Jameson, M.B. and Baguley, B.C. (2002). Induction of endothelial cell apoptosis by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid. Br J Cancer 86 (12), 1937-1942.
18. Ching, L.M., Goldsmith, D., Joseph, W.R., Korner, H., Sedgwick, J.D. and Baguley, B.C. (1999). Induction of intratumoral tumor necrosis factor (TNF) synthesis and hemorrhagic necrosis by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF knockout mice. Cancer Res 59 (14), 3304-3307.
19. Ching, L.M., Joseph, W.R., Crosier, K.E. and Baguley, B.C. (1994). Induction of tumor necrosis factor-alpha messenger RNA in human and murine cells by the flavone acetic acid analogue 5,6-dimethylxanthenone-4-acetic acid (NSC 640488). Cancer Res 54 (4), 870-872.
20. Ching, L.M., Xu, Z.F., Gummer, B.H., Palmer, B.D., Joseph, W.R. and Baguley, B.C. (1995). Effect of thalidomide on tumor necrosis factor production and anti-tumor activity induced by 5,6-dimethylxanthenone-4-acetic acid. Br J Cancer 72 (2), 339-343.
21. Ching, L.M., Zwain, S. and Baguley, B.C. (2004). Relationship between tumor endothelial cell apoptosis and tumor blood flow shutdown following treatment with the antivascular agent DMXAA in mice. Br J Cancer 90 (4), 906-910.
22. Cliffe, S., Taylor, M.L., Rutland, M., Baguley, B.C., Hill, R.P. and Wilson, W.R. (1994). Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid. Int J Radiat Oncol Biol Phys 29 (2), 373-377.
23. Cummings, J., Double, J.A., Bibby, M.C., Farmer, P., Evans, S., Kerr, D.J., Kaye, S.B. and Smyth, J.F. (1989). Characterization of the major metabolites of flavone acetic acid and comparison of their disposition in humans and mice. Cancer Res 49 (13), 3587-3593.
24. Edwards, H.S., Bremner, J.C. and Stratford, I.J. (1991). Induction of hypoxia in the KHT sarcoma by tumor necrosis factor and flavone acetic acid. Int J Radiat Biol 59, 419-32.
25. Edwards, H.S., Bremner, J.C. and Stratford, I.J. (1991). Induction of tumor hypoxia by FAA and TNF: interaction with bioreductive drugs. Int J Radiat Biol 60, 373-377.
26. Galbraith, S.M., Rustin, G.J., Lodge, M.A., Taylor, N.J., Stirling, J.J., Jameson, M., Thompson, P., Hough, D., Gumbrell, L. and Padhani, A.R. (2002). Effects of 5,6-dimethylxanthenone-4-acetic acid on human tumor microcirculation assessed by dynamic contrast-enhanced magnetic resonance imaging. J Clin Oncol 20 (18), 3826-3840.
27. Gobbi, S., Rampa, A., Bisi, A., Belluti, F., Piazzi, L., Valenti, P., Caputo, A., Zampiron, A. and Carrara, M. (2003). Synthesis and biological evaluation of 3-alkoxy analogues of flavone-8-acetic acid. J Medicinal Chem 46 (17), 3662-3669.
28. Gobbi, S., Rampa, A., Bisi, A., Belluti, F., Valenti, P., Caputo, A., Zampiron, A. and Carrara, M. (2002). Synthesis and antitumor activity of new derivatives of xanthen-9-one-4-acetic acid. J Medicinal Chem 45 (22), 4931-4939.
29. Havsteen, B. (1983). Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 32 (7), 1141-1148.
30. Hendrix, M.J., Seftor, E.A., Hess, A.R. and Seftor, R.E. (2003). Vasculogenic mimicry and tumor-cell plasticity: lessons from melanoma. Nature Rev Cancer 3 (6), 411-421.
31. Jameson, M.B., Thompson, P.I., Baguley, B.C., Evans, B.D., Harvey, V.J., Porter, D.J., McCrystal, M.R. and Kestell, P. (2000). Phase I pharmacokinetic and pharmacodynamic study of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Proc Am Soc Clin Oncol 19, 705.
32. Jameson, M.B., Thompson, P.I., Baguley, B.C., Evans, B.D., Harvey, V.J., Porter, D.J., McCrystal, M.R., Small, M., Bellenger, K., Gumbrell, L., Halbert, G.W. and Kestell, P. (2003). Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Br J Cancer 88 (12), 1844-1850.
33. Kelland, L.R. (2005). Targeting established tumor vasculature: a novel approach to cancer treatment. Curr Cancer Ther Rev 1, 1-9.
34. Kerr, D.J., Kaye, S.B., Cassidy, J., Bradley, C., Rankin, E.M., Adams, L., Setanoians, A., Young, T., Forrest, G., Soukop, M. and ••. (1987). Phase I and pharmacokinetic study of flavone acetic acid. Cancer Res 47 (24), 6776-6781.
35. Kestell, P., Paxton, J.W., Rewcastle, G.W., Dunlop, I. and Baguley, B.C. (1999). Plasma disposition, metabolism and excretion of the experimental antitumor agent 5,6-dimethylxanthenone-4-acetic acid in the mouse, rat and rabbit. Cancer Chemother Pharmacol 43 (4), 323-330.
36. Kestell, P., Zhao, L., Baguley, B.C., Palmer, B.D., Muller, G., Paxton, J.W. and Ching, L.M. (2000). Modulation of the pharmacokinetics of the antitumor agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in mice by thalidomide. Cancer Chemother Pharmacol 46 (2), 135-141.
37. Kestell, P., Zhao, L., Jameson, M.B., Stratford, M.R., Folkes, L.K. and Baguley, B.C. (2001). Measurement of plasma 5-hydroxyindoleacetic acid as a possible clinical surrogate marker for the action of antivascular agents. Clinica Chimica Acta 314 (1/2), 159-166.
38. Lash, C.J., Li, A.E., Rutland, M., Baguley, B.C., Zwi, L.J. and Wilson, W.R. (1998). Enhancement of the anti-tumor effects of the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by combination with 5-hydroxytryptamine and bioreductive drugs. Br J Cancer 78 (4), 439-445.
39. Mace, K.F., Hornung, R.L., Wiltrout, R.H. and Young, H.A. (1990). Correlation between in vivo induction of cytokine gene expression by flavone acetic acid and strict dose dependency and therapeutic efficacy against murine renal cancer. Cancer Res 50 (6), 1742-1747.
40. Moilanen, E., Thomsen, L.L., Miles, D.W., Happerfield, D.W., Knowles, R.G. and Moncada, S. (1998). Persistent induction of nitric oxide synthase in tumors from mice treated with the anti-tumor agent 5,6-dimethylxanthenone-4-acetic acid. Br J Cancer 77 (3), 426-433.
41. Murata, R., Overgaard, J. and Horsman, M.R. (2001). Potentiation of the anti-tumor effect of hyperthermia by combining with the vascular targeting agent 5,6-dimethylxanthenone-4-acetic acid. Int J Hyperthermia 17 (6), 508-519.
42. Murata, R., Siemann, D.W., Overgaard, J. and Horsman, M.R. (2001). Improved tumor response by combining radiation and the vascular-damaging drug 5,6-dimethylxanthenone-4-acetic acid. Radiat Res 156 (5), 503-509.
43. Nakanishi, M., Oe, T., Tsuruda, M., Matsuo, H., Sakuragi, S. and Maruyama, Y. (1975). Studies on the synthesis and anti-inflammatory activity of xanthenyl-and benzopyranopyridinylacetic acid derivatives. Studies on Anti-Inflammatory Agents. XXXI.
44. O'Dwyer, P.J., Shoemaker, D., Zaharko, D.S., Grieshaber, C., Plowman, J., Corbett, T., Valeriote, F., King, S.A., Cradock, J., Hoth, D.F. and Leyland-Jones, B. (1987). Flavone acetic acid (LM 975, NSC 347512) a novel antitumor agent. Cancer Chemother Pharmacol 19, 6-10.
45. Oreilly, S.M., Rustin, G.J., Farmer, K., Burke, M., Hill, S. and Denekamp, J. (1993). Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma: I. Clinical and vascular studies. Br J Cancer 67 (6), 1342-1345.
46. Olver, I.N., Webster, L.K., Bishop, J.F. and Stokes, K.H. (1992). A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. Cancer Chemother Pharmacol 29 (5), 354-360.
47. Parkins, C.S., Chadwick, J.A. and Chaplin, D.J. (1994). Enhancement of chlorambucil cytotoxicity by combination with flavone acetic acid in a murine tumor. Anticancer Res 14 (4A), 1603-1608.
48. Parkins, C.S., Denekamp, J. and Chaplin, D.J. (1993). Enhancement of mitomycin-C cytotoxicity by combination with flavone acetic acid in a murine tumor. Anticancer Res 13 (5A), 1437-1442.
49. Pedley, R.B., Begent, R.H., Boden, J.A., Boxer, G.M., Boden, R. and Keep, P.A. (1994). Enhancement of radioimmunotherapy by drugs modifying tumor blood flow in a colonic xenograft model. Int J Cancer 57 (6), 830-835.
50. Pedley, R.B., Boden, J.A., Boden, R., Boxer, G.M., Flynn, A.A., Keep, P.A. and Begent, R.H. (1996). Ablation of colorectal xenografts with combined radioimmunotherapy and tumor blood flow-modifying agents. Cancer Res 56 (14), 3293-3300.
51. Philpott, M., Baguley, B.C. and Ching, L.M. (1995). Induction of tumor necrosis factor-alpha by single and repeated doses of the antitumor agent 5,6-dimethylxanthenone-4-acetic acid. Cancer Chemother Pharmacol 36 (2), 143-148.
52. Philpott, M., Ching, L. and Baguley, B.C. (2001). The antitumor agent 5,6-dimethylxanthenone-4-acetic acid acts in vitro on human mononuclear cells as a co-stimulator with other inducers of tumor necrosis factor. Eur J Cancer 37 (15), 1930-1937.
53. Plowman, J., Narayanan, V.L., Dykes, D., Szarvasi, E., Briet, P., Yoder, O.C. and Paull, K. D. (1986). Flavone acetic acid: a novel agent with preclinical antitumor activity against colon adenocarcinoma 38 in mice. Cancer Treatment Reports 70 (5), 631-635.
54. Pruijn, F.B., van Daalen, M., Holford, N.H. and Wilson, W.R. (1997). Mechanisms of enhancement of the antitumor activity of melphalan by the tumor-blood-flow inhibitor 5,6-dimethylxanthenone-4-acetic acid. Cancer Chemother Pharmacol 39 (6), 541-546.
55. Rewcastle, G.W., Atwell, G.J., Baguley, B.C., Boyd, M., Thomsen, L.L., Zhuang, L. and Denny, W.A. (1991) Potential antitumor agents. 63. Structure-activity relationships for side-chain analogues of the colon 38 active agent 9-oxo-9H-xanthene-4-acetic acid. J Medicinal Chem 34 (9), 2864-2870.
56. Rewcastle, G.W., Atwell, G.J., Baguley, B.C., Calveley, S.B. and Denny, W.A. (1989). Potential antitumor agents. 58. Synthesis and structure-activity relationships of substituted xanthenone-4-acetic acids active against the colon 38 tumor in vivo. J Medicinal Chem 32 (4), 793-799.
57. Rewcastle, G.W., Atwell, G.J., Li, Z.A., Baguley, B.C. and Denny, W.A. (1991) Potential antitumor agents. 61. Structure-activity relationships for in vivo colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids. J Medicinal Chem 34 (1), 217-222.
58. Rewcastle, G.W., Atwell, G.J., Palmer, B.D., Boyd, P.D., Baguley, B.C. and Denny, W.A. (1991c). Potential antitumor agents. 62. Structure-activity relationships for tricyclic compounds related to the colon tumor active drug 9-oxo-9H-xanthene-4-acetic acid. J Medicinal Chem 34 (2), 491-496.
59. Rustin, G.J., Bradley, C., Galbraith, S., Stratford, M., Loadman, P., Waller, S., Bellenger, K., Gumbrell, L., Folkes, L. and Halbert, G. (2003). 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent: phase I clinical and pharmacokinetic study. Br J Cancer 88 (8), 1160-1167.
60. Siegenthaler, P., Kaye, S.B., Monfardini, S. and Renard, J. (1992). Phase II trial with flavone acetic acid (NSC.347512, LM975) in patients with non-small cell lung cancer. Ann Oncol 3 (2), 169-170.
61. Siemann, D.W., Mercer, E., Lepler, S. and Rojiani, A.M. (2002). Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy. Int J Cancer 99 (1), 1-6.
62. Siim, B.G., Laux, W.T., Rutland, M.D., Palmer, B.N. and Wilson, W.R. (2000). Scintigraphic imaging of the hypoxia marker (99m)technetium-labeled 2,2¢-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; Prognox): noninvasive detection of tumor response to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid. Cancer Res 60 (16), 4582-4588.
63. Siim, B.G., Lee, A.E., Shalal-Zwain, S., Pruijn, F.B., McKeage, M.J. and Wilson, W.R. (2003). Marked potentiation of the antitumor activity of chemotherapeutic drugs by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Cancer Chem Pharmacol 51 (1), 43-52.
64. Siim, B.G., Wong, E., Kelland, L. and Wilson, W.R. (2005). Antitumor activity of paclitaxel in combination with the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA; AS1404) against murine and human tumor models. submitted.
65. Slaviero, K.A., Clarke, S.J. and Rivory, L.P. (2003). Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol 4 (4), 224-232.
66. Sun, J.R. and Brown, J.M. (1989). Enhancement of the antitumor effect of flavone acetic acid by the bioreductive cytotoxic drug SR 4233 in a murine carcinoma. Cancer Res 49 (20), 5664-5670.
67. Thomsen, L.L., Ching, L.M., Zhuang, L., Gavin, J.B. and Baguley, B.C. (1991). Tumordependent increased plasma nitrate concentrations as an indication of the antitumor effect of flavone-8-acetic acid and analogues in mice. Cancer Res 51 (1), 77-81.
68. Tozer, G.M., Kanthou, C. and Baguley, B.C. (2005). Disrupting tumor blood vessels: combretastatins, DMXAA and other low molecular weight drugs. Nature Rev Cancer 5, 423-435.
69. Valenti, P., Bisi, A., Rampa, A., Belluti, F., Gobbi, S., Zampiron, A. and Carrara, M. (2000). Synthesis and biological activity of some rigid analogues of flavone-8-acetic acid. Bioorganic Medicinal Chem 8 (1), 239-246.
70. Veszelovsky, E., Holford, N.H., Thomsen, L.L., Knowles, R.G. and Baguley, B.C. (1995). Plasma nitrate clearance in mice: modeling of the systemic production of nitrate following the induction of nitric oxide synthesis. Cancer Chemother Pharmacol 36 (2), 155-159.
71. Vincent, P.W., Roberts, B.J., Elliot, W.L. and Leopold, W.R. (1997). Chemotherapy with DMXAA (5,6-dimethylxanthenone-4-acetic acid) in combination with CI-1010 (1Himidazole-1-ethanol,alpha-[[(2-bromoethyl)amino]methyl]-2-nitro-,mono hydrobromide (R isomer)) against advanced stage murine colon carcinoma 26. Oncol Rep 4, 143-147.
72. Wang, L.C., Reddy, C.B., Baguley, B.C., Kestell, P., Sutherland, R. and Ching, L.M. (2004). Induction of tumor necrosis factor and interferon-gamma in cultured murine splenocytes by the antivascular agent DMXAA and its metabolites. Biochem Pharmacol 67 (5), 937-945.
73. Wilson, W.R., Denny, W.A., Pullen, S.M., Thompson, K.M., Li, A.E., Patterson, L.H. and Lee, H.H. (1996). Tertiary amine N-oxides as bioreductive drugs: DACA N-oxide, nitracrine N-oxide and AQ4N. Br J Cancer Supplement 27, S43-S47.
74. Wilson, W.R., Li, A.E., Cowan, D.S. and Siim, B.G. (1998). Enhancement of tumor radiation response by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid. Int J Radiat Oncol Biol Phys 42 (4), 905-908.
75. Wilson, W.R. and Pruijn, F.B. (1995). Hypoxia-activated prodrugs as antitumor agents: strategies for maximizing tumor cell killing. Clin Exp Pharmacol Physiol 22 (11), 881-885.
76. Woon, S.T., Baguley, B.C., Palmer, B.D., Fraser, J.D. and Ching, L.M. (2002). Uptake of the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and activation of NF-kappaB in human tumor cell lines. Oncol Res 13 (2), 95-101.
77. Zhao, L., Ching, L.M., Kestell, P. and Baguley, B.C. (2002). The antitumor activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice. Br J Cancer 87 (4), 465-470.
78. Zhao, L., Ching, L.M., Kestell, P. and Baguley, B.C. (2003). Improvement of the antitumor activity of intraperitoneally and orally administered 5,6-dimethylxanthenone-4-acetic acid by optimal scheduling. Clin Cancer Res 9 (17), 6545-6550.
79. Zhao, L., Ching, L.M., Kestell, P., Kelland, L.R. and Baguley, B.C. (2005). Mechanisms of tumor vascular shut-down induced by 5,6-dimethylxanthenone-4-acetic acid (DMXAA); increased tumor vascular permeability. Int J Cancer, 116, 322-326.
80. Zhao, L., Edgar, S., Marshall, E., Kelland, L. and Baguley, B.C. (2004). Inhibition of vasculogenic mimicry in melanoma by the antivascular drug 5,6 dimethylxanthenone-4-acetic acid (DMXAA). Eur J Cancer Supplement 2, 47.
81. Zhao, L., Kestell, P., Philpott, M., Ching, L.M., Zhuang, L. and Baguley, B.C. (2001). Effects of the serotonin receptor antagonist cyproheptadine on the activity and pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Cancer Chemother Pharmacol 47 (6), 491-497.
82. Zhou, S., Kestell, P., Baguley, B.C. and Paxton, J.W. (2002) 5,6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier for cancer therapy. Invest New Drugs 20 (3), 281-295.
83. Zhou, S., Kestell, P., Tingle, M.D., Ching, L.M. and Paxton, J.W. (2001) A difference between the rat and mouse in the pharmacokinetic interaction of 5,6-dimethylxanthenone-4-acetic acid with thalidomide. Cancer Chemother Pharmacol 47 (6), 541-544.
84. Zhou, S., Kestell, P., Tingle, M.D. and Paxton, J.W. (2002) Gender differences in the metabolism and pharmacokinetics of the experimental anticancer agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Cancer Chemother Pharmacol 49 (2), 126-132.
85. Zhou, S., Paxton, J.W., Kestell, P., Tingle, M.D. and Ching, L.M. (2001). In vitro and in vivo kinetic interactions of the antitumor agent 5,6-dimethylxanthenone-4-acetic acid with thalidomide and diclofenac. Cancer Chemother Pharmacol 47 (4), 319-326.
86. Zhou, S.F., Paxton, J.W., Tingle, M.D., Kestell, P., Jameson, M.B., Thompson, P.I. and Baguley, B.C. (2001). Identification and reactivity of the major metabolite (beta-1-glucuronide) of the anti-tumor agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in humans. Xenobiotica 31 (5), 277-293.
87. Zhou, S.F., Tingle, M.D., Kestell, P. and Paxton, J.W. (2002). Species differences in the metabolism of the antitumor agent 5,6-dimethylxanthenone-4-acetic acid in vitro: implications for prediction of metabolic interactions in vivo. Xenobiotica 32 (2), 87-107.
88. Zwi, L.J., Baguley, B.C., Gavin, J.B. and Wilson, W.R. (1989). Blood flow failure as a major determinant in the antitumor action of flavone acetic acid. J Nat Cancer Inst 81 (13), 1005-1013.
89. Zwi, L.J., Baguley, B.C., Gavin, J.B. and Wilson, W.R. (1994). Correlation between immune and vascular activities of xanthenone acetic acid antitumor agents. Oncol Res 6 (2), 79-85.