Vascular Targeting Agents As Cancer Therapeutics

Clinical Cancer Research

Volumn 10, Issue 2, 2004, Pages 415-427

  Thorpe, Philip E ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5,6 DIMETHYLXANTHENONE 4 ACETIC ACID; ANGIOGENESIS INHIBITOR; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; AURISTATIN PE; CARBOPLATIN; CISPLATIN; COMBRETASTATIN A1 PHOSPHATE; COMBRETASTATIN A4 PHOSPHATE; CYCLOPHOSPHAMIDE; CYTOKINE; DOLASTATIN 10; DOXORUBICIN; FLAVONOID; FLUOROURACIL; GEMCITABINE; HYBRID PROTEIN; IMMUNOTOXIN; LIGAND; LIPOSOME; MELPHALAN; N ACETYLCOLCHINOL PHOSPHATE; PACLITAXEL; PRODRUG; SERINE 2 METHOXY 5 [2 (3,4,5 TRIMETHOXYPHENYL)VINYL]ANILIDE; UNINDEXED DRUG; VANDETANIB; VASCULAR TARGETING AGENT; ZINOSTATIN;

ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ANXIETY; ATAXIA; BLOOD VESSEL OCCLUSION; BONE MARROW SUPPRESSION; CANCER; CANCER PAIN; CANCER RADIOTHERAPY; CANCER THERAPY; CARDIOTOXICITY; CELL DEATH; CELL KILLING; CHEMOSENSITIVITY; CHEMOTHERAPY INDUCED EMESIS; CLINICAL TRIAL; CONSTIPATION; CONTRAST ENHANCEMENT; DOSE RESPONSE; DRUG CLASSIFICATION; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG MECHANISM; DRUG PENETRATION; DRUG POTENTIATION; DRUG RESISTANCE; DRUG SELECTIVITY; DYNAMIC CONTRAST ENHANCED MAGNETIC RESONANCE IMAGING; DYSPNEA; EDEMA; FATIGUE; GENE THERAPY; HEADACHE; HUMAN; HYPERKALEMIA; HYPERTHERMIC THERAPY; HYPOKALEMIA; HYPOTENSION; HYPOXEMIA; MOTOR NEUROPATHY; MULTIMODALITY CANCER THERAPY; NAUSEA; NEUROTOXICITY; NON INVASIVE MEASUREMENT; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; RADIOIMMUNOTHERAPY; RADIOSENSITIVITY; REVIEW; SIDE EFFECT; SLURRED SPEECH; SYNCOPE; TUMOR NECROSIS; TUMOR VASCULARIZATION; URINE INCONTINENCE; VISUAL IMPAIRMENT;

ANGIOGENESIS INHIBITORS; ANOXIA; ANTIBODIES, MONOCLONAL; CELL DIVISION; CLINICAL TRIALS; DIPHOSPHATES; GENE THERAPY; HUMANS; IMMUNOTOXINS; LIGANDS; MODELS, BIOLOGICAL; NECROSIS; NEOPLASMS; ORGANOPHOSPHORUS COMPOUNDS; PEPTIDES; RADIOIMMUNOTHERAPY; STILBENES; TIME FACTORS; UP-REGULATION; XANTHONES;

EID: 0842311621     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-0642-03     Document Type: Review

References (142)

1. Denekamp, J. Endothelial cell proliferation as a novel approach to targeting tumour therapy. Br. J. Cancer, 45: 136-139, 1982.
2. Denekamp, J. Review article: angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br. J. Radiol., 66: 181-196, 1993.
3. Burrows, F. J., Watanabe, Y., and Thorpe, P. E. A murine model for antibody-directed targeting of vascular endothelial cells in solid tumors. Cancer Res., 52: 5954-5962, 1992.
4. Burrows, F. J., and Thorpe, P. E. Vascular targeting-a new approach to the therapy of solid tumors. Pharmacol. Ther., 64: 155-174, 1994.
5. Burrows, F. J., and Thorpe, P. E. Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature. Proc. Natl. Acad. Sci. USA, 90: 8996-9000, 1993.
6. Hill, S. A., Lonergan, S. J., Denekamp, J., and Chaplin, D. J. Vinca alkaloids: anti-vascular effects in a murine tumour. Eur. J. Cancer, 9: 1320-1324, 1993.
7. Hill, S. A., Lonergan, S. J., Denekamp, J., and Chaplin, D. J. The effect of vinca alkaloids on tumour blood flow. Adv Exp. Med. Biol., 345: 417-422, 1994.
8. Siemann, D. W., and Rojiani, A. M. The novel vascular-targeting agent ZD6126 shows enhanced anti-tumour efficacy in large, bulky tumours. 14th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Abstract 119, 2002.
9. Landuyt, W., Verdoes, O., Darius, D. O., Drijkoningen, M., Nuyts, S., Theys, J., Stockx, L., Wynendaele, W., Fowler, J. F., Maleux, G., Van den Bogaert, W., Anne, J., van Oosterom, A., and Lambin, P. Vascular targeting of solid tumours: a major "inverse" volume-response relationship following combretastatin A-4 phosphate treatment of rat rhabdomyosarcomas. Eur. J. Cancer, 36: 1833-1843, 2000.
10. Fox, S. B., Gatter, K. C., Bicknell, R., Going, J. J., Stanton, P., Cooke, T. G., and Harris, A. L. Relationship of endothelial cell proliferation to tumor vascularity in human breast cancer. Cancer Res., 53: 4161-4163, 1993.
11. Wedge, S. R., Kendrew, J., Ogilvie, D. J., Hennequin, L. F., S. R. Brave, S. R., Ryan, A. J., Ashton, S. E., Calvete, J. A., and Blakey, D. C. Combination of the VEGF receptor tyrosine kinase inhibitor ZD6474 and vascular-targeting agent ZD6126 produces an enhanced anti-tumor response. Proc. Am. Assoc. Cancer Res., 43: 1081, 2002.
12. Siemann, D. W., Mercer, E., Lepler, S., and Rojiani, A. M. Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy. Int. J. Cancer, 99: 1-6, 2002.
13. Siim, B. G., Lee, A. E., Shalal-Zwain, S., Pruijn, F. B., McKeage, M. J., and Wilson, W. R. Marked potentiation of the antitumour activity of chemotherapeutic drugs by the antivascular agent 5, 6-dimethylxanthenone-4-acetic acid (DMXAA). Cancer Chemother Pharmacol, 51: 43-52, 2003.
14. Denekamp, J. Vascular attack as a therapeutic strategy for cancer. Cancer Metastisis Rev., 9: 267-282, 1990.
15. Denekamp, J., and Hobson, B. Endothelial-cell proliferation in experimental tumours. Br. J. Cancer, 46: 711-720, 1982.
16. Thorpe, P. E., Chaplin, D. J., and Blakey, D. C. The first international conference on vascular targeting: meeting overview. Cancer Res., 63: 1144-1147, 2003.
17. Nihei, Y., Suzuki, M., Okano, A., Tsuji, T., Akiyama, Y., Tsuruo, T., Saito, S., Hori, K., and Sato, Y. Evaluation of antivascular and antimitotic effects of tubulin binding agents in solid tumor therapy. Jpn. J. Cancer Res., 90: 1387-1395, 1999.
18. Baguley, B. C., Holdaway, K. M., Thomsen, L. L., Zhuang, L., and Zwi, L. J. Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism. Eur. J. Cancer, 27: 482-487, 1991.
19. Dark, G. G., Hill, S. A., Prise, V. E., Tozer, G. M., Pettit, G. R., and Chaplin, D. J. Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res., 57: 1829-1834, 1997.
20. Pettit, G. R., Singh, S. B., Hamel, E., Lin, C. M., Alberts, D. S., and Garcia-Kendall, D. Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia, 45: 209-211, 1989.
21. Pettit, G. R., Temple, C., Narayanan, V. L., Varma, R., Simpson, M. J., Boyd, M. R., Rener, G. A., and Bansal, N. Antineoplastic agents 322, synthesis of combretastatin A-4 prodrugs. Anticancer Drug Des., 10: 299-309, 1995.
22. Chaplin, D. J., and Hill, S. A. The development of combretastatin A4 phosphate as a vascular targeting agent. Int. J. Radiat. Oncol. Biol. Phys., 54: 1491-1496, 2002.
23. Beauregard, D. A., Thelwall, P. E., Chaplin, D. J., Hill, S. A., Adams, G. E., and Brindle, K. M. Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status. Br. J. Cancer, 77: 1761-1767, 1998.
24. Horsman, M. R., Ehrnrooth, E., Ladekarl, M., and Overgaard, J. The effect of combretastatin A-4 disodium phosphate in a C3H mouse mammary carcinoma and a variety of murine spontaneous tumors. Int. J. Radiat. Oncol. Biol. Phys., 42: 895-898, 1998.
25. Malcontenti-Wilson, C., Muralidharan, V., Skinner, S., Christophi, C., Sherris, D., and O'Brien, P. E. Combretastatin A4 prodrug study of effect on the growth and the microvasculature of colorectal liver metastases in a murine model. Clin. Cancer Res., 7: 1052-1060, 2001.
26. Tozer, G. M., Prise, V. E., Wilson, J., Cemazar, M., Shan, S., Dewhirst, M. W., Barber, P. R., Vojnovic, B., and Chaplin, D. J. Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability. Cancer Res., 61 6413-6422, 2001.
27. Tozer, G. M., Prise, V. E., Wilson, J., Locke, R. J., Vojnovic, B., Stratford, M. R., Dennis, M. F., and Chaplin, D. J. Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues. Cancer Res., 59: 1626-1634, 1999.
28. Grosios, K., Holwell, S. E., McGown, A. T., Pettit, G. R., and Bibby, M. C. In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug. Br. J. Cancer, 81: 1318-1327, 1999.
29. Galbraith, S. M., Chaplin, D. J., Lee, F., Stratford, M. R., Locke, R. J., Vojnovic, B., and Tozer, G. M. Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro and relationship to tumour vascular targeting activity in vivo. Anticancer Res., 21: 93-102, 2001.
30. Kanthou, C., and Tozer, G. M. The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells. Blood, 99: 2060-2069, 2002.
31. Davis, P. D., Tozer, G. M., Naylor, M. A., Thomson, P., Lewis, G., and Hill, S. A. Enhancement of vascular targeting by inhibitors of nitric oxide synthase. Int. J. Radiat. Oncol. Biol. Phys., 54: 1532-1536, 2002.
32. Li, L., Rojiani, A., and Siemann, D. W. Targeting the tumor vasculature with combretastatin A-4 disodium phosphate: effects on radiation therapy. Int. J. Radiat. Oncol. Biol. Phys., 42: 899-903, 1998.
33. Chaplin, D. J., Pettit, G. R., and Hill, S. A. Anti-vascular approaches to solid tumour therapy: evaluation of combretastatin A4 phosphate. Anticancer Res., 19: 189-195, 1999.
34. Landuyt, W., Ahmed, B., Nuyts, S., Theys, J., Op de Beeck, M., Rijnders, A., Anne, J., van Oosterom, A., van den Bogaert, W., and Lambin, P. In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment. Int. J. Radiat. Oncol. Biol. Phys., 49: 443-450, 2001.
35. Murata, R., Siemann, D. W., Overgaard, J., and Horsman, M. R. Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumors. Radiother. Oncol., 60: 155-161, 2001.
36. Murata, R., Siemann, D. W., Overgaard, J., and Horsman, M. R. Improved tumor response by combining radiation and the vascular-damaging drug 5, 6-dimethylxanthenone-4-acetic acid. Radiat. Res., 156: 503-509, 2001.
37. Murata, R., Overgaard, J., and Horsman, M. R. Potentiation of the anti-tumour effect of hyperthermia by combining with the vascular targeting agent 5, 6-dimethylxanthenone-4-acetic acid. Int. J. Hyperthermia, 17: 508-519, 2001.
38. Eikesdal, H. P., Bjerkvig, R., Raleigh, J. A., Mella, O., and Dahl, O. Tumor vasculature is targeted by the combination of combretastatin A-4 and hyperthermia. Radiother. Oncol., 61: 313-320, 2001.
39. Eikesdal, H. P., Bjerkvig, R., Mella, O., and Dahl, O. Combretastatin A-4 and hyperthermia;a potent combination for the treatment of solid tumors. Radiother. Oncol., 60: 147-154, 2001.
40. Grosios, K., Loadman, P. M., Swaine, D. J., Pettit, G. R., and Bibby, M. C. Combination chemotherapy with combretastatin A-4 phosphate and 5-fluorouracil in an experimental murine colon adenocarcinoma. Anticancer Res., 20: 229-233, 2000.
41. Horsman, M. R., Murata, R., Breidahl, T., Nielsen, F. U., Maxwell, R. J., Stodkiled-Jorgensen, H., and Overgaard, J. Combretastatins novel vascular targeting drugs for improving anti-cancer therapy. Combretastatins and conventional therapy. Adv Exp. Med. Biol., 476: 311-323, 2000.
42. Nelkin, B. D., and Ball, D. W. Combretastatin A-4 and doxorubicin combination treatment is effective in a preclinical model of human medullary thyroid carcinoma. Oncol. Rep., 8: 157-160, 2001.
43. Pedley, R. B., Hill, S. A., Boxer, G. M., Flynn, A. A., Boden, R., Watson, R., Dearling, J., Chaplin, D. J., and Begent, R. H. Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin a-4 3-O-phosphate. Cancer Res., 61: 4716-4722, 2001.
44. Pedley, R. B., El-Emir, E., Flynn, A. A., Boxer, G. M., Dearling, J., Raleigh, J. A., Hill, S. A., Stuart, S., Motha, R., and Begent, R. H. Synergy between vascular targeting agents and antibody-directed therapy. Int. J. Radiat. Oncol. Biol. Phys., 54: 1524-1531, 2002.
45. Pettit, G. R., and Lippert, J. W. Antineoplastic agents 429. Syntheses of the combretastatin A-1 and combretastatin B-1 prodrugs. Anticancer Drug Des., 15: 203-216, 2000.
46. Holwell, S. E., Cooper, P. A., Grosios, K., Lippert, J. W., Pettit, G. R., Shnyder, S. D., and Bibby, M. C. Combretastatin A-1 phosphate a novel tubulin-binding agent with in vivo anti vascular effects in experimental tumours. Anticancer Res., 22: 707-711, 2002.
47. Hill, S. A., Toze, G. M., Pettit, G. R., and Chaplin, D. J. Preclinical evaluation of the antitumour activity of the novel vascular targeting agent Oxi 4503. Anticancer Res., 22: 1453-1458, 2002.
48. Nihei, Y., Suga, Y., Morinaga, Y., Ohishi, K., Okano, A., Ohsumi, K., Hatanaka, T., Nakagawa, R., Tsuji, T., Akiyama, Y., Saito, S., Hori, K., Sato, Y., and Tsuruo, T. A novel combretastatin A-4 derivative, AC-7700, shows marked antitumor activity against advanced solid tumors and orthotopically transplanted tumors. Jpn. J. Cancer Res., 90: 1016-1025, 1999.
49. Ohno, T., Kawano, K., Sasaki, A., Aramaki, M., Tahara, K., Etoh, T., and Kitano, S. Antitumor and antivascular effects of AC-7700, a combretastatin A-4 derivative, against rat liver cancer. Int. J. Clin. Oncol., 7: 171-176, 2002.
50. Hori, K., Saito, S., and Kubota, K. A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs. Br. J. Cancer, 86: 1604-1614, 2002.
51. Hori, K., Saito, S., Sato, Y., and Kubota, K. Stoppage of blood flow in 3-methylcholanthrene-induced autochthonous primary tumor due to a novel combretastatin A-4 derivative, AC7700, and its antitumor effect. Med. Sci. Monit., 7: 26-33, 2001.
52. Ohsumi, K., Hatanaka, T., Nakagawa, R., Fukuda, Y., Morinaga, Y., Suga, Y., Nihei, Y., Ohishi, K., Akiyama, Y., and Tsuji, T. Synthesis and antitumor activities of amino acid prodrugs of amino-combretastatins. Anticancer Drug Des., 14: 539-548, 1999.
53. Hori, K., Saito, S., Nihei, Y., Suzuki, M., and Sato, Y. Antitumor effects due to irreversible stoppage of tumor tissue blood flow: evaluation of a novel combretastatin A-4 derivative, AC7700. Jpn. J. Cancer Res., 90: 1026-1038, 1999.
54. Chaplin, D. J., Pettit, G. R., Parkins, C. S., and Hill, S. A. Antivascular approaches to solid tumour therapy: evaluation of tubulin binding agents. Br. J. Cancer, 27 (Suppl.): S86-S88, 1996.
55. Natsume, T., Koh, Y., Kobayashi, M., Fukumoto, H., Takahashi, F., Nakamura, T., Ohe, Y., Saijo, N., and Nishio, K. Enhanced antitumor activities of TZT-1027 against TNF-α or IL-6 secreting Lewis lung carcinoma in vivo. Cancer Chemother. Pharmacol., 49: 35-47, 2002.
56. Kobayashi, M., Natsume, T., Tamaoki, S., Watanabe, J., Asano, H., Mikami, T., Miyasaka, K., Miyazaki, K., Gondo, M., Sakakibara, K., and Tsukagoshi, S. Antitumor activity of TZT-1027, a novel dolastatin 10 derivative. Jpn. J. Cancer Res., 88: 316-327, 1997.
57. Otani, M., Natsume, T., Watanabe, J. I., Kobayashi, M., Murakoshi, M., Mikami, T., and Nakayama, T. TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor cell death. Jpn. J. Cancer Res., 91: 837-844, 2000.
58. Blakey, D. C., Ashton, S. E., Westwood, F. R., Walker, M., and Ryan, A. J. ZD6126: a novel small molecule vascular targeting agent. Int. J. Radiat. Oncol. Biol. Phys., 54: 1497-1502, 2002.
59. Blakey, D. C., Douglas, S., Revill, M., and Ashton, S. E. The novel vascular targeting agent ZD6126 causes rapid morphology changes leading to endothelial cell detachment at non-cytotoxic concentrations. Clin. Exp. Metastasis, 17: 776, 1999.
60. Blakey, D. C., Westwood, F. R., Walker, M., Hughes, G. D., Davis, P. D., Ashton, S. E., and Ryan, A. J. Antitumor activity of the novel vascular targeting agent ZD6126 in a panel of tumor models. Clin. Cancer Res., 8: 1974-1983, 2002.
61. Goertz, D. E., Yu, J. L., Kerbel, R. S., Burns, P. N., and Foster, F. S. High-frequency Doppler ultrasound monitors the effects of antivascular therapy on tumor blood flow. Cancer Res., 62: 6371-6375, 2002.
62. Davis, P. D., Dougherty, G. J., Blakey, D. C., Galbraith, S. M., Tozer, G. M., Holder, A. L., Naylor, M. A., Nolan, J., Stratford, M. R., Chaplin, D. J., and Hill, S. A. ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature. Cancer Res., 62: 7247-7253, 2002.
63. Davis, P. D., Hill, S. A., Galbraith, S. M., Chaplin, D. J., Naylor, M. A., Nolan, J., and Dougherty, G. J. ZD6126: a new agent causing selective damage of tumor vasculature. Proc. Am. Assoc. Cancer Res., 41: 2085, 2000.
64. Siemann, D. W., and Rojiani, A. M. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126. Int. J. Radiat. Oncol. Biol. Phys., 54: 1512-1517, 2002.
65. Goto, H., Yano, S., Zhang, H., Matsumori, Y., Ogawa, H., Blakey, D. C., and Sone, S. Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice. Cancer Res., 62: 3711-3715, 2002.
66. Bruns, C. J., Köhl, G., Kleespies, A., Friedrich, D., Ryan, A., Barge, A., and Jauch, K-W. Vascular-targeting activity of ZD6126 against primary pancreatic tumour growth and lymph node metastasis following orthotopic tumour cell injection in a nude mouse model. 14th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Abstract 118, 2002.
67. Siemann, D. W., and Rojiani, A. M. Enhancement of radiation therapy by the novel vascular targeting agent ZD6126. Int. J. Radiat. Oncol. Biol. Phys., 53: 164-171, 2002.
68. Arezzo, J., Zotova, E., and Horner, S. ZD6126 administration is not associated with de novo neurotoxicity or exacerbation of paclitaxel neurotoxicity in the rat: Electrophysiological measures. Proc. Am. Assoc. Cancer Res., 43: 155, 2002.
69. Horner, S. A., Gould, S., Noakes, J. P., Allen, S. L., Zotova, E., and Arezzo, J. ZD6126 showed no evidence of peripheral neuropathy or neurotoxicity following chronic intravenous dosing in the rat. Proc. Am. Assoc. Cancer Res., 43: 269, 2002.
70. Kerr, D. J., Maughan, T., Newlands, E., Rustin, G., Bleehen, N. M., Lewis, C., and Kaye, S. B. Phase II trials of flavone acetic acid in advanced malignant melanoma and colorectal carcinoma. Br. J. Cancer, 60: 104-106, 1989.
71. Philpott, M., Baguley, B. C., and Ching, L. M. Induction of tumour necrosis factor-α by single and repeated doses of the antitumour agent 5, 6-dimethylxanthenone-4-acetic acid. Cancer Chemother. Pharmacol., 36: 143-148, 1995.
72. Mahadevan, V., Malik, S. T., Meager, A., Fiers, W., Lewis, G. P., and Hart, I. R. Role of tumor necrosis factor in flavone acetic acid-induced tumor vasculature shutdown. Cancer Res., 50: 5537-5542, 1990.
73. Rewcastle, G. W., Atwell, G. J., Li, Z. A., Baguley, B. C., and Denny, W. A. Potential antitumor agents. 61. Structure-activity relationships for in vivo colon 38 activity among disubstituted 9-oxo-9H-xanthene-4-acetic acids. J. Med. Chem., 34: 217-222, 1991.
74. Wilson, W. R., Li, A. E., Cowan, D. S., and Siim, B. G. Enhancement of tumor radiation response by the antivascular agent 5, 6-dimethylxanthenone-4-acetic acid. Int. J. Radiat. Oncol. Biol. Phys., 42: 905-908, 1998.
75. Murata, R., Overgaard, J., and Horsman, M. R. Comparative effects of combretastatin A-4 disodium phosphate and 5, 6-dimethylxanthenone-4-acetic acid on blood perfusion in a murine tumour and normal tissues. Int. J. Radiat. Biol., 77: 195-204, 2001.
76. Ching, L. M., Cao, Z., Kieda, C., Zwain, S., Jameson, M. B., and Baguley, B. C. Induction of endothelial cell apoptosis by the antivascular agent 5, 6-Dimethylxanthenone-4-acetic acid. Br. J. Cancer, 86: 1937-1942, 2002.
77. Zhao, L., Ching, L. M., Kestell, P., and Baguley, B. C. The antitumour activity of 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice. Br. J. Cancer, 87: 465-470, 2002.
78. Baguley, B. C. Antivascular therapy of cancer: DMXAA. Lancet Oncol., 4: 141-148, 2003.
79. Philpott, M., Ching, L. M., and Baguley, B. C. The antitumour agent 5, 6-dimethylxanthenone-4-acetic acid acts in vitro on human mononuclear cells as a co-stimulator with other inducers of tumour necrosis factor. Eur. J. Cancer, 37: 1930-1937, 2001.
80. Cao, Z., Baguley, B. C., and Ching, L. M. 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: 1517-1521, 2001.
81. Baguley, B. C., Zhuang, L., and Kestell, P. 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: 55-60, 1997.
82. Zhou, S., Kestell, P., Baguley, B. C., and Paxton, J. W. 5, 6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier for cancer therapy. Investig. New Drugs, 20: 281-295, 2002.
83. Pruijn, F. B. van Daalen, M., Holford, N. H., and Wilson, W. R. Mechanisms of enhancement of the antitumour activity of melphalan by the tumour-blood-flow inhibitor 5, 6-dimethylxanthenone-4-acetic acid. Cancer Chemother. Pharmacol., 39: 541-546, 1997.
84. Pedley, R. B., Boden, J. A., Boden, R., Boxer, G. M., Flynn, A. A., Keep, P. A., and Begent, R. H. Ablation of colorectal xenografts with combined radioimmunotherapy and tumor blood flow-modifying agents. Cancer Res., 56: 3293-3300, 1996.
85. Kanwar, J. R., Kanwar, R. K., Pandey, S., Ching, L. M., and Krissansen, G. W. Vascular attack by 5, 6-dimethylxanthenone-4-acetic acid combined with B7.1 (CD80)-mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci. Cancer Res., 61: 1948-1956, 2001.
86. Horsman, M. R., and Murata, R. Combination of vascular targeting agents with thermal or radiation therapy. Int. J. Radiat. Oncol. Biol. Phys., 54: 1518-1523, 2002.
87. Burrows, F. J., Derbyshire, E. J., Tazzari, P. L., Amlot, P. Gazdar, A. F., King, S. W., Letarte, M., Vitetta, E. S., and Thorpe, P. E. Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy. Clin. Cancer Res., 1: 1623-1634, 1995.
88. Huang, X., Molema, G., King, S., Watkins, L., Edgington, T. S., and Thorpe, P. E. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science (Wash. DC), 275: 547-550, 1997.
89. Ran, S., Gao, B., Duffy, S., Watkins, L., Rote, N., and Thorpe, P. E. Infarction of solid Hodgkin's tumors in mice by antibody-directed targeting of tissue factor to tumor vasculature. Cancer Res., 58: 4646-4653, 1998.
90. Nilsson, F., Kosmehl, H., Zardi, L., and Neri, D. Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. Cancer Res., 61: 711-716, 2001.
91. Liu, C., Huang, H., Donate, F., Dickinson, C., Santucci, R., El-Sheikh, A., Vessella, R., and Edgington, T. S. Prostate-specific membrane antigen directed selective thrombotic infarction of tumors. Cancer Res., 62: 5470-5475, 2002.
92. Arora, N., Masood, R., Zheng, T., Cai, J., Smith, D. L., and Gill, P. S. Vascular endothelial growth factor chimeric toxin is highly active against endothelial cells. Cancer Res., 59: 183-188, 1999.
93. Ramakrishnan, S., Olson, T. A., Bautch, V. L., and Mohanraj, D. Vascular endothelial growth factor-toxin conjugate specifically inhibits KDR/flk-1-positive endothelial cell proliferation in vitro and angiogenesis in vivo. Cancer Res., 56: 1324-1330, 1996.
94. Veenendaal, L. M., Jin, H., Ran, S., Cheung, L., Navone, N., Marks, J. W., Waltenberger, J., Thorpe, P., and Rosenblum, M. G. In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors. Proc. Natl. Acad. Sci. USA, 99: 7866-7871, 2002.
95. Matsuno, F., Haruta, Y., Kondo, M., Tsai, H., Barcos, M., and Seon, B. K. Induction of lasting complete regression of preformed distinct solid tumors by targeting the tumor vasculature using two new antiendoglin monoclonal antibodies. Clin. Cancer Res., 5: 371-382, 1999.
96. Tsunoda, S., Ohizumi, I., Matsui, J., Koizumi, K. Wakai, Y., Makimoto, H., Tsutsumi, Y., Utoguchi, N., Taniguchi, K., Saito, H., Harada, N., Ohsugi, Y., and Mayumi, T. Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy. Br. J. Cancer, 81: 1155-1161, 1999.
97. Halin, C., Rondini, S., Nilsson, F., Berndt, A., Kosmehl, H., Zardi, L., and Neri, D. Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature. Nat. Biotechnol., 20: 264-269, 2002.
98. Carnemolla, B., Borsi, L., Balza, E., Castellani, P., Meazza, R., Berndt, A., Ferrini, S., Kosmehl, H., Neri, D., and Zardi, L. Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix. Blood, 99: 1659-1665, 2002.
99. Marty, C., Odermatt, B., Schott, H., Neri, D., Ballmer-Hofer, K., Klemenz, R., and Schwendener, R. A. Cytotoxic targeting of F9 terato-carcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes. Br. J. Cancer, 87: 106-112, 2002.
100. Masood, R., Gordon, E. M., Whitley, M. D., Wu, B. W., Cannon, P., Evans, L., Anderson, W. F., Gill, P., and Hall, F. L. Retroviral vectors bearing IgG-binding motifs for antibody-mediated targeting of vascular endothelial growth factor receptors. Int. J. Mol. Med., 8: 335-343, 2001.
101. Savontaus, M. J., Sauter, B. V., Huang, T. G., and Woo, S. L. Transcriptional targeting of conditionally replicating adenovirus to dividing endothelial cells. Gene Ther., 9: 972-979, 2002.
102. Jin, N., Chen, W., Blazar, B. R., Ramakrishnan, S., and Vallera, D. A. Gene therapy of murine solid tumors with T cells transduced with a retroviral vascular endothelial growth factor-immunotoxin target gene. Hum. Gene Ther., 13: 497-508, 2002.
103. Oh, P., Czarny, M., Smith, T., Durr, E., Testa, J. E., and Schnitzer, J. E. Tumor vascular proteomics: Immunotargeting of breast cancer via tumor-induced caveolar proteins. Proc. Am. Assoc. Cancer Res., 43: 844, 2002.
104. Carson-Walter, E. B., Watkins, D. N., Nanda, A., Vogelstein, B., Kinzler, K. W., and St. Croix, B. Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res., 61: 6649-6655, 2001.
105. St Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K. E., Montgomery, E., Lal, A., Riggins, G. J., Lengauer, C., Vogelstein, B., and Kinzler, K. W. Genes expressed in human tumor endothelium. Science (Wash. DC), 289: 1197-1202, 2000.
106. Trepel, M., Arap, W., and Pasqualini, R. In vivo phage display and vascular heterogeneity: implications for targeted medicine. Curr. Opin. Chem. Biol., 6: 399-404, 2002.
107. Arap, W., Kolonin, M. G., Trepel, M., Lahdenranta, J., Cardo-Vila, M., Giordano, R. J., Mintz, P. J., Ardelt, P. U., Yao, V. J., Vidal, C. I., Chen, L., Flamm, A., Valtanen, H., Weavind, L. M., Hicks, M. E., Pollock, R. E., Botz, G. H., Bucana, C. D., Koivunen, E., Cahill, D., Troncoso, P., Baggerly, K. A., Pentz, R. D., Do, K. A., Logothetis, C. J., and Pasqualini, R. Steps toward mapping the human vasculature by phage display. Nat. Med., 8: 121-127, 2002.
108. Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med., 315: 1650-1659, 1986.
109. Ran, S., Downes, A., and Thorpe, P. E. Increased exposure of anionic phospholipids on the surface of tumor blood vessels. Cancer Res., 62: 6132-6140, 2002.
110. Ran, S., and Thorpe, P. E. Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy. Int. J. Radiat. Oncol. Biol. Phys., 54: 1479-1484, 2002.
111. Kerbel, R. S., Yu, J., Tran, J., Man, S., Viloria-Petit, A., Klement, G., Coomber, B. L., and Rak, J. Possible mechanisms of acquired resistance to anti-angiogenic drugs: implications for the use of combination therapy approaches. Cancer Metastisis Rev., 20: 79-86, 2001.
112. Ran, S., and Thorpe, P. E. Antibodies to anionic phospholipids as vascular targeting agents for cancer treatment. Abstract 12 presented at Angiogenesis 2 Meeting, Paris, June 19-20, 2003.
113. Kennel, S. J., Lankford, T., Davern, S., Foote, L., Taniguchi, K., Ohizumi, I., Tsutsumi, Y., Nakagawa, S., Mayumi, T., and Mirzadeh, S. Therapy of rat tracheal carcinoma IC-12 in SCID mice: vascular targeting with [213Bi]-MAb TES-23. Eur. J. Cancer, 38: 1278-1287, 2002.
114. Anderson, H., Price, P., Blomley, M., Leach, M. O., and Workman, P. Measuring changes in human tumour vasculature in response to therapy using functional imaging techniques. Br. J. Cancer, 85: 1085-1093, 2001.
115. Robinson, S. P., McIntyre, D. J., Checkley, D., Tessier, J. J., Howe, F. A., Griffiths, J. R., Ashton, S. E., Ryan, A. J., Blakey, D. C., and Waterton, J. C. Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging. Br. J. Cancer, 88: 1592-1597, 2003.
116. Evelhoch, J. L., He, Z., Polin, L., Corbett, T. H., Blakey, D. C., and Waterton, J. C. MRI evaluation of the effects of ZD6126 on tumor vasculature. Proc. Am. Assoc. Cancer Res., 42: 580, 2001.
117. Beauregard, D. A., Hill, S. A., Chaplin, D. J., and Brindle, K. M. The susceptibility of tumors to the antivascular drug combretastatin A4 phosphate correlates with vascular permeability. Cancer Res., 61: 6811-6815, 2001.
118. Galbraith, S. M., Lodge, M. A., Taylor, N. J., Rustin, G. J., Bentzen, S., Stirling, J. J., and Padhani, A. R. Reproducibility of dynamic contrast-enhanced MRI in human muscle and tumours: comparison of quantitative and semi-quantitative analysis. NMR Biomed., 15: 132-142, 2002.
119. Evelhoch, J., LoRusso, P., Latif, Z., Morton, P., Wolf, W., Mc-Kinley, M., Waterton, J. C., and Barge, A. Reproducibility of dynamic contrast-enhanced (DCE-MRI) assessment of tumor vascularity. Proc. Am. Soc. Clin. Oncol., 20: Abstract 399, 2001.
120. DelProposto, Z., LoRusso, P., Latif, Z., Morton, P., Wheeler, C., Barge, A., and Evelhoch, J. MRI evaluation of the effects of the vascular-targeting agent ZD6126 on tumor vasculature, Proc. Am. Soc. Clin. Oncol., 21: Abstract 440, 2002.
121. Galbraith, S. M., Maxwell, R. J., Lodge, M. A., Tozer, G. M., Wilson, J., Taylor, N. J., Stirling, J. J., Sena, L., Padhani, A. R., and Rustin, G. J. Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging. J. Clin. Oncol., 2003.
122. 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. Effects of 5, 6-dimethylxanthenone-4-acetic acid on human tumor microcirculation assessed by dynamic contrast-enhanced magnetic resonance imaging. J. Clin. Oncol., 20: 3826-3840, 2002.
123. Dowlati, A., Robertson, K., Cooney, M., Petros, W. P., Strafford, M., Jesberger, J., Rafie, N., Overmoyer, B., Makkar, V., Stambler, B., Taylor, A., Waas, J., Lewin, J. S., McCrae, K. R., and Remick, S. C. A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin a-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer. Cancer Res., 62: 3408-3416, 2002.
124. Neeman, M., Dafni, H., Bukhari, O., Braun, R. D., and Dewhirst, M. W. In vivo BOLD contrast MRI mapping of subcutaneous vascular function and maturation: validation by intravital microscopy. Magn. Reson. Med., 45: 887-898, 2001.
125. Robinson, S. P., Howe, F. A., Rodrigues, L. M., Stubbs, M., and Griffiths, J. R. Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow. Semin. Radiat. Oncol., 8: 197-207, 1998.
126. 2 mapping. J. Biomed. Opt., 8: 53-62, 2003.
127. Kragh, M., Quistorff, B., Horsman, M. R., and Kristjansen, P. E. Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy. Neoplasia, 4: 263-267, 2002.
128. Beauregard, D. A., Pedley, R. B., Hill, S. A., and Brindle, K. M. Differential sensitivity of two adenocarcinoma xenografts to the antivascular drugs combretastatin A4 phosphate and 5, 6-dimethylxanthenone-4-acetic acid, assessed using MRI and MRS. NMR Biomed., 15: 99-105, 2002.
129. Maxwell, R. J., Nielsen, F. U., Breidahl, T., Stodkilde-Jorgensen, H., and Horsman, M. R. Effects of combretastatin on murine tumours monitored by 31P MRS, 1H MRS and 1H MRI. Int. J. Radiat. Oncol. Biol. Phys., 42: 891-894, 1998.
130. Thomas, J. P., Arzoomanian, R. Z., Alberti, D., Marnocha, R., Lee, F., Friedl, A., Tutsch, K., Dresen, A., Geiger, P., Pluda, J., Fogler, W., Schiller, J. H., and Wilding, G. Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin in patients with advanced solid tumors. J. Clin. Oncol., 21: 223-231, 2003.
131. Zhao, S., Moore, J. V., Waller, M. L., McGown, A. T., Hadfield, J. A., Pettit, G. R., and Hastings, D. L. Positron emission tomography of murine liver metastases and the effects of treatment by combretastatin A-4. Eur. J. Nucl. Med., 26: 231-238, 1999.
132. Anderson, H., Yap, J., and Price, P. Measurement of tumour and normal tissue (NT) perfusion by positron emission tomography (PET) in the evaluation of antivascular therapy: results in the Phase I study of combretastatin A4 phosphate (CA4P). Proc. Am. Soc. Clin. Oncol., 19: 695, 2000.
133. Anderson, H. L., Yap, J. T., Miller, M. P., Robbins, A., Jones, T., and Price, P. M. Assessment of pharmacodynamic vascular response in a Phase I trial of combretastatin A4 phosphate. J. Clin. Oncol., 21: 2823-2830, 2003.
134. Baguley, B. C., and Ching, L. M. DMXAA: an antivascular agent with multiple host responses. Int. J. Radiat. Oncol. Biol. Phys., 54: 1503-1511, 2002.
135. Kestell, P., Zhao, L., Jameson, M. B., Stratford, M. R., Folkes, L. K., and Baguley, B. C. Measurement of plasma 5-hydroxyindoleacetic acid as a possible clinical surrogate marker for the action of antivascular agents. Clin. Chim. Acta, 314: 159-166, 2001.
136. Radema, S. A., Beerepoot, L. V., Witteveen, P. O., Gebbink, M. F., Wheeler, C., and Voest, E. E. Clinical evaluation of the novel vascular-targeting agent, ZD6126: assessment of toxicity and surrogate markers of vascular damage. Proc. Am. Soc. Clin. Oncol., 21: 439, 2002.
137. Rustin, G. J., Galbraith, S. M., Anderson, H., Stratford, M., Folkes, L. K., Sena, L., Gumbrell, L., and Price, P. Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and pharmacokinetic results. J. Clin. Oncol., 21: 2815-2822, 2003.
138. Bilenker, J. H., Stevenson, J. P., Rosen, M. A., Gallagher, M., Flaherty, K. T., Algazy, K. M., Sun, W., Schnall, M., and O'Dwyer, P. J. Phase Ib trial of combretastatin A-4 phosphate (CA4P) in combination with carboplatin in patients with advanced cancer. Proc. Am. Soc. Clin. Oncol., 22: 889, 2003.
139. Tolcher, A. W., Forero, L., Celio, P., Hammond, L. A., Patnaik, A., Hill, M., Verat-Follet, C., Haacke, M., Besenval, M., and Rowinsky, E. K. Phase I, pharmacokinetic, and DCE-MRI correlative study of AVE8062A, an antivascular combretastatin analogue, administered weekly for 3 weeks every 28-days. Proc. Am. Soc. Clin. Oncol., 22: 834, 2003.
140. Gadgeel, S. M., LoRusso, P. M., Wozniak, A. J., and Wheeler, C. A dose-escalation study of the novel vascular-targeting agent, ZD6126, in patients with solid tumors. Proc. Am. Soc. Clin. Oncol., 21: 438, 2002.
141. Rustin, G. J., Bradley, C., Galbraith, S., Stratford, M., Loadman, P., Waller, S., Bellenger, K., Gumbrell, L., Folkes, L., and Halbert, G. 5, 6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent: phase I clinical and pharmacokinetic study. Br. J. Cancer, 88: 1160-1167, 2003.
142. 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. Clinical aspects of a phase I trial of 5, 6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Br. J. Cancer, 88: 1844-1850, 2003.