Oligosaccharides as anti-angiogenic agents

Expert Opinion on Biological Therapy

Volumn 8, Issue 3, 2008, Pages 351-362

  Cole, Claire Louise ^a   Jayson, Gordon C ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Angiogenesis; Bevacizumab; FGF2; Fibroblast growth factor 2; Heparan sulfate; Heparin; HS; LMWH; Low molecular weight heparin; Pentosan polysulfate; Phosphomannopentaose; PI 88; PPS; Tyrosine kinase inhibitors; VEGF; VEGF trap

Indexed keywords

ALPHA INTERFERON; ANGIOGENESIS INHIBITOR; ANTIBODY; BEVACIZUMAB; CHONDROITIN SULFATE; CISPLATIN; CYCLOPHOSPHAMIDE; DACARBAZINE; DALTEPARIN; EPIRUBICIN; GEMCITABINE; HEPARAN SULFATE; HEPARIN; HYALURONIC ACID; HYDROCORTISONE; LOW MOLECULAR WEIGHT HEPARIN; OLIGOSACCHARIDE; PACLITAXEL; PENTOSAN POLYSULFATE; PI 88; PLACEBO; PROTEIN TYROSINE KINASE INHIBITOR; SORAFENIB; SUNITINIB; TECOGALAN; TINZAPARIN; UNINDEXED DRUG; VATALANIB; VINCRISTINE; WARFARIN;

ANGIOGENESIS; ANTICOAGULATION; AREA UNDER THE CURVE; BLEEDING; BONE MARROW DISEASE; BREAST ADENOCARCINOMA; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CLINICAL TRIAL; COLON CARCINOMA; COLORECTAL CANCER; CONTINUOUS INFUSION; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DOSE RESPONSE; DRUG MECHANISM; DRUG TARGETING; DYSPEPSIA; FATIGUE; HUMAN; HYPERTENSION; KIDNEY CARCINOMA; LUNG CARCINOMA; LUNG EMBOLISM; LUNG SMALL CELL CANCER; MELANOMA; NAUSEA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PROSTATE ADENOCARCINOMA; PROTEINURIA; REVIEW; SIDE EFFECT; STOMATITIS; THROMBOCYTOPENIA; THROMBOEMBOLISM; TUMOR GROWTH; UNSPECIFIED SIDE EFFECT; WOUND HEALING IMPAIRMENT;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; OLIGOSACCHARIDES;

EID: 41149139565     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712598.8.3.351     Document Type: Review

References (127)

1. Giantonio BJ. High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group (ECOG) study E3200. Proc Am Soc Clin Oncol 2005;(Abstract no. 2)
2. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42
3. Miller KD, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for merastatic breast cancer. N Engl J Med 2007;357:2666-76
4. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355:2542-50
5. Wedam SB, Low JA, Yang SX, et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol 2006;24:769-77
6. Willett CG, Boucher Y, Tomaso ED, et al. Direct evidence that the VEGF specific antibody bevacizumab has antivascular effects in human rectal carcinoma. Nat Med 2004;10:145-7.
7. Yang, JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349:427-34
8. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57 •• Excellent review of angiogenesis.
9. Conway EM, Collen D, Carameliet P. Molecular mechanism of blood vessel growth. Cardiovasc Res 2001;49:507-21
10. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70 • Gives a good overview of cancer.
11. Schoell WM, Pieber D, Reich O, et al. Tumour angiogenesis as a prognostic factor in ovarian carcinoma: quantification of endothelial mmunoreactivity by image analysis. Cancer 1997;80:2257-62
12. Silberman MA, Partin AW, Veltri RW, Epstein JI. Tumour angiogenesis correlates with progression after radical prostatectomy but not with pathological stage in Gleason sum 5 to 7 adenocarcinoma of the prostate. Cancer 1997;79:772-9
13. Takanami I, Takeuchi K, Naruke M. Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma. Cancer 2000;88:2686-92
14. Kamba T, Tam BYY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol 2006;290:H560-76
15. Takebayashi Y, Aklyama S, Yamada K, et al. Angiogenesis as an unfavourable prognostic factor in human colorectal carcinoma. Cancer 1996;78:226-31
16. Weidner N, Semple JP, Welch WR, Folkman J. Tumour angiogenesis and metastasis correlation in invasive breast carcinoma. N Engl J Med 1991;324:1-8
17. Oprana A, Salven P. Angiogenic and lymphangiogenic molecules in haematological malignancies. Leuk Lymphoma 2002;43:219-24
18. Blackhall FH, Merry CL, Davies EJ, Jayson GC. Heparan sulphate proteoglycans and cancer. Br J Cancer 2001;85:1094-8
19. Catlow K, Deakin JA, Delehedde M, et al. Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate. Biochem Soc Trans 2003;31:352-3
20. Fuster MM, Wang L, Castagnola J, et al. Genetic alteration of endothelial heparan sulphate selectively inhibits tumour angiogenesis. J Cell Biol 2007;177:539-49
21. Guimond S, MacCarana M, Olwin BB, et al. Activating and inhibitory heparin sequences for FGF-2 (basic FGF). J Biol Chem 1993;268:23906-14
22. Ashikari-Hada S, Habuchi H, Kariya Y, et al. Characterization of growth factor-binding structures in heparin/heparin sulphate using an octasaccharide library. J Biol Chem 2004;279:12346-54
23. Noti C, Seeberger PH. Chemical approaches to define the structure-activity relationship of heparin-like glycosaminoglycans. Chem Biol 2005;12:731-56
24. Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol 2001;2:1-12
25. Lee PL, Johnson DE, Cousens LS, et al. Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor. Science 1989;245:57-60
26. Sleeman M, Fraser J, McDonald M, et al. Identification of a new fibroblast growth factor receptor, FGFR5. Gene 2001;271:171-82
27. Kwabi-Addo B, Ozen M, Ittmann M. The role of fibroblast growth factors and their receptors in prostate cancer. Endocr Relat Cancer 2004;11:709-24
28. Ishibe T, Nakayama T, Okamoto T, et al. Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy. Clin Cancer Res 2005;11:2702-12
29. Ding Q, Gladson CL, Guidry CR, et al. Extracellular FGF-1 inhibits cytoskeletal organization and promotes fibroblast motility. Growth Factors 2000;18:93-107
30. Olwin BB, Rapraeger A. Repression of myogenic differentiation by aFGF, bFGF, and K-FGF is dependent on cellular heparan sulfate. J Cell Biol 1992;118:631-9
31. Feng S, Wang F, Matsubara A, et al. Fibroblast growth factor receptor 2 limits and receptor 1 accelerates tumorigenicity of prostate epithelial cells. Cancer Res 1997;57:5369-78
32. Giavazzi R, Sennino B, Coltrini D, et al. Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis. Am J Pathol 2003;162:1913-26
33. Ogawa T, Takayama K, Takakura N, et al. Anti-tumor angiogenesis therapy using soluble receptors: enhanced inhibition of tumor growth when soluble fibroblast growth factor receptor-1 is used with soluble vascular endothelial growth factor receptor. Cancer Gene Ther 2002;9:633-40
34. Coleman AB. Positive and negative regulation of cellular sensitivity to anti-cancer drugs by FGF-2. Drug Resist Updat 2003;6:85-94
35. Presta M, Dell'era P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 2005;16:159-78 •• Excellent insight into the FGF/FGFR system.
36. Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun 1992;189:824-31
37. Auguste P, Gursel DB, Lemiere S, et al. Inhibition of fibroblast growth factor/fibroblast growth factor receptor activity in glioma cells impedes tumor growth by both angiogenesis-dependent and -independent mechanisms. Cancer Res 2001;61:1717-26
38. Ozen M, Giri D, Ropiquet F, et al. Role of fibroblast growth factor receptor signaling in prostate cancer cell survival. J Natl Cancer Inst 2001;93:1783-90
39. Rofstad EK, Halsor EF. Vascular endothelial growth factor, interleukin 8, platelet-derived endothelial cell growth factor, and basic fibroblast growth factor promote angiogenesis and metastasis in human melanoma xenografts. Cancer Res 2000;60:4932-8
40. Grose R, Dickson C. Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev 2005;16:179-86
41. Turnbull JE, Fernig DG, Ke Y, et al. Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate. J Biol Chem 1992;267:10337-41
42. Pye DA, Vives RR, Turnbull JE, et al. Heparan sulfate oligosaccharides require 6-O-sulfation for promotion of basic fibroblast growth factor mitogenic activity. J Biol Chem 1998;273:22936-42
43. Lundin L, Larsson H, Kreuger J, et al. Selectively desulfated heparin inhibits fibroblast growth factor-induced mitogenicity and angiogenesis. J Biol Chem 2000;275:24653-60
44. Ishihara M, Takano R, Kanda T, et al. Importance of 6-O-sulfate groups of glucosamine residues in heparin for activation of FGF-1 and FGF-2. J Biochem (Tokyo) 1995;118:1255-60
45. Rusnati M, Coltrini D, Caccia P, et al. Distinct role of 2-O-, N-, and 6-O-sulfate groups of heparin in the formation of the ternary complex with basic fibroblast growth factor and soluble FGF receptor-1. Biochem Biophys Res Commun 1994;203:450-8
46. Aviezer D, Levy E, Safran M, et al. Differential structural requirements of heparin and heparan sulfate proteoglycans that promote binding of basic fibroblast growth factor to its receptor. J Biol Chem 1994;269:114-21
47. Bikfalvi A, Klein S, Pintucci G, Rifkin DB. Biological roles of fibroblast growth factor-2. Endocr Rev 1997;18:26-45
48. Rusnati M, Presta M. Interaction of angiogenic basic fibroblast growth factor with endothelial cell heparan sulfate proteoglycans. Biological implications in neovascularization. Int J Clin Lab Res 1996;26:15-23
49. Folkman J, Sting Y. Control of angiogenesis by heparin and other sulfated polysaccharides. Adv Exp Med Biol 1992;313:355-64
50. Robinson CJ, Stringer SE. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 2001;114:853-65 • Good overview of VEGF system.
51. Bicknell R, Harris AL. Novel angiogenic signaling pathways and vascular targets. Ann Rev Pharmacol and Toxicol 2004;44:219-38
52. Stringer SE. The role of heparan sulphate proteoglycans in angiogenesis. Biochem Soc Trans 2006;34:451-3
53. Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 2001;280:1358-66
54. Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol 2001;106:148-56
55. Gitay-Goren H, Soker S, Vlodavsky I, Neufeld G. The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules. J Biol Chem 1992;267:6093-8
56. Hong X, Jiang F, Kalkanis SN, et al. SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion. Cancer Lett 2006;236:39-45
57. Kryczek I, Frydman N, Gaudin F, et al. The chemokine SDF-1/CXCL12 contributes to T lymphocyte recruitment in human pre-ovulatory follicles and coordinates with lymphocytes to increase granulosa cell survival and embryo quality. Am J Reprod Immunol 2005;54:270-83
58. Boehm T, Folkman J, Browder T, O'Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997;390:404-7
59. Herbst RS, Hess KR, Tran HT, et al. Phase I study of recombinant human endostatin in patients with advanced solid tumors. J Clin Oncol 2002;20:3792-803
60. Wen W, Moses MA, Wiederschain D, et al. The generation of endostatin is mediated by elastase. Cancer Res 1999;59:6052-6
61. Felbor U, Dreier L, Bryant RA, et al. Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J 2000;19:1187-94
62. O'Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997;88:277-85
63. Yamaguchi N, Anand-Apte B, Lee M, et al. Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. EMBO J 1999;18:4414-23
64. Clamp A, Blackhall FH, Henrioud A, et al. The morphogenic properties of oligomeric endostatin are dependent on cell surface heparan sulfate. J Biol Chem 2006;281:14813-22
65. Bornstein P, Armstrong LC, Hankerson KD, et al. Thrombospondin 2, a matricellular protein with diverse functions. Matrix Biol 2000;19:557-68
66. Laderoute KR, Alarcon RM, Brody MD, et al. Opposing effects of hypoxia on expression of the angiogenic inhibitor thrombospondin-1 and the angiogenic inducer vascular endothelial growth factor. Clin Cancer Res 2000;6:2941-50
67. Doll JA, Reiher FK, Crawford SE, et al. Thrombospondin-1, vascular endothelial growth factor and fibroblast growth factor-2 are key functional regulators of angiogenesis in the prostate. Prostate 2001;49:293-305
68. Guan M, Pang CP, Yam HF, et al. Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor. Cancer Gene Ther 2004;11:325-32
69. Taraboletti G, Belotti D, Borsotti P, et al. The 140-kilodalton antiangiogenic fragment of thrombospondin-1 binds to basic fibroblast growth factor. Cell Growth Differ 1997;8:471-9
70. Castelli R, Porro F, Tarsia P. The heparins and cancer: review of clinical trials and biological properties. Vasc Med 2004;9:205-13 • Good review of clinical trials with heparins.
71. Bobek V, Kovarik J. Antitumor and antimetastatic effect of warfarin and heparins. Biomed Pharmacother 2004;58:213-9
72. Mousa SA, Mohamed S. Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anti-cancer efficacy. Oncol Rep 2004;12:683-8
73. Mousa SA. Anti-angiogenesis effect of low molecular weight heparin is primarily mediated by tissue factor pathway inhibitor. Haematol Rep 2005;1:Poster 9, 111
74. Jayson GC, Gallagher JT. Heparin oligosaccharides: inhibitors of the biological activity of bFGF on Caco-2 cells. Br J Cancer 1997;75:9-16
75. Mousa SA. Anticoagulants in thrombosis and cancer: the missing link. Semin Thromb Hemost 2002;28:45-52
76. Nakayama Y, Iwahana M, Sakamoto N, et al. Inhibitory effects of a bacteria-derived sulphated polysaccharide against basic fibroblast growth factor-induced endothelial cell growth and chemotaxis. J Cell Physiol 1993;154:1-6
77. Sakamoto T, Ishibashi T, Kimura H, et al. Effect of recogalan sodium on angiogenesis in vitro by choroidal endothelial cells. Invest Ophthalmol Vis Sci 1995;36:1076-83
78. Yunmbam MK, Wellstein A. The bacterial polysaccharide tecogalan blocks growth of breast cancer cells in vivo. Oncol Rep 2001;8:161-4
79. Zugamaier G, Lippman ME, Wellstein A. Inhibition by pentosan polysulfate (PPS) of heparin-binding growth factors released from tumor cells and blockage by PPS of tumor growth in animals. J Natl Cancer Inst 1992;84:1716-24
80. Zaslau S, Sparks S, Riggs D, et al. Pentosan polysulfate (Elmiron): in vitro effects on prostate cancer cells regarding cell growth and vascular endothelial growth factor production. Am J Surg 2006;192:640-3
81. Nguyen NM, Lehr JE, Pienta KJ. Pentosan inhibits angiogenesis in vitro and suppresses prostate tumor growth in vivo. Anticancer Res 1993;13:2143-7
82. Zugamaier G, Favoni R, Jaeger R, et al. Polysulfated heparinoids selectively inactivate heparin-binding angiogenesis factors. Annals NY Acad Sci 1996;886:243-8
83. McKenzie EA. Heparanase: a target for drug discovery in cancer and inflammation. Br J Pharm 2007;151:1-14
84. Parish CR, Freeman C, Brown KJ, et al. Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity. Cancer Res 1999;59:3433-41
85. Takahashi H, Ebihara S, Okazaki T, et al. A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol 2005;146:333-43
86. Fernandez PM, Chou DS, Aquilina JW, et al. Unfractinated heparin (UHF) and a low molecular weight heparin (dalteparin) exhibit anti-angiogenic effects using in vitro, ex vivo and in vivo angiogenesis models. Proc AACR 2003;94, Meeting: 698-9
87. Smiley SL, Henry DO, Wong MK. The mechanism of low molecular weight heparin (LMWH) inhibition of tumour growth. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings Part I 2006;24:13093
88. Hasan J, Shnyder SD, Clamp AR, et al. Heparin octasaccharides inhibit angiogenesis in vivo. Clin Cancer Res 2005;11:8172-9
89. Murata T, Ishibashi T, Yoshikawa H, et al. Tecogalan sodium inhibits corneal neovascularization induced by basic fibroblast growth factor. Ophthal Res 1995;27:330-4
90. Chleboun JO, Sellers P, Muir G, et al. The effect of tecogalan sodium on the development of the collateral circulation after acute arterial occlusion. Biochem Biophys Res Commun 1994;202:1149-55
91. Rocchetti R, Talevi S, Margiotta C, et al. Antiangiogenic drugs for chemotherapy of bladder tumours. Chemotherapy 2005;51:291-9
92. Pienta KJ, Murphy BC, Isaacs WB, et al. Effect of pentosan, a novel cancer chemotherapeutic agent, on prostate cancer cell growth and motility. Prostate 1992;20:233-41
93. Iversen PO, Sorensen DR, Benestad HB. Inhibitors of angiogenesis selectively reduce the malignant cell load in rodent models of human myeloid leukemias. Leukemia 2002;16:376-81
94. Joyce JA, Freeman C, Meyer-Morse N, et al. A functional heparan sulphate mimetic implicates both heparanase and heparan sulphate in tumor angiogenesis and invasion in a mouse model of multistage cancer. Oncogene 2005;24:4037-51
95. Zacharski LR, Henderson WG, Rickles FR, et al. Effect of Warfarin Anticoagulation on Survival in Carcinoma of the Lung, Colon, Head and Neck, and Prostate Final Report of VA Cooperative Study #75. Cancer 1984;53:2046-52
96. Lebeau B, Chastang C, Brechot JM, et al. Subcutaneous heparin treatment increases survival in small cell lung cancer. Cancer 1994;74:38-45
97. Hull RD, Pineo GF, Brant RF, et al. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 2006;119:1062-72
98. Kakkar AK, Levine MN, Kadziola Z, et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 2004;22:1944-48
99. Altinbas M, Coskun HS, ER O, et al. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost 2004;2:1266-71
100. Icli F, Akbulut H, Utkan G, et al. Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer. Proc Ann Meeting Am Soc Clin Oncol 2003;22:A1149
101. Tsimafeyeu I, Madzhuga A, Demidov L, et al. Low molecular weight heparin (LMWH) increases the efficacy of immunotherapy in metastatic renal cell carcinoma patients with abnormal coagulation. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings Part I 2007;25:15591
102. Eckhardt SG, Burris HA, Eckardt JR, et al. Phase I assessment of the novel angiogenesis inhibitor DS4152 (tecogalan sodium). Proc Ann Meeting Am Soc Clin Oncol 1994;13:A23
103. Parker BW, Swain SM, Zugamier G, et al. Detectable inhibition of heparin-binding growth factor activity in sera from patients treated with pentosan polysulfate. J Natl Cancer Inst 1993;85:1068-73
104. Lush RM, Figg WD, Pluda JM, et al. A phase I study of pentosan polysulphate sodium in patients with advanced malignancies. Ann Oncol 1996;7:939-44
105. Schwartsmann G, Sprinz E, Kalakun L, et al. Phase II study of pentosan polysulphate (PPS) in patients with AIDS-related Kaposi's sarcoma. Tumori 1996;82:360-3.
106. Basche M, Gustafson DL, Holden SN, et al. A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors. Clin Cancer Res 2006;12:5471-80
107. Rosenthal MA, Rischin D, McArthur G, et al. Treatment with the novel antiangiogenic agent PI-88 is associated with immune-mediated thrombocytopenia. Ann Oncol 2002;13:770-6
108. Millward M, Hamilton A, Thomson D, et al. Final results of a Phase I study of daily PI-88 as a single agent and in combination with dacarbazine (D) in patients with metastatic melanoma. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings Part I 2007;25:8532
109. Progen Pharmaceuticals - PI88 in clinical trials. Available at: URL: www.progen.com.au/?page=pitrials.html
110. Patel VP, Bong M, Di Cesare PE. Heparin-induced thrombocytopenia and thrombosis. Am J Orthop 2007;36:255-60
111. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:16-24
112. Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006;295:2516-24
113. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon-alfa in metastatic renal cell carcinoma. New Engl J Med 2007;356:115-24
114. Steeghs N, Nortier JWR, Gelderblom H. Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann Surg Oncol 2006;14:942-53 • Good review of tyrosine kinase inhibitors.
115. Dupont J, Schwartz L, Koutcher J, et al. Phase I and pharmacokinetic study of VEGF trap administered subcutaneously (sc) to patients (pts) with advanced solid malignancies. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings 2004;22:3009
116. Rixe O, Verslype C, Meric JB, et al. Safety and pharmacokinetics if intravenous VEGF-trap plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in a combination phase I clinical trial of patients with advanced solid tumours. J Clin Oncol, ASCO Annual Meeting Proceedings 2006;24:13161
117. Massarelli E, Miller VA, Leighl NB, et al. Phase II study of the efficacy and safety of intravenous (iv) AVE0005 (VEGF-trap) given every 2 weeks in patients (pts) with platinum- and erlotinib-resistant adenocarcinoma of the lung (NSCLA). J Clin Oncol, 2007 ASCO Annual Meeting Proceedings 2007;25:7627
118. Tew WP, Colombo N, Ray-Coquard I, et al. VEGF-trap for patients (pts) with recurrent platinum-resistant epithelial ovarian cancer (EOC): preliminary results of a randomized, multicenter phase II study. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings 2007;25:5508
119. Dupont J, Rothenberg ML, Spriggs DR, et al. Safety and pharmacokinetics of intravenous VEGF-trap in a Phase I clinical trial of patients with advanced solid tumours. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings 2005;23:3029
120. Ferrara N, Gerber HP, Lecouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-76
121. Lee TH, Avraham HK, Jiang S, Avraham S. Vascular endothelial growth factor modulates the transendothelial migration of MDA-MB-231 breast cancer cells through regulation of brain microvascular endothelial cell permeability. JBC 2003;278:5277-84
122. Johnson DH, Fehrenbacher L, Novotny WF, et al. Randomised Phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 2004;22:2184-91
123. Hurwitz H, Saini S. Bevacizumab in the treatment of metastatic colorectal cancer: safety profile and management of adverse effects. Semin Oncol 2006;33:S26-34
124. Lorat-Jacob H, Garrone P, Banchereau J, Grimaud JA. Human interleukin 4 is a glycosaminoglycan-binding protein. Cytokine 1997;9:101-5
125. Hasan M, Najjam S, Gordon MY, et al. IL-12 is a heparin-binding cytokine. J Immunol 1999;162:1064-70
126. Rolny C, Spillmann D, Lindahl U, Claesson-Welsh L. Heparin amplifies platelet-derived growth factor (PDGF)-BB-induced PDGF alpha receptor but not PDGF beta-receptor tyrosine phosphorylation in heparan sulfate-deficient cells. Effects on signal transduction and biological responses. J Biol Chem 2002;277:19315-21
127. Affiliation Claire Louise Cole † & Gordon C Jayson