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Expert Opinion on Therapeutic Targets Volume 11, 2007 - Issue 11
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Review

Tumour targeting by microtubule-depolymerising vascular disrupting agents

Chryso Kanthou University of Sheffield, Cancer Research UK Tumour Microcirculation Group, Academic Unit of Surgical Oncology, School of Medicine & Biomedical Sciences, Beech Hill Road, Sheffi eld, S10 2RX, UK +44 114 271 1725; C.Kanthou@sheffi eld.ac.uk
&
Gillian M Tozer University of Sheffield, Cancer Research UK Tumour Microcirculation Group, Academic Unit of Surgical Oncology, School of Medicine & Biomedical Sciences, Beech Hill Road, Sheffi eld, S10 2RX, UK +44 114 271 1725; C.Kanthou@sheffi eld.ac.uk
Pages 1443-1457 | Published online: 26 Oct 2007

Bibliography

  • FOLKMAN J: What is the evidence that tumors are angiogenesis dependent? J. Natl. Cancer Inst. (1990) 82:4-6.
  • FERRARA N: Angiogenesis as a therapeutic target. Nature (2005) 438:967-974.
  • FOLKMAN J: Angiogenesis inhibitors: a new class of drugs. Cancer Biol. Ther. (2003) 2(4 Suppl. 1):S127-S133.
  • BALUK P, HASHIZUME H, MCDONALD DM: Cellular abnormalities of blood vessels as targets in cancer. Curr. Opin. Genet. Dev. (2005) 15:102-111.
  • TONRA JR, HICKLIN DJ: Targeting the vascular endothelial growth factor pathway in the treatment of human malignancy. Immunol. Invest. (2007) 36:3-23.
  • TOZER GM, KANTHOU C, BAGULEY BC: Disrupting tumour blood vessels. Nat. Rev. Cancer (2005) 5(6):423-435.
  • NERI D, BICKNELL R: Tumour vascular targeting. Nat. Rev. Cancer (2005) 5(6):436-446.
  • CHAPLIN DJ, HORSMAN MR, SIEMANN DW: Current development status of small-molecule vascular disrupting agents. Curr. Opin. Investig. Drugs (2006) 7(6):522-528.
  • PATTERSON DM, RUSTIN GJS: Vascular damaging agents. Clin. Oncol. (2007) 19:443-456.
  • PASQUIER E, HONORE S, BRAGUER D: Microtubule-targeting agents in angiogenesis: where do we stand? Drug Res. Updates (2006) 9:74-86.
  • BOYLAND E, BOYLAND ME: Studies in tissue metabolism. IX. The action of colchicine and B. typhosus extract. Biochem. J. (1937) 31:454-460.
  • LUDFORD RJ: Factors determining the action of colchicine on tumour growth. Br. J. Cancer (1948) 2:75-86.
  • HILL SA, LONERGAN SJ, DENEKAMP J, CHAPLIN DJ: Vinca alkaloids: anti-vascular effects in a murine tumour. Eur. J. Cancer (1993) 29A(9):1320-1324.
  • PETTIT GR, CRAGG GM, SINGH SB: Antineoplastic agents, 122. Constituents of Combretum caffrum. J. Nat. Prod. (1987) 50:386-391.
  • PETTIT GR, SINGH SB, HAMEL E et al.: Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A4. Experientia (1989) 45:205-211.
  • LIN CM, SINGH SB, CHU PS et al.: Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study. Mol. Pharmacol. (1988) 34(2):200-208.
  • CHAPLIN DJ, PETTIT GR, PARKINS CS, HILL SA: Antivascular approaches to solid tumour therapy: evaluation of tubulin binding agents. Br. J. Cancer Suppl. (1996) 27:S86-S88.
  • PETTIT GR, TEMPLE C, NARAYANAN VL et al.: Antineoplastic agents 322. Synthesis of combretastatin A-4 prodrugs. Anticancer Drug Des. (1995) 10:299-309.
  • MCGOWN AT, FOX BW: Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4 and amphethinile. Anticancer Drug Des. (1989) 3:249-254.
  • DARK GG, HILL SA, PRISE VE et al.: Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res. (1997) 57(10):1829-1834.
  • BEAUREGARD DA, THELWALL PE, CHAPLIN DJ et al.: Magnetic resonance imaging and spectroscopy of combretastain A4 prodrug-induced disruption of tumour perfusion and energetic status. Br. J. Cancer (1998) 77:1761-1767.
  • HORSMAN M, EHRNROOTH E, LADEKARL M, 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. (1998) 42:895-898.
  • MAXWELL RJ, NIELSEN FU, BREIDAHL T, STODKILDE-JORGENSEN H, HORSMAN MR: Effects of combretastatin on murine tumours monitored by 31P MRS, 1H MRS and 1H MRI. Int. J. Radiat. Oncol. Biol. Phys. (1998) 42:891-894.
  • CHAPLIN DJ, PETTIT GR, HILL SA: Anti-vascular approaches to solid tumour therapy: evaluation of combretastatin A4 phosphate. Anticancer Res. (1999) 19(1A):189-195.
  • TOZER GM, PRISE VE, WILSON J et al.: Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues. Cancer Res. (1999) 59(7):1626-1634.
  • TOZER GM, PRISE VE, WILSON J et al.: Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability. Cancer Res. (2001) 61(17):6413-6422.
  • LI L, ROJIANI A, SIEMANN D: Targeting the tumor vasculature with combretastatin A-4 disodium phosphate: effects on radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. (1998) 42:899-903.
  • HORSMAN MR, MURATA R, BREIDHAL T et al.: Combretastatins: novel vascular targeting drugs for improving anti-cancer therapy. Combretastatins and conventional therapy. Adv. Exp. Med. Biol. (2000) 476:311-323.
  • MURATA R, SIEMANN DW, OVERGAARD J, HORSMAN HR: Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumors. Radiother. Oncol. (2001) 60:155-161.
  • NELKIN BD, BALL DW: Combretastatin A-4 and doxorubicin combination treatment is effective in a preclinical model of human medullary thyroid carcinoma. Oncol. Rep. (2001) 8:157-160.
  • SIEMANN DW, MERCER E, LEPLER S, ROJIANI AM: Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy. Int. J. Cancer (2002) 99(1):1-6.
  • PEDLEY RB, HILL SA, BOXER GM et al.: Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin A-4 3-O-phosphate. Cancer Res. (2001) 61(12):4716-4722.
  • LANKESTER KJ, MAXWELL RJ, PEDLEY RB et al.: Combretastatin A-4-phosphate effectively increases tumor retention of the therapeutic antibody, 131I-A5B7, even at doses that are sub-optimal for vascular shut-down. Int. J. Oncol. (2007) 30:453-460.
  • SENGUPTA S, EAVARONE D, CAPILA I et al.: Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature (2005) 436:568-572.
  • TOZER GM, AMEER-BEG SM, BAKER J et al.: Intravital imaging of tumour vascular networks using multi-photon fluorescence microscopy. Adv. Drug Deliv. Rev. (2005) 571:135-152.
  • REYES-ALDASORO CC, WILSON I, PRISE VE et al.: Estimation of apparent tumour vascular permeability from multiphoton fluorescence microscopic images of P22 rat sarcomas in vivo. Microcirculation (2007) (In Press).
  • PRISE VE, HONESS DJ, STRATFORD MR, WILSON J, TOZER GM: The vascular response of tumor and normal tissues in the rat to the vascular targeting agent, combretastatin A-4-phosphate, at clinically relevant doses. Int. J. Oncol. (2002) 21(4):717-726.
  • PETTIT GR, LIPPERT JW III: Antineoplastic agents 429. Syntheses of the combretastatin A-1 and combretastatin B-1 prodrugs. Anticancer Drug Des. (2000) 15:203-216.
  • HILL SA, TOZER GM, CHAPLIN DJ: Preclinical evaluation of the antitumour activity of the novel vascular targeting agent Oxi 4503. Anticancer Res. (2002) 22:1453-1458.
  • HUA J, SHENG Y, PINNEY KG et al.: Oxi4503, a novel vascular targeting agent: effects on blood flow and antitumor activity in comparison to combretastatin A-4 phosphate. Anticancer Res. (2003) 23(2B):1433-1440.
  • HOLWELL SE, COOPER PA, GROSIOS K et al.: Combretastatin A-1 phosphate a novel tubulin-binding agent with in vivo vascular effects in experimental tumours. Anticancer Res. (2002) 22:707-711.
  • KIRWAN IG, LOADMAN PM, SWAINE DJ et al.: Comparative preclinical pharmacokinetic and metabolic studies of the combretastatin prodrugs combretastatin A4 phosphate and A1 phosphate. Clin. Cancer Res. (2004) 10(4):1446-1453.
  • EL-EMIR E, BOXER GM, PETRIE IA et al.: Tumour parameters affected by combretastatin A-4 phosphate therapy in a human colorectal xenograft model in nude mice. Eur. J. Cancer (2005) 41(5):799-806.
  • WACHSBERGER PR, BURD R, MARERO N et al.: Effect of the tumor vascular-damaging agent, ZD6126, on the radioresponse of U87 glioblastoma. Clin. Cancer Res. (2005) 11(2 Part 1):835-842.
  • BOEHLE AS, SIPOS B, KLICHE U, KALTHOFF H, DOHRMANN P: Combretastatin A-4 prodrug inhibits growth of human non-small cell lung cancer in a murine xenotransplant model. Ann. Thorac. Surg. (2001) 71(5):1657-1665.
  • SHENG Y, HUA J, PINNEY KG et al.: Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis. Int. J. Cancer (2004) 111(4):604-610.
  • SHAKED Y, CIARROCCHI A, FRANCO M et al.: Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science (2006) 313(5794):1785-1787.
  • SHI W, SIEMANN DW: Targeting the tumor vasculature: enhancing antitumor efficacy through combination treatment with ZD6126 and ZD6474. In Vivo (2005) 19(6):1045-1050.
  • SIEMANN DW, SHI W: Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors. Int. J. Radiat. Oncol. Biol. Phys. (2004) 60(4):1233-1240.
  • STEVENSON JP, ROSEN M, SUN W et al.: Phase I trial of the antivascular agent combretastatin A4 phosphate on a 5-day schedule to patients with cancer: magnetic resonance imaging evidence for altered tumor blood flow. J. Clin. Oncol. (2003) 21(23):4428-4438.
  • DOWLATI A, ROBERTSON K, COONEY M et al.: 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. (2002) 62(12):3408-3416.
  • RUSTIN GJ, GALBRAITH SM, ANDERSON H et al.: Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and pharmacokinetic results. J. Clin. Oncol. (2003) 21(15):2815-2822.
  • ANDERSON HL, YAP JT, MILLER MP et al.: Assessment of pharmacodynamic vascular response in a Phase I trial of combretastatin A4 phosphate. J. Clin. Oncol. (2003) 21(15):2823-2830.
  • GALBRAITH SM, MAXWELL RJ, LODGE MA et al.: Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging. J. Clin. Oncol. (2003) 21(15):2831-2842.
  • PATTERSON DM, ROSS P, KOETZ A et al.: Phase I evaluation of Oxi4503, a vascular disrupting agent, in patients with advanced solid tumours. J. Clin. Oncol., ASCO Annual Meeting Proceedings Part I (2007) 25(18S):14146.
  • JORDAN AM, WILSON L: Microtubules as a target for anticancer drugs. Nat. Rev. Cancer (2004) 4:253-264.
  • HONORE S, PASQUIER E, BRAGUER D: Understanding microtubule dynamics for improved cancer therapy. Cell Mol. Life Sci. (2005) 62:3039-3056.
  • KANTHOU C, TOZER GM: The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells. Blood (2002) 99:2060-2069.
  • MITCHISON TJ, KIRSCHNER M: Dynamic instability of microtubule growth. Nature (1984) 312:237-242.
  • GOODE BL, DRUBIN DG, BARNES G: Functional cooperation between the microtubule and actin cytoskeletons. Curr. Opin. Cell Biol. (2000) 12:63-71.
  • GRUNDERSEN GG, COOK TA: Microtubules and signal transduction. Curr. Opin. Cell Biol. (1999) 11:81-94.
  • POURROY B, HONORE S, PASQUIER E et al.: Antiangiogenic concentrations of vinflunine increase the interphase microtubule dynamics and decrease the motility of endothelial cells. Cancer Res. (2006) 66:3256-3263.
  • GROSIOS K, HOLWELL SE, MCGOWN AT, PETTIT GR, BIBBY MC: In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug. Br. J. Cancer (1999) 81(8):1318-1327.
  • GALBRAITH SM, CHAPLIN DJ, LEE F et al.: Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro and relationship to tumour vascular targeting activity in vivo. Anticancer Res. (2001) 21:93-102.
  • RIDLEY AJ: Rho family proteins: coordinating cell responses. Trends Cell Biol. (2001) 11(12):471-477.
  • RIDLEY AJ, HALL A: The small GTP-binding protein Rho regulates the assembly of focal adhesions and actin stress fibers in respones to growth factors. Cell (1992) 70:389-399.
  • AMANO M, ITO M, KIMURA K et al.: Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J. Biol. Chem. (1996) 271(34):20246-20249.
  • KOHAMA K, YE LH, HAYAKAWA K, OKAGAKI T: Myosin light chain kinase: an actin-binding protein that regulates an ATP-dependent interaction with myosin. Trends Pharmacol. Sci. (1996) 17:284-287.
  • MICHELETTI G, POLI M, BORSOTTI P et al.: Vascular-targeting activity of ZD6126, a novel tubulin-binding agent. Cancer Res. (2003) 63(7):1534-1537.
  • GUAY J, LAMBERT H, GINGRAS-BRETON G et al.: Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27. J. Cell Sci. (1997) 110(3):357-368.
  • HUOT J, HOULE F, ROUSSEAU S et al.: SAPK2/p-38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis. J. Cell Biol. (1998) 43(5;30):1361-1373.
  • FINCHAM VJ, JAMES M, FRAME MC, WINDER SJ: Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. EMBO J. (2000) 19(12):2911-2923.
  • HOULE F, ROUSSEAU S, MORRICE N et al.: Extracellular signal-regulated kinase mediates phosphorylation of tropomyosin-1 to promote cytoskeleton remodeling in response to oxidative stress: impact on membrane blebbing. Mol. Biol. Cell (2003) 14(4):1418-1432.
  • REN XD, KIOSSES WB, SCHWARTZ MA: Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J. (1999) 18(3):578-585.
  • HOULE F, HUOT J: Dysregulation of the endothelial cellular response to oxidative stress in cancer. Mol. Carcinog. (2006) 45(6):362-367.
  • KURATA S: Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress. J. Biol. Chem. (2000) 275(31):23413-23416.
  • FANG L, HE Q, HU Y, YANG B: MZ3 induces apoptosis in human leukemia cells. Cancer Chemother. Pharmacol. (2007) 59(3):397-405.
  • WOJCIAK-STOTHARD B, RIDLEY AJ: Rho GTPases and the regulation of endothelial permeability. Vasc. Pharmacol. (2002) 39:187-199.
  • BAZZONI G, DEJANA E: Endothelial cell-to-cell junctions: molecular organisation and role in vascular homeostasis. Physiol. Rev. (2004) (84):869-901.
  • VINCENT L, KERMANI P, YOUNG LM et al.: Combretastatin A4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling. J. Clin. Invest. (2005) 115(11):2992-3006.
  • REN Y, LI R, ZHENG Y, BUSCH H: Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases. J. Biol. Chem. (1998) 273(52):34954-34960.
  • KRENDEL M, ZENKE FT, BOKOCH GM: Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nat. Cell Biol. (2002) 4(4):294-301.
  • BAYLESS KJ, DAVIS GE: Microtubule depolymerisation rapidly collapses capillary tube networks in vitro and angiogenic vessels in vivo through the small GTPase Rho. J. Biol. Chem. (2004) 279:11686-11695.
  • AHMED B, VAN EIJK LI, BOUMA-TER STEEGE JC et al.: Vascular targeting effect of combretastatin A-4 phosphate dominates the inherent angiogenesis inhibitory activity. Int. J. Cancer (2003) 105(1):20-25.
  • SENGUPTA S, KIZILTEPE T, SASISEKHARAN R: A dual-color fluorescence imaging-based system for the dissection of antiangiogenic and chemotherapeutic activity of molecules. FASEB J. (2004) 18(13):1565-1567.
  • ETTENSON DS, GOTLIEB AI: Centrosomes, microtubules and microfilamens in the reendothelialization and remodeling of double sided in vitro wounds. Lab. Invest. (1992) 66:722-733.
  • VACCA A, IURLARO M, RIBATTI D et al.: Antiangiogenesis is produced by nontoxic doses of vinblastine. Blood (1999) 94:4143-4155.
  • BOCCI G, NICOLAOU KC, KERBEL RS: Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res. (2002) 62:6938-6943.
  • BIJMAN MN, VAN NIEUW AMERONGEN GP, LAURENS N, VAN HINSBERGH VW, BOVEN E: Microtubule-targeting agents inhibit angiogenesis at subtoxic concentrations, a process associated with inhibition of Rac1 and Cdc42 activity and changes in the endothelial cytoskeleton. Mol. Cancer Ther. (2006) 5(9):2348-2357.
  • DAVIS GE, CAMARILLO CW: Regulation of endothelial cell morphogenesis by integrins, mechanical forces and matrix guidance pathways. Exp. Cell Res. (1995) 216:113-123.
  • CONNOLLY JO, SIMPSON N, HEWLETT L, HALL A: Rac regulates endothelial morphogenesis and capillary assembly. Mol. Biol. Cell (2002) 13:2474-2485.
  • MERAJVER SD, USMANI SZ: Multifaceted role of Rho proteins in angiogenesis. J. Mammary Gland Biol. Neoplasia (2005) 10(4):291-298.
  • CASCONE I, GIRAUDO E, CACCAVARI F et al.: Temporal and spatial modulation of Rho GTPases during in vitro formation of capillary vascular network. Adherens junctions and myosin light chain as targets of Rac1 and RhoA. J. Biol. Chem. (2003) 278(50):50702-50713.
  • VAN NIEUW AMERONGEN GP, KOOLWIJK P, VERSTEILEN A, VAN HINSBERGH VW: Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro. Arterioscler. Thromb. Vasc. Biol. (2003) 23(2):211-217.
  • LIU Y, SENGER DR: Matrix-specific activation of Src and Rho initiates capillary morphogenesis of endothelial cells. FASEB J. (2004) 18:457-468.
  • UCHIDA S, WATANABE G, SHIMADA Y et al.: The suppression of small GTPase Rho signal transduction pathway inhibits angiogenesis in vitro and in vivo. Biochem. Biophys. Res. Commun. (2000) 269:633-640.
  • HOANG MV, WHELAN MC, SENGER DR: Rho activity critically and selectively regulates endothelial cell organisation during angiogenesis. Proc. Natl. Acad. Sci. USA (2004) 101:1874-1879.
  • GRIGORIEV I, BORISY G, VOROBJEV I: Regulation of microtubule dynamics in 3T3 fibroblasts by Rho family GTPases. Cell Motil. Cytoskeleton (2006) 63(1):29-40.
  • COOK TA, NAGASAKI T, GUNDERSEN GG: Rho guanosine triphosphatase mediates the selective stabilization of microtubules induced by lysophosphatidic acid. J. Cell Biol. (1998) 141(1):175-185.
  • PALAZZO AF, COOK TA, ALBERTS AS, GUNDERSEN GG: mDia mediates Rho-regulated formation and orientation of stable microtubules. Nat. Cell Biol. (2001) 3(8):723-729.
  • LIU BP, CHRZANOWSKA-WODNICKA M, BURRIDGE K: Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho. Cell Adhes. Commun. (1998) 5:249-255.
  • RODRIGUEZ OC, SCHAEFER AW, MANDATO CA et al.: Conserved microtubuleactin interactions in cell movement and morphogenesis. Nat. Cell Biol. (2003) 5(7):599-609.
  • GUNDERSEN GG, BULINSKI JC: Selective stabilization of microtubules oriented toward the direction of cell migration. Proc. Natl. Acad. Sci. USA (1988) 85(16):5946-5950.
  • PALAZZO AF, ENG CH, SCHLAEPFER DD, MARCANTONIO EE, GUNDERSEN GG: Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science (2004) 303(5659):836-839.
  • ETIENNE-MANNEVILLE S: Actin and microtubules in cell motility: which one is in control? Traffic (2004) 5(7):470-477.
  • MAVRIA G, VERCOULEN Y, YEO M et al.: ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell (2006) 9:33-44.
  • KANTHOU C, GRECO O, STRATFORD A et al.: The tubulin-binding agent combretastatin A-4-phosphate arrests endothelial cells in mitosis and induces mitotic cell death. Am. J. Pathol. (2004) 165(4):1401-1411.
  • IYER S, CHAPLIN D, ROSENTHAL D et al.: Induction of apoptosis in proliferating human endothelial cells by the tumor-specific antiangiogenesis agent combretastatin A-4. Cancer Res. (1998) 58:4510-4514.
  • RUDNER A, MURRAY A: The spindle assembly checkpoint. Curr. Opin. Cell Biol. (1996) 8:773-780.
  • HILL SA, CHAPLIN DJ, LEWIS G, TOZER GM: Schedule dependence of combretastatin A4 phosphate in transplanted and spontaneous tumour models. Int. J. Cancer (2002) 102(1):70-74.
  • WOJCIAK-STOTHARD B, POTEMPA S, EICHHOLTZ T, RIDLEY AJ: Rho and Rac but not Cdc42 regulate endothelial cell permeability. J. Cell Sci. (2001) 114(Part 7):1343-1355.
  • MEHTA D, MALIK AB: Signaling mechanisms regulating endothelial permeability. Physiol. Rev. (2006) 86(1):279-367.
  • GOROVOY M, NEAMU R, NIU J et al.: RhoGDI-1 modulation of the activity of monomeric RhoGTPase RhoA regulates endothelial barrier function in mouse lungs. Circ. Res. (2007) 101(1):50-58.
  • MAMMOTO T, PARIKH SM, MAMMOTO A et al.: Angiopoietin-1 requires p190RhoGAP to protect against vascular leakage in vivo. J. Biol. Chem. (2007):[Epub ahead of print].
  • HORI K, SAITO S: Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br. J. Cancer (2003) 89(7):1334-1344.
  • RIENTO K, RIDLEY AJ: Rocks: multifunctional kinases in cell behaviour. Nat. Rev. Mol. Cell Biol. (2003) 4(6):446-456.
  • BEEREPOOT LV, RADEMA SA, WITTEVEEN EO et al.: Phase I clinical evaluation of weekly administration of the novel vascular-targeting agent, ZD6126, in patients with solid tumors. J. Clin. Oncol. (2006) 24(10):1491-1498.
  • SHAKED Y, BERTOLINI F, EMMENEGGER U, LEE CR, KERBEL RS: On the origin and nature of elevated levels of circulating endothelial cells after treatment with a vascular disrupting agent. J. Clin. Oncol. (2006) 24(24):4040; author reply 4040-4041.
  • NIHEI Y, SUZUKI M, OKANO A et al.: Evaluation of antivascular and antimitotic effects of tubulin binding agents in solid tumor therapy. Jpn J. Cancer Res. (1999) 90(12):1387-1395.
  • PARKINS CS, HOLDER AL, HILL SA, CHAPLIN DJ, TOZER GM: Determinants of anti-vascular action by combretastatin A-4 phosphate: role of nitric oxide. Br. J. Cancer (2000) 83(6):811-816.
  • BROOKS AC, KANTHOU C, COOK IH et al.: The vascular targeting agent combretastatin A-4-phosphate induces neutrophil recruitment to endothelial cells in vitro. Anticancer Res. (2003) 23(4):3199-3206.
  • BEAUREGARD DA, HILL SA, CHAPLIN DJ, BRINDLE KM: The susceptibility of tumors to the antivascular drug combretastatin A4 phosphate correlates with vascular permeability. Cancer Res. (2001) 61(18):6811-6815.
  • JAIN RK: Molecular regulation of vessel maturation. Nat. Med. (2003) 9(6):685-693.
  • AKERMAN S, KANTHOU C, PETTYJOHN K et al.: Tumour cells expressiong only single VEGF isoforms (120,164 or 188) form tumours with very different vascular maturities and response to Combretastatin A-4-P. Angiogenesis (BACR/BMS Special Conference: “Tumour Vasculature: New Targets and Therapies”) (2006) 9:29.
  • WOJCIAK-STOTHARD B, TSANG LY, HAWORTH SG: Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) 288(4):L749-L760.
  • WOJCIAK-STOTHARD B, TSANG LY, PALEOLOG E, HALL SM, HAWORTH SG: Rac1 and RhoA as regulators of endothelial phenotype and barrier function in hypoxia-induced neonatal pulmonary hypertension. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) 290(6):L1173-L1182.
  • HADDAD JJ: Hypoxia and the regulation of mitogen-activated protein kinases: gene transcription and the assessment of potential pharmacologic therapeutic interventions. Int. Immunopharmacol. (2004) 4(10-11):1249-1285.
  • DENEKAMP J, HOBSON B: Endothelial cell proliferation in experimental tumours. Br. J. Cancer (1982) 46:711-720.
  • ST CROIX B, RAGO C, VELCULESCU V et al.: Genes expressed in human tumor endothelium. Science (2000) 289(5482):1197-1202.
  • DACHS GU, STEELE AJ, CORALLI C et al.: Anti-vascular agent combretastatin A-4-P modulates hypoxia inducible factor-1 and gene expression. BMC Cancer (2006) 6:280.
  • NOZAWA H, CHIU C, HANAHAN D: Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc. Natl. Acad. Sci. USA (2006) 103(33):12493-12498.
  • WATERMAN-STORER CM, WORTHYLAKE RA, LIU BP, BURRIDGE K, SALMON ED: Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nat. Cell Biol. (1999) 1(1):45-50.
  • WITTMANN T, BOKOCH GM, WATERMAN-STORER CM: Regulation of leading edge microtubule and actin dynamics downstream of Rac1. J. Cell Biol. (2003) 161(5):845-851.

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