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Combretastatin A-4 phosphate (CA-4-P) is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent.

Gabi U Dachs et al.

BMC Cancer 6 (7), 07 Dec 2006

Combretastatin A-4 phosphate (CA-4-P), a tubulin-depolymerising agent structurally related to colchicines, is in clinical trials as a vascular disrupting agent.

Gabi U Dachs et al.

BMC Cancer 6 (7), 07 Dec 2006

Combretastatin A-4 was originally isolated from the South African bush willow Combretum caffrum .

Gabi U Dachs et al.

BMC Cancer 6 (7), 07 Dec 2006

New syntheses of the combretastatin A-4 prodrug Anticancer Drug Des 1998 13 183 91 9595032 Galbraith SM Chaplin DJ Lee F Stratford MR Locke RJ Vojnovic B Tozer GM 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 11299795 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 9 11877280 10.1182/blood.V99.6.2060 Perona R Montaner S Saniger L Sanchez-Perez I Bravo R Lacal JC Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins Genes Dev 1997 11 463 75 9042860 Kanthou C Greco O Stratford A Cook I Knight R Benzakour O Tozer G The tubulin-binding agent combretastatin A-4-phosphate arrests endothelial cells in mitosis and induces mitotic cell death Am J Pathol 2004 165 1401 11 15466404 Tozer GM Prise VE Wilson J Locke RJ Vojnovic B Stratford MR Dennis MF Chaplin DJ Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues Cancer Res 1999 59 1626 34 10197639 Tozer GM Prise VE Wilson J Cemazar M Shan S Dewhirst MW Barber PR Vojnovic B Chaplin DJ Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability Cancer Res 2001 61 6413 22 11522635 Horsman MR 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 8 9845117 10.1016/S0360-3016(98)00299-5 El-Emir E Boxer GM Petrie IA Boden RW Dearling JL Begent RH Pedley RB Tumour parameters affected by combretastatin A-4 phosphate therapy in a human colorectal xenograft model in nude mice Eur J Cancer 2005 41 799 806 15763657 10.1016/j.ejca.2005.01.001 Dachs GU Tozer GM Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic exploitation Eur J Cancer 2000 36 1649 60 10959051 10.1016/S0959-8049(00)00159-3 Dark GG Hill SA Prise VE Tozer GM Pettit GR Chaplin DJ Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature Cancer Res 1997 57 1829 34 9157969 Pugh CW Ratcliffe PJ The von Hippel-Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis Semin Cancer Biol 2003 13 83 9 12507560 10.1016/S1044-579X(02)00103-7 Zhong H De Marzo AM Laughner E Lim M Hilton DA Zagzag D Buechler P Isaacs WB Semenza GL Simons JW Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases Cancer Res 1999 59 5830 5 10582706 Sheta EA Trout H Gildea JJ Harding MA Theodorescu D Cell density mediated pericellular hypoxia leads to induction of HIF-1alpha via nitric oxide and Ras/MAP kinase mediated signaling pathways Oncogene 2001 20 7624 34 11753640 10.1038/sj.onc.1204972 Wang GL Semenza GL Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction Blood 1993 82 3610 5 8260699 Tozer GM Kanthou C Parkins CS Hill SA The biology of the combretastatins as tumour vascular targeting agents Int J Exp Pathol 2002 83 21 38 12059907 10.1046/j.1365-2613.2002.00211.x Kallio PJ Okamoto K O'Brien S Carrero P Makino Y Tanaka H Poellinger L Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1α EMBO J 1998 17 6573 86 9822602 10.1093/emboj/17.22.6573 Stevenson JP Rosen M Sun W Gallagher M Haller DG Vaughn D Giantonio B Zimmer R Petros WP Stratford M Chaplin D Young SL 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 4428 38 14645433 10.1200/JCO.2003.12.986 Tian H McKnight SL Russell DW Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells Genes Dev 1997 11 72 82 9000051 Sowter HM Raval RR Moore JW Ratcliffe PJ Harris AL Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia Cancer Res 2003 63 6130 4 14559790 Jung YJ Isaacs JS Lee S Trepel J Neckers L Microtubule disruption utilizes an NFκB-dependent pathway to stabilize HIF-1α protein J Biol Chem 2003 278 7445 52 12488445 10.1074/jbc.M209804200 Anwar KN Fazal F Malik AB Rahman A RhoA/Rho-associated kinase pathway selectively regulates thrombin-induced intercellular adhesion molecule-1 expression in endothelial cells via activation of I kappa B kinase beta and phosphorylation of RelA/p65 J Immunol 2004 173 6965 72 15557193 Sheng Y Hua J Pinney KG Garner CM Kane RR Prezioso JA Chaplin DJ Edvardsen K Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis Int J Cancer 2004 111 604 10 15239140 10.1002/ijc.20297 Theodoropoulos VE Lazaris ACh Sofras F Gerzelis I Tsoukala V Ghikonti I Manikas K Kastriotis I Hypoxia-inducible factor 1 alpha expression correlates with angiogenesis and unfavorable prognosis in bladder cancer Eur Urol 2004 46 200 8 15245814 10.1016/j.eururo.2004.04.008 Figures and Tables Figure 1 Effect of CA-4-P on cellular HIF-1 localisation and nuclear morphology.

Gabi U Dachs et al.

BMC Cancer 6 (7), 07 Dec 2006

 
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