Combretastatin-A4 disrupts neovascular development in non-neoplastic tissue

Combretastatin-A4 phosphate (cis -CA-4) is a tubulin-binding agent currently undergoing clinical trials as an anti-tumour drug. We have investigated whether CA-4 functions as a tumour-specific anti-vascular agent using the hyperplastic thyroid as a novel in vivo model of neovascularization. CA-4 elicited pathological changes in normal tissue, manifested as the induction of multiple, discrete intravascular thrombi. These vascular-damaging effects indicate that CA-4P does not function as a tumour-specific agent but targets neovasculature irrespective of the primary angiogenic stimulus. © 2001 Cancer Research Campaign

[1]  R. Hesketh,et al.  Targeting tumour vasculature: the development of combretastatin A4. , 2001, The Lancet. Oncology.

[2]  M. Lippman,et al.  Anti-vascular therapy: a new approach to cancer treatment. , 2000, The Western journal of medicine.

[3]  M. Bibby,et al.  In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug , 1999, British Journal of Cancer.

[4]  B Vojnovic,et al.  Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues. , 1999, Cancer research.

[5]  D. Hill,et al.  Growth factors and goitrogenesis. , 1999, The Journal of endocrinology.

[6]  M. Stratford,et al.  Antineoplastic agents 393. Synthesis of the trans-isomer of combretastatin A-4 prodrug. , 1998, Anti-cancer drug design.

[7]  D. Chaplin Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status , 1998, British Journal of Cancer.

[8]  K. Brindle,et al.  Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status. , 1998, British Journal of Cancer.

[9]  G. Pettit,et al.  Antineoplastic agents 389. New syntheses of the combretastatin A-4 prodrug. , 1998, Anti-cancer drug design.

[10]  D. Hill,et al.  Presence and possible role of vascular endothelial growth factor in thyroid cell growth and function. , 1998, The Journal of endocrinology.

[11]  G. Viglietto,et al.  Upregulation of the angiogenic factors PlGF, VEGF and their receptors (Flt-1, Flk-1/KDR) by TSH in cultured thyrocytes and in the thyroid gland of thiouracil-fed rats suggest a TSH-dependent paracrine mechanism for goiter hypervascularization , 1997, Oncogene.

[12]  F. Pelizzoni,et al.  Synthesis of biologically active polyphenolic glycosides (combretastatin and resveratrol series). , 1997, Carbohydrate research.

[13]  G. Tozer,et al.  Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. , 1997, Cancer research.

[14]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.

[15]  M. Stevens,et al.  Synthesis of water-soluble prodrugs of the cytotoxic agent Combretastatin A4 , 1996 .

[16]  K. Yamazaki,et al.  Stimulation by thyroid-stimulating hormone and Grave's immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo. , 1995, The Journal of clinical investigation.

[17]  M. Boyd,et al.  Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6(1a) , 1995, Journal of medicinal chemistry.

[18]  P. Groscurth,et al.  Comparison of FRTL-5 cell growth in vitro with that of xenotransplanted cells and the thyroid of the recipient mouse. , 1991, Endocrinology.

[19]  D. Wynford‐Thomas,et al.  Dissociation of growth and function in the rat thyroid during prolonged goitrogen administration. , 1982, Acta endocrinologica.

[20]  D. Wynford‐Thomas,et al.  Goitrogen-induced thyroid growth in the rat: a quantitative morphometric study. , 1982, The Journal of endocrinology.