title: The pharmacological bases of the antiangiogenic activity of paclitaxel.
abstract: In the mid 1990s, researchers began to investigate the antiangiogenic activity of paclitaxel as a possible additional mechanism contributing to its antineoplastic activity in vivo. In the last decade, a number of studies showed that paclitaxel has antiangiogenic activity that could be ascribed to the inhibition of either tubule formation or cell migration, and to an antiproliferative effect towards activated endothelial cells. Furthermore, paclitaxel was shown to downregulate VEGF and Ang-1 expression in tumor cells, and to increase the secretion of TSP-1 in the tumor microenvironment. Moreover, the new pharmaceutical formulations of paclitaxel (such as liposome-encapsulated paclitaxel, ABI-007, and paclitaxel entrapped in emulsifying wax nanoparticles) enhanced the in vivo antiangiogenic activity of the drug. Thus, the preclinical data of paclitaxel may be exploited to implement a novel and rational therapeutic strategy to control tumor progression in patients.
authors: Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors: Guido
authors: G
authors: Bocci
authors: Antonello
authors: A
authors: Di Paolo
authors: Romano
authors: R
authors: Danesi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000803:Angiotensin I / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008081:Liposomes; D008958:Models, Molecular; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D000803:Angiotensin I; D017239:Paclitaxel
references: Br J Cancer. 2008 Apr 22;98(8):1312-9
references: 18362940
references: Cancer Chemother Pharmacol. 1995;36(4):279-82
references: 7543028
references: Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4331-8
references: 16857808
references: Adv Drug Deliv Rev. 2008 Dec 14;60(15):1615-26
references: 18840489
references: Clin Cancer Res. 2009 Apr 15;15(8):2594-601
references: 19351751
references: Cancer Chemother Pharmacol. 2004 Jan;53(1):68-74
references: 14569416
references: Cancer Lett. 2001 Feb 26;163(2):191-200
references: 11165754
references: Curr Cancer Drug Targets. 2007 Sep;7(6):566-81
references: 17896922
references: Int Immunopharmacol. 2003 Dec;3(13-14):1699-714
references: 14636822
references: Neoplasia. 2011 Jan;13(1):40-8
references: 21245939
references: Cancer Res. 1997 Jan 1;57(1):81-6
references: 8988045
references: J Invest Dermatol. 2003 Mar;120(3):476-82
references: 12603862
references: Clin Cancer Res. 2012 Aug 1;18(15):4114-21
references: 22693353
references: Drug Resist Updat. 2006 Feb-Apr;9(1-2):74-86
references: 16714139
references: Anticancer Drugs. 2009 Jun;20(5):355-63
references: 19318912
references: Angiogenesis. 2001;4(3):187-91
references: 11911016
references: J Control Release. 2012 Jun 28;160(3):618-29
references: 22410114
references: AAPS PharmSciTech. 2010 Jun;11(2):752-9
references: 20443090
references: Int J Cancer. 2003 Mar 10;104(1):121-9
references: 12532428
references: J Control Release. 2006 May 30;112(3):312-9
references: 16626835
references: J Asian Nat Prod Res. 2003 Jun;5(2):121-9
references: 12765196
references: Mol Cancer Ther. 2006 Sep;5(9):2348-57
references: 16985069
references: Am J Clin Oncol. 2003 Jun;26(3):e45-53
references: 12796615
references: Eur J Cancer. 2009 Feb;45(3):470-7
references: 19046877
references: Oncol Rep. 2009 Aug;22(2):321-6
references: 19578772
references: Anticancer Drugs. 2003 Jan;14(1):13-9
references: 12544254
references: Anticancer Drugs. 2004 Oct;15(9):871-5
references: 15457127
references: Mol Cancer Ther. 2004 Oct;3(10):1301-10
references: 15486197
references: Oncology. 2009;77(3-4):182-91
references: 19729975
references: Int J Oncol. 2002 Aug;21(2):417-25
references: 12118340
references: J Hematother Stem Cell Res. 2002 Feb;11(1):103-18
references: 11847007
references: J Clin Invest. 2000 Apr;105(8):R15-24
references: 10772661
references: Semin Radiat Oncol. 2012 Oct;22(4):277-83
references: 22985810
references: Cancer Chemother Pharmacol. 2006 Sep;58(3):354-60
references: 16333676
references: Eur J Pharm Biopharm. 2013 Jan;83(1):87-94
references: 23085332
references: Ann Surg Oncol. 2008 Dec;15(12):3407-14
references: 18795370
references: Clin Cancer Res. 1996 Nov;2(11):1843-9
references: 9816139
references: Cancer Lett. 1996 Oct 22;107(2):265-72
references: 8947523
references: J Pharmacol Sci. 2003 Oct;93(2):197-203
references: 14578588
references: J Clin Invest. 1998 Apr 1;101(7):1401-13
references: 9525983
references: Clin Cancer Res. 2003 Jun;9(6):2335-41
references: 12796403
references: Cancer Res. 2004 Feb 1;64(3):821-4
references: 14871806
references: Pancreas. 2003 Mar;26(2):166-72
references: 12604915
references: Anticancer Res. 2004 Mar-Apr;24(2A):397-404
references: 15152936
references: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12917-22
references: 14561896
references: Int J Biol Markers. 2000 Oct-Dec;15(4):308-11
references: 11192826
references: Biochim Biophys Acta. 1992 Jun 29;1135(3):269-74
references: 1623013
references: Exp Cell Res. 2004 Oct 1;299(2):286-93
references: 15350528
references: Angiogenesis. 2012 Jun;15(2):275-86
references: 22382585
references: APMIS. 2004 Mar;112(3):201-9
references: 15153162
references: Anticancer Res. 1998 Jul-Aug;18(4C):2977-80
references: 9713495
references: Cancer Res. 2002 Dec 1;62(23):6938-43
references: 12460910
references: Cancer Res. 2005 Mar 15;65(6):2433-40
references: 15781659
references: Cancer Invest. 2010 Jan;28(1):74-84
references: 20001297
references: Eur J Pharm Biopharm. 2009 Jun;72(2):418-27
references: 19462478
references: Biomed Pharmacother. 2005 Oct;59 Suppl 2:S337-9
references: 16507404
references: Eur J Cancer. 2000 Jun;36(10):1248-57
references: 10882863
references: Crit Rev Ther Drug Carrier Syst. 2009;26(4):333-72
references: 20001890
references: Mol Cancer Ther. 2002 Nov;1(13):1191-200
references: 12479700
references: Cancer Biother Radiopharm. 1999 Feb;14(1):31-6
references: 10850285
references: Int J Cancer. 2005 Jan 20;113(3):490-8
references: 15455390
references: J Mammary Gland Biol Neoplasia. 2012 Dec;17(3-4):229-39
references: 23011602
references: Neoplasia. 2012 Sep;14(9):846-54
references: 23019416
references: Nat Rev Cancer. 2004 Jun;4(6):423-36
references: 15170445
references: APMIS. 2003 Nov;111(11):995-1003
references: 14629265
references: Clin Cancer Res. 2002 Oct;8(10):3226-31
references: 12374693
references: Cancer Res. 2000 Apr 1;60(7):1878-86
references: 10766175
references: Int J Nanomedicine. 2009;4:99-105
references: 19516888
references: Recent Pat Anticancer Drug Discov. 2009 Nov;4(3):262-72
references: 19538176
references: Onco Targets Ther. 2011;4:123-36
references: 21792318
references: Mol Ther. 2010 Jun;18(6):1233-43
references: 20372107
references: Biomed Pharmacother. 2005 Oct;59 Suppl 2:S306-10
references: 16507399
references: Cancer Res. 1982 Apr;42(4):1412-22
references: 7060015
references: Cancer Res. 2006 Aug 15;66(16):8192-9
references: 16912198