Combination of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) to improve angiogenic gene therapy

被引:5
作者
Diane Bouïs
Mirjam C. Boelens
Erna Peters
Pieter Koolwijk
Gerrie Stob
Ido P. Kema
Marco Klinkenberg
Nanno H. Mulder
Geke A.P. Hospers
机构
[1] Department of Medical Oncology, University Hospital Groningen, Groningen
[2] Dept. of Pathol. and Lab. Medicine, University Hospital Groningen, Groningen
[3] Dept. Vasc./Connective Tissue Res., Gaubius Laboratory TNO-PG, Leiden
[4] Department of Medical Oncology, University Hospital Groningen, 9700 RB Groningen
关键词
Angiogenesis; Gene therapy; Gliostatin; PD-ECGF; TP; VEGF;
D O I
10.1023/B:AGEN.0000021389.49659.31
中图分类号
学科分类号
摘要
To improve current angiogenic gene therapy with a vascular endothelial growth factor (VEGF)-encoding plasmid (Baumgartner et al. Circulation 1998; 97: 1114-23 [1]; Kusumanto et al. Fifth Annual Meeting of the American Society of Gene Therapy, Boston, 2002, Abstr. 621 [2]), we have generated a combination plasmid, encoding the VEGF gene and the thymidine phosphorylase (TP, also known as platelet-derived endothelial growth factor (PD-ECGF) or gliostatin (GLS)) gene: phVEGF165-TP.MB. Upon transfection in COS-7 cells both gene products were expressed and functional as shown by Western blots, ELISAs and bioassays. Culture supernatants of COS-7 cells transfected with this plasmid were able to induce endothelial proliferation. In an in vitro angiogenesis assay with recombinant proteins, TP was able to increase VEGF-induced tube formation. The phVEGF165-TP.MB plasmid is therefore a promising candidate for in vivo angiogenesis studies.
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页码:185 / 192
页数:7
相关论文
共 48 条
[1]  
Baumgartner I., Pieczek A., Manor O., Et al., Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia, Circulation, 97, pp. 1114-1123, (1998)
[2]  
Kusumanto Y.H., Mulder N.H., Dullaart R.P.F., Et al., Phase III comparison of intramuscular delivery of naked plasmid encoding Vascular Endothelial Growth Factor with placebo in diabetic patients with critical limb ischemia, Fifth Annual Meeting of the American Society of Gene Therapy, (2002)
[3]  
Isner J.M., Pieczek A., Schainfeld R., Et al., Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb, Lancet, 348, pp. 370-374, (1996)
[4]  
Shyu K.G., Chang H., Wang B.W., Et al., Intramuscular vascular endothelial growth factor gene therapy in patients with chronic critical leg ischemia, Am J Med, 114, pp. 85-92, (2003)
[5]  
Simovic D., Isner J.M., Ropper A.H., Et al., Improvement in chronic ischemic neuropathy after intramuscular phVEGF165 gene transfer in patients with critical limb ischemia, Arch Neurol, 58, pp. 761-768, (2001)
[6]  
Makinen K., Manninen H., Hedman M., Et al., Increased vascularity detected by digital subtraction angiography after VEGF gene transfer to human lower limb artery: A randomized, placebo-controlled, double-blinded phase II study, Mol Ther, 6, pp. 127-133, (2002)
[7]  
Lathi K.G., Vale P.R., Losordo D.W., Et al., Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease: Anesthetic management and results, Anesth Analg, 92, pp. 19-25, (2001)
[8]  
Sylven C., Sarkar N., Ruck A., Et al., Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A165 plasmid in patients with inoperable angina pectoris, Coron Artery Dis, 12, pp. 239-243, (2001)
[9]  
Losordo D.W., Vale P.R., Hendel R.C., Et al., Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia, Circulation, 105, pp. 2012-2018, (2002)
[10]  
Rajagopalan S., Mohler III E.R., Lederman R.J., Et al., Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: A phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication, Circulation, 108, pp. 1933-1938, (2003)