Back to Search
Start Over
Adenovirus-mediated gene therapy with an antiangiogenic fragment of thrombospondin-1 inhibits human leukemia xenograft growth in nude mice.
- Source :
-
Leukemia research [Leuk Res] 2003 Aug; Vol. 27 (8), pp. 701-8. - Publication Year :
- 2003
-
Abstract
- Recent investigations support the idea that angiogenesis is involved in the pathophysiology of leukemia. Within a given microenvironment, the angiogenic response is regulated by a delicate balance of angiogenesis inducers and inhibitors. Thrombospondin-1 (TSP-1) is a multifunctional extracellular glycoprotein showing angiostatic properties in multiple in vitro and in vivo assays. Interestingly, there is also proangiogenic domain in this complex molecule. Development of TSP-1 as an antiangiogenic drug has been hindered by multiplicity of its functional effects, difficulties in its production and its poor pharmacokinetics. The aim of the present study was to establish a recombinant adenovirus (ADV.TSP-1(f)) expressing antiangiogenic fragment of TSP-1 (TSP-1(f)), and to determine the feasibility for use of the adenovirally expressed TSP-1(f) in leukemia gene therapy. The results of this investigation showed that TSP-1(f) was expressed efficiently in adenovirus-transduced human myelogenous leukemia K562 cells. Compared to the controls, although there was almost no effect on proliferation of K562 cells in vitro, adenovirus-mediated TSP-1(f) transduction inhibited the growth of K562 xenografts dramatically. Furthermore, the microvessel density (MVD) was much lower in the ADV.TSP-1(f)-treated tumors compared to the controls. These data support the use of in vivo gene delivery approach to produce antiangiogenic fragment of TSP-1 for leukemia therapy.
- Subjects :
- Adenoviridae genetics
Angiogenesis Inhibitors genetics
Angiogenesis Inhibitors pharmacology
Animals
Cell Division drug effects
Female
Genetic Vectors
Humans
K562 Cells
Mice
Mice, Nude
Neovascularization, Pathologic drug therapy
Peptide Fragments administration & dosage
Peptide Fragments genetics
Peptide Fragments pharmacology
Thrombospondin 1 genetics
Thrombospondin 1 pharmacology
Transduction, Genetic
Transplantation, Heterologous
Treatment Outcome
Angiogenesis Inhibitors administration & dosage
Genetic Therapy methods
Leukemia therapy
Thrombospondin 1 administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 0145-2126
- Volume :
- 27
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 12801528
- Full Text :
- https://doi.org/10.1016/s0145-2126(02)00346-6