ABSTRACT
The purpose of this study was to devise an expanded ischemic flap model and to investigate the role of AMD-3100 (Plerixafor, chemokine receptor 4 inhibitor) in this model by confirming its effect on mobilization of stem cells from the bone marrow. Male Sprague-Dawley rats were used as an animal research model. The mobilization of stem cells from the bone marrow was confirmed in the AMD-3100-treated group. The fractions of endothelial progenitor cells (EPC) and the vascular endothelial growth factor receptor (VEGFR) 2+ cells in the peripheral blood were increased in groups treated with AMD-3100. The expression of vascular endothelial growth factor (VEGF) was increased in response to expansion or AMD injection. The expression of stromal cell derived factor (SDF)-1 and VEGFR2 were increased only in unexpanded flap treated with AMD-3100. Treatment with AMD-3100 increased both the number and area of blood vessels. However, there were no statistically significant differences in the survival area or physiologic microcirculation in rats from the other groups. This endogenous neovascularization induced by AMD-3100 may be a result of the increase in both the area and number of vessels, as well as paracrine augmentation of the expression of VEGF and EPCs. However, the presence of a tissue expander under the flap could block the neovascularization between the flap and the recipient regardless of AMD-3100 treatment and expansion.
Subject(s)
Animals , Male , Rats , Anti-HIV Agents/pharmacology , Bone Marrow Cells/cytology , Chemokine CXCL12/biosynthesis , Endothelial Progenitor Cells/cytology , Hematopoietic Stem Cells/cytology , Heterocyclic Compounds/pharmacology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neovascularization, Physiologic , Nitric Oxide Synthase Type III/metabolism , Rats, Sprague-Dawley , Receptors, CXCR4/antagonists & inhibitors , Surgical Flaps/blood supply , Tissue Expansion/methods , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor Receptor-2/biosynthesisABSTRACT
Triple-negative breast cancer(TNBC)is a special subtype of breast cancer which is invalid to endocrine therapy.Anti-Her2 targeted therapies such as herceptin and lapatinib are not suitable to TNBC.At present,conventional chemotherapy is the only way for the medical therapy of TNBC.Thus,searching for novel therapeutic agents for TNBC is one of hot researches of breast cancer.New targeted therapy drugs such as PARP-1 inhibitors,EGFR inhibitors,CXCR4 inhibitors,anti-angiogenesis drugs,Src tyrosine kinase inhibitor,and mTOR inhibitor are being researched.