Document Detail

Use of thymidine kinase gene-modified endothelial progenitor cells as a vector targeting angiogenesis in glioma gene therapy.
MedLine Citation:
PMID:  20357517     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The poor prognosis of patients with glioma is due to infiltrative growth of glioma cells, which correlates with their ability to induce angiogenesis. Tumor angiogenesis is supported by the mobilization and functional incorporation of endothelial progenitor cells (EPCs). The aim of this study was to propose the use of gene-modified EPCs as a vector system that allowed systemic gene delivery into multiple areas of tumor angiogenesis for glioma therapy. METHODS: Thymidine kinase (TK) gene-modified EPCs were mixed with glioma cells or human umbilical vein endothelial cells (HUVECs) at varying ratios for ganciclovir in vitro. Cell proliferation was evaluated by MTT assay, and apoptosis was examined by annexin-V and phosphatidylserine (propidium iodide) staining. EPCs were injected via tail vein into nude mice bearing glioma, and EPC incorporation into the tumor was determined immunohistochemically. The antitumor effects of TK gene-modified EPCs in vivo were evaluated by apoptosis assay and microvessel density analysis. RESULTS: TK gene-modified EPCs exerted a potent bystander effect on glioma cells and HUVECs by induction of apoptosis via caspase activation in vitro. EPCs incorporated preferentially into glioma vasculatures. Furthermore, TK gene-modified EPCs clearly augmented the antitumor effect by inhibition of angiogenesis following repeated intravenous injection in vivo. CONCLUSION: The results indicate the feasibility of EPC-based gene delivery into disseminated areas of tumor angiogenesis as a rational strategy for glioma gene therapy.
Jun-xia Zhang; Chun-sheng Kang; Lei Shi; Peng Zhao; Ning Liu; Yong-ping You
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-31
Journal Detail:
Title:  Oncology     Volume:  78     ISSN:  1423-0232     ISO Abbreviation:  Oncology     Publication Date:  2010  
Date Detail:
Created Date:  2010-04-30     Completed Date:  2010-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0135054     Medline TA:  Oncology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  94-102     Citation Subset:  IM    
Copyright Information:
Copyright 2010 S. Karger AG, Basel.
Department of Neurosurgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
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MeSH Terms
Antigens, CD / analysis
Apoptosis / drug effects,  physiology*
Cell Division / drug effects
Endothelium, Vascular / cytology,  physiology
Fetal Blood / cytology
Ganciclovir / pharmacology
Gene Therapy / methods*
Glioma / genetics,  therapy*
Glycoproteins / analysis
Leukocytes, Mononuclear / cytology
Mice, Inbred BALB C
Mice, Nude
Neovascularization, Pathologic / prevention & control*
Peptides / analysis
Stem Cell Transplantation*
Stem Cells / cytology,  enzymology*
Thymidine Kinase / genetics*,  metabolism
Transplantation, Heterologous
Umbilical Veins
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/Glycoproteins; 0/Peptides; 82410-32-0/Ganciclovir; EC Kinase

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