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Title: Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation

Abstract

Purpose: Previous studies have shown that the plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are regulated by hypoxia and irradiation and are involved in neoangiogenesis. The aim of this study was to determine in vivo whether changes in PAI-1 and VEGF during fractionated irradiation could predict for radiation resistance. Methods and Materials: Six xenografted tumor lines from human squamous cell carcinomas (HSCC) of the head and neck were irradiated with 0, 3, 5, 10, and 15 daily fractions of 2 Gy. The PAI-1 and VEGF antigen levels in tumor lysates were determined by enzyme-linked immunosorbent assay kits. The amounts of PAI-1 and VEGF were compared with the dose to cure 50% of tumors (TCD{sub 50}). Colocalization of PAI-1, pimonidazole (hypoxia), CD31 (endothelium), and Hoechst 33342 (perfusion) was examined by immunofluorescence. Results: Human PAI-1 and VEGF (hVEGF) expression levels were induced by fractionated irradiation in UT-SCC-15, UT-SCC-14, and UT-SCC-5 tumors, and mouse VEGF (msVEGF) was induced only in UT-SCC-5 tumors. High hVEGF levels were significantly associated with radiation sensitivity after 5 fractions (P=.021), and high msVEGF levels were significantly associated with radiation resistance after 10 fractions (P=.007). PAI-1 staining was observed in the extracellular matrix, the cytoplasmmore » of fibroblast-like stroma cells, and individual tumor cells at all doses of irradiation. Colocalization studies showed PAI-1 staining close to microvessels. Conclusions: These results indicate that the concentration of tumor-specific and host-specific VEGF during fractionated irradiation could provide considerably divergent information for the outcome of radiation therapy.« less

Authors:
 [1];  [1];  [1];  [2];  [1]; ; ;  [3];  [1];  [1];  [2]
  1. Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany)
  2. (Germany)
  3. OncoRay Center for Radiation Research, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany)
Publication Date:
OSTI Identifier:
22149607
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 84; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; ANTIGENS; CARCINOMAS; CYTOPLASM; ENDOTHELIUM; ENZYMES; FIBROBLASTS; FRACTIONATED IRRADIATION; GROWTH FACTORS; HEAD; IN VIVO; MICE; MONITORING; NECK; PLASMINOGEN; RADIATION DOSES; RADIOTHERAPY; SENSITIVITY; TUMOR CELLS

Citation Formats

Bayer, Christine, E-mail: christine.bayer@yahoo.com, Kielow, Achim, Schilling, Daniela, HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden, Maftei, Constantin-Alin, Zips, Daniel, Yaromina, Ala, Baumann, Michael, Molls, Michael, Multhoff, Gabriele, and HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden. Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2012.04.033.
Bayer, Christine, E-mail: christine.bayer@yahoo.com, Kielow, Achim, Schilling, Daniela, HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden, Maftei, Constantin-Alin, Zips, Daniel, Yaromina, Ala, Baumann, Michael, Molls, Michael, Multhoff, Gabriele, & HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden. Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation. United States. doi:10.1016/J.IJROBP.2012.04.033.
Bayer, Christine, E-mail: christine.bayer@yahoo.com, Kielow, Achim, Schilling, Daniela, HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden, Maftei, Constantin-Alin, Zips, Daniel, Yaromina, Ala, Baumann, Michael, Molls, Michael, Multhoff, Gabriele, and HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden. Thu . "Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation". United States. doi:10.1016/J.IJROBP.2012.04.033.
@article{osti_22149607,
title = {Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation},
author = {Bayer, Christine, E-mail: christine.bayer@yahoo.com and Kielow, Achim and Schilling, Daniela and HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden and Maftei, Constantin-Alin and Zips, Daniel and Yaromina, Ala and Baumann, Michael and Molls, Michael and Multhoff, Gabriele and HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden},
abstractNote = {Purpose: Previous studies have shown that the plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are regulated by hypoxia and irradiation and are involved in neoangiogenesis. The aim of this study was to determine in vivo whether changes in PAI-1 and VEGF during fractionated irradiation could predict for radiation resistance. Methods and Materials: Six xenografted tumor lines from human squamous cell carcinomas (HSCC) of the head and neck were irradiated with 0, 3, 5, 10, and 15 daily fractions of 2 Gy. The PAI-1 and VEGF antigen levels in tumor lysates were determined by enzyme-linked immunosorbent assay kits. The amounts of PAI-1 and VEGF were compared with the dose to cure 50% of tumors (TCD{sub 50}). Colocalization of PAI-1, pimonidazole (hypoxia), CD31 (endothelium), and Hoechst 33342 (perfusion) was examined by immunofluorescence. Results: Human PAI-1 and VEGF (hVEGF) expression levels were induced by fractionated irradiation in UT-SCC-15, UT-SCC-14, and UT-SCC-5 tumors, and mouse VEGF (msVEGF) was induced only in UT-SCC-5 tumors. High hVEGF levels were significantly associated with radiation sensitivity after 5 fractions (P=.021), and high msVEGF levels were significantly associated with radiation resistance after 10 fractions (P=.007). PAI-1 staining was observed in the extracellular matrix, the cytoplasm of fibroblast-like stroma cells, and individual tumor cells at all doses of irradiation. Colocalization studies showed PAI-1 staining close to microvessels. Conclusions: These results indicate that the concentration of tumor-specific and host-specific VEGF during fractionated irradiation could provide considerably divergent information for the outcome of radiation therapy.},
doi = {10.1016/J.IJROBP.2012.04.033},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 3,
volume = 84,
place = {United States},
year = {2012},
month = {11}
}