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Title: Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: Inhibition of tumor angiogenesis with extensive tumor necrosis

Abstract

Purpose: Toward improved glioblastoma multiforme treatment, we determined whether celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, could enhance glioblastoma radiosensitivity by inducing tumor necrosis and inhibiting tumor angiogenesis. Methods and Materials: U-87MG cells treated with celecoxib, irradiation, or both were assayed for clonogenic survival and angiogenic factor protein analysis (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor [VEGF]). In vivo, survival of mice intracranially implanted with U-87MG cells and treated with celecoxib and/or irradiation was monitored. Isolated tumors were assessed for tumor necrosis and tumor microvascular density by von Williebrand's factor (vWF) immunohistochemical staining. Results: Celecoxib (4 and 30 {mu}M; 24, 48, and 72 h) enhanced U-87MG cell radiosensitivity by significantly reducing clonogenic survival of irradiated cells. Angiopoietin-1 and VEGF proteins were decreased, whereas angiopoietin-2 expression increased after 72 h of celecoxib alone and when combined with irradiation. In vivo, median survival of control mice intracranially implanted with U-87MG cells was 18 days. Celecoxib (100 mg/kg/day, 2 weeks) significantly extended median survival of irradiated mice (24 Gy total) from 34 to 41 days, with extensive tumor necrosis [24.5 {+-} 8.6% of tumor region, compared with irradiation alone (2.7 {+-} 1.8%)]. Tumor microvascular density was significantly reduced in combined celecoxib and irradiated tumorsmore » (52.5 {+-} 2.9 microvessels per mm{sup 2} tumor region), compared with irradiated tumors alone (65.4 {+-} 4.0 microvessels per mm{sup 2}). Conclusion: Celecoxib significantly enhanced glioblastoma radiosensitivity, reduced clonogenic survival, and prolonged survival of glioblastoma-implanted mice by inhibition of tumor angiogenesis with extensive tumor necr0010os.« less

Authors:
 [1];  [2];  [2];  [3];  [4];  [2];  [5]
  1. Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre (Singapore). E-mail: dmskkb@nccs.com.sg
  2. Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre (Singapore)
  3. Department of Pathology, Singapore General Hospital (Singapore)
  4. Baker Heart Research Institute, Melbourne (Australia)
  5. Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre (Singapore) and National Neuroscience Institute, Singapore General Hospital Campus (Singapore)
Publication Date:
OSTI Identifier:
20944743
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2006.09.055; PII: S0360-3016(06)03364-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; GLIOMAS; GROWTH FACTORS; IN VIVO; INHIBITION; IRRADIATION; MICE; NECROSIS; RADIOSENSITIVITY

Citation Formats

Kang, Khong Bee, Wang, Ting Ting, Woon, Chow Thai, Cheah, Elizabeth S., Moore, Xiao Lei, Zhu Congju, and Wong, Meng Cheong. Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: Inhibition of tumor angiogenesis with extensive tumor necrosis. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.09.055.
Kang, Khong Bee, Wang, Ting Ting, Woon, Chow Thai, Cheah, Elizabeth S., Moore, Xiao Lei, Zhu Congju, & Wong, Meng Cheong. Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: Inhibition of tumor angiogenesis with extensive tumor necrosis. United States. doi:10.1016/j.ijrobp.2006.09.055.
Kang, Khong Bee, Wang, Ting Ting, Woon, Chow Thai, Cheah, Elizabeth S., Moore, Xiao Lei, Zhu Congju, and Wong, Meng Cheong. Thu . "Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: Inhibition of tumor angiogenesis with extensive tumor necrosis". United States. doi:10.1016/j.ijrobp.2006.09.055.
@article{osti_20944743,
title = {Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: Inhibition of tumor angiogenesis with extensive tumor necrosis},
author = {Kang, Khong Bee and Wang, Ting Ting and Woon, Chow Thai and Cheah, Elizabeth S. and Moore, Xiao Lei and Zhu Congju and Wong, Meng Cheong},
abstractNote = {Purpose: Toward improved glioblastoma multiforme treatment, we determined whether celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, could enhance glioblastoma radiosensitivity by inducing tumor necrosis and inhibiting tumor angiogenesis. Methods and Materials: U-87MG cells treated with celecoxib, irradiation, or both were assayed for clonogenic survival and angiogenic factor protein analysis (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor [VEGF]). In vivo, survival of mice intracranially implanted with U-87MG cells and treated with celecoxib and/or irradiation was monitored. Isolated tumors were assessed for tumor necrosis and tumor microvascular density by von Williebrand's factor (vWF) immunohistochemical staining. Results: Celecoxib (4 and 30 {mu}M; 24, 48, and 72 h) enhanced U-87MG cell radiosensitivity by significantly reducing clonogenic survival of irradiated cells. Angiopoietin-1 and VEGF proteins were decreased, whereas angiopoietin-2 expression increased after 72 h of celecoxib alone and when combined with irradiation. In vivo, median survival of control mice intracranially implanted with U-87MG cells was 18 days. Celecoxib (100 mg/kg/day, 2 weeks) significantly extended median survival of irradiated mice (24 Gy total) from 34 to 41 days, with extensive tumor necrosis [24.5 {+-} 8.6% of tumor region, compared with irradiation alone (2.7 {+-} 1.8%)]. Tumor microvascular density was significantly reduced in combined celecoxib and irradiated tumors (52.5 {+-} 2.9 microvessels per mm{sup 2} tumor region), compared with irradiated tumors alone (65.4 {+-} 4.0 microvessels per mm{sup 2}). Conclusion: Celecoxib significantly enhanced glioblastoma radiosensitivity, reduced clonogenic survival, and prolonged survival of glioblastoma-implanted mice by inhibition of tumor angiogenesis with extensive tumor necr0010os.},
doi = {10.1016/j.ijrobp.2006.09.055},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 67,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2007},
month = {Thu Mar 01 00:00:00 EST 2007}
}