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Title: Reducing intratumour acute hypoxia through bevacizumab treatment, referring to the response of quiescent tumour cells and metastatic potential.
Authors: Masunaga, S  kyouindb  KAKEN_id
Liu, Y
Tanaka, H  kyouindb  KAKEN_id
Sakurai, Y  kyouindb  KAKEN_id  orcid (unconfirmed)
Suzuki, M  kyouindb  KAKEN_id  orcid (unconfirmed)
Kondo, N  kyouindb  KAKEN_id
Maruhashi, A
Ono, K
Author's alias: 増永, 慎一郎
Keywords: acute hypoxia
quiescent cell
antiangiogenic agent
mild temperature hyperthermia
Issue Date: Dec-2011
Publisher: British Institute of Radiology
Journal title: The British journal of radiology
Volume: 84
Start page: 1131
End page: 1138
Abstract: [Objectives]The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours. [Methods]B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. [Results]3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment. [Conclusion]Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide.
Rights: © 2011 The British Institute of Radiology.
DOI(Published Version): 10.1259/bjr/38457938
PubMed ID: 21586505
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