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Title: Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis.
Authors: Masunaga, Shin-Ichiro  kyouindb  KAKEN_id
Sakurai, Yoshinori
Tano, Keizo  kyouindb  KAKEN_id
Tanaka, Hiroki  kyouindb  KAKEN_id
Suzuki, Minoru  kyouindb  KAKEN_id
Kondo, Natsuko  kyouindb  KAKEN_id
Narabayashi, Masaru
Watanabe, Tsubasa  kyouindb  KAKEN_id
Nakagawa, Yosuke
Maruhashi, Akira
Ono, Koji
Author's alias: 増永, 慎一郎
Issue Date: Jul-2014
Publisher: Spandidos Publications
Journal title: Experimental and therapeutic medicine
Volume: 8
Issue: 1
Start page: 291
End page: 301
Abstract: The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a (10)B-carrier [L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a (10)B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide.
Rights: © Spandidos Publications
URI: http://hdl.handle.net/2433/199604
DOI(Published Version): 10.3892/etm.2014.1704
PubMed ID: 24944637
Appears in Collections:Journal Articles

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