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Materials and Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2\u0027-deoxyuridine (BrdU) to label all proliferating (P) cells. They received gamma-ray irradiation following loading with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The sensitivity of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P + Q) tumor cell population was determined from BrdU non-treated tumors. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results In the total cells, a more marked enhancement in sensitivity was observed with nicotinamide than MTH. In Q cells, MTH combination induced a more marked enhancement than nicotinamide. Both nicotinamide and MTH reduced the size of the hypoxic fraction in the two cell populations, especially nicotinamide in the total cells and MTH in Q cells. Without gamma-ray irradiation, nicotinamide loading tended to decrease the number of lung metastases. With gamma-ray irradiation, nicotinamide loading and MTH, especially the former, reduced the number of metastases more than gamma-ray irradiation only. Conclusion Hypoxia manipulation in solid tumors has the potential to influence lung metastases. 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Significance of manipulating intratumor hypoxia in the effect on lung metastases in radiotherapy, with reference to its effect on the sensitivity of intratumor quiescent cells.
https://repo.qst.go.jp/records/45702
https://repo.qst.go.jp/records/45702a1a34c27-021b-4b62-96a3-3ce04cd0a021
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2009-12-26 | |||||
タイトル | ||||||
タイトル | Significance of manipulating intratumor hypoxia in the effect on lung metastases in radiotherapy, with reference to its effect on the sensitivity of intratumor quiescent cells. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Masunaga, Shinichiro
× Masunaga, Shinichiro× Matsumoto, Yoshitaka× Hirayama, Ryoichi× Kashino, Genro× Tanaka, Hiroki× Suzuki, Minoru× Kinashi, Yuko× Liu, Yong× Ando, Koichi× Ono, Koji× 増永 慎一郎× 松本 孔貴× 平山 亮一× 田中 浩基× 小野 公二 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Purpose To evaluate the effect of manipulating intratumor hypoxia during radiotherapy on lung metastasis, referring to its effect on the sensitivity of quiescent tumor cells. Materials and Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. They received gamma-ray irradiation following loading with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The sensitivity of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. That of the total (=P + Q) tumor cell population was determined from BrdU non-treated tumors. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results In the total cells, a more marked enhancement in sensitivity was observed with nicotinamide than MTH. In Q cells, MTH combination induced a more marked enhancement than nicotinamide. Both nicotinamide and MTH reduced the size of the hypoxic fraction in the two cell populations, especially nicotinamide in the total cells and MTH in Q cells. Without gamma-ray irradiation, nicotinamide loading tended to decrease the number of lung metastases. With gamma-ray irradiation, nicotinamide loading and MTH, especially the former, reduced the number of metastases more than gamma-ray irradiation only. Conclusion Hypoxia manipulation in solid tumors has the potential to influence lung metastases. Notably, acute hypoxia-releasing nicotinamide may be promising for reducing the number of lung metastases. | |||||
書誌情報 |
Clinical & Experimental Metastasis 巻 26, 号 7, p. 693-700, 発行日 2009-05 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0262-0898 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1007/s10585-009-9268-5 | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.springerlink.com/content/k4j1788551622t41/fulltext.pdf | |||||
関連名称 | http://www.springerlink.com/content/k4j1788551622t41/fulltext.pdf |