| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○著者 (必須): | 1. | (英) Fujimoto Shota (日) 藤本 将太 (読) ふじもと しょうた
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| ○学籍番号 (推奨): | □ | ****
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| 2. | 六車 直樹
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| 3. | 岡本 耕一 ([徳島大学.病院.診療科.内科.消化器内科])
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| 4. | (英) Kurihara Takeshi (日) (読)
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| 5. | 佐藤 康史 ([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域消化器・総合内科学])
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| 6. | (英) Miyamoto Yoshihiko (日) 宮本 佳彦 (読) みやもと よしひこ
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| ○学籍番号 (推奨): | □ | ****
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| 7. | 北村 晋志
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| 8. | 宮本 弘志 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学]/[徳島大学.病院.診療科.内科.消化器内科])
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| 9. | (英) Taguchi Takahiro (日) (読)
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| 10. | 常山 幸一 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.疾患病理学])
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| 11. | 高山 哲治 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])
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| ○題名 (必須): | □ | (英) A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors. (日)
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| ○要約 (任意): | □ | (英) It is difficult to distinguish gastrointestinal stromal tumors (GISTs) from other types of submucosal tumors under conventional gastrointestinal endoscopy. We aimed to detect GISTs by molecular fluorescence imaging using a near-infrared (NIR) photosensitizer (IR700)-conjugated anti-c-KIT antibody and to treat GISTs by photoimmunotherapy with NIR irradiation as a non-invasive theranostic procedure. We also investigated the therapeutic mechanisms. Human GIST cell lines GIST-T1 and GIST-882M were incubated with IR700-conjugated anti-c-KIT antibody, IR700-12A8, and observed by confocal laser microscopy. Mice with GIST-T1 xenografts or rats with orthotopic xenografts were injected with IR700-12A8 or AF488-conjugated antibody, and observed under IVIS or autofluorescence imaging (AFI) endoscopy. GIST cells were treated with IR700-12A8 and NIR light and vivo, and cell viability, histology and apoptosis were evaluated. Strong red fluorescence of IR700-12A8 was observed on the cell membrane of GIST cells and was gradually internalized into the cytoplasm. Tumor-specific accumulation of IR700-12A8 was observed in GIST-T1 xenografts in mice. Under AFI endoscopy, a strong fluorescence signal was observed in orthotopic GIST xenografts in rats through the normal mucosa covering the tumor. The percentage of dead cells significantly increased in a light-dose-dependent manner and both acute necrotic and late apoptotic cell death was observed with annexin/PI staining. Cleaved PARP expression was significantly increased after IR700-12A8-mediated NIR irradiation, which was almost completely reversed by NaN. All xenograft tumors (7/7) immediately regressed and 4/7 tumors completely disappeared after IR700-12A8-mediated NIR irradiation. Histologic assessment and TUNEL staining revealed apoptosis in the tumors. NIR fluorescence imaging using IR700-12A8 and subsequent NIR irradiation could be a very effective theranostic technology for GIST, the underlying mechanism of which appears to involve acute necrosis and supposedly late apoptosis induced by singlet oxygen. (日)
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| ○キーワード (推奨): |
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| ○誌名 (必須): | □ | Theranostics (Ivyspring International Publisher)
(eISSN: 1838-7640)
| ○ISSN (任意): | □ | 1838-7640
ISSN: 1838-7640
(eISSN: 1838-7640) Title: TheranosticsTitle(ISO): TheranosticsPublisher: Ivyspring International Publisher (NLM Catalog)
(Scopus)
(CrossRef)
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| ○巻 (必須): | □ | 8
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| ○号 (必須): | □ | 9
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| ○頁 (必須): | □ | 2313 2328
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2018年 3月 21日 (平成 30年 3月 21日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.7150/thno.22027 (→Scopusで検索)
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| ○PMID (任意): | □ | 29721082 (→Scopusで検索)
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| ○CRID (任意): |
| ○Scopus (任意): | 1. | 2-s2.0-85044356978
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.7150/thno.22027 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) KeywordList.Keyword: c-KIT (日)
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| 4. | (英) KeywordList.Keyword: fluorescence endoscopy (日)
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| 5. | (英) KeywordList.Keyword: gastrointestinal stromal tumors (GIST) (日)
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| 6. | (英) KeywordList.Keyword: near-infrared photoimmunotherapy (日)
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| 7. | (英) CoiStatement: Competing Interests: The authors have declared that no competing interest exists. (日)
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