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Advantages and Molecular Mechanisms of Heavy-Ion Radiotherapy for Refractory Pancreatic Cancer

https://repo.qst.go.jp/records/73025
https://repo.qst.go.jp/records/73025
96f27d94-65fc-4150-a1bf-1b64aaa32982
Item type 会議発表用資料 / Presentation(1)
公開日 2018-11-19
タイトル
タイトル Advantages and Molecular Mechanisms of Heavy-Ion Radiotherapy for Refractory Pancreatic Cancer
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_c94f
資源タイプ conference object
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 崔, 星

× 崔, 星

WEKO 719631

崔, 星

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Kim, Eun Ho

× Kim, Eun Ho

WEKO 719632

Kim, Eun Ho

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鈴木, 雅雄

× 鈴木, 雅雄

WEKO 719633

鈴木, 雅雄

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藤森, 亮

× 藤森, 亮

WEKO 719634

藤森, 亮

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崔 星

× 崔 星

WEKO 719635

en 崔 星

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Kim Eun Ho

× Kim Eun Ho

WEKO 719636

en Kim Eun Ho

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鈴木 雅雄

× 鈴木 雅雄

WEKO 719637

en 鈴木 雅雄

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藤森 亮

× 藤森 亮

WEKO 719638

en 藤森 亮

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内容記述タイプ Abstract
内容記述 Purpose Pancreatic cancer (adenocarcinoma) is a lethal disease with the worst prognosis among all solid tumors. Over the past two decades, more than 600 patients with locally advanced pancreatic cancer were treated by Heavy Ion Medical Accelerator in Chiba (HIMAC) and achieved promising outcomes. High linear energy transfer (LET) heavy ion beam radiotherapy has several advantages over conventional low LET photon beam radiotherapy. In the present study, we try to explore the molecular mechanisms of how high LET carbon ion beams alone or in combination with DNA damaging drugs or with micro RNA 200c mimic effectively destroy pancreatic cancer stem cells (CSCs) in vitro and in vivo.
Methods Human pancreatic CSCs sorted from PANC1, PK45 cell lines were treated with carbon ion beam alone or in combination with
gemcitabine or miRNA200c mimic, and then cell viability assay, colony, spheroid formation ability assay, and real time PCR analysis, and xenograft tumor growth delay and immunohistochemistry analyses were performed.
Results The relative biological effectiveness (RBE) values for the carbon ion beams relative to X-rays at the D10 levels for CSCs were 2.1-2.4. The colony and spheroid formation capability of CSCs were significantly inhibited by carbon ion beam combined with gemcitabine or with micro RNA 200c mimic. Carbon ion beam combined with gemcitabine or miR200c mimic significantly induced expressions of apoptosis-, autophagy- and angiogenesis-related genes such as BAX, Beclin1, p62, compared to carbon ion alone or X-ray combined with gemcitabine or miR200c mimic. Xenograft tumors from pancreatic cells were effectively disrupted by 25 Gy of carbon ion beam combined with 50 mg/kg gemcitabine accompanied with high expression of LC3, Beclin1, and low expression of HIF1a in pancreatic xenograft tumors. Conclusions Carbon ion beam combined with gemcitabine or with microRNA 200 mimic has high potential to eradicate pancreatic CSCs, and can achieve high curability compared to carbon ion beam alone.
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 AACR-KCA Joint Conference on Precision Medicine in Solid Tumors
発表年月日
日付 2018-11-16
日付タイプ Issued
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