@misc{oai:repo.qst.go.jp:00073025,
 author = {崔, 星 and Ｋｉｍ, Ｅｕｎ Ｈｏ and 鈴木, 雅雄 and 藤森, 亮 and 崔 星 and Ｋｉｍ Ｅｕｎ Ｈｏ and 鈴木 雅雄 and 藤森 亮},
 month = {Nov},
 note = {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., AACR-KCA Joint Conference on Precision Medicine in Solid Tumors},
 title = {Advantages and Molecular Mechanisms of Heavy-Ion Radiotherapy for Refractory Pancreatic Cancer},
 year = {2018}
}