题目：HEAVY ION IRRADIATION ALONE OR INCOMBINATION WITH CHEMOTHRAPY EFFECTIVELY DISRUPTS PUTATIVE PANCREATIC CANCERSTEM CELLS

报告人：Sei Sai(崔星）主任研究员

Medical Physics Research Program, Research Centerfor Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.

时间：9月1日（星期二）上午9:00

地点：独墅湖校区401号楼一楼会议室

欢迎广大师生踊跃参加！

报告人介绍：

崔星，1992年毕业于上海同济大学临床医学系，1998年东京大学大学院医学系研究科博士，2000年东京大学大学院药学系遗传学教室博士后研究员；2001年  日本国立环境研究所环境健康研究领域研究员；2006 年至今，日本放射线医学综合研究所重粒子医学科学中心主任研究员；总计发表学术论文40余篇，日本国内学术会议发表80 余篇，国际学术会议发表30 余篇，国内外招待演讲10 余篇。

主要代表作：

1. Sai S*, VaresG, Karasawa K, Wang B, Nenoi M, Horimoto Y, Kim EH, and Hayashi M.Carbon IonBeam Combined with Cisplatin Effectively Disrupts Triple Negative Breast CancerStem-Like Cells In Vitro 2015 Mol Cancer in press (impact factor 5.39)

2. Sai S*, WakaiT, Vares G, Yamada S, Kamijo T, Kamada T, and Shirai T. Combination of CarbonIon Beam and Gemcitabine Causes Unreparable DNA Damage and Death ofRadioresistant Pancreatic Cancer Stem-Like Cells In Vitro and In Vivo 2015Oncotarget 6 (8), 5517-5535. (impact factor 6.63)

3. Cui X*, OonishiK, Tsujii H, Yasuda T, Matsumoto Y, Furusawa Y,Akashi M, Kamada T, Okayasu R.Effects of Carbon Ion Irradiation on Colon Cancer Stem-like Cells and ItsComparison with X-rays. 2011 Cancer Res 71(10): 3676-87. (impact factor 9.33)

Abstract

To examine different effects of carbon ionbeam alone or in combination with chemotherapy on putative pancreatic cancerstem cell (CSC) survival and DNA repair in comparison with X-ray, human pancreaticCSCs sorted from PANC1 and PK45 cells were treated with carbon ion beam, X-rayalone or in combination with gemcitabine. We found that the number of colonyand spheroid formed from CSCs (CD44+/ESA+) after carbon ion beam wassignificantly reduced compared to that of X-ray, and it was extremelysuppressed when combined with gemcitabine or 5-FU. The relative biologicaleffectiveness (RBE) values for the carbon ion beam relative to X-ray at the D10levels for CSCs were 2.23-2.66. RT Profiler PCR Array analysis showed thatexpressions of apoptosis-related genes (Bax, Cytochrome c), autophagy-relatedgenes (LC3, p62), and senescence-related gene p21 were remarkably induced aftercarbon ion beam combined with gemcitabine compared to carbon ion beam alone orX-ray combined with gemcitabine. Not only the number but also the size of γH2AXfoci in CSCs were lager 24 h after carbon ion beam combined with gemcitabine or5-FU compared tocarbon ion beam alone or X-ray combined with gemcitabine.Xenograft tumor control analysis showed that the tumors were not completelycontrolled even treated with 60 Gy of X-ray, but it was destroyed with 25 Gy ofcarbon ion beam combined with 50 mg/kg gemcitabine. In conclusion, carbon ionbeam combined with gemcitabine or 5-FU has superior potential to killpancreatic CSCs via unrepairable clustered DSB, and multiple cell deathpathways.