主题：Effects of tumor microenvironments on cell cycle kinetics following X-irradiation
主讲人：Dr. Atsushi Kaida
时间: 2月23号上午9:00-10:00
地点：401栋一楼会议室
欢迎广大师生踊跃参加！
欧洲杯官网
专家简历：
Education:
2002-2008 Faculty of Dentistry, Tokyo Medical and Dental University. Awarded the degree of D.D.S.
2009-2012 Department of Oral Radiation Oncology, Graduate School of Medical and Dental
Sciences, Tokyo Medical and Dental University. Awarded the degree of Ph.D. in
radiobiology for a thesis entitled “Visualizing the effect of hypoxia on fluorescence
kinetics in living HeLa cells using the fluorescent ubiquitination-based cell cycle
indicator (Fucci)..” Work supervised by Professor Masahiko Miura.
Research and professional experience:
2008-2009 Trainee Resident of Dentistry at Tokyo Medical and Dental University Dental Hospital and Yamanashi Prefectural Central Hospital.
2012-2013 Dental Resident at Tokyo Medical and Dental University Dental Hospital.
2013 Research Fellow of Japan Society for the Promotion of Science at Department of Oral Radiation Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
2013-present Assistant Professor at the Department of Oral Radiation Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University.
Abstract
In most of tumor cells lacking normal p53 functions, DNA double-strand breaks (DSBs) produced after irradiation trigger activation of the G2/M, but not G1/S checkpoint, resulting in only G2 arrest. Such radiation-induced cell kinetics are thought to be a critical response to maintain the genome integrity and cell survival. However, the kinetics in in vivo conditions are still largely unknown due to complicated structures including tumor microenvironments and immature techniques. To overcome those problems, we applied a fluorescent ubiquitination-based cell cycle indicator (Fucci), which is a novel technique to visualize dynamics of cell cycle progression in live cells. Here, I will show you some of our studies regarding cell cycle kinetics after X-irradiation in xenografted tumors using cervical cancer cell line, HeLa cells, and tongue squamous cell carcinoma cell line, SAS cells, by using the Fucci system.
After 10 Gy irradiation, the duration of G2 arrest was significantly prolonged in tumor xenografts derived from HeLa cells and SAS cells, compared with that in monolayer cultures. Furthermore, red cells, as a marker of G1/G0 phases, were predominant over green ones, as a marker of S/G2/M phases, in the whole areas of each tumor without irradiation. However, 24 hours after irradiation, red and green cells were clearly separated depending on the areas; perinecrotic areas, pimonifazole-positive, mostly consisted of red cells and other peripheral areas consisted of green cells due to G2 arrest. Moreover, the former red cells isolated by the FACS sorting were more radioresistant than the latter green cells. Taken together, it was for the first time demonstrated that cell cycle kinetics following irradiation and radiosensitivities of quiescent and growing cancer cells irradiated under tumor microenvironments in in vivo conditions. I am also going to show you some possible molecular mechanisms underlying the different G2 arrest kinetics between in vitro and in vivo conditions.