Effect of heavy ion beam irradiation on radioresistance and differentiation of cancer stem cells in neuronal tumors

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390304
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Nara Medical University
• Principal Investigator: HASEGAWA Masatoshi 奈良県立医科大学, 医学部, 教授 (50251111)
• Co-Investigator(Kenkyū-buntansha): OHNO Tatsuya 群馬大学, 重粒子線医学研究センター, 教授 (10344061) ; KATO Shingo 埼玉医科大学, 国際医療センター, 教授 (00370875) ; INOUE Kazuya 奈良県立医科大学, 医学部, 研究員 (20596952) ; KATAYAMA Emiko 奈良県立医科大学, 医学部, 助教 (00596950)
• Research Collaborator: 若月 優 放射線医学総合研究所 ; 村上 健 放射線医学総合研究所 ; 吉田 由香里 群馬大学, 大学院・医学系研究科 ; 中野 隆史 群馬大学, 大学院・医学系研究科 ; 石内 勝吾 琉球大学, 医学部 ; 武田 麻衣子 奈良県立医科大学, 医学部 ; 藤谷 信将 奈良県立医科大学, 医学部 ; 藤村 浩子 奈良県立医科大学, 医学部 ; 川島 真紀 奈良県立医科大学, 医学部 ; 榎本 喜久子 奈良県立医科大学, 医学部 ; 内田 雅代 奈良県立医科大学, 医学部 ; 浅川 勇雄 奈良県立医科大学, 医学部 ; 玉本 哲郎 奈良県立医科大学, 医学部 ; 大林 千穂 奈良県立医科大学, 医学部 ; 大西 武雄 奈良県立医科大学, 医学部
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 癌幹細胞 / 神経幹細胞 / 放射線抵抗性 / アポトーシス / p53

Research Abstract

The purpose is to investigate the radiobiological effect of heavy ion (CI) beams on radioresistance and differentiation of human tumor cells, especially cancer stem cells. Human ependymoblastoma with wild-type p53 and glioblastoma with mutant-type p53 were transplanted into nude mice and irradiated with CI beams or 150-kV X-rays. Tumors were excised for cDNA microarray analysis 6- 48 hours or 6 weeks after 2-24 Gy irradiation. CD133, CD44, Nestin, p53, PTEN, Ki67, and GFAP expressions were evaluated immunohistochemically. In ependymoblastoma, p53 signaling and apoptosis-related pathways were suggested to be involved following irradiation. The tumors showed a significant decrease in growth fraction and a slight increase of the CD133-positive rate after high-dose irradiation. These results suggest that CD133-positive and Ki-67-negative cells may be resistant to both X-rays and CI beams.

Research Products

• [Journal Article] The biochemical recurrence-free rate in patients who underwent prostate low-dose-rate brachytherapy, using two different definitions (2014)
  • Author(s): Tanaka N, Asakawa I, Katayama E, Hirayama A, Hasegawa M, Konishi N, Fujimoto K
  • Journal Title: Radiat Oncol Volume: 9(1) Pages: 107
  • DOI: 10.1186/1748-717X-9-107
  • Peer Reviewed
• [Journal Article] Periodical assessment of genitourinary and gastrointestinal toxicity in patients who underwent prostate low-dose-rate brachytherapy (2013)
  • Author(s): Tanaka N, Asakawa I, Anai S, Hirayama A, Hasegawa M, Konishi N, Fujimoto K
  • Journal Title: Radiat Oncol Volume: 8 Pages: 25
  • DOI: 10.1186/1748-717X-8-25
  • Peer Reviewed
• [Journal Article] Efficacy of FDG-PET for defining gross tumor volume of head and neck cancer (2013)
  • Author(s): Kajitani C, Asakawa I, Uto F, Katayama E, Inoue K, Tamamoto T, Shirone N, Okamoto H, Kirita T, Hasegawa M
  • Journal Title: J Radiat Res Volume: 54(4) Pages: 671-8
  • DOI: 10.1093/jrr/rrs131
  • Peer Reviewed
• [Journal Article] Pathological and clinical impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer (2013)
  • Author(s): Sho M, Akahori T, Tanaka T, Kinoshita S, Tamamoto T, Nomi T, Yamato I, Hokuto D, Yasuda S, Kawaguchi C, Nishiofuku H, Marugami N, Enomonoto Y, Kasai T, Hasegawa M, Kichikawa K, Nakajima Y
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 20(2) Pages: 197-205
  • DOI: 10.1007/s00534-012-0532-8
  • Peer Reviewed
• [Journal Article] Minimal percentage of dose received by 90% of the urethra (%UD90) is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer (2012)
  • Author(s): Tanaka N, Asakawa I, Fujimoto K, Anai S, Hirayama A, Hasegawa M, Konishi N, Hirao Y
  • Journal Title: BMC Urol Volume: 12 Pages: 28
  • DOI: 10.1186/1471-2490-12-28
  • Peer Reviewed
• [Journal Article] Preoperative concurrent chemoradiotherapy for stages II-IV oral squamous cell carcinoma : a retrospective analysis and the future possibility of this treatment strategy (2012)
  • Author(s): Kirita T, Yamanaka Y, Imai Y, Yamakawa N, Aoki K, Nakagawa Y, Yagyuu T, Hasegawa M
  • Journal Title: Int J Oral Maxillofac Surg Volume: 41(4) Pages: 421-8
  • DOI: 10.1016/j.ijom.2011.12.003
  • Peer Reviewed
• [Journal Article] Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination (2012)
  • Author(s): Shirone N, Shinkai T, Yamane T, Uto F, Yoshimura H, Tamai H, Imai T, Inoue M, Kitano S, Kichikawa K, Hasegawa M
  • Journal Title: Ann Nucl Med Volume: 26(3) Pages: 248-52
  • DOI: 10.1007/s12149-011-0568-x
  • Peer Reviewed
• [Journal Article] Intra-arterial chemoinfusion prior to chemoradiotherapy with full-dose systemic gemcitabine for management of locally advanced pancreatic cancer (2011)
  • Author(s): Tanaka T, Nishiofuku H, Tamamoto T, Sho M, Anai H, Sueyoshi S, Sakaguchi H, Hasegawa M, Nakajima Y, Kichikawa K
  • Journal Title: Anticancer Res Volume: 31(11) Pages: 3909-12
  • Peer Reviewed
• [Journal Article] Bone scan can be spared in asymptomatic prostate cancer patients with PSA of <=20 ng/ml and Gleason score of <=6 at the initial stage of diagnosis (2011)
  • Author(s): Tanaka N, Fujimoto K, Shinkai T, Nakai Y, Kuwada M, Anai S, Miyake M, Hirayama A, Hasegawa M, Hirao Y
  • Journal Title: Jpn J Clin Oncol Volume: 41(10) Pages: 41(10)
  • DOI: 10.1093/jjco/hyr118
  • Peer Reviewed
• [Journal Article] A comparison of surgery and radiation therapy for cT1 esophageal squamous cell carcinoma (2011)
  • Author(s): Matsumoto S, Takayama T, Tamamoto T, Wakatsuki K, Enomoto K, Tanaka T, Migita K, Asakawa I, Hasegawa M, Nakajima Y
  • Journal Title: Dis Esophagus Volume: 24(6) Pages: 411-7
  • DOI: 10.1111/j.1442-2050.2010.01163.x
  • Peer Reviewed
• [Presentation] 粒子線治療の放射線生物学 (2013)
  • Author(s): 長谷川正俊 , 他
  • Organizer: 日本放射線腫瘍学会第26回学術大会
  • Place of Presentation: 青森
  • Year and Date: 2013-10-19
• [Presentation] Changes of Gene Expression Profiles and Cancer Stem Cell Markers in Brain Tumors Following Carbon Ion Beam Irradiation (2013)
  • Author(s): Hasegawa M , et al
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-04
• [Presentation] Cancer Stem Cell Markers and Gene Expression Profiles in Human Brain Tumors Following Carbon Ion Beam Irradiation (2013)
  • Author(s): Hasegawa M, et al
  • Organizer: 第55回アメリカ放射線腫瘍学会(ASTRO)
  • Place of Presentation: アメリカ合衆国アトランタ
  • Year and Date: 2013-09-23
• [Presentation] Gene Expression Profiles Induced by Carbon Ion Beams and X-rays in Human Brain Tumors (2012)
  • Author(s): Hasegawa M, et al
  • Organizer: 第54回アメリカ放射線腫瘍学会(ASTRO)
  • Place of Presentation: アメリカ合衆国ボストン
  • Year and Date: 2012-10-29
• [Presentation] Gene expression profiles induced by carbon ion beams in glioblastoma : close relation to anti-apoptosis and survival (2012)
  • Author(s): 長谷川正俊, 他
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] 放射線抵抗性の p53 変異型膠芽腫における炭素線照射による遺伝子発現の検討 (2012)
  • Author(s): 長谷川正俊, 他
  • Organizer: 第71回日本医学放射線学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-04-15
• [Presentation] 放射線治療とアポトーシス (2011)
  • Author(s): 長谷川正俊, 他
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸
  • Year and Date: 2011-11-17
• [Presentation] IAP and NF-kappaB activation induced by carbon ion beams in human radioresistant glioblastoma cells with mutant-type p53 in vivo (2011)
  • Author(s): Hasegawa M, et al
  • Organizer: 第53回アメリカ放射線腫瘍学会(ASTRO)
  • Place of Presentation: アメリカ合衆国マイアミ
  • Year and Date: 2011-10-03