Role of cancer stem in determining radiosensitivity in vitro and in vivo

• Project/Area Number: 24591860
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Akimoto Tetsuo 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (10261851)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 放射線感受性 / がん幹細胞 / 放射線抵抗性 / 放射線生物学 / 放射線治療 / HPV感染 / 頭頚部癌 / 治療抵抗性 / 頭頸部癌 / 放射線応答 / 放射線生物

Outline of Final Research Achievements

The main purpose of this study is to establish effective radiosensitizing approach based in the role of cancer stem cells in determining radiosensitivity and/or cellular response to cancer cells. In 2013 and 2014, we performed basic research using cultured cancer cells, and then, we investigated the correlation between clinical outcomes after definitive IMRT for oropharyngeal cancer and the expression of p16 and CD44, cancer stem cell marker. Finally, we demonstrated that the PFS and LRC rates in the CD44(-) patients (86% and 93%, respectively) were significantly higher than those in the CD44(+) patients (57% and 70%, respectively), and concluded that profiling of CD44 and p16 protein expressions by immunohistochemical staining is useful for predicting the treatment outcomes in patients with OPSCC undergoing definitive intensity modulated radiation therapy.

Research Products

• [Journal Article] Impact of expression of CD44, a cancer stem cell marker, on the treatment outcomes of intensity-modulated radiotherapy in patients with oropharyngeal squamous cell carcinoma. (2016)
  • Author(s): Motegi A, Arahira S, Zenda S, Hayashi R, Fujii M, Akimoto T
  • Journal Title: Int J Radiat Oncol Biol Phys Volume: 94(3) Issue: 3 Pages: 461-468
  • DOI: 10.1016/j.ijrobp.2015.11.019
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phase II study of proton beam therapy as a nonsurgical approach for mucosal melanoma of the nasal cavity or para-nasal sinuses (2016)
  • Author(s): Zenda S, Akimoto T, Mizumoto M, Hayashi R, Arahira S, Okumura T, Sakurai H
  • Journal Title: Radiother Oncol Volume: 118(2) Issue: 2 Pages: 267-71
  • DOI: 10.1016/j.radonc.2015.10.025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neuropathic Pain Features in Patients with Bone Metastases (2016)
  • Author(s): Nakamura N, Takahashi O, Zenda S, Kawamori J, Ogita M, Onozawa M, Arahira S, Toshima M, Motegi A, Hirano Y, Hojo H, Akimoto T
  • Journal Title: Clin Oncol (R Coll Radiol) Volume: 28 Issue: 3 Pages: 204-208
  • DOI: 10.1016/j.clon.2015.10.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phase II trial of chemoradiotherapy with S-1 plus cisplatin for unresectable locally advanced head and neck cancer (JCOG0706). (2015)
  • Author(s): ahara M, Kiyota N, Mizusawa J, Nakamura K, Hayashi R, Akimoto T, Hasegawa Y, Iwae S, Monden N, Matsuura K, Fujii H, Onozawa Y, Homma A, Kubota A, Fukuda H, Fujii M.
  • Journal Title: Cancer Science Volume: 12 Issue: 6 Pages: 132-136
  • DOI: 10.1111/cas.12657
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between the changes in the EPIC QOL scores and the dose-volume histogram parameters in high-dose-rate brachytherapy combined with hypofractionated external beam radiation therapy for prostate cancer (2015)
  • Author(s): 4.Hashimoto Y, Akimoto T, Iizuka J, Tanabe K, Mitsuhashi N.
  • Journal Title: Jpn J Clin Oncol. Volume: 45(1) Issue: 1 Pages: 81-87
  • DOI: 10.1093/jjco/hyu173
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Accelerated radiotherapy for T1-T2 glottic cancer. (2014)
  • Author(s): Atsushi Motegi, Mitsuhiko Kawashima, Satoko Arahira, Sadamoto Zenda, Masamichi Toshima, Masakatsu Onozawa, Ryuichi Hayashi, Tetsuo Akimoto
  • Journal Title: Head and Neck Volume: in press Issue: 4 Pages: 579-84
  • DOI: 10.1002/hed.23641
  • Peer Reviewed / Open Access
• [Journal Article] Working Subgroup of Urological Cancers in Japanese Radiation Oncology Study Group. Patterns of practice in the radiation therapy for bladder cancer: survey of the Japanese Radiation Oncology Study Group (JROSG). (2014)
  • Author(s): 5.Maebayashi T, Ishikawa H, Yorozu A, Yoshida D, Katoh H, Nemoto K, Ishihara S, Takemoto S, Ishibashi N, Tokumaru S, Akimoto T;
  • Journal Title: Jpn J Clin Oncol Volume: 44(11): Issue: 11 Pages: 1109-15
  • DOI: 10.1093/jjco/hyu129
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Accelerated radiotherapy for T1―T2 glottic cancer (2014)
  • Author(s): Motegi A, Akimoto T
  • Journal Title: Head and Neck Volume: 23 Pages: 23-27
  • Peer Reviewed
• [Journal Article] Phase II Study of Cetuximab Plus Concomitant Boost Radiotherapy in Japanese Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck. (2013)
  • Author(s): 1. Okano S, Yoshino T, Fujii M, Onozawa Y, Kodaira T, Fujii H, Akimoto T, Ishikura S, Oguchi M, Zenda S, de Blas B, Tahara M
  • Journal Title: Jpn J Clin Oncol Volume: 43(5) Pages: 476-82
  • Peer Reviewed
• [Journal Article] Pancreatic resection for metastatic melanoma originating from the nasal cavity: a case report and literature review (2013)
  • Author(s): 2. Sugimoto M, Gotohda N, Kato Y, Takahashi S, Kinoshita T, Shibasaki H, Kojima M, Ochiai A, Zenda S, Akimoto T, Konishi M
  • Journal Title: Anticancer Res Volume: 33(2) Pages: 567-73
  • Peer Reviewed
• [Presentation] 頭頸部癌の生物学多様性と放射線治療 (2015)
  • Author(s): 秋元
  • Organizer: 第17回癌治療増感研​究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 2015-02-07
  • Invited
• [Presentation] 中咽頭癌におけるがん幹細胞マーカー発現とHPV感染の相関の研究 (2014)
  • Author(s): 茂木 厚、林 隆一、全田貞幹、秋元哲夫
  • Organizer: 日本放射線腫瘍学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-12-11 – 2014-12-13
• [Presentation] 中咽頭癌に対する強度変調放射線治療の遡及的検討 (2014)
  • Author(s): 茂木 厚、全田貞幹、荒平聡子、小野澤正勝、林 隆一、秋元哲夫
  • Organizer: 頭頚部癌学会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-12 – 2014-06-13
• [Presentation] 頭頸部がん治療医の養成の現状と今後の方向について (2014)
  • Author(s): 秋元哲夫
  • Organizer: 頭頚部癌学会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-12 – 2014-06-13
  • Invited
• [Presentation] 生物学的アプローチと放射線治療の臨床 (2014)
  • Author(s): 秋元哲夫
  • Organizer: 第１１回癌治療増感研究会シンポジウム
  • Place of Presentation: 奈良
  • Invited
• [Presentation] 化学放射線療法総論 (2013)
  • Author(s): 秋元哲夫
  • Organizer: 第51回日本癌治療学会総会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 分子生物学的見地からみた分子標的治療と放射線治療の併用の有用性と課題 (2013)
  • Author(s): 秋元哲夫
  • Organizer: 第26回日本放射線腫瘍学会
  • Place of Presentation: 青森
  • Invited
• [Presentation] 食道癌に対する分子標的薬と放射線治療併用の安全性 (2013)
  • Author(s): 秋元哲夫
  • Organizer: 第11回日本臨床腫瘍学会
  • Place of Presentation: 仙台
  • Invited
• [Book] Intensity-Modulated Radiation Therapy (2015)
  • Author(s): Hidenobu Tachibana, Tetsuo Akimoto
  • Total Pages: 473
  • Publisher: Springer