Radiosensitive change by the Hsp90 inhibitor combination carbon ion radiotherapy.

• Project/Area Number: 25861072
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Gunma University
• Principal Investigator: MUSHA ATSUSHI 群馬大学, 重粒子線医学推進機構, 助教 (60637122)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Hsp90阻害剤 / 炭素線治療

Outline of Final Research Achievements

Carbon ion radiotherapy (C-ion RT) is a potential therapy for radio-resistant malignant tumors. However, in cases of progressive malignant tumors, achieving a complete response is difficult. Therefore, chemotherapy (with an Hsp90 inhibitor, 17-AAG) in combination with C-ion RT was employed. This study was designed to clarify the cell killing effect of 17-AAG, in combination with X-rays or carbon-ion beams in oral squamous cell carcinoma cells. 17-AAG and X-rays in combination showed enhanced antitumor effect compared to C-ion RT, which had an adequate antitumor effect even when used alone. The difference in the effectiveness of the two combination therapies was attributable to the difference in their therapeutic mechanisms. At high doses, the difference between the invasive effect of the combination treatments and that of the individual treatments decreased. However, since 17-AAG shows sufficient combined effects even at low doses, we investigated the invasive effects at low doses.

Research Products

• [Journal Article] Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460. (2015)
  • Author(s): Kubo N, Noda SE, Takahashi A, Yoshida Y, Oike T, Murata K, Musha A, Suzuki Y, Ohno T, Takahashi T, Nakano T.
  • Journal Title: J Radiat Res. Volume: 56 Issue: 2 Pages: 229-238
  • DOI: 10.1093/jrr/rru085
  • Peer Reviewed
• [Journal Article] Evaluation of therapeutic gain for fractionated carbon-ion radiotherapy using the tumor growth delay and crypt survival assays. (2015)
  • Author(s): Yoshida Y, Ando K, Ando K, Murata K, Yoshimoto Y, Musha A, Kubo N, Kawamura H, Koike S, Uzawa A, Takahashi T, Ohno T, Nakano T.
  • Journal Title: Radiother Oncol. Volume: 117 Issue: 2 Pages: 315-317
  • DOI: 10.1016/j.radonc.2015.09.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prediction of acute radiation mucositis using an oral mucosal dose surface model in carbon ion radiotherapy for head and neck tumors. (2015)
  • Author(s): Musha A, Shimada H, Shirai K, Saitoh J, Yokoo S, Chikamatsu K, Ohno T, Nakano T.
  • Journal Title: PLoS ONE Volume: 10 Issue: 10 Pages: e0141734-e0141734
  • DOI: 10.1371/journal.pone.0141734
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Hsp90阻害剤17-AAGによる放射線増感効果の検討 (2015)
  • Author(s): 武者 篤、横尾 聡
  • Organizer: 第33回日本口腔腫瘍学会
  • Place of Presentation: 奈良県新公会堂(奈良県奈良市)
  • Year and Date: 2015-01-29 – 2015-01-30
• [Book] 患者さんと家族のための放射線治療Q&A 2015年版 日本放射線腫瘍学会編 (2015)
  • Author(s): 武者 篤、他
  • Total Pages: 184
  • Publisher: 金原出版