Development of oral cancer treatment by hyperthermia generated with contrast agent Resovist and Cetuximab

• Project/Area Number: 26463053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Yokohama City University
• Principal Investigator: KOIZUMI Toshiyuki 横浜市立大学, 附属病院, 講師 (80323575)
• Co-Investigator(Kenkyū-buntansha): 來生 知 横浜市立大学, 医学部, 准教授 (30545059) ; 藤内 祝 横浜市立大学, 医学研究科, 教授 (50172127) ; 光藤 健司 横浜市立大学, 医学部, 准教授 (70303641)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 口腔癌 / ハイパーサーミア / セツキシマブ / 交流磁場 / 温熱 / 分子標的薬 / 温熱療法 / 磁性体ナノ粒子

Outline of Final Research Achievements

The purpose of this study is the development of a new treatment for oral cancer indicating the resistance for the anticancer effect of cetuximab by using hyperthermia generated with contrast agent Resovist in an alternating magnetic field(AMF) and Cetuximab.We found that the expression of EGFR in human oral squamous cell carcinoma cells increased by thermal stimulation.Therefore, we thought that the sensitivity of Cetuximab-resistant human oral squamous cell carcinoma cells for cetuximab can be activated by thermal stimulation-induced high expression of EGFR.As a result of the study using mouse models based on this speculation, the anti-cancer effect were observed in the group treated with combination of cetuximab and hyperthermia generated with contrast agent Resovist in AMF.

Research Products

• [Journal Article] Treatment of oral cancer using magnetized paclitaxel (2018)
  • Author(s): Nakakaji Rina、Umemura Masanari、Mitsudo Kenji、Kim Jeong-Hwan、Hoshino Yujiro、Sato Itaru、Masuda Takatsugu、Yamamoto Masahiro、Kioi Mitomu、Koizumi Toshiyuki、Fujita Takayuki、Yokoyama Utako、Iida Masaki、Sato Motohiko、以下7名
  • Journal Title: Oncotarget Volume: 9 Issue: 21 Pages: 15591-15605
  • DOI: 10.18632/oncotarget.24570
  • Peer Reviewed / Open Access
• [Journal Article] Chemoradiotherapy using retrograde superselective intra-arterial infusion for tongue cancer: Analysis of therapeutic results in 118 cases (2018)
  • Author(s): Mitsudo Kenji、Hayashi Yuichiro、Minamiyama Shuhei、Ohashi Nobuhide、Iida Masaki、Iwai Toshinori、Oguri Senri、Koizumi Toshiyuki、Kioi Mitomu、Hirota Makoto、Koike Izumi、Hata Masaharu、Tohnai Iwai
  • Journal Title: Oral Oncology Volume: 79 Pages: 71-77
  • DOI: 10.1016/j.oraloncology.2018.02.002
  • Peer Reviewed / Open Access
• [Journal Article] Retrograde superselective intra-arterial chemoradiotherapy combined with hyperthermia and cetuximab for carcinoma of the buccal mucosa with N3 lymph node metastasis: a case report (2018)
  • Author(s): Sakuma Kaname、Koizumi Toshiyuki、Mitsudo Kenji、Ueda Jun、Hayashi Yuichiro、Iwai Toshinori、Hirota Makoto、Kioi Mitomu、Yoshii Haruka、Kaizu Hisashi、Hata Masaharu、Tanaka Akira、Tohnai Iwai
  • Journal Title: Oral Radiology Volume: 印刷中 Issue: 1 Pages: 77-83
  • DOI: 10.1007/s11282-018-0319-y
  • Peer Reviewed
• [Journal Article] Clinical outcomes of retrograde intra-arterial chemotherapy concurrent with radiotherapy for elderly oral squamous cell carcinoma patients aged over 80?years old (2017)
  • Author(s): Hayashi Y, Mitsudo K, Sakuma K, Iida M, Iwai T, Nakashima H, Okamoto Y, Koizumi T, Oguri S, Hirota M, Kioi M, Koike I, Hata M, Tohnai I.
  • Journal Title: Radiation Oncology Volume: 12 Issue: 1 Pages: 112-112
  • DOI: 10.1186/s13014-017-0847-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for advanced oral cancer: Efficacy of cervical lymph node metastases (2016)
  • Author(s): 光藤健司，小泉敏之，飯田昌樹，岩井俊憲，中島英行，小栗千里，廣田 誠，來生 知，藤内 祝
  • Journal Title: Journal of Japanese Society of Oral Oncology Volume: 28 Issue: 2 Pages: 27-32
  • DOI: 10.5843/jsot.28.27
  • NAID: 130005158514
  • ISSN: 0915-5988, 1884-4995
  • Peer Reviewed
• [Presentation] Thermochemoradiation therapy using superselective intra-arterial infusion for advanced oral cancer with cervical lymph node metastasis contacted with the mandible. (2018)
  • Author(s): Toshiyuki Koizukmi, Masaki Iida , Kenji Mitsudo
  • Organizer: The 7th Asian Congress of Hyperthermic Oncology
  • Int'l Joint Research
• [Presentation] Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases. (2017)
  • Author(s): Mitsudo K, Koizumi T, Hayashi Y, Sugiura K, Iida M, Iwai T, Nakashima H, Oguri S, Kioi M, Hirota M, Tohnai I
  • Organizer: 6th World Oral Cancer Congress of the International Academy of Oral Oncology
  • Int'l Joint Research
• [Presentation] 進行口腔癌に対する超選択的動注化学放射線療法とハイパーサーミアの併用治療―下顎骨に接した頸部リンパ節転移に対する治療― (2017)
  • Author(s): 小泉敏之，光藤健司，飯田昌樹，佐藤 格，飯坂友宏，南山周平，林 雄一郎，野里朋代, 中鍛治里奈，大澤昂平，藤内 祝
  • Organizer: 日本ハイパーサーミア学会第34回大会
• [Presentation] 進行口腔癌に対する超選択的動注化学放射線療法とハイパーサーミアの併用治療 ―下顎骨浸潤した頸部リンパ節転移に対する治療― (2016)
  • Author(s): 9.小泉敏之，光藤健司，飯田昌樹，佐藤 格，飯坂友宏，小栗千里，岩井俊憲，廣田 誠，來生 知，藤内 祝
  • Organizer: 日本ハイパーサーミア学会第33回大会
  • Place of Presentation: 筑波国際会議場（茨城県つくば市）
  • Year and Date: 2016-09-02
• [Presentation] Organ preservation with daily concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion for locally advanced tongue cancer: analysis of therapeutic results in 101 cases. (2016)
  • Author(s): 7.Mitsudo K, Oguri S, Minamiyama S, Iida M, Iwai T, Nakashima H, Koizumi T, Kioi M, Hirota M, Tohnai I
  • Organizer: 2016 American Society of Clinical Oncology (ASCO) Annual Meeting
  • Place of Presentation: Chicago,USA
  • Year and Date: 2016-06-03
  • Int'l Joint Research
• [Presentation] A case report of thermobiochemoradiation therapy using superselective intra-arterial infusion for carcinoma of the buccal mucosa with N3 lymph node metastases. (2016)
  • Author(s): 1.Toshiyuki Koizumi, Kenji Mitsudo, Masaki Iida, Hideyuki Nakashima, Jun Ueda, Senri Oguri, Toshinori Iwai, Makoto Hirota, Mitomu Kioi, Iwai Tohnai
  • Organizer: The 12th International congress of hyperthermic oncology
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-04-11
  • Int'l Joint Research
• [Presentation] Chemoradiotherapy using retrograde superselective intra-arterial infusion for advanced oral cancer -Therapeutic effect for squamous cell carcinoma of buccal mucosa-. (2015)
  • Author(s): Koizumi T, Mitsudo K, Iida M, Oguri S, Iwai T, Nakashima H, Hirota M, Kioi M, Tohnai I.
  • Organizer: 22nd International Oral and Maxillofacial Surgery
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2015-10-27
  • Int'l Joint Research
• [Presentation] 進行口腔癌に対する逆行性超選択的動注化学放射線療法－頬粘膜癌に対する治療効果－ (2015)
  • Author(s): 小泉敏之，光藤健司，小栗千里，岩井俊憲，飯田昌樹,上田 潤，中島英行，廣田 誠，來生 知，藤内 祝.
  • Organizer: 第60回日本口腔外科学会総会・学術大会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-16
• [Presentation] Cetuximab併用超選択的動注化学放射線療法と頸部リンパ節転移への温熱療法の併用療法を行った頬粘膜癌（N3）の1例. (2015)
  • Author(s): 小泉敏之，光藤健司，飯田昌樹，上田 潤，小栗千里，岩井俊憲，廣田 誠，來生 知，藤内 祝.
  • Organizer: 日本ハイパーサーミア学会第32回大会
  • Place of Presentation: KKRホテル大阪（大阪府大阪市）
  • Year and Date: 2015-09-04
• [Presentation] Thermochemoradiotherapy using intra-arterial infusion for lymph node metastases of oral cancer. (2015)
  • Author(s): Koizumi T, Mitsudo K, Iida M, Nakashima H, Iwai T, Oguri S, Hirota M, Kioi M, Tohnai I.
  • Organizer: Asian Society of Head and Neck Oncology
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 2015-06-04
  • Int'l Joint Research