Combination therapy using hyperthermia and IL-6 inhibitor for oral cancer

• Project/Area Number: 16K11730
• 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: Mitsudo Kenji 横浜市立大学, 医学研究科, 教授 (70303641)
• Co-Investigator(Kenkyū-buntansha): 佐藤 格 横浜市立大学, 医学研究科, 客員研究員 (00737710) ; 藤内 祝 横浜市立大学, 医学研究科, 客員教授 (50172127)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 口腔癌 / 温熱療法 / IL-6阻害薬 / IL-6阻害剤 / Interleukin-6阻害剤 / ハイパーサーミア / ヒト扁平上皮癌細胞株 / Interleukin-6

Outline of Final Research Achievements

We examined the anticancer effects of Interleukin-6 inhibitor for oral cancer cells combined with hyperthermia. Interleukin-6 receptor was highly expressed under heat treatment in the oral cancer cells. In a mouse oral cancer model, the tumor size in the Interleukin-6 inhibitor-injected group and hyperthermia group were no significant differences compared to the control group.

Academic Significance and Societal Importance of the Research Achievements

頭頸部扁平上皮癌においては抗EGFR 抗体であるセツキシマブが臨床に導入され、その有効性が報告されている。我々は、リウマチに対する分子標的薬として応用されているサイトカインInterleukin-6(IL-6)阻害薬(抗IL-6R抗体、トシリズマブ, アクテムラ)が口腔扁平上皮癌に対しても抗腫瘍効果を示すと報告されていることから、IL-6阻害薬と温熱療法を併用し、癌標的分子の発現誘導と腫瘍の増殖抑制の効果について研究を行った。

Research Products

• [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] Swallowing function in advanced tongue cancer patients before and after bilateral neck dissection following superselective intra-arterial chemoradiotherapy for organ preservation: a case control study. (2018)
  • Author(s): Ohashi N, Iwai T, Tohara H, Chiba Y, Oguri A, Koizumi T, Mitsudo K, Tonai I.
  • Journal Title: Oral Radiology Volume: - Issue: 3 Pages: 1-9
  • DOI: 10.1007/s11282-018-0341-0
  • Peer Reviewed / Open Access
• [Journal Article] Atypical Protein Kinase C λ/ι Expression Is Associated with Malignancy of Oral Squamous Cell Carcinoma (2018)
  • Author(s): BABA JUNICHI、KIOI MITOMU、AKIMOTO KAZUNORI、NAGASHIMA YOJI、TAGURI MASATAKA、INAYAMA YOSHIAKI、AOKI ICHIRO、OHNO SHIGEO、MITSUDO KENJI、TOHNAI IWAI
  • Journal Title: Anticancer Research Volume: 38 Issue: 11 Pages: 6291-6297
  • DOI: 10.21873/anticanres.12985
  • Peer Reviewed / Open Access
• [Journal Article] Daily Cisplatin and Weekly Docetaxel versus Weekly Cisplatin Intra-Arterial Chemoradiotherapy for Late T2-3 Tongue Cancer: A Pilot and Feasibility Trial (2018)
  • Author(s): Hayashi Yuichiro、Minamiyama Shuhei、Ohya Takashi、Iida Masaki、Iwai Toshinori、Koizumi Toshiyuki、Oguri Senri、Hirota Makoto、Kioi Mitomu、Hata Masaharu、Taguri Masataka、Mitsudo Kenji
  • Journal Title: Medicina Volume: 54 Issue: 4 Pages: 52-52
  • DOI: 10.3390/medicina54040052
  • Peer Reviewed
• [Journal Article] Proton beam therapy in combination with intra-arterial infusion chemotherapy for T4 squamous cell carcinoma of the maxillary gingiva. (2018)
  • Author(s): 6.Endo H, Takayama K, Mitsudo K, Nakamura T, Seto I, Yamaguchi H, Ono T, Suzuki M, AzamiY, Wada H, Murakami M, Tohnai I
  • Journal Title: Cancers Volume: 10(9) Issue: 9 Pages: 333-333
  • DOI: 10.3390/cancers10090333
  • Peer Reviewed / Open Access
• [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] Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in predicting pathological response to preoperative super-selective intra-arterial chemoradiotherapy for advanced squamous cell carcinoma of the mandible (2018)
  • Author(s): Shibasaki Maiko、Iwai Toshinori、Oguri Senri、Koizumi Toshiyuki、Hirota Makoto、Mitsudo Kenji、Ozawa Yukihiko、Tohnai Iwai
  • Journal Title: Journal of Bone Oncology Volume: 11 Pages: 33-37
  • DOI: 10.1016/j.jbo.2018.02.001
  • Peer Reviewed / Open Access
• [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 T2-4N0 tongue cancer. control of occult neck metastasis. (2017)
  • Author(s): Minamiyama S, Mitsudo K, Hayashi Y, Iida M, Iwai T, Nakashima H, Oguri S, Ozawa T, Koizumi T, Hirota M, Kioi M, Tohnai I
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol. Volume: 124 Pages: 16-23
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Chemoradiotherapy using retrograde superselective intra-arterial infusion for tongue cancer: analysis of therapeutic results in 118 cases. (2018)
  • Author(s): Mitsudo K., Hayashi Y, Minamiyama S, Ohashi N, Ohya T, Iida M, Iwai T, Oguri S, Koizumi T, Kioi M, Hirota M, Tohnai I.
  • Organizer: 13th Asian Congress of Oral and Maxillofacial Surgery.
  • Int'l Joint Research
• [Presentation] Intraoral minor salivary gland tumors: a retrospective clinicopathological study of 131 cases in Japanease population. (2018)
  • Author(s): Hayashi Y, Iwai T, Sugiyama S, Osawa K, Minamiyama S, Mitsudo K
  • Organizer: XXIIIth Congress of the European Association for Cranio-Maxillofacial Surgery
  • Int'l Joint Research
• [Presentation] ハイパーサーミア・診療ガイドラインの作成に向けて． (2018)
  • Author(s): 高橋健夫、大栗 隆、櫻井英幸、播磨洋子、光藤健司、矢原勝哉、石川 剛、齋藤淳一
  • Organizer: 日本ハイパーサーミア学会第35回大会
  • Invited
• [Presentation] 薬効成分を磁性化した新規パクリタキセルを用いた口腔癌治療の開発 (2018)
  • Author(s): 中鍛治里奈，佐藤 格，小泉敏之，光藤健司
  • Organizer: 第63回日本口腔外科学会総会・学術大会
• [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とハイパーサーミアの併用療法 頸部リンパ節転移に対する治療効果 (2018)
  • Author(s): 野里朋代，小泉敏之，飯田昌樹，林雄一郎，南山周平，中鍛治里奈，大澤昂平，小栗千里，岩井俊憲，廣田 誠，来生 知，光藤 健司
  • Organizer: 日本ハイパーサーミア学会第35回大会
• [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 / Invited
• [Presentation] Targeting of interleukin-13 receptor α2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-β and PTEN signaling (2017)
  • Author(s): Nakashima H, Kioi M, Yanagida K, Okubo M, Sugiura K, Mitsudo K, Tohnai I
  • Organizer: 6th World Oral Cancer Congress of the International Academy of Oral Oncology
  • Int'l Joint Research
• [Presentation] 磁性を有する新規抗がん剤を用いたドラッグデリバリーとハイパーサーミア併用癌治療法の開発 (2017)
  • Author(s): 中鍛治里奈，光藤健司，梅村将就，佐藤 格，大竹 誠，小泉敏之，石川義弘，藤内 祝
  • Organizer: 日本ハイパーサーミア学会第34回大会
• [Presentation] ヒト口腔扁平上皮癌細胞に対するmild-hyperthermiaとcetuximab併用効果の検討 (2016)
  • Author(s): 飯坂友宏，中島英行，來生 知，大久保牧子，杉浦 圭，小栗千里，小泉敏之，光藤健司，藤内 祝
  • Organizer: 日本ハイパーサーミア学会第33回大会
  • Place of Presentation: つくば国際会議場（茨城県つくば市）
  • Year and Date: 2016-09-04
• [Presentation] 進行口腔癌の頸部リンパ節転移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療法 (2016)
  • Author(s): 光藤健司、藤内 祝
  • Organizer: 日本ハイパーサーミア学会第33回大会
  • Place of Presentation: つくば国際会議場（茨城県つくば市）
  • Year and Date: 2016-09-04
• [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): 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 Annual Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2016-06-02
  • Int'l Joint Research
• [Presentation] Hyperthermia enhances the therapeutic efficacy of IL-13 cytotoxin in human oral squamous cell carcinoma. (2016)
  • Author(s): Nakashima H, Okubo M, Kioi M, Miyajima A, Iisaka T, Sugiura K, Itaru S, Koizumi T, Mitsudo K, Tohnai I
  • 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] 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): Koizumi T, Mitsudo K, Iida M, Nakashima H, Ueda J, Oguri S, Iwai T, Hirota M, Kioi M, Tohnai T.
  • Organizer: The 12th International congress of hyperthermic oncology
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-04-11
  • Int'l Joint Research