Immunochemotherapy combined with hyperthermia for distant metastases of oral cancer using magnetic anticancer drug

• Project/Area Number: 25463116
• 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, 医学部, 准教授 (70303641)
• Co-Investigator(Kenkyū-buntansha): 小栗 千里 横浜市立大学, 医学部, 助教 (30400394) ; 藤内 祝 横浜市立大学, 医学研究科, 教授 (50172127)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 温熱免疫化学療法 / 口腔癌の遠隔転移 / 新規磁性抗癌剤 / 口腔癌 / 遠隔転移 / 温熱療法 / 免疫賦活 / ヒト由来扁平上皮癌細胞株 / 口腔多発癌 / 重複癌 / ハイパーサーミア / 磁性抗癌剤 / アポトーシス / 電子顕微鏡

Outline of Final Research Achievements

This study is to evaluate the immunostimulation activity treated with immunochemotherapy combined with local hyperthermia using new magnetic anticancer drug.
We examined the expression of heat shock protein 70 and heat shock protein 90 (HSP70/HSP90) treated with 42.5 degree hyperthermia using magnetic anticancer drug in cultured human oral cancer cells. Expression of HSP70/HSP90 has been increased after local hyperthermia, indicating that immunostimulation activity is provided by hyperthermia. Cultured human oral cancer cells are inoculated on both side of the leg in nude mice and magnetic anticancer drug was injected into the left tumor. The leg tumor is irradiated with a magnetic field, the tumor-specific local hyperthermia induces decrease of both tumors after treatment. These results suggest that local hyperthermia treatment induced immunostimulation activity.

Research Products

• [Journal Article] Simultaneous hyperthermia-chemotherapy with controlled drug delivery using single-drug nanoparticles (2016)
  • Author(s): Itaru Sato, Masanari Umemura, Kenji Mitsudo, Hidenobu Fukumura, Jeong-Hwan Kim, Yujiro Hoshino Hideyuki Nakashima, Mitomu Kioi, Rina Nakakaji, Motohiko Sato, Takayuki Fujita, Utako Yokoyama, Satoshi Okumura, Hisashi Oshiro, Haruki Eguchi, Iwai Tohnai and Yoshihiro Ishikawa.
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 24629-24629
  • DOI: 10.1038/srep24629
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Simultaneous hyperthermia-chemotherapy with controlled drug delivery using single-drug nanoparticles. (2016)
  • Author(s): Sato I, Umemura M, Mitsudo K, Fukumura H, Kim J-H, Hoshino Y, Nakashima H, Kioi M, Nakakaji R, Sato M, Fujita T, Yokoyama U, Okumura S, Eguchi H, Oshiro H, Tohnai I, Ishikawa Y
  • Journal Title: Scientific Reports Volume: in press
  • Peer Reviewed
• [Journal Article] Prognostic value of 2-[18 F]fluoro-2-deoxy-D-glucose positron emission tomography for patients with oral squamous cell carcinoma treated with retrograde superselective intraarterial chemotherapy and daily concurrent radiotherapy. (2016)
  • Author(s): Shimizu M, Mitsudo K, Koike I, Taguri M, Iwai T, Koizumi T, Oguri S, Kioi M, Hirota M, Inoue T, Tohnai I.
  • Journal Title: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology Volume: 142 Issue: 3 Pages: 239-247
  • DOI: 10.1016/j.oooo.2015.10.018
  • Peer Reviewed
• [Journal Article] Retrograde intra-arterial chemotherapy and daily concurrent proton beam therapy for recurrent oral cavity squamous cell carcinoma: Analysis of therapeutic results in 46 cases. (2016)
  • Author(s): Hayashi Y, Nakamura T, Mitsudo K, Yamaguchi H, Ono T, Azami Y, Takayama K, Suzuki M, Hatayama Y, Tsukiyama I, Hareyama M, Kikuchi Y, Fuwa N, Tohnai I.
  • Journal Title: Head Neck. Volume: 未定 Issue: 8 Pages: 1145-1151
  • DOI: 10.1002/hed.24421
  • Peer Reviewed
• [Journal Article] Increase of Peripheral Blood CD57+ T-Cells in Patients with Oral Squamous Cell Carcinoma. (2014)
  • Author(s): Iida M, Takayama E, Naganawa K, Mitsudo K, Adachi M, Baba J, Fujimoto-Muto M, Motohashi M, Mizuno-Kamiya M, Kawaki H, Kioi M, Ichinose M, Sumitomo S, Muramatsu Y, Shikimori M, Tohnai I, Kondoh N.
  • Journal Title: Anticancer Res Volume: 9 Issue: 1 Pages: 5729-5734
  • DOI: 10.2174/1874210601509010120
  • Peer Reviewed / Open Access
• [Journal Article] Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases (2014)
  • Author(s): Mitsudo K, Koizumi T, Iida M, Iwai T, Nakashima H, Oguri S, Kioi M, Hirota M, Koike I, Hata M, Tohnai I
  • Journal Title: Radiother Oncology Volume: 111 Pages: 306-310
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Thermochemoradiotherapy using superselective intra-arterial infusion for N3 cervical lymph node metastases of tongue cancer. (2013)
  • Author(s): Nishiguchi H, Mitsudo K, Yamamoto N, Tohnai I.
  • Journal Title: J Cancer Res Ther Volume: 9(7) Issue: 4 Pages: 718-720
  • DOI: 10.4103/0973-1482.126465
  • Peer Reviewed
• [Presentation] 薬効成分を磁性化した新しいパクリタキセルの口腔癌に対する治療法の開発 (2017)
  • Author(s): 中鍛治里奈，光藤健司，梅村将就，小泉敏之，佐藤 格，來生 知，廣田 誠，石川義弘，藤内 祝
  • Organizer: 第35回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2017-01-25
• [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: 2016-09-02
• [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: 2016-09-02
• [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): 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] Intra-arterial Infusion for Oral Cancer. (2015)
  • Author(s): Mitsudo K, Tohnai I
  • Organizer: 22nd International Oral and Maxillofacial Surgery
  • Place of Presentation: オーストラリアメルボルン
  • Year and Date: 2015-10-27
  • Int'l Joint Research / Invited
• [Presentation] 口腔癌における温熱療法と分子標的薬の併用療法の開発 (2015)
  • Author(s): 中島英行、大久保真紀子、宮島章嘉、飯坂友宏、杉浦 圭、飯田昌樹、佐藤 格、小泉俊之、來生 知、光藤健司，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] Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for advanced oral cancer. (2015)
  • Author(s): Mitsudo K, 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: 2015-06-03
  • Int'l Joint Research / Invited
• [Presentation] Thermochemoradiotherapy using superselective intra-arterial infusion for N3 cervical lymph node metastases of tongue squamous cell cancer (2014)
  • Author(s): Mitsudo K, Nishiguchi H, Yamamoto N, Tohnai I
  • Organizer: 6th Asian Congress of Hyperthermic Oncology
  • Place of Presentation: 福井県県民ホール（福井県福井市）
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] Preoperative thermochemoradiotherapy using retrograde superselective intraarterial infusion for locally advanced oral cancer with cervical lymph node metastases (2014)
  • Author(s): Koizumi T, Mitsudo K, Iida M, Nakashima H, Iwai T, Oguri S, Kioi M, Hirota M, Tohnai I
  • Organizer: 6th Asian Congress of Hyperthermic Oncology
  • Place of Presentation: 福井県県民ホール（福井県福井市）
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] Clinical evaluation of thermochemoradiotherapy using retrograde superselective intra-arterial infusion for advanced oral squamous cell carcinoma with cervical lymph node metastases (2014)
  • Author(s): Iida M, Mitsudo K, Ohara Y, Ohya T, Koizumi T, Nakashima H, Iwai T, Oguri S, Kioi M, Hirota M, Tohnai I
  • Organizer: 6th Asian Congress of Hyperthermic Oncology
  • Place of Presentation: 福井県県民ホール（福井県福井市）
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] Development of combination therapy with cisplatin and hyperthermia generated with ferucarbotran (Resovist) in an alternating magnetic field for oral cancer (2014)
  • Author(s): Sato I, Mitsudo K, Umemura M, Nakashima H, Kioi M, Eguchi H, IshikawaY, Tohnai I
  • Organizer: 6th Asian Congress of Hyperthermic Oncology
  • Place of Presentation: 福井県県民ホール（福井県福井市）
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] Development of thermochemotherapy using cisplatin and ferucarbotran (Resovist®) in head and neck cancer (2014)
  • Author(s): Sato I, Umemura M, Mitsudo K, Feng X, Nakashima H, Kioi M, Eguchi H, Tohnai I, Ishikawa Y
  • Organizer: American Association for Cancer Research Annual meeting 2014
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Organ preservation with daily concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion for stage III, IV oral cancer: analysis of therapeutic results in 112 Cases. (2013)
  • Author(s): Mitsudo K, Koizumi T, Iwai T, Nakashima H, Oguri S, Kioi M, Hirota M, Tohnai I.
  • Organizer: 2013 American Society of Clinical Oncology (ASCO) Annual Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] 臓器別シンポジウム16「口腔外科治療の最前線」：Stage III, IV上顎歯肉・硬口蓋癌に対する逆行性超選択的動注化学放射線療法 (2013)
  • Author(s): 光藤健司、小泉敏之、藤内 祝
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 京都国際会議場（京都）
• [Presentation] Novel thermo-chemotherapy using a new magnetic anti-cancer drug. (2013)
  • Author(s): Sato I, Umemura M, Mitsudo K, Feng X, Nakashima H, Kioi M, Eguchi H, Tohnai I, Ishikawa Y.
  • Organizer: American Association for Cancer Research (AACR) Annual Meeting 2013.
  • Place of Presentation: Washington, DC, USA
• [Presentation] 新規抗癌剤を用いた口腔癌に対するハイパーサーミアの開発 (2013)
  • Author(s): 佐藤 格，光藤健司，梅村将就，江口晴樹，石川義弘，藤内 祝．
  • Organizer: 第37回日本頭頸部癌学会
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] 進行口腔癌N2, 3症例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． (2013)
  • Author(s): 光藤健司、飯田昌樹、小泉敏之、大原良仁、中島英行、岩井俊憲、小栗千里、來生 知、小池 泉、幡多政治、藤内 祝．
  • Organizer: 日本放射線腫瘍学会第26回学術大会
  • Place of Presentation: ホテル青森（青森）
• [Book] Hyperthermic Oncology from Bench to Bedside (2016)
  • Author(s): Mitsudo K, Tohnai I (Editor: Ohnishi T, Yoshikawa T, Kokura S.)
  • Total Pages: 444
  • Publisher: Springer
• [Book] Hyperthermic Oncology from Bench to Bedside (2016)
  • Author(s): Mitsudo K., Tohnai I
  • Publisher: Springer
• [Book] Chemotherapy Oral Cancer: Diagnosis and Therapy (2015)
  • Author(s): Tohnai I, Mitsudo K
  • Total Pages: 426
  • Publisher: Springer