Development of combination therapy for head and neck squamous cell carcinoma to reduce the side effects of EGFR inhibitors

• Project/Area Number: 25870841
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry; Functional basic dentistry
• Research Institution: Kanagawa Dental College
• Principal Investigator: MIYAMOTO Chihiro 神奈川歯科大学, 歯学研究科(研究院), 研究員 (50633963)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: CXCl14/BRAK / 頭頚部扁平上皮癌 / ケモカイン / 歯科薬理学 / CXCL14/BRAK / fasudil / cetuximab / 薬理学 / 悪性腫瘍 / 遺伝子

Outline of Final Research Achievements

We previously reported that fasudil can be used anti-tumor drug via targeted CXCL14/BRAK secretion. This finding indicate that fasudil shows the potential to enhance the effect of cetuximab via increase secretion of BRAK protein. In this study, we examined the combination of cetuximab and fasudil. As a result, BRAK protein generated by cetuximab is to be secreted effectively by fasudil. This result suggests that fasudil reinforces an effect of cetuximab or reduces consumption of cetuximab, and can reduce a side effect.

Research Products

• [Journal Article] Effect of Low-Intensity Pulsed Ultrasound (LIPUS) in Rats With Healing Socket. (2015)
  • Author(s): Hidaka K, Miyamoto C, Takahashi SW, Saita M, Kawamata R, Maehata Y, Minabe M, Takahashi S, Mikuni-Takagaki Y.
  • Journal Title: Journal of Orthopaedic Trauma Volume: 29
  • DOI: 10.1097/01.bot.0000462954.94859.a3
  • Peer Reviewed / Open Access
• [Journal Article] Humoral response to therapeutic low-intensity pulsed ultrasound (LIPUS) treatment of rat maxillary socket after the removal of a molar tooth. (2015)
  • Author(s): Hidaka K, Miyamoto C, Wada-Takahashi S, Saita M, Kawata A, Kawamata R, Maehata Y, Minabe M, Takahashi S-S, Mikuni-Takagaki Y
  • Journal Title: International Journal of Analytical Bio-Science Volume: 3 Pages: 17-24
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXCL14/BRAK transgenic mice. (2015)
  • Author(s): Hata R, Izukuri K, Kato Y, Sasaki S, Mukaida N, Maehata Y, Miyamoto C, Akasaka T, Yang X, Nagashima Y, Takeda K, Kiyono T, Taniguchi M.
  • Journal Title: Sci Rep Volume: 5 Pages: 9083-9083
  • DOI: 10.1038/srep09083
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Medical-grade collagen peptide in injectables provides antioxidant protection (2015)
  • Author(s): Kobayashi K, Maehata Y, Okada Y, Kusubata M, Hattori S, Tanaka K, Miyamoto C, Yoshino F, Yoshida A, Tokutomi F, Wada-Takahashi S, Komatsu T, Otsuka T, Takahashi SS, Lee MC
  • Journal Title: Pharmaceutical Development and Technology, Volume: online Pages: 219-226
  • DOI: 10.3109/10837450.2013.860547
  • Peer Reviewed / Open Access
• [Journal Article] <b>Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell car</b><b>cinoma </b> (2014)
  • Author(s): Miyamoto C., Maehata Y, Motohashi K, Ozawa S, Ikoma T, Hidaka K, Wada-Takahashi S, Yoshino F, Yoshida A, Kubota E, Hata R, Lee M.C
  • Journal Title: Biomed. Res. Volume: 35 Issue: 6 Pages: 381-388
  • DOI: 10.2220/biomedres.35.381
  • NAID: 130004903867
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reactive oxygen species scavenging activity of Jixueteng evaluated by electron spin resonance (ESR) and photon emission. (2014)
  • Author(s): Toyama T, Wada-Takahashi S, Takamichi M, Watanabe K, Yoshida A, Yoshino F, Miyamoto C, Maehata Y, Sugiyama S, Takahashi SS, Todoki K, Lee MC, Hamada N.
  • Journal Title: Natural Product Communications Volume: 9 Pages: 1755-1759
  • Peer Reviewed
• [Journal Article] Blue light from dental resin curing unit causes light-induced vasoconstriction in isolated rat aorta. (2014)
  • Author(s): Yoshida A, Iwata S, Iizuka J, Takahashi S-S, Wada-Takahashi S, Miyamoto C, Maehata Y, Ogura Y, Lee M-C, Yoshino F.
  • Journal Title: Oral Health and Dental Management Volume: 13 Pages: 1147-1151
  • Peer Reviewed / Open Access
• [Journal Article] Reactive oxygen species production in mitochondria of human gingival fibroblast induced by blue light irradiation (2013)
  • Author(s): Yoshida A, Yoshino F, Makita T, Maehata Y, Higashi K, Miyamoto C, Wada-Takahashi S, Takahashi S-S, Takahashi O, Lee M-C
  • Journal Title: Journal of photochemistry and photobiology. B, Biology. Volume: 129 Pages: 1-5
  • DOI: 10.1016/j.jphotobiol.2013.09.003
  • Peer Reviewed
• [Journal Article] Acidic extracellular microenvironment and cancer. (2013)
  • Author(s): Kato Y, Ozawa S, Miyamoto C, Maehata Y, Suzuki A, Maeda T, Baba Y
  • Journal Title: Cancer Cell International. Volume: 13 Pages: 89-89
  • DOI: 10.1186/1475-2867-13-89
  • Peer Reviewed
• [Presentation] Low-intensity Pulsed Ultrasound Prevents Malhealing of Infected Rat Extraction Socket. (2015)
  • Author(s): Hidaka K, Miyamoto C, Kawamata R, Wada-Takahashi S, Takahashi S-S, Maehata Y, Saita M, Sato T, Taniguchi M, Kawata M, Ozaki Y, Funayama Y, Watabe H, Tani-Ishii N, Hamada N, Deguchi S, Mikuni-Takagaki Y
  • Organizer: 93rd General Session & Exhibition of the IADR/44th Annual Meeting of the AADR/39th Annual Meeting of the CADR
  • Place of Presentation: Boston, Massachusetts, USA
  • Year and Date: 2015-03-11 – 2015-03-14
• [Presentation] ラット抜歯窩に照射した低出力超音波パルスが全身的に及ぼす影響 Effect of Low-intensity Pulsed Ultrasound in Rats with Healing Socket. (2015)
  • Author(s): 日髙恒輝，宮本千央，高橋聡子，斉田牧子，川股亮太，前畑洋次郎，三辺正人，高橋俊介，高垣裕子
  • Organizer: 第18回 超音波骨折治療研究会
  • Place of Presentation: ANAクラウンプラザホテル神戸（兵庫県）
  • Year and Date: 2015-01-17
• [Presentation] ラット抜歯窩治癒に及ぼす低出力超音波パルス（LIPUS）の影響 (2015)
  • Author(s): 日髙恒輝, 宮本千央, 高橋聡子, 斉田牧子, 川股亮太, 前畑洋次郎, 三辺正人, 高橋俊介, 高垣裕子
  • Organizer: 第146回神奈川歯科大学学会例会
  • Place of Presentation: 神奈川歯科大学（神奈川県）
  • Year and Date: 2015-01-08
• [Presentation] 頭頚部扁平上皮癌における抗腫瘍ケモカインCXCL14/BRAKの局在を標的とした新規多剤併用療法の研究開発 (2015)
  • Author(s): 宮本千央, 生駒丈晴, 近藤忠稚, 小澤重幸, 畑隆一郎, 久保田英朗, 前畑 洋次郎
  • Organizer: 第146回神奈川歯科大学学会例会
  • Place of Presentation: 神奈川歯科大学（神奈川県）
  • Year and Date: 2015-01-08
• [Presentation] ット抜歯窩に照射した低出力超音波パルス (LIPUS) が全身に及ぼす影響 (2014)
  • Author(s): 日髙恒輝, 宮本千央, 高橋聡子, 斉田牧子, 川股亮太, 前畑洋次郎, 三辺正人, 高橋俊介, 高垣裕子
  • Organizer: 第49回神奈川歯科大学学会総会
  • Place of Presentation: 神奈川歯科大学（神奈川県）
  • Year and Date: 2014-11-29
• [Presentation] Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell carcinoma. (2014)
  • Author(s): 本橋一彦，宮本千央，前畑洋次郎，吉田彩佳，高橋聡子，高橋俊介，吉野文彦:
  • Organizer: 第49回 神奈川歯科大学学会総会
  • Place of Presentation: 神奈川歯科大学（神奈川県）
  • Year and Date: 2014-11-29
• [Presentation] eactive oxygen species scavenging activity of Jixueteng evaluated by electron spin resonance (ESR) and photon emission. (2014)
  • Author(s): 高道麻臣，遠山歳三，高橋聡子，吉田彩佳，吉野文彦，宮本千央，前畑洋次郎，渡辺清子，杉山秀太，塗々木和男，李 昌一，浜田信城，高橋俊介
  • Organizer: 第49回 神奈川歯科大学学会総会
  • Place of Presentation: 神奈川歯科大学（神奈川県）
  • Year and Date: 2014-11-29
• [Presentation] ROCK 阻害剤 Fasudil の頭頚部扁平上皮癌における CXCL14/BRAK を介した抗腫瘍効果の検討 (2014)
  • Author(s): ○宮本 千央 、前畑 洋次郎 、高橋 聡子 、吉野 文彦 、吉田 彩佳 、高橋 俊介 、李 昌一
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡国際会議場（福岡県）
  • Year and Date: 2014-09-25 – 2015-09-27
• [Presentation] ROCK sp ecific inhibitor fasudil suppresseshead and neck squamous carcinoma growthby stimu lating gene expre ssion and proteinsecretion of the chemokine CXCL14/BRAK (2014)
  • Author(s): C. Miyamoto, S. Ozawa, T. Ikoma, S. Wada-Takahashi,S.-S. Takahashi, A. Yoshida, F. Yoshino, R.-I. Hata,M. C.-I. Lee, Y. Maehata
  • Organizer: FEBS EMBO 2014 Conference
  • Place of Presentation: Paris, France,
  • Year and Date: 2014-08-30 – 2014-09-04
• [Presentation] The novel collagen peptide reduced thephoto-aging induced by UVA irradiation (2014)
  • Author(s): Y. Maehata, K. Kobayashi, C. Miyamoto, S.-S. Takahashi,F. Yoshino, S. Wada-Takahashi, A. Yoshida, M. C.-I. Lee
  • Organizer: FEBS EMBO 2014 Conference
  • Place of Presentation: Paris, France,
  • Year and Date: 2014-08-30 – 2014-09-04
• [Presentation] Effect of Therapeutic Low-intensity Pulsed Ultrasound (LIPUS) after the Treatment of Rat Extraction Socket. (2014)
  • Author(s): Hidaka K, Chihiro M, Wada-Takahashi S, Kawamata R, Maehata Y, Minabe M, Takahasi S-S, Mikuni-Takagaki Y
  • Organizer: FEBS EMBO 2014 Conference
  • Place of Presentation: Paris, France,
  • Year and Date: 2014-08-30 – 2014-09-04
• [Presentation] 歯科におけるブルーライトハザード─歯肉線維芽細胞へ及ぼす影響の検討. (2014)
  • Author(s): 吉田彩佳，高橋俊介，高橋聡子，前畑洋次郎，宮本千央，李 昌一，吉野文彦
  • Organizer: 第14回 日本抗加齢医学会総会
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-06-06 – 2014-06-08
• [Presentation] ハムスターを用いた癌化学療法に併発する口内炎における活性酸素評価 (2014)
  • Author(s): 吉野文彦，吉田彩佳，高橋俊介，高橋聡子，前畑洋次郎，宮本千央，李 昌一
  • Organizer: 第14回 日本抗加齢医学会総会
  • Place of Presentation: 大阪国際会議場（大阪府）
  • Year and Date: 2014-06-06 – 2014-06-08
• [Presentation] Fasudil Suppresses Head and Neck Squamous Cell Carcinoma Growth by Stimulating Gene Expression and Secretion of the Chemokine CXCL14/BRAK. (2013)
  • Author(s): Miyamoto C., Ozawa S., Takahashi S-S., W-Takahashi S., Yoshino F., Lee M-C., Hata R-I., Maehata Y.
  • Organizer: Pharmacology 2013
  • Place of Presentation: London, England
• [Presentation] 頭頸部扁平上皮癌における ROCK 阻害剤による CXCL14/BRAK を介した抗腫瘍効果の検討.
  • Author(s): 宮本千央，生駒丈晴，小澤重幸，高橋俊介，高橋聡子，吉野文彦，吉田彩佳，畑隆一郎，李 昌一，前畑洋次郎
  • Organizer: 神奈川歯科大学学会 第 143 回例会
  • Place of Presentation: 横須賀