Development of a new oral cancer treatment via regulation of the anti-tumor factor BRAK expression with DNA methylation inhibitors.

• Project/Area Number: 25463101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kanagawa Dental College
• Principal Investigator: MAEHATA YOJIRO 神奈川歯科大学, 歯学研究科(研究院), 講師 (80410009)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); 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); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 口腔癌 / CXCL14/BRAK / BRAK / EGCG / DNAメチル化阻害 / HNSCC / 口腔扁平上皮癌 / エピガロカテキンガレート

Outline of Final Research Achievements

In this study, we examined the effect of anti-tumor activity via upregulation of CXCL14/BRAK expression by treatment of the epigallocatechin gallate (EGCG) in oral squamous cell carcinoma (HNSCC). As a result, EGCG did not showed significantly increased of the expression of BRAK.Therefore, we examined the effects of DAC on expression of BRAK by using a potent methylation inhibitor decitabine. As a result, we confirmed the inhibitory effect of tumor growth via upregulation of BRAK in vivo. These data indicate that it is very useful in oral cancer treatment strategy by using the methylation inhibitors or natural products with a methylation inhibitory effect.

Research Products

• [Journal Article] Expression of the chemokine CXCL14 and cetuximab-dependent tumour suppression in head and neck squamous cell carcinoma. (2016)
  • Author(s): 1.Kondo T, Ozawa S, Takeharu Ikoma T, Yang Xiao-Yan, Knamori K, Suzuki K, Iwabuchi H, Maehata Y, Miyamoto C, Taguchi T, Kiyono T, Kubota E, Hata R-I
  • Journal Title: Oncogenesis Volume: in press
  • Peer Reviewed
• [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: Scientific Reports Volume: 5 Pages: 9083-9083
  • Peer Reviewed / Open Access
• [Journal Article] Medical-grade collagen peptide in injectables provides antioxidant protection. Pharmaceutical Development and Technology (2015)
  • Author(s): Kobayashi K, Maehata Y, ,(equal to 1st author) Okada Y, Kusubata M, Hattori S, Tanaka K, Miyamoto C, Yoshino F, Yoshida A, Tokutomi F, Wada-Takahashi S, Komatsu T, Otsuka T, Takahashi S-S, Lee M-C
  • Journal Title: Pharmaceutical Development and Technology Volume: 20 Pages: 219-226
  • Peer Reviewed
• [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: 2 Pages: 17-24
  • 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
  • Journal Title: Natural Product Communications Volume: 12 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
• [Journal Article] Fasudil, a Rho kinase inhibitor, suppresses tumor growth by inducing CXCL14/BRAK in head and neck squamous cell carcinoma (2014)
  • Author(s): Miyamoto C, Maehata Y(equal to 1st author, Corresponding anther), Motohashi K, Ozawa S, Ikoma T, Kouki H, Wada-Takahashi S, Takahashi S-S, Yoshino F, Yoshida A, Kubota E, Hata R-I, Lee M-C
  • Journal Title: Biomedical Research Volume: 35 Pages: 381-388
  • NAID: 130004903867
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] EC-SOD levels in pre-dialysis sera and the relationship with HOMA-R (2014)
  • Author(s): Maehata Y, Maehata K, Adachi T, Tanaka A4, Ikoshi N, Kuroda N, Kishikawa N, Shiba T, Matsushita M, Yanagisawa T, Maehata E, Shimomura H
  • Journal Title: International Journal of Analytical Bio-Science Volume: 2 Pages: 155-162
  • NAID: 40020305092
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Medical-grade collagen peptide in injectables provides antioxidant protection (2013)
  • Author(s): Kobayashi K, Maehata Y.,(equal to 1st author), Okada Y, Kusubata M, Hattori S, Tanaka K, Miyamoto C, Yoshino M, Yoshida A, Tokutomi1 F, Wada-Takahashi S, Komatsu T, Otsuka T, Takahashi S, and Lee M-C
  • Journal Title: Pharmaceutical Development and Technology Volume: Nov.29
• [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 Int Volume: 13(1) Pages: 89-89
• [Presentation] Rho Kinase (ROCK) Inhibitor Fasudil Suppresses Head and Neck Squamous Carcinoma Growth by Stimulating Gene Expression and Protein Secretion of the CXCL14/BRAK (2016)
  • Author(s): Miyamoto C, Ozawa C, Ikoma T, Izukuri K, Hata R, Maehata Y,
  • Organizer: The 13th Asia Pacific Federation of Pharmacologist (APFP) Meeting,
  • Place of Presentation: Bangkok
  • Year and Date: 2016-02-01
  • Int'l Joint Research
• [Presentation] Scavenger of reactive oxygen species is effective for the inhibition of angiogenesis and tumor proliferation in human head and neck squamous cell carcinoma cells by regulation gene expression of chemokines (2016)
  • Author(s): ●Maehata Y, Miyamoto C, Yoshino F, Ozawa S, Takahashi SS, Wada-Takahashi S, Yoshida A, Izukuri K, Hata R, Tsukinoki K
  • Organizer: The 13th Asia Pacific Federation of Pharmacologist (APFP) Meeting
  • Place of Presentation: Bangkok
  • Year and Date: 2016-02-01
  • Int'l Joint Research
• [Presentation] The novel collagen peptide reduced the photo-aging induced by UVA irradiation (2014)
  • Author(s): Maehata Y, Kobayashi k, Miyamoto C, Takahashi S-S, Yoshino F, Takahashi-wada S,Yoshida A, Masaichi C.-I. Lee
  • Organizer: FEBS EMBO 2014 Conference
  • Place of Presentation: Paris, France
  • Year and Date: 2014-08-30 – 2014-09-04
• [Presentation] ROCK specific inhibitor fasudil suppresses head and neck squamous carcinoma growth by stimulating gene expression and protein secretion of the CXCL14/BRAK (2014)
  • Author(s): Miyamoto C, Ozawa T, Ikoma T, Wada-Takahashi S, Takahashi S-S, Yoshida A, Yoshino F, Hata R, Lee M-C, Maehata Y
  • Organizer: FEBS EMBO 2014 Conference
  • Place of Presentation: Paris, France
  • Year and Date: 2014-08-30 – 2014-09-04
• [Presentation] CXCL14のプロモーターのメチル化は頭頸部扁平上皮癌に対するセツキシマブの抗腫瘍効果に関与する (2013)
  • Author(s): 近藤忠稚，小澤重幸，生駒丈晴，鈴木健司，前畑洋次郎，宮本千央，畑隆一郎，久保田英朗
  • Organizer: 神奈川歯科学会総会
  • Place of Presentation: 神奈川県横須賀
• [Presentation] 化学療法において併発する口内炎における活性酸素評価 (2013)
  • 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: 神奈川歯科学会総会
  • Place of Presentation: 神奈川県横須賀
• [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 (2013)
  • Author(s): 宮本千央，前畑洋次郎，小澤重幸，生駒丈晴，畑隆一郎，李昌一
  • Organizer: 神奈川歯科学会総会
  • Place of Presentation: 神奈川県横須賀
• [Presentation] Fasudil Suppresses Head and Neck Squamous Carcinoma Growth by Stimulating Gene Expression and Secretion of the Chemokine CXCL14/BRAK (2013)
  • Author(s): C Miyamoto, S Ozawa, SS Takahashi, SW Takahashi, F Yoshino, MC Lee, RI Hata, Y Maehata
  • Organizer: Pharmacology 2013, London
  • Place of Presentation: London