Development of the therapy for oral cancer by S-1 and proteasome inhibitor in combination with concurrent radiotherapy

• Project/Area Number: 19592339
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Yamaguchi University (2008); The University of Tokushima (2007)
• Principal Investigator: HARADA Koji Yamaguchi University, 大学院・医学研究科, 助教 (60253217)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: プロテアソーム阻害剤 / 5-FU / TS-1 / 放射線 / 併用療法 / NF-κB / アポトーシス、オートファジー / NF-KB / 口腔癌

Research Abstract

プロテアソーム阻害剤1(PSI1)は口腔扁平上皮癌細胞に対して、単剤で細胞増殖抑制効果を示し、5-FUおよび放射線(RT)との3者併用処理にて強い細胞増殖抑制効果が見られた。ヌードマウス腫瘍に対してもPSI1は単剤で抗腫瘍効果を示し、TS-1およびRTとの3者併用では顕著な抗腫瘍効果を示した。なおin vitroにおいてPSI1は口腔扁平上皮癌細胞のNF-κB活性を有意に抑制し、PSI1と5-FUはともにRTで活性化された口腔扁平上皮癌細胞のNF-κB活性を抑制した。

Research Products

• [Journal Article] Cepharanthine inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing expression of vascular endothelial growth factor and interleukin-8 (2009)
  • Author(s): Harada K, Ferdous T, Itashiki Y, TakiiM, Mano T, Mori Y, Ueyama Y.
  • Journal Title: Int J Oncol.
  • Peer Reviewed
• [Journal Article] Effects of cepharanthine alone and in combination with fluoropyrimidine anticancer agent, S-1, on tumor growth of human oral squamous cell carcinoma xenografts in nude mice (2009)
  • Author(s): Harada K, Ferdous T, Itashiki Y, Takii M, Mano T, Mori Y, Ueyama Y.
  • Journal Title: Anticancer Res. 29(4) Pages: 1263-70
  • Peer Reviewed
• [Journal Article] Clinical phase I trial of S-1 in the combination with DOC using super-selective intra-arterial infusion with oral cancer. (2009)
  • Author(s): Ueyama Y, Okafuji M, Harada K, Mano T, Mihara M, Uchida K, Horinaga D, Wada N.
  • Journal Title: Gan To Kagaku Ryoho. 36(3) Pages: 395-9
  • Peer Reviewed
• [Journal Article] Cepharanthine inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing expression of vascular endothelial growth factor and interleukin-8. (2009)
  • Author(s): Koji Harada
  • Journal Title: Int J Oncology (in press)
  • Peer Reviewed
• [Journal Article] Effects of Cepharanthine alone and in Combination with Fluoropyrimidine Anticancer Agent, S-1, on Tumor Growth of Human Oral Squamous Cell Carcinoma Xenografts in Nude Mice. (2009)
  • Author(s): Koji Harada
  • Journal Title: Anticancer Res (in press)
  • Peer Reviewed
• [Journal Article] Clinical phase I trial of S-1 in the combination with DOC using super-selective intra-arterial infusion with oral cancer (2009)
  • Author(s): Yoshiya Ueyama
  • Journal Title: Gan To Kagaku Ryoho 36 Pages: 395-399
  • Peer Reviewed
• [Journal Article] Differential involvement of TGF-beta1 in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells. (2008)
  • Author(s): Motegi K, Harada K, Ohe G, Jones SJ, Ellis IR, Crouch DH, Schor SL, Schor AM.
  • Journal Title: Exp Cell Res. 1 ; 314(13) Pages: 2323-33
  • Peer Reviewed
• [Journal Article] Oral Cancer Study Group of Chugoku-Shikoku. Multi-institutional phase II trial of S-1 in patients with oral squamous cell carcinoma (2008)
  • Author(s): Harada K, Sato M, Ueyama Y, Nagayama M, Hamakawa H, Nagahata S, Yoshimura Y, Osaki T, Ryoke K
  • Journal Title: Anticancer Drugs. 19(1) Pages: 85-90
  • Peer Reviewed
• [Journal Article] Differential involvement of TGF-betal in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells. (2008)
  • Author(s): Katsumi Motegi
  • Journal Title: Exp Cell Res 314 Pages: 2323-2333
  • Peer Reviewed
• [Journal Article] Multi-institutional phase II trial of S-1 in patients with oral squamous cell carcinoma. (2008)
  • Author(s): Koji Harada
  • Journal Title: Anticancer Drugs 19 Pages: 85-90
  • Peer Reviewed
• [Journal Article] Multi-institutional phase II trial of S-1 in patients with oral squamous cell carcinoma (2008)
  • Author(s): Koji Harada
  • Journal Title: Anticancer Drugs 19 Pages: 85-90
  • Peer Reviewed
• [Journal Article] Investigation of optimal schedule of concurrent radiotherapy with S-1 for oral squamous cell carcinoma (2007)
  • Author(s): Harada K, Ferdous T, Yoshida H.
  • Journal Title: Oncol Rep. 18(5) Pages: 1077-83
  • Peer Reviewed
• [Journal Article] A case of oral squamous cell carcinoma responding to S-1.(Japanese) (2007)
  • Author(s): Harada K, Tamatani T, Bando T, YoshidaH.
  • Journal Title: Gan To Kagaku Ryoho. 34(9) Pages: 1455-8
  • Peer Reviewed
• [Journal Article] Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with fluoropyrimidine anticancer agent, S-1, on tumor growth of human oral squamous cell carcinoma xenografts in nude mice. (2007)
  • Author(s): Itashiki Y, Harada K, Ferdous T,Yoshida H.
  • Journal Title: Anticancer Res. 27(4B) Pages: 2365-75
  • Peer Reviewed
• [Journal Article] A case of advanced oral squamous cell carcinoma responding to concurrent radiotherapy with S-1.(Japanese) (2007)
  • Author(s): Harada K, Kawashima Y, Uchida D,Yoshida H.
  • Journal Title: Gan To Kagaku Ryoho. 34(5) Pages: 745-7
  • Peer Reviewed
• [Journal Article] S-1 inhibits tumorigenicity and angiogenesis of human oral squamous cell carcinoma cells by suppressing expression of phosphorylated Akt (2007)
  • Author(s): Harada K, Supriatno, Kawashima Y,Yoshida H, Sato M.
  • Journal Title: vascular endothelial growth factor nd fibroblast growth factor-2. Int J Oncol. 30(2) Pages: 365-74
  • Peer Reviewed
• [Journal Article] Investigation of optimal schedule of concurrent radiotherapy with S-1 for oral squamous cell carcinoma (2007)
  • Author(s): Koji Harada
  • Journal Title: Oncol Rep. 18 Pages: 1077-1083
  • Peer Reviewed
• [Journal Article] Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with fluoropyrimidine anticancer agent,S-1,on tumor growth of human oral squamous cell carcinoma xenografts in nude mice (2007)
  • Author(s): Yasutaka Itashiki
  • Journal Title: Anticancer Res. 27 Pages: 1455-1458
  • Peer Reviewed
• [Presentation] 口腔扁平上皮癌に対するTS-1とDocetaxel併用療法の有用性の検討 (2009)
  • Author(s): 原田耕志
  • Organizer: 日本口腔腫瘍学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2009-01-29
• [Presentation] ヒト口腔扁平上皮癌におけるTS-1による血管新生阻害因子TSP-1の誘導 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本口腔科学会地方会
  • Place of Presentation: 米子
  • Year and Date: 2008-11-29
• [Presentation] ヒトロ腔扁平上皮癌におけるTS-1による血管新生阻害因子TSP-1の誘導 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本口腔科学会地方会
  • Place of Presentation: 米子
  • Year and Date: 2008-11-29
• [Presentation] 口腔扁平上皮癌に対するTS-1・プロテアソーム阻害剤・放射線同時併用療法の開発 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本癌治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-31
• [Presentation] 口腔扁平上皮癌に対するTS-1 ・プロテアソーム阻害剤・放射線同時併用療法の開発 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本癌治療学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-31
• [Presentation] TS-1配合成分ギメラシルのDNA二重鎖断裂修復機構への影響 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 口腔扁平上皮癌におけるTS-1の感受性予測因子の検討 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本口腔外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2008-10-21
• [Presentation] 口腔癌に対する5-FU ・プロテアソーム阻害剤・放射線同時併用療法の開発 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本口腔外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2008-10-21
• [Presentation] 口腔癌に対する5-FU・プロテアソーム阻害剤・放射線同時併用療法の開発 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本口腔外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2008-10-20
• [Presentation] 口腔扁平上皮癌に対するレンチナンのフッ化ピリミジン系抗癌剤増強効果 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本頭頚部癌学会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-11
• [Presentation] 口腔扁平上皮癌細胞に対するDocetaxelと5-FUの投与順序による抗腫瘍効果の検討 (2008)
  • Author(s): 原田耕志
  • Organizer: 日本口腔科学会総会
  • Place of Presentation: 博多
• [Presentation] 口腔扁平上皮癌に対するCepharanthineによるTS-1の抗癌作用増強効果の解析 (2007)
  • Author(s): 原田 耕志
  • Organizer: 日本癌治療学会
  • Place of Presentation: 京都
  • Year and Date: 2007-10-24
• [Presentation] Thymidylate Synthase and dihydropyrimidine dehydrogenase mRNA Expressions in Oral Squamous Cell Carcinoma Predicts for Response to Chemoradiotherapy with S-1 (2007)
  • Author(s): 原田 耕志
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03