Basic analysis of anti-allergic agent MMKY-01, which accelerating drug sensitivity to gemicitabine in pancreatic cancer cell.

• Project/Area Number: 20591632
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Saga University
• Principal Investigator: KITAJIMA Yoshihiko Saga University, 医学部, 客員研究員 (30234256)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 膵癌 / 胆嚢癌 / ジェムシタビン / MMKY-01 / RRM1 / ユビキチン / TGF-β / ジェムシタビン耐性 / GB-d1R / TGF-beta / cDNAアレイ / アポトーシス / MMYK-01 / ジェムシタビン(GEM) / GEM耐性株 / DNAアレイ / 増強効果

Research Abstract

The present study demonstrated that MMKY-01 accelerates drug sensitivity to gemcitabine via decreasing RRM1 expression in pancreatic and gall bladder (GB) cancer cells. The reduced RRM1 expression was derived through ubiquitin-proteosome pathway in pancreatic cancer. Further analysis revealed that MMKY-01 rendered gemcitabine resistant GB cancer cell to apoptosis. These results indicated that MMKY-01 plus gemcitabine is possibly effective to pancreatic as well as GB cancer. Especially, MMKY-01 treatment was revealed to reverse the gemcitabine resistance in GB cancer.

Research Products

• [Journal Article] Tranilast strongly sensitizes pancreatic cancer cells to gemcitabine via decreasing protein expression of ribonucleotide reductase 1. (2010)
  • Author(s): Mayumi Mitsuno, Yoshihiko Kitajima, Kazuma Ohtaka, Keita Kai, Kazuyoshi Hashiguchi, Jun Nakamura, Masatsugu Hiraki, Hirokazu Noshiro, Kohji Miyazaki.
  • Journal Title: Int J Oncol 36 Pages: 341-349
  • Peer Reviewed
• [Journal Article] Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistory predicts the efficacy of gemcitabine in biliary tract carcinoma. (2010)
  • Author(s): Nakamura J, Kohya N, Kai K, Ohtaka K, Hashiguchi K, Hiraki M, Kitajima Y, Tokunaga O, Noshiro H, Miyazaki K.
  • Journal Title: Int J Oncol 37 Pages: 845-852
  • Peer Reviewed
• [Journal Article] Tranilast strongly sensitizes pancreatic cancer cells (2010)
  • Author(s): Mayumi Mitsuno
  • Journal Title: International Journal of Oncology Volume: 36 Pages: 341-349
  • Peer Reviewed
• [Journal Article] Tranilast strongly sensitizes pancreatic cancer cells to gemcitabine via decreasing protein expression of ribonucleotide reductase 1 (2010)
  • Author(s): M Mituno, Y Kitajima, at al
  • Journal Title: International Journal of Oncology 36 Pages: 341-349
  • Peer Reviewed
• [Presentation] GEM耐性胆道癌細胞株におけるTranilastのapoptosis誘導作用の検討 (2009)
  • Author(s): 橋口和義、北島吉彦, 他
  • Organizer: 日本消化器癌発生学会
  • Place of Presentation: オリエンタルホテル広島
  • Year and Date: 2009-11-27
• [Presentation] Gemcitabine耐性胆道癌細胞株におけるTranilastのApoptosis誘導作用の検討 (2009)
  • Author(s): 橋口和義、北島吉彦、平木将紹、中村淳、能城浩和、宮崎耕治
  • Organizer: 第20回日本消化器癌発生学会総会
  • Place of Presentation: オリエンタルホテル広島
• [Presentation] Gemcitabine耐性胆道癌細胞株におけるTranilastのApoptosis誘導機構についての検討 (2009)
  • Author(s): 橋口和義、北島吉彦、平木将紹、中村淳、光野真由美、宮崎耕治
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 膵癌に対するRRM1を分子標的としたTranilast+GEM併用療法の可能性 (2008)
  • Author(s): 光野真由美, 北島吉彦, 他
  • Organizer: 日本外科学会総会
  • Place of Presentation: 長崎ブリックホール(長崎)
  • Year and Date: 2008-05-15
• [Presentation] 膵癌におけるTranilastのRRM1発現抑制効果に基づいたTranilast+Gemcitabine(dFdC)併用療法の可能性 (2008)
  • Author(s): 北島吉彦、光野真由美、橋口和義、中村淳、平木将紹、大塚隆生、神谷尚彦、宮崎耕治
  • Organizer: 第19回日本消化器癌発生学会
  • Place of Presentation: 別府亀の井ホテル
• [Presentation] 胆道癌細胞株におけるTranilastのRRM1発現抑制効果を介したGemcitabine感受性増強作用 (2008)
  • Author(s): 橋口和義、光野真由美、北島吉彦、大高和真、平木将紹、中村淳、神谷尚彦、中房祐司、宮崎耕治
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎ブリックホール
• [Presentation] 膵癌に対するRRM1を分子標的としたTranilast+Gemcitabine併用療法の可能性 (2008)
  • Author(s): 光野真由美、北島吉彦、平木将紹、橋口和義、中村淳、神谷尚彦、宮崎耕治
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎ブリックホール
• [Presentation] Tranilast increased the drug effect of gemcitabine via protain degradation of RRM1 in pancreatic cancer cells. (2008)
  • Author(s): Yoshihiko Kitajima, Mayumi Mitsuno, Kazuyoshi Hashiguchi, Jun Nakamnura, Masatsugu Hiraki, Kohji Miyazaki
  • Organizer: AACR annual meeting 2008
  • Place of Presentation: San Diego, USA
• [Remarks] ホームページ等