Development of the pancreatic cancer therapy by identification of EMT inducer by chemotherapy

• Project/Area Number: 23591016
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa Medical University
• Principal Investigator: SHIMASAKI Takeo 金沢医科大学, 総合医学研究所, 講師 (50377420)
• Co-Investigator(Kenkyū-buntansha): ISHIGAKI Yasuhito 金沢医科大学, 総合医学研究所, 准教授 (20232275) ; TOMOSUGI Naohisa 金沢医科大学, 総合医学研究所, 教授 (80155580)
• Co-Investigator(Renkei-kenkyūsha): MOTOO Yoshiharu 金沢医科大学, 医学部, 教授 (80210095) ; MINAMOTO Toshinari 金沢大学, がん研究所, 教授 (50239323)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 化学療法 / EMT / ドラッグリポジショニング / 膵臓がん / GSK３β / 化学療法誘導性EMT / 膵臓癌治療薬 / GSK3β / 膵臓癌

Research Abstract

Pancreatic cancer is obstinate and results in a highly invasive and metastatic tumor phenotype that is a major obstacle to chemotherapy. We found that the pancreatic cancer cell lines exposed low concentration of gemcitabine triggered the cellular morphological change showing epithelial to mesenchymal transition (EMT) and up-regulated motility. These phenomenon are inhibited by GSK3beta inhibitor. We proposed a new strategy of inhibiting EMT-induced by chemotherapy by GSK3beta inhibiting drugs. In order to investigate the safety and antitumor response to this combination of GSK3beta inhibiting drugs, Investigator initiated phase I clinical trial are conducted with advanced pancreatic cancer. This research may contribute to the development of a new pancreatic cancer treatment.

Research Products

• [Journal Article] Aberrant glycogen synthase kinase 3βis involved in pancreatic cancer cell invasion and resistance to therapy (2013)
  • Author(s): Kitano A, Shimasaki T, Chikano Y, Nakada M, Hirose M, Higashi T, Ishigaki Y, Endo Y, Takino T, Sato H, Sai Y, Miyamoto K, Motoo Y, Kawakami K, Minamoto T.
  • Journal Title: PLoS One Volume: 8(2)
  • Peer Reviewed
• [Journal Article] GSK3β阻害作用を持つ医薬品を用いた難治性膵癌の新規治療法の開発 (2013)
  • Author(s): 島崎猛夫、上田順彦、源利成
  • Journal Title: がん治療のあゆみ Volume: 第33巻
• [Journal Article] Aberrant glycogen synthase kinase 3β in pancreatic cancer development, progression and resistance to therapy. (2013)
  • Author(s): Shimasaki T, Kitano A, Motoo Y, Minamoto T
  • Journal Title: J Carcinog Volume: 11 Issue: 1 Pages: 15-15
  • DOI: 10.4103/1477-3163.100866
  • Peer Reviewed
• [Journal Article] Aberrant glycogen synthase kinase 3β is involved in pancreatic cancer cell invasion and resistance to therapy (2013)
  • Author(s): Kitano A
  • Journal Title: PLoS One Volume: 8 Issue: 2 Pages: 15-15
  • DOI: 10.1371/journal.pone.0055289
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/
  • Peer Reviewed
• [Journal Article] Glycogen synthase kinase 3βinhibition sensitizes pancreatic cancer cells to gemcitabine (2012)
  • Author(s): Shimasaki T, Ishigaki Y, Nakamura Y, Takata T, Nakaya N, Nakajima H, Sato I, Zhao X, Kitano A, Kawakami K, Tanaka T, Takegami T, Tomosugi N, Minamoto T, Motoo Y.
  • Journal Title: J Gastroenterol Volume: 47(3) Pages: 321-33
  • NAID: 10030560208
  • Peer Reviewed
• [Journal Article] Glycogen synthase kinase 3β inhibition sensitizes pancreatic cancer cells to gemcitabine (2012)
  • Author(s): Shimasaki T, Kawakami K, Minamoto T, et al
  • Journal Title: J Gastroenterol Volume: 47 (3) Issue: 3 Pages: 321-33
  • DOI: 10.1007/s00535-011-0484-9
  • NAID: 10030560208
  • URL: http://www.kanazawa-u.ac.jp/~ganken/shuyoseigyo/
  • Peer Reviewed
• [Journal Article] Scanning electron microscopy with an ionic liquid reveals the loss of protrusions in TGF-β1-treated mitotic cells. (2011)
  • Author(s): YasuhitoIshigaki,YoshimichiUeda,他11名
  • Journal Title: Microsc ResTech Volume: 74 Issue: 11 Pages: 1024-31
  • DOI: 10.1002/jemt.20989
  • Peer Reviewed
• [Journal Article] Human SMG-1 is involved in gemcitabine-induced primary microRNA-155/BIC up-regulation in human pancreatic cancer PANC-1 cells (2011)
  • Author(s): Xia QS
  • Journal Title: Pancreas Volume: 40(1) Issue: 1 Pages: 55-60
  • DOI: 10.1097/mpa.0b013e3181e89f74
  • Peer Reviewed
• [Presentation] Phase I clinical trial of the combination therapy using gemcitabine and GSK3beta inhibiting drugs for gemcitabine-resistant advanced pancreatic cancer patients (2014)
  • Author(s): Shimasaki T, Tomosugi N, Minamoto T, et al.
  • Organizer: DDW 2014
  • Place of Presentation: Chicago, USA
• [Presentation] GSK3βを標的治療とした既存医薬品による膵がんの新規治療 (2013)
  • Author(s): 島崎猛夫,石垣靖人,源利成,友杉直久他
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台国際センター
• [Presentation] GSK3βis an emerging therapeutic target in pancreatic cancer : its implication for cancer cell migration and invasion (2013)
  • Author(s): Shimasaki T, Ishigaki Y, Tomosugi N, Minamoto T, et al.
  • Organizer: DDW 2013
  • Place of Presentation: Orland, FL, USA
• [Presentation] GSK3β is an emerging therapeutic target in pancreatic cancer: its implication for cancer cell migration and invasion (2013)
  • Author(s): 島崎猛夫
  • Organizer: DDW 2013
  • Place of Presentation: アメリカ、オーランド、Orange County Convention Center.
• [Presentation] GSK3β標的治療を併用した膵癌の新規治療戦略と分子基盤 (2012)
  • Author(s): 島崎猛夫,石垣靖人,源利成,友杉直久他
  • Organizer: 第20回JDDW
  • Place of Presentation: 神戸国際展示場・ポートピアホテル・神戸こうくさい会議場
• [Presentation] 膵癌の新規治療標的としてのglycogen synthase kinase (GSK) 3β:がん浸潤に対する作用 (2012)
  • Author(s): 島崎猛夫,石垣靖人,源利成,友杉直久他
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌
• [Presentation] GSK3β標的治療と化学療法を併用する膵がんの新規治療戦略と分子基盤 (2012)
  • Author(s): 島崎猛夫,石垣靖人,源利成,友杉直久他
  • Organizer: 第43回日本膵臓学会大会
  • Place of Presentation: ホテルメトロポリタン山形
• [Presentation] 膵癌細胞におけるgemcitabine誘導性EMTに関連する新規分子の同定 (2011)
  • Author(s): 島崎 猛夫
  • Organizer: 第22回日本消化器癌発生学会
  • Place of Presentation: ホテルニューオータニ佐賀（佐賀県）
• [Presentation] 切除不能進行膵癌に対するGSK3βを標的とした新規治療戦略 (2011)
  • Author(s): 島崎 猛夫
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: マリンメッセ福岡（福岡県）
• [Presentation] 膵癌の新規治療標的としてのglycogen synthase kinase(GSK)3β: 化学療法戦略の新展開 (2011)
  • Author(s): 島崎 猛夫
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
• [Presentation] ゲムシタビン単剤療法の壁への挑戦: 新規標的分子の同定と膵癌化学療法への展望 (2011)
  • Author(s): 島崎 猛夫
  • Organizer: 第42回日本膵臓学会大会
  • Place of Presentation: ホテルニューキャッスル（青森県）
• [Presentation] イオン液体を用いた走査型電子顕微鏡観察法の確立とEMTを誘導した細胞 (2011)
  • Author(s): 石垣 靖人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] GSK3β標的治療を併用した膵癌の新規治療戦略と分子基盤
  • Author(s): 島崎 猛夫
  • Organizer: 第54回日本消化器病学会大会
  • Place of Presentation: 神戸(神戸国際展示場)
• [Presentation] 膵癌の新規治療標的としてのglycogen synthase kinase(GSK)3Bβ: がん浸潤に対する作用
  • Author(s): 島崎 猛夫
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌(札幌市教育文化会館）
• [Presentation] GSK3βの異常活性に起因する膵がん細胞の浸潤と治療抵抗性
  • Author(s): 島崎 猛夫
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪（大阪国際会議場）
• [Presentation] GSK3β標的治療と化学療法を併用する膵がんの新規治療戦略と分子基盤
  • Author(s): 島崎 猛夫
  • Organizer: 第43回日本膵臓学会大会
  • Place of Presentation: 山形（ホテルメトロポリタン山形）
• [Patent(Industrial Property Rights)] 細胞培養容器 (2013)
  • Inventor(s): 島崎猛夫、北野裕美子、山田秀樹
  • Industrial Property Rights Holder: 学校法人金沢医科大学、伸晃化学株式会社
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-164907
  • Filing Date: 2013-08-08
  • Overseas
• [Patent(Industrial Property Rights)] 膵臓癌治療剤 (2013)
  • Inventor(s): 島崎猛夫、中田光俊、源利成
  • Industrial Property Rights Holder: 学校法人金沢医科大学、国立大学法人金沢大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-093072
  • Filing Date: 2013-04-25
  • Overseas
• [Patent(Industrial Property Rights)] 膵臓癌治療剤 (2013)
  • Inventor(s): 島崎 猛夫
  • Industrial Property Rights Holder: 島崎 猛夫
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-093072
  • Filing Date: 2013-04-25