Innovation of novel therapeutic approach to pancreatic cancer using galectin-3 and AMF

• Project/Area Number: 23592017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: SHIMURA Tatsuo 福島県立医科大学, 医学部, 准教授 (00282393)
• Co-Investigator(Kenkyū-buntansha): SHIBATA Masahiko 福島県立医科大学, 医学部, 教授 (10226178) ; TAKENOSHITA Seiichi 福島県立医科大学, 医学部, 教授 (10167489)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: galectin-3 / 膵癌 / ＡＭＦ / AMF / IPMC / galectin

Research Abstract

Galectin-3 (Gal-3) is beta-galactoside-binding protein, having binding capacity with glycoprotein and glycolipid on a cell surface. Gal-3 engages in cell differentiation, organ formation, tumor progression, apoptosis and so on, however, precise mechanisms of them have not yet been clarified.
We investigated the relationship between Gal-3 and pancreatic cancer, especially on cell proliferation, migration and invasion using pancreatic cancer cell lines. We also analyzed changes of tolerance toward anti-cancer drugs when expression level of Gal-3 was inhibited in the cell lines. Inhibition of Gal-3 expression led to inhibition of migration and invasion of the cells. It also augmented their susceptibility to anti-cancer agents, like gemcitabine and cisplatinum.

Research Products

• [Journal Article] Serum levels of vascular endothelial growth factor are increased and correlate with malnutrition, immunosuppression invoving MDSCs and systemic inflammation in patients with cancer of the digestive system (2013)
  • Author(s): Nakamura I, Shibata M, Gonda K, Yazawa T, Shimura T, Anazawa T, Suzuki S, Sakurai K, Koyama Y, Ohto H, Tomita R, Gotoh M, Takenoshita S.
  • Journal Title: Oncology Letters Volume: 5巻 Pages: 1682-1688
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678612/
  • Peer Reviewed
• [Journal Article] Increased IL-17 production correlates with immunosuppression involving myeloid-derived suppressor cells and nutritional impairment in patients with various gastrointestinal cancers (2013)
  • Author(s): Yazawa T, Shibata M, Gonda K, Machida T, Suzuki S, Kenjo A, Nakamura I, Tsuchiya T, Koyama Y, Sakurai K, Shimura T, Tomita R, Ohto H, Gotoh M, Takenoshita S.
  • Journal Title: Mol Clin Oncol Volume: 1巻 Pages: 675-679
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916208/
  • Peer Reviewed
• [Journal Article] A case of mesenteric cystic lymphangioma in an adult which caused duodenal stenosis after resection. (2013)
  • Author(s): Watanabe A, Suzuki H, Kubo N, Kobayashi T, Araki K, Sasaki S, Shimura T, Oyama T, Kuwano H.
  • Journal Title: Int J Surg Case Rep. Volume: 4（2） Issue: 2 Pages: 212-215
  • DOI: 10.1016/j.ijscr.2012.10.023
  • Peer Reviewed
• [Journal Article] 1. Serum levels of vascular endothelial growth factor are increased and correlate with malnutrition, immunosuppression involving MDSCs and systemic inflammation in patients with cancer of the digestive system. (2013)
  • Author(s): Nakamura I, Shibata M, Gonda K, Yazawa T, Shimura T, Anazawa T, Suzuki S, Sakurai K, Koyama Y, Ohto H, Tomita R, Gotoh M, Takenoshita S.
  • Journal Title: Ｏｎｃｏｌｏｇｙ Ｌｅｔｔｅｒｓ Volume: 5（5） Pages: 1682-1688
  • Peer Reviewed
• [Journal Article] Increased IL-17 production correlates with immunosuppression involving myeloid-derived suppressor cells and nutritional impairment in patients with various gastrointestinal cancers. (2013)
  • Author(s): Yazawa T, Shibata M, Gonda K, Machida T, Suzuki S, Kenjo A, Nakamura I, Tsuchiya T, Koyama Y, Sakurai K, Shimura T, Tomita R, Ohto H, Gotoh M, Takenoshita S.
  • Journal Title: Mol Clin Oncol. Volume: 1（4） Pages: 675-679
  • Peer Reviewed
• [Journal Article] IgG4-related intrahepatic sclerosing cholangitis resulting in sepsis caused by secondary suppurative inflammation: report of a case. (2013)
  • Author(s): Saito M, Shimura T, Hashimoto Y, Ishigame T, Yashima R, Koyama Y, Takenoshita S.
  • Journal Title: Surg Today Volume: 43（10） Issue: 10 Pages: 1175-1179
  • DOI: 10.1007/s00595-012-0448-6
  • NAID: 10031201394
  • Peer Reviewed
• [Journal Article] Circulating myeloid-derived suppressor cells are increased and correlate to immune suppression, inflammation and hypoproteinemia in patients with cancer. (2012)
  • Author(s): Ohki S, Shibata M, Gonda K, Machida T, Shimura T, Nakamura I, Ohtake T, Koyama Y, Suzuki S, Ohto H, Takenoshita S.
  • Journal Title: Oncology Report Volume: 28 Issue: 2 Pages: 453-458
  • DOI: 10.3892/or.2012.1812
  • Peer Reviewed
• [Journal Article] Description of pylorus-preserving pancreaticoduodenectomy in elderly patients (2012)
  • Author(s): Shimura T, Morinaga N, Suzuki H, Araki K, Kobayashi T, Koyama Y, Yashima R, Shibata M, Takenoshita S, Kuwano H.
  • Journal Title: Hepatogastroenterology Volume: 59巻 Pages: 903-906
  • Peer Reviewed
• [Journal Article] Clinical evaluation of dedritic cells vaccination for advanced cancer patients at Fukushima Medical University (2012)
  • Author(s): Nakamura I, Kanazawa M, Sato Y, Irisawa A, Takagi T, Ogata T, Kashimura S, Kenjo A, Suzuki H, Shibata M, Shimura T, Ohira H, Goto M, Takenoshita S, Ohto H.
  • Journal Title: Fukushima J Med Sci. Volume: 58巻 Pages: 40-48
  • URL: https://www.jstage.jst.go.jp/article/fms/58/1/58_40/_article
  • Peer Reviewed
• [Journal Article] Description of pylorus-preserving pancreaticoduodenectomy in elderly patients. (2012)
  • Author(s): Shimura T, Morinaga N, Suzuki H, Araki K, Kobayashi T, Koyama Y, Yashima R, Shibata M, Takenoshita S, Kuwano H.
  • Journal Title: Hepatogastroenterology Volume: 59 Pages: 903-906
  • Peer Reviewed
• [Journal Article] Clinical evaluation of dendritic cells vaccination for advanced cancer patients at Fukushima Medical University. (2012)
  • Author(s): Nakamura I, Kanazawa M, Sato Y, Irisawa A, Takagi T, Ogata T, Kashimura S, Kenjo A, Suzuki H, Shibata M, Shimura T, Ohira H, Goto M, Takenoshita S, Ohto H.
  • Journal Title: Fukushima J Med Sci. Volume: 58 Pages: 40-48
  • NAID: 130002153558
  • Peer Reviewed
• [Journal Article] Transient gene silencing of galectin-3 suppresses pancreatic cancer cell migration and invasion through degradation of β-catenin (2011)
  • Author(s): Kobayashi T, Shimura T, Yajima T, Kubo N, Araki K, Tsutsumi S, Suzuki H, Kuwano H, Raz A.
  • Journal Title: Int J Cancer Volume: 20 Issue: 12 Pages: 2775-2786
  • DOI: 10.1002/ijc.25946
  • Peer Reviewed
• [Journal Article] Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells (2011)
  • Author(s): Kobayashi T, Shimura T, Yajima T, Kubo N, Araki K, Wada W, Tsutsumi S, Suzuki H, Kuwano H, Raz A.
  • Journal Title: Clin Exp Metastasis Volume: 28巻 Issue: 4 Pages: 367-376
  • DOI: 10.1007/s10585-011-9376-x
  • Peer Reviewed
• [Journal Article] Mixed ductal-endocrine carcinoma of the pancreas occurring as a double cancer : report of a case (2011)
  • Author(s): Araki K, Shimura T, Kobayashi T, Saito K, Wada W, Sasaki S, Suzuki H, Kashiwabara K, Nakajima T, Kuwano H.
  • Journal Title: Int Surg Volume: 96巻 Pages: 153-158
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22026308
  • Peer Reviewed
• [Journal Article] E/N-cadherin switch mediates cancer progression via TGF-beta-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma (2011)
  • Author(s): Araki K, Shimura T, Suzuki H, Tsutsumi S, Wada W, Yajima T, Kobayashi T, Kubo N, Kuwano H.
  • Journal Title: Br J Cancer Volume: 105巻 Issue: 12 Pages: 1885-1893
  • DOI: 10.1038/bjc.2011.452
  • Peer Reviewed
• [Journal Article] Transient gene silencing of galectin-3 suppresses pancreatic cancer cell migration and invasion through degradation of β-catenin. (2011)
  • Author(s): Kobayashi T, Shimura T, Yajima T, Kubo N, Araki K, Tsutsumi S, Suzuki H, Kuwano H, Raz A
  • Journal Title: Int J Cancer Volume: 129 Pages: 2775-2786
  • Peer Reviewed
• [Journal Article] Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells. (2011)
  • Author(s): Kobayashi T, Shimura T, Yajima T, Kubo N, Araki K, Wada W, Tsutsumi S, Suzuki H, Kuwano H, Raz A.
  • Journal Title: Clin Exp Metastasis Volume: 28 Pages: 367-376
  • Peer Reviewed
• [Journal Article] Mixed ductal-endocrine carcinoma of the pancreas occurring as a double cancer: report of a case. (2011)
  • Author(s): Araki K, Shimura T, Kobayashi T, Saito K, Wada W, Sasaki S, Suzuki H, Kashiwabara K, Nakajima T, Kuwano H.
  • Journal Title: Int Surg Volume: 96 Pages: 153-158
  • Peer Reviewed
• [Journal Article] E/N-cadherin switch mediates cancer progression via TGF-β-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma. (2011)
  • Author(s): Araki K, Shimura T, Suzuki H, Tsutsumi S, Wada W, Yajima T, Kobayahi T, Kubo N, Kuwano H.
  • Journal Title: Br J Cancer Volume: 105 Pages: 1885-1893
  • Peer Reviewed
• [Presentation] Myeloid-derived suppressor cells (MDSC) are increased and correlated with immune suppression and chronic inflammation in patients with cancer. (2013)
  • Author(s): Gonda K, Shibata M, Shimura T, Nakamura I, Ohki T, Ohtake S, Suzuki S, Ohto S, Takenoshita S.
  • Organizer: American Association for Cancer Research annual meeting 2012
  • Place of Presentation: シカゴ
• [Presentation] Circulating myeloid-derived suppressor cells (MDSC) and correlation to poor prognosis, Th2 polarization, and nutritional damages in patients with gastric cancer. (2013)
  • Author(s): Gonda K, Shibata M, Kanke T, Yazawa T, Monma T, Suzuki S, Nakamurea S, Ohki S, Shimura T, Ohto H, Takenoshita S.
  • Organizer: 49th Annual Meeting, ASCO
  • Place of Presentation: シカゴ
• [Presentation] Myeloid-derived suppressor cells (MDSC) are increased and correlated with immune suppression and chronic inflammation in patients with cancer. (2013)
  • Author(s): K. Gonda, M. Shibata, T, Shimura, I. Nakamura, S. Ohki, T. Ohtake, S. Suzuki, H. Ohto, S. Takenoshita
  • Organizer: AACR (American Association for Cancer Research) annual meeting 2012
  • Place of Presentation: Chicago
• [Presentation] Myeloid-derived suppressor cells (MDSC) is increased and correlated to immune suppression and inflammatory markers in patients with gastrointestinal cancer. (2012)
  • Author(s): Shibata M, Shimura T, Gonda K, Suzuki S, Nakamura I, Ohki S, Takenoshita S.
  • Organizer: 2012 ASCO Gastrointestinal Cancer Symposium
  • Place of Presentation: サンフランシスコ
• [Presentation] Myeloid–Derived Suppressor Cells (MDSC) is increased and correlated to immune suppression, nutritional impairment and inflammatory markers in patients with gastrointestinal cancer. (2012)
  • Author(s): Shibata, M., Shimura, T., Gonda, K., Suzuki, S., Nakamura, I., Ohki, S, Takenoshita, S.
  • Organizer: 2012 ASCO Gastrointestinal Cancer Symposium
  • Place of Presentation: San Francisco
• [Presentation] Appraisal of antecolic vertical duodenojejunostomy with internal stent and omental wrapping in pylorus-preserving pancreaticoduodenectomy. (2011)
  • Author(s): Shimura T, et al.
  • Organizer: International Surgical Week
  • Place of Presentation: 横浜
  • Year and Date: 2011-08-30
• [Presentation] PPPD術後再建方法の工夫:膵液瘻の完全克服を目指して (2011)
  • Author(s): 志村龍男、他
  • Organizer: 第23回日本肝胆膵外科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-10
• [Presentation] IPMNをめぐる諸問題―切除例における検討 (2011)
  • Author(s): 志村龍男、他
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京
• [Presentation] 幽門輪温存膵頭十二指腸切除術における合併症対策と入院期間短縮への挑戦
  • Author(s): 志村龍男、他
  • Organizer: 第66回日本消化器外科学会
  • Place of Presentation: 名古屋
• [Presentation] ＩＰＭＮをめぐる諸問題―切除例における検討
  • Author(s): 志村龍男、鈴木秀樹、持田泰、佐々木滋、和田渉、岡田幸士、新木健一郎、小林力、小山善久、八島玲、細内康男、竹之下誠一、桑野博行
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京
• [Presentation] PPPD術後再建方法の工夫：膵液瘻の完全克服を目指して
  • Author(s): 志村龍男、鈴木秀樹、新木健一郎、小林力、八島玲、小山善久、柴田昌彦、竹之下誠一、桑野博行
  • Organizer: 第23回日本肝胆膵外科学会学術集会
  • Place of Presentation: 東京
• [Presentation] 幽門輪温存膵頭十二指腸切除術における合併症対策と入院期間短縮への挑戦
  • Author(s): 志村龍男、鈴木秀樹、新木健一郎、小林力、八島玲、小山善久、森永暢浩、石崎政利、柴田昌彦、竹之下誠一、桑野博行
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 名古屋
• [Presentation] Appraisal of antecolic vertical duodenojejunostomy with internal stent and omental wrapping in pylorus-preserving pancreaticoduodenectomy.
  • Author(s): Shimura T, Suzuki H, Araki K, Kobayashi T, Koyama Y, Shibat M, Takenoshita S, Kuwano H
  • Organizer: International Surgical Week 2011
  • Place of Presentation: 横浜