The prevention of pancreatic diseases targeting for the pancreatic stem/progenitor cell niche

• Project/Area Number: 24591003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: KIKUTA Kazuhiro 東北大学, 医学(系)研究科(研究院), 非常勤講師 (80420024)
• Co-Investigator(Kenkyū-buntansha): MASAMUNE Atsushi 東北大学, 医学系研究科, 准教授 (90312579)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 急性膵炎 / 慢性膵炎 / 糖尿病 / 膵星細胞 / 膵線維化

Outline of Final Research Achievements

To clarify the role of pancreatic stellate cells for the progression of pancreatic endocrine and exocrine dysfunction, the role of kindlin-2, a key regulator for integrin signaling, in pancreatic stellate cells was studied. Pancreatic stellate cells expressed kindlin-2. The decreased expression of kindlin-2 inhibited the migration of pancreatic stellate cells. Kindlin-2 may have a role in the pancreatic microenvironment. The epidemiological association between pancreatic dysfunction and pancreatitis was also studied. Sixty five point seven percent and 45.7% of chronic pancreatitis patients who were diagnosed as definite chronic pancreatitis within a year showed pancreatic exocrine and endocrine dysfunction, respectively. Acute pancreatitis patients had higher morbidity of diabetes mellitus than normal population. Idiopathic or elder acute pancreatitis patients with diabetes mellitus had a higher mortality.

Research Products

• [Journal Article] Sudden disappearance of the blood flow in a case of pancreatic acinar cell carcinoma (2014)
  • Author(s): Kanno A, Masamune A, Hamada S, Kikuta K, Kume K, Hirota M, Shima K, Okada T, Motoi F, Fujishima F, Ishida K, Unno M, Shimosegawa T
  • Journal Title: Intern Med Volume: 53 Pages: 2589-2593
  • NAID: 130004713252
  • Peer Reviewed
• [Journal Article] Bismuth classification is associated with the requirement for multiple biliary drainage in preoperative patients with malignant perihilar biliary stricture (2014)
  • Author(s): Miura S, Kanno A, Masamune A, Hamada S, Takikawa T, Nakano E, Yoshida N, Hongo S, Kikuta K, Kume K, Hirota M, Yoshida H, Katayose Y, Unno M, Shimosegawa T
  • Journal Title: Surg Endosc Volume: in press Issue: 7 Pages: 1862-1870
  • DOI: 10.1007/s00464-014-3878-y
  • Peer Reviewed
• [Journal Article] The seventh nationwide epidemiological survey for chronic pancreatitis in Japan: clinical significance of smoking habit in Japanese patients (2014)
  • Author(s): Hirota M, Shimosegawa T, Masamune A, Kikuta K, Kume K, Hamada S, Kanno A, Kimura K, Tsuji I, Kuriyama S; Research Committee of Intractable Pancreatic Diseases
  • Journal Title: Pancreatology Volume: 14 Issue: 6 Pages: 490-496
  • DOI: 10.1016/j.pan.2014.08.008
  • Peer Reviewed
• [Journal Article] The usefulness of endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic neuroendocrine tumors based on the World Health Organization classification (2014)
  • Author(s): Unno J, Kanno A, Masamune A, Kasajima A, Fujishima F, Ishida K, Hamada S, Kume K, Kikuta K, Hirota M, Motoi F, Unno M, Shimosegawa T
  • Journal Title: Scand J Gastroenterol Volume: 49 Issue: 11 Pages: 1367-1374
  • DOI: 10.3109/00365521.2014.934909
  • Peer Reviewed
• [Journal Article] Nationwide epidemiological survey of acute pancreatitis in Japan (2014)
  • Author(s): Hamada S, Masamune A, Kikuta K, Hirota M, Tsuji I, Shimosegawa T; Research Committee of Intractable Diseases of the pancreas
  • Journal Title: Pancreas Volume: 43 Issue: 8 Pages: 1244-1248
  • DOI: 10.1097/mpa.0000000000000200
  • Peer Reviewed
• [Journal Article] 慢性膵炎に伴う線維化機構 (2014)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Journal Title: 胆と膵 Volume: 35 Pages: 1035-1039
• [Journal Article] 我が国の急性膵炎の予後 (2014)
  • Author(s): 菊田和宏、正宗淳、濱田晋、下瀬川徹
  • Journal Title: 膵臓 Volume: 29 Pages: 151-156
  • Peer Reviewed
• [Journal Article] 慢性膵炎の膵内外分泌機能と臨床像 - 全国調査から (2014)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Journal Title: 胆と膵 Volume: 35 Pages: 343-347
• [Journal Article] 膵星細胞と膵島細胞の相関 (2014)
  • Author(s): 菊田和宏、正宗淳、濱田晋、滝川哲也、中野絵里子、下瀬川徹、
  • Journal Title: 胆と膵 Volume: 35 Pages: 339-342
• [Journal Article] 全国調査から見たアルコール性急性膵炎の疫学的特徴 (2014)
  • Author(s): 菊田和宏、正宗淳、粂潔、下瀬川徹
  • Journal Title: アルコールと医学生物学 Volume: 32
• [Journal Article] 高齢者急性膵炎の臨床的特徴 (2014)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Journal Title: 消化器内科 Volume: 58 Pages: 95-101
• [Journal Article] 全国調査からみた急性膵炎における耐糖能障害 (2014)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Journal Title: 消化と吸収 Volume: 36
  • Peer Reviewed
• [Journal Article] 慢性膵炎の膵内外分泌機能と臨床像-全国調査から (2014)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Journal Title: 胆と膵 Volume: 35 Pages: 343-347
• [Journal Article] 我が国の急性膵炎の予後：全国調査から (2014)
  • Author(s): 菊田和宏、正宗淳、濱田晋、下瀬川徹
  • Journal Title: 膵臓 Volume: 29
  • NAID: 130004496059
• [Journal Article] CONUTによる急性膵炎の栄養評価 (2013)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Journal Title: 消化と吸収 Volume: 35 Pages: 193-196
  • NAID: 10031169262
  • Peer Reviewed
• [Journal Article] Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreaticβ-cells (2013)
  • Author(s): Kikuta K, Masamune A, Hamada S, Takikawa T, Nakano E, Shimosegawa T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 433 Issue: 3 Pages: 292-7
  • DOI: 10.1016/j.bbrc.2013.02.095
  • Peer Reviewed
• [Journal Article] The angiotensin II type I receptor blocker olmesartan inhibits the growth of pancreatic cancer by targeting stellate cell activities in mice (2013)
  • Author(s): Masamune A, Hamada S, Kikuta K, Takikawa T, Miura S, Nakano E, Shimosegawa T.
  • Journal Title: Scand J Gastroenterol Volume: 48 Issue: 5 Pages: 602-609
  • DOI: 10.3109/00365521.2013.777776
  • Peer Reviewed
• [Journal Article] miR-197 induces epithelialmesenchymal transition in pancreatic cancer cells by targeting p120 catenin. J Cell Physiol (2013)
  • Author(s): Hamada S, et al
  • Journal Title: J Cell Physiol Volume: 228(6) Issue: 6 Pages: 1255-63
  • DOI: 10.1002/jcp.24280
  • Peer Reviewed
• [Journal Article] Pancreati duct drainage using EUS-guided rendezvous technique for stenotic pancreaticojejunostomy (2013)
  • Author(s): Takikawa T, Kanno A, Masamune A, Hamada S, Nakano E, Miura S, Ariga H, Unno J, Kume K, Kikuta K, Hirota M, Yoshida H, Katayose Y, Unno M, Shimosegawa T
  • Journal Title: World J Gastroenterol Volume: 19 Issue: 31 Pages: 5182-5186
  • DOI: 10.3748/wjg.v19.i31.5182
  • Peer Reviewed
• [Journal Article] The angiotensin II type I receptor blocker olmesartan inhibits the growth of pancreatic cancer by targeting stellate cell activities in mice. (2013)
  • Author(s): Masamune A, Hamada S, Kikuta K, Takikawa T, Miura S, Nakano E, Shimosegawa T.
  • Journal Title: Scand J Gastroenterol Volume: in press
  • Peer Reviewed
• [Journal Article] Connexins Regulate Cell Functions in Pancreatic Stellate Cells. (2013)
  • Author(s): Masamune A, Suzuki N, Kikuta K, Ariga H, Hayashi S, Takikawa T, Kume K, Hamada S, Hirota M, Kanno A, Egawa S, Unno M, Shimosegawa T.
  • Journal Title: Pancreas Volume: in press
  • Peer Reviewed
• [Journal Article] [Case report; Multiple gastrointestinal stromal tumors associated with neurofibromatosis type I preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration: report of a case and review of literature]. (2012)
  • Author(s): Miura S, Kume K, Hamada S, Kanno A, Unno J, Kikuta K, Hirota M, Masamune A, Shimosegawa T.
  • Journal Title: Nihon Naika Gakkai Zasshi Volume: 101 Pages: 3510-3512
  • Peer Reviewed
• [Journal Article] Distinct clinical features of two patients that progressed from the early phase of chronic pancreatitis to the advanced phase. (2012)
  • Author(s): Hirota M, Shimosegawa T, Kanno A, Kikuta K, Kume K, Hamada S, Unno J, Masamune A.
  • Journal Title: Tohoku J Exp Med Volume: 228 Pages: 173-180
  • NAID: 10031127345
  • Peer Reviewed
• [Journal Article] Diagnosis of autoimmune pancreatitis by EUS-FNA by using a 22-gauge needle based on the International Consensus Diagnostic Criteria. (2012)
  • Author(s): Kanno A, Ishida K, Hamada S, Fujishima F, Unno J, Kume K, Kikuta K, Hirota M, Masamune A, Satoh K, Notohara K, Shimosegawa T.
  • Journal Title: Gastrointest Endosc Volume: 76 Issue: 3 Pages: 594-602
  • DOI: 10.1016/j.gie.2012.05.014
  • Peer Reviewed
• [Journal Article] Early detection of low enhanced pancreatic parenchyma by contrast-enhanced computed tomography predicts poor prognosis of patients with acute pancreatitis. (2012)
  • Author(s): Hirota M, Satoh K, Kikuta K, Masamune A, Kume K, Hamada S, Satoh A, Kanno A, Unno J, Ito H, Ariga H, Shimosegawa T.
  • Journal Title: Pancreas Volume: 41 Issue: 7 Pages: 1099-1104
  • DOI: 10.1097/mpa.0b013e318249a904
  • Peer Reviewed
• [Journal Article] Kanno A, Masamune A, Hirota M, Kikuta K, Shimosegawa T. (2012)
  • Author(s): Successful treatment of benign biliary stricture by a covered self-expandable metallic stent in a patient with chronic pancreatitis.
  • Journal Title: Dig Endosc Volume: 24 Suppl 1 Issue: s1 Pages: 43-48
  • DOI: 10.1111/j.1443-1661.2012.01263.x
  • Peer Reviewed
• [Journal Article] Do genetic variants in the SPINK1 gene affect the level of serum PSTI? (2012)
  • Author(s): Kume K, Masamune A, Ariga H, Hayashi S, Takikawa T, Miura S, Suzuki N, Kikuta K, Hamada S, Hirota M, Kanno A, Shimosegawa T.
  • Journal Title: J Gastroenterol Volume: 47 Issue: 11 Pages: 1267-1274
  • DOI: 10.1007/s00535-012-0590-3
  • NAID: 10031126959
  • Peer Reviewed
• [Journal Article] Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells (2012)
  • Author(s): Hamada S, Masamune A, Takikawa T, Suzuki N, Kikuta K, Hirota M, Hamada H, Kobune M, Satoh K, Shimosegawa T
  • Journal Title: Biochem Biophys Res Commun Volume: 421(2) Issue: 2 Pages: 349-354
  • DOI: 10.1016/j.bbrc.2012.04.014
  • Peer Reviewed
• [Journal Article] Research Committee on Intractable Diseases of Pancreas. Nationwide epidemiological survey of autoimmune pancreatitis in Japan (2012)
  • Author(s): Kanno A, Nishimori I, Masamune A, Kikuta K, Hirota M, Kuriyama S, Tsuji I, Shimosegawa T
  • Journal Title: Pancreas Volume: 41 Issue: 6 Pages: 835-9
  • DOI: 10.1097/mpa.0b013e3182480c99
  • Peer Reviewed
• [Journal Article] 急性膵炎の成因と疫学 (2012)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Journal Title: 消化器外科 Volume: 35 Pages: 1725-1730
• [Presentation] The impact of diabetes mellitus on clinical outcome of acute pancreatitis in Japan (2014)
  • Author(s): Kazuhiro Kikuta, Atsushi Masamune, Shin Hamada, Tooru Shimosegawa
  • Organizer: APA/JPS 45th anniversary meeting
  • Place of Presentation: Hawaii (USA)
  • Year and Date: 2014-11-05 – 2014-11-09
• [Presentation] 急性膵炎発症早期の造影CTによる膵壊死予測診断能 (2014)
  • Author(s): 菊田和宏、正宗淳、濱田晋、廣田衛久、下瀬川徹
  • Organizer: 第56回日本消化器病学会大会
  • Place of Presentation: 神戸国際展示場・ポートピアホテル・神戸国際会議場 (神戸)
  • Year and Date: 2014-10-23 – 2014-10-26
• [Presentation] 全国調査から見た慢性膵炎患者における栄養状態の実態 (2014)
  • Author(s): 菊田和宏、正宗淳、廣田衛久、下瀬川徹
  • Organizer: 第45回日本膵臓学会大会
  • Place of Presentation: 北九州国際会議場 (小倉)
  • Year and Date: 2014-07-11 – 2014-07-12
• [Presentation] 全国調査からみた急性膵炎における生活習慣病 (2014)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京国際フォーラム (東京)
  • Year and Date: 2014-04-23 – 2014-04-24
• [Presentation] 内視鏡下経胃的ネクロセクトミーが有効であった感染性膵壊死の1例 (2014)
  • Author(s): 竹内智、菊田和宏、粂潔、菅野敦、中野絵里子、有賀啓之、濱田晋、廣田衛久、正宗淳、下瀬川徹
  • Organizer: 第111回日本内科学会総会
  • Place of Presentation: 東京国際フォーラム (東京)
  • Year and Date: 2014-04-11 – 2014-04-12
• [Presentation] The nutritional index 'CONUT' is useful for predicting prognosis of acute pancreatitis (2013)
  • Author(s): Kazuhiro Kikuta, Atsushi Masamune, Tooru Shimosegawa
  • Organizer: 米国Digestive Disease Week 2013
  • Place of Presentation: Orlando, USA
• [Presentation] Prognosis of acute pancreatitis in Japan based on nationwide survey (2013)
  • Author(s): Kazuhiro Kikuta, Atsushi Masamune, Tooru Shimosegawa
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台
• [Presentation] 全国調査に基づく慢性膵炎の膵内外分泌機能と臨床像の解析 (2013)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Organizer: 第44回日本膵臓学会大会
  • Place of Presentation: 仙台
• [Presentation] 全国調査からみた急性膵炎における耐糖能障害 (2013)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Organizer: Japan Digestive Disease Week 2013
  • Place of Presentation: 東京
• [Presentation] 全国調査から見た アルコール性急性膵炎の疫学的特徴 (2013)
  • Author(s): 菊田和宏、正宗淳、粂潔、下瀬川徹
  • Organizer: 第32回アルコール医学生物学研究会
  • Place of Presentation: 東京
• [Presentation] 高齢者急性膵炎の疫学的検討 (2013)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島
• [Presentation] 全国調査をもとにした 急性膵炎の成因と病態、予後に関する疫学的検討 (2012)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Organizer: 第43回日本膵臓学会大会
  • Place of Presentation: 山形
• [Presentation] CONUTによる急性膵炎の栄養評価 (2012)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Organizer: 第54回日本消化器病学会大会
  • Place of Presentation: 神戸