Mechanism of tissue regeneration after acute pancreatitis, focusing on pancreatic transcription factor ptf1a

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591771
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: MASUI Toshihiko 京都大学, 医学研究科, 非常勤講師 (20452352)
• Co-Investigator(Kenkyū-buntansha): DOI Ryuichiro 京都大学, 医学研究科, 非常勤講師 (20301236) ; KODAMA Sota 京都大学, 医学研究科, 非常勤講師 (10583875) ; KAWAGUCHI Yoshiya 京都大学, iPS細胞研究所, 教授 (60359792)
• Project Period (FY): 2009 – 2011
• Keywords: ptf1a / 急性膵炎 / 膵発生 / Notch / 膵外分泌組織維持

Research Abstract

Based on a hypothesis that embryonic organogenic pathway is reactivated in the regenerative process after injury in the exocrine pancreatic tissue, we aimed to reveal an involvement of ptf1a transcription factor in the tissue regeneration after Cerulein induced acute pancreatitis model in mice. First, we tested the dosage of ptf1a by injecting Cerulein to the hypomorphic ptf1a mice(ptf1a-cbll/cbll). However, we could not determine the role of ptf1a in the regenerative process since most of the mice died after Cerulein treatment. Then we inactivated ptf1a in adult pancreatic duct cells in Sox9 CreER ; ptf1a floxed ; ROSA26r mice. Surprisingly, we observed lack of labeled acinar cell even in the non-Cerulein treated mice indicating that ptf1a is indispensable in the physiological organ maintenance of the exocrine pancreas tissue.

Research Products

• [Journal Article] Delayed gastric emptying improved by straight stomach reconstruction with twisted anastomosis to the jejunum after pylorus-preserving pancreaticoduodenectomy(PPPD) in 118consecutive patients at a single institution (2012)
  • Author(s): Masui T, Doi R, Kawaguchi Y, Uemoto S.
  • Journal Title: Surg Today Volume: 42(5) Pages: 441-446
  • DOI: DOI:10.1007/s00595-011-0097-1
  • Peer Reviewed
• [Journal Article] The flow angle beneath the gastrojejunostomy in Roux-en-Yreconstruction after distal gastrectomypredicts delayed gastric emptying (2011)
  • Author(s): Masui T, Kubota T, Nakanishi Y, Aoki K, Sugimoto S, Takamura M, Takeda H, Hashimoto K, Tokuka A.
  • Journal Title: Gastric Cancer
  • DOI: DOI:10.1007/s10120-011-0107-4
  • Peer Reviewed
• [Journal Article] A phase I/II study of gemcitabine-basedchemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer (2011)
  • Author(s): Kanai M, Yoshimura K, Asada M, Imaizumi A, Suzuki C, Matsumoto S, Nishimura T, Mori Y, Masui T, Kawaguchi Y, Yanagihara K, Yazumi S, Chiba T, Guha S, Aggarwal BB
  • Journal Title: Cancer Chemother Pharmacol Volume: 68(1) Pages: 157-64
  • DOI: DOI:10.1007/s00280-010-1470-2
  • Peer Reviewed
• [Journal Article] Continuous cell supply from aSox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine (2011)
  • Author(s): Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, Hosokawa S, Elbahrawy A, Soeda T, Koizumi M, Masui T, Kawaguchi M, Takaori K, Doi R, Nishi E, Kakinoki R, Deng JM, Behringer RR, Nakamura T, Uemoto S.
  • Journal Title: Nat Genet Volume: 43(1) Pages: 34-41
  • DOI: DOI:10.1038/ng.722
  • Peer Reviewed
• [Journal Article] The distribution of atypical epithelium in main-duct type intraductal papillarymucinous neoplasms of the pancreas (2011)
  • Author(s): Ito T, Doi R, Yoshizawa A, Sakikubo M, Nagai K, Kida A, Koizumi M, Masui T, Kawaguchi Y, Manabe T, Uemoto S.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 18(2) Pages: 241-246
  • DOI: DOI:10.1007/s00534-010-0337-6
  • Peer Reviewed
• [Journal Article] Noninvasive intraductal papillary mucinousneoplasm with para-aortic lymph node metastasis : report of a case (2011)
  • Author(s): Nagai K, Doi R, Koizumi M, Masui T, Kawaguchi Y, Yoshizawa A, Uemoto S.
  • Journal Title: Surg Today Volume: 41(1) Pages: 147-52
  • DOI: DOI:10.1007/s00595-009-4210-7
  • Peer Reviewed
• [Journal Article] A case of progressive digital ischemia after early withdrawal of gemcitabine and S-1 in a patient with systemic sclerosis (2011)
  • Author(s): Zaima C, Kanai M, Ishikawa S, Kawaguchi Y, Masui T, Mori Y, Nishimura T, Matsumoto S, Yanagihara K, Chiba T, Mimori T.
  • Journal Title: Jpn J Clin Oncol. Volume: 41(6) Pages: 803-806
  • DOI: DOI:10.1093/jjco/hyr045
  • Peer Reviewed
• [Journal Article] Success fulneoadjuvant Treatment with Radiochemo therapy and Systemic Chemotherapy for the Locally Advanced Pancreatic Head Cancer : Report of a Case (2011)
  • Author(s): Masui T, Doi R, Ogawa K, Kami K, Machimoto T, Seo S, Kawaguchi Y, Egawa H, Matsugu Y, Uemoto S.
  • Journal Title: Hepato-Gastroenterology Volume: 58(110) Pages: 1809-1813
  • DOI: DOI:10.5754/hge08054
  • Peer Reviewed
• [Journal Article] Aden endocrine cell carcinoma of the extrahepatic bile duct : a case report and review of the literature (2011)
  • Author(s): Masui T, Doi R, Kawaguchi Y, Iwanaga, Y, Ito T, Koizumi M, Uemoto S.
  • Journal Title: Clinical Journal of Gastroenterology Volume: 4(3) Pages: 174-178
  • DOI: DOI:10.1007/s12328-011-0220-2
  • Peer Reviewed
• [Journal Article] A rare case of carcinosarcoma of the liver (2011)
  • Author(s): Masui T, Watanabe E, Onuma H, Tokuka A.
  • Journal Title: Rinsho Gekagakkai Zasshi Volume: 72(7) Pages: 195-199
  • Peer Reviewed
• [Journal Article] Preoperative assessment of para-aorticlymph node metastasis in patients with pancreatic cancer (2010)
  • Author(s): Imai H, Doi R, Kanazawa H, Kamo N, Koizumi M, Masui T, Iwanaga Y, Kawaguchi Y, Takada Y, Isoda H, Uemoto S.
  • Journal Title: Int J Clin Oncol Volume: 15(3) Pages: 294-300
  • DOI: DOI:10.1007/s10147-010-0066-5
  • Peer Reviewed
• [Journal Article] Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography for pancreatic neuroendocrinetumors with reference to the World Health Organization classification (2010)
  • Author(s): Masui T, Doi R, Ito T, Kami K, Ogawa K, Harada D, Uemoto S.
  • Journal Title: Oncology Letters Volume: 1(1) Pages: 155-159
  • DOI: DOI:10.3892/ol_00000029
  • Peer Reviewed
• [Journal Article] Abdominal wall recurrence of Hilar bile duct cancer 12 years after a curative resection : report of a case (2009)
  • Author(s): Machimoto T, Doi R, Ogawa K, Masui T, Seo S, Uemoto S.
  • Journal Title: Surg Today Volume: 39(1) Pages: 72-76
  • DOI: DOI:10.1007/s00595-008-3791-x
  • Peer Reviewed
• [Journal Article] Prognostic value of metastin expression in human pancreatic cancer (2009)
  • Author(s): Nagai K, Doi R, Katagiri F, Ito T, Kida A, Koizumi M, Masui T, Kawaguchi Y, Tomita K, Oishi S, Fujii N, Uemoto S.
  • Journal Title: J Exp Clin Cancer Res Volume: 28 Pages: 9
  • DOI: DOI:10.1186/1756-9966-28-9
  • Peer Reviewed
• [Journal Article] Single-institution validation of the international consensus guidelines for treatment of branch duct intraductal papillarymucinous neoplasms of the pancreas (2009)
  • Author(s): Nagai K, Doi R, Ito T, Kida A, Koizumi M, Masui T, Kawaguchi Y, Ogawa K, Uemoto S
  • Journal Title: J Hepatobiliary Pancreat Surg Volume: 16(3) Pages: 353-358
  • DOI: DOI:10.1007/s00534-009-0068-8
  • Peer Reviewed
• [Presentation] #16転移のある膵癌術後10年後のSMA周囲再発に対して再切除施行し得た1例 (2011)
  • Author(s): 増井俊彦、久保田豊成、青木恵子、中西保貴、杉本真一、高村通生、武田啓志、橋本幸直、徳家敦夫
  • Organizer: 第42回膵臓学会大会
  • Place of Presentation: 弘前市、青森県
  • Year and Date: 2011-07-29
• [Presentation] 残胃の形態から見た幽門側胃切除後のRoux stasis syndromeの検討 (2011)
  • Author(s): 増井俊彦、久保田豊成、青木恵子、中西保貴、杉本真一、高村通生、武田啓志、橋本幸直、徳家敦夫
  • Organizer: 第66回消化器外科学会総会
  • Place of Presentation: 名古屋市、愛知県
  • Year and Date: 2011-07-13
• [Presentation] 肝細胞癌派生の肝癌肉腫の1例 (2011)
  • Author(s): 増井俊彦、渡邉栄一郎、中西保貴、久保田豊成、青木恵子、高村通生、杉本真一、武田啓志、徳家敦夫
  • Organizer: 第23回肝胆膵外科学会定期集会
  • Place of Presentation: 新宿、東京都
  • Year and Date: 2011-06-08
• [Presentation] 郭清度から見た膵頭十二指腸切除後脂肪肝発生因子の検討 (2011)
  • Author(s): 増井俊彦、土井隆一郎、川口義弥、小泉将之、高折恭一、上本伸二
  • Organizer: 第111回外科学会総会
  • Year and Date: 2011-05-25
• [Presentation] 膵癌術後補助化学療法としてのS12投1休投薬法の可能性 (2010)
  • Author(s): 増井俊彦、土井隆一郎、川口義弥、上和宏、小泉将之、長井和之、高折恭一、上本伸二
  • Organizer: 第65回消化器外科学会総会
  • Place of Presentation: 下関市、山口県
  • Year and Date: 2010-07-13
• [Presentation] 術者の経験から見た不完全外瘻術による膵空腸吻合の成績 (2010)
  • Author(s): 増井俊彦、土井隆一郎、川口義弥、小川晃平、上和宏、小泉将之、上本伸二
  • Organizer: 第22回肝胆膵外科学会定期集会
  • Place of Presentation: 仙台市、宮城県
  • Year and Date: 2010-05-27
• [Presentation] 局所進行膵癌に対する術前GEM/S1併用療法の成績 (2010)
  • Author(s): 増井俊彦、土井隆一郎、川口義弥、小川晃平、上和宏、小泉将之、上本伸二
  • Organizer: 第22回肝胆膵外科学会定期集会
  • Place of Presentation: 仙台市、宮城県
  • Year and Date: 2010-05-27
• [Presentation] 幽門輪温存膵頭十二指腸切除術における胃排出遅延の試み (2010)
  • Author(s): 増井俊彦、土井隆一郎、川口義弥、小泉将之、長井和之、高折恭一、上本伸二
  • Organizer: 第110回外科学会総会
  • Place of Presentation: 名古屋市、愛知県
  • Year and Date: 2010-04-08
• [Presentation] IMPROVED DELAYED GASTRIC EMPTYING WITH STRAIGHT STOMACH RECONSTRUCTION AND TWISTEDANSTOMOSIS TO JEJUNUM AFTER PYLORUS PRESERVING PANCREATICODUODENECTOMY(PPPD): 118 CONSECUTIVE CASES IN A SINGLE INSTITUSION (2009)
  • Author(s): Masui T, R. Doi, K. Kami, K. Ogawa, Y. Kawaguchi, K. Fujimoto, M. Koizumi, K. Nagai and S. Uemoto.
  • Organizer: APA and JPS40th Anniversary Meeting
  • Place of Presentation: Hawaii, USA
  • Year and Date: 20091100
• [Presentation] Improvement of the dissection of the perineural tissue of superior mesenteric artery by detaching splenic vein from portal vein in the pancreatic head cancer (2009)
  • Author(s): Masui T, Ryuichiro Doi, Yasuhiro Takada, Yoshiya Kawaguchi, Masayuki Koizumi, Masayuki Nagai, Tatsuo Ito, Atsushi Kida, Shinji Uemoto
  • Organizer: 19th World congress of the IASGO
  • Place of Presentation: Beijing, China
  • Year and Date: 20090923-26
• [Presentation] Gemcitabine and S-1 combined neoadjuvant chemotherapy for patients with locally advanced pancreatic cancer (2009)
  • Author(s): T. Masui, R. Doi, Y. Kawaguchi, M. Koizumi, A. Kida, K. Nagai, T. Ito, S. Uemoto.
  • Organizer: ASCO-GI
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 20090100