Effects of rapamycin on granulation formation in response to centrally-doubled coiled stents as a tracheal substitute.

• Project/Area Number: 24659773
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: Niigata University
• Principal Investigator: KUBOTA Masayuki 新潟大学, 医歯学系, 教授 (50205150)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Yasunobu 新潟大学, 医歯学系, 准教授 (40334669)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: mTOR / rapamycin / trachea / tracheal substitute / coil / tracheal defect / granulation / metallic

Outline of Final Research Achievements

In order to prevent a formation of granulation tissue around the original artificial trachea, made of super-elastic wire, mTOR signal system in the granulation tissue was examined using rabbit tracheal defect model. In granulation tissue, mTOR activity was increased up to 20―40 folds in comparison with tracheal epithelium. Application of rapamycin, which blocked the mTOR signal system, partially blocked the mTOR activation. At the same time, the granulation tissue changed into the pathological condition, which induced respiratory infection. We have examined the proper method of application of rapamycin and it was found that the application of rapamycin starting from the 2 weeks after operation induced the favorable results. It is also suggested that the natural healing process of the tracheal wall defect is compromised and obtaining an improvement in this healing process should be one of the treatment strategies for tracheal pathologies.

Research Products

• [Journal Article] The area and attachment abnormalities of the gubernaculum in patients with undescended testes in comparison with those with retractile testes. (2014)
  • Author(s): Kubota M, Nakaya K, Arai Y, Ohyama T, Yokota N, Nagai Y.
  • Journal Title: Pediatr Surg Int Volume: 30 (11) Issue: 11 Pages: 1149-1154
  • DOI: 10.1007/s00383-014-3597-4
  • Peer Reviewed
• [Journal Article] Hepatitis B virus X stimulates redox signaling through activation of ataxia telangiectasia mutated kinase (2014)
  • Author(s): Matsuda, Y. Sanpei A, Wakai T, Kubota M, Osawa M, Hirose Y, Sakata J, Kobayashi T, Fujimaki S, Takamura M, Yamagiwa S, Yano M, Ohkoshi S, Aoyagi Y
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 2032-2043
  • Peer Reviewed
• [Journal Article] Valproic acid overcomes transforming growth factor-beta-mediated sorafenib resistance in hepatocellular carcinoma (2014)
  • Author(s): Matsuda Y, Wakai T, Kubota M, Osawa M, Hirose Y, Sakata J, Kobayashi T, Fujimaki S, Takamura M, Yamagiwa S, Aoyagi Y.
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 1299-1313
  • Peer Reviewed
• [Journal Article] Effects of rapamycin on granulation formation in response to centrally-doubled coiled stents as a tracheal substitute. (2013)
  • Author(s): Kubota M, Matsuda Y, Fujimaki S, Osawa M, Wakai T, Nakaya K
  • Journal Title: J Pediatr Surg Volume: 48 Issue: 12 Pages: 2416-2424
  • DOI: 10.1016/j.jpedsurg.2013.08.013
  • Peer Reviewed
• [Journal Article] P21-activated kinase-2 is a critical mediator of transforming growth factor-b-induced hepatoma cell migration. (2013)
  • Author(s): Sato M, Matsuda Y, Wakai T, Kubota M, Osawa M, Fujimaki S, Sanpei A, Takamura M, Yamagiwa S, Aoyagi Y
  • Journal Title: J Gastroenterol Hepatol Volume: 28 Issue: 6 Pages: 1047-1055
  • DOI: 10.1111/jgh.12150
  • Peer Reviewed
• [Journal Article] Risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts. (2013)
  • Author(s): Ohashi T, Wakai T, Kubota M, Matsuda Y, Arai Y, Ohyama T, Nakaya K, Okuyama N, Sakata J, Shirai Y, Ajioka Y
  • Journal Title: J Gastroenterol Hepatol Volume: 28 Issue: 2 Pages: 243-247
  • DOI: 10.1111/j.1440-1746.2012.07260.x
  • Peer Reviewed
• [Journal Article] Clinical significance of cell cycle inhibitors in hepatocellular carcinoma. (2013)
  • Author(s): Matsuda Y, Wakai T, Kubota M, Takamura M, Aoyagi Y, Osawa M, Fujimaki S, Sanopei A, Genda T, Ichida T
  • Journal Title: Med Mod Morphol Volume: 46 Issue: 4 Pages: 185-192
  • DOI: 10.1007/s00795-013-0047-7
  • Peer Reviewed
• [Journal Article] Mycotoxins are onventional and novel risk biomarkers for hepatocellular carcinoma (2013)
  • Author(s): Matsuda Y, Wakai T, Kubota M, Osawa M, Sanpei A, Fujimaki S
  • Journal Title: World J Gastroenterol Volume: 19 Issue: 17 Pages: 2587-2590
  • DOI: 10.3748/wjg.v19.i17.2587
  • Peer Reviewed
• [Journal Article] Tracheoplasty using a metallic fusiform centrally-doubled coiled stent for a major tracheal defect in rabbits. (2012)
  • Author(s): Kubota M, Wakai T, Okuyama N, Kobayashi K, Sato K, Nakaya K. Arai Y, Ohyama T
  • Journal Title: J Pediatr Surg Volume: 47 Pages: 2234-2238
  • Peer Reviewed
• [Presentation] Compromised natural healing process of large tracheal wall defects in rabbits (2015)
  • Author(s): Kubota M
  • Organizer: 48th Anuual Meeting of Pacific Association of Pediatric Surgeons
  • Place of Presentation: Jeju, South Korea Hotel Shilla Jeju Korea
  • Year and Date: 2015-05-17 – 2015-05-21
• [Presentation] 家兎における代用気管としての中心部二重コイルと周囲肉芽形成に対するラパマイシンの効果 (2014)
  • Author(s): 窪田 正幸
  • Organizer: 第25回小児呼吸器外科研究会
  • Place of Presentation: 秋葉原コンベンションホール
  • Year and Date: 2014-10-25
• [Presentation] The area and attachment abnormalities of the gubernaculum in patients with undescended testes (2014)
  • Author(s): Kubota M
  • Organizer: 47th Anuual Meeting of Pacific Association of Pediatric Surgeons
  • Place of Presentation: Banff, Canada Hotel Fairmont Banff Springs
  • Year and Date: 2014-05-25 – 2014-05-29
• [Presentation] 46th Anuual Meeting of Pacific Association of Pediatric Surgeons (2013)
  • Author(s): Kubota M, Matsuda Y, Fujimaki S, Osawa M, Wakai T, Nakaya K
  • Organizer: Effects of rapamycin on the granulation formation in response to using a centrally-doubled coiled stent as a tracheal substitute.
  • Place of Presentation: Hunter Valley, Australia
• [Presentation] Tracheoplasty using a fusiform metallic coil with a centrally double coiled for a major tracheal defect in rabbits (2012)
  • Author(s): Kubota M, Okuyama N, Kobayashi K, Sato K, Nakaya K, Arai Y, Oyama N
  • Organizer: 45th Anuual Meeting of Pacific Association of Pediatric Surgeons
  • Place of Presentation: Shanghai （中国）
• [Patent(Industrial Property Rights)] 代用気管 (2012)
  • Inventor(s): 窪田 正幸
  • Industrial Property Rights Holder: 窪田 正幸
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-12-08
  • Overseas