The mechanism of liver atrophy after portal vein hypoperfusion and therapeutic method using LSKL peptide

• Project/Area Number: 26462046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: IKUTA Yoshiaki 熊本大学, 医学部附属病院, 非常勤診療医師 (70452894)
• Co-Investigator(Kenkyū-buntansha): 近本 亮 熊本大学, 医学部附属病院, 准教授 (10419640) ; 馬場 秀夫 熊本大学, 大学院生命科学研究部(医), 教授 (20240905) ; 林 洋光 熊本大学, 医学部附属病院, 非常勤診療医師 (80625773)
• Research Collaborator: KUROKI Hideyuki 熊本大学, 医学部附属病院, 非常勤診療医師 (50594876) ; MIYAKE Keisuke 熊本大学, 大学院生命科学研究部(医), リサーチスペシャリスト
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 門脈血流低下 / 肝萎縮 / TSP-1 / 肝細胞増殖抑制 / 肝細胞アポトーシス誘導 / 肝類洞内皮細胞 / 増殖抑制 / アポトーシス / 肝血流低下 / 肝肥大 / 増殖 / Smad2

Outline of Final Research Achievements

Liver atrophy was induced right portal vein ligation of wild type mouse. PCNA expression elevated at 6 hour after portal vein ligation and decreased thereafter in ligated liver (atrophic liver). TUNEL stained nuclei in liver cells increased over time. TSP-1 expression in cytoplasm of ligated liver increased since 6 hour after portal vein ligation. cDNA microarray assay was performed on ligated and non-ligated human liver for therapeutic hepatectomy. TSP-1 was most induced among 132 genes in ligated liver than in none ligated liver.
These results show hypoperfusion of portal vein induce TSP-1 expression in hepatocyte and suppress proliferation and induce apoptosis of hepatocyte.

Research Products

• [Journal Article] Thrombospondin-1 expression may be implicated in liver atrophic mechanism due to obstructed portal venous flow. (2016)
  • Author(s): Hayashi H, Kuroki H, Higashi T, Takeyama H, Yokoyama N, Okabe H, Nitta H, Beppu T, Takamori H, Baba H.
  • Journal Title: Hepatol Res Volume: Epub Issue: 8 Pages: 803-812
  • DOI: 10.1111/hepr.12792
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Heat injury to the inferior vena cava by bipolar tissue sealer. (2016)
  • Author(s): Chikamoto A, Kaida T, Arima K, Higashi T, Taki K, Ida S, Okabe H, Nitta H, Hayashi H, Hashimoto D, Watanabe M, Beppu T, Baba H.
  • Journal Title: Surg Endosc Volume: 30(4) Issue: 4 Pages: 1519-22
  • DOI: 10.1007/s00464-015-4365-9
  • Peer Reviewed
• [Journal Article] An Imbalance in TAZ and YAP Expression in Hepatocellular Carcinoma Confers Cancer Stem Cell-like Behaviors Contributing to Disease Progression. (2015)
  • Author(s): Hayashi H, Higashi T, Yokoyama N, Kaida T, Sakamoto K, Fukushima Y, Ishimoto T, Kuroki H, Nitta H, Hashimoto D, Chikamoto A, Oki E, Beppu T, Baba H.
  • Journal Title: Cancer Res. Volume: 75(22) Issue: 22 Pages: 4985-97
  • DOI: 10.1158/0008-5472.can-15-0291
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic value of Ki-67 expression in conversion therapy for colorectal liver-limited metastases. (2015)
  • Author(s): Hayashi H, Beppu T, Sakamoto Y, Miyamoto Y, Yokoyama N, Higashi T, Nitta H, Hashimoto D, Chikamoto A, Baba H.
  • Journal Title: Am J Cancer Res Volume: 15;5(3) Pages: 1225-33
  • Peer Reviewed
• [Journal Article] Functional assessment versus conventional volumetric assessment in the prediction of operative outcomes after major hepatectomy (2015)
  • Author(s): Hayashi H, Beppu T, Okabe H, Kuroki H, Nakagawa S, Imai K, Nitta H, Chikamoto A, Ishiko T, Baba H
  • Journal Title: Surgery Volume: 157(1) Issue: 1 Pages: 20-6
  • DOI: 10.1016/j.surg.2014.06.013
  • Peer Reviewed
• [Journal Article] The modified Glasgow Prognostic Score (mGPS) is a good predictor of indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers (2014)
  • Author(s): Ikuta Y, Takamori H, Sakamoto Y, Hashimoto D, Chikamoto A, Kuroki H, Sakata K, Sakamoto K, Hayashi H, Imai K, Nitta H, Hirota M, Kanemitsu K, Beppu T, Baba H
  • Journal Title: Int J Clin Oncol Volume: 19(4) Issue: 4 Pages: 629-33
  • DOI: 10.1007/s10147-013-0613-y
  • Peer Reviewed
• [Journal Article] Neuroendocrine tumor in the Glissonean pedicle of the hepatic hilum (2014)
  • Author(s): Kaida T, Chikamoto A, Kiyozumi Y, Nitta H, Imai K, Nakahara O, Ikuta Y, Doi K, Ishiko T, Takamori H, Beppu T, Baba H
  • Journal Title: Int Canc Conf J Volume: 3(2) Issue: 2 Pages: 72-6
  • DOI: 10.1007/s13691-013-0118-6
  • Peer Reviewed
• [Journal Article] Definitive diagnosis of a duplicate gallbladder can only be made intraoperatively: report of a case (2014)
  • Author(s): Ozaki N, Hashimoto D, Ikuta Y, Chikamoto A, Takamori H, Baba H
  • Journal Title: Clin J Gastroenterol Volume: 7(4) Issue: 4 Pages: 338-41
  • DOI: 10.1007/s12328-014-0494-2
  • Peer Reviewed
• [Journal Article] Pancreatic metastasis from mixed adenoneuroendocrine carcinoma of the uterine cervix: a case report. (2013)
  • Author(s): Nishimura C, Naoe H, Hashigo S, Tsutsumi H, Ishii S, Konoe T, Watanabe T, Shono T, Sakurai K, Takaishi K, Ikuta Y, Chikamoto A, Tanaka M, Iyama K, Baba H, Katabuchi H, Sasaki Y.
  • Journal Title: Case reports in oncology Volume: 6（2） Issue: 4 Pages: 256-62
  • DOI: 10.1007/s13691-014-0159-5
  • Peer Reviewed
• [Presentation] 肝再生および肝萎縮におけるトロンボスポンディン1の役割解明と臨床応用への探索 (2017)
  • Author(s): 林洋光、黒木秀幸、東孝暁、武山秀晶、岡部弘尚、今井克憲、山下洋市、高森啓史、馬場秀夫
  • Organizer: 第117回日本外科学会定期学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] 肝切除後の血漿中Thrombospondin-1変化の肝障害の予測因子としての可能性 (2016)
  • Author(s): 黒木秀幸、林洋光、中川茂樹、東孝暁、橋本大輔、新田英利、近本 亮、石河隆敏、別府 透、馬場秀夫
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪国際会議場（大阪府）
• [Presentation] Hippo-pathwayを介した癌幹細胞性獲得機構の解明と治療への応用 (2016)
  • Author(s): 林洋光、東孝暁、横山奈穂美、甲斐田剛圭、新田英利、橋本大輔、近本 亮、別府 透、高森啓史、馬場秀夫
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪国際会議場（大阪府）