Clinical implication of Farnesoid-X-receptor agonist in liver regeneration after hepatectomy

• Project/Area Number: 26462047
• 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: TAKAMORI Hiroshi 熊本大学, 医学部附属病院, 非常勤診療医師 (90363514)
• Co-Investigator(Kenkyū-buntansha): 岡部 弘尚 熊本大学, 医学部附属病院, 非常勤診療医師 (40573621) ; 別府 透 熊本大学, 医学部附属病院, 非常勤診療医師 (70301372) ; 林 洋光 熊本大学, 医学部附属病院, 非常勤診療医師 (80625773)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: FXR agonist / 肝再生 / 肝切除 / FXR / 胆汁酸 / Farnesoid受容体X

Outline of Final Research Achievements

Mouse model of 70 % hepatectomy was established. Protocol was prepared for the experiment with FXR agonist. In clinical experiment with paraffin embedded section, immunohistochemistry was performed with FXR antibody (PPMX corp., Clone No. A9033A). Staining pattern was appropriate and nuclear localization of FXR was confirmed. On the other hand, nuclear localization of FXR in more than 50% of hepatocytes in background liver was seen in almost all samples (n > 50). Therefore, it was hard to assign them into two groups with/without FXR activation. Other methodology is required for evaluating activation status of FXR in hepatocytes.

Research Products

• [Journal Article] Neutrophil-to-lymphocyte ratio predicts metachronous liver metastasis of pancreatic neuroendocrine tumors. (2017)
  • Author(s): Arima K, Okabe H, Hashimoto D, Chikamoto A, Nitta H, Higashi T, Kaida T, Yamamura K, Kitano Y, Komohara Y, Yamashita Y, Beppu T, Takeya M, Baba H.
  • Journal Title: Int J Clin Oncol Volume: in press Issue: 4 Pages: 734-739
  • DOI: 10.1007/s10147-017-1111-4
  • Peer Reviewed
• [Journal Article] Shape and enhancement characteristics of pancreatic neuroendocrine tumor on preoperative contrast-enhanced computed tomography may be prognostic indicators. (2017)
  • Author(s): Okabe H, Hashimoto D, Chikamoto A, Morikatsu Y, Taki K, Arima K, Imai K,Tamura Y, Ikeda O, Ishiko T, Uchiyama H, Ikegami T, Harimoto N, Itoh S, Yamashita Y, Yoshizumi T, Beppu T, Yamashita Y, Baba H, Maehara Y.
  • Journal Title: Ann Surg Oncol Volume: 24(5) Issue: 5 Pages: 1399-1405
  • DOI: 10.1245/s10434-016-5630-4
  • Peer Reviewed / Open Access
• [Journal Article] Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice. (2016)
  • Author(s): Okabe H, Yang J, Sylakowski K, Yovchev M, Miyagawa Y, Nagarajan S, Chikina M, Thompson M, Oertel M, Baba H, Monga SP, Nejak-Bowen KN.
  • Journal Title: Hepatology Volume: 64(5) Issue: 5 Pages: 1652-1666
  • DOI: 10.1002/hep.28774
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diverse basis of β-catenin activation in human hepatocellular carcinoma: Implications in biology and prognosis. (2016)
  • Author(s): Okabe H, Kinoshita H, Imai K, Nakagawa S, Higashi T, Arima K, Uchiyama H, Ikegami T, Harimoto N, Itoh S, Ishiko T, Yoshizumi T, Beppu T, Monga SP, Baba H and Maehara Y.
  • Journal Title: PLoS One Volume: 11(4) Issue: 4 Pages: e0152695-e0152695
  • DOI: 10.1371/journal.pone.0152695
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Portal Vein Embolization Followed by Right-Side Hemihepatectomy for Hepatocellular Carcinoma Patients: A Japanese Multi-Institutional Study. (2016)
  • Author(s): Beppu T, Okabe H, Okuda K, Eguchi S, Kitahara K, Taniai N, Ueno S, Shirabe K, Ohta M, Kondo K, Nanashima A, Noritomi T, Okamoto K, Kikuchi K, Baba H, FujiokaH.
  • Journal Title: J Am Coll Surg. Volume: 222 Issue: 6 Pages: 1138-1148
  • DOI: 10.1016/j.jamcollsurg.2016.03.023
  • Peer Reviewed
• [Journal Article] The diagnostic role of the neutrophil-to-lymphocyte ratio in predicting pancreatic ductal adenocarcinoma in patients with pancreatic diseases. (2016)
  • Author(s): Arima K, Okabe H, Hashimoto D, Chikamoto A, Tsuji A, Yamamura K, Kitano Y, Inoue R, Kaida T, Higashi T, Taki K, Imai K, Komohara Y, Beppu T, Takeya M, Baba H.
  • Journal Title: Int J Clin Oncol. Volume: 21(5) Issue: 5 Pages: 940-945
  • DOI: 10.1007/s10147-016-0975-z
  • Peer Reviewed
• [Journal Article] Salvage splenic artery embolization for saving falling living donor graft due to portal overflow. (2016)
  • Author(s): Okabe H, Yoshizumi T, Ikegami T, Uchiyama H, Harimoto N, Itoh S, Kimura K, Baba H, Maehara Y.
  • Journal Title: Transplant Proc Volume: 48(9) Issue: 9 Pages: 3171-3173
  • DOI: 10.1016/j.transproceed.2016.07.023
  • Peer Reviewed
• [Journal Article] A long survivor with local relapse of hilar cholangiocarcinoma after R1 surgery treated with chemoradiotherapy: a case report and literature review. (2016)
  • Author(s): Okabe H, Chikamoto A, Maruno M, Hashimoto D, Imai K, Taki K, Arima K, Ishiko T, Uchiyama H, Ikegami T, Harimoto N, Itoh S, Yoshizumi T, Beppu T, Baba H, Maehara Y.
  • Journal Title: Surg Case Rep Volume: 2(1) Issue: 1 Pages: 69-69
  • DOI: 10.1186/s40792-016-0195-9
  • Peer Reviewed
• [Journal Article] A case report of bacteremia manifesting as an overwhelming postsplenectomy infection due to Streptococcus pneumoniae post vaccination. (2016)
  • Author(s): Hirose K, Okabe H, Yoshizumi T, Uchiyama H, Ikegami T, Harimoto N, Itoh S, Kimura K, Baba H, Maehara Y.
  • Journal Title: Surg Case Rep Volume: 2(1) Issue: 1 Pages: 48-48
  • DOI: 10.1186/s40792-016-0173-2
  • Peer Reviewed
• [Journal Article] Inducible factors for cancer-associated fibroblasts in liver cancer versus myofibroblasts in inflammatory liver disease. (2016)
  • Author(s): Okabe H, Hayashi H, Nakagawa S, Imai K, Nitta H, Arima K, Hashimoto D, Chikamoto A, Ishiko T, Beppu T, Baba H.
  • Journal Title: Histol Histopathol Volume: 31(2) Pages: 141-8
  • Peer Reviewed
• [Journal Article] CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin β1 clustering and invasiveness in gastric cancer. (2016)
  • Author(s): Izumi D, Ishimoto T, Miyake K, Sugihara H, Eto K, Sawayama H, Yasuda T, Kiyozumi Y, Kaida T, Kurashige J, Imamura Y, Hiyoshi Y, Iwatsuki M, Iwagami S, Baba Y, Sakamoto Y, Miyamoto Y, Yoshida N, Watanabe M, Takamori H, Araki N, Tan P, Baba H.
  • Journal Title: Int J Cancer Volume: 1;138(5) Issue: 5 Pages: 1207-19
  • DOI: 10.1002/ijc.29864
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study. (2015)
  • Author(s): Baba H, Baba Y, Uemoto S, Yoshida K, Saiura A, Watanabe M, Maehara Y, Oki E, Ikeda Y, Matsuda H, Yamamoto M, Shimada M, Taketomi A, Unno M, Sugihara K, Ogata Y, Eguchi S, Kitano S, Shirouzu K, Saiki Y, Takamori H, Mori M, Hirata T, Wakabayashi G, Kokudo N.
  • Journal Title: Oncotarget Volume: 20;6(32) Issue: 32 Pages: 34004-13
  • DOI: 10.18632/oncotarget.5227
  • NAID: 120006986836
  • Peer Reviewed
• [Journal Article] Mucinous cystic neoplasm of the pancreas activated during pregnancy (2015)
  • Author(s): Kosumi K, Takamori H, Hashimoto D, Tanaka H, Abe S, Nakahara O, Horino K, Baba H
  • Journal Title: Surg Case Rep Volume: 1(1) Issue: 1 Pages: 13-13
  • DOI: 10.1186/s40792-014-0012-2
  • Peer Reviewed
• [Journal Article] Pyoderma gangrenosum in an abdominal surgical site: a case report. (2015)
  • Author(s): Ogata K, Takamori H, Ikuta Y, Tanaka H, Ozaki N, Hayashi H, Ogawa K, Doi K.
  • Journal Title: Surg Case Rep Volume: 1(1) Issue: 1 Pages: 122-122
  • DOI: 10.1186/s40792-015-0124-3
  • Peer Reviewed
• [Journal Article] Complete response of Ctnnb1-mutated tumours to β-catenin suppression by locked nucleic acid antisense in a mouse hepatocarcinogenesis model (2015)
  • Author(s): Delgado E, Okabe H, Preziosi M, Russell JO, Alvarado TF, Oertel M, Nejak-Bowen KN, Zhang Y, Monga SP
  • Journal Title: J Hepatol Volume: 62 Issue: 2 Pages: 380-7
  • DOI: 10.1016/j.jhep.2014.10.021
  • Peer Reviewed
• [Journal Article] EZH2 Is Associated with Malignant Behavior in Pancreatic IPMN via p27Kip1 Downregulation (2014)
  • Author(s): Kuroki H, Hayashi H, Okabe H, Hashimoto D, Takamori H, Nakahara O, Nakagawa S, Fukushima Y, Chikamoto A, Beppu T, Hirota M, Iyama K, Baba H
  • Journal Title: PLOS ONE Volume: 9(8) Issue: 8 Pages: e100904-e100904
  • DOI: 10.1371/journal.pone.0100904
  • Peer Reviewed
• [Journal Article] Rank classification based on the combination of indocyanine green retention rate at 15 min and (99m)Tc-DTPA-galactosyl human serum albumin scintigraphy predicts the safety of hepatic resection (2014)
  • Author(s): Okabe H, Beppu T, Hayashi H, Masuda T, Mima K, Nakagawa S, Kuroki H, Imai K, Nitta H, Masuda T, Hashimoto D, Chikamoto A, Wanatanabe M, Ishiko T, Yoshida M, Yamashita Y, Baba H.
  • Journal Title: Nucl Med Commun Volume: 35 Issue: 5 Pages: 478-483
  • DOI: 10.1097/mnm.0000000000000075
  • Peer Reviewed
• [Presentation] 肝細胞癌の発育進展と間葉系形質獲得からみた原発性肝癌取り扱い規約の組織構造分類の意義 (2016)
  • Author(s): 岡部弘尚、調 憲、吉住朋晴、内山秀昭、池上徹、播本憲史、伊藤心二、木村光一、馬場秀夫、前原喜彦
  • 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] 肝細胞癌の再発形式・生存予後に関与する，組織構造分類の新たな提言 (2016)
  • Author(s): 岡部弘尚、調 憲、吉住朋晴、内山秀昭、池上徹、播本憲史、伊藤心二、木村光一、馬場秀夫、前原喜彦
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: アスティとくしま（徳島県）
• [Presentation] 肝細胞癌切除後再発に対して局所凝固療法を行った症例における予後規定因子の探索 (2016)
  • Author(s): 岡部弘尚、山下洋市、今井克憲、甲斐田剛圭、石河隆敏、馬場秀夫
  • Organizer: 第35回Microwave Surgery研究会
  • Place of Presentation: メルパルク熊本（熊本県）